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Q: Python Pandas: Counting the frequency of a specific value in each row of dataframe? I have a dataframe df: domain country out1 out2 out3 oranjeslag.nl NL 1 0 NaN pietervaartjes.nl NL 1 1 0 andreaputting.com.au AU NaN 1 0 michaelcardillo.com US 0 0 NaN I would like to define two columns sum_0 and sum_1 and count the number of 0s and 1s in columns (out1,out2,out3),per row. So expected results would be: domain country out1 out2 out3 sum_0 sum_1 oranjeslag.nl NL 1 0 NaN 1 1 pietervaartjes.nl NL 1 1 0 1 2 andreaputting.com.au AU NaN 1 0 1 1 michaelcardillo.com US 0 0 NaN 2 0 I have this code for counting the number of 1s, but I do not know how to count the number of 0s. df['sum_1'] = df[['out_1','out_2','out_3']].sum(axis=1) Can anybody help? A: You can call sum for each condition, the 1 condition is simple just a straight sum on axis=1, for the second you can compare the df against 0 value and then call sum as before: In [102]: df['sum_1'] = df[['out1','out2','out3']].sum(axis=1) df['sum_0'] = (df[['out1','out2','out3']] == 0).sum(axis=1) df Out[102]: domain country out1 out2 out3 sum_0 sum_1 0 oranjeslag.nl NL 1 0 NaN 1 1 1 pietervaartjes.nl NL 1 1 0 1 2 2 andreaputting.com.au AU NaN 1 0 1 1 3 michaelcardillo.com US 0 0 NaN 2 0 | Mid | [
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Q: Big O of empty loops If I have a loop construction like this for(int i=1; i<n;i++) for(int j=1; j<n;j++); O(n2) or O(0)? Assume that inside the loop is an if: for(int i=1; i<n;i++) for(int j=1; j<n;j++) if(a==b) do(); and I want to know best and worst case, assuming do() is O(1). Worst: O(n2) if statement always true Best: O(0) if statement always false Is that correct? A: There's no such thing as O(0), in our context; it'd be effectively constant-time (O(1)), if optimized away. As for whether that's the case, no. As written, it's still O(N^number of nested loops). An optimizer might remove the code entirely, but the "worst case" is that it doesn't, and the CPU's spinning its wheels. through those loops. A: Take n = 3, for the first loop, the following happens: i = 1 i < 3 => true j = 1 j < 3 => true j++ j < 3 => true j++ j < 3 => false i++ i < 3 => true j = 1 ... All these increments and checks still need to happen regardless of whether or not there's any other code in the loop. So it will be best + worst case O(n2). There is of course the possibility that the optimiser will see nothing happens in the loop and removes it completely. But saying the best-case for loop is O(1) will probably be considered wrong, even though it's technically correct. | Mid | [
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Circumventing Locks and Access Controls Modern operating systems typically restrict access to critical or sensitive resources. For example, an internal database may not be intended for users to view or a resource may be currently in use. Such is the case when attempting to access the password databases maintained on systems running Microsoft Windows. When conducting a penetration test, circumvention techniques are usually required to extract a copy of such files because they are locked by the Windows kernel. It is recognized that the ability to acquire password hashes from a local system is not new. However, existing popular techniques present certain complications in an ethical penetration testing scenario. | Mid | [
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--- abstract: | \*\* [PACS: \*\*\*]{}[MSC: \*\*\*]{} author: - 'P.G.L. PortaManaLuca[`<mana.se>`]{}' date: '[12 June 2017]{}' title: | Geometry of maximum-entropy proofs:\ stationary points, convexity,\ Legendre transforms, exponential families --- =1 Most proofs of the traditional maximum-entropy formulae [@jaynes1963; @sivia1996_r2006 [ch.]{} 5] $$\begin{gathered} {\bm{p}}=\frac{\exp({\bm{{l}}}{\bm{{\varEpsilon}}}+ \ln{\bm{q}})}{Z({\bm{{l}}})}\qquad Z({\bm{{l}}}) = {\bm{\varSigma}}{}\exp({\bm{{l}}}{\bm{{\varEpsilon}}}+ \ln{\bm{q}})\qquad \frac{{\partialup}\ln Z}{{\partialup}{\bm{{l}}}}={\bm{{\epsilon}}}, \end{gathered}$$ with or without ${\bm{q}}$ terms, rely on the method of Lagrange multipliers, and many of them also show that the constrained maximization of the Shannon entropy is equivalent to the minimization of a “potential function” via a Lagrange transform. Examples are Mead [&]{} Papanicolaou’s \[[§]{} II\][meadetal1984]{} and Jaynes’s \[[§]{} 11.6\][jaynes1994\_r2003]{} proofs. This note is a geometric commentary on such proofs. Its purpose is to help you visualize some of the geometric structures involved and to explain more in detail why we end up *minimizing* a potential function to *maximize* the entropy, and how Lagrange transforms emerge. A synopsis of the main functions involved in the proof and of their very different properties is given at the end, together with a brief discussion of exponential families of probabilities, which appear in the proof. I assume that you have some familiarity with the maximum-entropy method and the standard proof of its formulae, as in the references above. The geometric commentary is formulated in terms of the *relative* Shannon entropy [@jaynes1963 [§]{} 4.c][kullback1982\_r2006,good1983b]{}, also called negative discrimination information [@kullback1959_r1978 [ch.]{} 3], with respect to a reference distribution, because only this formulation is coordinate-independent in the continuum limit [@hobsonetal1973; @good1983b]. Notation ======== I hope you will indulge me in using vector-covector notation, which produces compact multidimensional formulae. A covector maps a vector into a scalar; it can be represented as a row matrix, and a vector as a column matrix. Here Latin letters will represent vectors; Greek, covectors. Juxtaposition of a vector and a covector always means their contraction or row-column multiplication, irrespective of their order; [[e.g.]{}]{}${\bm{{\epsilon}}}{\bm{{l}}}={\bm{{l}}}{\bm{{\epsilon}}}=\sum_n{\epsilon}^n{l}_n$. I also use the convention that the logarithm maps vectors into covectors elementwise, and vice versa for the exponential; for example $\ln{\bm{p}}{\coloneqq}(\ln p_1, \ln p_2, \dotsc)$ and is a covector. Finally, *convex* means $\cup$-shaped, and *concave* means $\cap$-shaped. Geometry of the proof ===================== We have $K$ states $k\in\set{1,\dotsc, K}$ and $N$ observables $n\in\set{1,\dotsc,N}$. A measurement of the $n$th observable when the state is $k$ gives the value ${\varEpsilon}^{n k}$. These values are grouped into the operator ${\bm{{\varEpsilon}}}=(\varEpsilon^{n k})$ which maps vectors to covectors. The distribution of probabilities ${\bm{p}}=(p_k)$, a vector, expresses our uncertainty about the actual state. The expectations for the $N$ observables under our state of uncertainty are ${\bm{{\varEpsilon}}}{\bm{p}}$. The $K$-dimensional covector ${\bm{\varSigma}}=(1, \dotsc, 1)$ and allows us very suggestively to write ${\bm{\varSigma}}{}{\bm{p}}=\sum_k p_k$. We want to choose a probability distribution for which the expectations are constrained to values ${\bm{{\epsilon}}}=({\epsilon}_n)$, represented by a covector. But the constraints ${\bm{{\varEpsilon}}}{}{\bm{p}}={\bm{{\epsilon}}}$ don’t select a unique ${\bm{p}}$ if $N<K-1$. We therefore ask that that the distribution meet an additional requirement that makes it unique: ${\bm{p}}$ must maximize the relative Shannon entropy $H({\bm{p}}) {\coloneqq}-{\bm{p}}\ln{\bm{p}}+{\bm{p}}\ln{\bm{q}}$, under those constraints, with respect to a reference distribution ${\bm{q}}$. We denote this unique distribution ${\bm{p}}_{{\bm{{\epsilon}}}}$, and the corresponding maximum value of the entropy $S({\bm{{\epsilon}}}){\coloneqq}H({\bm{p}}_{{\bm{{\epsilon}}}})$; it’s called the *Gibbs entropy*. The Shannon and Gibbs entropies are different functions, of completely different quantities. To find the constrained maximum of the relative Shannon entropy we use the method of Lagrange multipliers [@boydetal2004_r2009 [ch.]{} 5]. I warmly recommend Rockafellar’s [rockafellar1993]{} brilliant review of the various meanings of Lagrange multipliers, which offers plenty of geometric insights. With scalar ${u}$ and vector ${\bm{{l}}}= ({l}_n)$, define the function of $({\bm{p}},{u},{\bm{{l}}})$ with parameter ${\bm{{\epsilon}}}$ $${L}_{{\bm{{\epsilon}}}}({\bm{p}},{u},{\bm{{l}}}){\coloneqq}-{\bm{p}}\ln{\bm{p}}+ {\bm{p}}\ln{\bm{q}}+ {u}\,({\bm{\varSigma}}{\bm{p}}-1) + {\bm{{l}}}\,({\bm{{\varEpsilon}}}{\bm{p}}-{\bm{{\epsilon}}}), \label{eq:Lagrangian}$$ usually called *Lagrangian* [@fangetal1997; @boydetal2004_r2009]. It’s defined on the $(K+N+1)$-dimensional manifold ${{\bm{\mathrm{R}}}_{{\geqslant}0}}^{K}\times{\bm{\mathrm{R}}}^{N+1}$, our “base manifold”. Proofs of the maximum-entropy formulae with linear constraints show that *the Lagrangian ${L}_{{\bm{{\epsilon}}}}({\bm{p}},{u},{\bm{{l}}})$ has a unique saddle point $({\bm{p}}_{{\bm{{\epsilon}}}},{u}_{{\bm{{\epsilon}}}},{\bm{{l}}}_{{\bm{{\epsilon}}}})$, and the saddle-point coordinate ${\bm{p}}_{{\bm{{\epsilon}}}}$ is the maximum-entropy solution*. ![(Colour-blind-friendly palette by Tol [-@tol2009_r2012])[]{data-label="fig:saddle"}](maxent_saddle_trim_small2.png){width="\linewidth"} Figure \[fig:saddle\] depicts our constrained maximization problem in the simplest nontrivial case: $K=3$, $N=1$. Our base manifold has therefore $5$ dimensions. The $3$-dimensional space represented in the figure is a section of our base manifold, obtained by selecting specific values of the coordinates $p_3$ and ${u}$ as functions – and – below – of the remaining ones. The **** in [fig.]{} \[fig:saddle\] are the contour levels of the Lagrangian . Their saddle is clearly visible. The saddle point is the **black dot**. Note that a section roughly parallel to the ${\bm{{l}}}$ axis is made within the figure for clearer visibility of the surfaces and curves involved. The value of the Lagrangian ${L}_{{\bm{{\epsilon}}}}$ at the saddle point is the value of the Gibbs entropy: $$\label{eq:G_saddle_is_entropy} {L}_{{\bm{{\epsilon}}}}({\bm{p}}_{{\bm{{\epsilon}}}},{u}_{{\bm{{\epsilon}}}},{\bm{{l}}}_{{\bm{{\epsilon}}}}) \equiv S({\bm{{\epsilon}}}).$$ It’s easy to check this: the constraint terms in vanish at the saddle-point and what remains is the maximized Shannon entropy, that is, the Gibbs entropy. Our saddle-point problem reduces, thanks to the continuous differentiability of the Lagrangian, to the system of three vector equations \[eq:con\_all\] [align]{} \[eq:con\_p\] -+ + + [u]{}&=0,\ \[eq:con\_u\] -1 &=0,\ \[eq:con\_l\] -&=0. They are the implicit equations of three submanifolds in our $(K+N+1)$-dimensional base manifold. The first is curved, $(N+1)$-dimensional. The second is flat, $(K+N)$-dimensional, and contains the simplex of normalized probability distributions; the $3$-dimensional space depicted in [fig.]{} \[fig:saddle\] is the intersection of our $5$-dimensional base manifold with this submanifold, and therefore [eq.]{} is identically satisfied in the figure. The third submanifold is flat, $(K + 1)$-dimensional; it is the **** in the figure. The saddle point is the intersection of these three submanifolds. The vector equations above can be recombined and written as a system of three new vector equations: \[eq:equations\_submanifolds\] [gather]{} \[eq:eq\_sub\_p\] =(+ ),\ \[eq:eq\_sub\_u\] [u]{}=1-Z(),\ \[eq:eq\_sub\_l\] (+ ) = , $$\label{eq:Z} \text{with }Z({\bm{{l}}}){\coloneqq}{\bm{\varSigma}}{}\exp({\bm{{l}}}{}{\bm{{\varEpsilon}}}+ \ln{\bm{q}}).$$ The first is the parametric equation of a curved $(N+1)$-dimensional submanifold, which is also submanifold of . The second is the parametric equation of a curved $(K+N)$-dimensional submanifold; the $3$-dimensional space of [fig.]{} \[fig:saddle\] is the intersection of this submanifold, besides , with our $5$-dimensional base manifold; [eq.]{} is thus also identically satisfied in the figure. The third equation in the system above is the implicit equation of a flat $(K+1)$ dimensional submanifold. This equation determines a unique value ${\bm{{l}}}_{{\bm{{\epsilon}}}}$, so it is simply the equation of the $(K+1)$-plane ${\bm{{l}}}={\bm{{l}}}_{{\bm{{\epsilon}}}}$, the **** in [fig.]{} \[fig:saddle\]. These three submanifolds , are distinct from the previous three , but they also intersect at the saddle point. The function $\ln Z({\bm{{l}}})$ defined in is called *normalization function* or *partition function*. Note that we could have formulated our constrained-maximization problem by imposing the normalization from the very beginning, for example defining $p_K = 1 - p_1 - p_2 - \dotsb$. The multiplier ${u}$ and [eqs]{} , wouldn’t have appeared, and our base manifold would have been $(K+N-1)$-dimensional. Figure \[fig:saddle\] can also be interpreted this way. The system [&]{} is equivalent to the system [&]{} , as can be verified by substitution; that is, the $N$-dimensional intersection submanifold of the first pair is also the intersection of the second pair. This submanifold is the in the figure. Projected onto the simplex of probability distributions – that is, disregarding the ${u}$ and ${\bm{{l}}}$ dimensions – this submanifold is an subset of the latter called an *exponential family*. Exponential families are briefly discussed in [§]{} \[sec:exponential\_families\]. The saddle point is the intersection of this $N$-dimensional submanifold with either the $(K+1)$-plane or the $(K+1)$-plane . The saddle point $({\bm{p}}_{{\bm{{\epsilon}}}}, {u}_{{\bm{{\epsilon}}}}, {\bm{{l}}}_{{\bm{{\epsilon}}}})$ could therefore be found by finding the root ${\bm{{l}}}={\bm{{l}}}_{{\bm{{\epsilon}}}}$ of [eq.]{} , and substituting this root in $\bigl( {\bm{p}}({\bm{{l}}}), {u}({\bm{{l}}})\bigr)$, the parametric form of [eqs]{} [&]{} . But it turns out that we do not need to solve [eq.]{} . There’s an interesting development. Looking at [fig.]{} \[fig:saddle\] we notice that *the $N$-dimensional manifold $\bigl( {\bm{p}}({\bm{{l}}}), {u}({\bm{{l}}})\bigr)$ extends from the pommel to the cantle of the saddle* (if the lower part is the cantle the horse is rearing). This was a priori not necessary: by construction this submanifold must pass through the saddle point, but it could have done so by going from the pommel down to the flaps of the saddle. It couldn’t have made a U-turn back to the pommel, however, because that implies the presence of a wedge, whereas our manifold is continuously differentiable. This placement of the $N$-dimensional submanifold implies that if we ride it we see the values of the Lagrangian decrease until we reach the saddle point, and then increase again. *The saddle point is therefore the minimum of the Lagrangian restricted to the $N$-dimensional submanifold.* This is true for the $N=1$ case of our figure, but it generalizes to larger $N$; here’s how. Consider the restriction of the Lagrangian ${L}_{{\bm{{\epsilon}}}}$, [eq.]{} , to the $N$-dimensional submanifold. This restriction, denoted ${\varGamma}_{{\bm{{\epsilon}}}}$, is usually called the potential function. It’s by construction a function of ${\bm{{l}}}$ alone, from [eqs]{} and : $$\label{eq:F_from_G} {\varGamma}_{{\bm{{\epsilon}}}}({\bm{{l}}}) {\coloneqq}{L}_{{\bm{{\epsilon}}}}[{\bm{p}}({\bm{{l}}}),{u}({\bm{{l}}}),{\bm{{l}}}] \equiv \ln Z({\bm{{l}}}) - {\bm{{l}}}{}{\bm{{\epsilon}}}.$$ In [fig.]{} \[fig:saddle\] the intersections of the blue surfaces with the thick purplish-red curve are the “contours” – just points in this case – of this function. The Hessian matrix of its second derivatives has non-negative eigenvalues: a simple calculation and a look at reveal that this is in fact the covariance matrix of the observable ${\bm{{\varEpsilon}}}$: $$\label{eq:hessian_covariance} \frac{{\partialup}^2{\varGamma}_{{\bm{{\epsilon}}}}}{{\partialup}{l}_n{\partialup}{l}_m} \equiv \frac{{\partialup}^2\ln Z}{{\partialup}{l}_n{\partialup}{l}_m} = \sum_k {\varEpsilon}^{n k}{\varEpsilon}^{mk}p_k({\bm{{l}}}) - \sum_k {\varEpsilon}^{n k}p_k({\bm{{l}}}) \, \sum_k {\varEpsilon}^{mk}p_k({\bm{{l}}}),$$ and covariance matrices have non-negative eigenvalues [@feller1966_r1971 [§]{} III.5]. The potential function ${\varGamma}_{{\bm{{\epsilon}}}}$ is therefore *convex* – strictly so, without flat regions, owing to the differential properties of the logarithm. Calculation of its unique minimum by derivation leads to [eq.]{} . The conclusion is that *the potential function ${\varGamma}_{{\bm{{\epsilon}}}}$ is convex in ${\bm{{l}}}$, and the saddle point of ${L}_{{\bm{{\epsilon}}}}$ in the $(K+N+1)$-dimensional base manifold is the unique minimum of ${\varGamma}_{{\bm{{\epsilon}}}}$ in the $N$-submanifold*. This is the geometric reason why the constrained-maximization problem in $K$ dimensions for the Shannon entropy $H({\bm{p}})$ can be transformed into an unconstrained-minimization problem in $N$ dimensions for the potential function $\ln Z({\bm{{l}}}) - {\bm{{l}}}{}{\bm{{\epsilon}}}$. The latter is usually called the *dual problem* [@fangetal1997; @boydetal2004_r2009]. This fact is enormously useful for numerical computations: it allows us to use convex optimization techniques [@pressetal1988_r2007] to find the extremizing Lagrange multipliers ${\bm{{l}}}_{{\bm{{\epsilon}}}}$ and thence the distribution ${\bm{p}}_{{\bm{{\epsilon}}}}$ and the Gibbs entropy $S({\bm{{\epsilon}}}) {\coloneqq}H({\bm{p}}_{{\bm{{\epsilon}}}})$. See Rockafellar’s [rockafellar1993]{} insightful discussion in this respect too. But the geometry of this extremization problem has further surprises. The Gibbs entropy $S({\bm{{\epsilon}}})$ is, from its definition, equal to ${L}_{{\bm{{\epsilon}}}}({\bm{p}}_{{\bm{{\epsilon}}}},{u}_{{\bm{{\epsilon}}}},{\bm{{l}}}_{{\bm{{\epsilon}}}}) \equiv {\varGamma}_{{\bm{{\epsilon}}}}({\bm{{l}}}_{{\bm{{\epsilon}}}}) \equiv \ln Z({\bm{{l}}}_{{\bm{{\epsilon}}}}) - {\bm{{l}}}_{{\bm{{\epsilon}}}}{}{\bm{{\epsilon}}}$, which is the unique minimum of ${\varGamma}_{{\bm{{\epsilon}}}}({\bm{{l}}})$. We can write this as $$\label{eq:F_lagrange_S} S({\bm{{\epsilon}}}) = \inf_{\smash{{\bm{{l}}}}}[\ln Z({\bm{{l}}}) - {\bm{{l}}}{}{\bm{{\epsilon}}}].$$ This formula is the proper definition of the negative *Legendre transform* of the normalization function $\ln Z({\bm{{l}}})$, that is, its negative convex conjugate [@fenchel1949]. This means that *the Gibbs entropy $S({\bm{{\epsilon}}})$ is a concave function of ${\bm{{\epsilon}}}$*. The concavity of the Gibbs entropy is an important property, completely distinct from the concavity of the Shannon entropy $H({\bm{p}})$. I said “proper” Legendre transform because the physics literature often defines the latter without the extremization indicated by “$\inf$” or “$\sup$”. Such simplified definition breaks down if the transformed function is not strictly convex – which may happen in important physical situations. See Wightman’s illuminating and pedagogical discussion [@wightman1979 pp. xxiv–xxix]. From the involutive property of the Legendre transform , *the normalization function $\ln Z({\bm{{l}}})$ is the negative Legendre transform of the negative Gibbs entropy*: $$\label{eq:F_lagrange_Z} \ln Z({\bm{{l}}}) = \inf_{\smash{{\bm{{\epsilon}}}}}[-S({\bm{{\epsilon}}}) - {\bm{{\epsilon}}}{\bm{{l}}}].$$ The appearance of these Lagrange transforms has many important connections with statistical mechanics; for interesting recent developments see Chomaz [&]{} al.’s [chomazetal2006,chomazetal2005b]{} reviews. I refrain from speaking about the relationship between the maximum-entropy method: it’s subtle and already too often oversimplified in the literature. Synopsis of the main functions ============================== It’s important to keep the main functions involved in the proof well-distinct from one another: - The *Shannon entropy* $H({\bm{p}})$ is a function of the probability distribution ${\bm{p}}$. It’s concave in ${\bm{p}}$. It isn’t the Legendre transform of anything. - The *Gibbs entropy* $$S({\bm{{\epsilon}}}) \equiv \sup_{\smash{{\bm{p}}}}^{\smash{{\bm{{\varEpsilon}}}{\bm{p}}={\bm{{\epsilon}}}}}H({\bm{p}}) \equiv \inf_{\smash{{\bm{{l}}}}}[\ln{\bm{\varSigma}}{}\exp({\bm{{l}}}{}{\bm{{\varEpsilon}}}+ \ln{\bm{q}})- {\bm{{l}}}{\bm{{\epsilon}}}] \equiv \inf_{\smash{{\bm{{l}}}}}[\ln Z({\bm{{l}}})- {\bm{{l}}}{\bm{{\epsilon}}}]$$ is a function of the expectation values ${\bm{{\epsilon}}}$. It’s concave in ${\bm{{\epsilon}}}$. It’s the constrained maximum of the relative Shannon entropy, the unconstrained minimum of the potential function, and the negative Legendre transform of the normalization function. - The *normalization function*, *partition function*, or *free entropy* $$\ln Z({\bm{{l}}}) \equiv \ln{\bm{\varSigma}}{}\exp({\bm{{l}}}{}{\bm{{\varEpsilon}}}+ \ln{\bm{q}}) \equiv \inf_{\smash{{\bm{{\epsilon}}}}}[-S({\bm{{\epsilon}}}) - {\bm{{\epsilon}}}{\bm{{l}}}]$$ is a function of the Lagrange multipliers ${\bm{{l}}}$. It’s convex in ${\bm{{l}}}$. It’s the negative Legendre transform of the negative Gibbs entropy. - The *potential function* ${\varGamma}_{{\bm{{\epsilon}}}}({\bm{{l}}}) \equiv \ln Z({\bm{{l}}})- {\bm{{l}}}{\bm{{\epsilon}}}$ is a function of the Lagrange multipliers ${\bm{{l}}}$ with a parametric dependence on the expectation values ${\bm{{\epsilon}}}$. It’s convex in ${\bm{{l}}}$. It isn’t the Legendre transform of anything. Not to be confused with the Gibbs entropy. Exponential families {#sec:exponential_families} ==================== The maximum-entropy method is essentially a function that maps a set of observables, a set of observable constraints, and a reference distribution to a probability distribution: $({\bm{{\varEpsilon}}},{\bm{{\epsilon}}},{\bm{q}}) \mapsto {\bm{p}}$. From this point of view all other quantities appearing in its proof and formulae are just auxiliary quantities – including the Lagrange multipliers ${\bm{{l}}}$. But the parametric submanifold of probabilities ${\bm{p}}({\bm{{l}}})$, [eq.]{} : $$\label{eq:exponential_family} {\bm{p}}({\bm{{l}}})=\frac{1}{Z({\bm{{l}}})}\exp({\bm{{l}}}{\bm{{\varEpsilon}}}+ \ln{\bm{q}}), \qquad Z({\bm{{l}}}){\coloneqq}{\bm{\varSigma}}{}\exp({\bm{{l}}}{}{\bm{{\varEpsilon}}}+ \ln{\bm{q}}),$$ has a meaning and an importance of its own, outside of the maximum-entropy method. It is an example of *exponential family*. Exponential families are particular submanifolds of a simplex of probability distributions characterized by an exponential parametric form like the above or more general . [r]{}[0.5]{} {width="\linewidth"}\ {width="\linewidth"} The figures on the right show an example of $2$-dimensional exponential family for the case with four states, $K=4$, two observables, $N=2$, having values $$\label{eq:observables_expfamily_example} ({\varEpsilon}^{nk}) \equiv \begin{pmatrix} {\varEpsilon}^{1\,k}\\{\varEpsilon}^{2\,k} \end{pmatrix} = \begin{pmatrix} 0 & 1 & 2 & 3\\ 1& 1& 0 & 0 \end{pmatrix},$$ and a uniform reference distribution ${\bm{q}}$. The **black lines** are the edges of the **simplex of probability distributions** ${\bm{p}}$, a tetrahedron. The **** is the ****, the same in both figures. In the top figure the **** are equally-spaced **** for the parametrization in terms of the Lagrange multipliers, ${\bm{{l}}}{\coloneqq}({l}_1, {l}_2) \in {\bm{\mathrm{R}}}^2$. In the bottom figure the **** are equally-spaced **** for the parametrization in terms of the expectations, ${\bm{{\epsilon}}}{\coloneqq}({\epsilon}_1, {\epsilon}_2) \in \clcl{0,3}\times\clcl{0,1}$. The relation between these two coordinate systems, [eq.]{} , is highly non-linear. The ${\bm{{l}}}$ coordinates have the advantage of parametrizing ${\bm{p}}({\bm{{l}}})$ in closed form, [eq.]{} , but are uncongenial to the convex structure of the simplex of probability distributions; their non-compact range must in fact cover a compact set. The ${\bm{{\epsilon}}}$ coordinates are clearly more congenial to the convex structure of the probability simplex, but they do not lend themselves to a parametrization ${\bm{p}}({\bm{{\epsilon}}})$ in closed form. Both ${\bm{{l}}}$- and ${\bm{{\epsilon}}}$-parametrizations are therefore important. The Bernoulli, Poisson, exponential, normal distributions belong to exponential families. See Bernardo [&]{} Smith \[[ch.]{} 4, esp. 4.5.3\][bernardoetal1994\_r2000]{} for a thorough discussion of these families, Barndorff-Nielsen [barndorffnielsen1978\_r2014]{} for their relation with Lagrange transforms, Dawid [dawid2013]{} for a broader context. Exponential families appear in the probability calculus when we assume that a particular fixed set of quantities from some measurements is all we need to make inferences about other similar measurements, a condition called *sufficiency* [@bernardoetal1994_r2000 [ch.]{} 4, esp.[§]{} 4.5.3; @barndorffnielsen1978_r2014; @dawid2013; @andersen1970]. The fact that they appear in the maximum-entropy formulae thus suggests a relation between maximum-entropy and sufficiency. A recent work which I don’t fully understand [@portamana2017] argues, however, that this relation has some downsides, and maximum-entropy distributions are best related to so-called *exchangeable* models [@bernardoetal1994_r2000 [§]{} 4.3]. I owe the inspiration for writing this note to Moritz Helias, Tobias K[ü]{}hn, and Vahid Rostami. I cordially thank Tobias for detecting some deficiencies in an early draft. It goes without saying that any deficiencies that may remain are therefore *his* fault, right? …ah, wait, it doesn’t work that way? | Mid | [
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If this is your first visit, be sure to check out the FAQ by clicking the link above. You may have to register before you can post: click the register link above to proceed. To start viewing messages, select the forum that you want to visit from the selection below. A friend and I were talking the other day of the subject of extracting for hobbyists. He lives in the Upper Penninsula of Michigan where beekeepers are far and few in between. He has a novel idea of having their club by a small 6-12 frame extractor and placing it in a covered trailer along with all the other extracting needs. That way it could be moved from one club member to the next. I think it would be a great idea even for clubs or associations to solve the uncapping problem. Does anyone else use this practice? And what do you see as the pros and cons of this practice? Bill: Some friends and I kicked this idea around once with a slightely different slant. We had received a gift of a 24 frame radial extractor, one person volunteered to set it up in a building on his property with 24 - 7 access , he would charge two cents a frame for the use of the water and electric. You would have the option of cleaning up the equipment or leaving the cappings and someone else would do the clean up. A survay of the beekeepers found this not to be a good idea, most of the hobbist never took any surplus honey and even those that were squeezing honey from comb through a stocking resented the charge and the cappings for the clean up. We dropped the idea and my wife is forever relegated to the position of chief extractor handle twister. I think your idea of a mobile extracting system has a lot of merit. Taking into consideration the frugal nature of the average beekeeper I would suggest that all agreements dealing with finances be made in writing and all participants make a up front financial commitment. I used to belong to a flying club that one could buy into and sell out of, but could not just quit , even if you quit flying you was still obligated for monthly dues. Regards Les in SC I offered the use of my extractor for what I thought was a lot less the the trouble was worth. Only one person took me up on it and I don't think he plans on doing it again. Of course I made suggestions on how he could process the honey himself without the extractor also. Our beekeeping association owns a 2 frame extactor, heated knife and all of the other things needed to extract their honey. We charge our association members $5 a day with a $5 deposit and it is used all summer. It is so nice to know we don't have to buy this equipment but have ready access to something we really need. They take this money and buy the necessary drugs that we need for our bees and distribute it free to the members of our association. This is something I have also thought about. We are in the prosess of starting out apiaries with 20 to 50 hives each. They will be from 5mi. to 80mi. from our home location.I hope to set up extraction in an 8 x 16 inclosed truck or trailer with 55 gal. drum honey storage .I do not know if this will work , any thoughts ? hello. sounds like you can make a go of it. I knew a man in fla. yrs ago that traveled with a old school bus and did that. he seem to have it going on. he had 20 frame radial and 55 gal drums and a barrel for bottleing he was sorta liveing in the bus and just followed the flows. Don The most difficult thing to rig is the water, but that is available for RV's. To be really convienint it would be nice to have hot and cold running water. But Probably not necessary. A couple of 5 gallon buckets of water might do until you can get to some water to do a better cleanup. | Mid | [
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Instagram Makes Serious Money Moves With New Payment Feature This means all iOS users can now watch Facebook and Instagram videos along with Youtube directly on the app without having to leave it. An Instagram spokesperson confirmed TechCrunch that the payments feature for booking appointments like at restaurants or salons is now live for a limited set of partners. Thankfully, with today's update to the service, you can now view videos from Facebook or Instagram right in a conversation thread itself without worrying that you would be force to leave WhatsApp for the duration of the video. Currently, a dinner reservation app named Resy is equipped with this new feature, where a user can book a table within the Instagram page of Resy. The company has a new payments feature where you can register a debit or credit card on your profile, set up a security pin and save the card for future use. Select users of the social media site have begun to notice the addition of a payment button to the app's existing booking feature. The feature, which is already accessible to some users, will achieve Instagram's transformation into a shopping powerhouse. After Facebook bought Instagram in 2012, the photo-sharing app been through an evolutionary change since its launch. Facebook, meanwhile, has been exploring e-commerce for years mainly via its Marketplace, also revamping its Messenger platform to make it a more effective bridge between businesses and users, alongside a raft of additional features announced at its F8 conference. This is also great news for brands as they now get to enable their target audience to buy rather than just show them promotions. WhatsApp is the world's most popular chat app, with over 1.5billion users each month. It let users transfer money to bank accounts and also pay for goods and services bought offline. So, players like BookMyShow and PayTM that sell movie tickets will be able to sell tickets on Instagram as well. Writing in a blog post at the time, a spokesman said: 'People come to Instagram to follow their passions - from travel and fashion to food, entertainment and everything in between. The feature is now said to be in beta testing and will soon be rolled out globally. Comments Latest Posts Women Sue Charlie Rose and CBS, Alleging Harassment But, according to the complaint, the defendants "unlawfully failed and refused to take any remedial action and allowed Mr". Rose sexually harassed them and that managers knew about complaints against him before November, when he was sacked . SA ranks third among African nations on media freedom The freedom of expression was enshrined as a human right under the Article 19 of the 1948 Universal Declaration of Human Rights. He said the government also responded to criticism or probing questions by making statements to ridicule the media. Tesla drops in premarket after Musk lets loose on call Tesla's key metric is hitting 5,00 per week and that their target for Model 3 production may not happen until late July. Tesla aims to boost production quickly from 2,270 Model 3 sedans per week in April to 5,000 by the end of June. Starting XI: Chelsea v Liverpool Liverpool are without Joe Gomez, who has an ankle injury, while Joel Matip, Emre Can and Alex Oxlade-Chamberlain are also out. The deposed champions are five points behind fourth placed Tottenham, with both teams having three games to play. Air pollution kills about 7 million people yearly About 3 billion people are breathing deadly fumes from domestic cooking stoves and fires, according to the Geneva-based agency. But the most disquieting fact is that among the worst affected cities in the world, Indian cities top the list. 2 dead in Russian fighter jet crash off Syria coast The disaster occurred as the aircraft was gaining altitude. "There was no fire impact on the plane", the Defense Ministry said. Preliminary reports claim a bird may have hit an engine during a take-off, according to RIA Novosti . Watch Tiger Woods pour in back-to-back birdie putts Last year's PGA final round drew a 3.6 overnight TV rating, the second-lowest since at least 1995 according to Sports Media Watch. Brian Harman, last year's victor at Eagle Point Golf Club, could only manage a one-over 72. "We're all going to be close". Apple Can Do No Wrong As iPhone Sales Rise Munster rated the quarter as an "A-", and said it wasn't a "blow-out quarter", but there's still room for positive growth. The services division continues to be one of its most lucrative, with a 31 per cent revenue growth year on year. | Low | [
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#include <elf.h> #include <limits.h> #include <sys/mman.h> #include <string.h> #include "pthread_impl.h" #include "libc.h" #include "atomic.h" #include "syscall.h" int __init_tp(void *p) { pthread_t td = p; td->self = td; int r = __set_thread_area(TP_ADJ(p)); if (r < 0) return -1; if (!r) libc.can_do_threads = 1; libc.has_thread_pointer = 1; td->tid = __syscall(SYS_set_tid_address, &td->tid); td->locale = &libc.global_locale; return 0; } #ifndef SHARED static long long builtin_tls[(sizeof(struct pthread) + 64)/sizeof(long long)]; struct tls_image { void *image; size_t len, size, align; } __static_tls ATTR_LIBC_VISIBILITY; #define T __static_tls void *__copy_tls(unsigned char *mem) { pthread_t td; if (!T.image) return mem; void **dtv = (void *)mem; dtv[0] = (void *)1; #ifdef TLS_ABOVE_TP mem += sizeof(void *) * 2; mem += -((uintptr_t)mem + sizeof(struct pthread)) & (T.align-1); td = (pthread_t)mem; mem += sizeof(struct pthread); #else mem += libc.tls_size - sizeof(struct pthread); mem -= (uintptr_t)mem & (T.align-1); td = (pthread_t)mem; mem -= T.size; #endif td->dtv = dtv; dtv[1] = mem; memcpy(mem, T.image, T.len); return td; } #if ULONG_MAX == 0xffffffff typedef Elf32_Phdr Phdr; #else typedef Elf64_Phdr Phdr; #endif void __init_tls(size_t *aux) { unsigned char *p; size_t n; Phdr *phdr, *tls_phdr=0; size_t base = 0; void *mem; libc.tls_size = sizeof(struct pthread); for (p=(void *)aux[AT_PHDR],n=aux[AT_PHNUM]; n; n--,p+=aux[AT_PHENT]) { phdr = (void *)p; if (phdr->p_type == PT_PHDR) base = aux[AT_PHDR] - phdr->p_vaddr; if (phdr->p_type == PT_TLS) tls_phdr = phdr; } if (tls_phdr) { T.image = (void *)(base + tls_phdr->p_vaddr); T.len = tls_phdr->p_filesz; T.size = tls_phdr->p_memsz; T.align = tls_phdr->p_align; } T.size += (-T.size - (uintptr_t)T.image) & (T.align-1); if (T.align < 4*sizeof(size_t)) T.align = 4*sizeof(size_t); libc.tls_size = 2*sizeof(void *)+T.size+T.align+sizeof(struct pthread); if (libc.tls_size > sizeof builtin_tls) { #ifndef SYS_mmap2 #define SYS_mmap2 SYS_mmap #endif mem = (void *)__syscall( SYS_mmap2, 0, libc.tls_size, PROT_READ|PROT_WRITE, MAP_ANONYMOUS|MAP_PRIVATE, -1, 0); /* -4095...-1 cast to void * will crash on dereference anyway, * so don't bloat the init code checking for error codes and * explicitly calling a_crash(). */ } else { mem = builtin_tls; } /* Failure to initialize thread pointer is fatal if TLS is used. */ if (__init_tp(__copy_tls(mem)) < 0 && tls_phdr) a_crash(); } #else void __init_tls(size_t *auxv) { } #endif | Mid | [
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Production of isoamylase by Pseudomonas amyloderamosa mutant strain JD210. Nutritional requirements for the production of isoamylase by Pseudomonas amyloderamosa mutant strain JD210 were investigated. The optimal initial pH for enzyme production in shake-flask cultivation was 5.0. Maltose and soybean protein hydrolyzate were found to be the best carbon source and nitrogen source, respectively. The enzyme production was drastically inhibited by Zn+2 and Cu+2. Other metal ions phosphates and surfactants exhibited no significant inhibitory or accelerating effect on enzyme production. According to auxanography and single omission experiments, proline and isoleucine were required for growth. The supplement of 0.1% proline increased enzyme production by around 30% compared with no addition. | Mid | [
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About this home: Overlook the surf and sand from the balcony of this 2-bedroom (and den), 2-bath oceanfront condo, featuring central air conditioning, washer and dryer. Kitchen was renovated in 2013. Just steps to Sea Colony's half mile of private beach and oceanfront pools, this resort condominium features a well-equipped kitchen, including stove, dishwasher, refrigerator and a complete complement of utensils and cookware. Community Amenities & Features: Sea Colony - The Premier Family Beach & Tennis Resort Community - features a half mile of private beach, 12 pools (2 indoor), world class tennis, fitness centers, activities for all ages, community shuttle and year-round security. Sea Colony is ranked among Tennis magazine's Best U.S. Resorts and by Tennis Resorts Online as one of the finest in the world. Sea Colony's oceanfront features five oceanfront pools, plus one indoor and three kiddie pools. The Beach Community also offers exercise facilities and more. The rates below reflect our published rent rates and do not include any additional fees that may be charged at the time of booking. You can always view our best rates and total costs when you hit Quick Quote or Book Now. If you have an eligible promo code, please enter it on the Quick Quote or Book Now screen to obtain the most competitive rates that we offer on your selected accommodation. Start Date End Date Nightly Rate Weekly Rate 08/01/15 08/07/15 From $557.00/night From $2,785.00/week 08/08/15 08/14/15 From $557.00/night From $2,785.00/week 08/15/15 08/21/15 From $501.00/night From $2,507.00/week 08/22/15 08/28/15 From $393.00/night From $1,988.00/week 08/29/15 09/04/15 From $276.00/night From $1,378.00/week 09/05/15 09/11/15 From $265.00/night From $1,298.00/week 09/12/15 09/18/15 From $250.00/night From $1,250.00/week 09/19/15 09/25/15 From $231.00/night From $1,156.00/week 09/26/15 10/13/15 From $219.00/night From $1,095.00/week 10/14/15 01/05/16 From $189.00/night From $946.00/week 01/06/16 03/23/16 From $189.00/night From $946.00/week 03/24/16 05/13/16 From $243.00/night From $1,217.00/week 05/14/16 05/27/16 From $260.00/night From $1,298.00/week 05/28/16 06/03/16 From $293.00/night From $1,461.00/week 06/04/16 06/10/16 From $315.00/night From $1,572.00/week 06/11/16 06/17/16 From $392.00/night From $1,959.00/week 06/18/16 06/24/16 From $399.00/night From $2,014.00/week 06/25/16 07/01/16 From $474.00/night From $2,367.00/week 07/02/16 07/08/16 From $474.00/night From $2,367.00/week 07/09/16 07/15/16 From $501.00/night From $2,507.00/week 07/16/16 07/22/16 From $529.00/night From $2,646.00/week 07/23/16 07/29/16 From $557.00/night From $2,785.00/week 07/30/16 08/05/16 From $557.00/night From $2,785.00/week 08/06/16 08/12/16 From $557.00/night From $2,785.00/week 08/13/16 08/19/16 From $501.00/night From $2,507.00/week 08/20/16 08/26/16 From $393.00/night From $1,988.00/week 08/27/16 09/02/16 From $276.00/night From $1,378.00/week 09/03/16 09/09/16 From $265.00/night From $1,298.00/week 09/10/16 09/16/16 From $250.00/night From $1,250.00/week 09/17/16 09/23/16 From $231.00/night From $1,156.00/week 09/24/16 10/11/16 From $219.00/night From $1,095.00/week 10/12/16 01/05/17 From $189.00/night From $946.00/week There are currently no active reviews for this property, please click below to be the first guest to provide a review. Island House, Sea Colony's most southerly building, features 2-bedroom-and-den and 2-bedroom-den-and-loft condominiums and sits just steps from the community's private beach and right next to Ocean Pool 5 ...more On the southern end of Sea Colony's Beach Community, Harbour House features 2-bedroom-and-den and 2-bedroom-den-and-loft condominiums and is just steps from the community's private beach and next to ...more Destinations and travel times are subject to availability and confirmed on a first come, first served basis. Price includes only accommodations and specifically excludes travel costs and other expenses that may be incurred. Price are based in U.S. dollars (USD), and do not include tax. Promotional discounts may not apply to all properties. Offer may not be combined with any other promotion, discount, or coupon. Other restrictions may apply. Offer void where prohibited by law. | Mid | [
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More Articles Wes Kantor drove through Whitehall this past winter and didn’t like what he saw in the streets. Kids on their way to school were avoiding the snow-clogged sidewalks by walking on the plowed roads. “We’re talking kindergarten to fifth-graders walking in the street,” said Kantor, a Whitehall city councilman. “It was safer to walk in the street ... than to walk in the knee-deep snow on the sidewalk.” Kantor checked with the city’s code-enforcement office to see whether it was enforcing a 1973 ordinance requiring residents to keep their sidewalks clear of snow and ice. It turned out they hadn’t written a citation in more than a decade. And so, Whitehall council members took an unusual action: They wiped the old sidewalk-shoveling rule from the books. “Basically all I did was, you know, some housekeeping,” Kantor said. “It’s kind of ridiculous to have a law on the books that can’t be enforced.” Many central Ohio cities have some form of ordinance addressing who’s responsible for clearing sidewalks. They vary in language — Bexley, for example, excuses people who physically can’t do it and can’t find help — but they all express the same sentiment: Clear it out or face the consequences. But often, there aren’t consequences. Some cities say a 1993 Ohio Supreme Court ruling in a Columbus case where a woman slipped on the snow-covered ice outside of a friend’s home rendered their local ordinances unenforceable. The court said the homeowners weren’t to blame. “Living in Ohio during the winter has its inherent dangers,” Ohio Supreme Court Justice Andrew Douglas wrote, saying that landowners don’t owe it to the general public to remove ice and snow from public sidewalks “even where a city ordinance requires the landowner to keep the sidewalks free of ice and snow.” Still, most cities keep those laws around, either because they do try to enforce them — as in the case of Columbus and Bexley, though punishment in both cities rarely progresses beyond a warning — or because they hope their existence encourages good behavior. Reynoldsburg Mayor Brad McCloud believes the latter works. “We try to appeal to home owners’ good will,” McCloud wrote in an email. “While I never misrepresent what the law is, I also don’t go out of my way to publicize it either.” In Whitehall, the unenforceable law didn’t sit well with Kantor. It felt like intimidation. Instead, he pushed to repeal it and instead form a kind of city volunteer shoveling network. On Tuesday, the council voted unanimously to do away with the old ordinance. “I don’t want anything in the law to intimidate our residents and businesses,” Kantor said. “It just shouldn’t be on the books.” | Low | [
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The Looney Tunes Show The Looney Tunes Show is an American animated sitcom produced by Warner Bros. Animation that ran from May 3, 2011 through August 31, 2014 on Cartoon Network. The series consists of two seasons each containing 26 episodes, and features characters from the Looney Tunes and Merrie Melodies theatrical cartoon shorts updated for the 21st century. On July 29, 2014, it was announced that the series would not be renewed for a third season in favor of Wabbit (2015–2020). A direct-to-video spin-off film named Looney Tunes: Rabbits Run was released on August 4, 2015 Premise The series revolves around roommates Bugs Bunny and Daffy Duck living in a suburb of Los Angeles with "colorful neighbors" and other characters including Lola Bunny, Tina Russo, Porky Pig, Foghorn Leghorn, Elmer Fudd, Sylvester, Tweety, Granny, Gossamer, Yosemite Sam, Speedy Gonzales, Marvin the Martian, Pete Puma and more. The series' episodes contain less slapstick, fewer visual gags and are more adult-oriented and dialogue-driven than has been seen in past Looney Tunes productions such as love triangles, employment and rooming. Wraparound segments The show also features two other segments which wrap around the main plot. These consist of: Merrie Melodies – Approximately two to three-minute music videos (with the exception of "Daffy Duck the Wizard", which runs for around four minutes) showcasing classic characters singing brand new original songs. They appear midway through most of the episodes in Season 1 and at the end of most episodes in Season 2 in place of the Road Runner and Wile E. Coyote shorts. Road Runner and Wile E. Coyote – A series of CGI-animated shorts depicting Wile E. Coyote's attempts to catch the Road Runner. These segments were dropped after season one. Episodes Characters Main Bugs Bunny (voiced by Jeff Bergman) – Bugs Bunny lives a life of upper-middle-class suburban leisure, based on income from a popular Carrot Peeler that he invented. He lives in a well-appointed house, drives a compact car, and provides room and board for his friend, Daffy Duck. He spends his time watching sports on TV, hanging out with his friends and neighbors (mostly drawn from the classic Looney Tunes roster), and dating Lola Bunny (the latter under some protest). He generally plays the straight man to Daffy and Lola's various bouts of insanity, although he is not without his own quirks. He has exhibited somewhat compulsive/addictive tendencies, like having a high caffeine intake with coffee, becoming addicted to an energy drink that had dangerous chemicals in it, nearly leveled his own house in an increasingly deranged attempt to put up a shelf and getting hooked on foods that contain butter. Despite being intelligent, he has shown some level of tomfoolery, such as when he found jail "a smart aleck's paradise" and mistook the Tasmanian Devil for a dog. Daffy Duck (voiced by Jeff Bergman) – Daffy Duck is the roommate of Bugs Bunny. Unlike Bugs and their neighbors, Daffy has no way of earning money and relies on Bugs for food and shelter. He has tried on numerous occasions to get rich quick but ended up failing repeatedly. While Daffy's greed and jealousy of Bugs remains, it appears less antagonistic in the show. In the first episode, Bugs openly admits that Daffy is his best friend, despite his faults. Daffy has worked, and been fired from, numerous jobs due to negligence and/or incompetence. Despite this, however, Daffy has shown to be a very skilled hairdresser and successfully graduated beauty school. Daffy's three possessions that he is proud of are his (broken) blue recliner, his white collar which he always wears (revealed in some episodes to be either a fine pearl choker or just a scrap of fabric), and his Papier-mâché parade float, constructed on top of a pickup truck, which is his main means of transport. Porky Pig (voiced by Bob Bergen) – Porky Pig is one of Bugs Bunny and Daffy Duck's friends. Despite being bright and bookish, Porky has an innocent, naïve quality that Daffy frequently uses to his advantage, tricking Porky into parting with large sums of money or accompanying him in bizarre schemes. Porky originally worked a boring office job, but got fired following Bugs' example. He started his own catering company afterwards. In "Dear John", Porky was shown to have served on the city council. He starts a relationship with Petunia in the end of "Here Comes The Pig". In "Best Friends Redux", Daffy meets Porky's young self and ensures that he becomes good friends with Bugs & Rodney in their cabin, finally showing Porky an act of kindness. Speedy Gonzales (voiced by Fred Armisen) – Speedy Gonzales is an extremely fast mouse who lives with Bugs and Daffy as their "mouse in the wall" and runs a pizza parlor called Pizzarriba. He is occasionally shown to act as Daffy's conscience. The episode "Sunday Night Slice" showed that Bugs bought his favorite restaurant Girardi's to prevent it from being closed and hired Speedy to help him. When Bugs decides he doesn't want to own a restaurant anymore, he hands ownership of it to Speedy who renames it "Pizzarriba". Yosemite Sam (voiced by Maurice LaMarche) – Yosemite Sam is one of Bugs and Daffy's neighbors. He is a liar, a thief and a cheat, amongst other things. Coming from a lower-class background, he tends to steal Bugs' possessions, causing Bugs and Daffy to resent him. His full name was revealed as Samuel Rosenbaum. Lola Bunny (voiced by Kristen Wiig) – Lola is Bugs' scatter-brained, bubbly and obsessive significant other, who has a habit of speaking rapidly, whether anyone else is listening or not. When they first meet, Bugs falls in love with her, but after learning how crazy and ditsy she is, he loses interest and often tries to escape her company. Lola develops a huge obsession with Bugs Bunny that he later finds creepy; Lola is never put off by Bugs' responses to behavior, that include taking photos of him in the shower, spying on him late at night and often stalking him. Later in the series however, Bugs eventually falls in love with Lola again which started when they went to Paris in the episode "Eligible Bachelors" and Bugs manages to stop her talking for a while. Her parents are members of a country club and her father likes Bugs so much that he considers him to be "The son he never had." Lola was redesigned in both appearance and personality to match the series. Tina Russo (voiced by Jennifer Esposito in season one, Annie Mumolo in season two) – A new character original to the show, Tina Russo is a female duck who is Daffy's significant other. She works at a copy store called "Copy Place". Tina is another straight character of the show, with a no-nonsense personality. She first starts dating Daffy because "she likes a project"; she tolerates his selfish and arrogant behavior as she has a keen astuteness which allows her to read between the lines when they first meet; she works out that Daffy is actually insecure and jealous, and that his vain attitude is really a front. Daffy is amazed she works this out so quickly and later reveals Tina, through email, that he can't believe someone "so kind, beautiful, generous, and intelligent" would ever want to be with someone like him. After reading this, Tina is touched, and tells Daffy she loves him. She is based on Melissa Duck from the original theatrical shorts. Recurring Tasmanian Devil (voiced by Jim Cummings) – In this show, the Tasmanian Devil is portrayed as walking on four legs like a real Tasmanian Devil and his eyes are bloodshot red (later turned yellow when Bugs uses a taming trick that Speedy Gonzales taught him). Initially, Bugs believed Taz to be a dog and kept him as a house pet much to Daffy's discomfort. Eventually, Bugs learned the truth and tried to return him to his home in Tasmania only to find out that Taz would rather live with him. When Taz is not causing trouble for Daffy, he has occasionally tried to eat Sylvester. In the episode "Ridiculous Journey," Taz spoke for the first time in the series and had bonded with Sylvester and Tweety while they evaded Blacque Jacques Shellacque. Mac (voiced by Rob Paulsen) and Tosh (voiced by Jess Harnell) – Two goofy gophers who run an antique store. Pete Puma (voiced by John Kassir) – A dimwitted puma who is one of Daffy Duck's friends and does various jobs around town. Marvin the Martian (voiced by Eric Bauza) – A Martian who is one of Daffy Duck's friends. Witch Lezah (voiced by Roz Ryan) – A witch who lives next door to Bugs Bunny and is often annoyed at the antics of Daffy Duck. Witch Lezah is also a hypnotherapist by trade. The character is very similarly based on Witch Hazel, with 'Lezah' being 'Hazel' spelled completely backwards. Gossamer (voiced by Kwesi Boakye) – A large orange furry monster who is Witch Lezah's son. In stark contrast to previous characterizations, Gossamer is portrayed as timid and kind-hearted. Emma Webster "Granny" (voiced by June Foray as an adult, Stephanie Courtney as young Granny) – An old lady who is one of Bugs Bunny's neighbors. Granny is revealed to have been a spy for the Allies in World War II. In "The Grand Old Duck of York," it is revealed that Granny also teaches piano lessons. This series marked the final time Foray provided the voice of Granny before her death in 2017. Sylvester (voiced by Jeff Bergman) – Granny's Tuxedo cat who is always trying to devour Tweety, but always fails when Granny catches him and spanks him hard enough to spit Tweety out. Tweety (voiced by Jeff Bergman) – Granny's Yellow canary who is frequently harassed by Sylvester. Tweety is revealed to have also been a spy for the Allies in World War II during Granny's youth. Foghorn Leghorn (voiced by Jeff Bergman) – Foghorn Leghorn is a rich rooster who has worked under various jobs. He and Daffy get on very well, and are often involved in various schemes. Pepé Le Pew (voiced by René Auberjonois in season one, Jeff Bergman in season two) – Pepé Le Pew is a skunk who's the local Casanova. In the episode "Members Only" he works as a wedding planner when he planned Bugs and Lola's wedding at the country club. Elmer Fudd (voiced by Billy West) – Elmer Fudd is the resident newsman. Wile E. Coyote and the Road Runner – Wile E. Coyote and the Road Runner are shown in short computer-animated segments in season one. They also make small cameos throughout the show. Others Dr. Weisberg (voiced by Garry Marshall) – Dr. Weisberg is a physician who Bugs and the other characters often visit. His appearance resembles to Dr.I.Q. Hi from Duck Dodgers. Walter Bunny (voiced by John O'Hurley) – Lola Bunny's father who idolizes Bugs. He then appears when they play in the father son tennis tournament. He dislikes Daffy. Patricia Bunny (voiced by Grey DeLisle in season one, Wendi McLendon-Covey in season two) – Lola Bunny's mother. Carol (voiced by Grey DeLisle) - A beautiful blonde woman who is Foghorn Leghorn's assistant and limo chauffeur who tries (and fails) to bring reason to Foghorn Leghorn. Henery Hawk (voiced by Ben Falcone) – A Chickenhawk that likes to target chickens. Cecil Turtle (voiced by Jim Rash) – A turtle who formerly worked as a customer service representative at the Trans-Visitron cable company. He later becomes a con artist and an enemy of Bugs Bunny. Frank Russo (voiced by Dennis Farina) – Tina Russo's dad. Slowpoke Rodriguez (voiced by Hugh Davidson) – Speedy Gonzales' cousin who is the Sheriff of Tacapulco, Mexico. Hugo the Abominable Snowman (voiced by John DiMaggio) – A Yeti that lives in Alaska. Blacque Jacque Shellacque (voiced by Maurice LaMarche) – A tracker who is the Canadian cousin of Yosemite Sam. The Three Bears (voiced by Maurice LaMarche, Grey DeLisle, and John DiMaggio) – A family of bears consisting of Henry Bear, Mama Bear, and Junior Bear. Beaky Buzzard (voiced by Jim Cummings) – A buzzard that rescues anyone in the desert in a hot-air balloon. Petunia Pig (voiced by Katy Mixon) – A female pig that Porky develops a relationship with starting in "Here Comes the Pig". Rodney Rabbit (voiced by Chuck Deezy) – A rabbit who is Bugs Bunny's old childhood best friend since summer camp. Production The Looney Tunes Show was first announced in July 2009 by Warner Bros. Animation. However, it was delayed several times before finally premiering on May 3, 2011 on Cartoon Network. The characters feature new designs created by Ottawa artist Jessica Borutski over the course of two years. The animation was produced by Yearim and Rough Draft Korea, along with Toon City Animation in the first season. The Wile E. Coyote and Road Runner CGI shorts were produced by Crew972. Broadcast The Looney Tunes Show premiered in the United States on May 3, 2011 through May 14, 2014 on Cartoon Network. In Australia, the first two seasons of the series began airing on 9Go! and Foxtel channel on Cartoon Network. The Looney Tunes Show premiered in the United States. In Middle East, on Cartoon Network Arabic and MBC3. Home media The Looney Tunes Show has received home video releases for Season 1. It is unknown when Season 2 will get home video releases The first episode was also released on Looney Tunes: Rabbits Run as a special feature. Reception Critical response Critical response to The Looney Tunes Show have been mixed. Though the voice acting has received praise, the series has been criticized for its direction and lack of slapstick, as well as the designs and personality changes of the characters. The show, however, remained consistently popular, garnering an average of 2 million viewers every episode. In a 2010 interview with CBC News, series animator Jessica Borutski said in response to fan criticism of the series' new character designs, that the original designs were intended for adults and that "[it is] time for a new generation to meet the characters." Borutski said, "a fresh, new design is the only way to keep characters alive." Cartoon historian Chris Robinson noted also that the mark the original characters have on fans is indelible and that fans are not receptive to change. "[Fans] just really become attached to these things," Robinson said. "It's just so strongly rooted in their childhood that they're unable to separate themselves." Awards and nominations The Looney Tunes Show has been nominated for three Primetime Emmy Awards. Music Two albums compiling songs from the show have been released digitally by WaterTower Music: Songs from The Looney Tunes Show, Season One (2012) Songs from The Looney Tunes Show, Season Two (2013) References External links The Looney Tunes Show at Cartoon Network Looney Tunes at WarnerBros.com The Looney Tunes Show: More Character Designs Revealed – /Film The Totally Odd Couple Animation Magazine Review: "The Looney Tunes Show" Variety Category:2010s American animated television series Category:2010s American children's television series Category:2010s American sitcoms Category:2011 American television series debuts Category:2014 American television series endings Category:American animated television programs featuring anthropomorphic characters Category:American flash animated television series Category:American animated television spin-offs Category:American children's animated comedy television series Category:American children's animated musical television series Category:Cartoon Network original programming Category:Teletoon original series Category:English-language television programs Category:Looney Tunes television series Category:Television series by Warner Bros. Animation Category:Television series created by Sam Register Category:Television shows set in Los Angeles Category:YTV shows Category:Television series created by Agnes Nixon | Mid | [
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Grace and peace to you in the incredible Name of our Messiah and Lord, Jesus Christ!! As most of you know, I have been invited to attend a gathering called by the Archbishop of Canterbury next week in Canterbury, England. The reasons he has not been able to call a meeting of the Primates of the Communion until this time is because the actions of The Episcopal Church and the Anglican Church of Canada have deeply torn the fabric of trust and fellowship in the Communion. In 2007 the Primates met in Dar es Salaam and unanimously agreed on a course of action to restore the godly fellowship of the Communion by asking these two provinces to repent and return to the Biblical teaching and practice of the Anglican Communion. When they did not repent, the previous Archbishop of Canterbury acted against the consensus of the Primates and ignored the consequences which were imposed. This has made the breach even wider. Since that time, the Global Anglican Future Conference (GAFCON) has met in Jerusalem (2008) and in Nairobi (2013), and through GAFCON, the Anglican Church in North America was birthed in 2009. Since that time our Province in North America has been recognized and is in full communion with the provinces represented by GAFCON and the Global South of the Anglican Communion. These provinces represent the vast majority of the Anglicans in the world and have been our partners in spreading the Good News of Jesus Christ and discipling people in Anglican Christianity. I have been asked many times why I am going. Firstly, as a group the GAFCON Primates all decided together that we would attend in good faith and see if there is a possibility of restoring order to the structures of the Anglican Communion. Secondly, the Archbishop of Canterbury, Justin Welby, invited me in good faith, and like my brother Primates, I am going in good faith. Thirdly, the Anglican Church in North America is now a Partner Province of the Global South who are also planning to attend. Fourthly, to not attempt to bring godly order and unity to the Church would be a sin against the Lord and His bride. I am writing to ask for your prayers, even fasting, as the Lord leads you. I travel to the UK this weekend for the meetings which begin on Monday morning at Canterbury Cathedral. I see no easy answers without repentance and Gospel Truth. Pray for wisdom. Pray for confidence in the Truth of God. Pray for boldness. Pray for humility. Pray for repentance. Pray for healing. What is at stake? It is really not about me or about the Anglican Church in North America. It is the reputation of Jesus Christ. It is the souls of millions of people who are being taught a false Gospel and are being led into spiritual and sexual bondage under the pretense of the Christian Faith. It is about the third largest expression of the Christian Faith being able to unite and bring Christian hope and godliness in the face of violent opposition all around the globe. Personally, I believe this will be an extremely challenging meeting for all involved, but I believe in a big and powerful God!! Thank you in advance for your prayers. “Now to Him who is able to do far more abundantly than we can ask or think, according to the power at work within us, to him be glory in the church and in Christ Jesus throughout all generations” (Ephesians 3:20f, ESV). Your brother in Christ, The Most Rev. Dr. Foley Beach Archbishop and Primate Anglican Church in North America | Mid | [
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789 N.E.2d 784 (2003) 338 Ill. App.3d 386 273 Ill.Dec. 610 Sophia Marie CASTRO, Plaintiff-Appellant, v. John B. BELLUCCI, Indiv. and as an Agent and/or Employee of Family Medicine Specialists, Inc., Family Medicine Specialists, Defendants-Appellees. No. 1-02-0604. Appellate Court of Illinois, First District, First Division. March 31, 2003. *785 Joseph A. Power, Jr., of Power, Rogers & Smith, P.C., of Chicago, for appellant. John A. Terselic, of Swanson, Martin & Bell, of Waukegan, for appellees. Justice O'MALLEY delivered the opinion of the court: Plaintiff, Sophia Marie Castro, appeals from the trial court's grant of dismissal as to portions of count III and count IV of her fourth amended complaint against defendants, Family Medicine Specialists, Inc. (Family Medicine) and John B. Bellucci, M.D. For the reasons that follow, we reverse the judgment of the trial court and remand for further proceedings. The facts necessary to our resolution of this appeal are as follows. On May 7, 1996, Castro had an initial office visit with Dr. Jennifer Bellucci-Jackson for dysfunctional uterine bleeding. Although Dr. Bellucci-Jackson did not take a complete history or perform a complete physical, she was made aware that Castro was experiencing painful headaches. Dr. Bellucci-Jackson scheduled Castro for a pelvic ultrasound. On May 12, Castro experienced a severe headache and dizziness, pursuant to which she was taken to the emergency room of Elmhurst Memorial Hospital. There, she was evaluated and subsequently discharged. On May 14, as a follow-up to both her emergency room visit and her May 7 visit with Dr. Bellucci-Jackson, Castro saw Dr. John Bellucci, one of Dr. Bellucci-Jackson's partners at Family Medicine. Dr. Bellucci was made aware of Castro's headaches and related symptoms. On May 15, Castro's mother, Stella Herrick, telephoned Dr. Bellucci-Jackson and informed her that Castro was suffering from a severe headache and dizziness. Mrs. Herrick wanted to take Castro to a chiropractor; Dr. Bellucci-Jackson stated that she did not know of one to suggest for referral purposes. Later that day, Castro saw W. John Cox, D.C., and underwent cervical manipulation. Castro, who was 31 at the time, subsequently suffered a stroke. On July 15, 1996, Castro filed a complaint at law against Dr. Cox and John Cox Chiropractic, Ltd., in which she alleged that Dr. Cox negligently failed to perform a neurologic exam prior to administering cervical manipulation. Castro filed a first amended complaint on May 12, 1998. Relevant to our decision here, in her first amended complaint, Castro named Drs. Bellucci and Bellucci-Jackson as respondents in discovery.[1] Both were subsequently deposed. *786 On February 11, 1999, Castro filed a second amended complaint, in which she converted Dr. Bellucci to a defendant on the basis of the May 14, 1996, visit. Specifically, Castro alleged in count VII of that complaint that Dr. Bellucci was negligent in one or more of the following respects: "(a) [he] failed to perform appropriate neurologic examination on SOPHIA prior to chiropractic treatment; or (b) [he] failed to refer SOPHIA to a neurologist; or (c) [he] was otherwise negligent in treating SOPHIA." Family Medicine was also named as a defendant, based upon its agency relationship with Dr. Bellucci.[2] On April 16, 1999, Dr. Bellucci-Jackson was dismissed from the case. On August 10, 2001, Castro filed a fourth amended complaint. The initial counts are essentially the same as the second amended complaint in that they are directed against Family Medicine through its agent, Dr. John Bellucci. Count III includes the following allegations: Castro's May 13 appointment with Dr. Jennifer Bellucci-Jackson was changed to May 14 at a different location; on May 14 Castro was evaluated by Dr. Bellucci; Dr. Belluci was negligent in his diagnosis and treatment on May 14 and those negligent acts were the direct and proximate cause of Castro's injuries. Count IV, however, is different in that 16 paragraphs of count IV make specific reference to allegedly negligent conduct on the part of Dr. Jennifer Bellucci-Jackson on dates in May 1996, when she either saw plaintiff or spoke with her mother on the phone. These allegations are identical or at least substantially the same (i.e. failing to diagnose and treat symptoms of potential stroke) as those alleged against her colleague, Dr. John Bellucci. Count IV alleges that Family Medicine, through its agents, was negligent in one or more of the following respects: "(a) failing to refer SOPHIA to a neurologist; or (b) failing to properly diagnose Sophia's condition; or (c) failing to properly evaluate and assess Sophia's condition; or (d) [was] otherwise negligent in treating SOPHIA." The physician's certificate of merit attached to the fourth amended complaint identifies the conduct of Dr. Jennifer Bellucci-Jackson as the basis of the amended claims against Family Medicine. Family Medicine moved to dismiss those portions of count III that made reference to physicians other than Dr. John Bellucci and dates other than May 14, 1996, and count IV in its entirety, on the grounds that these claims are barred by the applicable statutes of limitations and repose. On November 13, 2001, the trial court granted that motion with prejudice pursuant to section 2-619(a)(5) of the Code of Civil Procedure (the Code), finding that the claims at issue are time-barred. 735 ILCS 5/2-619(a)(5) (West 1998). On January 30, 2002, the trial court granted plaintiff's request for a finding pursuant to Supreme Court Rule 304(a) (155 Ill.2d R. 304(a)) that there was no just reason to delay enforcement or appeal of the November 13 order of dismissal. *787 In this timely appeal, Castro contends that the trial court's dismissal of portions of count III and all of count IV was in error, because the claims at issue relate back to the timely filed second amended complaint under section 2-616(b) of the Code. 735 ILCS 5/2-616(b) (West 1998). Review of a trial court's order granting dismissal pursuant to section 2-619 is de novo. Epstein v. Chicago Board of Education, 178 Ill.2d 370, 383, 227 Ill. Dec. 560, 687 N.E.2d 1042 (1997). The question on appeal is "whether the existence of a genuine issue of material fact should have precluded the dismissal or, absent such an issue of fact, whether dismissal is proper as a matter of law." Kedzie & 103rd Currency Exchange v. Hodge, 156 Ill.2d 112, 116-17, 189 Ill.Dec. 31, 619 N.E.2d 732 (1993). The statute of limitations for a medical malpractice action is found in section 13-212(a) of the Code and provides: "[N]o action for damages for injury or death against any physician * * * arising out of patient care shall be brought more than 2 years after the date on which the claimant knew, or through the use of reasonable diligence should have known, or received notice in writing of the existence of the injury or death for which damages are sought in the action, whichever of such date occurs first, but in no event shall such action be brought more than 4 years after the date on which occurred the act or omission or occurrence alleged in such action to have been the cause of such injury or death." 735 ILCS 5/13-212(a) (West 1998). Castro's fourth amended complaint, filed over five years after the events giving rise to the claims of medical negligence, is accordingly time-barred unless the amendments "relate back" to the second amended complaint, in which Family Medicine was first made a party defendant. Section 2-616 governs amendments to pleadings filed after the statute of limitations period has expired. That section provides in relevant part: "(b) The cause of action * * * set up in any amended pleading shall not be barred by lapse of time under any statute or contract prescribing or limiting the time within which an action may be brought or right asserted, if the time prescribed or limited had not expired when the original pleading was filed, and if it shall appear from the original and amended pleadings that the cause of action asserted * * * in the amended pleading grew out of the same transaction or occurrence set up in the original pleading * * *." 735 ILCS 5/2-616(b)(West 1998). The purpose of section 2-616(b) is to insure fairness to litigants rather than to unduly enhance the technical considerations of common law pleadings. Sompolski v. Miller, 239 Ill.App.3d 1087, 1090, 180 Ill.Dec. 932, 608 N.E.2d 54 (1992), citing Albany Park Service, Inc. v. Kenny-Pashen Joint Venture, 209 Ill.App.3d 432, 436, 154 Ill.Dec. 230, 568 N.E.2d 230 (1991); United Parcel Service v. Church's Fried Chicken, Inc., 174 Ill.App.3d 378, 380, 123 Ill.Dec. 822, 528 N.E.2d 367 (1988). To further this purpose, this court should liberally construe the requirements of section 2-616(b) in favor of hearing a plaintiff's claim. Sompolski, 239 Ill.App.3d at 1090, 180 Ill.Dec. 932, 608 N.E.2d 54, citing Williams v. Board of Education, 222 Ill. App.3d 559, 565, 165 Ill.Dec. 78, 584 N.E.2d 257 (1991). "Medical malpractice plaintiffs, in particular, are afforded every reasonable opportunity to establish a case, and to this end, amendments to pleadings are liberally allowed to enable the action to be heard on the merits rather than brought to an end because of procedural technicalities." Avakian v. Chulengarian, *788 328 Ill.App.3d 147, 154, 262 Ill.Dec. 663, 766 N.E.2d 283 (2002). Central to our inquiry is the question of whether the record reveals that the defendant was on notice, before the expiration of the statutory time period, of the facts upon which the claim set out in the amended complaint is based. Cammon v. West Suburban Hospital Medical Center, 301 Ill.App.3d 939, 946, 235 Ill.Dec. 158, 704 N.E.2d 731 (1998), citing Wolf v. Meister-Neiberg, Inc., 143 Ill.2d 44, 46-48, 155 Ill.Dec. 814, 570 N.E.2d 327 (1991). In determining whether the subsequent pleading relates back to the filing of the initial pleading, the focus is not on the nature of the causes of action, but on the identity of the transaction or occurrence. Zeh v. Wheeler, 111 Ill.2d 266, 272-73, 95 Ill.Dec. 478, 489 N.E.2d 1342 (1986); Figueroa v. Illinois Masonic Medical Center, 288 Ill.App.3d 921, 924, 224 Ill.Dec. 82, 681 N.E.2d 64 (1997). However, the cause of action asserted in the later complaint need not be identical to or substantially the same as the claim raised in the original pleading. Weber v. Cueto, 253 Ill.App.3d 509, 516, 191 Ill.Dec. 593, 624 N.E.2d 442 (1993). Relation back will be allowed where the defendant has been made aware of the occurrence or transaction that is the basis for the plaintiff's claim. Zeh, 111 Ill.2d at 279, 95 Ill.Dec. 478, 489 N.E.2d 1342. The rationale for this rule is that a defendant will not be prejudiced so long as his attention has been directed within the limitations period to the facts that form the basis of the claim asserted against him. Zeh, 111 Ill.2d at 273, 95 Ill.Dec. 478, 489 N.E.2d 1342, citing Simmons v. Hendricks, 32 Ill.2d 489, 495, 207 N.E.2d 440 (1965). Family Medicine contends that its attention was not directed to the allegations at issue in the fourth amended complaint prior to the expiration of the statutes of limitations and repose. On the contrary, Family Medicine argues, the original complaint did not involve Family Medicine, Dr. John Bellucci or Dr. Jennifer Bellucci-Jackson. Both Drs. Bellucci and Bellucci-Jackson were named as respondents in discovery in the first amended complaint, after which the second amended complaint named only Dr. Bellucci as a defendant (and Family Medicine as Dr. Bellucci's principal). Dr. Bellucci-Jackson was dropped from the lawsuit entirely. As such, Family Medicine asserts, there was no reason for it to have explored the potential negligence of Dr. Bellucci-Jackson in the discovery that has taken place thus far in the litigation. Castro insists that the fourth amended complaint neither adds party defendants nor sets forth any new theories of liability. According to Castro, the allegations against Family Medicine (already a defendant) made in the fourth amended complaint grew out of the same occurrence alleged in the second amended complaint, i.e., the conduct of Family Medicine via its employee or agent prior to Castro's May 15, 1996, stroke. This, she urges, constitutes sufficient notice to trigger the application of the relation back doctrine. In support, Castro relies upon the holdings in McArthur v. St. Mary's Hospital of Decatur, 307 Ill.App.3d 329, 240 Ill.Dec. 408, 717 N.E.2d 501 (1999), Cammon v. West Suburban Hospital, 301 Ill.App.3d 939, 235 Ill.Dec. 158, 704 N.E.2d 731 (1998), and Marek v. O.B. Gyne Specialists, II, S.C., 319 Ill.App.3d 690, 253 Ill. Dec. 759, 746 N.E.2d 1 (2001). In McArthur, the plaintiff sued the defendant hospital and several defendant doctors for the death of a baby due to complications during the birth process. In the original complaint, the only allegation made against the hospital was that it "`[f]ailed to implement and/or enforce a *789 policy requiring a permanent radiographic image of all ultrasound sonogram examinations be maintained.'" McArthur, 307 Ill. App.3d at 331, 240 Ill.Dec. 408, 717 N.E.2d 501. The allegations against other defendants included the failure to correctly read the sonograms and X rays taken and the failure to diagnose the hydrocephalus from which the deceased infant suffered. First and second amended complaints were subsequently filed with the same sole allegation against the hospital. McArthur, 307 Ill.App.3d at 331-32, 240 Ill.Dec. 408, 717 N.E.2d 501. Discovery proceeded among the parties, and during the deposition of one of the defendant radiologists, it was discovered that the radiologist never evaluated the X rays at issue and that, instead, one of the hospital technicians had that responsibility. McArthur, 307 Ill.App.3d at 332, 240 Ill. Dec. 408, 717 N.E.2d 501. Though outside of the statute of limitations period by that time, the plaintiffs moved for leave to file a third amended complaint, in which seven new allegations were added against the hospital, relating to the negligent interpretation of the sonogram and X rays by one of its agents on a date different from that specified in earlier complaints. The hospital moved for and was granted summary judgment, arguing that the new allegations set forth different conduct by different people than in the original pleadings, and were therefore time barred. McArthur, 307 Ill.App.3d at 333, 240 Ill. Dec. 408, 717 N.E.2d 501. This court reversed, finding that from the beginning of the litigation, the hospital was aware that the plaintiffs were asserting negligence in connection with the reading of the sonogram and X ray in that these claims had already been asserted against certain agents of the hospital (the doctors). The court found neither prejudice nor unfair surprise to the hospital in allowing the amended claims to relate back, since the hospital knew the involvement of its own personnel in the reading of the films from the suit's inception. McArthur, 307 Ill. App.3d at 336, 240 Ill.Dec. 408, 717 N.E.2d 501. In Cammon, the defendant hospital was sued vicariously in the original complaint for the negligence of three doctors in misinterpreting the decedent's CT scans. In separate counts, the defendant surgeon was accused of failing to achieve adequate hemostasis (arrest of bleeding) following surgery on the decedent. Cammon, 301 Ill.App.3d at 942, 235 Ill.Dec. 158, 704 N.E.2d 731. After summary judgment motions by certain defendants, the plaintiff voluntarily dismissed all of the defendants except for the hospital and the surgeon. Although the original complaint specifically attributed negligence in decedent's postoperative care to the surgeon and not the hospital (other than as his employer), the plaintiff filed a second amended complaint, after the statute of limitations had run, in which she asserted several claims against the hospital itself for the acts and omissions of unnamed nurses, residents, medical technicians, anesthesiologists and other health care professionals for the failure to achieve adequate hemostasis. Cammon, 301 Ill.App.3d at 943, 235 Ill.Dec. 158, 704 N.E.2d 731. The trial court granted the hospital's motion for dismissal of the hemostasis allegations against hospital employees other than the surgeon originally named pursuant to section 2-619(a)(5). Although the negligence alleged against the hospital involved different conduct by different persons than alleged against the hospital in the original complaint, this court reversed. Specifically, the court in Cammon stated that because an allegation related to the failure to achieve adequate hemostasis was made against the surgeon in the original *790 complaint, claims related to the decedent's surgery in the amended complaint related back to the original complaint. Cammon, 301 Ill.App.3d at 947, 235 Ill.Dec. 158, 704 N.E.2d 731. The court reasoned that, based on the record, the defendant hospital was put on notice from the outset of the litigation, prior to the expiration of the limitations period, that the plaintiff was claiming that a failure to achieve adequate hemostasis in connection with the abdominal wall surgery was a proximate cause of the decedent's injury and subsequent death. Cammon, 301 Ill.App.3d at 947, 235 Ill.Dec. 158, 704 N.E.2d 731. Most recently, in Marek, the plaintiff appealed the trial court's dismissal of her second amended complaint against the defendant entity, O.B. Gyne, based on the running of the statute of limitations. The original complaint named O.B. Gyne and several other defendants, and alleged that these medical care providers failed to properly diagnose, advise and treat her for breast cancer. Marek, 319 Ill.App.3d at 691, 253 Ill.Dec. 759, 746 N.E.2d 1. In count III of her original complaint, the plaintiff sued Dr. Lupo for negligence, and sued O.B. Gyne, Dr. Lupo's employer, as a principal. In count I of her second amended complaint, filed well after the statute of limitations had run, the plaintiff alleged that her gynecologist, Dr. McGill, was an agent of O.B. Gyne, upon his retirement all of his records became the property of O.B. Gyne and, therefore, O.B. Gyne was directly negligent for failing to advise Marek of the abnormalities discovered in a mammography report subsequent to Dr. McGill's retirement. Marek, 319 Ill. App.3d at 694, 253 Ill.Dec. 759, 746 N.E.2d 1. In count II of her second amended complaint, Marek alleged that she was unaware of her direct cause of action against O.B. Gyne until it answered discovery, at which time she determined that O.B. Gyne possessed McGill's records and only after this discovery did she realize that a direct cause of action existed against O.B. Gyne. Marek, 319 Ill.App.3d at 694, 253 Ill.Dec. 759, 746 N.E.2d 1. Further, the second amended complaint alleged that Lupo was negligent by failing to refer Marek for further diagnostic testing. This court reversed the trial court's dismissal of the entire case and remanded, holding that O.B. Gyne's attention was directed to the allegations of negligence made against its agent at the time the original complaint was filed, despite the fact that the allegations made against it directly in earlier complaints were based upon the conduct of a different agent. The court reasoned that because O.B. Gyne had been made aware of the occurrence that formed basis for the claim (the failure to properly diagnose and treat the plaintiff's cancer), it was able to adequately prepare to meet the plaintiff's claims regardless of the theory under which they were brought. Marek, 319 Ill.App.3d at 698, 253 Ill.Dec. 759, 746 N.E.2d 1, citing Zeh, 111 Ill.2d at 279, 95 Ill.Dec. 478, 489 N.E.2d 1342. We find the reasoning employed in McArthur, Cammon and Marek to be persuasive in the case at bar and reflective of the court's liberal application of the relation back doctrine to achieve resolution on the merits in medical malpractice cases. First, we note that the second amended complaint naming Dr. John Bellucci and Family Medicine as defendants was filed within the statutory period and it is that complaint which is relevant in our analysis. The second amended complaint essentially alleged that Dr. John Bellucci and vicariously, Family Medicine, were negligent in failing to identify and diagnose plaintiff's symptoms which proximately led to a stroke. Four years later and outside the statutory period, plaintiff filed a fourth *791 amended complaint claiming that a different agent, Dr. Jennifer Bellucci-Jackson (as well as Family Medicine, which was already named) was negligent for the same conduct and on related, but different, dates in May 1996. Family Medicine does not dispute that Dr. Bellucci-Jackson was also its employee and agent in May 1996 when she saw Castro at the clinic. As such, Family Medicine was, at all relevant times, aware that Dr. Bellucci-Jackson was involved in Castro's treatment. Though Family Medicine claims to have been prejudiced by the lack of focus on the actions of Dr. Bellucci-Jackson, we find that it was nevertheless supplied with the essential information necessary to prepare a defense to a claim related to her part in the same occurrence, when the identical allegations were later leveled with respect to her conduct. See Zeh, 111 Ill.2d at 272-73, 95 Ill.Dec. 478, 489 N.E.2d 1342. We believe that Family Medicine was aware, from the outset, of plaintiff's potential claim against Dr. Bellucci-Jackson because she treated Castro for the same symptomsalbeit on dates immediately prior and subsequent to the time she was seen by Dr. John Bellucci. The fact that she was dismissed from the case after being named a respondent in discovery does not diminish our conviction that the hospital was aware of this agent's role in plaintiff's treatment long before her dismissal. Family Medicine, therefore, had the opportunity to investigate. Family Medicine, however, contends that the allegations contained in Counts III and IV of the fourth amended complaint "vastly broaden" its exposure in that they allege different conduct as grounds for vicarious liability and new dates on which the allegedly negligent conduct occurred. In support, Family Medicine relies on Bailey v. Petroff, 170 Ill.App.3d 791, 121 Ill.Dec. 472, 525 N.E.2d 278 (1988). In Bailey, the plaintiff's child was born with serious birth defects. In her original complaint, the plaintiff alleged medical malpractice against the defendant doctor in that he: "(a) Negligently and carelessly gave plaintiff, Barbara Bailey, a prescription for the drug Bendectin when defendant knew or should have known of its ability to cause birth defects; (b) Negligently and carelessly failed to keep informed of the medical literature concerning adverse effects of Bendectin when prescribed for pregnancy; (c) Failed to recommend the proper dosage of Bendectin for the plaintiff, Barbara Bailey." Bailey, 170 Ill.App.3d at 793-94, 121 Ill.Dec. 472, 525 N.E.2d 278. After the expiration of the statute of limitations period, the plaintiff filed a first amended complaint, in which she dropped all references to the prescribing of the drug Bendectin and instead alleged: "(a) Defendant [doctor] negligently and carelessly failed to inform the plaintiff that the complications of her pregnancy were not normal; (b) Defendant negligently and carelessly failed to inform the plaintiff of the availability of diagnostic tests to detect abnormalities of fetuses; (c) Defendant negligently and carelessly failed to prescribe diagnostic tests to determine whether the fetus was normal; (d) Defendant negligently and carelessly assured the plaintiff that her pregnancy was proceeding normally, when there was reason to believe that it was not." Bailey, 170 Ill.App.3d at 794, 121 Ill. Dec. 472, 525 N.E.2d 278. Affirming the trial court's dismissal of the first amended complaint on the grounds that it was time barred and did *792 not relate back to the original complaint, the court in Bailey noted that the negligent conduct alleged in the two complaints was wholly different. In particular, the original complaint charged active negligence in the form of prescribing a drug that was known to cause birth defects, whereas the first amended complaint abandoned that approach altogether and instead charged negligence based on the failure to recommend prenatal testing and to otherwise diagnose the baby's disorder. Bailey, 170 Ill.App.3d at 797-98, 121 Ill. Dec. 472, 525 N.E.2d 278. Stating that this was "obviously" not "a situation where the two versions of the complaint merely set forth different theories of liability," the court concluded that the original complaint did not adequately inform the defendant of the facts necessary to investigate the claim that was ultimately asserted against him in the second amended complaint. Bailey, 170 Ill. App.3d at 798, 121 Ill.Dec. 472, 525 N.E.2d 278, citing Whitney v. City of Chicago, 155 Ill.App.3d 714, 719, 108 Ill.Dec. 132, 508 N.E.2d 293 (1987). We find Bailey distinguishable. Here, it was Castro's theory, from the time Family Medicine was first named, that the failure to properly diagnose and treat Castro's symptoms proximately caused her to suffer a stroke. Unlike Bailey, Castro did not drop all or any of the allegations contained in her second amended complaint, nor did she replace allegations earlier stated with ones that are entirely new. On the contrary, the earlier made allegations of negligence are repeated in the fourth amended complaint, and the facts upon which the claims in counts III and IV of the complaint are based did not change, despite the fact that the conduct of a different agent or agents were called into question. We find this case more analogous to McArthur where the court stated: "Because these allegations were made against the hospital's codefendants and were at the heart of plaintiff's case, the hospital was aware of them and knew the extent of the involvement of its own personnel." McArthur, 307 Ill.App.3d at 335, 240 Ill.Dec. 408, 717 N.E.2d 501. Accordingly, we are unable to conclude that Family Medicine suffered prejudice or unfair surprise as a result of the additional claims. For the reasons set forth herein, we determine that Family Medicine was adequately apprised, before the expiration of the statutory time period, of the facts upon which the claims set out in counts III and IV of the fourth amended complaint are based. The trial court's order dismissing those claims is therefore reversed, and the cause remanded for further proceedings. Reversed and remanded. GORDON, P.J., and McNULTY, J., concur. NOTES [1] Drs. Richard De Angelo and Lee Nicholas Dennis, their professional corporations and Elmhurst Hospital were also named as respondents in discovery. Dr. De Angelo and Elmhurst Hospital were later converted to defendants in a third amended complaint. Their inclusion is not a subject of this appeal. [2] Count VII of the second amended complaint contained identical allegations and was brought on behalf of Castro's husband, Conrad, for loss of consortium. | Mid | [
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STYLE: Pure silk printed tunic with silver work neckline and assymetrically placed embroided bunches worked in silver, ivory and gold thread with outlines in print in silver. BELT: Optional fabric belts given for the youth without any loop on outfit.Fabric: Pure SilkColor: GreenEnsemble: 1 PCDelivery Time: 30 Working days. | Low | [
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Soup Hams Thick cut slices of pasture raised ham. These juicy cuts of pork come out great when they are cooked slowly in juices or with your favorite pea soup recipe. To achieve maximum tenderness I recommend cooking them 20 min. w/ a cup of water in a pressure cooker or try my pea soup recipe (Ask to have it included w/ purchase of ham steak!) | Low | [
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Beer Guide 2014: Stickmen Open-air kitchens are one thing, open-air breweries are another. After you finally find a parking spot in the Albertsons lot and scramble across busy State Street, you open the door to Stickmen Brewery to find yourself enveloped in clouds of steam and bleach stink. Thirst, gone. Then, you see Stickmen’s food menu, a terrifying and slightly racist mish-mash of pub food and Asian fusion. (Ho’tasian buns—seriously?) Still, the views of the lake are glorious. The waitstaff is friendly and accommodating. And the beer is palatable, if leaning to the sweet side. Avoid the darker beers, which range from so-so to downright bad. The coffee porter, in particular, is like sucking on old grounds. But a seasonal saison incorporates Hood River apple cider and is crisp and dry, and the most popular beer, the imperial kolsch Big Honey, appeals to anyone who has ever taken a sip of golden Pilsner and thought, “Hmm, I’m just not getting drunk fast enough.” In the summer, though, we’ll look past everything to bask on that lakeside patio. ADRIENNE SO. DRINK THIS: Bananas on Fire, a dunkelweizen with a nice vanilla finish. | Low | [
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291 S.W.2d 22 (1956) Hattie WHITE, Individually, et al., Appellants, v. Elijah M. HOGGE, Administrator of Estate of Guar Fyffe, et al., Appellees. Court of Appeals of Kentucky. June 1, 1956. *23 Diederich & Lycan, Ashland, for appellants. Lester Hogge, Morehead, B. E. Mullins, W. A. Johnson, Paintsville, James H. Moore, Jr., Ashland, for appellees. Diederich & Lycan, Ashland, for Rainbow Production Corp. CULLEN, Commissioner. The judgment appealed from determined the rights of the widow and children of Robert Fyffe, deceased, in certain real estate he had owned during his lifetime. Involved in the determination were Robert Fyffe's will, two deeds executed by him prior to his death, and the statutes of descent, particularly KRS 391.020(2) and 391.050. The statutes of descent were involved because one of the children, an infant, died shortly after his father's death. This child, and two brothers, were children of Robert Fyffe by a second wife. There also were four other children by a first wife. The judgment determined the rights of the parties on the basis that the two deeds in question were invalid because of non-delivery, and on the basis that the share the deceased child received under the will *24 passed in equal shares to the other six children of Robert Fyffe as ancestral property, under KRS 391.020(2). The widow and the two children by her contend that the deeds were validly delivered; also that under KRS 391.050 the other four children should have received only half-shares in the estate of the deceased child. The widow also claims an interest by inheritance from the deceased child. Robert Fyffe's will was executed in April 1948. It devised his entire estate to his widow and to his three children by her (Guar, Homer and Cassie), in equal shares, with a provision that if his widow should remarry her share should go to the three children in equal shares. The four children by his first wife were expressly excluded from any share in his estate. In August 1948 Robert Fyffe executed deeds (in which his wife joined) conveying one tract of his land to his son Guar, and the remaining tracts to his sons Homer and Cassie. The deed to Guar contained this clause: "Life control of the said lands is reserved by the grantors so long as either or both of them may live and this includes all rentals and royalties and income from or connected with the oil and gas under said lands. But the life control reserved by and in favor of Hattie Fyffe shall continue only so long as she remains the widow of Robert Fyffe. After the termination of said life controls, the rentals, royalties and income from the said property from oil and gas is to go in three equal parts to the grantee, Guar Fyffe and his two brothers, Homer Paul Fyffe and Cassie Francis Fyffe." The deed to Homer and Cassie contained a similar clause. The circumstances with respect to the alleged delivery of these deeds will be discussed at a later point in this opinion. In March 1950 Robert Fyffe died. In 1953 the widow remarried. In 1954 the son Guar, an infant, died intestate. The basic questions concern what interest Guar had in the estate, and what happened to his interest upon his death. Initially, these questions depend upon whether the deeds were validly delivered. The widow was the only witness to testify concerning delivery. She said that following execution of the deeds she, at her husband's request, put the deeds in a lock box in the bank. Previously she had put the will in the same box. The deeds and the will were the only things kept in the box. Her husband had arranged for the rental of the box, but she kept in her possession the only key to the box. After the deeds had been put in the box they remained there until after her husband's death, when she removed them and had them recorded. At the time the deeds were executed the three children named as grantees were, respectively, ten, six and two and one-half years of age. The widow was asked, in her deposition, "Were you taking care of these deeds for yourself and your children?", and answered in the affirmative. We think it is clear that a valid delivery was effected if Robert Fyffe, in handing the deeds to his wife with directions to place them in the lock box, intended to relinquish control of the deeds. In the absence of any express statement of intent, the question must be determined by an evaluation of all the circumstances, and in so doing resort may be had to certain so-called presumptions. In the case of voluntary deeds, particularly family settlement deeds, the law presumes more in favor of delivery than in the case of deeds of bargain and sale. Preston v. Harlow, 276 Ky. 799, 125 S.W.2d 726; 26 C.J.S., Deeds, § 183, p. 592. The fact that a deed contains a reservation of a life estate in the grantor has been held to create a strong presumption of delivery, on the theory that the reservation indicates an intent that title should immediately vest in the grantee. 26 C.J.S., Deeds, § 183, p. 592. *25 In Pittmon v. Flowers, 131 Ky. 804, 115 S.W. 786, it was held that where a deed conveying land to an infant was delivered to the infant's mother, with no specific directions, there was a presumption of delivery to the child. See also Beatty v. Beatty, 151 Ky. 547, 152 S.W. 540, and Bates v. Hall, 305 Ky. 467, 204 S.W.2d 487. It is true that in the last three cases the grantor was a person other than the parent of the child, but the cases nevertheless are in point on the proposition that the law favors a finding of delivery where the grantee is an infant. There is considerable authority from other jurisdictions recognizing a presumption in favor of delivery where the grantee is an infant, especially where the grantor is the parent. 16 Am. Jur., Deeds, sec. 385, p. 656. Another fact in the case before us, supporting a finding of delivery, is that the wife was herself a partial grantee, who was entitled to accept delivery on behalf of all the grantees. 16 Am.Jur., Deeds, sec. 150, p. 522. We think some significance can be given to the fact that Robert Fyffe, after he had handed the deeds to his wife, did not attempt to exercise any further control over the deeds, or do any act inconsistent with the view that he had made an effective conveyance to his sons. In view of all the circumstances, we are constrained to hold that a valid delivery of the deeds was effected, and that the lower court erred in its holding to the contrary. The next question concerns the devolution, upon Guar Fyffe's death, of the property he received under the deed to him and under the will. Because Guar was not named as a grantee in the deed to his brothers, and they were not named as grantees in the deed to him, the attempted disposition of part of the oil and gas royalties, by the deeds, was ineffective, and thus a share in this part passed to Guar under the will. See Sword v. Sword, Ky., 252 S.W.2d 869. The lower court held that since the property Guar received, both under the deed and under the will, was derived by gift or devise from his father, it passed to the father's kindred under KRS 391.020(2), and since the four children by the first wife bore the same relationship to the father as the two surviving children by the second wife, each of the six received an equal share. The appellants maintain that KRS 391.050 also must be considered, and therefore the four children by the first wife, being collaterals of the half blood as to Guar, should receive only one-half shares. It is their contention that KRS 391.020(2) operates only to exclude the mother's kindred, and that the surviving children take, not as lineal descendants from the father, but as collaterals on the father's side. The contention of the appellants is supported by Talbott's Heirs v. Talbott's Heirs, 56 B.Mon. 1, and King v. Middles-borough Town & Lands Co., 106 Ky. 73, 50 S.W. 37, 1108. However, upon reconsideration of the question, it is our opinion that those cases made an erroneous interpretation of the statutes, and they hereby are overruled. We think that KRS 391.020(2), in stating that the estate "shall descend to that parent and that parent's kindred," means what it says, and that the descent is to be determined in accordance with the relationship of the kindred to the parent rather than to the deceased child. A contention advanced on behalf of the widow is that the interest created in her, by the deeds, in the oil and gas royalties, was something in excess of or different from an ordinary life estate terminable on remarriage; that upon her remarriage this interest did not terminate but remained in existence as a separate estate for the remainder of her life, and passed to her three children as a "shifting use." Accordingly, she argues, when Guar died she inherited, either under KRS 391.010 or 391.020(2), his share of this shifting use estate. We think this argument employs too much artificial theory of the law of property to warrant acceptance. The clear meaning *26 of the deeds is that upon the widow's remarriage, her interest should terminate. Whatever interests Guar received in the property he received by gift or devise from his father, and not from his mother. The parties seem to be in agreement as to what fractional division of the property will result from the conclusions we have reached in this opinion so there is no need to encumber the opinion by an enumeration of the fractional share each child will receive. The judgment is reversed in part and affirmed in part, with directions to enter a judgment in conformity with this opinion. HOGG, J., not sitting. | Low | [
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Q: Improve performance of COUNT/GROUP-BY in large PostgresSQL table? I am running PostgresSQL 9.2 and have a 12 column relation with about 6,700,000 rows. It contains nodes in a 3D space, each one referencing a user (who created it). To query which user has created how many nodes I do the following (added explain analyze for more information): EXPLAIN ANALYZE SELECT user_id, count(user_id) FROM treenode WHERE project_id=1 GROUP BY user_id; QUERY PLAN --------------------------------------------------------------------------------------------------------------------------- HashAggregate (cost=253668.70..253669.07 rows=37 width=8) (actual time=1747.620..1747.623 rows=38 loops=1) -> Seq Scan on treenode (cost=0.00..220278.79 rows=6677983 width=8) (actual time=0.019..886.803 rows=6677983 loops=1) Filter: (project_id = 1) Total runtime: 1747.653 ms As you can see, this takes about 1.7 seconds. This isn't too bad considering the amount of data, but I wonder if this can be improved. I tried to add a BTree index on the user column, but this didn't help in any way. Do you have alternative suggestions? For the sake of completeness, this is the complete table definition with all it's indices (without foreign key constraints, references and triggers): Column | Type | Modifiers ---------------+--------------------------+------------------------------------------------------ id | bigint | not null default nextval('concept_id_seq'::regclass) user_id | bigint | not null creation_time | timestamp with time zone | not null default now() edition_time | timestamp with time zone | not null default now() project_id | bigint | not null location | double3d | not null reviewer_id | integer | not null default (-1) review_time | timestamp with time zone | editor_id | integer | parent_id | bigint | radius | double precision | not null default 0 confidence | integer | not null default 5 skeleton_id | bigint | Indexes: "treenode_pkey" PRIMARY KEY, btree (id) "treenode_id_key" UNIQUE CONSTRAINT, btree (id) "skeleton_id_treenode_index" btree (skeleton_id) "treenode_editor_index" btree (editor_id) "treenode_location_x_index" btree (((location).x)) "treenode_location_y_index" btree (((location).y)) "treenode_location_z_index" btree (((location).z)) "treenode_parent_id" btree (parent_id) "treenode_user_index" btree (user_id) Edit: This is the result, when I use the query (and index) proposed by @ypercube (query takes about 5.3 seconds without EXPLAIN ANALYZE): EXPLAIN ANALYZE SELECT u.id, ( SELECT COUNT(*) FROM treenode AS t WHERE t.project_id=1 AND t.user_id = u.id ) AS number_of_nodes FROM auth_user As u; QUERY PLAN ---------------------------------------------------------------------------------------------------------------------------------------------------------- Seq Scan on auth_user u (cost=0.00..6987937.85 rows=46 width=4) (actual time=29.934..5556.147 rows=46 loops=1) SubPlan 1 -> Aggregate (cost=151911.65..151911.66 rows=1 width=0) (actual time=120.780..120.780 rows=1 loops=46) -> Bitmap Heap Scan on treenode t (cost=4634.41..151460.44 rows=180486 width=0) (actual time=13.785..114.021 rows=145174 loops=46) Recheck Cond: ((project_id = 1) AND (user_id = u.id)) Rows Removed by Index Recheck: 461076 -> Bitmap Index Scan on treenode_user_index (cost=0.00..4589.29 rows=180486 width=0) (actual time=13.082..13.082 rows=145174 loops=46) Index Cond: ((project_id = 1) AND (user_id = u.id)) Total runtime: 5556.190 ms (9 rows) Time: 5556.804 ms Edit 2: This is the result, when I use an index on project_id, user_id (but no schema optimization, yet) as @erwin-brandstetter suggested (the query runs with 1.5 seconds at the same speed as my original query): EXPLAIN ANALYZE SELECT user_id, count(user_id) as ct FROM treenode WHERE project_id=1 GROUP BY user_id; QUERY PLAN --------------------------------------------------------------------------------------------------------------------------- HashAggregate (cost=253670.88..253671.24 rows=37 width=8) (actual time=1807.334..1807.339 rows=38 loops=1) -> Seq Scan on treenode (cost=0.00..220280.62 rows=6678050 width=8) (actual time=0.183..893.491 rows=6678050 loops=1) Filter: (project_id = 1) Total runtime: 1807.368 ms (4 rows) A: Main problem is the missing index. But there is more. SELECT user_id, count(*) AS ct FROM treenode WHERE project_id = 1 GROUP BY user_id; You have many bigint columns. Probably overkill. Typically, integer is more than enough for columns like project_id and user_id. This would also help the next item. While optimizing the table definition, consider this related answer, with an emphasis on data alignment and padding. But most of the rest applies, too: Configuring PostgreSQL for read performance The elephant in the room: there is no index on project_id. Create one. This is more important than the rest of this answer. While being at it, make that a multicolumn index: CREATE INDEX treenode_project_id_user_id_index ON treenode (project_id, user_id); If you followed my advice, integer would be perfect here: Is a composite index also good for queries on the first field? user_id is defined NOT NULL, so count(user_id) is equivalent to count(*), but the latter is a bit shorter and faster. (In this specific query, this would even apply without user_id being defined NOT NULL.) id is already the primary key, the additional UNIQUE constraint is useless ballast. Drop it: "treenode_pkey" PRIMARY KEY, btree (id) "treenode_id_key" UNIQUE CONSTRAINT, btree (id) Aside: I'd not use id as column name. Use something descriptive like treenode_id. Added information Q: How many different project_id and user_id? A: not more than five different project_id. That means Postgres has to read about 20% of the whole table to satisfy your query. Unless it can use an index-only scan, a sequential scan on the table will be faster than involving any indexes. No more performance to gain here - except by optimizing the table and server settings. As for the index-only scan: To see how effective that can be, run VACUUM ANALYZE if you can afford that (locks the table exclusively). Then try your query again. It should now be moderately faster using only the index. Read this related answer first: Optimize simple query using ORDER BY date and text As well as the manual page added with Postgres 9.6 and the Postgres Wiki on index-only scans. A: I'd first add an index on (project_id, user_id) and then in 9.3 version, try this query: SELECT u.user_id, c.number_of_nodes FROM users AS u , LATERAL ( SELECT COUNT(*) AS number_of_nodes FROM treenode AS t WHERE t.project_id = 1 AND t.user_id = u.user_id ) c -- WHERE c.number_of_nodes > 0 ; -- you probably want this as well -- to show only relevant users In 9.2, try this one: SELECT u.user_id, ( SELECT COUNT(*) FROM treenode AS t WHERE t.project_id = 1 AND t.user_id = u.user_id ) AS number_of_nodes FROM users AS u ; I assume you have a users table. If not, replace users with: (SELECT DISTINCT user_id FROM treenode) | Mid | [
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Create Wishlist * Make wishlist public Reviews Hide Reviews FRINGE ♥ Straight Bangs AWESOME (Y) Janessa on 13th Dec 2011 I tried the bangs today! it is natural and soft except for the fact that it was a little glossy. And, i could also see a small part of the bone of the fringe when i put it on. But still, it looks really good. (Y)(Y) FRINGE ♥ Straight Bangs Impressed! Felicity on 14th Nov 2011 Just received my package today! Like stated in the other reviews, it looks really natural and soft. It blended well in my hair. My only problem is that I can see the "bone" of the fringe when I put the wig on. Maybe it was the way I fixed it on, i don't know. But I would definitely recommend my friends to get this wig. (: FRINGE ♥ Straight Bangs straight bangs sari on 7th Nov 2011 the bangs is so natural and nice. although its abit too shiny bt after a wash it will be fabulous.my mum thought i've just gotten a new haircut ! its so much better den my real hair! FRINGE ♥ Straight Bangs review shasha on 15th Jul 2011 yesh! I am the first to review! I was thinking if I should buy this clip in bangs but the were no reviews on this bangs, I was afraid the fringe will look shiny and fake. but I really want to know how to look with "the china doll bangs look" so in the end I bought it. NICE NICE. Quality of the fringe is superb, I swear there will be no regrets. Its so soft and real, when I hold it in my hands I feel so blessed and overly satisfied. | Low | [
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/* This file is part of libswirl */ #include "license/bsd" #pragma once #include "types.h" struct ASIC; void YUV_init(ASIC* asic); void YUV_data(u32* data, u32 count, u8* vram); | Low | [
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Factors associated with self-reported unprotected anal sex among male sex workers in Mombasa, Kenya. : To identify social and behavioral characteristics associated with sexual risk behaviors among male sex workers who sell sex to men in Mombasa, Kenya. : Using time-location sampling, 425 men who had recently sold, and were currently willing to sell sex to men were invited to participate in a cross-sectional survey. A structured questionnaire was administered using handheld computers. Factors associated with self-reported unprotected anal sex with male clients in the past 30 days were identified and subjected to multivariate analysis. : Thirty-five percent of respondents did not know HIV can be transmitted via anal sex, which was a significant predictor of unprotected anal sex [adjusted odds ratio (AOR) 1.92; 95% confidence interval (95% CI), 1.16-3.16]. Other associated factors included drinking alcohol 3 or more days per week (AOR, 1.63; 95% CI, 1.05-2.54), self-report of burning urination within the past 12 months (AOR, 2.07; 95% CI, 1.14-3.76), and having never been counseled or tested for HIV (AOR, 1.66; 95% CI, 1.07-2.57). Only 21.2% of respondents correctly knew that a water-based lubricant should be used with latex condoms. : Male sex workers who sell sex to men in Mombasa are in acute need of targeted prevention information on anal HIV and STI transmission, consistent condom use, and correct lubrication use with latex condoms. HIV programs in Africa need to consider and develop specific prevention strategies to reach this vulnerable population. | Mid | [
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Washington (CNN) – Hillary Clinton has firmly planted herself with the White House and those who say the United States should not provide military assistance – particularly airstrikes – to the Iraqi government in response to the rise of the Islamic State of Iraq and Syria and other militants. In both lengthy remarks at a George Washington University book event and an interview with the BBC on Friday, Clinton blasted Iraqi Prime Minister Nuri al-Maliki and the current state of Iraq that, she argued, allowed radical Islamist militants to surge through the country and threaten the capital Baghdad. Clinton characterized the Maliki government as "dysfunctional, unrepresentative, authoritarian" in front of an audience of 1,500 in Washington. For that reason, she added – to sustained applause – that "there's no reason on earth that I know of that we would ever sacrifice a single American life for that." "We certainly don't want to fight," Clinton added. The jihadist group, known as ISIS, wants to establish an Islamic caliphate, or state, in the region. It has already had significant success to date in Syria, where it has fought against President Bashar al-Assad's government as well as other rebel groups in a bloody civil war, and in Iraq, where its fighters recently took over Mosul, the nation's second-largest city. Iraqi Foreign Minister Hoshyar Zebari told CNN on Thursday that the army had "collapsed, basically" around Mosul, causing commanders to flee and the city to fall into the jihadists' control. Clinton, whose support of the 2002 Iraq War Resolution has hung with her for more than a decade, said that the fact that army abandoned its posts was evidence that the United States should not consider airstrikes "at this time." "You don't have a government that can inspire loyalty even among its army," she said. "It's a recipe for a horrendous conflict." Although Clinton focused much of her attention on Maliki in describing the current state of Iraq and the reasons against military action, the Iraqi leader only gets one mention in Clinton's memoir "Hard Choices." On Friday, President Barack Obama stressed again that he "will not be sending U.S. troops back into combat in Iraq," but told reporters that he is asking his national security teams to come up with other options. The president said, however, that it was up to Iraq's leaders "to make hard decisions" on the future of their country. U.S. officials have discussed bolstering ongoing efforts to send arms, equipment and intelligence information to help Iraq and its military. Airstrikes are among the options being considered, White House spokesman Jay Carney said. Earlier on Friday, the BBC released a 20-minute interview with Clinton, where the former secretary of state said airstrikes in Iraq were not appropriate "at this time." "That is not a role for the United States," Clinton said. "There needs to be a number of steps that Maliki and his government must take to demonstrate that he is committed to an inclusive Iraq – something he has not done up to date." Clinton also said that the Iraqi Army – "which has not been able to hold territory" – needs "an injection of discipline and professionalism" before any help could be considered. Clinton ruled out troops on the ground during her interview with the BBC, saying that is "not going to happen... at any foreseeable future." The former secretary of state, however, would "never say never" to troops on the group because "the world is so unpredictable." Clinton's history with support for the Iraq War has defined much of her political career and her 2002 vote to give then-President George W. Bush the authority to go into Iraq was "probably the hardest decision I have ever had to make." During the 2008 Democratic presidential primaries, Obama – who was against the war – used Clinton's support as a bludgeon to hammer her campaign with liberal Democrats. In her recent memoir Clinton writes that she "should have stated my regret" on Iraq "sooner and in the plainest, most direct language possible." "When I voted to authorize force in 2002, I said that it was 'probably the hardest decision I have ever had to make,'" she writes. "I thought I had acted in good faith and made the best decision I could with the information I had. And I wasn't alone in getting it wrong. But I still got it wrong. Plain and simple." soundoff(65 Responses) Hey Hillary, I see you can back pedal very well. Try going forward for once in your lousy life you nasty old woman. June 13, 2014 03:36 pm at 3:36 pm | Sniffit "The Senate Democrats COULD have stopped that invasion, if they had to guts to stand up against Bush. If Hillary couldn't stand up to, or see through, W's lies, how can we expect her to handle Putin?" What with the obsession with Putin? He's nothing. Russia is in abysmal shape economically and militarily and has been essentially reduced to a regional power. Their currency performed worst amongst all major industrial nations last year. His wang waving in Ukraine is specifically designed to pretend otherwise, to present a show of force and strength to hide his country's weakening position behind some bravado, but in a manner in which he knew very well nobody could really do anything about. Now, the sanctions for his behavior are making it worse economically for Russia. We have nothing to fear from him. He has no designs on us other than trying to recapture status as an equal, which he desperately fears Russia is losing. Stop clinging to the Cold War. June 13, 2014 03:36 pm at 3:36 pm | Tommy G Sniffit My point is simply that you have to take into consideration that what they believed at the time was based on what they were told, and they were told KNOWING lies. -- and your proof of this is what??? oh, you have none. so it is you that are knowing posting lies. June 13, 2014 03:37 pm at 3:37 pm | Silence DoGood There is a part of me that enjoys seeing the unbridled irrational anger leveled towards her. She is really worrying a lot of radical right folks. Go Ms.Clinton. You must be on the right track! June 13, 2014 03:37 pm at 3:37 pm | Dominican mama 4 Obama Oh and ivan, if in fact you did fight for OUR country, thanks for your service and welcome back home. June 13, 2014 03:37 pm at 3:37 pm | Bill from GA Sniffit – " ... to be held appropriately accountable " Thanks for clearing that up. And to my mind " to be held appropriately accountable " means acknowledging that Hillary is not qualified to be President. Naive or gutless, we can do better. I want a leader who takes making war, and especially an unprovoked invasion of another country, as the most serious duty of the President. Or a Senator enabling the President. June 13, 2014 03:39 pm at 3:39 pm | it must be said Sniffit -- "The book pandering road show of Hilary – What Difference Does it Make – Clinton continues... and nobody cares." -- Really? It's been the single most talked about thing in the MSM all week and you're saying "nobody cares"? LOL. The bubble is an evidence free zone. -- The only people excited about the content free book are the lefties that now have the opportunity to grill Hillary Clinton and make her squirm and attack. The far left Democrat Party has started its attack on Hillary already. And her poll numbers are falling faster than cities in Iraq. June 13, 2014 03:40 pm at 3:40 pm | Dominican mama 4 Obama Lynda/Minnesota @ Dominican mama Goodness. They're closing down threads faster than I can reply (I'll give this one a try): Hi there stranger. Glad I caught up with you ... Friday's aren't the same if I can't wish you a great weekend ----------------------------------------------------- My Fridays haven't been the same since this promotion that has kept me away from you and the rest of my buddies on this thread. I wish you a safe and happy weekend mys ister friend. Keep up the good fight, and tell "ivan" that I said thank you for his service and welcome home. I'll be seeing you....:( June 13, 2014 03:41 pm at 3:41 pm | Lynda/Minnesota "My point is simply that you have to take into consideration that what they believed at the time was based on what they were told, and they were told KNOWING lies." WE were certainly told we were heading into Iraq to find those pesky WMDs. One suspects that our congress people were given an even more harrowing doom and gloom scenario than the public was given. They were, after all, being called upon to vote for the invasion. June 13, 2014 03:43 pm at 3:43 pm | Let's prosecute W Time to bring back the draft so all you armchair heroes can shut the hell up. Very easy to talk about troops on the ground and bombing this and bombing that when you've got no skin in the game. She needs to stay with her book signing tour. For as a Sec of State she left 4 Americans to die, and today there are still just under 10,000 U.S. Troops there, I guess she is willing to sacrifice them so that TERRORIST can continue killing, or worst they could take the Americans HOSTAGE and force more TERRORIST held in GITMO to be released. Perhaps that's what her objective is. June 13, 2014 04:00 pm at 4:00 pm | Paul I think Hillary should be sent to Iraq as a goodwill ambassador from the US..... "Really what difference would it make" if she didn't come back? June 13, 2014 04:01 pm at 4:01 pm | Getoverit Isn't she a private citizen? June 13, 2014 04:04 pm at 4:04 pm | ivan Let me just say this. Regardless why or how we ended up in Iraq, under what pretence. Which I state here and now we should have not gone there. Even though Saddam killed his own people by the thousands, he kept them under control. Think of how many more will now die by other Irag hands and total chaos. We need to fininsh what we started otherwise it will be a new strongthold for Terroists. | Low | [
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With warm weather now gracing much of the country, many are heading to the great outdoors to camp, hike and fish. Depending on how great these outdoors are, keeping hydrated and finding clean water sources can be paramount. You don’t want to be burdened with carrying bottles upon bottles of drinking water, but at the same time, you don’t want to risk drinking water from streams, lakes and rivers, which can contain waterborne protozoa such as Giardia. The Katadyn Exstream water bottle allows to drink such water without consuming bacteria and harmful contaminants. The bottle uses an advanced Virustat technology to kill 99.9999% of waterborne viruses. Just dip the bottle into any water source and you instantly have safe and delicious drinking water. I know what you’re thinking: doesn’t that take some of the fun out of “roughing it”? Well don’t think for a second that MacGyver himself would prefer a paper clip, a piece of gum and some fishing line over this water bottle. When you’re outdoors and clean drinking water is scarce, this water bottle can be a lifesaver.Katadyn also makes a variety of pocket filters, siphons and emergency water tabs to ensure you’ll be safe and hydrated when on your next camping or hiking trip.. | Mid | [
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package gitlab import ( "net/http" "testing" "github.com/stretchr/testify/require" ) func TestSearchService_Users(t *testing.T) { mux, server, client := setup(t) defer teardown(server) mux.HandleFunc("/api/v4/search", func(w http.ResponseWriter, r *http.Request) { testMethod(t, r, "GET") mustWriteHTTPResponse(t, w, "testdata/search_users.json") }) opts := &SearchOptions{PerPage: 2} users, _, err := client.Search.Users("doe", opts) require.NoError(t, err) want := []*User{{ ID: 1, Username: "user1", Name: "John Doe1", State: "active", AvatarURL: "http://www.gravatar.com/avatar/c922747a93b40d1ea88262bf1aebee62?s=80&d=identicon", WebURL: "http://localhost/user1", }} require.Equal(t, want, users) } func TestSearchService_UsersByGroup(t *testing.T) { mux, server, client := setup(t) defer teardown(server) mux.HandleFunc("/api/v4/groups/3/-/search", func(w http.ResponseWriter, r *http.Request) { testMethod(t, r, "GET") mustWriteHTTPResponse(t, w, "testdata/search_users.json") }) opts := &SearchOptions{PerPage: 2} users, _, err := client.Search.UsersByGroup("3", "doe", opts) require.NoError(t, err) want := []*User{{ ID: 1, Username: "user1", Name: "John Doe1", State: "active", AvatarURL: "http://www.gravatar.com/avatar/c922747a93b40d1ea88262bf1aebee62?s=80&d=identicon", WebURL: "http://localhost/user1", }} require.Equal(t, want, users) } func TestSearchService_UsersByProject(t *testing.T) { mux, server, client := setup(t) defer teardown(server) mux.HandleFunc("/api/v4/projects/6/-/search", func(w http.ResponseWriter, r *http.Request) { testMethod(t, r, "GET") mustWriteHTTPResponse(t, w, "testdata/search_users.json") }) opts := &SearchOptions{PerPage: 2} users, _, err := client.Search.UsersByProject("6", "doe", opts) require.NoError(t, err) want := []*User{{ ID: 1, Username: "user1", Name: "John Doe1", State: "active", AvatarURL: "http://www.gravatar.com/avatar/c922747a93b40d1ea88262bf1aebee62?s=80&d=identicon", WebURL: "http://localhost/user1", }} require.Equal(t, want, users) } | Mid | [
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Q: Rails need advice on controller practices I try to follow RESTfull approach in controllers, but sometimes I need action which won't fit into default ones. E.g. I have an index action rendering all articles which is def index @articles = Article.all end but what if I also want search them? should I create separate actions for it, or should I bloat existing controller, like: def index if params[:search] @articles = Article.where(id: params[:search_id]) else @articles = Article.all end end What is the right way? A: You should use same action and create a index action only. And search logic goes to Article model. You should follow this | Low | [
0.510588235294117,
27.125,
26
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That year also registered as the city's worst for the crime since at least 1969. Cops, criminologists and community leaders disagree about what is driving the ups and downs in the city's crime rates. Gangs or Gentrification? Oakland Police Chief Sean Whent says Oakland's 50 or so gangs shifted the way they make money -- from drugs to, in part, robberies. "We used to get significantly more drug hotline calls than we do now," says Whent, "many more calls about street drug dealing. And that's really reduced. And so what have those groups and gangs done? Well, we have seen the increase obviously in the street robberies and fraud crimes." Whent says police had some success curbing those robberies in 2014. He points to Ceasefire, the city's chief anti-violence strategy. Its purpose is to reduce homicides, which fell 10 percent last year. But Whent says the heavy focus on certain gang members is turning the robbery rate around, too. Youth Uprising Director Olis Simmons is skeptical of Whent's view that gangs were responsible for the increase in robbery. "Big-time crime syndicates went away 20 years ago," says Simmons, "What we see is acts of desperation. People are robbing their neighbors, their community members, out of hunger." She and other Oakland community leaders say the surge in robberies was more like a canary in the coal mine. A sign that as Oakland enters its so-called renaissance, the economic gap is widening. "While Oakland is realizing the dream of economic vitality -- a renaissance right? -- sadly, there is a concentration of people who are locked out," says Simmons. She says she thinks for many years those people, largely in East and West Oakland, felt that as the city did better, their neighborhoods would also turn around; they'd get a job, maybe a store would open. "The realization that it's never going to happen for (them) is what's new," she says. Simmons says the best way for Oakland to fight crime is by helping the community. That means helping kids like Morris, who says he empathizes with the people who stole from him. "It just be the lack of having, like, because if a kid got everything he needs, he don't need to be in no gang, he don't need to be out here stealing. Why?" asks Morris, "'Cause he got his own. But somebody else that ain't got nothing to take. … 'Hey, What I'm gonna lose? Go to jail? I ain't got nothing out here anyway.' " A power relationship But none of that reasoning convinces UC Berkeley crime expert Franklin Zimring. The first thing to know about robbery, he says, is that it's usually not about money. "You go into a 7-Eleven store and you come out with $93. And for this you're risking 10 years of your life in Pelican Bay," says Zimring, a law professor at Cal. He says robbery as a criminal career nets vastly less than minimum wage. "Robbery is on a risk/reward basis literally the worst way of making a criminal living you can imagine," he says. "So you have to think that there's a mix of recreation and power and a playing out of envy." Many cities face the pressures of gentrification and displacement, but not all of them can claim Oakland's distinction of robbery capital of the U.S. for three consecutive years, according to the latest FBI data. So how does Zimring explain the uptick? High-status recreation, he says, or put more simply, a fad. And when it comes to the drop, he says crediting Ceasefire might be wishful thinking. Zimring says catching even a few robbers could account for last year's dip. Others who study crime, such as UCLA's Mark Kleiman, agree, saying that nearly 5,000 robberies could easily be accomplished by just 100 people over the course of a year. Meanwhile, the statistics reveal just how hard it may be for Oakland to reduce crime overall. As robberies dropped last year, drug crimes rose once again, by about the same percentage. | Low | [
0.506024096385542,
31.5,
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Multimodal acute pain management. Unrelieved postoperative pain following arthroplasty has been shown to delay patients' recovery and discharge from the hospital. Undertreatment of acute pain may also result in greater use of healthcare resources and ultimately lead to poor outcomes. This article reviews a multimodal approach to reduce pain at each step of the pain nocioception process by combining various analgesics that each operate through a different site or mechanism of action, allowing the physician to tailor the regimen to the patient. A therapeutic combination of analgesics (eg, opioids, nonsteroidal anti-inflammatory drugs, and bupivicaine) can provide adequate pain relief; however, regional anesthesia is fraught with side effects. The use of multimodal analgesia reduces hospital stay, decreases medical complications, and increases patient satisfaction. | High | [
0.685796269727403,
29.875,
13.6875
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Q: Using KSOAP in Android to access Webservice don't work i'm using the webservice from http://www.w3schools.com/webservices/tempconvert.asmx But I can't get out any data... This is my code: public class MainActivity extends Activity { private static final String SOAP_ACTION="http://tempuri.org/CelsiusToFahrenheit"; private static final String METHOD_NAME="CelsiusToFahrenheit"; private static final String NAMESPACE="http://tempuri.org/"; private static final String URL="http://www.w3schools.com/webservices/tempconvert.asmx"; @Override protected void onCreate(Bundle savedInstanceState) { super.onCreate(savedInstanceState); setContentView(R.layout.activity_main); TextView tv = (TextView) findViewById(R.id.textView1); SoapObject Request = new SoapObject(NAMESPACE, METHOD_NAME); Request.addProperty("Celsius", "32"); SoapSerializationEnvelope soapEnvelope = new SoapSerializationEnvelope(SoapEnvelope.VER11); soapEnvelope.dotNet = true; soapEnvelope.setOutputSoapObject(Request); HttpTransportSE aht = new HttpTransportSE(URL); try{ aht.call(SOAP_ACTION, soapEnvelope); SoapPrimitive resultString = (SoapPrimitive)soapEnvelope.getResponse(); tv.setText("Farenheit: " + resultString); } catch(Exception e) { e.printStackTrace(); } } Ps: I have imported ksoap2-android-assembly-3.2.0-jar-with-dependencies.jar and I have set permission for internet please help A: Solved it with a Asynctask => AsyncCallWS, thnx Raghunandan. Remember to download the Ksoap from here and add it to the libs folder in Eclipse Here is all my code: import org.ksoap2.SoapEnvelope; import org.ksoap2.serialization.PropertyInfo; import org.ksoap2.serialization.SoapObject; import org.ksoap2.serialization.SoapPrimitive; import org.ksoap2.serialization.SoapSerializationEnvelope; import org.ksoap2.transport.HttpTransportSE; import android.os.AsyncTask; public class MainActivity extends Activity { private final String NAMESPACE = "http://www.w3schools.com/webservices/"; private final String URL = "http://www.w3schools.com/webservices/tempconvert.asmx"; private final String SOAP_ACTION = "http://www.w3schools.com/webservices/CelsiusToFahrenheit"; private final String METHOD_NAME = "CelsiusToFahrenheit"; private String TAG = "PGGURU"; private static String celcius; private static String fahren; Button b; TextView tv; EditText et; public void onCreate(Bundle savedInstanceState) { super.onCreate(savedInstanceState); setContentView(R.layout.activity_main); //Celcius Edit Control et = (EditText) findViewById(R.id.editText1); //Fahrenheit Text control tv = (TextView) findViewById(R.id.tv_result); //Button to trigger web service invocation b = (Button) findViewById(R.id.button1); //Button Click Listener b.setOnClickListener(new OnClickListener() { public void onClick(View v) { //Check if Celcius text control is not empty if (et.getText().length() != 0 && et.getText().toString() != "") { //Get the text control value celcius = et.getText().toString(); //Create instance for AsyncCallWS AsyncCallWS task = new AsyncCallWS(); //Call execute task.execute(); //If text control is empty } else { tv.setText("Please enter Celcius"); } } }); } public void getFahrenheit(String celsius) { //Create request SoapObject request = new SoapObject(NAMESPACE, METHOD_NAME); //Property which holds input parameters PropertyInfo celsiusPI = new PropertyInfo(); //Set Name celsiusPI.setName("Celsius"); //Set Value celsiusPI.setValue(celsius); //Set dataType celsiusPI.setType(double.class); //Add the property to request object request.addProperty(celsiusPI); //Create envelope SoapSerializationEnvelope envelope = new SoapSerializationEnvelope( SoapEnvelope.VER11); envelope.dotNet = true; //Set output SOAP object envelope.setOutputSoapObject(request); //Create HTTP call object HttpTransportSE androidHttpTransport = new HttpTransportSE(URL); try { //Invole web service androidHttpTransport.call(SOAP_ACTION, envelope); //Get the response SoapPrimitive response = (SoapPrimitive) envelope.getResponse(); //Assign it to fahren static variable fahren = response.toString(); } catch (Exception e) { e.printStackTrace(); } } private class AsyncCallWS extends AsyncTask<String, Void, Void> { @Override protected Void doInBackground(String... params) { Log.i(TAG, "doInBackground"); getFahrenheit(celcius); return null; } @Override protected void onPostExecute(Void result) { Log.i(TAG, "onPostExecute"); tv.setText(fahren + "° F"); } @Override protected void onPreExecute() { Log.i(TAG, "onPreExecute"); tv.setText("Calculating..."); } @Override protected void onProgressUpdate(Void... values) { Log.i(TAG, "onProgressUpdate"); } } } I had to add permission in Manifest for internet, otherwise I got null as response. <uses-permission android:name="android.permission.INTERNET" /> And this is my layout.xml file: <?xml version="1.0" encoding="utf-8"?> <LinearLayout xmlns:android="http://schemas.android.com/apk/res/android" android:layout_width="match_parent" android:layout_height="wrap_content" android:orientation="vertical" > <TextView android:id="@+id/textView1" android:layout_width="fill_parent" android:layout_height="wrap_content" android:layout_marginTop="10dp" android:gravity="center" android:text="Celsius to Farenheit" android:textSize="30dp" /> <EditText android:id="@+id/editText1" android:layout_width="fill_parent" android:layout_height="wrap_content" android:gravity="center" android:numeric="integer" android:singleLine="true" /> <Button android:id="@+id/button1" android:layout_width="fill_parent" android:layout_height="wrap_content" android:layout_gravity="center_horizontal" android:gravity="center" android:text="Convert to Farenheit" /> <TextView android:id="@+id/tv_result" android:layout_width="fill_parent" android:layout_height="wrap_content" android:gravity="center" android:text="" android:textSize="26dp"/> </LinearLayout> PS: If you have created your own WebService in Asp.Net and made it public, remember to change default namespace http://tempuri.org/ to something unique. You change it in the WebService.asmx.cs Like this: [WebService(Namespace = "http://microsoft.com/webservices/")] | Mid | [
0.6162790697674411,
26.5,
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Introduction ============ The discovery of microsatellites, and other hypervariable genetic markers, has enabled the study of genetic differentiation and population subdivision at small scales (e.g. [@b57]), even down to the level of the individual (e.g. [@b7]; [@b51]; [@b52]). The information gathered can have important implications for conservation work intended to preserve genetic variation. The significance of this objective increased following the World Summit on Sustainable Development and the publication of the framework for action on biodiversity and ecosystem management, which identifies genetic variation as one of the three levels of biodiversity recommended for conservation ([@b76]). Information on the scale over which genetic differentiation occurs also has important implications for the management of natural resources and the potential for local adaptation. Studies into freshwater salmonid fishes have revealed that genetic differentiation can occur over very short distances within river catchments. This can be associated with physical barriers to movement, which can isolate populations that then differentiate by genetic drift ([@b33]). In addition, differentiation has also been noted where salmonids exist without such barriers, including populations of the many anadromous species that could potentially be linked by gene flow ([@b69]; [@b65]; [@b2]; [@b55]). As such, these species represent an interesting case for studying processes of population differentiation. Specifically, the propensity towards population subdivision appears linked to two key factors: (a) the well-known ability of salmonids to home back to specific natal rivers ([@b68]) and (b) the patchy distribution of spawning areas within rivers ([@b44]) that may act to restrict gene flow among fish in different areas of a river (although other processes e.g. extinction-recolonization dynamics have also been described; [@b47]). Amongst salmonid species, the brown trout (*Salmo trutta*) is typified by having a particularly complex within catchment genetic structure, with high levels of genetic differentiation and an apparent lack of correlation between genetic and geographic distance ([@b4]; [@b12]; [@b22]; [@b43]; [@b61]; [@b62]; but also see [@b8]; [@b19]). Recently there has been an increasing emphasis placed on understanding the deeper biological significance of this complex population structure and there is a need to understand the underlying evolutionary models that may explain the observed patterns of genetic differentiation, which also have important implications for the ecology of brown trout, as well as the conservation of genetic diversity and management of the species. However, brown trout are under pressure from habitat destruction, pollution, over-exploitation and stocking with non-native fish, i.e. local factors that may erode the high levels of genetic variation observed and cause the extinction of unique varieties and loss of unique traits ([@b22]). Although the River Dart is no exception to the pressures that threaten the persistence of brown trout at a local scale, it does drain a National Park and so benefits from a relatively high level of statutory protection. Regular electrofishing surveys undertaken by the Environment Agency (EA; the national regulatory body in England and Wales) suggest that numbers of brown trout within the River Dart are significant and stable, although there has been a negative trend since records began in the 1960s ([@b70]; [@b14]). Changes in land use have led to habitat degradation in the headwaters, although a major threat facing trout in the River Dart arises from both human mediated and natural acidification. The low pH values which characterize the River Dart, combined with the fact that brown trout may spawn in small rivers ([@b17]), may make Dart trout more susceptible to catastrophic events. In turn, this may lead to localized extinctions and recolonizations, with important implications for patterns of genetic differentiation among groups of brown trout ([@b28]; [@b47]). Alternatively, the naturally low pH of rivers on Dartmoor may actually have promoted the tolerance of high acidity in indigenous populations of trout, generating the potential for local adaptation ([@b72]). The purpose of this study was to investigate the population genetic structure of brown trout at the scale of a single river catchment and to reconcile the potential for environmental instability to cause localized extinction events (e.g. [@b47]; [@b37]; [@b44]) with the apparently stable trout numbers present in the River Dart. [@b24] have previously proposed three scenarios that form an appropriate framework for addressing this question. Under the member-vagrant model, nursery areas play a vital role in determining population structure and selection favours individuals that return to their natal spawning grounds to reproduce, which maximizes survival of the young and promotes the development of locally adapted gene pools. Thus, fish that complete this process of homing are considered 'members', contributing to local adaptation and those that do not return to natal areas are known as 'vagrants' ([@b34]; [@b24]). This model predicts temporal stability of population structure, a significant effect of isolation-by-distance and strong genetic differentiation among populations. Under the second model, the metapopulation model, the degree of genetic structuring depends on the temporal stability of habitats, so in an unstable environment the occurrence of locally adapted gene pools can be curtailed because of local extinctions (and subsequent recolonizations, reviewed in [@b3]; [@b41]; [@b59]). The key features of this model are that local populations (or subpopulations) are interconnected not only by migration but also recolonization and empty/unoccupied patches have an important role in metapopulaton dynamics. This model predicts that there would be lower levels of temporal stability in population structure, no significant effect of isolation-by-distance and lower genetic divergence between subpopulations (but still statistically significant because of founder effects, [@b24]; [@b41]; [@b59]). The third scenario is panmixia, where gene flow is unrestricted across the catchment and suggests the absence of genetic differentiation, such that neither of the previous two models applies. Elucidation of the evolutionary model appropriate to Dart trout offers the potential not only to aid local management and conservation, but also to begin to address the relative scarcity of population genetics research completed on salmonids in England and Wales. The present study examined the variability at nine microsatellite loci in brown trout sampled from the River Dart over a 3-year period, with the specific aim of ascertaining the pattern of genetic differentiation within a river system that is particularly vulnerable to severe pH depressions. The results from this analysis, which included application of the decomposed pairwise regression (DPR) method that allowed the relative strengths of genetic drift and gene flow to be accessed in each sample, were then used to consider which evolutionary model (member-vagrant, metapopulation or panmixia) best fitted the data. In addition, spatial autocorrelation was also employed to determine the geographic scale over which genetic differentiation occurred in Dart trout: the conservation implications of these results are discussed. Methods ======= The study area -------------- The River Dart catchment is located in Devon, southwest England ([Fig. 1](#fig01){ref-type="fig"}). It is approximately 75 km long, covers an area of 475 km^2^ and flows into the English Channel through the Dart Estuary and into Start Bay. The river rises on Dartmoor National Park, an upland granite mass that reaches over 600 m high. The catchment is a typical moorland system, characterized by high rainfall and a peaty, acidic soil. The area represents the largest unglaciated expanse of upland in Great Britain and the largest granite surface in England. There are no real aquifers on Dartmoor and water is primarily stored in wetlands and bogs. The river is formed from two main tributaries, the East and West Dart. The upper reaches support small-scale livestock farming, which becomes more intensive and incorporates arable farming once it flows off the moor. {ref-type="table"}. Significant barriers to fish movement are indicated by double lines perpendicular to the river.](eva0002-0537-f1){#fig01} The catchment supports a locally important stock of resident and anadromous trout (see rod-catch data below), with all the tributaries and several stretches of the main river containing excellent spawning and nursery areas. In particular, many of the headwaters provide valuable spawning grounds, not only for brown trout, but also Atlantic salmon (*Salmo salar* L.). The river also supports a rod/game fishery, as well as a limited commercial estuary (seine) net fishery. Catches of sea trout in 2002, the year this study began, were 712 for rod catches and 727 for net catches ([@b15]). Formal records of brown trout stocking in the UK were first collected by the national river boards during the 1950s and show that in the period up to 2005, 145 212 individual ova, fry or smolt were stocked into the River Dart. These comprised 65 separate stocking events at a minimum of 18 discrete locations within the river. The largest single stocking incident was of 96 000 eyed ova into the headwaters of the East Dart in 1961 (this single event accounts for the majority of all recorded stocking on the River Dart). The source of most stocked trout is thought to be various local hatcheries from southwest England, but the ultimate origin of hatchery stocks has been impossible to uncover ([@b23]). In the last decade local fisheries groups have taken to stocking the lower reaches of the River Dart with much smaller numbers (in the hundreds) of hatchery reared smolt which are typically bred from trout of Dart origin. Sample collection ----------------- A total of l1225 brown trout of multiple year classes, but predominantly parr and excluding fry (to avoid collecting siblings; [@b30]), were collected by electrofishing from 22 sites spread across 14 tributaries within the River Dart catchment. Five of these sites were isolated above barriers; the Gata and the Ash above man-made weirs and the Rud group of samples above a natural waterfall ([Fig. 1](#fig01){ref-type="fig"}). The average in-water distance among sample sites was 22.7 km, with a range of 0.8--64.4 km. Sampling was carried out each summer (July--September), from 2002 to 2004 ([Table 1](#tbl1){ref-type="table"}; [Fig. 1](#fig01){ref-type="fig"}). The adipose fin was removed from each fish and preserved in 98% ethanol, after which the fish was released; removal of the adipose fin provided a permanent mark so the same individuals were not sampled again in subsequent years. ###### Sample site abbreviations Abbreviation Latitude Longitude Details Year *n* -------------- ------------ ----------- ---------------------------------- ------ ----- Amm 50°28′27″N 3°39:44″W Amm Brook, Amm house weir 2002 32 Ash 50°31′50″N 3°45′26″W Ashburn, Belford Hill 2002 36 Dury 50°35′06″N 3°53′26″W Dury Brook, Dury Farm 2002 33 EDar 50°35′44″N 3°54′49″W East Dart, Postbridge 2002 21 EWebB 50°35′21″N 3°48′27″W East Webburn, Bagpark Estate 2003 28 EWebD 50°34′12″N 3°48′40″W East Webburn, Dunstone Bridge 2004 57 EWebV 50°34′32″N 3°48′25″W East Webburn, Veton Bridge 2003 49 EWebW 50°35′08″N 3°48′26″W East Webburn, Wooder Manor 2002 25 EWebW 50°35′08″N 3°48′26″W East Webburn, Wooder Manor 2003 52 Gata 50°27′08″N 3°37′49″W Gatacombe River 2002 34 Har 50°25′55″N 3°46′54″W Harbourne, Hatcheries Fish Farm 2002 41 Hem 50°27′45″N 3°40′08″W River Hems 2002 40 Hol 50°30′15″N 3°49′47″W Holly Brook 2002 29 LChe 50°33′27″N 3°55′55″W Cherry Brook, Lower Bridge 2002 32 LChe 50°33′27″N 3°55′55″W Cherry Brook, Lower Bridge 2003 27 RudB 50°32′55″N 3°47′46″W Ruddycleave, Bowden Farm 2003 42 RudB 50°32′55″N 3°47′46″W Ruddycleave, Bowden Farm 2004 54 RudC 50°32′39″N 3°48′05″W Ruddycleave, Ruddycleave Cottage 2003 36 RudP 50°33′28″N 3°47′11″W Ruddycleave, Pudsham Down 2002 21 RudP 50°33′28″N 3°47′11″W Ruddycleave, Pudsham Down 2003 38 RudP 50°33′28″N 3°47′11″W Ruddycleave, Pudsham Down 2004 39 Swin 50°32′33″N 3°54′36″W River Swincombe, Wydemeet 2002 32 Swin 50°32′33″N 3°54′36″W River Swincombe, Wydemeet 2004 48 UChe 50°34′38″N 3°55′58″W Cherry Brook, Upper Bridge 2003 29 UChe 50°34′38″N 3°55′58″W Cherry Brook, Upper Bridge 2004 41 WDar 50°33′47″N 3°57′53″W West Dart, Cockern Tor 2002 39 WDar 50°33′47″N 3°57′53″W West Dart, Cockern Tor 2003 32 WDar 50°33′47″N 3°57′53″W West Dart, Cockern Tor 2004 48 Web 50°31′35″N 3°47′43″W River Webburn, Mistresses Piece 2002 32 WWeb 50°33′03″N 3°50′03″W West Webburn, Pondsworthy Bridge 2002 47 WWeb 50°33′03″N 3°50′03″W West Webburn, Pondsworthy Bridge 2003 32 WWeb 50°33′03″N 3°50′03″W West Webburn, Pondsworthy Bridge 2004 46 WWebL 50°34′26″N 3°51′02″W West Webburn, Lower Cator Bridge 2002 33 Location details, year of sample collection and numbers of fish sampled (*n*). See [Fig. 1](#fig01){ref-type="fig"} for locations. Microsatellites --------------- DNA was extracted from the fin tissue according to an ammonium acetate precipitation method, similar to that described in [@b5]. Genetic variation was determined at nine di-nucleotide microsatellite loci: Str15, Str60, Str73 ([@b18]), Str85 ([@b54]), SsoSL417, SsoSL25 ([@b64]), Strutta58 ([@b53]), SsoSL438 (A. Slettan, unpublished data, GenBank accession no. Z49134) and SsHaeIII.14.20 (J. L. Goodier unpublished, GenBank accession no. U10050). Genotypes were assayed through polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis with fluorescently labelled primers. PCR reactions were carried out in 10 μL reaction volumes and standard PCR reagents were used in a mixture containing 10--100 ng DNA, 0.5 μ[m]{.smallcaps} of each primer, 1--1.5 m[m]{.smallcaps} MgCl~2~, 200 μ[m]{.smallcaps} of each dNTP, 1× reaction buffer and 0.5 U of *Taq* DNA polymerase (Bioline, London, UK). The PCR profile consisted of: a single denaturing set lasting 3 min at 94°C, 30 iterations of 94°C for 30 s, annealing temperatures 51°C (Str85), 52°C (Str15 & Sso417), 54°C (Sso25 & Strutta58), 58°C (SsHae), 60°C (Str 73) or 65°C (Str60) for 30 s and 72°C for 30 s with a single elongation step of 72°C for 10 min. However, the Sso438PCR profile was a stepwise program, with the annealing stage made up of six iterations at 1° intervals between 54°C and 48°C. For those loci producing weak products (SsHae, Str15 and Str73) 40 iterations were generally used. Size determination of the labelled PCR products was performed using a Beckman-Coulter (Fullerton, California, USA) CEQ8000 automated DNA sequencer with an internal size standard, according to the manufacturer\'s instructions. The raw data were analysed with the platform\'s-associated fragment analysis software (Beckman-Coulter). Genetic diversity analysis -------------------------- ARLEQUIN version 3 ([@b63]) was used to estimate the variance components in allele frequencies among years ([@b20]) and all samples were found to exhibit temporal stability (see Results). Therefore, in subsequent analyses temporal samples from a location were combined to estimate population allele frequencies, as recommended by [@b75]. Each sample at each locus was tested for conformity to Hardy--Weinberg equilibrium (HWE; [@b26]) using GENEPOP 3.4 ([@b56]) and any deviations were further investigated with Microchecker ([@b46]). Critical levels of significance for simultaneous tests were adjusted using the sequential Bonferroni procedure for multiple tests ([@b58]). In addition, Powermarker version 3.25 ([@b40]) was used to calculate expected and observed heterozygosity, and FSTAT version 2.9 ([@b25]) was used to calculate allelic richness (allele number corrected for sample size using the rarefaction method of [@b16]) and the inbreeding coefficient. To examine the levels of genetic differentiation between pairs of samples a test of the homogeneity of allele frequency distributions (the so-called test of 'genic differentiation') was run in GENPOP ([@b56]) and *F*~ST~ values were calculated ([@b77]) in ARLEQUIN. Critical levels of significance for simultaneous tests were adjusted using the sequential Bonferroni procedure for multiple tests ([@b58]). The chord distance (*D*~CE,~[@b10]) was also used to quantify genetic differentiation between samples. This measure was chosen because the close proximity of samples included in the study means mutation is unlikely to have contributed to population divergence and the *D*~CE~ distance is based on geometric distances, which are independent of models of microsatellite mutation ([@b40]). It has also been shown to be one of the most efficient methods for obtaining correct tree topology using microsatellite data ([@b71]). Neighbour-joining (NJ) phylograms were constructed and confidence intervals on tree topology were estimated by bootstrap resampling of loci 1000 times utilizing the programs P[owermarker]{.smallcaps} version 3.23 ([@b40]), C[onsense]{.smallcaps} (from Phylip 3.6; [@b21]) and T[ree]{.smallcaps} V[iew]{.smallcaps} version 1.6 ([@b48]). Decomposed pairwise regression analysis --------------------------------------- To detect outlier populations and accurately elucidate patterns of isolation-by-distance, the DPR ([@b37]) was applied. The DPR can also estimate the relative strengths of genetic drift and gene flow for each sample, by decomposing the regression of the pairwise genetic and geographic distances ([@b60]). Briefly, genetic distance \[*F*~ST~/(1 − *F*~ST~)\] is plotted against geographic distance for all pairwise comparisons. Outlier analysis then determines which samples have exceptional characteristics that may falsely influence the pattern of IBD (e.g. founder effects, bottlenecks, physical barriers, all of which can strongly affect the overall pattern). These outlying samples were determined based on the systematic bias of the regression residuals (process one, which identifies 'putative' outliers). The outliers were then sequentially removed from the analysis and the best model was selected based on the AIC (Akaike\'s information criteria) value (process two, which identifies 'true' outliers); the smallest values indicate the most plausible model ([@b6]). Because of the small sample sizes, the corrected AIC (AIC~C~) was used. Finally, after determining the best model and the 'true' outliers, the pairwise genetic and geographic distances were regressed separately for each sample (including the outlier samples) against the nonoutlier samples, to investigate the different patterns of geneflow and drift. The significance of the relationship was assessed by ordinary least-squares regression. Spatial autocorrelation analysis -------------------------------- Spatial genetic structure was tested with the software package [genalex]{.smallcaps} version 6.1 ([@b50] and according to [@b55]). A Mantel test of matrix correspondence was used to examine the association between pairwise *F*~ST~ values and the in-water distance between sampling sites by estimating the *r*~*xy*~ measure that is analogous to an autocorrelation coefficient ([@b67]), with 999 permutations used to test the statistical significance of the values. At the scale of individual specimens, a multivariate microspatial autocorrelation approach was also employed ([@b66]; [@b51]). This test employed the squared distances measure (PhiPT; [@b51]) to estimate individual genetic distance, and the same in-water distances between sample sites used in the Mantel test for distance between individual specimens (with the exception that all individuals caught from the same sample site were assigned a distance value of zero). To assess the extent of nonrandom genetic structure among individuals ([@b51]), a correlogram of the autocorrelation coefficient (*r*) was plotted as a function of distance, specifically five distance classes: 0--5, 6--15, 16--25, 26--45, 46--65 km; a range of alternate distance classes from 5 to 25 km were also analysed. A multi-distance class (MDC) analysis was also used to give a more accurate estimate of the scale over which genetic structure was detected ([@b51]). In this approach the same classes as above were utilized, except that multiple analyses were performed with automatically increasing distance size classes, such that individuals from more distant classes were added to the previous groups ([@b51]). One thousand bootstrap replicates were used to ascertain the 95% confidence interval (CI) of the *r* estimates, and 999 permutations were used to resolve the 95% CI about the null hypothesis of no spatial genetic structure. Significant genetic autocorrelation was concluded when the CI of *r* and those of the null hypothesis did not overlap ([@b51]). Results ======= Genetic diversity ----------------- Pairwise testing of temporal samples revealed only one case of significant genetic heterogeneity between 2003 and 2004 samples at the RudB site in locus Strutta58 (*P* \< 0.05, corrected across loci; *k* = 9). Furthermore, quantitative estimates of hierarchical gene diversity across the whole dataset showed that while a significant amount of genetic variation (*P* \< 0.00001) was identified both within samples and among different sample sites (96% within samples and 4% between sites), a nonsignificant estimate of 0% variation was attributed to variation among temporal samples. Therefore, all temporal samples collected at individual sites were pooled in subsequent analyses. Genetic diversity indices for each locus and population are presented in [Table 2](#tbl2){ref-type="table"}. Significant deviations from HWE (*P* \< 0.05, corrected across loci; *k* = 9) for pooled samples were detected in two cases (EDar at SsoSL25 and EWebW at Str73). Further analysis of these cases with Microchecker did not reveal any evidence of null alleles or scoring errors, although the EDar case was associated with a significantly positive *F*~is~ value ([Table 2](#tbl2){ref-type="table"}), which could result from the nonrepresentative sampling of juveniles fish ('family sampling'; [@b1]; [@b30]; [@b78]). The mean number of alleles at a locus, across the whole dataset was 10.7 and ranged from 3 (Str60) to 27 (Str58). The mean number of alleles per locus within samples had an average of 6.6 and ranged from 4.4 (RudB) to 8.0 (Har). The allelic richness (the average allele number within samples, corrected for a minimum sample size of 16 in this case) was smaller, with an average of 5.5 and ranged between 4.0 (RudB) and 6.6 (Har). The average observed heterozygosity (H~O~) across all samples was 0.6 and varied from 0.55 (RudP) to 0.74 (Amm). ###### Microsatellite diversity indices of the samples collected from 22 sites and results of the Hardy--Weinberg equilibrium test Sample Indices SsHae Str15 Str58 Str60 Sso25 Sso438 Str73 Sso417 Str85 Mean -------- --------- -------- -------- ----------- -------- ----------- ----------- ---------- -------- -------- -------- Amm *N* 32 32 32 32 32 27 32 32 31 *A* 10 5 13 2 10 4 4 8 6 6.889 A~R~ 8.616 4.488 10.919 2 8.32 3.83 3.5 7.632 5.389 6.077 H~E~ 0.843 0.695 0.88 0.482 0.812 0.582 0.604 0.829 0.64 0.708 H~O~ 0.875 0.844 0.969 0.438 0.844 0.593 0.625 0.813 0.677 0.742 *F*~is~ 0.294 −0.198 −0.085 0.109 −0.024 0.001 −0.018 0.036 −0.041 −0.032 HWE −0.22 0.142 0.112 0.744 0.567 0.761 0.61 0.161 0.96 Ash *N* 36 33 35 36 36 36 34 35 36 *A* 9 5 11 2 8 3 5 9 5 5.889 A~R~ 7.51 4.223 8.22 2 6.494 2.606 4.955 6.997 4.138 5.238 H~E~ 0.824 0.671 0.644 0.277 0.766 0.155 0.74 0.782 0.639 0.611 H~O~ 0.916 0.667 0.657 0.277 0.805 0.111 0.823 0.828 0.722 0.645 *F*~is~ −0.098 0.022 −0.006 0.014 −0.037 0.3 −0.099 −0.045 −0.116 −0.042 HWE 0.453 0.986 0.708 1 0.858 0.858 0.094 0.363 0.374 Dury *N* 33 33 33 33 33 33 33 33 32 *A* 7 5 10 2 8 4 3 9 5 6.222 A~R~ 5.931 4.608 8.451 2 6.828 3.738 3 6.925 4.827 5.145 H~E~ 0.74 0.695 0.817 0.5 00 0.733 0.639 0.633 0.777 0.535 0.674 H~O~ 0.909 0.757 0.787 0.575 0.727 0.696 0.636 0.727 0.593 0.712 *F*~is~ −0.214 −0.075 0.052 −0.136 0.024 −0.074 0.01 0.08 −0.094 −0.041 HWE 0.31 0.459 0.454 0.489 0.121 0.058 0.987 0.093 0.361 EDar *N* 21 21 20 21 21 21 16 21 21 *A* 6 6 11 2 8 4 3 8 6 6 A~R~ 5.699 5.522 9.963 2 7.233 3.946 3 7.471 5.472 5.59 H~E~ 0.732 0.68 0.837 0.495 0.783 0.620 0.646 0.781 0.594 0.685 H~O~ 0.619 0.666 0.85 0.619 0.619 0.571 0.437 0.857 0.666 0.656 *F*~is~ 0.179 0.044 0.011 −0.226 **0.233** 0.103 0.352 −0.073 −0.098 −0.098 HWE 0.144 0.822 0.549 0.384 0.002 0.279 0.065 0.945 0.904 EWebB *N* 25 26 27 28 28 28 27 28 28 *A* 7 5 13 2 8 4 4 5 6 6 A~R~ 6.142 4.942 10.906 2 6.994 3.809 3.592 4.792 5.103 5.364 H~E~ 0.712 0.686 0.872 0.492 0.686 0.447 0.59 0.689 0.582 0.639 H~O~ 0.72 0.692 0.851 0.571 0.821 0.5 0.629 0.821 0.607 0.69 *F*~is~ 0.03 0.031 0.061 −0.125 −0.161 −0.082 −0.028 −0.156 −0.005 −0.041 HWE 0.969 0.516 0.265 0.705 0.845 0.332 0.965 0.763 0.632 EWebD *N* 53 56 57 57 57 52 56 57 52 *A* 8 5 16 2 9 4 5 10 5 7.111 A~R~ 6.618 4.805 11.322 2 6.829 3.957 3.569 8.182 4.259 5.727 H~E~ 0.769 0.687 0.862 0.49 0.683 0.526 0.605 0.805 0.617 0.671 H~O~ 0.811 0.642 0.877 0.508 0.701 0.634 0.535 0.754 0.634 0.677 *F*~is~ −0.036 0.083 0 −0.02 −0.008 −0.187 0.132 0.081 −0.007 0.009 HWE 0.553 0.28 0.1 1 0.769 0.51 0.336 0.237 0.078 EWebV *N* 48 48 49 48 49 48 48 49 47 *A* 8 5 17 2 9 4 4 11 6 7.333 A~R~ 7.165 4.795 12.381 2 6.752 3.838 3.333 8.405 5.521 6.021 H~E~ 0.809 0.722 0.875 0.477 0.691 0.457 0.603 0.8 0.612 0.672 H~O~ 0.75 0.75 0.918 0.479 0.653 0.458 0.667 0.877 0.489 0.671 *F*~is~ 0.095 −0.017 −0.028 0.017 0.076 0.02 −0.084 −0.075 0.222 0.023 HWE 0.079 0.476 0.858 1 0.485 0.677 0.209 0.651 0.045 EWebW *N* 77 77 77 77 77 77 77 77 77 *A* 7 5 17 2 9 5 4 11 6 7.333 A~R~ 6.245 4.34 11.712 2 6.496 3.608 3.738 8.059 4.227 5.603 H~E~ 0.749 0.688 0.882 0.494 0.668 0.455 0.628 0.77 0.414 0.639 H~O~ 0.853 0.727 0.868 0.467 0.71 0.447 0.608 0.84 0.446 0.663 *F*~is~ −0.125 −0.044 0.029 0.067 −0.05 0.031 0.046 −0.076 −0.06 −0.024 HWE 0.337 0.649 0.115 0.648 0.097 0.27 0.001 0.13 0.142 Gata *N* 34 34 34 34 34 32 32 34 34 *A* 6 4 7 2 7 3 3 5 4 4.556 A~R~ 5.925 3.991 6.185 2 6.579 2.5 3 3.94 2.941 4.118 H~E~ 0.803 0.711 0.805 0.389 0.82 0.494 0.642 0.638 0.517 0.647 H~O~ 0.823 0.764 0.823 0.411 0.764 0.468 0.656 0.647 0.47 0.647 *F*~is~ −0.01 −0.059 −0.008 −0.043 0.083 0.068 −0.006 0.001 0.106 0.014 HWE 0.036 0.76 0.182 1 0.994 0.572 0.485 0.372 0.866 Har *N* 35 39 39 40 41 39 26 38 37 *A* 9 6 19 2 11 4 4 10 7 8 A~R~ 7.81 5.649 13.924 2 7.815 3.635 3.615 8.712 6.364 6.614 H~E~ 0.843 0.798 0.912 0.488 0.775 0.487 0.633 0.845 0.812 0.733 H~O~ 0.8 0.794 0.82 0.45 0.658 0.41 0.615 0.868 0.891 0.701 *F*~is~ 0.066 0.018 0.114 0.092 0.162 0.171 0.049 −0.014 −0.084 0.057 HWE 0.353 0.552 0.145 0.752 0.351 0.294 0.783 0.394 0.888 Hem *N* 40 39 31 40 40 40 40 40 40 *A* 9 5 18 2 11 4 4 9 7 7.667 A~R~ 7.466 4.655 14.027 2 9.235 3.858 3.877 8.033 5.785 6.548 H~E~ 0.824 0.751 0.907 0.474 0.858 0.556 0.674 0.825 0.609 0.72 H~O~ 0.75 0.794 0.935 0.375 0.875 0.575 0.65 0.85 0.6 0.711 *F*~is~ 0.103 −0.045 −0.014 0.222 −0.006 −0.02 0.048 −0.018 0.028 0.025 HWE 0.281 0.831 0.616 0.185 0.735 0.808 0.371 0.845 0.323 Hol *N* 26 29 29 29 29 17 24 25 28 *A* 10 6 13 3 9 4 3 9 6 7 A~R~ 9.109 5.535 10.373 2.552 7.718 3.998 3 8.017 5.806 6.234 H~E~ 0.826 0.775 0.848 0.463 0.717 0.624 0.6 0.752 0.718 0.703 H~O~ 0.807 0.724 0.862 0.482 0.758 0.47 0.541 0.8 0.714 0.684 *F*~is~ 0.043 0.083 0.002 −0.025 −0.04 0.275 0.119 −0.042 0.024 0.046 HWE 0.353 0.309 0.191 1 0.898 0.08 0.308 0.588 0.735 LChe *N* 58 59 57 55 58 58 52 59 57 *A* 8 5 16 2 9 5 4 10 5 7.111 A~R~ 6.95 4.555 10.839 2 6.37 4.155 3.846 8.651 4.677 5.783 H~E~ 0.789 0.625 0.872 0.495 0.745 0.622 0.629 0.851 0.571 0.689 H~O~ 0.741 0.627 0.807 0.472 0.793 0.724 0.73 0.949 0.578 0.713 *F*~is~ 0.078 0.014 **0.093** 0.063 −0.047 −0.147 −0.141 −0.098 0.004 −0.018 HWE 0.403 0.686 0.171 0.787 0.488 0.107 0.719 0.364 0.372 RudB *N* 90 92 94 96 93 92 90 94 92 *A* 5 5 8 2 3 3 4 6 4 4.444 A~R~ 4.508 4.679 7.681 2 2.994 2.744 3.069 5.137 3.615 4.047 H~E~ 0.677 0.704 0.828 0.496 0.554 0.426 0.524 0.687 0.555 0.606 H~O~ 0.722 0.75 0.787 0.479 0.58 0.326 0.422 0.659 0.543 0.585 *F*~is~ −0.055 −0.053 0.061 0.045 −0.037 **0.245** 0.206 0.052 0.033 0.045 HWE 0.334 0.58 0.434 0.686 0.453 0.014 0.021 0.022 0.927 RudC *N* 35 36 36 36 36 36 35 34 36 *A* 6 6 9 2 4 3 4 6 4 4.889 A~R~ 5.332 5.262 7.957 2 3.693 2.953 3.825 5.839 3.953 4.535 H~E~ 0.625 0.576 0.832 0.475 0.569 0.519 0.591 0.781 0.664 0.626 H~O~ 0.628 0.556 0.972 0.583 0.583 0.472 0.685 0.852 0.778 0.679 *F*~is~ 0.025 0.065 −0.14 −0.199 0.003 0.119 −0.131 −0.061 −0.144 −0.056 HWE 0.093 0.172 0.754 0.305 0.11 0.685 0.122 0.578 0.312 RudP *N* 96 94 94 98 95 92 96 96 95 *A* 5 5 10 2 3 3 4 8 4 4.889 A~R~ 4.904 4.67 7.256 2 2.817 2.538 3.852 5.251 3.27 4.062 H~E~ 0.706 0.644 0.802 0.462 0.467 0.428 0.595 0.64 0.246 0.554 H~O~ 0.708 0.595 0.787 0.489 0.505 0.445 0.5 0.645 0.242 0.546 *F*~is~ 0.008 0.086 0.03 −0.049 −0.069 −0.028 **0.17** 0.003 0.027 0.026 HWE 0.745 0.007 0.106 0.669 0.136 0.768 0.109 0.174 0.097 Swin *N* 76 80 80 80 80 74 80 80 74 *A* 9 5 17 2 11 4 5 10 8 7.889 A~R~ 6.327 4.667 11.744 2 7.182 3.858 3.688 9.061 6.225 6.084 H~E~ 0.753 0.707 0.886 0.471 0.786 0.558 0.636 0.849 0.707 0.706 H~O~ 0.802 0.737 0.912 0.425 0.837 0.621 0.7 0.85 0.783 0.741 *F*~is~ −0.052 −0.03 −0.017 0.111 −0.052 −0.099 −0.088 0.012 −0.094 −0.036 HWE 0.292 0.335 0.428 0.352 0.133 0.594 0.217 0.186 0.445 UChe *N* 68 70 69 68 67 66 68 64 67 *A* 7 5 15 2 9 5 4 10 7 7.111 A~R~ 6.01 4.86 11.507 2 7.525 3.921 3.417 8.267 5.35 5.837 H~E~ 0.773 0.684 0.891 0.492 0.796 0.588 0.659 0.814 0.599 0.699 H~O~ 0.735 0.657 0.898 0.441 0.716 0.651 0.691 0.796 0.641 0.692 *F*~is~ 0.064 0.054 0.007 0.118 **0.116** −0.093 −0.033 0.038 −0.056 0.026 HWE 0.765 0.086 0.244 0.462 0.17 0.592 0.735 0.535 0.865 WDar *N* 114 112 116 119 118 103 112 118 117 *A* 8 6 15 2 9 5 5 11 7 7.556 A~R~ 5.884 4.62 11.142 2 6.042 3.426 3.286 8.167 4.754 5.48 H~E~ 0.746 0.695 0.89 0.495 0.755 0.544 0.654 0.829 0.579 0.688 H~O~ 0.78 0.687 0.922 0.512 0.779 0.514 0.687 0.813 0.572 0.696 *F*~is~ −0.036 0.02 −0.027 −0.026 −0.023 0.065 −0.041 0.027 0.021 −0.004 HWE 0.736 0.271 0.939 0.854 0.427 0.703 0.991 0.279 0.099 Web *N* 32 32 32 31 32 21 29 28 31 *A* 10 2 12 2 9 4 4 8 6 6.333 A~R~ 8.276 4.994 9.874 2 7.129 3.751 3.551 7.341 5.009 5.769 H~E~ 0.788 0.758 0.871 0.481 0.68 0.447 0.618 0.785 0.53 0.662 H~O~ 0.75 0.781 0.875 0.483 0.656 0.285 0.758 0.785 0.516 0.654 *F*~is~ 0.064 −0.014 0.011 0.011 0.052 **0.383** −0.21 0.017 0.044 0.029 HWE 0.706 0.493 0.474 1 0.029 0.045 0.417 0.11 0.492 WWeb *N* 122 122 114 125 125 115 120 125 112 *A* 11 5 18 2 9 4 4 10 7 7.778 A~R~ 7.546 4.732 11.109 2 6.298 3.875 3.58 8.011 4.844 5.777 H~E~ 0.775 0.728 0.88 0.497 0.681 0.544 0.632 0.838 0.595 0.686 H~O~ 0.778 0.721 0.877 0.44 0.728 0.547 0.633 0.864 0.642 0.692 *F*~is~ 0.005 0.019 0.013 0.124 −0.06 0.002 0.007 −0.022 −0.07 −0.001 HWE 0.276 0.07 0.742 0.221 0.646 0.709 0.191 0.489 0.668 WWebL *N* 29 24 33 33 33 31 31 31 26 *A* 8 5 15 2 8 4 3 11 5 6.778 A~R~ 6.675 4.968 11.846 2 6.531 3.76 3 9.709 4.546 5.893 H~E~ 0.763 0.749 0.891 0.477 0.64 0.493 0.608 0.868 0.507 0.666 H~O~ 0.827 0.75 0.939 0.545 0.515 0.387 0.741 0.87 0.461 0.671 *F*~is~ −0.067 0.02 −0.039 −0.127 **0.21** 0.231 −0.204 0.014 0.11 0.01 HWE 0.176 0.024 0.337 0.711 0.14 0.155 0.406 0.161 0.176 Mean *N* 1178 1188 1187 1216 1213 1137 1150 1196 1158 *A* 13 7 27 3 13 6 5 13 10 A~R~ 6.666 4.798 10.424 2.025 6.54 3.559 3.513 7.39 4.822 H~E~ 0.795 0.734 0.902 0.499 0.741 0.533 0.676 0.836 0.6 H~O~ 0.775 0.705 0.863 0.473 0.707 0.504 0.628 0.802 0.585 *n*, number of individuals; A, number of alleles; A~R~, allelic richness; H~O~, observed heterozygosity; H~E~, expected heterozygosity; *F*~is~, inbreeding coefficient (values in bold differ significantly from zero at the 5% level, although none remained significant after table-wide Bonferroni correction); HWE, *P*-value of the Hardy--Weinberg equilibrium test. Tests for the homogeneity of allele frequency distributions revealed significant genetic differentiation occurred between the majority of the 231 pairwise comparisons, except in nine cases (upper diagonal, [Table 3](#tbl3){ref-type="table"}), of which approximately half involved samples collected from within the same tributary. Quantification of genetic differentiation with *F*~ST~ values (lower diagonal, [Table 3](#tbl3){ref-type="table"}), demonstrated a range of 0.00--0.16, with a global *F*~ST~ of 0.04. The highest *F*~ST~ occurred between samples above significant barriers to fish movement, whereas the lowest, and nonsignificant *F*~ST~ values, tended to occur between (but not exclusively between) proximate samples from the same or neighbouring tributaries. ###### Tests for genetic differentiation between pairs of samples Amm Ash Dury EDar EWebB EWebD EWebV EWebW Gata Har Hem Hol LChe RudB RudC RudP Swin UChe WDar Web WWeb WWebL ------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ----------- ---------- ---------- ------------ Amm **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** NS **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** ***^\*^*** Ash **0.050** **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** ***^\*^*** Dury **0.021** **0.091** **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** EDar 0.016 **0.068** 0.021 **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** EWebB **0.023** **0.085** 0.017 0.023 **--** **^\*^** NS NS **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** NS **^\*^** **^\*^** EWebD **0.025** **0.068** **0.021** 0.016 0.005 **--** NS **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** NS **^\*^** **^\*^** EWebV **0.021** **0.054** **0.020** 0.013 0.007 0.007 **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** NS **^\*^** **^\*^** EWebW **0.023** **0.077** 0.012 **0.021** 0.000 0.004 0.004 **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** Gata **0.050** **0.067** **0.086** **0.073** **0.087** **0.079** **0.058** **0.076** **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** Har **0.013** **0.068** **0.042** **0.040** **0.040** **0.032** **0.028** **0.045** **0.079** **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** Hem 0.000 **0.041** **0.021** 0.020 0.020 **0.018** 0.018 **0.017** **0.031** 0.011 **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** Hol **0.014** **0.050** **0.028** 0.016 **0.029** **0.019** 0.005 **0.020** **0.053** 0.018 0.007 **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** LChe **0.019** **0.077** 0.013 0.007 **0.024** **0.019** **0.020** **0.019** **0.077** **0.043** **0.023** **0.026** **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** RudB **0.076** **0.119** **0.056** **0.072** **0.039** **0.045** **0.046** **0.044** **0.140** **0.073** **0.071** **0.067** **0.054** **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** RudC **0.068** **0.122** **0.056** **0.061** **0.026** **0.027** **0.045** **0.031** **0.129** **0.067** **0.066** **0.065** **0.048** **0.021** **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** RudP **0.092** **0.153** **0.053** **0.095** **0.059** **0.078** **0.064** **0.053** **0.160** **0.112** **0.090** **0.090** **0.071** **0.033** **0.061** **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** Swin **0.016** **0.079** 0.015 0.013 **0.024** **0.021** **0.026** **0.029** **0.083** **0.027** **0.018** **0.029** 0.011 **0.060** **0.050** **0.090** **--** **^\*^** **^\*^** **^\*^** **^\*^** **^\*^** UChe **0.016** **0.081** 0.012 0.008 0.020 **0.017** **0.021** **0.019** **0.072** **0.036** 0.013 **0.027** 0.000 **0.050** **0.044** **0.071** 0.006 **--** **^\*^** **^\*^** **^\*^** **^\*^** WDar **0.021** **0.065** **0.024** 0.013 **0.034** **0.031** **0.023** **0.034** **0.075** **0.041** **0.018** **0.026** **0.009** **0.063** **0.076** **0.088** **0.014** **0.011** **--** **^\*^** **^\*^** **^\*^** Web **0.029** **0.091** 0.013 0.023 0.000 0.000 0.008 0.002 **0.086** 0.036 0.017 0.022 **0.020** **0.025** 0.018 **0.050** **0.021** 0.014 **0.030** **--** **^\*^** NS WWeb **0.021** **0.077** 0.013 **0.033** 0.011 **0.012** **0.012** **0.011** **0.081** **0.023** **0.019** **0.024** **0.029** **0.040** **0.039** **0.060** **0.025** **0.025** **0.034** 0.005 **--** NS WWebL **0.021** **0.099** 0.013 **0.026** 0.015 0.009 0.010 0.013 **0.086** 0.027 **0.016** **0.025** **0.024** **0.037** **0.034** **0.063** 0.013 **0.016** **0.025** 0.000 0.000 **--** The upper diagonal shows pairwise *F*~ST~ values; all significant values (*P* \< 0.05) are highlighted in bold. The lower diagonal shows the result of tests for homogeneity of allele frequencies: NS, not significant; ^\*^significant at the 5% level. Table-wide significance levels were applied using the sequential Bonferroni procedure (*k* = 231) for all tests. The NJ *D*~CE~ phylogram ([Fig. 2](#fig02){ref-type="fig"}) reveals several samples that have high bootstrap support and relatively long branch lengths, namely the Rud group of samples and the Gata and Ash; this relates well to their positions above significant barriers to fish movement ([Fig. 1](#fig01){ref-type="fig"}) that may have acted to isolate these samples from the rest of the catchment. Moderate support is also noted on the phylogram among groups of samples from the upper west (Che, WDar, Swin, Dury and EDar), upper east (Web, EWeb and WWeb) and lower (Amm, Har, Hol and Hem) areas of the catchment. In addition, there is some support for proximate groups of samples, especially those collected within the same tributary, e.g. within the West and the East Webburn. A principal component analysis (PCA) was also performed on these data using the default settings in [genalex]{.smallcaps} 6 ([@b50]), the findings of which support the main conclusions of the phylogram; the PCA plot in [Fig. S1](#SD1){ref-type="supplementary-material"}. {ref-type="table"}.](eva0002-0537-f2){#fig02} Decomposed pairwise regression ------------------------------ Genetic distance was positively correlated with geographic distance when comparing all pairwise sample combinations, but the correlation was weak and nonsignificant (*P* = 0.137, *r*^2^ = 0.036; [Fig. 3](#fig03){ref-type="fig"}). Based on the systematic bias of the regression residuals (process one) nine putative outlier samples were detected; RudP, Ash, Gata, RudB, RudC, Hem, Amm, WDar and UChe. The AIC values were compared for models with and without putative outliers (process two) and the best model included 17 samples (indicating RudP, Ash, Gata, RudB and RudC were true outliers; [Table 4](#tbl4){ref-type="table"}). This result is consistent with *a priori* predictions as all these samples originated from sites above significant barriers to fish movement. The exclusion of these samples strengthened the positive correlation between genetic and geographic distance, which also become statistically significant (*P* \< 0.001, *r*^2^ = 0.476; [Fig. 3](#fig03){ref-type="fig"}). Each of the outlier samples was individually regressed with the nonoutlier samples, which indicated that the majority of outlier samples were significantly diverged from adjacent populations but exhibited strong and significant correlations between genetic and geographic distance ([Fig. 4](#fig04){ref-type="fig"}). This suggests that despite of a strong effect of genetic drift acting on the isolated samples (either through small effective population size or founder effects or bottleneck) evidence of gene-flow still remains. The Ash sample was the exception; while significantly divergent from the other samples, it showed no correlation between genetic and geographic distance, suggesting that the effect of genetic drift far outweighs that of gene flow. The decomposed regressions of the 17 nonoutlier samples showed similar regression lines with significant relationships between genetic and geographic distance, except for the Amm, Hol and Swin ([Fig. 4](#fig04){ref-type="fig"}). This suggests that these samples are close to, or at, equilibrium between drift and gene flow. ![Relationship between genetic distance \[*F*~ST~/(1 − *F*~ST~)\] and geographic distance (km) for all 22 samples (open and closed diamonds combined; *r*~*xy*~ = 0.191, *P* = 0.137, *r*^2^ = 0.036, upper line) and excluding the five outlier samples (filled diamonds only; *r*~*xy*~ = 0.690, *P* \< 0.001, *r*^2^ = 0.476, lower line).](eva0002-0537-f3){#fig03} ###### Fit of alternative models with and without the putative outlier samples Samples excluded *n* *k* *r*^*2*^ *P* value AIC~C~ ΔAIC~C~ --------------------------------------------------- ----- ----- ---------- ----------- --------- --------- RudP, Ash, Gata, RudB, RudC 17 1 0.4768 \<0.001 −108.49 0.00 RudP, Ash, Gata, RudB, RudC, Hem 16 1 0.5281 \<0.001 −103.26 5.23 RudP, Ash, Gata, RudB, RudC, Hem, Amm 15 1 0.6292 \<0.001 −99.37 9.12 RudP, Ash, Gata, RudB, RudC, Hem, Amm, WDar 14 1 0.6504 \<0.001 −94.50 13.98 RudP, Ash, Gata, RudB 18 1 0.1353 0.064 −90.73 17.76 RudP, Ash, Gata, RudB, RudC, Hem, Amm, WDar, UChe 13 1 0.6459 \<0.001 −87.68 20.81 RudP, Ash, Gata 19 1 0.0612 0.1099 −86.11 22.38 RudP, Ash 20 1 0.0880 0.066 −75.52 32.97 RudP 21 1 0.0589 0.076 −72.33 36.16 None 22 1 0.0335 0.142 −68.86 39.63 *n* refers to the number of samples and *k* the number of parameters. ![Decomposed pairwise regression of genetic distance \[*F*~ST~/(1 − *F*~ST~)\] and geographic (km) distances for the 22 samples. Each of the five outlier samples was regressed with the 17 nonoutlier samples, whilst each of the 15 nonoutliers was regressed with the other 14 samples. Solid and dashed lines represent statistically significant or nonsignificant regressions respectively.](eva0002-0537-f4){#fig04} Spatial autocorrelation ----------------------- Tests of microspatial autocorrelation at the level of the individual were carried out on samples not isolated above barriers to fish movement (this included all 17 samples not identified in the DPR as true outliers). The results showed that the genetic autocorrelation coefficient (*r*) was significantly positive at the 0--5 and 5--15 km size classes, and intercepted the *x*-axis at 20 km ([Fig. 5A](#fig05){ref-type="fig"}); results from the analysis of alternative classes produced broadly similar results, with intercepts ranging from 15 to 20 km (results not shown). In all size classes above 15 km, *r* was significantly negative, meaning that proximal individuals showed greater genetic divergence than that expected for a random distribution of genotypes, although in the largest size classes *r* approached the null hypothesis of no significant structure. The MDC analysis with increasing distance size classes revealed that *r* was significantly positive for distance classes up to and including 25 km ([Fig. 5B](#fig05){ref-type="fig"}). The inclusion of specimens separated by \>45 km meant that significant positive genetic autocorrelation was no longer observed. The addition of samples collected above barriers did not radically alter the results of the spatial autocorrelation (analysis not shown), except in the correlogram ([Fig. 5A](#fig05){ref-type="fig"}), in which case *r* was not as strongly negative (*r* = −0.015 in the 25 km class) and at the largest distance class the null hypothesis could not be rejected. However, because of the uncertainties of applying an individual-based test to samples collected at specific sample sites (where separation between individuals is assumed to be zero), these findings should be interpreted with some caution. {#fig05} Discussion ========== The purpose of this study was to examine, within-catchment population structure of brown trout in a region that despite being a focus for salmonid fishing and conservation, has until now, received relatively little attention. The results revealed significant differentiation among samples collected within a single river catchment and, in the case of the Ruddycleave and Cherry Brook, even between sample sites within a tributary. These results demonstrate that Dart trout do not represent a single panmictic population in which gene flow is unrestricted across the catchment. The global *F*~ST~ across all 22 samples sites was 0.04, with a range of 0.000--0.160 for pairwise *F*~ST~ estimates, which accords with previous work on brown trout employing microsatellites (e.g. [@b9], *F*~ST~ = 0.00--0.114; [@b35], 0.009--0.065; [@b31], 0.010--0.071; [@b47], 0.004--0.154). Effect of barriers ------------------ What is particularly striking from the phylogram ([Fig. 2](#fig02){ref-type="fig"}) and pairwise *F*~ST~ estimates ([Table 3](#tbl3){ref-type="table"}) is the effect barriers have on population structure; the largest values all occur between comparisons involving samples isolated above a barrier to fish movement. The significant effect of barriers on population structure has been previously documented and has been associated with reductions in population size, bottlenecks and genetic drift ([@b33]; [@b42]; [@b49]; [@b73]). Such processes may also have been in operation in these isolated samples identified within the River Dart, as the levels of heterozygosity and allelic richness were also depressed ([@b11]). The results of the DPR analysis also afford some further insight into the demographic processes occurring within these samples. In the case of the Ash sample, genetic drift has acted to obscure any correlation between genetic and geographic distance between samples; as the barrier to migration on this tributary is man-made (and therefore not ancient), small effective population size and founder effects appear to be the most likely explanation for the patterns of genetic divergence observed. In the case of the other highly diverged and isolated samples (RudC, RudB, RudP and Gata) a relatively strong correlation between genetic and geographic distance remains, suggesting that effective population sizes have not been reduced to the level that genetic drift is strong enough to obscure the correlation. Alternatively, some form of gene flow could be occurring, perhaps associated with barriers being by-passed in high flows. However, it is interesting to postulate that unidirectional, downstream migration from the isolated areas could act to partially restore the correlation between genetic and geographic distance. The importance of identifying barriers to fish movement has been highlighted for a number of conservation issues, in particular, the negative effects of genetic drift in small populations and the isolation of indigenous stocks from the effects of stocking undertaken below barriers ([@b79]; [@b73]), both topics that appear to warrant further investigation within the River Dart. Population structure and evolutionary models -------------------------------------------- The phylogram ([Fig. 2](#fig02){ref-type="fig"}) shows that genetic structuring among samples within the catchment is present; moderate levels of bootstrap support occurred between three groups of proximate samples from the upper east, upper west and lower Dart. This association between genetic and geographic distance is further supported by a significant effect of isolation-by-distance, as demonstrated by DPR analysis ([Fig. 4](#fig04){ref-type="fig"}). However, a strongly negative genetic correlation (*r*) was identified at the 25 and 45 km size classes used in the spatial autocorrelation on Dart trout ([Fig. 5A](#fig05){ref-type="fig"}), meaning that proximal individuals showed greater genetic divergence than that expected for a random distribution of genotypes. Such a finding may be the result of a discontinuity in gene flow between trout in different tributaries or could reflect the fact that some sampling was completed outside of the spawning season, and therefore, may include adult specimens of trout that may have moved away from nursery areas. The observation of isolation-by-distance at the intra-catchment level is somewhat at odds with many of previous studies describing the population structure of brown trout ([@b12]; [@b22]; [@b43]; [@b4]; [@b61]), although, it is not unique ([@b19]; [@b8]). Recent studies of anadromous brown trout inhabiting relatively small rivers in Denmark and the Baltic Sea ([@b39]; [@b47]; [@b35]) suggested a population structure consisting of a system of highly interconnected, small and unstable populations where, in accordance with the metapopulation model, there was no significant effect of isolation-by-distance and a lack of temporal stability (even over the short-term). This pattern was generally linked to high levels of gene flow and occasional extinction--recolonization events caused by environmental instability, e.g. low summer water levels ([@b47]). These results sharply contrast with the population structure described in this study, where a significant effect of isolation-by-distance (once outliers have been excluded) and at least short-term temporal stability of population structure was observed. Therefore, it appears that, despite the potential for low pH to perturb the environment, the population structure of brown trout inhabiting the tributaries of the River Dart is determined more by ecological events and natal homing, than by rare stochastic extinction events, with migration occurring mostly between neighbouring groups. The key to reconciling these contrasting results among studies appears to be catchment size, whereby larger population systems appear to be stable and smaller systems tend to undergo localized extinction--recolonization events ([@b31]; [@b47]; [@b35]; [@b44]; [@b55]). Historical and temporal effects ------------------------------- There are some limitations to this study; in particular, the effects of postglacial recolonization and stocking on population structure of Dart trout still await assessment. Although, the results of the DPR analysis suggests the majority of the samples are at, or close to, drift--migration equilibrium following such perturbation ([Fig. 4](#fig04){ref-type="fig"}). In particular, these processes (especially artificial stocking), would generally have acted to obscure the strong pattern of isolation-by-distance identified in this study ([@b38]; [@b45]), suggesting they are not the strongest determinants of population structure in this case. In addition, the temporal samples collected in the study represent only a subset of sites from across the catchment and cover a relatively short period: 2002--2004. [@b49] found that the probability of detecting significant allele frequency differences between temporal samples taken from the same population, but spaced only a few years apart, could be small. Indeed, if extinction events happen infrequently, i.e. over the scale of decades, then this instability may not become evident in samples taken only a few years apart (although the strong pattern of isolation-by-distance identified suggests longer term temporal stability, at least as long as it takes for drift--migration equilibrium to be established after perturbation). Evolutionary hypotheses ----------------------- The hypotheses proposed by [@b24] provide a useful framework within which to analyse population structure; however, they remain quite general and any situation in which gene flow is limited by geographic distance may yield similar results. Indeed, work on genetic population structure of Dolly Varden charr (*Salvelinus malma*; [@b37]) yielded analogous results to the present study, but the authors suggested that a source-sink metapopulation structure best fitted their results. In that case, outlier samples were identified in the absence of barriers to migration, suggesting founder effects or bottlenecks had occurred; such factors have not been identified within the current study of the River Dart (where the results of the DPR actually suggest relatively stable population structure). Additionally, many of the predictions of the proposed models are quite simplistic, e.g. the prediction that that there would be no significant pattern of isolation by distance in a metapopulation may not hold true if recolonization and gene flow occurred predominantly between neighbouring populations (a scenario made more likely by the linear nature of a river). Another prediction, that the level of genetic structuring would be expected to be lower under a metapopulation model, can also be questioned. It has been shown that the range of *F*~ST~ estimates in this study is similar to that used previously to describe both small temporally unstable populations ([@b35]) and large stable populations ([@b31]). It appears that levels of differentiation, especially *F*~ST~ values, may not differ under the two evolutionary models summarized by [@b24] and are dependant on the complex mechanics of recolonization ([@b32]; [@b44]). Indeed, extinction--recolonization events may act to increase levels of genetic differentiation ([@b28]; [@b27]). Delineating demographic units ----------------------------- Spatial autocorrelation analyses were used to determine the geographic scale of genetic structuring within the River Dart. [Figure 4B](#fig04){ref-type="fig"} illustrates the tendency for genetic distance between individuals to decrease with increasing distance, such that at in-water distances of \>45 km gene flow is minimal. It has also been proposed that the *x*-axis intercept of the correlogram ([Fig. 5A](#fig05){ref-type="fig"}) be considered as a minimum distance that can conserve genetic diversity at a lower cost ([@b13]), resulting in a management unit size of approximately 15--20 km for the River Dart. The results from spatial autocorrelation analyses bear some similarities to work on Atlantic salmon in the Varzuga River in Russia ([@b55]), which also highlighted the importance of conserving multiple spawning and nursery areas for the long-term preservation of fish populations. However, most striking difference is the distance across which gene flow was observed within the Varzuga; the genetic correlation remained positive at distances up to 120 km and the *x*-axis intercept of the correlogram occurred at 34 km. This may reflect the larger size of the Varzuga River (when compared with the River Dart), and the fact that samples were separated by greater average in-water distances ([@b74]). Alternatively, it is interesting to hypothesize that the lower distance over which gene flow occurs in brown trout may reflect their resident life history, resulting in more restricted gene flow and greater genetic differentiation ([@b29]; [@b36]; [@b44]). Conclusions =========== Brown trout inhabiting the River Dart demonstrate significant within-river population differentiation; this differentiation is most significant when associated with barriers to movement, but otherwise demonstrates a pattern of isolation-by-distance and at least short-term temporal stability. These results are taken as evidence that ecological events are more important in shaping the population structure of Dart trout than stochastic extinction events, and certainly do not contradict the expectations of a member-vagrant evolutionary model of population structure for Dart trout ([@b24]). However, the results of the spatial autocorrelation demonstrate gene flow does occur between neighbouring samples, suggesting the need to conserve not only different spawning areas within the basin (particularly in different tributaries), but links between them as well. This research was supported by funding from the Natural Environment Research Council (NERC), UK through the award of a CASE studentship (NER/S/A/2001/06178) with the Westcountry Rivers Trust (CASE partner) and the award of a NERC training grant to work at the Sheffield Molecular Genetics Facility (SMGF/047). The EA is acknowledged for assistance in sample collection, in particular Fisheries Officers Dave Hoskin and Adam Bailey, without whom the project would not have been possible. Further acknowledgement is also due to all those who helped with fieldwork, especially Jan Shears and Phil Shears, and to Anna Finnegan for provision of stocking data and GIS support. This study also benefited from technical training by members of the Sheffield Molecular Genetics Facility: Terry Burke, Deborah Dawson and Andy Krupa. Supporting Information ====================== Additional Supporting Information may be found in the online version of this article: **Figure S1.** Principal componentanalysis plotted from a matrix of pairwise Nei\'s geneticdistances between all populations and computed using the programgenalex (Peakall andSmouse 2006). Axis 1 explains 36% of the variation and axis 2, 22%of the variation. Populations analysed are the same as thoseanalysed in the phylogram ([Fig. 2](#fig02){ref-type="fig"}); sample abbreviationsmatch [Table 1](#tbl1){ref-type="table"}. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. | High | [
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‘Westworld’ Season 2 Will Mess With Reddit to Preserve Spoilers Westworld fans are champing at the bit to unravel Season 2’s mysteries, but showrunners are prepared this time. Co-creator Jonathan Nolan hints that they’ve developed a “controversial” strategy to avoid Reddit piecing together every twist ahead of schedule. Nolan and co-creator Lisa Joy suggested as much from the WestworldSXSW panel, joking that “We love to f— with Reddit as much as possible.” The first season was famously picked apart by legions of fans, who predicted early on that – spoiler alert – Season 1 took place in two timelines thirty years apart, and that Jimmi Simpson’s “William” would be revealed as a younger version of Ed Harris’ character. It isn’t clear how exactly Nolan and Joy plan to protect Season 2 plotlines, though they acknowledge the problem requires a new strategy (via Polygon): Part of it stems from other shows. True Detective had a lot of fan theories that proved to be theories. There are lot of theories about Westworld’s first season that proved to be plot twists. I think for every fan theory, we actually had an episode that dealt with it. We’re figuring out how to sort of interact with that in the second season. A somewhat controversial plan that we’re working on; we’ll have an announcement about it in a couple weeks. It’s incredibly gratifying to see people put that much work — not just into deciphering the season, but the fan art and music. The creativity you see coming back at you when you’re making one of these things is extraordinary. Some have suggestedWestworld might look to Game of Thrones for inspiration, as those with advance knowledge of George R.R. Martin’s books often work together to preserve the experience for newcomers. An avalanche of deliberately fake Westworld theories, perhaps? The game begins anew on April 22, so watch the trailer and stay tuned for the latest on Westworld Season 2. | Mid | [
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@php use Illuminate\Support\Facades\Route; @endphp <!DOCTYPE html> <html lang="{{ config('app.locale') }}"> <head> <meta charset="utf-8"> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="viewport" content="width=device-width, initial-scale=1"> <meta name="csrf-token" content="{{ csrf_token() }}"> <title>@yield('title', app_name())</title> <!-- Meta --> <meta name="description" content="@yield('meta_description', 'Laravel AdminPanel')"> <meta name="author" content="@yield('meta_author', 'Viral Solani')"> <meta name="keywords" content="@yield('meta_keywords', 'Laravel AdminPanel')"> @yield('meta') <!-- Styles --> @yield('before-styles') <!-- Check if the language is set to RTL, so apply the RTL layouts --> <!-- Otherwise apply the normal LTR layouts --> @langrtl {{ Html::style(getRtlCss(mix('css/frontend.css'))) }} @else {{ Html::style(mix('css/frontend.css')) }} @endlangrtl {!! Html::style('js/select2/select2.min.css') !!} @yield('after-styles') <!-- Scripts --> <script> window.Laravel = <?php echo json_encode([ 'csrfToken' => csrf_token(), ]); ?> </script> <?php if (!empty($google_analytics)) { echo $google_analytics; } ?> </head> <body id="app-layout"> <div id="app"> @include('includes.partials.logged-in-as') @include('frontend.includes.nav') <div class="container"> @include('includes.partials.messages') @yield('content') </div><!-- container --> </div><!--#app--> <!-- Scripts --> @yield('before-scripts') {!! Html::script(mix('js/frontend.js')) !!} @yield('after-scripts') {{ Html::script('js/jquerysession.min.js') }} {{ Html::script('js/frontend/frontend.min.js') }} {!! Html::script('js/select2/select2.min.js') !!} <script type="text/javascript"> if("{{Route::currentRouteName()}}" !== "frontend.user.account") { $.session.clear(); } </script> @include('includes.partials.ga') </body> </html> | Low | [
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I. Field of the Invention This invention relates generally to apparatus for refurbishing pipes, valves, flanges and the like in industrial plants, such as power generation facilities, petroleum pipeline facilities and the like, and more particularly to a portable lathe machine that can be rapidly set up and used in the field to accurately machine flat or beveled surfaces on pipe flanges, valve, fittings and pipe ends within close tolerance ranges. II. Discussion of the Prior Art Various portable machines for performing different machining operations are known in the art. In the refurbishment of industrial tubing, such as is found in refineries, pipelines, steam power plants and the like, it is often necessary to cut through a pipe and then perform one or more end prep operations, such as beveling, facing, threading, etc. to thereby facilitate the joining of pipe ends or flanges. The Wachs et al. U.S. Pat. No. 4,411,178 describes a typical prior art machine for end prepping pipes and piping components. In that machine, separate drive motors are required for causing radial and axial feed of the tool. The feed rates are controlled by controlling the speed of the two motors. Moreover, the design reflected in the Wachs et al. '178 patent precludes the tool slide and tool supported thereby to be placed at an angle to the base plate 30, thus making it more difficult to accurately bevel the end of a pipe workpiece. The present invention also comprises an improvement over my earlier portable end prep machine described in U.S. Pat. No. 4,799,409. For example, in that earlier design, no provision is made for an adjustable radial feed rate of the cutting tool, nor is any provision made for tilting the tool slide at a desired angle to the axis of the pipe to facilitate mitering or beveling of the pipe end being machined. Further, no provision is made for accurately gauging movement in the axial feed direction as an operator manually attempts to adjust axial displacement of the housing on which the tool head is mounted. | Mid | [
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import Vue from 'vue'; import IssuableHeaderWarnings from './issuable_header_warnings.vue'; export default function issuableHeaderWarnings(store) { return new Vue({ el: document.getElementById('js-issuable-header-warnings'), store, render(createElement) { return createElement(IssuableHeaderWarnings); }, }); } | Low | [
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1 Suppose 29 = 3*b + z, 4*b + 2*z = 3*z + 34. Calculate the remainder when 34 is divided by b. 7 Let v = 7 - 6. Calculate the remainder when 7 is divided by 3*(-6)/(-9) + v. 1 Let b be ((-18)/(-45))/(1/5). Suppose 2*p + 450 = 5*h, 2*h + p - 179 = b*p. Calculate the remainder when h is divided by 31. 30 Let w(i) = -3*i**2 + 11 - i + 5 - 2*i**2 + 4*i**2. What is the remainder when 63 is divided by w(0)? 15 Suppose f = -0*f. Suppose f*x - 21 = -3*x. What is the remainder when x is divided by 3? 1 Let o = 170 + -154. What is the remainder when 79 is divided by o? 15 Suppose 9 = 4*z + 33. Let u be (245/15)/(2/z). Calculate the remainder when 50 is divided by u/(-3) - (-2)/3. 16 Let j = 1 + 4. Let d = 14 - j. What is the remainder when d is divided by 2? 1 Suppose 4*a + 80 = 96. What is the remainder when 12 is divided by a? 0 Let n = 30 + -22. What is the remainder when 14 is divided by n? 6 Suppose -5*b + 4*b = -5*z + 108, -4*z + 5*b + 99 = 0. Suppose -5*t + z - 117 = -4*u, -t = -3*u + 72. What is the remainder when 71 is divided by u? 23 Suppose -2*d = -4*h - 22, -5*h = -2*d + 3 + 24. Let c = 6 + d. Calculate the remainder when (-10)/4*(-11 - -3) is divided by c. 6 Suppose 26*p - 40 = 22*p. Calculate the remainder when p is divided by 6. 4 Calculate the remainder when (1 + 138/3)*1 is divided by 16. 15 Let r(h) be the second derivative of h**4/12 - h**3 + 3*h**2 + 4*h. Calculate the remainder when r(-6) is divided by 20. 18 Let k(n) = -n**2 + 7*n - 3. Let r be k(6). Suppose w - 20 - r = 0. Calculate the remainder when w is divided by 8. 7 Suppose 0 = -3*u + 12. What is the remainder when u is divided by 3? 1 Let c(z) = 4*z. Let l be c(1). Suppose k + 2 = -3, l*m - k = 29. Calculate the remainder when 11 is divided by m. 5 Suppose -3 = -4*u + 93. Suppose -3*l = -2*l - 2. Suppose 2*s = 3*z - 41, -2*s - 2 = l*z - 26. Calculate the remainder when u is divided by z. 11 Let s(a) = a**2 + 8*a + 6. Let p be s(-7). Let j be (4/10)/(p/(-90)). What is the remainder when 35 is divided by j*2/(12/3)? 17 Let t(l) = 2*l**3 - 8*l**2 + 7*l + 7. Let y be t(7). Suppose 2*k = -0*k + y. Suppose -7*h = -2*h - k. What is the remainder when h is divided by 12? 11 Let t be (-104 + -6)*(-12)/(-5). Calculate the remainder when ((t/(-2))/3)/2 is divided by 8. 6 Let k(l) = l**3 - 3*l**2 - 15*l + 12. What is the remainder when 149 is divided by k(6)? 29 Let b(j) = j**2 + 5*j + 4 - 5*j + 4*j. Let r be b(-4). Suppose -3*o + r*a = -42, 2*a + 0*a - 34 = -4*o. Calculate the remainder when o is divided by 6. 4 Calculate the remainder when 75 is divided by (-1)/1*(-8 + -11). 18 Let f = 69 - 109. Let u = 57 + f. Calculate the remainder when u is divided by 6. 5 Suppose -3*i - i + 3*x = -388, 2*i - 176 = -3*x. Let r be (-6)/(-27) + i/(-18). Let f = 5 - r. What is the remainder when f is divided by 4? 2 Let z(u) = -u**2 + 5*u + 3. Suppose 10 - 30 = -5*n. What is the remainder when z(4) is divided by n? 3 Suppose 2*v = 117 - 1. What is the remainder when v is divided by 10? 8 Let d = -138 - -146. What is the remainder when 19 is divided by d? 3 Calculate the remainder when -43*(2 - 3)/1 is divided by 4. 3 Suppose 3 = -4*o + 19. Calculate the remainder when 19 is divided by (-448)/(-44) + o/(-22). 9 Let j = -4 + 4. Let q(c) = 3 - 3 + 20 - 2*c + 3*c. What is the remainder when 38 is divided by q(j)? 18 Let d = 6 - -1. Calculate the remainder when d is divided by 4. 3 Suppose 0 = 21*r - 18*r - 981. What is the remainder when r is divided by 41? 40 Suppose 4*c + 8 = 6*c. Let o(m) = -m**3 + 2. Let z be 6/(-2) + -1 + 4. What is the remainder when c is divided by o(z)? 0 Suppose 5*k + 303 = -132. Suppose 8 = 5*c - c. What is the remainder when ((-12)/18)/(c/k) is divided by 10? 9 Suppose -y + 44 = 2*y + 4*a, 0 = -2*y - 3*a + 31. Calculate the remainder when y is divided by 3. 2 Let h be 4/(-6)*9/(-3). Suppose h*q - 78 - 36 = 0. Calculate the remainder when q is divided by 12. 9 Let v = 12 - 27. Let l be ((-8)/5)/(6/v). Calculate the remainder when 12 is divided by l/(-6) - (-23)/3. 5 Let m(c) = c**3 + 3*c**2 - 4*c + 2. Let o be m(-4). Let x = 38 - 6. Calculate the remainder when x is divided by (-22)/(o*(-3 + 2)). 10 Suppose 0*s = -4*s + 296. What is the remainder when s is divided by 9/(-63) - 1232/(-49)? 24 Let v be (-1796)/(-10) + 14/35. Let p = -115 + v. Calculate the remainder when p is divided by 22. 21 Let z(p) = 2*p**2 + 16*p - 22. What is the remainder when 32 is divided by z(-10)? 14 Suppose 8*h - 80 = 3*h. What is the remainder when 31 is divided by h? 15 What is the remainder when (-3)/6*2 + 50 is divided by 13? 10 Let j(t) = -3*t + 4. What is the remainder when 12 is divided by j(0)? 0 Let g(w) = -w + 10. Let j be g(6). Suppose -176 = -j*d + 4*r, d + 4*r + 0*r - 44 = 0. Let u = -34 + 49. What is the remainder when d is divided by u? 14 Let r = 35 + -9. Let p = r + -16. Let w(h) = -h**3 + 9*h**2 + 13*h - 3. What is the remainder when w(p) is divided by 10? 7 Suppose 0 = -t + 2 + 6. Suppose -2*j = -a - 45, -j - a + 12 = -9. What is the remainder when j is divided by t? 6 Let z(t) = -2*t + 2*t - t - 2 + 1 + 6*t**2 + t**3. Let i be z(-6). Suppose 3*l = i + 52. Calculate the remainder when l is divided by 10. 9 Let t(w) = -w**3 + 4*w**2 + 4*w - 7. Let x(d) = -d + 17. What is the remainder when t(4) is divided by x(14)? 0 Suppose 3*x - 21 = 2*h + h, -5 = h. Suppose -5*g + 24 = x*c, -c + g + g = -30. Calculate the remainder when 43 is divided by c. 21 Suppose -d - 29 = -v, 2*v = -2*v + 3*d + 117. Let k = -3 - -19. Calculate the remainder when v is divided by k. 14 Let n(z) = -z**3 + 22*z**2 + 25*z - 23. Calculate the remainder when 65 is divided by n(23). 19 Let y(m) = 13*m**3 + 1. Let n be 8*(-3)/(-6) + -3. What is the remainder when 40 is divided by y(n)? 12 Let z(c) = -3*c. Suppose 2*s - 4 + 2 = 0. Let w be z(s). Calculate the remainder when 51 is divided by -3 + w*(-7)/1. 15 Let h(f) = 2*f**2 + 4*f + 2. Let b be h(-3). Let t = b + 19. Suppose 4*g - 72 = -4*x, -t + 71 = 2*x + 4*g. Calculate the remainder when x is divided by 5. 4 Let k(r) = r**3 - 6*r**2 + 7*r + 2. Let n be k(5). Calculate the remainder when 19 is divided by 130/12 + 2/n. 8 Suppose 0 = -2*y + 2*j - 6, -j = -3*y + 4*j - 11. Suppose -2*c - f = -30, 4*c - 46 = 5*f - 0. Calculate the remainder when -26*(-3)/(-6)*y is divided by c. 12 Suppose 0 = 3*i, 42 = 4*k - 2*i - 2. Let j = 5 - 4. Let y = 3 + j. What is the remainder when k is divided by y? 3 Let k(w) = 6*w - 4 - 4*w**2 + 0*w + w**3 - 2*w. What is the remainder when k(4) is divided by 5? 2 Suppose 0*y = y. Let b = 9 + y. Let h(n) = -3*n + 17. Calculate the remainder when h(-3) is divided by b. 8 Let f = 11 + -7. Let j = 7 + f. Calculate the remainder when 41 is divided by j. 8 Let p(a) = a + 11. Let t be p(-8). Suppose -163 = -4*h + 5*j, j + t = -0. What is the remainder when h is divided by 19? 18 Suppose -4*q - 39 = -7*q. What is the remainder when 63 is divided by q? 11 Let p(z) = 5*z**2 + 2*z + 3. Suppose 2*w + 385 = 9*w. Calculate the remainder when w is divided by p(-2). 17 What is the remainder when 58 is divided by (-4)/6 + (-806)/(-39)? 18 Suppose 0 = 4*x - 345 - 3. What is the remainder when x is divided by 22? 21 Suppose 0 = 4*k + 3*p - 111, 0*k = -5*k - p + 136. Suppose -d - 5 = -k. What is the remainder when d is divided by 6? 4 Let c(u) be the third derivative of u**5/10 + u**4/4 + u**3 - 2*u**2. Calculate the remainder when c(-4) is divided by 20. 18 Let b(c) = c. Suppose 0 = -2*t + 4. Let m be b(t). What is the remainder when (-27)/m*4/(-6) is divided by 6? 3 Let a be 4/(-18) + (-263)/(-9). Let m = -2 + a. Calculate the remainder when m is divided by 360/26 - 6/(-39). 13 Let v(x) be the third derivative of -4/3*x**3 + 1/30*x**5 - 2*x**2 + 0 + 0*x + 1/4*x**4. Calculate the remainder when v(-6) is divided by 15. 13 Let r be (-12)/(-54) - 850/18. Let t = r - -81. Suppose -4*h - 10 = -t. Calculate the remainder when 10 is divided by h. 4 Suppose 0*z - z - 26 = 0. Let h = z - -37. Let w = h + -4. Calculate the remainder when w is divided by 4. 3 Calculate the remainder when (3 - -39)/3 - 3 is divided by 7 + (1 + -2)*1. 5 Suppose 6*r - 4*r = -3*x + 12, -r = x - 4. Suppose r = -3*k - 13 + 43. What is the remainder when k is divided by 4? 2 Let n = -66 - | Low | [
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More from Rugby League Steve McNamara: Rugby League losing its 'jewel in the crown' in Sam Burgess Steve McNamara says rugby league is losing its "jewel in the crown" with Sam Burgess switching codes to union with Bath. Last Updated: 17/02/14 10:02pm Steve McNamara: Sam Burgess a huge loss McNamara gave Burgess his Super League debut at Bradford in 2006, though the England forward then moved to South Sydney Rabbitohs. McNamara will now prepare for the end-of-season Four Nations Series in Australia and New Zealand without the 25-year-old and he is hoping Burgess' brothers, Tom and George, - who are also at South Sydney - will fill the void left by their brother's absence. McNamara, who is working as an assistant coach at Sydney Roosters, is also confident that the Super League can continue to produce world-class players. "We recognise Same is a huge loss to the game of rugby league, and particularly the England team, but we'll just have to deal with it," McNamara said. "We produce fantastic players and, because we do such a good job in that area, other sports will look our players. "It's very difficult to replace someone like Sam like for like, but you've seen the rise to prominence of George Burgess and Tom Burgess and there could be a few others who spring up as well. | Mid | [
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EXCLUSIVE: Patrick Melrose Emmy nominee Edward Berger has been set to direct Rio, the Steven Knight-penned psychological thriller that’s in advanced development from Studiocanal, SunnyMarch and Nine Stories. This is the project that I told you about last year with Benedict Cumberbatch and Jake Gyllenhaal being courted to star. Their attachments are now confirmed and they will also produce. Studiocanal is fully financing and has international sales on the film which Cumberbatch and Adam Ackland are producing under their SunnyMarch banner. Gyllenhaal and Riva Marker are producing via their Nine Stories. Rio, from the mind of Peaky Blinders, Taboo and Locke‘s Knight, centers on two old friends who meet again in the titular city. One is a journalist, the other a hugely successful financier. Plot details are under wraps, although there is also a strong female lead character. Related Story Netflix Lands Jake Gyllenhaal-Antoine Fuqua Package 'The Guilty' In $30 Million WW Deal Berger is joining the project after working with Cumberbatch on the Showtime/Sky miniseries Patrick Melrose which is up for five Emmys. He is stepping in for Luca Guadagnino who was originally attached but bowed out over scheduling conflicts. Berger’s other credits include AMC’s The Terror; landmark series Deutschland 83, which won the International Emmy in 2016; and the widely praised German feature Jack, which premiered at the Berlin Film Festival in 2014. Cumberbatch and Ackland say, “We are delighted to be working with Ed Berger again on this very special project. Together with Studiocanal and Nine Stories this promises to be a terrific collaboration, we can’t wait to bring Rio to life.” Gyllenhaal and Marker call Berger’s work “superb” and say they’re “thrilled to be collaborating with him, Studiocanal and SunnyMarch — an undeniably talented group of filmmakers.” Studiocanal CEO Didier Lupfer and EVP International Production Ron Halpern add that Berger is “a director we have wanted to work with since we first saw Jack and Deutschland 83. Steve has written a great thriller and we couldn’t be more excited to work with the directing, writing, producing and acting caliber behind this project.” Ron Halpern and Shana Eddy are overseeing for Studiocanal. Berger is represented by ICM Partners, Anonymous Content and Casarotto Ramsay; Gyllenhaal and Nine Stories are represented by WME and Bloom Hergott; Cumberbatch is repped by UTA and Conway van Gelder Grant; and Knight is with United Agents and CAA. | Mid | [
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Description Our Patchouli Clove Natural Soap Bar is one of our very favorites! It’s richly scented with earthy Patchouli and spicy Clove Essential Oils that combine wonderfully to create a scent you can’t resist! Not only does this natural soap emit a wonderful aroma, but it also has many skin benefiting features! Patchouli Essential Oil helps to soothe inflammation, treat eczema, heal cuts, and speed up the fading of scars. Clove oil, due to its antiseptic properties, is useful for cuts, scabies, athlete’s foot, fungal infections, and bruises. It can also be used for treating insect bites and stings, as well as acne. How to use your Natural Soap Bar: Work our Patchouli Clove Natural Soap Bar into lather and massage over body. Rinse lather off thoroughly. May be used in bath or shower. How to care for your Natural Soap Bar: A happy soap is a dry soap! To prolong the life of your Patchouli Clove Natural Soap Bar, place on a well draining soap dish. The best soap dish will allow any excess water to drain so that there is no contact of pooled water to your Patchouli Clove Natural Soap Bar. For long-term storage, store your Patchouli Clove Natural Soap Bar in a brown paper bag in a cool dark location such as a bathroom cabinet or if stored in back of towel cabinet, your towels will smell fresh like your Patchouli Clove Natural Soap Bar. How long should your Natural Soap Bar last? A quick snapshot comparison of our Patchouli Clove Natural Soap Bars to commercial liquid body wash will reveal that a single bar of Patchouli Clove Natural Soap will outlast an equally priced bottle of liquid body wash. A properly maintained Patchouli Clove Natural Soap Bar will last the average person one shower/bath per day for 30 days. If you purchase our Patchouli Clove Natural Soap with one of our bulk discounts, your Patchouli Clove Natural Soap Bar will knock the liquid body wash out of the park on price and cost-effectiveness. Try it today to find out! | Mid | [
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Introduction ============ Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment and cause adverse environmental effects. The exploration and exploitation of crude oil and gas resources are a major source of PAHs. Even though improved technologies have been introduced in the petroleum industry, accidents continue to occur, resulting in hydrocarbon pollution of the environment (both land and water) in most oil producing countries, including Nigeria.[@i2156-9614-9-24-191204-b1] Oil from the petroleum industry enters the aquatic environment through gas flaring, disposal of used lubrication oils, washings from oil tanks, leakage from marine vessels, erosion and run off from crude oil polluted lands, refinery effluents, and ruptures from poorly maintained flow lines/installations. Leakage of oil into the environment could be due to sabotage or maintenance and engineering errors. Upon entry into the aquatic environment, the fraction either mixes with water or sinks into the sediment, causing severe damage to benthic organisms. Hydrocarbon pollution impacts fish, crustaceans and mollusks with objectionable odor or flavor, reducing their market value and acceptability.[@i2156-9614-9-24-191204-b1] Major routes of PAH exposure in fish are ingestion of contaminated food and diffusion of water across their gills and skin.[@i2156-9614-9-24-191204-b2] The lipophilic nature and high chemical stability of PAHs make it easier to penetrate biological membranes and accumulate in the fatty tissues of organisms following their uptake. Polycyclic aromatic hydrocarbons have been reported to be readily absorbed by fish and other aquatic organisms on exposure to contaminated materials, thereby reaching elevated levels over that of the surrounding medium.[@i2156-9614-9-24-191204-b2] The bioaccumulation pattern of PAHs vary in aquatic organisms depending on the trophic levels they occupy, however, the organic PAHs physiological burden is dependent on the biotransformative effect of the organisms.[@i2156-9614-9-24-191204-b3] Macrobenthic invertebrates (shrimps, crayfish, mollusks and crabs) are an important and integral part of the aquatic ecosystem and thus reflect any negative effects caused by pollution in the community structure which can affect trophic relationships.[@i2156-9614-9-24-191204-b4] Fish have been reported to be the most sensitive living organism to trace concentrations of toxicants in aquatic habitats.[@i2156-9614-9-24-191204-b5] Shrimps, crabs and fishes are therefore good indicators of pollution in coastal waters and have been used extensively for environmental monitoring.[@i2156-9614-9-24-191204-b6] Polycyclic aromatic hydrocarbons are classified into two main groups, low and high molecular weights, based on their physical and biological properties and number of fused aromatic rings contained in their structure. Light or low molecular weight (LMW) PAHs consist of 2--3 aromatic rings, and heavy or high molecular weight (HMW) PAHs consist of 4--6 rings.[@i2156-9614-9-24-191204-b7],[@i2156-9614-9-24-191204-b8] The HMW PAHs are more persistent and recalcitrant (less readily bio-degraded by indigenous microorganisms) than LMW PAHs and can persist in an aqueous environment and bioaccumulate in aquatic organisms like fish and shrimps, and are more carcinogenic.[@i2156-9614-9-24-191204-b9] The LMW PAHs, although less carcinogenic, also pose toxic risks to many aquatic organisms.[@i2156-9614-9-24-191204-b10] The stability and distribution of PAHs in the natural environment is influenced by the chemical structure, chemical configuration and physical and chemical properties of the aromatic rings.[@i2156-9614-9-24-191204-b8],[@i2156-9614-9-24-191204-b11] The spectrum of PAHs in the water ecosystem, including water, fish, and sediment can provide some information about their emission source. Higher concentrations of LMW PAHs (e.g., acenaphthene, fluorene) are usually related to naturally occurring PAHs, either of petrogenic or pyrogenic origin, while PAHs emitted from combustion processes (pyrolytic origin) often contain elevated concentrations of HMW (e.g., phenanthrene, fluoranthene, pyrene) and fewer LMW PAHs.[@i2156-9614-9-24-191204-b11] Polycyclic aromatic hydrocarbons have received attention due to their potential negative effects on human and ecosystem health. Adverse effects of PAHs have also been observed in marine organisms, which include impairment in growth and development, growth reduction, endocrine alteration, malformations of embryo and larvae and DNA damage.[@i2156-9614-9-24-191204-b12] *ERL* : Effect range low *ERM* : Effect range median *HMW* : High molecular weight *LMW* : Low molecular weight *SV* : Screening value *TEF* : Toxicity equivalency factor *TEQ* : Toxic equivalent quotient *USEPA* : United States Environmental Protection Agency Aquatic foods are high in nutritive value and thus highly desirable due to their contribution of high-quality protein and low fat content. This attracts consumers to these foods due to their health benefits in addition to their widespread availability and relatively low price, although exposures to toxic chemicals have been a concerning issue for years. In Nigerian markets, fish are one of the most common aquatic organisms available for consumption and reportedly provide over 60% of protein intake.[@i2156-9614-9-24-191204-b15] Food consumption has been identified as an important pathway of human exposure to many contaminants, including PAHs. Therefore, PAH contamination of widely consumed fish species among the populace may have serious health implications as some of these aquatic organisms are caught in water polluted by hydrocarbons.[@i2156-9614-9-24-191204-b16] The objectives of the present study are to determine the concentration of PAHs in sediment samples and in two commercially important fish species, Drepane africana and Pomadasys jubelini, crabs, and shrimps around the Atlas Cove jetty. Additionally, the present study aims to assess the health risk associated with the consumption of fish species and shellfish in the study area. Methods ======= The study was carried out around the Atlas Cove jetty *([Figure 1](#i2156-9614-9-24-191204-f01){ref-type="fig"})*, which is an offloading and storage depot for imported refined oil prior to distribution to other depots. Oil spillage has been reported in the process of operations in Commodore channel. The channel is approximately 10 m deep at the entrance, 12--15 m deep inward, 0.5 - 1 km wide, and 10 km long. It is tidal, and water from the Atlantic Ocean moves in during high tides and recedes during low tides. Turbulence is very high due to its proximity to the Atlantic Ocean. In addition to oil-related activities that go on around the jetty, it is well known for the movement of shipping vessels along the waterways. {#i2156-9614-9-24-191204-f01} The jetty is located in Lagos State between latitudes 6°21′ N to 6°34′ N and longitudes 3°01′ E to 3°27′ E in the southwestern region of Nigeria. The water around Atlas Cove jetty is brackish (mixture of fresh and marine water). The lagoon plays an important role for the human community due to the large prosperous molluscan and fishing exploitation and commerce. It is also used for artisanal fishing, as a large part of the domestic fish supply in Nigeria comes from inland waters, such as lagoons, and thus provides a means of livelihood for fishermen. However, this industry is being threatened by concentrations of PAHs in this area. Sample collection ----------------- A total of 45 surface sediment samples were collected in five different locations, at 5 cm depth, around Atlas Cove jetty between June to August 2016. Sediment samples were collected from five different sites, all of which were impacted by anthropogenic activities such as ship traffic and offloading. Sediment samples were collected using sediment grab and transferred onto aluminum foil papers. Twelve (12) samples of each fish species and 20 samples of shrimps and crabs were purchased from local fishermen at the landing site of the study area and transported to the laboratory on ice packs. Upon arrival at the laboratory, the samples were removed from the ice, thawed, and cleaned under running tap water to remove any dirt and then rinsed again with distilled water. The shrimp, crab and fish samples were taxonomically identified using standard reference sources by experts at the Department of Zoology of Obafemi Awolowo University, Ile-Ife Nigeria. Samples were stored separately at −20°C in a freezer. Sample identification --------------------- Two species of fishes were identified as Pomadasys jubelini, (common name: grunter) *([Figure 2](#i2156-9614-9-24-191204-f02){ref-type="fig"})* and Drepane africana, (local name: akaraba) *([Figure 3](#i2156-9614-9-24-191204-f03){ref-type="fig"})*. The crab was identified to be the male species of Callinectes amnicola, (common name: marine blue crab) *([Figure 4](#i2156-9614-9-24-191204-f04){ref-type="fig"})*, the shrimp was identified as Penaeus notialis, (common name: pink shrimp) *([Figure 5](#i2156-9614-9-24-191204-f05){ref-type="fig"})*. The sampled fish, shrimp, and crab were identified as either demersal, benthopelagic or pelagic species. {#i2156-9614-9-24-191204-f02} {#i2156-9614-9-24-191204-f03} {#i2156-9614-9-24-191204-f04} {#i2156-9614-9-24-191204-f05} ### Ecology and habitat of Pomadasys jubelini and Drepane Africana Pomadasys jubelini is found in sandy and muddy bottoms in coastal waters and estuaries and occurs in freshwater and brackish waters. It feeds on fish, small crustaceans, and mollusks.[@i2156-9614-9-24-191204-b17] It is a bottom-living, but periodically pelagic species usually inhabiting littoral waters to about 25 m depth, but has been reported to extend down to about 90 m. It is locally abundant in shallow waters throughout its range. Drepane africana is a neritic, coastal species and occurs in lagoon and estuarine habitats over sandy and muddy substrata between 20 and 50 cm depth. It feeds on fish eggs, benthic invertebrates, and detritus.[@i2156-9614-9-24-191204-b18] ### Ecology and habitat of Callinectes amnicola and Penaeus notialis Callinectes amnicola (blue marine crab) is a genus of crab from the family Portunidae usually found in the lagoon. The crabs may be considered as euryphagous, feeding on fishes, mollusks, crustaceans, higher plant materials, algae and diatoms. It is found in sand and ocean bottoms.[@i2156-9614-9-24-191204-b19] Penaeus notialis (pink shrimp) is a species of shrimp known to feed on diatoms, green algae, plants materials, as well as crustaceans and fish fragments. It spends a part of its life cycle in open water (ocean), but is mostly found in estuaries, lagoons, open sea and creeks. Its primary habitat (especially adults) is sand, sand- shell or coral- mud bottoms from intertidals.[@i2156-9614-9-24-191204-b20] Sample pre-treatment -------------------- Sediment samples were air dried for several days, after which stones and debris were removed from the samples and then pulverized and passed through a 2-mm mesh sieve to remove other unwanted materials. Samples for PAH analyses were further sieved through 0.5-mm mesh sieve and stored in foil papers until extraction was performed. The fish samples were allowed to thaw, the scales were removed and washed with running water and then distilled water before dissecting and removing the flesh and other parts which were put in sample bottles. Samples included fillets containing only fleshy parts and whole fish, including bone, fleshy parts and organs. The fish samples were weighed using an analytical weighing balance (wet weight) and homogenized with anhydrous sodium sulphate in a mortar with pestle. The mixture was labeled and wrapped in aluminum foil. It was left till the next day to cake, prior to extraction. Reference standards ------------------- Standard mix solutions of the United State Environmental Protection Agency\'s (USEPA) 16 priority PAHs, each at 100 μg/L in dichloromethane, were purchased from Sigma-Aldrich (St. Louis, MO, USA). The surrogate standard was a mixture containing naphthalene-d~8~ (N-d~8~), acenaphthene-d~10~ (Ace-d~10~), phenanthrene-d~10~ (Phen-d~10~), chrysene-d~12~ (Ch-d~12~) and perylene-d~12~ (Per-d~12~), which was added to the samples before extraction and used as internal standards for quantification. Stock solutions were used to prepare working standard solutions for calibration and spiking experiments. Extraction procedure for PAHs in sediment and aquatic organisms --------------------------------------------------------------- Polycyclic aromatic hydrocarbons in sediment samples were extracted using a Soxhlet extraction according to the method described by the Association of Official Analytical Chemists.[@i2156-9614-9-24-191204-b21] Five (5) g of each sediment sample was weighed and 5 g of anhydrous sodium sulphate was added to each sample. The samples were placed in a cellulose thimble and extracted for 16 to 24 hours using 150 ml of dichloromethane in a Soxhlet extractor. The extract was concentrated by evaporation overnight in a fume cupboard and covered with a perforated aluminum foil. Polycyclic aromatic hydrocarbons in the biota samples were determined according to the method of USEPA 3540C.[@i2156-9614-9-24-191204-b22] A total of 5 g of each species of shrimp, crab and fish samples that had been previously homogenized with anhydrous sodium sulfate were poured into 100 ml beakers and 40 ml of n-hexane and dichloromethane (1:1 vol/vol) was used as an extracting solvent. The beaker with the content was placed on a magnetic stirrer and shaken for about 25 minutes. The extract was decanted into a clean conical flask, then 20 ml of fresh solvent was added, and the process repeated. The extracts were combined and filtered through a small glass funnel containing a layer of anhydrous sodium sulphate over a plug of glass wool into a receiving conical flask. The extracts were concentrated by allowing to stand overnight in a fume cupboard and covered with perforated aluminum foil. Sample clean-up was carried out for both sediment and biota using USEPA Method 3630C.[@i2156-9614-9-24-191204-b23] A 600 × 19 mm clean up column was prepared. The hole was blocked with glass wool, 3 g of activated silica gel (60 mesh) was added and the column was topped with sodium sulfate. The column was rinsed by eluting with 20 ml n-hexane and discarded. The concentrated extract was loaded onto the prepared column and eluted with 50 ml n-hexane. The eluates were then concentrated to 1 ml using a rotary evaporator under a gentle stream of pure nitrogen. One (1) ml of the extract was then transferred into a well labeled vial and stored at 4°C prior to gas chromatograph mass spectrometry analysis. Instrumental and analytical conditions -------------------------------------- Analyses of PAHs were performed for both sediment and biota samples using a gas chromatograph mass spectrometer with selected ion monitoring (Shimadzu QP 2010 gas chromatograph mass spectrometry equipped with AOC 5000 auto injector). The column used was a Varian Factor Four fused silica capillary column (30 m × 0.25 mm × 0.25 μm film thickness) for separating target analytes. Helium was used as the carrier gas at a flow rate of 1.2 mL/min. The sample injector temperature was set at 250°C and 300°C and samples were injected at a volume of 1 mL in splitless mode. An initial column temperature of 60°C was held for 1 min and ramped from 60°C to 200°C at 10°C/min held for 2 min and finally to 300°C at 10°C/min and held for 6 min. The mass spectrometry conditions were set as follows: ionization source: electron ionization at -- 70 eV: ion source temperature: 200°C: store mass range m/z 47 - 400 μm. Identification of the individual PAHs was based on comparison of retention time between samples and standard solutions. Quality control --------------- The blanks were treated the same way as the samples. Sediment and biota samples were spiked. These fortified matrices were used as calibration standards, and the range of concentrations added to both sediment and biota matrices were used to produce the calibration curves of 20 - 100 mgkg^−1^. The surrogate internal standards were added to the spiked sediment and biota samples at 100 mgkg^−1^. The response factors were then calculated using the response obtained from desorption of a standard solution containing 40 mgkg^−1^ of the 16 PAHs of interest and 100 mgkg^−1^ of each internal standard. Spiked samples were extracted and analyzed. Recovery yields were 75 - 110% and limit of detection for individual PAHs ranged from 0.02 to 30.00 mgkg^−1^ in sediment and biota with a signal to noise ratio of three (3) and limit of quantization of signal to noise ratio of ten (10). Human health risk assessment ---------------------------- Toxicological risks associated with PAH concentrations in the biota samples were assessed through comparison of the observed concentrations with regulatory limits and guidelines. ### Potential human health risk To assess human health risks from exposure to PAHs through consumption of possibly contaminated biota samples (dietary intake), the dietary daily intake concentrations of PAH\'s from consumption of contaminated shrimps, crabs and fish species were determined. The dietary daily intake of PAHs in contaminated biota samples were assessed for the adult population using [Equations 1](#i2156-9614-9-24-191204-e01){ref-type="disp-formula"}, [2](#i2156-9614-9-24-191204-e02){ref-type="disp-formula"} and [3](#i2156-9614-9-24-191204-e03){ref-type="disp-formula"}. The daily intake of PAHs from the biota samples was calculated by multiplying the respective PAH concentration in each sample by the consumption rate of an average weight adult (70 kg). where, 0.0685 kg/day is based on the assumption that an average Nigerian consumes 25 kg of fish per annum and an average of 0.0016 and 0.0219 kg/day of crabs and shrimp, respectively.[@i2156-9614-9-24-191204-b5],[@i2156-9614-9-24-191204-b15] ### Carcinogenic risk assessment of polycyclic aromatic hydrocarbons in biota samples Cancer risk due to dietary exposure to PAHs in fish was assessed. The carcinogenic potencies of individual PAHs were evaluated by multiplying the PAH concentrations in the sample by the individual toxicity equivalency factor (TEF) as shown in [Equation 4](#i2156-9614-9-24-191204-e04){ref-type="disp-formula"}.[@i2156-9614-9-24-191204-b24] The toxicity equivalency factor is an estimate of the relative toxicity of individual PAH fractions compared to benzo(a)pyrene. Toxic equivalency factors have been applied as useful tools for the regulation of compounds with common mechanisms of action (e.g. PAHs). The TEFs developed by Nisbet and LaGoy were applied and these values were used to calculate PAH as equivalents for benzo\[a\]pyrene for a standard adult with 70 kg body weight.[@i2156-9614-9-24-191204-b25] The toxic equivalent quotient (TEQ) was derived by adding the carcinogenic potencies of individual PAHs shown in [Equation 5](#i2156-9614-9-24-191204-e05){ref-type="disp-formula"}.[@i2156-9614-9-24-191204-b24] where, B(A)Pteq is the carcinogenic potencies of individual PAHs and C~i~ is the PAH concentration. The screening value (SV) was calculated as shown in [Equation 6](#i2156-9614-9-24-191204-e06){ref-type="disp-formula"}, and then compared with the estimated TEQ value to assess the health risk of PAHs associated with consumption of the biota samples. The screening value is referred to as the threshold concentration of chemicals in edible tissue(s) that is of potential risk to consumers. It was calculated using the formula of Nozar *et al*.[@i2156-9614-9-24-191204-b5] where, RL is the maximum acceptable risk level (10^−5^),CSF is the oral cancer slope factor (7.3 mg/kg/day), BW is body weight (70 kg)\*, and CONR is the fish consumption rate. *\*Body weight of 70 kg applies to the adult population.*[@i2156-9614-9-24-191204-b15] Histopathological examination ----------------------------- The fish samples were dissected to remove the target organs, while the shrimps and crabs were dissected to obtain the fleshy parts. The gills, fillet, liver of fish and the fleshy parts of the crab and shrimp were put in a separate well labeled bottle, fixed in 5% formalin for at least 48 hours and transferred into a sampling bottle rack. Tissue processing for the histopathological analyses was done according to standard methods.[@i2156-9614-9-24-191204-b26] The tissues were removed from the fixative, and samples were rinsed in tap water for 5 minutes, and dehydrated in ascending ethanol concentrations (70%, 80% and 90% alcohol) for a minimum of 2 minutes each. The dehydrated tissues were cleaned in a wax miscible agent (xylene) for 2 minutes and then embedded in paraffin. Tissue sectioning and staining ------------------------------ The fish tissues were then cut into sections approximately 5 μm thick from the block using a rotary microtome (Yamato Kohki, serial no: 75010JO). The cut samples were dried in a hot air oven to remove moisture and each section was mounted on a glass slide. The sections were de-waxed in a wax-miscible agent and rehydrated through descending concentrations of ethanol (90%, 80% and 70% alcohol) for at least 2 minutes each. The sections were then stained with hematoxylin and eosin, after which the tissues were placed in hematoxylin solution for 3 minutes and aqueous eosin for 3 minutes, mounted on a slide and covered with cover slip and labeled.[@i2156-9614-9-24-191204-b27] The tissues were examined, and their microphotographs were taken using a digital binocular compound LED microscope (model MD827S30L series). Statistical analysis -------------------- The obtained data were subjected to descriptive statistics and analysis of variance. The significant treatment means were separated using Duncan\'s multiple range tests using the Statistical Package for the Social Sciences software (SPSS) version 19.0. Results ======= Concentrations of PAHs in sediment samples are presented in [Table 1](#i2156-9614-9-24-191204-t01){ref-type="table"}. A total of 17 PAHs compounds (naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, acenaphthylene acenaphthene, fluorene, phenanthrene, anthracene, pyrene, fluoranthene, benzo(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(k) fluoranthene, benzo(a)pyrene, indeno(1,2,3-cd) pyrene, benzo(ghi) perylene) were detected in the sediment samples. Concentration of PAHs ranged from 2.15 - 36.46 mgkg^−1^ across the sampling points. Sampling point 5 had the highest (36.46 mg/kg) concentration of PAHs compared to those detected from other points. In the present study, 47.06% of PAHs had 2--3 rings, 23.53% of PAHs had 4-rings, and 29.41% of PAHs had 5--6 rings. The percentage composition pattern of PAHs detected in the sediment samples by number of rings is presented in [Table 2](#i2156-9614-9-24-191204-t02){ref-type="table"}. The phenanthrene to anthracene (Ph/An) ratio for sediment samples were 0.65, 2.43 and 1.72 in sampling points 1, 4 and 5, respectively, but were below detection limit in points 2 and 3. The respective values for fluoranthene to pyrene (Fl/Py) ratio were 0.38, 0.66, 0.47 and 1.02 in sampling points 1, 2, 4, and 5, respectively. ###### Concentrations of PAHs in Sediment (mg/kg) PAHs Sampling locations ------------------------ -------------------- -------------- --------------- --------------- -------------- Naphthalene 1.03±0.12^a^ 1.17±0.01^a^ 0.95±0.00^ab^ 0.70±0.00^c^ 0.66±0.01^c^ 1-Methylnaphthalene 0.36±0.03^a^ 0.41±0.02^a^ 0.31±0.03^a^ 0.19±0.02^ab^ 0.23±0.00^a^ 2-Methylnaphthalene 0.23±0.06^a^ 0.27±0.01^a^ 0.19±0.03^a^ 0.15±0.03^a^ 0.12±0.00^a^ Acenaphthylene 1.42±1.11^a^ BDL BDL BDL 0.45±0.13^b^ Acenaphthene 0.23±0.19^a^ 0.09±0.01^b^ 0.03±0.01^b^ 0.04±0.01^b^ 0.05±0.01^b^ Fluorene 1.05±0.53^a^ BDL BDL BDL BDL Phenanthrene 2.00±0.19^a^ BDL BDL 0.17±0.02^c^ 0.74±0.07^b^ Anthracene 3.25±0.14^a^ BDL BDL 0.07±0.01^c^ 0.43±0.07^b^ Pyrene 5.43±0.18^a^ 0.97±0.04^c^ BDL 0.49±0.00^d^ 4.63±2.30^b^ Fluoranthene 2.07±0.08^b^ 0.64±0.02^d^ 1.63±0.01^c^ 0.23±0.02^e^ 4.73±2.10^a^ Benzo(a)anthracene 0.76±0.66^b^ BDL BDL 0.11±0.01^c^ 2.48±0.45^a^ Chrysene BDL BDL BDL BDL 4.97±2.45 Benzo(k)fluoranthene BDL BDL BDL BDL 3.03±1.44 Benzo(b)fluoranthene BDL BDL BDL BDL 2.80±1.67 Benzo(a)pyrene BDL BDL BDL BDL 4.10±1.95 Benzo(ghi)perylene BDL BDL BDL BDL 3.38±1.89 Dibenzo(a,h)anthracene BDL BDL BDL BDL BDL Indeno(1,2,3-cd)pyrene BDL BDL BDL BDL 3.67±2.34 ∑CPAHs 0.76 \- \- 0.11 20.76 Total PAHs 17.82 3.55 3.11 2.15 36.46 ^\*^Mean concentrations with different superscripts along the same row are significantly different (P≤0.05). Abbreviations: BDL, below detection limit (detection limit − 0.001 mg/kg); CPAHS, carcinogenic PAH. ###### Percentage Composition of LMW and HMW of Total PAHs Detected in Sediment Samples Number of Rings \% Abundance ----------------- -------------- 2--3 ring PAHs 47.06% 4 ring PAHs 29.41% 5--6 ring PAHs 23.53% Polycyclic aromatic hydrocarbon concentrations in Drepane africana and Pomadasys jubelini ----------------------------------------------------------------------------------------- Concentration of PAHs in Drepane africana and Pomadasys jubelini samples are presented in [Table 3](#i2156-9614-9-24-191204-t03){ref-type="table"}. The concentration of total PAHs in the fillet (i.e. muscle) was 22.67 mg/kg, and 33.97 mg/kg in the whole fish in Drepane africana. For the individual PAH compounds, naphthalene had the highest concentration (28.53±9.19 mg/kg) which was observed in the whole fish sample, while anthracene had the lowest concentration (0.02±0.01 mg/kg) and was observed in the fillet of the fish sample. ###### Mean Concentrations of PAHs in Drepane africana and Pomadasys jubelini (mg/kg) PAHs Drepane africana Pomadasys jubeli ------------------------ ------------------ ------------------ -------------- ---------------- Naphthalene 19.17±20.13^b^ 28.53±9.19^a^ 9.44±3.42^b^ 27.60±12.20^a^ 1-MethylNaphthalene 1.46±0.86^b^ 1.74±0.06^a^ 0.76±0.68^b^ 2.54±2.04^a^ 2-MethylNaphthalene 0.93±0.47^a^ 1.05±0.36^a^ 0.45±0.37^b^ 1.71±1.33^a^ Acenaphthylene 0.07±0.12^a^ 0.24±0.04^a^ 0.15±0.13^a^ 0.33±0.11^a^ Acenaphthene 0.22±0.17^a^ 0.14±0.11^a^ 0.15±0.13^b^ 0.54±0.33^a^ Fluorene 0.34±0.30^a^ 0.20±0.17^ab^ 0.10±0.11^b^ 0.50±0.46^a^ Phenanthrene 0.25±0.21^ab^ 0.70±0.62^a^ 0.39±0.11^b^ 0.91±1.01^a^ Anthracene 0.02±0.01^a^ 0.17±0.16^a^ 0.08±0.06^a^ 0.02±0.01^a^ Pyrene 0.07±0.03^b^ 0.52±0.43^a^ 0.17±0.05^b^ 0.40±0.25^a^ Fluoranthene 0.14±0.11^b^ 0.69±0.44^a^ 0.20±0.07^b^ 0.48±0.35^a^ Benzo(a)anthracene BDL BDL BDL BDL Chrysene BDL BDL BDL BDL Benzo(k)fluoranthene BDL BDL BDL BDL Benzo(b)fluoranthene BDL BDL BDL BDL Benzo(a)pyrene BDL BDL BDL BDL Benzo(ghi)perylene BDL BDL BDL BDL Dibenzo(a,h)anthracene BDL BDL BDL BDL Indeno(1,2,3-cd)pyrene BDL BDL BDL BDL Total PAHs 22.67 33.97 11.89 35.02 ^\*^Mean concentrations with different superscripts along the same row are significantly different at P≤0.05. Abbreviation: BDL, below detection limit (detection limit − 0.001 mg/kg) Moreover, the concentration of total PAHs in the fillet was 11.89 mg/kg and 35.02 mg/kg in the whole fish in Pomadasys jubelini samples. A total of 10 PAH compounds were detected in the samples. Naphthalene had the highest concentration (27.60±12.20 mg/kg) of individual PAH compounds and was observed in the whole fish sample, while anthracene had lowest concentration (0.02±0.01 mg/kg) and was observed in the whole fish sample. In the present study, 80% of PAHs had 2--3 rings, 20% had 4-rings, and no PAHs with 5--6 rings were detected in Drepane africana and Pomadasys jubelini samples *([Table 4](#i2156-9614-9-24-191204-t04){ref-type="table"})*. ###### Percentage composition of LMW and HMW of total PAHs detected in Drepane africana and Pomadasys jubelini Number of rings \% Abundance ----------------- -------------- 2--3 ring PAHs 80% 4 ring PAHs 20% Polycyclic aromatic hydrocarbon concentrations in Callinectes amnicola (blue marine crab) and Penaeus notialis (pink shrimp) ---------------------------------------------------------------------------------------------------------------------------- Concentrations of PAHs in Callinectes amnicola and Penaeus notialis samples are presented in [Table 5](#i2156-9614-9-24-191204-t05){ref-type="table"}. A total of 9 PAHs were detected in C. amnicola, while 10 PAH congeners (naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, pyrene, fluoranthene) were detected in P. notialis. All of the LMW PAHs tested for were present except for fluorene, which was not detected in crab. The concentration of total PAHs in the crab sample was 60.30 mg/kg. The highest concentration (46.50±15.66 mg/kg) of individual PAH compounds were obtained in naphthalene and the lowest concentration (0.05±0.02 mg/kg) was obtained in anthracene. The result obtained in this study (6 0030 ng/g) for crab was higher than the result reported for crab; young (1 2138.07 ng/g) and mature crabs with eggs (5629.80 ng/g) collected from Lagos lagoon.[@i2156-9614-9-24-191204-b28] In the present study, 77.78% of PAHs had 2--3 rings, 22.22% of PAHs had 4-rings, and no 5--6 ring PAHs were detected in Callinectes amnicola and Penaeus notialis samples. Concentration of PAHs in shrimp ranged from 0.08±0.13 to 50.65 ± 21.88 mgkg^−1^. The highest concentration was found in naphthalene and lowest concentration was found in acenaphthylene.[@i2156-9614-9-24-191204-b29]The percentage composition pattern of PAHs detected in the samples by the number of rings is shown in [Table 6](#i2156-9614-9-24-191204-t06){ref-type="table"}. ###### Concentrations of PAHs in Callinectes amnicola and Penaeus notialis (mg/kg) Wet Weight PAHs Crab Shrimp ------------------------- ---------------- ---------------- Naphthalene 46.50±15.66^b^ 50.65±21.88^a^ 1-Methylnaphthalene 7.01±8.38^a^ 6.57±7.82^b^ 2-Methylnaphthalene 4.70±5.94^a^ 4.21±5.27^b^ Acenaphthylene 0.18±0.16^a^ 0.08±0.13^a^ Acenaphthene 0.29±0.15^b^ 1.31±1.72^a^ Fluorene BDL 1.78±3.07 Phenanthrene 0.79±1.02^b^ 1.65±2.04^a^ Anthracene 0.05±0.02^b^ 3.34±2.10^a^ Pyrene 0.27±0.16^b^ 0.57±0.59^a^ Fluoranthene 0.51±0.29^b^ 0.91±1.20^a^ Benzo(a)anthracene BDL BDL Chrysene BDL BDL Benzo(k)fluoranthene BDL BDL Benzo(b)fluoranthene BDL BDL Benzo(a)pyrene BDL BDL Benzo(ghi)perylene BDL BDL Dibenz(a,h)anthracene BDL BDL Indeno(-1,2,3-cd)pyrene BDL BDL Total PAHs 60.30 71.06 ^\*^Mean concentrations with different superscripts along the same row are significantly different at P≤0.05. Abbreviation: BDL, below detection limit (detection limit − 0.001 mg/kg) ###### Percentage composition of PAHs in samples of Callinectes amnicola and Penaeus notialis Number of Rings \% Abundance ----------------- -------------- 2--3 ring PAHs 77.78% 4 ring PAHs 22.22% Health risk assessment ---------------------- The estimated dietary intake values of total PAHs for fillet and whole fish were 1.55 and 2.33 mg/kg body weight/day, respectively. The fish consumption rate was set at 0.0685 kg/day from the annual per capita fish consumption of 25 kg for Nigeria.[@i2156-9614-9-24-191204-b15] The values obtained in this study exceeded the values reported for fish samples from Degele community, Sapele, Nigeria which was reported to be 0.02 - 0.94 mg/kg body weight/day (O. niloticus), 0.02--0.12 mg/kg body weight/day (C. gariepinus), 0.12--0.16 mg/kg body weight/day (H. longifilis) and 0.14--0.58 mg/kg body weight/day (L. falcipinnis), respectively.[@i2156-9614-9-24-191204-b30] The estimated dietary intakes of sampled fish species are shown in [Table 7](#i2156-9614-9-24-191204-t07){ref-type="table"}. ###### Estimated Dietary Intake of PAHs from Sampled Organisms Organisms Estimated dietary Intake (mgkg; body weight/day) ----------------------------- -------------------------------------------------- Drepane Afrieana (fillet) 1.55 Drepane Afrieana (whole) 2.33 Pomadasys jubelini (fillet) 0.81 Pomadasys jubelini (whole) 2.40 Crab 0.10 Shrimp 1.56 Dietary intake of polycyclic aromatic hydrocarbons from Callinectes amnicola and Penaeus notialis ------------------------------------------------------------------------------------------------- The estimated dietary intake values of total PAHs for crab and pink shrimp were 0.10 and 1.56 mg/kg body, respectively. The carcinogenic potencies of individual PAHs and TEQ values are presented in [Table 8](#i2156-9614-9-24-191204-t08){ref-type="table"}. The TEQ values obtained from TEF values were used to assess the carcinogenicity of PAH contamination in the sampled biota.[@i2156-9614-9-24-191204-b31] The TEQ values of PAHs in the biota samples were 6.08×10^−2^, 1.01×10^−1^, 2.29×10^−2^, 3.55 × 10^−2^, 1.26×10^−2^ and 3.52×10^−2^ mg/kg for crab, shrimp, Drepane africana (fillet), Drepane africana (whole), Pomadasys jubelini (fillet), Pomadasys jubelini (whole), respectively. ###### Carcinogenic Potencies of Individual PAHs and Toxic Equivalent Quotient Values B(a)Pteq values (mg/kg) ------------------------- ------- ------------- ------------- -------------- ------------- ------------- ------------- Naphthalene 1- 0.001 4.67×10^−2^ 5.06×10^−2^ 1.92×10^−2^ 2.85×10^−2^ 9.44×10^−3^ 2.76×10^−2^ Methylnaphthalene 2- 0.001 7.00×10^−3^ 6.57×10^−3^ 1.46×10^−3^ 1.74×10^−3^ 7.60×10^−4^ 2.54×10^−3^ Methylnaphthalene 0.001 5.00×10^−3^ 4.21×10^−3^ 9.30×10^−4^ 1.05×10^−3^ 4.50×10^−4^ 1.71×10^−3^ Acenaphthylene 0.001 1.8×10^−4^ 8.00×10^−5^ 7.00×10^−5;^ 2.40×10^−4^ 1.50×10^−4^ 3.30×10^−4^ Acenaphthene 0.001 2.9×10^−4^ 1.31×10^−3^ 2.20×10^−4^ 1.40×10^−3^ 1.50×10^−4^ 5.40×10^−4^ Fluorene 0.001 \- 1.78×10^−3^ 3.40×10^−4^ 2.00×10^−4^ 1.00×10^−4^ 5.00×10^−4^ Phenanthrene 0.001 7.9×10^−4^ 1.65×l0^−3^ 2.50×10^−4^ 7.00×10^−4^ 3.90×10^−4^ 9.10×10^−4^ Anthracene 0.01 5.00×10^−4^ 3.34×10^−3^ 2.00×10^−4^ 1.70×10^−3^ 8.00×10^−4^ 2.00×10^−4^ Pyrene 0.001 2.70×10^−4^ 5.70×10^−4^ 7.00×10^−5^ 5.20×10^−4^ 1.70×10^−4^ 4.00×10^−4^ Fluoranthene 0.001 5.1 ×10^−4^ 9.10×10^−4^ 1.40×10^−4^ 6.90×10^−4^ 2.00×10^−4^ 4.80×10^−4^ TEQ (values mg/kg) 6.08×10^−2^ 1.01×10^−1^ 2.29×10^−2^ 3.55×10^−2^ 1.26×10^−2^ 3.52×10^−2^ Abbreviation: B(a)Pteq, carcinogenic potencies of individual PAHs Carcinogenic potency of individual polycyclic aromatic hydrocarbons and toxic equivalent quotient ------------------------------------------------------------------------------------------------- The carcinogenic potencies of individual PAHs and TEQ values are presented in [Table 8](#i2156-9614-9-24-191204-t08){ref-type="table"}. The TEFs method was developed to evaluate structurally related compounds and has been applied as a useful tool for the regulation of compounds with a common mechanism of actions (e.g. PAHs). The TEF is an estimate of the relative toxicity of an individual PAH fraction compared to benzo(a)pyrene. The TEF values are used to calculate other PAHs to benzo(a)pyrene equivalents (the most toxic PAHs) for an average adult with 70 kg body weight.[@i2156-9614-9-24-191204-b24] The carcinogenic potency of individual PAHs is represented by the value resulting from the product of the concentration and TEF value of each congener. The TEQ value is the summation of carcinogenic potencies of individual PAH values obtained from a particular sample. It expresses an aggregate measure of toxicity based on a number of contributing compounds. Screening value --------------- The SV was evaluated to assess the health risks posed by PAHs to humans from consuming the sampled organisms. The screening value is defined as the threshold concentration of chemicals in edible tissue that is of potential public health concern.[@i2156-9614-9-24-191204-b16],[@i2156-9614-9-24-191204-b32] An estimated SV of 0.0599, 0.0044 and 0.0014 mg/kg was obtained for crab, shrimp and fish samples, respectively. The resulting TEQ values obtained for the sampled biota exceeded the screening values *([Figure 6](#i2156-9614-9-24-191204-f06){ref-type="fig"})*. {#i2156-9614-9-24-191204-f06} Histopathological examination ----------------------------- In the present study, the major changes observed in the gills of Drepane africana and Pomadasys jubelini were hypertrophy of the primary lamellae and hyperplasia of the secondary lamellae. Shortening and fusion of the secondary lamellae were observed in Drepane africana, while hyperplasia of the epithelial cells was observed in Pomadasys jubelini. In the muscle of Drepane africana and Pomadasys jubelini, splitting and atrophy of the muscle bundles were observed, while necrosis of the muscle bundles was seen in Pomadasys jubelini only *([Figures 7a](#i2156-9614-9-24-191204-f07a){ref-type="fig"}--[c](#i2156-9614-9-24-191204-f07c){ref-type="fig"}).* Splitting of the muscle myofibrils was observed in shrimp only, while splitting and atrophy of the muscle bundles were observed in the muscles of shrimp and crab *([Figures 8a](#i2156-9614-9-24-191204-f08a){ref-type="fig"}--[b](#i2156-9614-9-24-191204-f08b){ref-type="fig"} and [9](#i2156-9614-9-24-191204-f09){ref-type="fig"})*. Changes observed in the liver of Drepane africana and Pomadasys jubelini included necrosis, hepatopancreas and cellular degeneration *([Figure 10a](#i2156-9614-9-24-191204-f10a){ref-type="fig"}--[d](#i2156-9614-9-24-191204-f10d){ref-type="fig"})*. {#i2156-9614-9-24-191204-f07a} {#i2156-9614-9-24-191204-f07b} {#i2156-9614-9-24-191204-f07c} {#i2156-9614-9-24-191204-f08a} {#i2156-9614-9-24-191204-f08b} {#i2156-9614-9-24-191204-f09} {#i2156-9614-9-24-191204-f10a} {#i2156-9614-9-24-191204-f10b} {#i2156-9614-9-24-191204-f10c} {#i2156-9614-9-24-191204-f10d} Discussion ========== The predominance of LMW and HMW PAHs in the sediments reflects the presence of significant combustion products from pyrolytic processes and/or petrogenic sources.[@i2156-9614-9-24-191204-b33],[@i2156-9614-9-24-191204-b34] The preponderance of LMW and HMW PAHs in the sediments indicates the presence of significant combustion products from pyrolytic processes and/or petrogenic sources. [@i2156-9614-9-24-191204-b33],[@i2156-9614-9-24-191204-b34] A sediment quality guideline of 1000 ng/g dry weight total PAHs was designed to protect estuarine fish against several important health effects.[@i2156-9614-9-24-191204-b35] Based on this guideline, the results of this study showed that the concentrations of total PAHs exceeded 1000 ng/g dry weight at all sampling points, indicating that aquatic organisms in the region could be at severe health and environmental risk. Polycyclic aromatic hydrocarbon concentrations in soil/sediment can be classified according to the following categories: \>1.0 mg/kg, 0.001 -- 1.0 mg/kg and \< 0.001 mg/kg for high risk, medium risk, and low risk, respectively.[@i2156-9614-9-24-191204-b36] In the present study, the concentration of PAHs from all sampling points were higher than 1.0 mg/kg, indicating that they presented a high risk. All sediment samples exceeded the USEPA guideline value of 2.5 mg/kg except sampling point 4, which was slightly lower (2.15 mg/kg) *([Table 1](#i2156-9614-9-24-191204-t01){ref-type="table"})*. In rural areas, PAHs adsorbed in atmospheric particles can be deposited on the surface of lakes, streams, and oceans by dry or wet deposition, where they could be dispersed by currents and eventually become integrated with sediment. Sediments near urban centers are influenced by atmospheric deposition of PAHs. Other sources of PAHs include storm and sanitary sewer effluents as well as roadway runoff. It was observed that the concentration of PAHs was higher in sediment samples than in water samples. This could be attributed to their hydrophobic tendencies and propensity towards adsorption to particles and solid phases. In addition, they settle and become part of the sedimentary record. Anthropogenic PAHs originate mainly from combustion of fossil fuels and spillage of petroleum products; from fuel combustion (pyrolytic) or from crude oil (petrogenic). Contamination may be identified by ratios of individual PAH compounds based on peculiarities in PAH composition and distribution patterns as a function of the emission source. Ratios of Ph/An and Fl/Py have been widely used to distinguish petrogenic and pyrogenic sources of PAHs.[@i2156-9614-9-24-191204-b37],[@i2156-9614-9-24-191204-b38] Polycyclic aromatic hydrocarbons of petrogenic origin are generally characterized by Ph/An values \> 10, whereas combustion processes often result in low Ph/An ratio \< 10. For the Fl/Py ratio, values \> 1 have been used to indicate pyrolytic origins and values \< 1 are attributed to petrogenic sources. The results from both Ph/An and Fl/Py ratios indicated that PAHs in the Atlas Cove jetty area may originate from both pyrolytic and petrogenic sources. It was observed that the PAHs have pyrolytic sources in sediment samples in all sampling points and this may be attributed to high ship traffic. Potential toxicity of PAHs in sediments on the surrounding aquatic organisms was assessed. The PAHs concentration in the sediments were compared with US National Oceanic sediment quality guidelines *([Table 9](#i2156-9614-9-24-191204-t09){ref-type="table"})*.[@i2156-9614-9-24-191204-b39] The recommended effect range low (ERL) and effect range median (ERM) target values were used to determine toxic effects in the sampling locations. When PAH concentrations vary between ERL and ERM values, a mild toxic effect is expected. In addition, no negative effect is expected for PAH concentrations lower than ERL values. [Table 9](#i2156-9614-9-24-191204-t09){ref-type="table"} indicates a high probability of risk for organisms that live in sampling locations 1 and 5. Naphthalene, acenaphthene, and fluoranthene exceeded the ERL values, but were within ERM values in both sampling locations, indicating a mild toxic effect. Anthracene exceeded the ERL and ERM values at sampling locations 1 and 5, but was within ERM value at sampling location 5. Anthracene, phenanthrene, pyrene and fluoranthene were below ERL values in sampling location 4. Anthracene, fluorene, phenanthrene, acenaphthylene and pyrene in sampling location 1 and pyrene and benzo(a)pyrene in sampling location 5 exceeded ERM values, suggesting that adverse biological effects such as cancer, reproductive and physiological disorder may occur in fish and mammals.[@i2156-9614-9-24-191204-b40] ###### Concentrations of PAHs in Sediment Compared with US National Oceanic Sediment Quality Guidelines PAHs ERL[@i2156-9614-9-24-191204-b39] (ngg-^1^) ERM[@i2156-9614-9-24-191204-b39] (nss-^1^) Sampling locations ------------------------ -------------------------------------------- -------------------------------------------- -------------------- ------ ------ ----- ------ Naphthalene 160 2100 1030 1170 950 700 660 Anthracene 85 1100 3250 \- \- 70 430 Fluorene 19 540 1050 \- \- \- \- Phenanthrene 240 1500 2000 \- \- 170 740 Acenaphthene 16 500 230 90 30 40 50 Acenaphthylene 44 640 1420 \- \- \- 450 Pyrene 665 2600 5430 970 1630 490 4630 Fluoranthene 600 5100 2070 640 \- 230 4730 Benzo (b) fluoranthene \- \- \- \- \- \- 2800 Benzo(a) pyrene 430 2800 \- \- \- \- 4100 Abbreviations: ERL, effective range low; ERM, effective range median. Polycyclic aromatic hydrocarbons concentrations in Drepane africana and Pomadasys jubelini ------------------------------------------------------------------------------------------ A total of 10 PAH compounds (naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, pyrene, fluoranthene) were detected in the samples *([Table 3](#i2156-9614-9-24-191204-t03){ref-type="table"})*. The less carcinogenic LMW PAHs were detected with naphthalene and its substituent present in the fish samples. The more carcinogenic HMW PAHs (benzo(a)anthracene, chrysene, benzo(k)fluoranthene, benzo(b)fluoranthene, benzo(ghi) perylene, dibenzo(a,h)anthracene, indeno(1,2,3-cd)pyrene) were not detected in the samples of Drepane africana. This result agreed with the report of PAHs in fish samples from the Degele community of Delta state, Nigeria and the bioaccumulation of PAHs in fish and invertebrates of Lagos lagoon.[@i2156-9614-9-24-191204-b30],[@i2156-9614-9-24-191204-b41] A significant (P≤0.05) difference was observed in the total PAH concentrations between fillet and whole fish of the fish species. The percentage composition pattern of PAHs detected in the samples by number of rings is shown in [Table 4](#i2156-9614-9-24-191204-t04){ref-type="table"}. The predominance of LMW PAHs as compared to HMW PAHs in the fish samples reflects the presence of significant petrogenic processes.[@i2156-9614-9-24-191204-b33],[@i2156-9614-9-24-191204-b34] The analysis showed that a total of 10 PAHs (8 of which are among the 16 PAHs prioritized by the USEPA) were present in the fish sample. The concentration of PAHs in fish was higher than the water column; this could be due to the fact that PAHs are more readily absorbed by fish than other aquatic organisms on exposure to contaminated materials, thus attaining elevated levels compared to those in the surrounding medium.[@i2156-9614-9-24-191204-b6] The trend for the less carcinogenic LMW PAHs and the more carcinogenic HMW PAHs in Pomadasys jubeli was similar to that observed in Drepane africana presented above. The concentration of total PAHs was lower in the whole fish and fillet of both fish species compared to that of crab and shrimp in the present study. This may be because fish have been reported to have physiological mechanism(s) of rapid PAH biotransformation or depuration and could be influenced by various factors, such as chemical exposure route and time, lipid content of tissues, environmental factors, exposure to multiple contaminants, and differences in species, age, sex, and health conditions of the test animals.[@i2156-9614-9-24-191204-b28] The biotransformation of hydrophobic-containing substances in fish is a major determinant of its toxicity, distribution and excretability.[@i2156-9614-9-24-191204-b6] A large percentage of the world\'s population depends on seafood, especially fish, to meet their nutritional requirements. In Nigeria, fish provides over 60% of protein intake and is recognized as a very important source of animal protein. Food consumption has been identified as an important pathway of human exposure to many contaminants, including PAHs. Due to the lipophilic nature and high chemical stability of PAHs, they accumulate in the fatty tissues of fish following their uptake.[@i2156-9614-9-24-191204-b42] Exposure pathways of PAHs to fish include bioconcentration from water across their gills, skin and ingestion of PAH-contaminated particulate matter along with food, as PAHs readily adsorb onto particulate organic matter especially soil sediments.[@i2156-9614-9-24-191204-b15] The concentrations of contaminants such as PAHs in fish reflect the state of contamination of the environment.[@i2156-9614-9-24-191204-b43] The observed concentrations of total PAHs in fish in this study indicate high levels of PAHs contamination around the Atlas Cove jetty. Polycyclic aromatic hydrocarbon concentrations in Callinectes amnicola (blue marine crab) ----------------------------------------------------------------------------------------- Crabs have been reported to have high lipid contents and this increases the chance of absorbing more hydrocarbon molecules, especially those that are not easily degraded or eliminated. The higher concentration of PAHs observed in the present study may be due to the proximity of the sampling points to the Atlas Cove jetty or the movement of ships along the waterways which may serve as a source of pollution. However, PAH concentrations were lower than the values (101.10 - 151.49 μg/g) reported for crabs (Callinectes sapidus) obtained from the coastal area of Ondo State, Nigeria.[@i2156-9614-9-24-191204-b29] The higher levels of PAHs in shrimps are presumably due to food chain bioaccumulation and can be harmful to human health. The concentration of PAHs in crab and shrimp were significant and may have wide environmental implications, affecting bioconcentration in their tissues due to their inability to metabolize PAHs efficiently. The relatively higher concentrations of total PAHs in tissues of shellfish than fish showed the bioaccumulative potency of PAHs by the studied organisms. It may also be due to the fact that shrimps and crabs live directly on and forage in the sediments, whereas fish live up in the water column. Several aquatic organisms such as bivalves, crabs, and shrimps have been reported to bioaccumulate and bioconcentrate organic pollutants in their target organs at levels higher than background concentrations.[@i2156-9614-9-24-191204-b44],[@i2156-9614-9-24-191204-b45] Therefore, they are excellent bioaccumulators of organic and inorganic pollutants. Higher concentrations of total PAHs in banana shrimp and blue crab were compared to Drepane punctata and Pomadasys kaakan, which had lower concentrations of PAHs.[@i2156-9614-9-24-191204-b5] Health risk assessment ---------------------- The consumption of Drepane africana at the rate of 68 g/day may induce adverse health effects over time in consumers. Dietary intake of *polycyclic aromatic hydrocarbons from* Pomadasys jubelini ---------------------------------------------------------------------------- The estimated dietary intake values in the present study (0.81 for fillet and 2.40 mg/kg body weight/day for whole fish) were considerably higher in comparison with values reported in other countries of 1.77 - 10.7 ng/kg body weight/day, 626 - 712 ng/day, 13.8 - 16.7 ng/kg body weight/day and 231 ng/day for Mumbai, India, Spain, Korea and Kuwait, respectively.[@i2156-9614-9-24-191204-b33],[@i2156-9614-9-24-191204-b46],[@i2156-9614-9-24-191204-b47] Comparison of toxic equivalency quotient values ----------------------------------------------- The lowest TEQ value was obtained in the fillet of Pomadasys jubelini. The TEQ values of PAHs in fish species, as reported by Tongo *et al.* were 0.22, 0.005, 0.30 and 0.03 mg/kg in Clarias gariepinus, Tilapia zilli, Ethmalosa fimbriata, and Scomber scombrus, respectively.[@i2156-9614-9-24-191204-b24] The consumption of species with the lowest total mean concentrations of PAHs have a higher potential to cause carcinogenic risk, which agrees with the findings of the present study. Furthermore, the calculated TEQ values were in agreement with the values reported by Iwegbue *et al*.[@i2156-9614-9-24-191204-b41] The results of the present study are in agreement with a study of PAHs contaminants in Chrysichthys nigrodigitatus in Rivers State, Nigeria, where Patrolecco *et al.* reported TEQ values above estimated SVs.[@i2156-9614-9-24-191204-b48],[@i2156-9614-9-24-191204-b49] In addition, higher TEQ values were reported when compared to calculated SVs for PAHs in seafood (fish, crab, and bivalves) in Iran, indicating potential health effects.[@i2156-9614-9-24-191204-b5] However, these results disagreed with reports of lower estimated TEQ values than the SV in studies of PAH concentrations in fish (feral finfish) from a Hong Kong market and the common eel (Anguilla anguilla) from the River Tiber, Italy.[@i2156-9614-9-24-191204-b16],[@i2156-9614-9-24-191204-b49] Histopathological examination ----------------------------- Histopathological biomarkers are sensitive indicators of subcellular stress in organisms exposed to a range of pollutants over short and long periods of time.[@i2156-9614-9-24-191204-b50] Changes caused by toxic substances can be observed in the gills, such as an increase in pollutant blood diffusion distance as a means for protection.[@i2156-9614-9-24-191204-b50] Fusion of secondary lamellae, which is a result of hyperplasia, brings about a reduction in free gas exchange, thus affecting the general health of the fish. Hypertrophy of the primary lamellae is the enlarging or increase in size of the organ in response to a stressor in the environment. This observation is similar to a report of a high incidence of hyperplasia in Clarias gariepinus and Oreochromis niloticus reported from the Sanyati basin in Lake Kariba, Zimbabwe, as well as hyperplasia in the gills of two species of sturgeons.[@i2156-9614-9-24-191204-b50],[@i2156-9614-9-24-191204-b51] This result is an indication that the fish have been exposed to stressors. Gills are sensitive organs which are easily damaged by numerous pollutants, even at low concentrations. Gills have been reported to perform various vital functions (respiration, osmoregulation, acid-base balance). Gills have a large surface area in contact with the external environment and are particularly sensitive to chemical and physical changes of the aquatic environment, thereby being a target organ in fish for pollutants carried by water.[@i2156-9614-9-24-191204-b51],[@i2156-9614-9-24-191204-b52] Changes in the structures of these organs as well as in the vital functions performed by the gills were observed due to toxic substances present in the aquatic environment.[@i2156-9614-9-24-191204-b53] The severity of damage depends on the concentration of toxicants and the period of exposure. With prolonged exposure, these lesions could lead to fish mortality. The observed separation of muscle bundles may be due to the initial stimulus of hexachlorocyclohexane, which can induce hyperactivity and excitability in animals, leading to a release of lactic acid and subsequent muscular fatigue. The atrophy observed in the muscle bundles may be due to the exposure to various contaminants.[@i2156-9614-9-24-191204-b54] A study detected changes in muscle tissue of grass carp (Ctenopharyngodon idella) as swelling and necrosis of muscle bundles due to the effect of rice herbicides.[@i2156-9614-9-24-191204-b55] Another study documented physiological disturbances and morphological damage in the muscle tissue of freshwater fish Hoplias malabaricus collected from Ponta Lake in southern Brazil due to bioaccumulation of chlorinated pesticides and PCBs.[@i2156-9614-9-24-191204-b56] Degeneration of muscle bundles with aggregation of inflammatory cells between them and focal areas of necrosis were observed by Gingerich.[@i2156-9614-9-24-191204-b57] The findings of the present study agreed with these previous reports. The liver is the largest organ in the body and performs several important physiological functions.[@i2156-9614-9-24-191204-b58] Although every tissue has some ability to metabolize chemicals, the liver is the major organ of metabolism or transformation of toxins, making it a target organ that is highly affected by toxins in the system. Necrosis is the death of cells in a tissue or organ caused by disease or injury or as a result of exposure to harmful or toxic contaminants. The necrotic cells are shrunk, and their intercellular attachments are broken.[@i2156-9614-9-24-191204-b58] Vascular dilation may be responsible for the cellular degeneration and necrosis in the liver. When the liver is damaged, excessive blood flows into the liver, blocking the sinusoids. Oxygen deficiency as a result of gill degeneration is the most common cause of cellular degeneration in the liver (*[Figures 9a--d](#i2156-9614-9-24-191204-f09){ref-type="fig"}*).[@i2156-9614-9-24-191204-b59] The results of this study agreed with previous reports on the effects of different pollutants on fish liver.[@i2156-9614-9-24-191204-b54],[@i2156-9614-9-24-191204-b60] Conclusions =========== In the present study, low and high molecular weights PAHs were present in the sediment samples. The concentration of total PAHs in the sediment samples exceeded safe limits, suggesting that the aquatic organisms around Atlas Cove may pose serious human health and environmental risks. The high ratio of LMW PAHs as compared to HMW PAHs suggests that PAH contamination around Atlas Cove may be of natural origin. The concentration of total PAHs in biota samples indicated that PAH contamination from Atlas Cove was relatively high (with dominance of the low molecular weight PAHs). The high concentration of total PAHs present in the organisms indicated that the compounds have bioaccumulated in their tissues and organs over a period of time. The calculated TEQ values were higher than the screening values, indicating potential health effects. Histopathological examination revealed that both fish and shellfish were exposed to high concentrations of PAHs which brought about changes in morphologic structure of these organs, necrosis of the muscle bundles and cellular degeneration. This study was funded as part of employment. | High | [
0.657963446475195,
31.5,
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Solution to Unemployment Problem In Nigeria by Egbo ikpechukwu (Enugu) unemployment has been at the root of the many evils facing Nigeria today.yet many of our politicians are not doing anything to help the situation rather they have come out with the idea or notion that most Nigerian graduates are not employable.therefore instead of erecting industries where our youths would be gainfully employed, they use our tax payers money to enrich themselves and families and either build hotels or bring one poverty alleviation program-mes that do little or nothing to help millions of our youths roaming the streets everyday in search of non existent jobs.China as you well know is among the world leading economies of the world today because they have industrialized their nation.Nigeria could also borrow a leaf from them. Comments for Solution to Unemployment Problem In Nigeria May all the David of our time begin to arise now and take their place in the scheme of things in this country in Jesus Name amen. Rating NIGERIA still evolvingNEWby: Egbo Desmond though it may seem there is no longer hope left,yes! it may seem we are immersed in an unending woes,yes our ideas and abilities may have failed us.0h!how my heart breeds for this great nation.oh! how i feel so humbled when i watch SHEKAU threatening and making caricature of our seeming weakness and helplessness like the Israelite of the old standing helplessly and hopelessly before that uncircumcised Philippian.who can ever imagined how traumatized and rejected they must have felt.but thank GOD because there would always be a DAVID,who not only deliver us from this nightmare but will utterly put an end to this evil. | Mid | [
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TOP = ../.. GHC = ghc .PHONY: check check: ./check-uniques.py $(TOP) | Low | [
0.48134328358208905,
32.25,
34.75
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Pop! Harry Potter 27 3 3/4" tall Vinyl Imported By Funko Harry Potter is given a fun, and funky, stylized look as an adorable collectible vinyl figure - sporting his "H" initialed sweater knitted for him by Mrs. Weasley.Hot Topic exclusive! PayPal/Venmo is currently not accepted on Presale and Backorder items. | Mid | [
0.5498007968127491,
34.5,
28.25
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/* * Compatibility layer to provide the same results youtube-comment-api * used to provide. */ var fetchVideoComments = require('youtube-comments-task') var fetchInfo = require('./fetch-video-info') module.exports = function (videoId, pageToken) { return Promise.all([ fetchInfo(videoId), fetchComments(videoId, pageToken) ]) .then(function (results) { var info = results[0] var page = results[1] if (!page) { throw new Error('No comment page received.') } var comments = page.comments || [] var nextPageToken = page.nextPageToken var compatComments = comments .map(compatComment) .map(function (c) { var replies = c.hasReplies ? c.replies.map(compatComment) : null return replies ? Object.assign({}, c, { replies: replies }) : c }) // build the response return { comments: compatComments, nextPageToken: nextPageToken, pageToken: pageToken, videoCommentCount: info.commentCount, videoTitle: info.title, videoThumbnail: info.thumbnailUrl } }) } function fetchComments (videoId, pageToken) { return new Promise(function (res, rej) { fetchVideoComments(videoId, pageToken) .fork(rej, res) }) } function compatComment (c) { const compat = { id: c.id, user: c.author, date: c.time, commentText: c.text, timestamp: c.timestamp, likes: c.likes } // return as-is if it's a reply if (c.hasReplies == null) { return compat } compat.hasReplies = c.hasReplies if (c.hasReplies) { compat.numberOfReplies = c.numReplies compat.replies = c.replies } return compat } | Mid | [
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Cortisol and immunity. The relationship between adrenocortical function and immunity is a complex one. In addition to the well-known detrimental effects of large, pharmacologic dosages of glucocorticoids upon the immune process, there is impressive evidence that physiologic amounts of cortisol, the chief glucocorticoid normally produced by the human adrenal cortex, is necessary for the development and maintenance of normal immunity. This evidence is reviewed, and the importance of differentiating between physiologic and pharmacologic dosages and effects is discussed. The popular use of synthetic derivatives of cortisol, which differ greatly from the natural hormone in strength, and the dynamic nature of the normal adrenocortical response, which varies with the degree of stress being experienced, have contributed to the confusion. Further studies of the nature of the beneficial effect of cortisol, and possibly of other normal adrenocortical hormones, upon immunity in humans are needed, especially in view of recent evidence of a feedback relationship between the immune system and the hypothalamic-pituitary-adrenal axis, and with the increasing awareness not only that the immune process provides protection against infection, but also that its impairment seems to be involved in the development of autoimmune disorders, malignancies and the acquired immunodeficiency syndrome (AIDS). | High | [
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36605613, -36605612, -36605611? h - 36605614 What is the y'th term of -197729, -790871, -1779431, -3163409, -4942805, -7117619? -197709*y**2 - 15*y - 5 What is the s'th term of -47549, -94756, -141963, -189170? -47207*s - 342 What is the v'th term of -784386, -784377, -784368, -784359, -784350, -784341? 9*v - 784395 What is the b'th term of -4646, -6146, -7646? -1500*b - 3146 What is the a'th term of 1122180, 2244391, 3366602, 4488813, 5611024? 1122211*a - 31 What is the p'th term of -2339, -4740, -7251, -9926, -12819? -9*p**3 - p**2 - 2335*p + 6 What is the v'th term of -2498, -1127, 4116, 13231, 26218, 43077, 63808? 1936*v**2 - 4437*v + 3 What is the f'th term of -19489581, -19489582, -19489583, -19489584? -f - 19489580 What is the k'th term of -1258207, -2516387, -3774531, -5032633, -6290687? k**3 + 12*k**2 - 1258223*k + 3 What is the m'th term of -9303, -14648, -19991, -25332, -30671? m**2 - 5348*m - 3956 What is the k'th term of 56700, 56594, 56488? -106*k + 56806 What is the t'th term of -10716, -20948, -31176, -41400, -51620? 2*t**2 - 10238*t - 480 What is the r'th term of 1314442401, 1314442400, 1314442399, 1314442398? -r + 1314442402 What is the k'th term of -11114, -10881, -10472, -9869, -9054? 3*k**3 + 70*k**2 + 2*k - 11189 What is the s'th term of -113689, -227437, -341247, -455113, -569029, -682989, -796987, -911017? s**3 - 37*s**2 - 113644*s - 9 What is the b'th term of 42549, 42698, 42949, 43302? 51*b**2 - 4*b + 42502 What is the t'th term of 4960905, 9921789, 14882649, 19843473, 24804249, 29764965? -2*t**3 + 4960898*t + 9 What is the h'th term of 2460649, 4921292, 7381935, 9842578, 12303221? 2460643*h + 6 What is the v'th term of 4592, 6899, 9206, 11513, 13820? 2307*v + 2285 What is the a'th term of -30740830, -61481662, -92222494, -122963326, -153704158? -30740832*a + 2 What is the w'th term of -7887, -62657, -211179, -500331, -976991, -1688037? -7813*w**3 + 2*w**2 - 85*w + 9 What is the t'th term of -138501, -276937, -415373? -138436*t - 65 What is the g'th term of -917158, -7337327, -24763534, -58698799, -114646142, -198108583, -314589142? -917170*g**3 + g**2 + 18*g - 7 What is the u'th term of 57411, 229615, 516621, 918429? 57401*u**2 + u + 9 What is the s'th term of -10046, -20747, -31440, -42125, -52802, -63471, -74132? 4*s**2 - 10713*s + 663 What is the l'th term of 65986678, 65986679, 65986682, 65986687? l**2 - 2*l + 65986679 What is the m'th term of 1132, 1491, 1864, 2251, 2652? 7*m**2 + 338*m + 787 What is the d'th term of 4897, 6356, 8789, 12196, 16577? 487*d**2 - 2*d + 4412 What is the r'th term of -98474001, -196948000, -295421997, -393895992, -492369985? r**2 - 98474002*r What is the t'th term of 41039, 43289, 45545, 47813, 50099, 52409, 54749, 57125? t**3 - 3*t**2 + 2252*t + 38789 What is the p'th term of -1311587, -2623174, -3934761, -5246348, -6557935? -1311587*p What is the t'th term of 11797881, 11797852, 11797811, 11797752, 11797669, 11797556, 11797407, 11797216? -t**3 - 22*t + 11797904 What is the q'th term of -1490, -6188, -14020, -24986, -39086, -56320, -76688? -1567*q**2 + 3*q + 74 What is the o'th term of 24406, 48800, 73164, 97486, 121754, 145956, 170080, 194114? -2*o**3 - 3*o**2 + 24417*o - 6 What is the j'th term of -367, -57, 1589, 5237, 11553, 21203? 111*j**3 + 2*j**2 - 473*j - 7 What is the a'th term of 1088, 807, 76, -1321, -3600, -6977, -11668? -36*a**3 - 9*a**2 - 2*a + 1135 What is the u'th term of -645435, -645647, -646001, -646497, -647135, -647915, -648837? -71*u**2 + u - 645365 What is the w'th term of 438, 2788, 7048, 13218, 21298, 31288, 43188? 955*w**2 - 515*w - 2 What is the j'th term of 70869656, 70869655, 70869654, 70869653, 70869652? -j + 70869657 What is the n'th term of -843, -5149, -12307, -22317, -35179, -50893, -69459? -1426*n**2 - 28*n + 611 What is the q'th term of -702, -1474, -2330, -3258, -4246, -5282, -6354, -7450? 2*q**3 - 54*q**2 - 624*q - 26 What is the g'th term of 3624, 16204, 37170, 66522, 104260, 150384? 4193*g**2 + g - 570 What is the t'th term of 717, 4074, 9919, 18252, 29073, 42382, 58179? 1244*t**2 - 375*t - 152 What is the y'th term of 349082, 698173, 1047264, 1396355, 1745446? 349091*y - 9 What is the b'th term of -33753, -68207, -102661, -137115? -34454*b + 701 What is the g'th term of -137705, -274542, -411331, -548048, -684669, -821170, -957527, -1093716? 4*g**3 - 136865*g - 844 What is the x'th term of -144258681, -288517365, -432776049? -144258684*x + 3 What is the k'th term of -6839, -54643, -184407, -437117, -853759, -1475319, -2342783? -6831*k**3 + 6*k**2 - 5*k - 9 What is the a'th term of 879, 5185, 12363, 22413, 35335, 51129? 1436*a**2 - 2*a - 555 What is the f'th term of -283998, -567991, -851984? -283993*f - 5 What is the q'th term of -66, -718, -1802, -3312, -5242, -7586? q**3 - 222*q**2 + 7*q + 148 What is the k'th term of -1264, -2960, -6784, -13552, -24080? -136*k**3 - 248*k**2 - 880 What is the k'th term of 620, -1502, -5040, -9988, -16340? k**3 - 714*k**2 + 13*k + 1320 What is the o'th term of 397932, 398019, 398162, 398361? 28*o**2 + 3*o + 397901 What is the b'th term of 510, 1164, 1934, 2802, 3750, 4760, 5814? -3*b**3 + 76*b**2 + 447*b - 10 What is the l'th term of -26, -117, -268, -467, -702? 2*l**3 - 42*l**2 + 21*l - 7 What is the n'th term of -4516065, -4516066, -4516067? -n - 4516064 What is the q'th term of 6548, 53273, 180110, 427115, 834344, 1441853, 2289698, 3417935? 6676*q**3 - 7*q - 121 What is the q'th term of 7466794, 7466788, 7466778, 7466764? -2*q**2 + 7466796 What is the t'th term of 388728, 388650, 388438, 388026, 387348, 386338, 384930? -11*t**3 - t**2 + 2*t + 388738 What is the p'th term of 564337, 1128652, 1692967, 2257282? 564315*p + 22 What is the g'th term of -1529, -5805, -10081, -14357? -4276*g + 2747 What is the z'th term of 1312337, 2624286, 3936235, 5248184, 6560133, 7872082? 1311949*z + 388 What is the c'th term of -56324852, -112649698, -168974542, -225299384, -281624224, -337949062? c**2 - 56324849*c - 4 What is the q'th term of 34066, 48877, 63690, 78505? q**2 + 14808*q + 19257 What is the u'th term of 729453, 1458900, 2188343, 2917782? -2*u**2 + 729453*u + 2 What is the g'th term of 762, 4314, 13926, 32628, 63450, 109422, 173574, 258936? 505*g**3 + 17*g + 240 What is the d'th term of 573246, 574280, 575312, 576342, 577370, 578396? -d**2 + 1037*d + 572210 What is the q'th term of 6229338, 12458673, 18688000, 24917319, 31146630, 37375933? -4*q**2 + 6229347*q - 5 What is the v'th term of -124778538, -124778533, -124778528, -124778523, -124778518? 5*v - 124778543 What is the a'th term of -6349, -13339, -20329, -27319, -34309, -41299? -6990*a + 641 What is the i'th term of -12689, -25234, -37781, -50330, -62881, -75434, -87989? -i**2 - 12542*i - 146 What is the w'th term of 303009, 303124, 303239, 303354? 115*w + 302894 What is the c'th term of -174097248, -174097247, -174097246, -174097245, -174097244, -174097243? c - 174097249 What is the d'th term of -124402, -248678, -372964, -497266, -621590, -745942, -870328, -994754? -d**3 + d**2 - 124272*d - 130 What is the h'th term of -17785, -17736, -17687, -17638? 49*h - 17834 What is the f'th term of 44334574, 88669143, 133003712? 44334569*f + 5 What is the i'th term of -211, -364, -415, -364, -211? 51*i**2 - 306*i + 44 What is the q'th term of -207, -404, -877, -1770, -3227? -24*q**3 + 6*q**2 - 47*q - 142 What is the s'th term of 1706922, 1706914, 1706906? -8*s + 1706930 What is the g'th term of -247962, -248050, -248196, -248400, -248662, -248982, -249360? -29*g**2 - g - 247932 What is the i'th term of -1706, -767, 810, 3025, 5878? 319*i**2 - 18*i - 2007 What is the n'th term of -18286, -18347, -18464, -18643, -18890, -19211, -19612? -n**3 - 22*n**2 + 12*n - 18275 What is the q'th term of -5358, -4845, -3990, -2793, -1254, 627, 2850? 171*q**2 - 5529 What is the f'th term of -129253, -129367, -129483, -129601? -f**2 - 111*f - 129141 What is the r'th term of -759, -3281, -5769, -8205, -10571? 3*r**3 - r**2 - 2540*r + 1779 What is the u'th term of 18727754, 18727752, 18727748, 18727742, 18727734, 18727724? -u**2 + u + 18727754 What is the c'th term of 195, 192, 179, 156? -5*c**2 + 12*c + 188 What is the d'th term of -866026, -866047, -866078, -866119? -5*d**2 - 6* | Low | [
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917 F.2d 1305 Unpublished DispositionNOTICE: Sixth Circuit Rule 24(c) states that citation of unpublished dispositions is disfavored except for establishing res judicata, estoppel, or the law of the case and requires service of copies of cited unpublished dispositions of the Sixth Circuit.Charles TILLEY and wife; Patricia Tilley, d/b/a StoneMountain Tavern & Music Hall, Plaintiffs-Appellantsv.ADRIATIC INSURANCE COMPANY, Defendant-Appellee No. 89-6459. United States Court of Appeals, Sixth Circuit. Nov. 6, 1990. Before MERRITT, Chief Judge; and BOYCE F. MARTIN, Jr., and ALAN E. NORRIS, Circuit Judges. MERRITT, Chief Judge. 1 In this diversity case, plaintiffs, the owners of a tavern and music hall, appeal from the grant of summary judgment for defendant, which denied plaintiffs recovery under their fire insurance policy because of material misrepresentations made by plaintiffs in their insurance application. The success of plaintiffs' appeal turns on whether, under Tennessee law, it is necessary for an insurer to attach an application to, or incorporate it within, the policy itself in order for the insurer to void the policy based upon misrepresentations made in the application. Because we hold that Tennessee law does not have such a requirement, we affirm. 2 Defendant Adriatic issued to plaintiffs Mr. and Mrs. Tilley a fire insurance policy covering plaintiffs' tavern and music hall. On June 16, 1988, which fell within the coverage period of the policy, a fire totally destroyed the building and its contents. Plaintiffs timely filed with defendant a statement of loss as required by their policy. Defendant denied plaintiffs' claim, alleging that the policy was void because of misrepresentations made by plaintiffs in their application concerning past loss experience and cancellations of prior insurance policies. 3 Plaintiffs admitted in the lower court proceeding that their application contained false statements. In response to specific questions in the application, plaintiffs failed to enumerate all past insurance losses they had experienced and to reveal that some of their past insurance policies had been cancelled. Under Tennessee law, an insurer may void an insurance policy where an oral or written misrepresentation is made in the application for an insurance policy when the misrepresentation concerns a matter which increases the risk of loss to the insurer. Tenn.Code Ann. Sec. 56-7-103 (1989).1 The lower court found, and plaintiffs do not challenge on appeal, that these misrepresentations increased the risk of loss within the meaning of the statute. 4 Instead, plaintiffs argue that defendant cannot rely on this statute because defendant failed to attach the application to, or incorporate the application within, the policy given to plaintiffs. They premise their argument on two other statutes, Tenn.Code Ann. Sec. 56-7-102 and Sec. 56-7-301(4). 5 We agree with the District Court that Tenn.Code Ann. Sec. 56-7-103 applies and hence we hold that defendant could void the insurance contract due to plaintiffs' misrepresentations in the policy application. The statutes cited by plaintiffs are inapposite. Tenn.Code Ann. Sec. 56-7-301(4) states that misrepresentations, made in the absence of fraud, cannot serve to void a policy unless the false statement is contained in the written policy, and a copy of the application is endorsed upon or attached to the policy when issued. However, this statute specifically applies to life insurance policies.2 The other statute cited by the plaintiffs, Tenn.Code Ann. Sec. 56-7-102, sets forth that "[e]very policy of insurance, issued to or for the benefit" of a Tennessee resident must "contain the entire contract of insurance between the parties." 6 These two statutes cannot be construed to defeat Tenn.Code Ann. Sec. 56-7-103 simply because the application in which the misrepresentations were made was not attached to the fire insurance policy given to plaintiffs. This result follows from Medley v. Cimmaron Ins. Co., 514 S.W.2d 426 (Tenn.1974), in which the Tennessee Supreme Court held that an application for an automobile liability insurance policy "need not be made a part of the policy, or attached to it, in order for the insurance company to deny coverage based upon misrepresentations contained in such application." Id. at 428. 7 In Medley, the court rejected the arguments that plaintiffs here make. First, the court refused to construe Tenn.Code Ann. Sec. 56-1102 (predecessor to Sec. 56-7-102) "to preclude the insurer from relying upon misrepresentations contained in an application," where the application was not attached to, or incorporated within, the policy. 514 S.W.2d at 428. Thus, based on this case, we hold that these similarly situated plaintiffs cannot rely on Tenn.Code Ann. Sec. 56-7-102 to defeat application of Tenn.Code Ann. Sec. 56-7-103. 8 Furthermore, relating to plaintiffs' second argument, the Medley court also noted that while Tenn.Code Ann. Sec. 56-111(4) (predecessor to Sec. 56-7-301(4)) "expressly requires an application to be endorsed upon or attached to certain kinds of life insurance policies," the section is not applicable to automobile insurance policies. Id. While no Tennessee court has ever specifically stated that Tenn.Code Ann. Sec. 56-7-301(4) does not apply to a fire insurance policy, we read Medley to mean that the Tennessee Supreme Court would limit application of Sec. 56-7-301(4) solely to life insurance policies. Such an interpretation most logically follows from a textual reading of the statute. 9 Under Tennessee law, defendant did not have to attach the application to, or endorse the application upon, plaintiffs' fire insurance policy in order to void the policy based upon the uncontested material misrepresentations that plaintiffs made in their application. 10 Accordingly, the judgment below is AFFIRMED. 1 Tenn.Code Ann. Sec. 56-7-103 (1989) provides, in relevant part, that [n]o written or oral misrepresentation or warranty ... made ... in the application [for a policy of insurance], by the assured or in his behalf, shall be deemed material or defeat or void the policy or prevent its attaching, unless such misrepresentation or warranty is made with actual intent to deceive, or unless the matter represented increases the risk of loss. 2 In relevant part, Tenn.Code Ann. Sec. 56-7-301 provides: No policy of life insurance shall be issued in this state ... unless the same shall contain the following provisions: (4) Statements Are Representations and Not Warranties in Absence of Fraud; Written Application Made Part of Policy. A provision, except in industrial policies, that all statements made by the insured shall, in the absence of fraud, be deemed representations and not warranties, and that no such statement shall void the policy unless it is contained in a written application, and a copy of such application shall be endorsed upon or attached to the policy when issued.... | Mid | [
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The evolutionarily conserved indolergic receptors of the non-hematophagous elephant mosquito Toxorhynchites amboinensis. The conservation of the mosquito indolergic receptors across the Culicinae and Anophelinae mosquito lineages, which spans 200 million years of evolution, is a testament to the central role of indolic compounds in the biology of these insects. Indole and skatole have been associated with the detection of oviposition sites and animal hosts. To evaluate the potential ecological role of these two compounds, we have used a pharmacological approach to characterize homologs of the indolergic receptors Or2 and Or10 in the non-hematophagous elephant mosquito Toxorhynchites amboinensis. We provide evidence that both receptors are narrowly tuned to indole and skatole like their counterparts from hematophagous mosquitoes. These findings indicate that Toxorhynchites detects indole and skatole in an ecological context to be determined and underscore the importance of understanding the role of these compounds in mosquitoes. | Mid | [
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Q: Get Google Maps v3 corner coordinates from iFrame to parent page I have a Google Map with marker data pulled from my database on my website inside an iFrame. I know that with Maps v3 it is possible to get the new corner GPS coordinates when the map is moved in JavaScript. Is it possible to pass this map information from the map page inside the iFrame to the parent page so I can change the content on the parent page to match what the map is showing with JavaScript? Both pages are on my same server. I imagine that worst case scenario I can just have the JavaScript write the map corner info to a session variable and read that on the parent, but is there a simpler way? A: You don't show any HTML or code, so I can't be specific, but it's pretty straightforward to get information from an iFrame. Suppose frameId is the ID of your iFrame and mapId is the ID of the map in that iFrame. Then: var iframe = document.getElementById('iframeId'); var iframeDoc = iframe.contentDocument || iframe.contentWindow.document; You now have the iFrame document and can do the usual: var map = iframeDoc.getElementById('mapId'); var bounds = map.getBounds(); | Mid | [
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Q: Setting timer interval based on stopwatch value I want my timer interval to be set based on the stopwatch value. Stopwatch calculates the execution time of a function and this execution time should be used for my timer interval. Timer t = new Timer(timercallbackfunc, null, 0, elapsedtime); Please provide some code examples. A: Do you mean something like this? Stopwatch stopwatch = new Stopwatch(); stopwatch.Start(); ... Timer t = new Timer(timercallbackfunc, null, 0, stopwatch.ElapsedMilliseconds); | Mid | [
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Sure — we love jewelry, chocolates and those little teddy bears holding heart-shaped pillows; but what do we love even more on Valentine’s Day? Flowers and food. Since we’re strong, independent ladies, we buy ourselves flowers on a regular basis, and we eat food almost every day. So how do we make this Valentine’s Day special?? What if we combine the two “F” words and make flowers into food?! Below are some tantalizing recipes that incorporate all the brightness and fragrance of flowers into things you can eat and drink. Put the pedal to the metal, or in this case, the petal to the cast iron, and get ready for food with flowers. Dinner — These savory recipes use flowers as the star of the dish, but don’t overwhelm the palate with an overly floral flavor. You can also use the petals or stem of the main-ingredient flower as a garnish for a pretty presentation. Dessert — Flowers and dessert make an excellent pair, and you’d be hard-pressed to find someone who doesn’t love lavender or rose with a little something sweet. Just make sure not to use more than what’s called for, as an overly floral treat can easily overwhelm the palate. Drinks — There are plenty of liqueurs out there that boast floral flavors (like creme de violette and St. Germain), but we think it’s more fun to use the actual flower in the cocktail. You can prepare a flower simple syrup, muddle the flowers at the bottom of the cocktail or use jarred flowers in syrup made just for cocktails. Bonus: Instead of using a petal or two for garnish, place some buds and flowers in your ice cube trays before freezing for an elegant touch. | Mid | [
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C4D202 - Cinema4D and After Effects in ProductionГод выпуска: 2009Производитель: fxphdСайт производителя: http://www.fxphd.com/Автор: Tim ClaphamПродолжительность: 6:54:43Тип раздаваемого материала: ВидеоурокЯзык: АнглийскийОписание: The main focus of the course will be using Cinema4D to create motion graphics. Through all the classes, general workflow and project management will be discussed, including organising the object manager, use of layers, XRefs, and managing layouts. We will look at practical uses for many of the available modules, including MoGraph, Thinking Particles, Hair, Cloth and Sketch and Toon. This will also involve use of Xpresso, materials, some post effects and lighting and rendering techniques. Throughout the term we will work on both tips and techniques, as well as project based motion graphics classes. Specifically taking a concept and developing the project, outputting various render passes and compositing these in After Effects. | High | [
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Off-Campus Study INSA Lyon, the oldest and largest school making up the INSA group, was founded in 1957 to train highly qualified engineers, support continuing education, and conduct research and testing. INSA is very interested in international exchange; about 600 foreign students from 35 countries study at the institute annually. INSA Lyon is known as the scientific and technological capital of France, with 22 research laboratories, more than 600 researchers and 650 PhD students. INSA has been repeatedly rated the number one engineering school in France. This program would be suitable for students that are ready to be abroad, but would still like some of the academic services that a U.S. college provides. It is a good choice for someone that is a world traveler OR has never left their hometown. However, studying in France does require independence to be successful in the bureaucratic university system. Learn more about INSA Lyon here! Read the ISEP Country Handbook to learn more about visa requirements, educational system, and culture. Program Type Exchange Locations Villeurbanne, France Languages of Instruction English Program Dates Fall 2018 only: September 2018 - January 2019* *INSA-Lyon may be able to work with students that need to complete early exams. All dates are tentative and may change. ISEP will alert all accepted students of final dates. Eligibility To be eligible to participate in this program, students must meet the following requirements: Good academic and judicial standing during time of application AND time of participation in program Undergraduates must have completed at least two semesters of study at Lake Forest College AND have junior status or higher before participation. At least 18 years of age by the program’s departure date. Be able to stay at the host program for the duration of the semester, including through the exam and travel periods Minimum GPA of 2.75. Students applying to ISEP must apply for an Exchange option (in any country) as a first choice but may apply to a Direct option as a back-up. Direct options may have an additional cost. Chance of placement for US students is generally Excellent. Location LyonTech-la Doua 0 - 5,000 on Campus 250,000+ residents in Villeurbanne Language(s) spoke on campus: French The INSA Lyon campus includes 11 residence halls connected to the Lyon city center by two tram lines. There are many extracurricular activities for students organized by the Maison des Etudiants, a 1,000 square meter building housing the Student Union with laundry facilities, a grocery store and more. There are over 130 clubs and societies on campus. Students can also take part in club sports and cultural and humanitarian activities. International students are giving priority access to on-campus housing, which includes three student restaurants, various sports facilities, a library, communal rooms with free WiFi and more. Academics The “Information Science & Technology Semester” is a program jointly organized by three engineering departments of INSA Lyon (Telecommunication Department, Computer Sciences and Engineering Department, Electrical Engineering Department) in collaboration with three research laboratories (CITI, CREATIS, LIRIS). This program targets foreign students in their last year of their bachelor’s degree. Full IST semester program is composed of six scientific courses (to be chosen among 12) associated with a research attachment within one of the IST research laboratories (CITI, CREATIS, LIRIS). The 30 ECTS of the IST Semester are obtained by: French universities operate in ways that are quite different from the system with which you are familiar. Understanding the differences will help you plan your program of study in France, use your time effectively while you are there and return with transferable credits. French students follow a highly structured curriculum specific to the degree they are pursuing from day one at the university. They do not take “liberal arts” or general education requirements for 2 years before focusing on a major or area of study as most U.S. students do. In general, French students have to assume more responsibility for their own lives on campus than American students. They do not have as many campus support systems as American students, and they too may experience frustration when they first begin their studies! The amount of information you receive before you leave and during the first days or weeks of your stay abroad may seem overwhelming. However, if you review the material sent to you by ISEP and your host institution carefully, you will be ready to meet the challenges of adjusting to a different system and find your coordinator and professors more willing to help you than if you had not prepared yourself. French professors are not as accessible as their American counterparts. Increasingly, however, professors do have office hours or may be available if you make an appointment. They will also be willing to answer questions and discuss problems before or immediately after class. It would be a good idea to introduce yourself to the professor at the beginning of the year, explaining that you are an international student. Do ask other students in class for advice or assistance if you do not understand something. Please review the country’s handbook for more information on the education system. COURSEWORK AND GRADING Registration (inscription) is the process of enrollment into the university; you will fill out many forms and hand in several passport-size photos in order to receive the various university cards signifying your enrollment. Course Selection: As an exchange student, you have greater flexibility in choosing courses than French students do. You do not need to take a complete package of courses at one level. However, if you focus on courses in one or two departments, you will find it easier to put together a schedule, your program of studies will be more cohesive, and you will have a better chance of getting to know French students because you will be seeing the same group on a regular basis. Selection of courses is done during registration. You should expect to have to go to each building that houses the faculté (department) of the course you wish to take, find the administrative office, ask for a course listing and sign up for the desired course. Students should be aware that the registration process can take several days. French universities are not as “service-oriented” as those in the United States and there are many students for few administrators. Ask questions of your ISEP host coordinator if you have trouble registering. Also, the add-drop process is very informal. You may want to observe several classes before making your final selection and to make sure that you will be able to follow the course and fulfill all course requirements. Remember to consult about any changes in your course selections with your host and home coordinators and advisors. Be sure to keep track of your courses, including course titles, hours, professors, and assignments for after your exchange. In all cases, you must verify all of your course information with your host coordinator to ensure that you have enrolled properly. Course Approvals Check to see if your department has pre-approved courseshere. If not, don’t worry. You can work with your advisor. EXAMS AND GRADING Student performance is assessed in two ways: Short quizzes given throughout the semester allow instructors to check what their students have learned in each unit. Examinations covering all of the material presented during the semester are given at the end of each semester, generally just before the February break and again in June, before the summer break. The atmosphere at a French university may seem low-pressure, but be on your guard. Even if a class does not require regular assignments, you must keep up with the reading and attend classes. Final examinations are given at the end of each course. ISEP students should check with professors to determine when the exam will be given as most professors do not provide a syllabus at the beginning of a course. As a foreign student, you may not be required to take the final exam. You may be able to substitute written assignments for the exam. Check with the professor to find out whether you are expected to take the exam in order to get a grade (in many instances, the exam might be the only evidence that you have taken the class) or whether you can substitute other assignments. Taking a final does not automatically entitle you to a grade since you must pass your exams to receive a grade. Also, make sure to register for the exam in addition to taking it. If you make any special arrangements with a professor, obtain the agreement in writing signed by both you and the professor. Provide a copy of the agreement to both your home and host ISEP coordinators and keep a copy for yourself. Without an agreement in writing, it is expected that you will take all final exams. Credit transfer is not guaranteed if you fail to take exams or provide written proof of other arrangements. Housing and Meals Students are housed in a studio apartment; one person per room. Read more information about living on the LyonTech Campus. Meals are through the university cafeteria. Financial Information For all approved programs for guaranteed financial aid transferability, students pay their Lake Forest College tuition plus a program fee. The program fee for a semester with the ISEP Exchange to INSA-Lyon includes orientation, on-site director, college fees, housing, and the equivalent of 19/meals per week. Here is an estimated budget for the Fall 2017/Spring 2018 semester: Budget Item Amount Lake Forest College Tuition $22,412 Program fee (estimated) Note: Spring may have added costs $5,100 College Deposit (credit) ($250) Total Expected Billed by Lake Forest College $27,512 ISEP Fee due on Stage 2 Application $325 College Deposit due on Acceptance (non-refundable, but shows as credit on bill for off-campus term) Tuition rates and program fees are subject to change each year, but this information was up-to-date as of February 2017. We will notify applicants, and update this page if the program fee or other estimates change. Keep in mind that you may spend more or less in certain areas like personal expenses, travel, meals, or airfare, depending on exchange rates and your own spending habits. Classroom or lab fees are not included in this estimate, nor fees to enroll in courses at partner institutions, and will depend on your course registration choices. | High | [
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Alan Gomez USA TODAY The number of undocumented immigrants living in the United States stayed steady for an eighth straight year in 2016 with 11.3 million people, according to a report published Tuesday. The gradual improvement of the Mexican economy, the federal government's additions to border security and a shift in the demographics of Latin America all contributed to the nearly decade-long freeze in illegal immigration, according to the report by Pew Research Center. There was nearly two decades of growth in immigration throughout the 1990s and 2000s. Still, President Trump is cracking down on illegal immigration and increasing deportations. White House counselor Kellyanne Conway said on Fox News that the proposed border wall with Mexico remains a priority for Trump but does not have to be funded in this week's spending bill, making it easier for Congress to avert a government shutdown. Critics say the numbers in the Pew report show how misguided those efforts are. "It feels like it's out of step with what the U.S. really needs right now," said Angela Kelley, senior strategic adviser for immigration at the Open Society Policy Center. "Of course we need to enforce our border, and we do that rigorously. But rather than the bluster of the border wall, it would show real leadership if this administration could deal sensibly with the 11 million people living here." The White House says it's simply responding to the will of the voters by making illegal immigration a central focus. On Monday, White House press secretary Sean Spicer was asked why the president insists on more funding for border security when the number of people caught crossing the southwest border with Mexico has plummeted in the first months of his term. "Just because you have a couple good months in a year, I think you want to make sure that you take prudent long-term steps," Spicer said. "(The wall) is a permanent step that will extend beyond his presidency. Eight years from now, the new president will have that wall in place to make sure that it doesn't continue." Read more: Government shutdown less likely now that Trump has relented on border wall White House may be relenting on demand for immediate border wall funding 'Physically imposing': Here are the design specs for Trump's border wall More Mexicans leave than enter USA in historic shift The report also shows how quickly the nature of illegal immigration has changed in recent years. Mexicans have made up a majority of the undocumented immigrant population for decades, but that was no longer the case in 2016. For the first time, Mexicans made up only 50% of the population, showing how much illegal immigration from America's southern neighbor has slowed. In fact, the number of undocumented immigrants from Mexico dropped from 6.4 million in 2009 to 5.6 million in 2015, according to Pew. Jeffrey Passel, senior demographer at Pew and co-author of the report, said several factors have contributed to the decline. The Mexican economy has improved in recent years, meaning Mexicans have more economic opportunities there. He said the U.S. Border Patrol has increased over several past presidential administrations, making crossing much harder and more expensive. And he said the demographics have changed considerably, with Mexican women giving birth to fewer children, leaving fewer potential immigrants and smaller networks for them living in the U.S. "It used to be that every kid in rural Mexico had an uncle in the United States," Passel said. "Now there's not as many." As illegal immigration from Mexico has slowed, people from other countries have stepped in. The number of Central Americans has increased from 1.6 million in 2009 to 1.8 million in 2015, as people from El Salvador, Guatemala and Honduras flee violence in their countries. The U.S. has also seen an increase in the number of undocumented immigrants from Asia, Africa and the Middle East. Passel said that shows the influence of visa overstays — people who legally enter the country on a valid visa but stay after it expires. And while that trend has been developing over the years, "It has been a fairly rapid change." | Mid | [
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Credit control may involve mechanisms that interact in real-time with accounts associated with end users, and may control or monitor the charges related to service usage associated with those end users' accounts. For example, credit control may involve checking whether credit is available for a given account, reserving credit, deducting credit from the end user account when service is completed, and/or refunding reserved credit that is not used. Credit control has particular applicability in the provision of network services, such as, for example, provision of cellular airtime in a cellular radio network, provision of multimedia data in a wired or wireless network, etc. Credit control may be implemented by a charging system (e.g., a credit control server) that monitors and controls charges related to service usage of end users, and that grants and/or denies credit authorizations to those end users, thus, enabling network service delivery to the end users. RFC 4006, entitled “Diameter Credit-Control Application” (DCCA), provides a specification that can be used to implement real-time credit-control for a variety of end user services such as network access services, Session Initiation Protocol (SIP) services, messaging services, and download services. RFC 4006 provides a general solution to real-time cost and credit-control in charging systems. | High | [
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After what feels like an eternity of waiting, Star Wars: The Last Jedi has finally reached cinemas, scoring a whopping $450 million opening weekend worldwide. While reviews have been unanimously positive for Rian Johnson’s blockbuster, there’s been huge backlash online, many fans expressing disappointment. There’s no better place to see the great divide between critics and fans than on Rotten Tomatoes, where the critical consensus scores 93% while audiences score The Last Jedi 56%. That difference of 37% marks an anomaly on the website, the audience score being the lowest of all Star Wars movies, meaning The Last Jedi is apparently worse than Phantom Menace, Attack of the Clones, and Revenge of the Sith. Conversely, critics say The Last Jedi equals A New Hope and The Force Awakens, only falling behind The Empire Strikes Back. 27 films to look out for in the first half of 2018 Show all 27 1 /27 27 films to look out for in the first half of 2018 27 films to look out for in the first half of 2018 Black Panther Released: 12 February Director: Ryan Coogler Cast: Chadwick Boseman, Michael B. Jordan, Lupita Nyong'o, Forest Whitaker, Danai Gurira, Martin Freeman 27 films to look out for in the first half of 2018 The Greatest Showman Released: 1 January Director: Michael Gracey Cast: Hugh Jackman, Zac Efron, Michelle Williams, Rebecca Ferguson, Zendaya, 27 films to look out for in the first half of 2018 Darkest Hour Released: 12 January Director: Joe Wright Cast: Gary Oldman, Kristin Scott Thomas, Ben Mendelsohn 27 films to look out for in the first half of 2018 Three Billboards Outside Ebbing Missouri Released: 12 January Director: Martin McDonagh Cast: Frances McDormand, Woody Harrelson, Sam Rockwell, Caleb Landry Jones > Twentieth Century Fox 27 films to look out for in the first half of 2018 Coco Released: 19 January Director: Lee Unkrich ,p>Cast: Anthony Gonzalez, Gael García Bernal, Benjamin Bratt, Renée Victor 27 films to look out for in the first half of 2018 Downsizing Released: 19 January Director: Alexander Payne Cast: Matt Damon, Christopher Waltz, Jong Chau, Kristen Wiig, Jason Sudeikis 27 films to look out for in the first half of 2018 Early Man Released: 26 January Director: Nick Park Cast: Eddie Redmayne, Tom Hiddleston, Maisie Williams, Timothy Spall 27 films to look out for in the first half of 2018 Fifty Shades Freed Released: 9 February Director: James Foley Cast: Dakota Johnson, Jamie Dornan, Kim Basinger 27 films to look out for in the first half of 2018 Maze Runner: The Death Cure Released: 9 February Director: Wes Ball Cast: Dylan O'Brien, Thomas Brodie Sangster, Kaya Scodelario, Giancarlo Esposito, Aidan Gillen 27 films to look out for in the first half of 2018 The Shape of Water Released: 16 February Director: Guillermo del Toro Cast: Sally Hawkins, Octavia Spencer, Michael Shannon, Michael Stuhlbarg, Doug Jones 27 films to look out for in the first half of 2018 Annihilation Released: 23 February Director: Alex Garland Cast: Natalie Portman, Jennifer Jason Lee, Gina Rodriguez, Tessa Thompson, Oscar Isaac 27 films to look out for in the first half of 2018 Dark River Released: 23 February Director: Clio Barnard Cast: Ruth Wilson, Mark Stanley, Sean Bean 27 films to look out for in the first half of 2018 Red Sparrow Released: 2 March Director: Francis Lawrence Cast: Jennifer Lawrence, Joel Edgerton, Jeremy Irons 27 films to look out for in the first half of 2018 Tomb Raider Released: 16 March Director: Roar Uthaug Cast: Alicia Vikander, Walton Goggins, Daniel Wu, Dominic West, 27 films to look out for in the first half of 2018 A Wrinkle in Time Released: 23 March Director: Ava DuVernay Cast: Oprah Winfrey, Reese Witherspoon, Mindy Kaling, Zach Galifianakis 27 films to look out for in the first half of 2018 Pacific Rim: Uprising Released: 23 March Director: Steven S. DeKnight Cast: John Boyega, Scott Eastwood, Charlie Day, Burn Gorman 27 films to look out for in the first half of 2018 Roman J Israel, Esq Released: 23 March Director: Dan Gilroy Cast: Denzel Washington, Colin Farrell, Carmen Ejogo Columbia Pictures 27 films to look out for in the first half of 2018 Isle of Dogs Released: 30 March Director: Wes Anderson Cast: Bill Murray, Bryan Cranston, Edward Norton, Tilda Swinton, Scarlett Johansson 27 films to look out for in the first half of 2018 Ready Player One Released: 30 March Director: Steven Spielberg Cast: Tye Sheridan, Olivia Cooke, Ben Mendelsohn, Mark Rylance, Simon Pegg 27 films to look out for in the first half of 2018 Avengers: Infinity War Released: 27 April Director: The Russo Brothers Cast: Robert Downey, Jr, Chris Hemsworth, Scarlett Johansson, Josh Brolin 27 films to look out for in the first half of 2018 Untitled Han Solo Film Released: 25 May Director: Ron Howard Cast: Alden Ehrenreich, Emilia Clarke, Woody Harrelson, Donald Glover 27 films to look out for in the first half of 2018 Jurassic World: Fallen Kingdom Released: 8 June Director: J.A. Bayona Cast: Bryce Dallas Howard, Chris Pine, B.D. Wong, Toby Jones 27 films to look out for in the first half of 2018 Deadpool 2 Released: 1 June Director: David Leitch Cast: Ryan Reynolds, Morena Baccarin, T.J. Miller, Zazie Beetz, Josh Brolin 27 films to look out for in the first half of 2018 Ocean's 8 Released: 22 June Director: Gary Ross Cast: Sandra Bullock, Cate Blanchett, Mindy Kaling, Sarah Paulson, Anne Hathaway, Olivia Munn, Helena Bonham Carter, Rihanna, Matt Damon 27 films to look out for in the first half of 2018 Ant-Man and the Wasp Released: 29 June Director: Peyton Reed Cast: Paul Rudd, Evangeline Lilly, Michael Douglas, Michelle Pfeiffer 27 films to look out for in the first half of 2018 Soldado Released: 29 June Director: Stefano Sollima Cast: Benicio del Toro, Josh Brolin, Jeffrey Donovan, Catherine Keener, Matthew Modine 27 films to look out for in the first half of 2018 The Incredibles 2 Released: 13 July Director: Brad Bird Cast: Craig T. Nelson, Holly Hunter, Sarah Vowell, Samuel L. Jackson But are audiences actually disliking The Last Jedi? One problem with Rotten Tomatoes’ audience score, along with IMDB, is there’s no vetting process. People don’t need to prove they’ve seen a movie and can vote multiple times through multiple accounts. Instead, we should look to the movie’s CinemaScore, an America-based exit poll system that scientifically works out an audience score. Movies are marked between A+ and F, the score often accurately hinting at how much a movie will make at the box-office. The Force Awakens earned an A score, with 90% of all respondents being positive, the average score being 4.5, while Rogue One earned an A, 91% positive feedback and the same score. By comparison, The Last Jedi also won an A CinemaScore, 89% positive feedback, and a five-out-of-five score. With those statistics being so positive, how can the negative online reaction be explained? According to Deadline, non-Disney sources are saying the backlash has been primarily online “trolling”. The publication also points to one Facebook page titled “Down With Disney’s Treatment of Franchises and Fanboys” who are claiming to use bot accounts to target the film’s score. There is, of course, some genuine debate over the movie’s quality to be had. Some people are frustrated by Luke Skywalker’s portrayal, others disliked the Finn/Rose side-story. According to the scientifically accumulated statistics, though, audiences really are enjoying The Last Jedi. Offering a statement on the backlash, Disney has said: “Rian Johnson, the cast, and the Lucasfilm team have delivered an experience that is totally Star Wars yet at the same time fresh, unexpected and new. “That makes this a Star Wars film like audiences have never seen – it’s got people talking, puzzling over its mysteries, and it’s a lot to take in, and we see that as all positive, that should help set the film up for great word-of-mouth and repeat viewing as we enter the lucrative holiday period.” | Low | [
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ROCKFORD, Ill. (WIFR) -- As more and more businesses continue to open up in the downtown Rockford area, we could soon see the groundbreaking of another hotel within the next couple of months. The hotel will take the place of the Millennium Center in the 200 block of South Madison Street. The hotel's developer, Peter Provenzano says a financing package is in the process of being finalized and hopes to break ground this fall. Provenzano says the downtown area has recently seen an increase in traffic and wants to create another place to draw people to downtown. “We see people running on a daily basis, jogging, on the west side we didn't often see that and we're starting to see sort of the day time foot traffic evolve in all of downtown and that's real exciting to witness,” said Chairman of the Rock River Development Partnership Peter Provenzano. The nearly $10 million project is expected to house 47 rooms, a restaurant and an athletic facility. | Mid | [
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Policies Life of Fred: Pre-Algebra 2 with Economics $29.00 You know what arithmetic books look like. They are all pretty much alike. Using very few words, they give a couple of examples and then have the students do a hundred identical problems. Then they give another couple of examples and another hundred problems. And for students, arithmetic becomes as much fun as cleaning up their rooms, eating yams, or going to the dentist. The books in the Life of Fred series take a different approach. Note that the subtitle on each book is “as serious as it needs to be”. Veteran math teacher, Stan Schmidt, has brought to life a character who will make math fun, relevant, and understandable. Don’t be surprised if your child who dreads math asks to do more at the end of a lesson. Each of the books tells a story—a story of one day in the life of a five-and-a-half-year-old boy. All of the math arises out of Fred’s life. Never again will students have to ask their perennial question: “When are we ever gonna use this stuff?” Don’t let the nontraditional method of teaching fool you. Each of these books contains more math than is normally taught at the college level. These are not skimpy. They offer solid preparation for SAT exams and upper-division mathematics. One of the reasons is that very few arithmetic books tell you the why of various math rules—they just say that “it’s a rule”. Fred will give you the reasoning behind the rules making the math much more meaningful and memorable. In all of the books in the Life of Fred series, the emphasis is on how to learn by reading. Students of normal academic ability can learn mathematics from Fred without your tutoring the material though you’ll enjoy reading about Fred’s adventures as much as your student does. You can relax. As students progress through high school, college, and graduate school, they find that less and less is learned in the classroom lecture format. Increasingly, it’s the written word that does the teaching. Let the book do the math teaching. These books are gloss-film laminated hardcovers with Smyth sewn binding. Fully indexed and illustrated. They are not workbooks to write in, and each book will be enjoyed by all your children (and grandchildren!) Fred begins his summer vacation. Learn . . .* How to get rid of snakes in sugar cane fields* The difference between freedom and liberty* Why Fred couldn’t be a movie star* . . . and even some algebra and economicsAll fun!Just open & enjoy Domain and codomain of a function, Conversion factors, Steps in Solving Word Problems, How Not to Bore Your Horse If You Are a Jockey, One-to-one Functions, Unit Analysis, Key to a Successful Business, Five Qualities that Money Should Have, the Tulip Mania in Holland, Definitions of Capitalism, Socialism, and Communism, Payday Loans, the Tragedy of the Commons, Partnerships, Cardinality of a Set, Four Ways to Kill Competition, Freedom vs. Liberty, Why We Have a High Standard of Living, Tariffs, Demand Curves, Venn Diagrams, Ricardo’s Law of Comparative Advantage. | High | [
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Prevalence of suicidal feelings in a sample of non-consulting medical students. Five hundred and sixteen final-year non-consulting medical students were studied as to the occurrence of different degrees of suicidal feelings. A total of 12.6% reported some degree of suicidal feelings during the past year. Responses ranged along a continuum such that subjects reporting the more intense feelings also reported the less intense feelings. In 5.6% of the subjects the maximum intensity was only a feeling that life was not worthwhile, 4% had thought of taking their life, 0.9% had seriously considered suicide or made plans, and 0.4% had made an actual suicide attempt. Subjects experiencing suicidal feelings in the past year had had more minor psychiatric symptoms, particularly of depression, and had experienced more stressful events and somatic illness. In these respects they resembled the description of completed suicide. | Mid | [
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Vegetable Barley Soup is one of my favorites. Of course I also love Beef and Barley soup or Barley and Mushroom soup too. However, I’ve never thought to venture far from the traditional preparation. Now we’ve gone a bit wild and are combining some of my favorite flavors together for a hearty, spicy and curry inspired dinner. For this week’s French Friday’s with Dorie, we made a Vegetable Barley Soup with the Taste of Little India. This soup could not have come at a better time. I’ve had a terrible cold for the past two weeks or so and nothing has really helped. It’s been on and off and I’ve pumped myself full of decongestants and ibuprofen in an attempt at some relief to little avail. However, the gentle heat of the ginger and red pepper flakes along with the fragrant, warm aromas from the Garam masala provided some much needed sensory appeal and soothed my symptoms greatly. I honestly felt myself breathe for the first time in quite a while. By today, I was completely better and I think it’s all because of this soup. I am very happy that this recipe made a generous amount as I’ve been eating it all weekend and still have some left over to take to work this week for lunch. The thing about barley though is that it expands. It also doesn’t seem to stop expanding, so the broth is nearly fully absorbed into the grain. Which of course, is fine, it’s just less liquidy by the second and third days. You can add more stock if you want, but I am enjoying the more stew like quality at this point. This recipe was super easy to make too- which is always a plus when you are feeling under the weather and don’t want to be bothered to prep too much. I can definitely see this one being made again (and again!). While I cannot share this delightful recipe, you can (and should!) buy the book and cook along with us. It’s great fun! Every Friday we make a new recipe. Looking forward to next weeks! For details and to see how others are recreating the dishes from this awesome book, check out the FFWD site. Even though this week’s French Fridays with Dorie recipe was for a trio of soups, Broccoli, Asparagus and Red Pepper, they were all extremely quick and easy to make- stock (or bouillon cube) based with the vegetables pureed with an immersion blender. Super simple! Just as the name implies. Because I didn’t need a quart of soup for each flavor, I cut the recipes down to one cup each. This was the perfect amount for us. The broccoli was by far the favorite of the three. The red pepper soup was quite good too, but in my opinion it would have benefited from charring the peppers over the flame and peeling them before being added to the stock. Next time. I am sure the asparagus soup would have been terrific too had the asparagus been somewhat decent. I, quite literally, bought the last sad looking bunch at the grocery store. They were so shriveled and the tips were already turning and just so pitiful that I actually think using frozen would have been a better option. But alas, I bought them and the soup had, well, a rather bitter aftertaste to it. Thankfully, it was only one cup so I didn’t feel so badly letting it go down the drain. Overall though, these would make great dinner party or brunch appetizers as they don’t require much fussing, can be made in advance and served either warmed, chilled or at room temperature. Dollop a bit of fresh whipped cream and top with a spice of your choice and “Voila!”, an instant starter. I used pink salt for the red pepper, curry for the broccoli and black salt for the asparagus, but the combinations are endless. While I cannot share the actual recipe, you can (and should!) buy the book and cook along with us. It’s great fun! Every Friday we make a new recipe. Looking forward to next weeks! For details and to see how others are recreating the dishes from this awesome book, check out the FFWD site. I’ve never been a fan of baked apples. As a matter of fact, I may actually hate them. It’s one of those things you get at your grandma’s house. (No offense to grandmas!) You’d have dinner at her house and you ate everything on your plate just so you could have dessert, because that’s the rule. You’re praying for a big piece of deep, rich chocolate cake with heaps of sugary icing or some warm, fresh baked chocolate chip cookies or a triple scoop ice cream sundae and then, she sits a baked apple in front of you… and it’s got raisins in it, and bits of weird fruit and its brown and shriveled and mushy. And you try not to cry. Because it would rude not to eat it and you’d be admonished into sitting there until it was finished anyways because it’s such a “special treat” that she’d made for you. So you can understand my disdain for baked apples. It’s not something I’d ever make on my own. However, since it’s this week’s recipe for French Fridays with Dorie, and I am committed to the task, I made them. Well, now I am an adult and I get to choose which fruits actually go into the recipe- no raisins in sight! (I will eat a few, once in a blue moon, otherwise, they are not really something I have in the pantry.) I also get to cook the apples until just spoon tender and not to the consistency of a mealy, almost applesauce like hot fruit. These apples are peeled too, so they don’t seem so ugly and shriveled when cooked. These small changes made a big difference. The filling is a simple mix of dried fruits, nuts and spices. I used dried mango, papaya, apricots, and dates. I chopped some walnuts and mixed them with the fruit, added some honey and a few dashes of cinnamon, nutmeg and ginger. There was actually quite a bit of this filling left over and I have saved it to top my morning oatmeal for the next few days. The recipe said it could be served with ice cream, crème fraiche or whipped cream. Instead, I chose to serve it with a dollop of mascarpone that I mixed with a bit of vanilla sugar. I absolutely love mascarpone on baked peaches and other fruits (plus mixed in to various other dishes- like last week’s mac & cheese). It’s almost a “super food” in my book since it goes so well with nearly everything! The mascarpone was the true savior for these. These apples were much better than I expected. I didn’t hate them. But they were not nearly of the same caliber of the Long, Slow Apples we made last year. Those were amazing! Sweet, velvety and delicious! These were fine, but really, it was no comparison to those other apples. Everyone here took a bite and turned their noses up. Spoiled! Apple pie, apple fritters, or even apple turnovers would have seen a better reception. This is a dish I will share with my neighbors. I hate to let food go waste and since I would be the only one to eat them, off they go. One is plenty for me. So that said, I won’t be making this recipe again. I also will not ever torture my kids and their future kids by making them sit at the table and eat baked apples when there must be some luscious chocolate dessert around someplace. Please don’t let my prejudice discourage you from making this if baked apples are your thing. The recipe works and the flavor is quite good. They are also very pretty. You’d probably love them! Really! They are just not my thing. While I cannot share the actual recipe, you can (and should!) buy the book and cook along with us. It’s great fun! Every Friday we make a new recipe. Looking forward to next weeks! For details and to see how others are recreating the dishes from this awesome book, check out the FFWD site. | Mid | [
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If this is your first visit, be sure to check out the FAQ by clicking the link above. You may have to register before you can post: click the register link above to proceed. To start viewing messages, select the forum that you want to visit from the selection below. Re: Figured it out, but another question Victoria, YOu were EXTREMELY lucky in the choice of dataes that you used to test you alogorithm, because this would fail, badly, with real dates...that is dates other than 1/1/YYYY. YOur arrys (which you called numbers) is declared using Dim numbers(1 to 5) is in fact an array of type VARIANT (those may look, to you, as if they are dates, but to the computer they are actually STRINGS - they just happen to look like dates) and they are actually being stored by Visual Basic as VARAINT types - a VARIANT is a variable type which can hold ANY kind of value. If you wanted this routine to act on REAL dates, you would need to do this: Dim numbers(1 to 5) as Date ' this declares that you will be using the special DATE data type in the above the # symbols serve to inform Visual Baisc to translate the 1/1/2000 into its internal representation of a DATE in VB, a Date variable is actually a FLOATING POINT number where the whole part of the number (to the left of the decimal point) is the number of days betweenDec 31, 1899 and the date you used, and the fractional part of the number (to the right of the decimal point) is the fraction of a day (number of milli-seconds /86400000 ) since midnight on the day indicated (a date like 1/1/2000 is treated as if it were MIDNIGHT - the start of that date - so the fractional part would therefore be .000000) in the second example, yoy have a different problem, since the array does NOT in fact contain the same kinds of values in the two dimensions. So the approach that you have take will NEVER work properly, since you want DTAES in the first dimension, and Numbers in the second...but an array is BY DEFINITION, made up of the SAME KIND of values in ALL of its dimensions. YOu cannot have an array where the values in one dimesuion are one kind of thing (dares) and in another dimension, a different kind of value (numbers). Form what you have shown, while this problem CAN be solved, it would appear that you are something of a beginner, and the solution is very much different than anything that you have tried. The simplest approach is to declare YOUR OWN TYPE of value (called a User DEfined Type or UDT) , which has two parts - a Date part, and a Number part - and the declare an array of THAT User-Defined Type (single dimension) Re: Figured it out, but another question > is in fact an array of type VARIANT (those may look, to you, as if they are > dates, but to the computer they are actually STRINGS - they just happen to > look like dates) and they are actually being stored by Visual Basic as VARAINT > types - a VARIANT is a variable type which can hold ANY kind of value. > > If you wanted this routine to act on REAL dates, you would need to do this: Since Variants are being used, he could have done this numbers(1) = CDate("1/1/2000") numbers(2) = CDate("1/1/2001") etc. in order to have stored real dates in his original arrray. > in the second example, yoy have a different problem, since the array does > NOT in fact contain the same kinds of values in the two dimensions. So the > approach that you have take will NEVER work properly, since you want DTAES > in the first dimension, and Numbers in the second...but an array is BY DEFINITION, > made up of the SAME KIND of values in ALL of its dimensions. That's not true for arrays defined as Variants. Each element of a Variant array can be different. Give this code a try Re: Figured it out, but another question Rick, I was not aware of that, though when I think about it, what you say makes sense (it was late, last night, when I answered Victoria's question). However, that reall does not address her question, and I doubt that she was even aware that she was unsing VARIANT types, any way. I avoid VARIANTS at all costs, because of the performance hit, and that was the real reason for my saying what I said. And by using variants, the sort algorithm for a multiple dimensioned array becomes quite a bit more obtuse - having to keep the additional columns in sync is not always obvious - where the use of a UDT makes everyting behave as one would expect, and it becomes almost trivial to extend to many "columns" (additional fields in the UDT), and even allows for the columns to be in an arbitrary order - the suggested code would work, without change, if the UDT were changed to: Private Type MyType NumberPart as Integer DatePart as Date End Type where using the Multiple dimensioned array of variants (with the meanings of the COLUMNS swithched) would require significant re-write of the sort routine. Arthur Wood "Rick Rothstein" <[email protected]> wrote: >> is in fact an array of type VARIANT (those may look, to you, as if they are >> dates, but to the computer they are actually STRINGS - they just happen to >> look like dates) and they are actually being stored by Visual Basic as VARAINT >> types - a VARIANT is a variable type which can hold ANY kind of value. >> >> If you wanted this routine to act on REAL dates, you would need to do this: > >Since Variants are being used, he could have done this > > numbers(1) = CDate("1/1/2000") > numbers(2) = CDate("1/1/2001") > etc. > >in order to have stored real dates in his original arrray. > > >> in the second example, yoy have a different problem, since the array does >> NOT in fact contain the same kinds of values in the two dimensions. So the >> approach that you have take will NEVER work properly, since you want DTAES >> in the first dimension, and Numbers in the second...but an array is BY DEFINITION, >> made up of the SAME KIND of values in ALL of its dimensions. > >That's not true for arrays defined as Variants. Each element of a Variant array can >be >different. Give this code a try > > Dim X As Integer > Dim Val(1 To 4) As Variant > Val(1) = "ABC" ' String > Val(2) = 12345 ' Integer > Val(3) = 67.89 ' Double > Val(4) = CDate("1/23/2001") ' Date > For X = 1 To 4 > Debug.Print TypeName(Val(X)) > Next > > >Rick > Re: Figured it out, but another question Arthur, Your points are well made. But Victoria needs to be aware that dates are not sorted by Month-Day-Year as her example showed. Rather they are sorted by Year-Month-Day. This is automatically done if you use a Date type, however, if you use a string time as in her original example the data would not be sorted correctly. She must either convert the string to a date via the mentioned CDate() or reorder the string so that it is in Year-Month-Day order. Of course, the year must be fully specified as a 4 digit number. | Low | [
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, Del. (WBOC/AP)- The cremated remains of nine victims of a 1978 mass cult suicide-murder in Jonestown, Guyana, have turned up in a former funeral home in Dover, officials said Thursday.It's part of a story WBOC first broke Wednesday evening.The Delaware Division of Forensic Science has taken possession of the remains, discovered at the former Minus Funeral Home on North Queen Street, and is working to make identifications and notify relatives, the agency and the Dover Police Department said in a statement.Last week, the DFS responded to a request to check the former dilapidated funeral home in Dover after 38 containers of cremated remains were discovered inside. Thirty-three containers were marked and identified. They spanned a period from about 1970 to the 1990s and included the Jonestown remains. The DFS said its staff will work to identify the current unidentified remains and will in turn notify family or arrange for final disposition. On Wednesday, the DFS, along with the Dover and New Castle County police departments, also conducted an "exploratory excavation" on the former funeral home property. "They decided they would check the exterior of the building," said Cpl. Mark Hoffman, spokesman for the Dover Police Department. "During that time they noticed three depressions with disturbed soil. At that time the decision was made to and excavate those areas." They discovered an arrowhead, two animal bones, oyster shells and charcoals. William Crawford has lived across the street from the old funeral home for years. He watched Wednesday as the digging was happening. "It's a mystery solved. Everybody was concerned," he said. "There were a lot of different concerns about what had actually taken place." On Nov. 18, 1978, gunmen from the Peoples Temple cult ambushed and killed U.S. Rep. Leo Ryan of California, three newsmen and a defector from the group at a remote jungle airstrip as they visited on a fact-finding mission to investigate reports of abuses of members.Cult leader Jim Jones then orchestrated a ritual of mass murder and suicide at the temple's nearby agricultural commune, ordering followers to drink cyanide-laced grape punch. Most of them complied, although survivors described some people being shot, injected with poison, or forced to drink the deadly beverage when they tried to resist.After the deaths, bodies of 911 massacre victims were brought to Dover Air Force Base, home to the U.S. military's largest mortuary. Many of the bodies were decomposed and could not be identified. Several cemeteries refused to take them until the Evergreen Cemetery in Oakland, California, stepped forward in 1979 and accepted 409 bodies. The remaining victims were cremated or buried in family cemeteries.WBOC spoke with officials at Air Force Mortuary Affairs Operations. They say they are looking into the situation. But finding information about something that happened so long ago is difficult.Crawford was living in Dover in 1978. He remembers the time right after Jonestown. "It was a sad occasion," said Crawford. "It was a lot of hustle and bustle, a lot of excitement, a lot of electricity in the air at the time and a lot of sadness, too, because so many souls were lost." Police do not suspect foul play. DFS calls this a simple case of unclaimed remains. Searchers also found several bronze grave site markers for deceased veterans who served in World War I through the Vietnam War during an initial check of the building. Officials said if family members can be located through the Veterans Administration, the markers will be given to them.Jones ran the Peoples Temple in San Francisco in the early 1970s. He established a free health clinic and a drug rehabilitation program, eventually emerging as a political force. He became chairman of the San Francisco Housing Authority in 1976. But allegations of wrongdoing mounted, and Jones moved the settlement to Guyana, the only English-speaking country in South America. The cult leader believed he would be safe there from what he perceived as media and police persecution. Hundreds of followers moved to Jonestown, seeking socialism and racial harmony. | Mid | [
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Disperse the Structure XL in water and stir until complete homogenity. Adjust pH to 3.5-4.0 with citric acid, diluted. Add the rest of ingredients in the listed order while stirring. (Irwinol must be added previously melted. | Mid | [
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Failure in diagnosis and under-treatment of osteoporosis in elderly patients with fragility fractures. We evaluated whether osteoporosis is adequately managed and treated in patients suffering from fragility fractures. Factors that influenced osteoporosis diagnosis and treatment rates were also assessed. To this end, patients with the principal diagnosis of low-energy hip, vertebral, or distal radius fractures were recruited for the study. Collected data included risk factors for osteoporosis, history of previous fractures, known history of osteoporosis, and osteoporosis treatment at the time of admission. The patients' prefracture risk profile was also assessed to determine whether osteoporosis could have been identified prior to the index fracture. We identified 308 patients with fragility fractures, including 214 hip, 41 vertebral, and 53 distal radius fractures. Overall, 238 patients (77.3%) had at least one risk factor for osteoporosis. Eighty-eight patients (28.6%) had sustained ≥ 1 prior fragility fractures in the past. However, only 79 patients (25.6%) were aware that they had osteoporosis and even fewer (66 patients, 21.4%) had been receiving osteoporosis treatment preceding the current admission. Anti-osteoporotic agents were more commonly prescribed in patients 66-75 years old (p = 0.008), with a family history of osteoporosis (p = 0.009) or history of a prior fragility fracture (p = 0.012). The treatment rate was higher in women than men (p = 0.026) and in patients with vertebral or multiple prior fractures compared to patients with prior hip fractures. The current study provides evidence that individuals who experience fragility fractures are not adequately managed for osteoporosis. Only few of the historically known risk factors for osteoporosis were adequately recognized and associated with osteoporosis evaluation and treatment. | High | [
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1. Introduction =============== The evolutionary relationship between a set of *k* homologous sequences of *N* nucleotides can be represented by a *k*-leaved bifurcating tree where each leaf node represents a known sequence and each internal node represents an ancestral sequence (which is almost always unknown). The phylogeny of the *k* sequences can be inferred by using maximum-likelihood methods, which rely on models of nucleotide substitution to infer the most likely tree. Popular phylogenetic methods, like those implemented in PHYLIP ([@b10-ebo-01-62]), PAUP\* ([@b41-ebo-01-62]), and Tree-Puzzle ([@b33-ebo-01-62]), use models of nucleotide substitution that assume the evolutionary process is stationary, homogeneous, and reversible. Although a detailed mathematical description of stationarity, homogeneity and reversibility can be found in [@b1-ebo-01-62], we will give a brief description of these terms in the context of molecular phylogenetics. Stationarity implies that the marginal probabilities of the four nucleotides remain constant over all the nodes of a given tree. Homogeneity implies that the instantaneous rate matrix (described in eg, [@b24-ebo-01-62], [@b23-ebo-01-62]) is constant over an edge (local homogeneity) or constant over the entire tree (global homogeneity). Reversibility implies that the probability of sampling nucleotide *i* from the stationary distribution and going to nucleotide *j* is the same as the probability of sampling nucleotide *j* from the stationary distribution and going to nucleotide *i*, where *i*, *j* = {*A*,*C*,*G*,*T*} ([@b6-ebo-01-62]). Reversibility, therefore, implies that the process is stationary and permits us to ignore the direction of evolution. The assumptions of stationarity, homogeneity and reversibility are often violated by the data, resulting in an elevated probability of incorrect phylogenetic results (for examples of the complexity of the problem, see [@b18-ebo-01-62]; [@b21-ebo-01-62]). In a landmark article, [@b3-ebo-01-62] considered a general Markov model for unrooted trees, the assumptions being that the process relating each pair of nodes in the tree is Markovian and the sites are independent and identically distributed. Their model does not make the assumption of stationarity, homogeneity (local or global) or reversibility, so it is more general than the non-stationary but locally homogeneous models considered by [@b45-ebo-01-62] and [@b46-ebo-01-62]. [@b3-ebo-01-62] considered a *k*-taxa tree with 2*k*−3 *Q*-matrices, one for each edge of the tree. Each *Q*-matrix represents the joint probability distribution of nucleotides at the two ends of the associated edge and is a 4 × 4 matrix. Since the sequences at internal nodes are not known, we can only observe the 4*^k^* different combinations of nucleotides at the leaf nodes. These combinations together represent the joint probability distribution of the nucleotides at leaf nodes and can be written as a function of the *Q*-matrices. Thus, the likelihood of the observed sequences is a function of the set of *Q*-matrices and can be maximised by determining the maximum-likelihood estimates of the *Q*-matrices. The algorithm for obtaining the maximum-likelihood estimates was suggested by [@b3-ebo-01-62] but has not received the attention that other aspects of their paper have, especially calculation of LogDet distance ([@b26-ebo-01-62]; [@b39-ebo-01-62]), probably because the large number of parameters was assumed to make the interpretation difficult. We revisit [@b3-ebo-01-62] model, and describe it and the estimation algorithm in new notation --- we also present a program written in Java^™^ to implement it. We examine the information that can be obtained from the estimates by applying their algorithm, henceforth referred to as the BH algorithm, to two sets of data, one comprising mitochondrial DNA from seven hominoids, where there is apparent stationarity and homogeneity, and another comprising 16S ribosomal RNA genes from five bacterial genomes, where problems due to lack of stationarity and homogeneity have been noted previously by [@b13-ebo-01-62] as well as [@b12-ebo-01-62]. Further, we compare the results obtained from our program with those obtained using simpler models, ie, the F84 model ([@b23-ebo-01-62]), implemented in DNAML from the PHYLIP program package ([@b10-ebo-01-62]), and the general time reversible (GTR) model ([@b24-ebo-01-62]), implemented in PAUP\* ([@b41-ebo-01-62]). A likelihood ratio test ([@b20-ebo-01-62]), based on the log likelihood values obtained using the phylogenetic programs, is used to determine whether one or more of the assumptions of stationarity, homogeneity, and reversibility are violated. The joint probability distribution values for each edge of the tree can be used to determine (*a*) marginal probabilities at the nodes (internal nodes as well as leaf nodes), and (*b*) the joint probability distribution of a pair of leaf nodes. The assumption of stationarity can be examined by comparing the marginal probabilities at different leaf nodes ([@b2-ebo-01-62]). Since [@b3-ebo-01-62] method gives estimates of the joint distribution of the two end points of each edge, we can evaluate the hypothesis of reversibility by examining the joint distribution --- it should be symmetric if the process is reversible. We do so for the two sets of data mentioned earlier, obtaining the surprising result that the stationary and homogeneous model for the hominoid data appears to be not reversible along some of the edges. Such comparisons seem to be possible for only a part of the tree for the bacterial data since this data set is not stationary. 2. A General Markov Model on Trees ================================== The general Markov model for phylogenetic trees proposed by [@b3-ebo-01-62] will be given using a notation that permits a more compact description. Consider an unrooted binary tree, *T*, (for definitions, see Chapter 1 of [@b34-ebo-01-62])) with *l* leaves, *l --* 2 internal nodes (or vertices), and 2*l* − 3 edges, for *l* ≥ 0. For convenience, we include *l* = 1 with 0 internal nodes and 0 edges. Denote leaves by *L* = {−1, ..., −*l*} and internal nodes by *I* = {1, ..., l − 2} (the notation of positives and negatives derives from the merge matrix given by the hierarchical clustering algorithm, *hclust*, in the S-PLUS or R packages). The set of all vertices is *V* = *L* ∪ *I*. Denote edges by *E* = {(*i*, *j*): *i*,*j*∈*V* and adjacent}. By inserting a node numbered 0, called a root node, on any edge, and thus increasing the number of nodes and the number of edges by one, the unrooted tree can be converted into a rooted binary tree. If an edge (*i*, *j*) of the unrooted tree is deleted then two rooted sub-trees *T*~(~*~i~*~,~*~j~*~)~ and *T*~(~*~j~*~,~*~i~*~)~ are formed with roots at *i* and *j*, respectively. The tree will be used to describe a model for evolutionary relationships at a site in the DNA, as in [@b3-ebo-01-62], by considering the joint distribution of the four bases *B* = {*A*,*C*,*G*,*T*} at the leaves. First consider the joint distribution at ends of any edge. Let *X~i~* and *X~j~* be the values taken by bases at nodes *i* and *j* of the edge (*i*, *j*). Write Q ( i , j ) ( x , y ) = P ( X i = x , X j = y ) for *x, y* ∈ *B*, as the joint probability. Note that, since consistency of marginal distributions at internal nodes is required, for *i* ∈ *I*, P ( X i = x ) = Q i ( x ) = ∑ y ∈ B Q ( i , j ) ( x , y ) for any *j* such that (*i*, *j*) is an edge. More generally, let **X** = (**X***~L~*, **X***~I~*) denote the vector of random variables with **X***~L~* = (*X*~−1~, ..., X~−l~) and **X***~I~* = (*X*~1~,...,*X~l~*~−2~), and with each *Xi* taking values in *B.* Let *Q~T~* (**x**) = *P*(**X** = **x**) be the joint distribution of the bases at the nodes of *T*. The joint distribution of the bases at the leaves is then Q L ( x L ) = ∑ x i : i ∈ I Q T ( x ) . Further, if *L*~(~*~i~*~,~ *~j~*~)~ = *L* ∩ *T*~(~*~i~*~,~ *~j~*~)~ and *I*~(~*~i~*~,~ *~j~*~)~ = *I* ∩ *T*~(~*~i~*~,~ *~j~*~)~ denote the sets of leaf nodes and internal nodes, respectively, in *T*~(~*~i~*~,~ *~j~*~)~, then **X**~(~*~i~*~,~ *~j~*~)~ and **X**~T(~*~i~*~,~ *~j~*~)~ denote the vectors of the values of bases in *L*~(~*~i~*~,~ *~j~*~)~ and *T*~(~*~i~*~,~ *~j~*~)~, respectively, and Q L ( i , j ) ( x L ( i , j ) ) = ∑ x k : k ∈ I ( i , j ) Q T ( i , j ) ( x T ( i , j ) ) Take the model to be Markovian, so that, given (*X~i~*, *X~j~*) = (*x~i~*, *x~j~*), the conditional distribution of the bases on the leaves of the rooted sub-trees *T*~(~*~i~*~,~ *~j~*~)~ and *T*~(~*~j~*~,~ *~i~*~)~, given by deleting edge (*i*, *j*), are independent. Under this Markovian model the joint distribution *Q~L~*(**x***~L~*) can be written as a product of terms involving only *Q*~(~*~i~*~,~ *~j~*~)~(*x~i~*, *x~j~*) and *Q~i~*(*x~i~*) for all edges (*i*, *j*) and all nodes *i*. At each site α = 1, ..., *N* the value of a base at the *i*-th leaf, *x~iα~* is known, but at internal nodes the base can take any value in *B*. Let *B~iα~* = {*x~iα~*} if *i* ∈ *L*, and *B* if *i* ∈ *I*. Then the joint probability distribution of leaf nodes at site α can be expressed as Q L , α ( x L ) = ∑ x i ∈ B ∑ x j ∈ B I ( x i ∈ B i α , x j ∈ B j α ) Q ( i , j ) ( x i , x j ) P ( L ( i , j ) \| x i ) P ( L ( j , i ) \| x j ) . where *I*(*x~i~* ∈ *B~iα~, x~j~* ∈ *B~jα~*) is an indicator function that takes the value 1 if both *x~i~* and *x~j~* represent leaf nodes, and 0 otherwise. Also, P ( L ( i , j ) \| x i ) = Q L ( i , j ) ∪ { x i } ( x L ( i , j ) , x i ) Q i ( x i ) This formula can be applied recursively to the joint distribution on a smaller tree, Q L ( i , j ) ( x L ( i , j ) ) until trees with only one edge are reached. Notice that it is not necessary in this general case to put any restrictions on the model producing the joint distributions on each edge, other than consistency at internal nodes noted earlier. 3. Estimation ============= For an unrooted binary tree, *T*, based on *k* homologous sequences, each having *N* sites, [@b3-ebo-01-62] gave a method of estimating the set of *Q*~(~*~i~*~,~ *~j~*~)~(*x*, *y*) for *x*, *y* ∈ *B*, (*i*, *j*) ∈ *E* by maximizing the log likelihood of the bases at the leaves. Using (4), the log likelihood for an unrooted tree is L = ∑ α = 1 N log Q L , α ( X L ) = ∑ α = 1 N log ∑ x ∈ B ∑ y ∈ B I ( x ∈ B i α , y ∈ B j α ) Q ( i , j ) ( x , y ) P ( L ( i , j ) \| x ) P ( L ( j , i ) \| y ) Now, maximizing *L* with respect to *Q*~(~*~i~*~,~ *~j~*~)~(*x*, *y*) subject to ∑ x , y ∈ B Q ( i , j ) ( x , y ) = 1 requires equating the derivatives of *L* + λ (∑*~x~*~,~ *~y~*~∈~ *~B~* *Q*~(~*~i~*~,~ *~j~*~)~(*x*, *y*) − 1) with respect to *Q*~(~*~i~*~,~ *~j~*~)~(*x*, *y*) and λ to zero, which leads to the updating equation Q ( i , j ) ( x , y ) = 1 N ∑ α = 1 N I ( x ∈ B i α , y ∈ B j α ) Q ( i , j ) ( x , y ) P ( L ( i , j ) \| x ) P ( L ( j , i ) \| y ) Q L ( x L ) . In order to minimize computational time, suitable initial values are chosen for all *Q*~(~*~i~*~,~*~j~*~)~(*x*, *y*). Then (6) is used repeatedly on all edges to update the left hand side using current values for the right hand side until the process converges. Call the values obtained Q \^ ( i , j ) ( x , y ) . 3.1. Precise Fit At Leaf Nodes ------------------------------ If *i* ∈ *L*, then summing in (6) over *y* ∈ *B* gives Q \^ i ( x ) = N i ( x ) N where *N~i~*(*x*) denotes the number of sites at leaf *i* that have base *x*. Thus the maximization leads to a precise fit at the leaves. 3.2. Internal Consistency ------------------------- If *i* ∈ *I* and edges (*i*, *j*) and (*i*, *k*) are in *E*, then, if the sum over *y* in *Q̂* ~(~*~i,\ j~*~)~ (*x, y*), and over *z* in *Q̂* ~(~*~i,k,~*~)~ (*x*,*z*), are equal, these estimates of the marginal probabilities at internal nodes are consistent. Now from (6) we get ∑ y ∈ B Q \^ ( i , j ) ( x , y ) = 1 N ∑ α = 1 N Σ y ∈ B I ( x ∈ B i α , y ∈ B j α ) Q \^ ( i , j ) ( x , y ) P ( L ( i , j ) \| x ) P ( L ( j , i ) \| y ) Q \^ L ( x L ) = 1 N ∑ α = 1 N Q \^ L ∪ { i } ( x L α , x ) Q \^ L ( x L α ) where **x***~Lα~* is the vector of values of bases of leaves at the αth site. The same formula is obtained by summing over *z* in Q \^ ( i , k ) ( x , z ) showing that the estimates are internally consistent. 4. Algorithm Implementation =========================== The BH algorithm was implemented in Java (Java*^™^* 2 Platform Standard Edition, Version 1.4.2_03) using an object-oriented approach. The main classes in the program are NewickTreeTraversal, BranchDetails and MaximumAverageLikelihood. The class NewickTreeTraversal reads the unrooted tree in Newick format ([@b11-ebo-01-62]) and constructs a binary tree. Each node is linked to a maximum of three nodes ie one parent node and two descendant nodes. The class BranchDetails stores the joint probability distribution values along each edge of the binary tree. The class MaximumAverage Likelihood makes use of the above-mentioned classes to compute the log likelihood values and update joint probability distribution values (using formulae described in Section 3) for a user-specified tree. It also generates an output file containing the final joint probability distribution values along each edge and the log likelihood value for the entire tree. The joint probability distribution values can be used to compute divergence matrices --- a helper program has been written in Java*^™^* for this purpose. We make use of recursion to compute the joint conditional probability distribution of all the leaf nodes connected to the sub-tree rooted at node *i*, ie *P*(*L*~(~*~i~*~,~ *~j~*~)~*\|x*). The method starts by calculating the joint probability of node *i* and its immediate descendant nodes. If node *i* is an internal node, *x* ∈ *B* and the joint probability distribution is the sum of joint probability values obtained for different nucleotide values at node *i*. If a descendant node is an internal node, we consider the sub-tree rooted at the descendant node and compute *P*(*L*~(~*~i~*~,~*~j~*~)~*\|x*). This process is repeated until the leaf nodes are reached. The initial joint probability distribution values (ie, the *Q*-values) along the edges of the binary tree are provided by the user. At the end of each iteration, we compare the *Q*-values before and after updation. If the sum of the square of differences is greater than the user-specified value, the *Q*-values are updated and the next iteration begins. If none of the edges need to be updated, it implies that convergence has been achieved, and the program terminates. To improve the program's performance, henceforth referred to as the BH program, for a given data set of matched nucleotide sequences, all unique patterns are identified at the beginning of the program. The log likelihood value is computed only once for each unique pattern and the result is multiplied by the number of times a particular pattern occurs --- this is a commonly used procedure to reduce the time needed to estimate the likelihood of a tree. The software will be available for download from <http://www.usyd.edu.au/SUBIT/>. 4.1. Computation of Edge Length ------------------------------- If the nucleotide sites are independent and identically distributed and the underlying model of evolution is stationary, homogeneous and reversible, we can compute edge lengths ([@b24-ebo-01-62]; [@b42-ebo-01-62]; [@b30-ebo-01-62]) using the formula δ i j = \- t ∑ h = 1 4 π h r h h where δ*~ij~* denotes the distance between sequences at nodes *i* and *j* in terms of expected number of substitutions per site, *t* denotes time, π*~h~* denotes the *h-*th element of the diagonal matrix of stationary probabilities, and *r~hh~* denotes the *h-*th diagonal element of the rate matrix. A method for determining asynchronous distances was proposed by [@b4-ebo-01-62]. Although their method can be applied to the general model, if the marginal probabilities at the two ends of an edge are different, the distances are asymmetric (ie, for an edge (*i*, *j*), the distance from *i* to *j* and from *j* to *i* are different). In our paper, we have averaged the distances over the two possible directions of traversal for the purpose of edge length comparison with DNAML. Since the BH algorithm is based on joint probability distributions along the edges and does not require branch length optimization, the averaging of branch lengths does not affect the maximum-likelihood computation. 4.2. Variation in log likelihood values --------------------------------------- For a given data set of homologous nucleotide sequences, the log likelihood value at convergence depends on the initial set of *Q*-values. This was observed in both five-taxa and seven-taxa trees irrespective of the tree selected. This indicates the presence of multiple local maxima on the likelihood surface even for the most likely tree. This is an important result because former studies of the problem of multiple maxima on the log likelihood surface have assumed stationary, homogeneous, and reversible models of evolution. [@b7-ebo-01-62] showed that even for simple models of evolution, multiple maxima are possible while [@b31-ebo-01-62] used simulation to show that the best tree is unlikely to have multiple maxima. For the two data sets analysed below, convergence to a local maximum, different from the global maximum, was observed only if the *Q*-values chosen were extreme; for example, a *Q*-matrix with all the joint probabilities being equal or a *Q*-matrix with diagonal elements much smaller than off-diagonal elements. From the *Q*-matrices that converged to the global maximum, we randomly selected one with a value of 1/8 along the main diagonal and 1/24 elsewhere for the computation of log likelihood values mentioned in section 5. 5. Application to two sets of homologous sequences ================================================== Under the Markovian model of DNA evolution, the process of evolution may or may not be stationary and homogeneous. We consider both cases and argue that the general model of DNA evolution proposed by [@b3-ebo-01-62] is useful in both cases. For each data set, we (*i*) used three matched-pairs tests of homogeneity ([@b5-ebo-01-62]; [@b40-ebo-01-62]; [@b2-ebo-01-62]) to determine whether the sequences could be assumed to have evolved under stationary and homogeneous conditions (a prerequisite for using most phylogenetics methods); (*ii*) determined the degrees of freedom needed in order to compare phylogenetic results using likelihood-ratio tests; (*iii*) estimated and compared the trees; and (*iv*) conducted a comparison of edge lengths, divergence matrices and substitutional biases. We show that [@b3-ebo-01-62] method provides a useful reference point for choosing appropriate models of substitution, and the means for assessing whether the evolutionary process is reversible; such a method appears to be unavailable in the current literature. 5.1 Hominoid Data ----------------- We considered an alignment of 1809 nucleotides from the mitochondrially-encoded NADH dehydrogenase subunit 5 genes of (with abbreviated name and Genbank Accession numbers given in parentheses): Human (Hsap, NC_001807), Chimpanzee (Ptro, NC_001643), Bonobo (Ppan, NC_001644), Gorilla (Ggor, NC_001645), Orangutan (Ppyg, NC_001646), Gibbon (Hlar, NC_002082), and Macaque (Msyl, NC_002764). The three codon sites were separated into different alignments using a program called CODONSPLIT (by IB Jakobsen) before being analysed. ### 5.1.1. Assessment of phylogenetic assumptions The alignments of first, second, and third codon sites were examined independently using the matched-pairs tests of symmetry ([@b5-ebo-01-62]), marginal symmetry ([@b40-ebo-01-62]), and internal symmetry ([@b2-ebo-01-62]). Given that each of these tests involve multiple comparisons of related sequences, it was necessary to interpret the *p*-values with caution. The matched-pairs tests of homogeneity produced *p*-values in the range of 1.000 to 0.024 for the first and second codon sites ([Tables 1](#t1-ebo-01-62){ref-type="table"} and [2](#t2-ebo-01-62){ref-type="table"}), and in the range of 0.996 to 0.006 for the third codon sites ([Table 3](#t3-ebo-01-62){ref-type="table"}). For the 21 pairwise comparisons, only 1 *p*-value was observed to be lower than 0.05 for the first and second codon sites whereas approximately one-fourth of the *p*-values for the third codon site were found to be lower than 0.05. These results are consistent with evolution under stationary and homogeneous conditions for first and second codon sites but not for third codon sites. Interestingly, all the low *p*-values observed for third codon sites involved comparisons with Orangutan, indicating real differences. Given that the alignment of third codon sites provides some evidence against the evolutionary process being stationary and homogeneous, the following phylogenetic analyses were done using an alignment of first and second codon sites only. Assuming stationarity, homogeneity, and reversibility, the GTR model, considered over the entire tree, would be appropriate for inferring the most likely tree. If we constrain the assumptions further by assuming that the six rate parameters in the GTR model can be reduced to two rate parameters (ie transitions and transversions), then the F84 ([@b23-ebo-01-62]) model would be sufficient to predict the most likely tree. We determined the most likely tree by using DNAML from the PHYLIP program package ([@b10-ebo-01-62]), PAUP\* ([@b41-ebo-01-62]), and the BH program. ### 5.1.2. Calculating the degrees of freedom In order to compare the fit of the alignment to trees inferred using DNAML ([@b10-ebo-01-62]), PAUP\* ([@b41-ebo-01-62]), and the BH program, the degrees of freedom are needed for each estimate. Both DNAML and PAUP\* consider a stationary, homogeneous, and reversible process, so a single rate matrix applies to the entire tree, and the degrees of freedom is the sum of the number of edges and the number of parameters in the rate matrix. The F84 model has five parameters in the rate matrix and the GTR model has nine parameters in the rate matrix. However, in order to obtain the edge lengths in terms of the expected number of substitutions per site, the expected rate of substitution is set to 1 ([@b46-ebo-01-62]), so the number of free parameters in the F84 and GTR models is reduced by one. Accordingly, for a seven taxa tree, the degrees of freedom is 15 for results obtained using the F84 model and 19 for results obtained using the GTR model; the difference in the degrees of freedom for these two models is four. The model proposed by [@b3-ebo-01-62], which does not assume stationarity, homogeneity or reversibility, has nine degrees of freedom along each edge and three degrees of freedom at each node. Thus, the degrees of freedom for a seven taxa tree inferred using the BH algorithm is 135, and the difference in the degrees of freedom is 116 and 120, respectively, for the GTR and F84 models (in relation to trees inferred using the BH algorithm). ### 5.1.3. Inferring and comparing the trees The most likely tree obtained using DNAML and PAUP\* is shown in [Figure 1](#f1-ebo-01-62){ref-type="fig"}. As the difference in log likelihood (ln*L*) obtained using these two programs is 9.2 (−3635.445 for PAUP\* and −3644.645 for DNAML), 2 × ln*L* = 18.4. Under the hypothesis that the GTR model can be reduced to the F84 model for these data, we might expect the difference to be distributed approximately as a chi-squared variate with four degrees of freedom. Thus, for the hominoid data set, there is evidence that the F84 model is not sufficient to explain the evolutionary process. To determine the most likely tree inferred by the BH program, we performed an exhaustive search of tree-space. The Newick representation of all the 945 possible unrooted binary trees was generated using the TreeGen program ([@b44-ebo-01-62]). The BH program used these trees as input to generate the log likelihood value for each tree. In all cases, the *Q*-matrices showed internal consistency and a precise fit at the leaf nodes. The three most likely trees and their log likelihood values are shown in [Table 4](#t4-ebo-01-62){ref-type="table"}. The most likely tree inferred by using the BH algorithm is the same as those inferred by DNAML and PAUP\*. Interestingly, the second most likely tree in [Table 4](#t4-ebo-01-62){ref-type="table"} is the one that is commonly thought to represent the hominoid evolution (see eg [@b28-ebo-01-62]) whereas the third most likely tree in [Table 4](#t4-ebo-01-62){ref-type="table"} is the one inferred by [@b19-ebo-01-62]. We compared the trees in [Table 4](#t4-ebo-01-62){ref-type="table"} using the SH-test by [@b36-ebo-01-62] and the approximately unbiased (AU) test by [@b35-ebo-01-62], which are implemented in CONSEL ([@b37-ebo-01-62]). The results in [Table 5](#t5-ebo-01-62){ref-type="table"} show that the two most likely trees are statistically indistinguishable, possibly due to the sequences being too short (1206 bp) to rule out stochastic error, which can interact with systematic errors and prevent identification of the correct tree. For the most likely tree presented in [Table 4](#t4-ebo-01-62){ref-type="table"}, the log likelihood values returned by PAUP\* and BH are −3635.445 and −3540.684, respectively, so 2 × ln*L* = 189.5226, which is large compared to a chi-squared distribution with 116 degrees of freedom. Since the large difference in log likelihood cannot be explained by the difference in the degrees of freedom of the two models, the likelihood ratio test suggests that one or more of the three assumptions of stationarity, homogeneity and reversibility are violated by the hominoid data set. Given the results from the matched-pairs tests of symmetry, marginal symmetry and internal symmetry, there is reason to suspect that the assumption of reversibility is violated. Given that there may be doubt about the accuracy of the asymptotic approximation in cases like this, we verified the results by using parametric bootstrapping. The parameters values for the GTR model were estimated on the most likely tree using the HyPhy program ([@b22-ebo-01-62]). One thousand alignments of 1206 nucleotides were generated on the parameter values and the most likely tree using the Seq-Gen program ([@b29-ebo-01-62]). For each alignment, we estimated the log likelihood of the data, given the tree and the GTR model or given the tree and the BH model. The values for 2 × ln*L* ranged from 68.29 to 152.60 with a mean of 109.90 and a median of 109.60. Approximately 71% of the values lay between 116 ± 15.23, where the latter value corresponds to the standard deviation of a χ^2^~116~. This shows that the large difference in log likelihood values returned by PAUP\* and BH program for the hominoid data set is significant. ### 5.1.4. Tree-dependent comparison of edge lengths The joint probability distribution values returned by BH were used to obtain edge lengths by averaging over the two possible directions of traversal. If the process is stationary, homogeneous, and reversible, the values obtained over the two directions of traversal would be the same. However, the alignment of first and second codon sites of the hominoid data is not consistent with evolution under stationary, homogeneous and reversible conditions, so the averaged edge lengths will only provide a rough estimate of the expected number of substitutions along each edge. Nonetheless, the edge lengths obtained using DNAML and BH are similar ([Table 6](#t6-ebo-01-62){ref-type="table"}). ### 5.1.5. Evaluation of Divergence Matrices and Substitution Biases Given two neighbouring edges (*i*, *j*) and (*k*, *j*), the joint probability distribution for the pair (*i*, *k*) can be estinated as ∑ x j = 1 4 Q ( i , j ) ( x i , x j ) Q ( j , k ) ( x j , x k ) Q j ( x j ) A generalisation of this formula, obtained by summing over all internal nodes in the path from node *l* to node *m*, and multiplying by *N* gives the estimated divergence matrix for any pair (*l*, *m*). For the hominoid data set, the divergence matrices computed using the estimated joint probability distribution values along each edge of the tree are close to the observed divergence matrices. In [Table 7](#t7-ebo-01-62){ref-type="table"} we give the estimated and observed divergence matrix values for the Macaque-Bonobo pair. The values indicate that the general model of DNA evolution approximates the actual process of evolution quite well. This is typical of the fit of divergence matrices for all pairs of leaf nodes. To compare the differences between observed and estimated divergence matrices within a statistical context, we calculated a chi-squared test statistic using the formula X 2 = ∑ i = 1 4 ∑ j = 1 4 ( O i j \- E i j ) 2 E i j where *O* denotes the observed divergence matrix, and *E* denotes the estimated divergence matrix. This goodness-of-fit index has values in the range 0.07 (Chimpanzee-Bonobo pair) to 8.19 (Human-Macaque pair). Since the marginal probabilities for each pair of leaf nodes are known, the degrees of freedom for the above-mentioned test statistic cannot exceed nine. We would obtain exactly nine degrees of freedom if *E* was known precisely apart from the marginal probabilities. The divergence matrices computed in section 5.1.1 were found to be symmetric for all comparisons between the leaf nodes ([Tables 1](#t1-ebo-01-62){ref-type="table"} and [2](#t2-ebo-01-62){ref-type="table"}). However, when we looked at the estimated joint probability distributions for individual edges, we observed a distinct lack of symmetry. We used the [@b5-ebo-01-62] and [@b40-ebo-01-62] test statistics using *NQ*(*x*, *y*), for *x*, *y* = 1, ..., 4, as pseudo-observations. The resulting pseudo-*p*-values are provided in [Table 8](#t8-ebo-01-62){ref-type="table"}. Although these values are based on *Q*-matrices estimated by the BH program and therefore are not the true *p*-values, they are useful indices for measuring symmetry and provide a clear indication of lack of symmetry for internal node to leaf node edges. An examination of the corresponding estimated joint probabilities shows a bias for *A* → *G* and *C* → *T* substitutions over *G* → *A* and *T* → *C* substitutions for ancestral to leaf node transitions ([Table 9](#t9-ebo-01-62){ref-type="table"}). Since a reversible Markov process would result in a symmetric joint distribution of the end points of an edge, there is evidence that the process in fact is not reversible. This observation is consistent with the earlier research on mammalian genes. [@b43-ebo-01-62] found a directional bias in nucleotide substitutions in the human mitochondrial genome whereas [@b8-ebo-01-62], using a stationary and infinite-sites model, found that a base composition bias in mammals cannot be explained by the mutation bias hypothesis. Subsequently, assuming a stationary model, [@b38-ebo-01-62] found that the synonymous codon bias in humans cannot be explained by the mutation bias hypothesis whereas [@b14-ebo-01-62] have argued that the evolution of GC-content in mammals is explained by a biased gene conversion hypothesis. 5.2 Bacterial Data ------------------ We analysed a second data set comprising an alignment of 1238 nucleotides from the 16S ribosomal RNA genes of (with abbreviated names given in parentheses): *Aquifex pyrophilus* (Apyr), *Thermotoga maritima* (Tmar), *Thermus thermophilus* (Tthe), *Deinococcus radiodurans* (Drad), and *Bacillus subtilis* (Bsub). This alignment is similar to that analyzed by [@b13-ebo-01-62] and by [@b12-ebo-01-62]. ### 5.2.1. Assessment of phylogenetic assumptions The matched-pairs tests of symmetry ([@b5-ebo-01-62]), marginal symmetry ([@b40-ebo-01-62]) and internal symmetry ([@b2-ebo-01-62]) show that the sequences are highly unlikely to have evolved under stationary and homogeneous conditions ([Table 10](#t10-ebo-01-62){ref-type="table"}). We analyzed this data set, in a similar manner to the hominoid data set, by (*i*) considering the maximum-likelihood results obtained using different models of DNA evolution; (*ii*) comparing the trees using the goodness-of-fit measure described in section 5.1.5; and (*iii*) comparing the trees based on tests of symmetry along individual edges. However, we did not perform the likelihood ratio test as the difference in log likelihood values obtained using the BH program and PAUP\* is extremely large and could not have arisen by chance. ### 5.2.2. Inferring the trees Using the BH program, log likelihood values were found to fall in the range from −4387.239 to −4289.511. The most likely tree obtained is shown in [Figure 2](#f2-ebo-01-62){ref-type="fig"} and henceforth referred to as tree \#1. Like the other data set, the marginal probabilities at the internal nodes are consistent and the marginal probabilities at the leaf nodes fit the observed data precisely. The most likely tree inferred using DNAML and PAUP\* is shown in [Figure 3](#f3-ebo-01-62){ref-type="fig"} and henceforth referred to as tree \#2. Even the BH program returned this particular tree as the second most likely with a log likelihood value of −4296.22. By contrast, the log likelihood value returned by PAUP\* for the same tree is −4401.41722. The large difference in log likelihood values returned by BH and PAUP\* is expected because the evolutionary process is highly unlikely to have been stationary and homogeneous ([Table 10](#t10-ebo-01-62){ref-type="table"}) and, hence, cannot be approximated by the GTR model of DNA evolution. For the bacterial data set, [@b12-ebo-01-62] considered rooted trees with locally homogeneous processes acting on them and concluded that two different rate matrices were sufficient to describe the evolutionary process. However, [@b12-ebo-01-62] method requires the frequency parameters to be known in advance and he chose two sets of frequency parameters (and hence two different rate matrices) based on the observation that the marginal probabilites at leaf nodes could be grouped into two different categories. For a large tree, intrepreting the closeness of frequency parameters might prove to be a difficult task. Another possible limitation of [@b12-ebo-01-62] approach is that the change in rate matrices owing to changes in parameters other than the frequency parameters are not considered. For example, the GTR model has five free parameters in addition to the frequency parameters and a change in those five parameters would also change the rate matrix. This limitation exists even for the N1 and N2 models proposed by [@b46-ebo-01-62]. In contrast, the BH model uses the available data to automatically adjust the parameters from edge to edge and can be used to identify the portions of the tree where the rate matrix is homogeneous. ### 5.2.3. Comparison of edge lengths The edge lengths calculated using BH can be used to obtain the distance between a pair of leaf nodes. For example, the distance from *Thermus* to *Thermotoga* for tree \#1 can be obtained by adding the distances along the edges (*Thermus, Node-3*), (*Node-3, Node2*), (*Node-2, Node-4*) and (*Node-4, Thermotoga*). For tree \#1 we found that the distances between *Deino-coccus-Thermus* (0.191) and *Thermus-Thermotoga* (0.194) are quite close ([Table 11a](#t11a-ebo-01-62){ref-type="table"}). Since the edge lengths are only an approximation, it is possible that phylogenetic programs that assume the process to be stationary, homogeneous and reversible would infer a tree favouring *Thermus* closer to the *Thermotoga-Aquifex* pair (tree \#2), an observation supported by the output from DNAML and PAUP\*, and by the fact that the five sequences can be divided into two groups according to their GC content, where the group containing GC-rich sequences comprises *Aquifex, Thermotoga* and *Thermus* and the other group comprises *Bacillus* and *Deinococcus* ([Figure 3](#f3-ebo-01-62){ref-type="fig"}). Although the evolutionary process is not stationary and homogeneous for the bacterial data set, the edge lengths obtained using BH for tree \#1 and tree \#2 are within the confidence interval specified by DNAML ([Table 11](#t11a-ebo-01-62){ref-type="table"}). The closeness of the edge lengths returned by these two programs for this data set shows that averaging of edge lengths might be considered an adequate approximation. ### 5.2.4. Evaluation of Divergence Matrices and Substitution Biases The closeness of estimated and observed divergence matrices can be measured using the goodness-of-fit index described in section 5.1.5. For tree \#1, the estimated and observed divergence matrices are quite close to one another except for the pair *Bacillus-Deinococcus* ([Table 12](#t12-ebo-01-62){ref-type="table"}). In contrast, the divergence matrices for tree \#2 has a low goodness-of-fit index value for the *Bacillus-Deinococcus* pair but high indices for the *Bacillus-Thermotoga* and the *Bacillus-Aquifex pairs* ([Table 13](#t13-ebo-01-62){ref-type="table"}). Since significant differences exist between observed and estimated divergence matrices for both tree topologies, the evidence is insufficient to favour one particular tree over the other. Since the marginal probabilities at the leaf nodes *Thermus*, *Thermotoga* and *Aquifex* and the internal nodes are quite close ([Table 14a, Table 14b and Table 14c](#t14-ebo-01-62){ref-type="table"}), and the marginal probabilities of *Bacillus* and *Deinococcus* ([Table 14a](#t14-ebo-01-62){ref-type="table"}) are close to one another, but different from those of the other taxa, tree \#2 is the simplest model agreeing with the tests of symmetry. However, the BH program returned a slightly higher log likelihood value of −4289.511 for tree \#1 compared to a value of −4296.22 for tree \#2 and some authors (see eg [@b15-ebo-01-62]) have favoured the close relationship of *Thermus* and *Deinococcus* (as in tree \#1). We performed tests of symmetry along each edge for tree \#1 and tree \#2 using *NQ*(*x*,*y*), for *x*, *y* = 1, ..., 4, as pseudo-observations (refer section 5.1.5) and the resulting pseudo-*p*-values are described in [Table 15](#t15-ebo-01-62){ref-type="table"}. As noted earlier, the evolutionary process is not stationary for the five-taxa tree and [Table 15b](#t15-ebo-01-62){ref-type="table"} suggests a stationary process for the sub-tree containing leaf nodes *Thermus*, *Thermotoga* and *Aquifex*, distinct from the process that gave rise to *Bacillus* and *Deinococcus*. An examination of the estimated joint probabilities for edges in tree \#1 shows that there are large biases in the patterns of substitutions along many of the edges. For example, in the case concerning the terminal edge to *Deinococcus*, there is a strong bias in A → C, A → G, T → C, and T → G substitutions over C → A, G → A, C → T, and G → T substitutions ([Table 16](#t16-ebo-01-62){ref-type="table"}). 6. Performance ============== We ran all programs on a dual processor 1.25 GHz PowerPC G4 with 512 MB of DDR SDRAM and Mac OS X version 10.3.9 as the operating system. For a five-taxa or seven-taxa tree with 1206 nucleotide sites per taxon, our program took approximately one second to compute the likelihood for a single tree. For a 10-taxa tree having 1202 sites per taxon, it took 4 seconds to compute the likelihood for a single tree. To compare the performance of BH program with PAUP\* ([@b41-ebo-01-62]), we considered seven hominoid species (refer Section 5.1) and computed the likelihood of each of the 945 unrooted trees using the two programs. In PAUP\* ([@b41-ebo-01-62]), we selected the GTR model ([@b24-ebo-01-62]) and determined the maximum-likelihood estimates of all the eight free parameters. We found that the BH program took 33% longer than PAUP\* ([@b41-ebo-01-62]) to compute the likelihood of the 945 trees. 7. Conclusion ============= By modifying the GTR model such that it still has the constraints of stationarity and homogeneity but not reversibility, we can obtain the general 12parameter model, where the 12-paramaters correspond to elements in the rate matrix (excluding the stationary probabilities). An even more general model can be obtained by considering the 12-parameter model over each edge of the tree. The only assumption made by such a model is that each edge (*i*, *j*) has a Markovian process defined over it; such a general non-homogeneous model was proposed by [@b3-ebo-01-62]. We have implemented the algorithm by [@b3-ebo-01-62] and used it to analyse two data sets -- a hominoid data set with apparent stationarity and homogeneity, and a bacterial data set with apparent violation of these assumptions. We have also compared the results obtained using two different approaches and found that if the tests of symmetry indicate the evolutionary process to be stationary and homogeneous, then the most likely trees inferred using the F84 model, the GTR model and the general non-homogeneous model are the same. However, the log likelihood values obtained under the GTR model differ significantly from the general non-homogeneous model, providing evidence that the evolutionary process violates some of the assumptions made by the GTR model. Although the assumptions of stationarity and homogeneity can be assessed using tests of symmetry, there is no test available for checking the reversibility condition. However, values of the joint probability distribution returned by the BH program can be examined for reversibility; a symmetric *Q*-matrix for edge (*i*, *j*) corresponds to a reversible process along that edge. For a stationary and homogeneous process, the edge lengths obtained from the general nonhomogeneous model are within the confidence interval specified by the F84 model and, in this respect, there is no obvious gain in using the general non-homogeneous model for the hominoid data set. If the process is not stationary and homogeneous, as in the case of bacterial data set, then the preferred tree obtained using the F84 and GTR models may differ from that obtained using the general nonhomogeneous model. The tests of symmetry using divergence matrices of leaf nodes favour the tree obtained using the F84/GTR model. However, these tests ignore the possibility of varying evolutionary rates along different edges of the tree. Similarly, the F84 and GTR models of nucleotide substitution assume a constant rate of substitution for the entire tree and are less likely to find instances of convergent evolution. In contrast, the general nonhomogeneous model incorporates rate heterogeneity along each edge and, therefore, is more likely to find instances of convergent evolution. Finally, we have shown that the trees obtained using the general non-homogeneous model can be compared using a goodness-of-fit index that measures the closeness of expected and observed divergence matrices. For both the hominoid and bacterial data sets, the estimated joint probability distribution matrices were found to be asymmetric for some of the edges connecting internal nodes to lead nodes. This bias in substitution implies a lack of reversibility, so it may be inappropriate to analyse the sequences using phylogenetic models that assume stationary, homogeneous and reversible conditions. 8. Future work ============== Our implementation of [@b3-ebo-01-62] algorithm assumes that the nucleotide sites are independent and identically distributed. However, to make their algorithm more general, we need to incorporate rate heterogeneity among sites. [@b9-ebo-01-62] proposed the inclusion of a hidden Markov model to allow for rate variations among sites; perhaps a similar model could be used in the context of the BH algorithm. Secondly, our implementation of [@b3-ebo-01-62] algorithm calculates the maximum-likelihood for a user-specified tree. It does not search the treespace for the most likely tree and therefore is limited to analysis of a small number of taxa (*k* ≤ 7). Although searching through the entire tree space is an NP-hard problem, the computation time can be reduced by using a search strategy such as branch and bound ([@b17-ebo-01-62]) or other heuristic methods. We have modified [@b25-ebo-01-62] to search through the tree space but the processing time is far greater than that required by PHYLIP ([@b10-ebo-01-62]) or PAUP\* ([@b41-ebo-01-62]). One possible way of reducing the processing time would be to implement a parallel version of the BH algorithm. Some of the other heuristic methods that might be useful are tree-fusing ([@b16-ebo-01-62]) and simulated annealing ([@b27-ebo-01-62]; [@b32-ebo-01-62]). We also need to search the likelihood surface more exhaustively and, if possible, identify the *Q*-values that converge to a global maximum. Finally, we need to understand better the statistical properties associated with assessment of symmetry of joint probability distribution matrices. This research was partly funded by a Discovery Grant (DP0453173) from the Australian Research Council. The hospitality of Patrick Forterre and the Pasteur Institute is gratefully acknowledged by LSJ. This is research paper \#015 from SUBIT. {#f1-ebo-01-62} {ref-type="table"}).](EBO-01-62-g002){#f2-ebo-01-62} {ref-type="table"}).](EBO-01-62-g003){#f3-ebo-01-62} ###### Probabilities obtained from matched-pairs tests of symmetry, marginal symmetry and internal symmetry using 1st codon sites from the hominoid data Ppan Ptro Hsap Ggor Ppyg Hlar ---------- --------- ------- ------- ------- ------- ------- ------- **Ptro** Bowker 0.206 Stuart 0.620 Ababneh 0.425 **Hsap** Bowker 0.217 0.709 Stuart 0.312 0.867 Ababneh 0.532 0.883 **Ggor** Bowker 0.032 0.219 0.302 Stuart 0.024 0.227 0.243 Ababneh 0.769 0.994 0.387 **Ppyg** Bowker 0.440 0.579 0.614 0.139 Stuart 0.092 0.095 0.239 0.078 Ababneh 1.000 1.000 1.000 0.680 **Hlar** Bowker 0.400 0.331 0.262 0.180 0.703 Stuart 0.517 0.419 0.576 0.106 0.696 Ababneh 0.268 0.404 0.127 0.688 0.499 **Msyl** Bowker 0.592 0.584 0.303 0.233 0.635 0.735 Stuart 0.327 0.304 0.303 0.056 0.242 0.522 Ababneh 0.759 0.786 0.313 0.914 0.989 0.913 ###### Probabilities obtained from matched-pairs tests of symmetry, marginal symmetry and internal symmetry using 2nd codon sites from the hominoid data Ppan Ptro Hsap Ggor Ppyg Hlar ---------- --------- ------- ------- ------- ------- ------- ------- Bowker 0.102 **Ptro** Stuart 0.206 Ababneh 1.000 Bowker 0.197 0.352 **Hsap** Stuart 0.348 0.826 Ababneh 1.000 0.754 Bowker 0.264 0.323 0.361 **Ggor** Stuart 0.437 0.706 0.334 Ababneh 1.000 0.352 0.558 Bowker 0.359 0.446 0.728 0.297 **Ppyg** Stuart 0.154 0.243 0.401 0.088 Ababneh 0.720 0.653 0.879 0.867 Bowker 0.157 0.444 0.126 0.331 0.165 **Hlar** Stuart 0.297 0.721 0.638 0.513 0.177 Ababneh 0.231 0.329 0.075 0.327 0.239 Bowker 0.710 0.957 0.890 0.605 0.46 0.801 **Msyl** Stuart 0.881 0.996 0.940 0.940 0.494 0.948 Ababneh 0.378 0.690 0.592 0.248 0.351 0.440 ###### Probabilities obtained from matched-pairs tests of symmetry, marginal symmetry and internal symmetry using 3rd codon sites from the hominoid data Ppan Ptro Hsap Ggor Ppyg Hlar ---------- --------- ------- ------- ------- ------- ------- ------- Bowker 0.670 **Ptro** Stuart 0.357 Ababneh 0.846 Bowker 0.517 0.504 **Hsap** Stuart 0.511 0.452 Ababneh 0.589 0.443 Bowker 0.257 0.767 0.171 **Ggor** Stuart 0.568 0.947 0.459 Ababneh 0.349 0.398 0.092 Bowker 0.019 0.028 0.016 0.046 **Ppyg** Stuart 0.016 0.029 0.242 0.011 Ababneh 0.180 0.160 0.010 0.662 Bowker 0.236 0.277 0.743 0.244 0.756 **Hlar** Stuart 0.083 0.135 0.623 0.093 0.535 Ababneh 0.715 0.584 0.627 0.678 0.748 Bowker 0.372 0.528 0.383 0.158 0.035 0.445 **Msyl** Stuart 0.151 0.261 0.354 0.386 0.006 0.142 Ababneh 0.996 0.986 0.567 0.100 0.811 0.948 ###### Log Likelihood values for the three most likely trees returned by the BH program Tree Log Likelihood ------------------------------------------------ ---------------- ((((((Ptro,Ppan),Ggor),Hsap),Ppyg),Hlar),Msyl) −3540.684 ((((((Ptro,Ppan),Hsap),Ggor),Ppyg),Hlar),Msyl) −3545.508 (((((Ptro,Ppan),(Hsap,Ggor)),Ppyg),Hlar),Msyl) −3554.946 ###### Shimodaira-Hasegawa (SH) Test and Approximately Unbiased (AU) Test Tree SH Test AU Test ------------------------------------------------ --------- --------- ((((((Ptro,Ppan),Ggor),Hsap),Ppyg),Hlar),Msyl) 0.811 0.716 ((((((Ptro,Ppan),Hsap),Ggor),Ppyg),Hlar),Msyl) 0.428 0.334 (((((Ptro,Ppan),(Hsap,Ggor)),Ppyg),Hlar),Msyl) 0.075 0.026 ###### Comparison of edge lengths obtained using BH and PHYLIP for the hominoid tree ((((((Ptro,Ppan), Ggor), Hsap), Ppyg), Hlar), Msyl). Refer [Figure 1](#f1-ebo-01-62){ref-type="fig"} for an explanation of node numbers. Edge Distance using BH Distance using DNAML Confidence Interval (DNAML) ---------------- ------------------- ---------------------- ----------------------------- Ppyg, Node-2 0.058 0.061 0.046--0.077 Node-2, Node-4 0.028 0.024 0.014--0.035 Node-2, Node-3 0.018 0.020 0.011--0.030 Node-4, Hlar 0.037 0.039 0.027--0.053 Node-4, Msyl 0.108 0.109 0.088--0.129 Node-3, Hsap 0.032 0.029 0.019--0.040 Node-3, 5-Node 0.009 0.009 0.003--0.016 Node-5, Ggor 0.043 0.042 0.029--0.055 Node-5, Node-6 0.010 0.009 0.003--0.015 Node-6, Ptro 0.017 0.017 0.009--0.025 Node-6, Ppan 0.016 0.015 0.007--0.022 ###### Macaque-Bonobo divergence matrix for the seven taxa hominoid tree ((((((Ptro, Ppan), Ggor), Hsap), Ppyg), Hlar), Msyl) based on (a) observed values and (b) joint probability distribution values --------- --- ------- ------- ------- ------- **(a)** **A** **C** **G** **T** A 306 11 18 15 C 10 279 2 47 G 20 4 142 2 T 6 40 2 302 **(b)** **A** **C** **G** **T** A 303.7 12.8 21.6 11.9 C 10.2 270.8 2.1 54.8 G 21.3 7.5 138.1 1.1 T 6.8 42.8 2.2 298.2 --------- --- ------- ------- ------- ------- ###### Probability values for Bowker's Test of Symmetry and Stuart's Test of Marginal Symmetry for all the edges of the most likely hominoid tree ((((((Ptro, Ppan), Ggor), Hsap), Ppyg), Hlar), Msyl). See [Figure 1](#f1-ebo-01-62){ref-type="fig"} for an explanation of node numbers Edge Bowker's Test Stuart's Test ---------------- --------------- --------------- Ppyg, Node-2 0.113 0.035 Node-2, Node-4 0.435 0.697 Node-2, Node-3 0.241 0.282 Node-3, Hsap 0.000 0.000 Node-3, Node-5 0.145 0.023 Node-5, Ggor 0.001 0.000 Node-5, Node-6 0.088 0.012 Node-6, Ptro 0.085 0.013 Node-6, Ppan 0.097 0.013 Node-4, Hlar 0.454 0.140 Node-4, Msyl 0.135 0.080 ###### Contingency table for the edge linking node 5 to the Gorilla leaf node. Rows correspond to internal node and columns to leaf node A C G T --- ------- ------- ------- ------- A 325.0 2.0 17.7 3.0 C 2.0 332.4 0.0 18.5 G 2.0 0.0 156.3 0.0 T 0.0 4.6 0.0 342.5 ###### Probabilities obtained from matched-pairs tests of symmetry, marginal symmetry and internal symmetry using all sites from the bacterial data Apyr Bsub Drad Tthe ---------- --------- ------- ------- ------- ------- Bowker 0.000 **Bsub** Stuart 0.000 Ababneh 0.295 Bowker 0.000 0.995 **Drad** Stuart 0.000 0.946 Ababneh 0.754 0.958 Bowker 0.509 0.000 0.000 **Tthe** Stuart 0.731 0.000 0.000 Ababneh 0.263 0.544 0.863 Bowker 0.132 0.000 0.000 0.415 **Tmar** Stuart 0.325 0.000 0.000 0.267 Ababneh 0.095 0.417 0.297 0.546 ###### Comparison of edge lengths obtained using the BH program and DNAML for tree \#1. Refer [Figure 2](#f2-ebo-01-62){ref-type="fig"} for tree diagram and an explanation of node numbers Edge Distance using BH Distance using DNAML Confidence Interval (DNAML) ---------------- ------------------- ---------------------- ----------------------------- Bsub, Node-2 0.122 0.127 0.104--0.150 Node-2, Node-3 0.040 0.039 0.024--0.053 Node-3, Tthe 0.060 0.069 0.051--0.087 Node-3, Drad 0.131 0.120 0.098--0.143 Node-2, Node-4 0.036 0.043 0.027--0.058 Node-4, Tmar 0.058 0.061 0.044--0.078 Node-4, Apyr 0.124 0.127 0.104--0.150 ###### Comparison of edge lengths obtained using the BH program and DNAML for tree \#2. Refer [Figure 3](#f3-ebo-01-62){ref-type="fig"} for tree diagram and an explanation of node numbers Edge Distance using BH Distance using DNAML Confidence Interval (DNAML) ---------------- ------------------- ---------------------- ----------------------------- Tthe, Node-2 0.064 0.068 0.050--0.086 Node-2, Node-3 0.050 0.050 0.033--0.066 Node-3, Bsub 0.106 0.105 0.083--0.126 Node-3, Drad 0.110 0.108 0.087--0.130 Node-2, Node-4 0.046 0.047 0.031--0.063 Node-4, Tmar 0.059 0.063 0.046--0.079 Node-4, Apyr 0.122 0.122 0.099--0.145 ###### Divergence matrices for tree \#1 for (a) Bacillus-Aquifex pair and (b) Bacillus-Deinococcus pair ----------------------------------------------------------------------------------- --- ------- ------- ------- ------- ---------- ------- ------- ------- ------- \(a\) Observed and estimated divergence matrix values for *Bacillus-Aquifex* pair **(i)** **A** **C** **G** **T** **(ii)** **A** **C** **G** **T** A 0.195 0.019 0.034 0.004 0.191 0.018 0.039 0.004 C 0.005 0.201 0.02 0.012 0.006 0.194 0.024 0.014 G 0.012 0.030 0.273 0.004 0.014 0.038 0.262 0.005 T 0.002 0.037 0.027 0.125 0.003 0.037 0.03 0.121 ----------------------------------------------------------------------------------- --- ------- ------- ------- ------- ---------- ------- ------- ------- ------- ###### Goodness of Fit index for all pairs of bacteria Sequence Pair Tree \#1 Tree \#2 --------------- ---------- ---------- Bsub-Tmar 3.06 17.94 Bsub-Apyr 7.01 25.37 Bsub-Tthe 1.26 0.91 Bsub-Drad 34.92 3.41 Tmar-Apyr 0.52 0.43 Tthe-Drad 2.10 13.65 Tmar-Drad 3.14 4.59 Apyr-Drad 5.99 6.85 Tmar-Tthe 7.90 1.42 Apyr-Tthe 9.06 1.77 -------------------------------------------------------------------- ------- ------- ------- ------- \(a\) Marginal probabilities at leaf nodes for bacterial data set. **Leaf Node** **A** **C** **G** **T** Tthe 0.219 0.278 0.354 0.149 Tmar 0.207 0.279 0.359 0.155 Apyr 0.214 0.287 0.354 0.145 Drad 0.250 0.233 0.321 0.195 Bsub 0.251 0.238 0.319 0.191 \(b\) Marginal probabilities at internal nodes for tree \#1. **Internal Node** **A** **C** **G** **T** Node-2 0.216 0.272 0.358 0.154 Node-3 0.218 0.269 0.357 0.156 Node-4 0.210 0.282 0.36 0.148 \(c\) Marginal probabilities atinternal nodes for tree \#2. **Internal Node** **A** **C** **G** **T** Node-2 0.214 0.275 0.360 0.151 Node-3 0.227 0.257 0.342 0.174 Node-4 0.212 0.281 0.361 0.146 -------------------------------------------------------------------- ------- ------- ------- ------- ###### Probability values for Bowker's Test of Symmetry and Stuart's Test of Homogeneity for all the edges of the bacterial tree ---------------------------------------------------------------------------------------------------- ------------------- ------------------- \(a\) Tree \#1. Refer [Figure 2](#f2-ebo-01-62){ref-type="fig"} for an explanation of node numbers **Edge** **Bowker's Test** **Stuart's Test** Bsub, Node-2 0.000 0.000 Node-2, Node-3 0.427 0.835 Node-2, Node-4 0.002 0.005 Node-3, Tthe 0.567 0.390 Node-3, Drad 0.000 0.000 Node-4, Tmar 0.646 0.359 Node-4, Apyr 0.135 0.742 ---------------------------------------------------------------------------------------------------- ------------------- ------------------- ###### Contingency table for the edge linking node 3 to the Deinococcus leaf node. Rows correspond to internal node and columns to leaf node. a A C G T ------- ------- ------- ------- ------- **A** 260.2 12.8 37.9 0.0 **C** 2.1 280.7 6.2 6.0 **G** 4.7 9.7 378.0 2.6 **T** 0.5 32.9 21.2 182.3 | High | [
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This project will provide extremely valuable specialized training in historical demographic techniques for analyzing longitudinal data to students and researchers working in a variety of demographic sub-fields. The rational for the project is simple: Historical demography has a long history of important contributions to the theory, methods, and practice of population studies, especially in the use of longitudinal data. Historical demographers are currently making important contributions to mainstream demographic research in fertility, mortality, family systems, aging, and migration. Indeed, the size, scope, and temporal and geographic coverage of databases currently available and under construction are unprecedented. Since historical data are often longitudinal and multi-level, they raise subtle methodological problems. Meaningful analysis often requires specialized methodologies, such as family reconstitution and back projection that are unique to historical research. Since they are based on fundamental principles of demographic theory, students trained in these methods are both prepared for historical research and better able to use complex contemporary sources. Historical data can be a perfect model for analysis of demographic processes. The number of observed covariates is usually limited, and historical demographers have excelled in creatively using longitudinal and genealogical information to construct contextual and time-varying covariates. The longitudinal analysis techniques students learn will provide a roadmap for use with any data set with a time dimension, including many large contemporary data sets collected through NIH funding. This program will offer both formal courses and opportunities for practical experience with active researchers. Students will be introduced to data sets and advanced statistical techniques at the forefront of current research. We also aim to secure and archive some of the classic data sets used in earlier research and to make them available for analysis with the most modern methods. | High | [
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Advantages and disadvantages of using robots in our life Robotics or the artificial intelligence (AI) are used in manufacturing , in the search , the rescue missions and in the military , They are used in the factories across the world and the people have been increasingly losing their jobs as the robots become more efficient and precise than the humans . Advantages of robots The people should know the importance of robots to help them to better determine when to use and when to not use the robots , The robots can go to the planets , They can be used to explore the space , They can spy on the people in ways the people can’t move and from views the humans can’t reach . The robots can gofar down into the unknown places where the humans would be crushed , They can give us the information that the humans can’t get , They can work at places 24/7 without any salary and food , Plus they don’t get bored . The robotscan perform the tasks faster than the humans and much more consistently and accurately , They become more common each and every day , The robotic pets can help the patients with depression and they keep them active . Robots Most of robots are automatic so , they can move without any human interference , They can entertain us and they can help us in certain tasks , You can send them to dangerous environment such as the deep sea or the war-zones . Youcan use the robots to produce the products in the factories such as assembling the cars , They can also be used to build the parts for many products such as the plane parts , the car parts and the construction supplies . The robots do anything which we need to be precise , accurate , New jobs are created because the people have to fix and design the robots , The robots can work without sleep , So , they can work 24/7/365 . The robots can endure the hostile environment of the interplanetary space , They are made that the planetary atmospheres do not affect their physical state and performance , They can replace the human beings in many areas of work , They can shoulder greater responsibilities and they can be programmed to manage themselves . The robots can be programmed to reach the Earth’s nadirs , They can be used to dig for the fuels , They can be used for mining purposes , They can be harnessed for exploring the depths of oceans , They can be used to overcome the limitations that humans have . The robots can be used in carrying out the repetitive & time-consuming tasks efficiently , They are used to do dangerous tasks , They can adjust their parameters like their speed & time , They can act quickly , unaffected by the factors that affect the humans . The robots do not require to sleep or take breaks , They are able to function without stopping , When employed to carry out dangerous tasks , the risk to the human health & safety is reduced , They can work long time without service or maintenance and they can be more productive than the people . The robots can not tremble or shake as the human hands do , They can have much smaller & versatile moving parts than the people , They have performed the medical surgeries because they can be faster and more precise than the people . The robots are designed to work in the harsh environments like in the space , without the air , underwater & in the fire , They can be used instead of the people when the human safety is a concern , They can come in any size , Whatever size needed for any task can be created . The robots can do the jobs that the people are unwilling to do , many robotic probes have been sent throughout the solar system to never return back to Earth , They can be stronger than the people , The robots in the warfare eliminate putting more people at risk . Disadvantages of robots The robots needs a supply of power , The people can lose jobs in the factories , They need the maintenance to keep them running , It costs a lot of money to make or buy the robots , The software and the equipment that you need to use with the robot cost much money . The robots can take the place of many humans in the factories , So , the people have to find new jobs or be retrained , They can take the place of the humans in several situations , If the robots begin to replace the humans in every field , They will lead to unemployment . The robotscost much money in the maintenance & repair , The programs need to be updated to suit the changing requirements , the machines need to be made smarter , In case of the breakdown , the cost of repair may be very high , The procedures to restore lost code or data may be time-consuming & costly . The robotscan store large amounts of data but the storage , access , retrieval is not as effective as the human brain , They can perform the repetitive tasks for long but they do not get better with experience such as the humans do . The robots are not able to act any different from what they are programmed to do , With the heavy application of robots , the humans may become overly dependent on the machines , losing their mental capacities , If the control of robotsgoes in the wrong hands , The robots may cause the destruction . The robotsare not intelligent or sentient , They can never improve the results of their jobs outside of their predefined programming , They do not think , They do not have emotions or conscience , This limits how the robots can help & interact with people . | High | [
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If you are thinking of joining ICHA you will need to contact the ICHA office, by e-mail for an application pack [email protected]. There is an initial one off administration fee of £75 and then your annual membership fee will be assessed on the number of beds you have. Currently (April 2017) the membership fee is £1.333p per bed per week with a minimum of £357.04 and a maximum of £6302.40. So for example, 8 beds would cost 8 x around £1.3266 x 52 £551.87 per annum. It is worth remembering that included as part of this fee is your entitlement to a page in the ICHA Commissioners Handbook, produced annually, which goes to Commissioners in Local Authorities in England and Wales. We know that a number of Commissioners do consult the Handbook when looking for placements, particularly so when they are unable to find a suitable placement through their usual day to day commissioning practices. How can I get a comparison of residential fees? – I want to see if our fees are competitive. jamin 2017-07-29T12:08:52+00:00 Essentially you can’t. One advantage of being an ICHA member is that the networking that is afforded does allow members to exchange such information on an informal basis. There are no published figures on this to our knowledge and equally one has to be careful in interpreting such figures. For example some of our members will charge a fixed fee but that will include their therapeutic services in the fee – therefore it is essential to look at the services that are provided – a criticism that ICHA has of a number of commissioners. Local authorities do have to publish amounts of over £500 that are paid out but again these figures are by and large unhelpful without knowing the needs of the young person concerned etc. There is nothing to stop you asking a local authority for fees paid but again without the underlying information the figures are unhelpful and the local authority may decline to release such information on the grounds they are commercially sensitive. If you were to make a freedom of information request a local authority can again decline to release such figures on the grounds they are commercially sensitive. If anyone comes across any such figures and underlying information that is helpful the ICHA would be happy to circulate to all members. We are not a member – would we be able to attend a meeting to see what you are about? jamin 2018-01-31T13:50:00+00:00 Please do note that if there is a confidential matter that is being discussed you may, as a non-member, be asked to leave the meeting whilst that item is under discussion. That said that is a very rare event! A local authority is in our view practicing dangerously with a child we are looking after – advice please? jamin 2017-07-29T12:08:06+00:00 By enlarge ICHA assumes that members should be aware of actions that they can take. That said we do appreciate that it is helpful in many such situations to seek advice from an experienced member who may have other observations that are helpful – in other words it’s always good to talk! Where a member has such concerns they should contact the ICHA office and we will endeavor to put you in touch with an experienced member in such matters. We are unable to assist non-members in this regard but would advise the obvious – in other words the child’s interests are paramount and it is important that there needs are met at the expense of any business relationship that you may have with the local authority concerned! ICHA has explored this in the past but is not currently running regional groups with the exception of WICHA which is, if you will, a regional group albeit that the region is the whole of Wales! ICHA does periodically convene regional meetings at the request of members where there is a particular issue(s) in that region. Where appropriate, non-members may be invited to these meetings. ICHA weekly bulletin – can I request to receive? – I am not an ICHA member. jamin 2017-07-29T12:07:27+00:00 No, the weekly ICHA E-Bulletin is for members only. We use it to inform members of developments in the practice, updates in policy & practice, relevant items in the press, training events and other associated topics. What benefits would I get by joining the ICHA? jamin 2018-01-12T12:29:24+00:00 ICHA is a trade association representing independent providers of residential children’s homes in England & Wales. We are actively involved in promoting the needs of the sector and the children and young people who benefit from our services, by: • Being the largest representative body of children’s homes providers in the UK with over 80% of all private & voluntary beds and over 50% of Homes in the country; 183 member organisations, 1155 children’s homes and more than 5747 beds in total (at 1 January 2018). • Meeting with Ministers and Government officials. • Political lobbying so that the voice of the sector is heard. We are member led and run on democratic lines – 1 member: 1 vote. We have a committee of 19, nominated by members. Each committee member takes a lead on certain issues – e.g. web-site, annual conference, membership, children’s rights, political activity, press and publicity. We also have Sub-Committees for Research & Development, Contracts and Commissioning and Finance. We hold General Meetings, usually in the Midlands for ease of access, where members can ‘network’ and share quality practice and discuss issues; and to which we regularly invite relevant speakers such as representatives from Ofsted, Children’s rights etc. We produce a Weekly E-Bulletin informing members of developments in the sector, relevant items in the press, training events and other associated topics. We hold a conference each year and/or we speak at other national conferences and events. We manage our own web-site – where our members are listed individually. We produce an annual Commissioners Handbook that we disseminate to Commissioners. Each ICHA member has a page within the book to describe the services they offer. We have office staff that are available to assist members whenever they can. We employ Jonathan Stanley, residential child care expert and formally of the National Centre for Excellence in Residential Child Care who joined ICHA in July 2011 as consultant for policy and practice. For more information about ICHA, or to join, contact us as follows: Email: [email protected] www.icha.org.uk Are there any providers that are willing to share procedures or is this available on the ICHA website? jamin 2017-07-29T12:06:41+00:00 Certain members do share procedures but there is no formalized process for doing this. If you are a member you can make this request through the ICHA office who will place your request either on the website or in the weekly bulletin. We are not able to assist non-members in this regard. Referrals are declining – are other providers finding same – any suggestions? jamin 2017-07-29T12:06:21+00:00 In summary, all providers are experiencing a reduction in referrals despite the number of childcare orders being on the increase (true as at March 2012). Experience would suggest that those referrals that are made relate to young people with significantly increased needs relative to those that were referred in previous years. It is also the case that many young people that would have been referred to residential care are now being referred to fostering agencies and this is a cause of concern to the ICHA since there is great deal of evidence that many referrals made are inappropriate to a foster placement, and often result in multiple failed placements. ICHA is unable to advise non-members further in this regard but on behalf of the membership are continually raising these concerns with certain local authorities and key people in central government. A young person is being removed on financial grounds – what can we do? jamin 2017-07-29T12:06:03+00:00 In this current financial climate such actions are sadly not rare. There are a number of examples of such actions been undertaken without convening a LAC review and where significant professionals believe this is contrary to the young person’s best interests. The Children’s Minister, ROGER MORGAN, the Children’s Rights Director for England (correct as at March 2012) has indicated that he will intervene in such circumstances and he can be approached directly. It is the case that a young person can complain to the local authority at any proposed such action but ICHA is aware of a number of cases where this process would seem to have failed the young person. If you are a member we will put you in touch with an experienced member within ICHA who may be able to advise you on possible courses of action that you can take; or you are welcome to attend a General or Committee meeting and seek advice from those experienced professionals attending. If you e-mail the ICHA office we will place your request in the weekly bulletin that is sent to all members and it may be that one of our members will contact you directly with suggestions. This is open to both members and non-members. ICHA does not recommend any of these contacts in terms of the quality of their work and it is for you to ascertain their level of competence! I’m looking for someone to do Regulation 44 reports – can you assist? jamin 2017-07-29T12:05:01+00:00 If you e-mail the ICHA office we will place your request in the weekly bulletin that is sent to all members and it may be that one of our members will contact you directly with suggestions. This is open to both members and non-members. The ICHA office does hold some details of professionals available to do such reports and if they are relevant to your geographic area these details will be forwarded to you. ICHA does not recommend any of these contacts in terms of the quality of their work and it is for you to ascertain their level of competence! I have a bad inspection report from Ofsted – what do I do and will ICHA help me deal with this issue? jamin 2017-07-29T12:04:43+00:00 If you are a member then ICHA can arrange for an experienced member to talk you through what actions you can take and will offer you observations based on your report. As an organization we have, in general, enjoyed a positive relationship with Ofsted and are able to ask specific questions on our member’s behalf. Our experience is that OFSTED reports can vary from inspector to inspector and region to region but where non-members have contacted us the criticism of the provider has in the main been valid and a more experienced provider would not have attracted the criticism/observation from the OFSTED inspection. ICHA cannot assist non-members in considering aspects of the bad/poor OFSTED report. Members and non-members are advised to consult the OFSTED website which does advise on the appeal process. I have a property that is empty and I am thinking of setting up a children’s Home – how do I do it? jamin 2017-07-29T12:02:42+00:00 We have had a number of enquiries in this regard. In the main they have been small property developers that have purchased and upgraded properties with a view to selling on and have then been unable to do so in the current financial climate; therefore are looking for an alternative use for those properties. A second area of enquiry has been from people working in the local authority sector, being somewhat disgruntled with the provision within the local authority and feeling they would be able to do a better job by setting up on their own. This answer is geared more for those “property developers” who have little or no experience in childcare. You are advised to refer to the OFSTED website: Ofsted: Children’s social care registration – Introduction to children’s homes 12 April 2012 – Ofsted A guide explaining in more detail what the law says anyone intending to open a children’s home must do to in order to apply for registration. http://www.ofsted.gov.uk/resources/childrens-social-care-registration-introduction-childrens-homes and consult carefully the regulations as they pertain to the running of children’s homes. The sector is highly regulated and you will need to be aware of the need to employ staff experienced in childcare and not least a Registered Manager who meets OFSTED requirements. The lead-in time to establishing a children’s home is not insignificant and you will be faced with significant setup costs not only in terms of the property but in terms of recruitment of staff, training, establishing written procedures etc etc. ICHA would caution anyone who is not experienced in residential childcare and is not up to speed with current market conditions against setting up a children’s home in these current difficult trading times or at least ensure that you have researched the need in your proposed geographic location very carefully. Be aware that many local authorities operate an approved provider list many of which are accessed through a tender exercise and it may be that you will have to wait until the approved list is re-tendered until you can tender to be on that approved supplier listing. | Low | [
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The healing session will last for one hour. You will relax in a quiet atmosphere with your eyes closed. You may either sit or lay down, but do not meditate. Do not consume alcohol or drugs prior to your session. After 45 minutes we will discuss the healing. Some people feel nothing while others can feel light movements. Sometimes the effects of the treatment are felt immediately, but more frequently an effect is not observed until a little later. Time delays may be an hour or up to 3 days. Occasionally, there may be a temporary worsening of symptoms before relief is obtained. Benefits of Esoteric Healing Esoteric Healing Session - $80 or 100SF ** Health Benefit 1: An Esoteric Healing will provide physical and etheric healing. Health Benefit 2: Balancing your energy field will benefit your emotional body. Health Benefit 3:An Esoteric Healing will benefit your mental body. . Health Benefit 4: An Esoteric Healing will benefit your Soul. Health Benefit 5: An Esoteric Healing will benefit your Spiritual Body. Health Benefit 6: An Esoteric Healing will benefit your Higher Self. Health Benefit 7: An Esoteric Healing will benefit your karma. Health Benefit 8: An Esoteric Healing will help you through predictive and preventative health. Our Services ESOTERIC HEALINGS"Energy Follows Thought" Absentee Esoteric Healing Session - $80 or 100SF ** Many healers believe that Absentee Healing Sessions are more potent than healings in person, since there are fewer energetic connections like sympathy, expectation, judgment and empathy. The healing session will last for one hour. Please contact me by telephone 5 minutes prior to your healing session to inform me that you are ready. Simply relax in a quiet place, either sitting or laying down, but not meditating. Do not consume alcohol or drugs prior to your session. After 45 minutes call (517)896-0080 to discuss the healing. Medical Disclaimer "Esoteric Healings" is not a medical organization and no medical diagnoses are made. An Esoteric Healing is not intended to replace your current medical treatment program, medication, counseling, diet or surgery. Insurance may not cover Esoteric Healing. Your payment for services will be interpreted to mean that you understand these conditions. Healings will be done in accordance to the best interests of your Soul. First Time Patients There is some information that you will need to provide before your Esoteric Healing. Please email, mail or telephone with the following information: Full Name, Address, Telephone, Email, Date for Healing, Time for Healing, Your Time Zone, Reason for Healing. **There will be an additional fee for translations and for healings performed at Healing Centers. | Mid | [
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Henry Cárdenas Henry Cárdenas Ordaz (born October 30, 1965 in Sogamoso, Boyacá) is a retired road cyclist from Colombia, who was a professional rider from 1986 to 1997. He was nicknamed "Cebollita". Major results 1987 1st in Stage 6 Criterium du Dauphiné Libéré (FRA) 2nd in General Classification Criterium du Dauphiné Libéré (FRA) 1995 1st in Stage 4 Clásico RCN, Espinal (COL) 2nd in General Classification Clásico RCN (COL) 1996 1st in Stage 2 Clásico RCN, Barbosa (COL) External links Category:1965 births Category:Living people Category:People from Sogamoso Category:Colombian male cyclists Category:Tour de France cyclists | Mid | [
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30.875,
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EYOTA, Minn. (KTTC) — A Wisconsin man was arrested after deputies said he stole a family member’s car and drove to Eyota. Deputies said 44-year-old Jeffrey Pelot said he was communicating with aliens and that the aliens made him steal the car. Deputies said Pelot stole a Ford Escape near Wausau at just before 6 a.m. on Thursday. Deputies said he then drove to Eyota and waited outside a friend’s house for a few hours before being taken into custody. Deputies said he is expected to be extradited back to Wisconsin Friday or Saturday After Pelot was read his Miranda rights, deputies said he allegedly told them he joined the Illuminati in 2006. Deputies said the charges Pelot is facing include possession of a stolen vehicle and burglary. | Low | [
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9 Solve -86*f + 43*f = -58*f - 135 for f. -9 Solve -269*z - 483*z + 5185 = 285*z for z. 5 Solve -18*z + 44 = 11*z - 14 for z. 2 Solve -221*s - 203*s - 950 = 51*s for s. -2 Solve -2*v = -31*v + 23*v - 72 for v. -12 Solve -37*c = -34*c for c. 0 Solve 79*m - 240 - 64 = 3*m for m. 4 Solve -23*m - 153 = 205 - 13 for m. -15 Solve -319 - 3 = 46*a for a. -7 Solve 0 = -4262*d + 4305*d - 430 for d. 10 Solve 0 = -37*y + 343 - 269 for y. 2 Solve 123*x + 95 = 104*x for x. -5 Solve -209 = 40*h - 9 for h. -5 Solve -264 = 43448*c - 43424*c for c. -11 Solve 772*r = 727*r + 765 for r. 17 Solve 4988 = 96*u + 3356 for u. 17 Solve 38827*m = 38824*m + 99 for m. 33 Solve 1079*h = 731*h for h. 0 Solve -6*m + 21 = 21*m - 6*m for m. 1 Solve 270 = -2896*c + 2869*c - 54 for c. -12 Solve 2194 = -16*w + 2050 for w. -9 Solve 1189*s - 18 = 1192*s for s. -6 Solve 14*d + 844 - 874 = -16*d for d. 1 Solve 81*w + 180*w - 3777 = 2748 for w. 25 Solve 0 = 315*t - 287*t + 588 for t. -21 Solve 1540 - 427 = 42*b + 11*b for b. 21 Solve 0 = 79*z + 16*z - 47*z + 384 for z. -8 Solve -863 - 2297 = 790*g for g. -4 Solve 74*o - 104*o = 180 for o. -6 Solve 1034*a - 1016*a - 252 = 0 for a. 14 Solve -68*w = -409 + 1361 for w. -14 Solve 63 = 2644*o - 2594*o - 337 for o. 8 Solve -82*n + 555 = 96*n - 141*n for n. 15 Solve 2 + 242 = 24*l + 4 for l. 10 Solve 300*a - 661*a + 216 = -334*a for a. 8 Solve 20826*c - 3317 = 20719*c for c. 31 Solve 1011*x - 991*x + 140 = 0 for x. -7 Solve -17*a = 18*a - 36*a + 10 for a. 10 Solve -28*n + 110*n + 133 = 625 for n. 6 Solve 0 = -105699*k + 105750*k + 459 for k. -9 Solve 51*p - 4791 = -4128 for p. 13 Solve 19*c - 5440 = -253*c for c. 20 Solve 24112 = -1481*b + 18445 - 47649 for b. -36 Solve 1983*w + 805 = 3953*w - 1993*w for w. -35 Solve 36*c - 267 = 57 for c. 9 Solve 310 = 160*x + 164*x - 355*x for x. -10 Solve -2993*b + 3037*b = -748 for b. -17 Solve -21 = 6*d - 9 - 96 for d. 14 Solve 86*c + 90*c - 198*c = -176 for c. 8 Solve 784 = -190*a + 24 for a. -4 Solve -261*g = 260*g - 518*g + 90 for g. -30 Solve 18568*n = 18597*n for n. 0 Solve 53*h = 4903 - 5645 for h. -14 Solve 625*l = 573*l + 1040 for l. 20 Solve -343 = 64140*v - 64189*v for v. 7 Solve 35*r + 2142 = -271*r for r. -7 Solve f - 383 = -374 for f. 9 Solve 0 = -256*s + 72*s - 188*s + 3348 for s. 9 Solve -7*y + 4*y + 11*y = 72 for y. 9 Solve 58*u + 15 = 28*u + 31*u for u. 15 Solve -303*k = -325*k + 308 for k. 14 Solve -40*f - 104 - 35 = 21 for f. -4 Solve 5671*o - 5646*o = 450 for o. 18 Solve -121 = 29*q + 82 for q. -7 Solve 0 = -208*h + 1191 + 1588 - 75 for h. 13 Solve 458*l + 3115 = 13*l for l. -7 Solve 20 = -13*g + 144 - 46 for g. 6 Solve -106*a = -675 - 385 for a. 10 Solve 4532*q - 296 = 4569*q for q. -8 Solve 45 = 11*v - 87 for v. 12 Solve -426*j - 2116 = -5950 for j. 9 Solve 0 = -124*v - 7385 + 3045 for v. -35 Solve -25*w + w + 16 + 8 = 0 for w. 1 Solve -11 = -48*m + 229 for m. 5 Solve 1472 = 4*y + 1468 for y. 1 Solve 63*s + 14*s - 784 = -21*s for s. 8 Solve 119*d - 11*d = 1080 for d. 10 Solve 150*a + 694*a - 91 = 10881 for a. 13 Solve 0 = 11*a + 2013 - 1892 for a. -11 Solve 0 = 380*p - 986*p - 16968 for p. -28 Solve -405 = 246*i - 534 - 2331 for i. 10 Solve -55*h = 11*h + 199 - 1651 for h. 22 Solve -35*p + 174 = -9*p + 3*p for p. 6 Solve 234*t - 164*t = 310 + 810 for t. 16 Solve -50*z + 917 - 267 = 0 for z. 13 Solve -13*h + 14 = -12 for h. 2 Solve -23*h + 75*h = 38*h - 168 for h. -12 Solve 0 = 22*k - 93*k - 781 for k. -11 Solve -203*v + 9 = -200*v - 30 for v. 13 Solve 26391*t - 26368*t = -321 + 45 for t. -12 Solve 280108*a - 1800 = 280158*a for a. -36 Solve 24 + 32 = 62*g - 6 for g. 1 Solve -36 = 40*r - 139 - 177 for r. 7 Solve -g - 360 = 30*g + 14*g for g. -8 Solve 154 = -m + 133 for m. -21 Solve -183*c = 217*c + 2400 for c. -6 Solve -12*z - 34*z = 12*z + 696 for z. -12 Solve -810 = -5025*k + 4995*k for k. 27 Solve -882*q + 880*q = 16 for q. -8 Solve 5*b + 12*b + 2*b = -399 for b. -21 Solve 712*n - 726*n + 107 = -33 for n. 10 Solve 90*t + 498 = -222 for t. -8 Solve 45*f - 80*f + 1648 = 68*f for f. 16 Solve -88*d - 275 + 389 - 202 = 0 for d. -1 Solve 143*v - 3182 = -7901 for v. -33 Solve -13*j - 3431 + 3106 = 0 for j. -25 Solve -70 + 397 = 39*c - 180 for c. 13 Solve 16773*g - 3306 = 16659*g for g. 29 Solve 0 = 150*x - 13*x - 2906 - 108 for x. 22 Solve -484*o - 9812 - 1519 + 1651 = 0 for o. -20 Solve -172*k - 68*k - 60*k = -6600 for k. 22 Solve 0 = -78*g + 1156 + 248 for g. 18 Solve 3942 - 2196 = 473*d - 2984 for d. 10 Solve 60 = 22*h + 68 + 36 for h. -2 Solve -111*c - 2244 = 21*c for c. -17 Solve 36074 - 35831 = 81*m for m. 3 Solve 70*r + 4448 = -598*r + 112*r for r. -8 Solve 453*w - 9*w - 12075 = -131*w for w. 21 Solve -188 - 85 = -47*q + 103 for q. 8 Solve -175 = -80*l + 159 + 466 for l. 10 Solve -27*y + 222 = -82*y + 1047 for y. 15 Solve 13*c + 5412 = 5451 for c. 3 Solve 0 = 49*h - 0*h - 245 for h. 5 Solve -42*w - 1629 = -2049 for w. 10 Solve 2272 - 2122 = -10*n for n. -15 Solve 12*z + 24511 - 24439 = 0 for z. -6 Solve 6*r - 13 = -10 + 21 for r. 4 Solve -5092*g + 1225 = -5043*g for g. 25 Solve -118*h + 44*h + 783 = -47*h for h. 29 Solve 74675 - 73047 = 44*a for a. 37 Solve 32*a - 148*a = 446*a - 14612 for a. 26 Solve -8*y - 92 = 24 - 52 for y. -8 Solve -327*r = -382*r + 550 for r. 10 Solve 600*a = -343 + 11743 for a. 19 Solve 163 - 53 = -38*u - 72*u for u. -1 Solve v + 16*v - 511 = -460 for v. 3 Solve -1257*z + 963*z = -4704 for z. 16 Solve -10 = 12*p - 16*p - 10 for p. 0 Solve 1095*n - 1061*n = -623 + 147 for n. -14 Solve 0 = -312*v + 264 + 788 + 2068 for v. 10 Solve -8*x = -44*x + 578 + 394 for x. 27 Solve 726*b - 1320 = -720*b + 1512*b for b. -20 Solve 291*q = 30*q - 340*q + 15626 for q. 26 Solve 3*h - 207*h + 2279 = -1393 for h. 18 Solve -81*m - 253 = -982 for m. 9 Solve -6177 = 819*a - 1263 for a. -6 Solve 56*v = 43*v + 44*v + 248 for v. -8 Solve 8 + 364 = -58*t + 82 for t. -5 Solve 11800 - 11534 = -14*v for v. -19 Solve -4*g - 36 = 7*g - 2*g for g. -4 Solve -2*i - 4*i + 1715 = 1715 for i. 0 Solve -45*r - 1766 = -1631 for r. -3 Solve 264 = -705*s + 683*s for s. -12 Solve -131*j + 6879 = 6093 for j. 6 Solve 44971 - 5321 = -1525*x for x. -26 Solve -192*p = 1139 + 973 for p. -11 Solve 0 = 169*a - 142*a - 702 for a. 26 Solve -189*l = -178*l - 110 for l. 10 Solve 207 - 779 = -44*u for u. 13 Solve -46*w = -18*w + 131*w - 3657 for w. 23 Solve 0 = -2*t - 11*t + 41*t - 224 for t. 8 Solve -378*a - 6264 = 144*a for a. -12 Solve 107*g + 27 = -526 - 196 for g. -7 Solve -941275*n + 45 + 189 = -941236*n for n. 6 Solve -342*u + 544*u - 6877 + 1019 = 0 for u. 29 Solve -8*y - 118 = 45*y - 12 for y. -2 Solve 1947*c + 45560 = -331*c for c. -20 Solve 210*x + 497 = 2177 for x. 8 Solve -220*s = 315*s + 173*s + 12036 for s. -17 Solve -496*o + 4901 = 123*o - 9955 for o. 24 Solve 399 = -58*x - 181 for x. -10 Solve 6*a - 5256 = -25*a - 188*a for a. 24 Solve 0 = -157*v - 353*v + 308*v - 202 for v. -1 Solve 85 = 80*j + 30*j + 415 for j. -3 Solve 4*a - 2 + 4 - 2 = 0 for a. 0 Solve -237*a = -13*a + 23*a + 3458 for a. -14 Solve 488*b - 562 = 6270 for b. 14 Solve -12625*v = -12612*v for v. 0 Solve -371*f + 358*f + 13 = 0 for f. 1 Solve -59*g + 606 = 143*g for g. 3 Solve 258*y + 2195 = -181*y for y. -5 Solve 186*t = -348*t - 12282 for t. -23 Solve 12*u + u = -101 + 179 for u. 6 Solve -11*s + 48 - 43 = -39 for s. 4 Solve -36*t = -897 + 357 for t. 15 Solve -61 + 561 - 84 = -26*a for a. -16 Solve -121*m + 114 = 2171 for m. -17 Solve -3288*m - 252 = -3302*m for m. 18 Solve 0 = -750*u + 804*u - 972 for u. 18 Solve -6293*q = -6236*q + 912 for q. -16 Solve -127*m - 23*m = 30*m + 4320 for m. -24 Solve 73 = 45*k - 1052 for k. 25 Solve 0 = 49*p - 16273 + 16616 for p. -7 Solve 42*m - 80 = 8*m - 6*m for m. 2 Solve -769 = -347*h - 3404 - 6734 for h. -27 Solve 190*b + 392 + 178 = 0 for b. -3 Solve -266*r + 148 = -192*r for r. 2 Solve 54 + 93 = 64*t + 19 for t. 2 Solve 12*x - 200 = -6*x + 232 for x. 24 Solve -i - 5861 + 5849 = 0 for i. -12 Solve 77*o + 5*o + 259 = 45*o for o. -7 Solve -64*d + 491 = 107 for d. 6 Solve -130 = 24*n - 91 + 249 for n. -12 Solve 16*f - 6*f + 24 = 12*f for f. 12 Solve -16*o = 43*o + 118 for o. -2 Solve 95 = 77*x + 1168 + 159 for x. -16 Solve 33*k - 6022 + 5758 = 0 for k. 8 Solve -404 + 60 = -43*j for j. 8 So | Low | [
0.537267080745341,
21.625,
18.625
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Q: CloudFlare and Dynamic DNS for Web Apps My understanding is that CloudFlare is a CDN that specializes in thwarting DDoS attacks for web apps; that is basically creates a read-only "cache" of your entire app so that, if you are DDoSed, your users can still access portions of your app and not experience a total denial of service. My understanding of Dynamic DNS is that it is a technology that somehow allows you to immediately change the DNS settings of your web app URL without having to wait the standard 24 hours for DNS changes to "ripple out" over all the DNS servers in the world and take affect. So first off, if anything I have said so far is misguided or incorrect, please begin by correcting me! Assuming I am more or less correct, I'm trying to protect my web app (as best as I can) against DDoS attacks. For one, I have decided to host my app with either Google App Engine or Heroku (haven't made the final decision yet), and I have to imagine that their IT staff is fully prepared to scale up/handle if my app is DDoSed while deployed to their servers. Unfortunately for me, that means they'll scale up and handle the attack (!), which means my billing would soar through the roof and I'd be out of business (I guess that's called a "cash attack"!). So I need a solution that handles both of the following scenarios: The DDoS is enormous, and even Google/Heroku say "enough is enough", we're not supporting this load! I specify a billing "ceiling" (which both Google and Heroku provide), and after that ceiling is reached, I somehow redirect traffic to my CloudFlare/read-only web app hosted elsewhere I suspect I will need to use Dynamic DNS somehow to handle the 2nd scenario, but without knowing how most web apps fortify themselves against DDoSes (i.e. I've hear of so called "bastion hosts"?!?) I'm not even sure if I'm heading down the right path or not. Thanks in advance! A: Some minor corrections: Heroku will not scale your app for you nor does it provide the ability to specify a billing ceiling. You should implement the appropriate monitoring and alerting strategy depending on how you want to react to specific scenarios. Preventing DDoS attacks is not something most app developers concern themselves with - but perhaps you're in a particularly susceptible domain? If so, a service like CloudFlare that does this automatically is a good option. You set your DNS to use their nameservers and they handle the IP address assignments on your behalf and in response to various threats and other optimization opportunities. | Mid | [
0.5913043478260871,
34,
23.5
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Tag Archives: Culture Ok, your mom probably did not teach you all of these things, or even some of these things. But that doesn’t mean we haven’t been nurtured in them by our culture in a very motherly fashion. Many of these “truths” have been the steady milk our society has caused us to drink for years now. Some of these things you may have learned from your mom. But you have learned from other voices that speak in our society that seem almost as authoritative as her. But, how do these things compare to the mind of Jesus Christ? What does He think in regard to them. 1. All religions are essentially the same, so long as you love one another. Jesus Christ did not die on a cross because He believes all religions are essentially the same. In fact, He died on a cross because His own people and the world we live in made no room for the faith He came and preached. And by rising from the dead, and being resurrected, Christ demonstrated the complete incompatibility of the faith He preached with all the other religions in this world. 2. America is a Christian nation. A nation that owns a stockpile of nuclear weapons and that is ready to use them at a moments notice in order to maintain shalom (peace) cannot even begin to claim it is a Christian nation. The truth of the matter is, America has never been nor will it ever be able to claim to be a Christian nation. While many Christians certainly had a hand in helping found this nation, and while many Christian principles were employed in order to do it, the truth of the matter is, there is only one nation on this earth that has the right to call itself Christian– and that is the church of Jesus Christ. 3. God helps those who help themselves. God has never helped nor will He ever help anybody who helps themselves. Such a notion is contrary to a proper understanding of God’s grace and favor. The truth of the matter is, God only helps those who cannot help themselves. He helps those who recognize they can bring nothing to the table, but can only humbly rely upon Him. 4. Home ownership is a wise financial investment. Owning a home is great. Paying a 30-year mortgage is not. If you were to take out a 30-year loan out at the ultra low rate of 5% on $200,000, by the time you pay off your mortgage, you will have actually paid closer to $400,000. This does not include annual property taxes, homeowners insurance, HOA fees, and general maintenance and upkeep costs. When it is all said and done, your $200,000 home will cost you near $500,000!!! While it is possible your home will have a 250% return on investment over the course of 30 years, the likelihood of that happening is very slim, unless you live in an area that experiences a large real estate boom. But even if your home does see a 250% return on it in 30 years, remember, that’s what you need just to break even! Of course, I am speaking here purely of the financial investment of home ownership. The emotional return you and your family receive from doing something like this may make it worth the personal destruction of your wealth. But keep in mind, as Christians we are called to be good stewards of the Lord’s money. If God has blessed you with the ability to make money, you should probably reconsider destroying your wealth with a 30-year mortgage. Consider buying a home in cash, or if you must, a 15-year 3.5 % fixed loan at the most. 5. You can be whatever you want to be when you grow up. While it may give one a sense of empowerment, and foster a creative mind that causes the child to set a personal goal and seek to achieve it, the truth of the matter is, you cannot be whatever you want when you grow up. While we live in a world of seemingly endless possibilities, at the end of the day, we are limited and finite. We can only do so much. We do not have infinite strength or resources. But a great truth is that we serve a God who is sovereign and in control. We serve a God who wants the best for us, who lacks nothing, and is able to do exceedingly above everything that we could ever think or ask. Instead of teaching children that they can be whatever they want to be when they grow up, we should teach them that God has a purpose and plan, and that He is inviting them to discover that and to participate in that plan. And by relying on the Lord, they can accomplish whatever He wills for them. 6. Retirement. The concept of working, saving, and investing for 40 years, so you can one day retire consumes the thoughts of many people today. Indeed, many look at a 401-k, IRA, pension, and social security as a right. Hasn’t the world always retired at the ripe old age of 65? Truth be told, the idea of retirement while not a new concept, is something that has not been the common experience for mankind– even in America. It’s mostly a recent concept that many have been able to experience because we live in a very wealthy society. And while I don’t knock the concept by any stretch of the imagination (as the priests of the Old Testament retired when they were old enough), we should never look at retirement as a Divine right. Nor should we all necessarily look at it as a goal that we should all strive to attain. Indeed, the idea that you and I could possibly spend the last 10, 20, or 30+ years of our life not working isn’t exactly a noble aspiration in the eyes of the Scripture. Such is more akin to sloth and laziness more than anything. 6 days shall you work and on the 7th you shall rest. That principle doesn’t stop just because you felt that you were old enough that it shouldn’t apply to you anymore. 7. Good people go to heaven. While it is true, there are good people who are in heaven, the concept is equally true, that there are good people who go to hell every single day. The truth of the matter is, no matter how good we think we or others might be, in the eyes of God, there is none good– not even one. The only people who go to heaven when they die are those who have been made righteous by the blood of Jesus Christ, and the mercy He offers to all who call upon His name. 8. Sex before marriage is like test driving a car… Ok, your mom probably did not teach you this one. But it is a commonly held belief. And it seems to make sense though, right? You would never buy a car without taking it for a test drive. So, you should never marry a person without having sex with them for a while too, right? While this seems like bullet proof logic, the logic in it is ultimately flawed. Cars and people are not the same. People are created in the image and likeness of God, and should not be likened to the same treatment as an inanimate hunk of metal. People are not meant to be test-driven. People are meant to be loved, respected, and treated as Jesus Christ would treat them. They are not meant to be used. 9. Don’t be so heavenly minded that you are no earthly good. While this saying probably originally had in mind some useless pillar-saint type individual, it has been recently expanded to include anybody who would have a serious devotional life. The saying has come to be used as a pejorative towards anybody who takes their faith “too seriously,” and is used by people who wish to justify their own carnal and hellish life. But as Leonard Ravenhill pointed out, there is no such thing as a man that is too heavenly minded. Indeed, what the world needs most is men who are consumed with heaven. To be heavenly minded is to be of earthly good. 10. You only get one shot at life, so you better make the most of it. This statement is true, but only if you are going to hell. For those of us who are amongst the redeemed, this life is not all that there is. Indeed, we as Christians look forward to life everlasting. We look forward to the day in which the dead shall be raised. We long for the resurrection and the age to come. As a result, if we are unable to fulfill all the desires on our “bucket list,” (the things we want to do before we die) then we shall die in perfect peace. Why? Because we who are living our lives in light of eternity realize that even should we not get to do all the things we want to do before we die, we ultimately have all of eternity to fulfill all the desires and longings of our heart. If you don’t get to visit Hawaii before you die… it’s ok. Hawaii as great as it is now will be all the better in the age to come. | Low | [
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/* Copyright The Kubernetes Authors. Licensed under the Apache License, Version 2.0 (the "License"); you may not use this file except in compliance with the License. You may obtain a copy of the License at http://www.apache.org/licenses/LICENSE-2.0 Unless required by applicable law or agreed to in writing, software distributed under the License is distributed on an "AS IS" BASIS, WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. See the License for the specific language governing permissions and limitations under the License. */ // Code generated by informer-gen. DO NOT EDIT. package v1 import ( time "time" corev1 "k8s.io/api/core/v1" metav1 "k8s.io/apimachinery/pkg/apis/meta/v1" runtime "k8s.io/apimachinery/pkg/runtime" watch "k8s.io/apimachinery/pkg/watch" internalinterfaces "k8s.io/client-go/informers/internalinterfaces" kubernetes "k8s.io/client-go/kubernetes" v1 "k8s.io/client-go/listers/core/v1" cache "k8s.io/client-go/tools/cache" ) // PersistentVolumeClaimInformer provides access to a shared informer and lister for // PersistentVolumeClaims. type PersistentVolumeClaimInformer interface { Informer() cache.SharedIndexInformer Lister() v1.PersistentVolumeClaimLister } type persistentVolumeClaimInformer struct { factory internalinterfaces.SharedInformerFactory tweakListOptions internalinterfaces.TweakListOptionsFunc namespace string } // NewPersistentVolumeClaimInformer constructs a new informer for PersistentVolumeClaim type. // Always prefer using an informer factory to get a shared informer instead of getting an independent // one. This reduces memory footprint and number of connections to the server. func NewPersistentVolumeClaimInformer(client kubernetes.Interface, namespace string, resyncPeriod time.Duration, indexers cache.Indexers) cache.SharedIndexInformer { return NewFilteredPersistentVolumeClaimInformer(client, namespace, resyncPeriod, indexers, nil) } // NewFilteredPersistentVolumeClaimInformer constructs a new informer for PersistentVolumeClaim type. // Always prefer using an informer factory to get a shared informer instead of getting an independent // one. This reduces memory footprint and number of connections to the server. func NewFilteredPersistentVolumeClaimInformer(client kubernetes.Interface, namespace string, resyncPeriod time.Duration, indexers cache.Indexers, tweakListOptions internalinterfaces.TweakListOptionsFunc) cache.SharedIndexInformer { return cache.NewSharedIndexInformer( &cache.ListWatch{ ListFunc: func(options metav1.ListOptions) (runtime.Object, error) { if tweakListOptions != nil { tweakListOptions(&options) } return client.CoreV1().PersistentVolumeClaims(namespace).List(options) }, WatchFunc: func(options metav1.ListOptions) (watch.Interface, error) { if tweakListOptions != nil { tweakListOptions(&options) } return client.CoreV1().PersistentVolumeClaims(namespace).Watch(options) }, }, &corev1.PersistentVolumeClaim{}, resyncPeriod, indexers, ) } func (f *persistentVolumeClaimInformer) defaultInformer(client kubernetes.Interface, resyncPeriod time.Duration) cache.SharedIndexInformer { return NewFilteredPersistentVolumeClaimInformer(client, f.namespace, resyncPeriod, cache.Indexers{cache.NamespaceIndex: cache.MetaNamespaceIndexFunc}, f.tweakListOptions) } func (f *persistentVolumeClaimInformer) Informer() cache.SharedIndexInformer { return f.factory.InformerFor(&corev1.PersistentVolumeClaim{}, f.defaultInformer) } func (f *persistentVolumeClaimInformer) Lister() v1.PersistentVolumeClaimLister { return v1.NewPersistentVolumeClaimLister(f.Informer().GetIndexer()) } | Low | [
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/** * Created by nono on 16-2-19. * 作为titleList和contentList的桥接 * * 使用了百度的编辑器， 简化了富文本编辑方面的开发 * @desc 大概思路; * 解压和压缩的实现 * 主要的main方法， 整个编辑器的初始化和事件的控制， 以及导出等； * 左侧的视图， 右侧的可编辑内容； * 约定标题名不能为"封面"; * */ define(["Construct/TitleList", "Construct/ContentList", "EpubBuilder", "Construct/DublinCore", "Construct/Preview" , "Construct/Lang"], function( TitleList, ContentList, EpubBuilder , DublinCore, Preview, Lang) { var epub = new EpubBuilder(); var dublinCore = new DublinCore(); var titleView = new TitleList.TitleView({ el : $("#left-nav") }); var contentListView = new ContentList.ContentListView({ el : $("#content-nav") }); titleView.bind("create", function( index ) { contentListView.create("", index); }); titleView.bind("clone", function( index ) { contentListView.clone(index); }); titleView.bind("remove", function( index ) { contentListView.remove(index); }); titleView.bind("click", function( index ) { contentListView.click(index); }); titleView.create(""); /** * @desc 获取界面编辑器的数据, 作为titleListView和ContntListView的辅助方法; * @return {Object} {tocArray:[], contentArray:[]}; * */ function getData() { var tocArray = titleView.$el.find("ul input").map(function() { return this.value; }); var contentArray = contentListView.$el.find(".edui-body-container").map(function() { return UM.getEditor(this.id).getContent(); }); return { tocArray : tocArray, contentArray : contentArray } } /** * @desc 设置数据到view中, 作为titleListView和ContntListView的辅助方法; * @param {Array}, {Array} * [], [] * @example setData( [1,2,3,4], [11,22,33,44] ); * */ function setData( tocArray, contentArray ) { var _this = this; titleView.$el.find("ul").html(""); contentListView.$el.html(""); $.each(tocArray, function (i, e) { //添加左侧nav titleView.add($.trim(e)); //添加右侧内容; contentListView.create( contentArray[i] ); }); } $("input[name*=coverImage]").change(function() { var _this = this; if( util.isImage(_this.files[0].type) ) { var file = _this.files[0]; //判断文件格式是否是image/* var fileReader = new FileReader(); fileReader.readAsDataURL( file ); fileReader.onload = function () { $(_this).attr("coverImage", arguments[0].target.result); }; } }); $("#build").bind("click", function( ev ) { var data = getData(); ev.stopPropagation(); ev.preventDefault(); //获取目录结构，并合并到data中; $.extend(data, dublinCore.getDublinCore()); epub.exportToEpub(data); }); $("#open").click(function() { epub.importEpub(setData); }); //初始化默认语言; new Lang().init(); new Preview(); }); | Low | [
0.48806941431670203,
14.0625,
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Memorial Plaque: Egyptian eye in pavement Site: Egyptian eye in pavement (1 memorial) NW1, Hampstead Road This is a real puzzle. Looks like the palmette in the Euston Road, also in the borough of Camden. They are both outside very interesting and tourist-worthy buildings. Neither arrow is pointing at the building in question but the stones could have been reoriented during pavement works. So we wonder if Camden once introduced some sort of sight-seeing walk, marked by flag-stones like these? Which leads to the intriguing question - are there more? See House Sparrow for the latest news on this puzzle. The Carreras building normally charms people but not Ornamental Passions, who point out that its site was once the Crescent Garden for the Georgian Terrace behind. | Mid | [
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The Observer calls it one of the ten best boutiques around the world and their trademark reflects the same. l'aumentare di prodotti come i kit tatuaggi non permanenti, dai pi. Before you do that though, you need to read the guidelines and policy of a certain site. Sunglasses were essentially a product used as a protective shield for the eyes against the harsh rays of the sun. - Consult an expert: Everything can be done fast and effective by means of asking for professional advice; most especially with regards to the right cure and how to prevent cracked heels from persistently coming back. Highs are crisp and detailed without getting overly sparkly or harsh. Article Source: mai organizzato un viaggio all’ultimo minuto. I was hardly surprised -the much-heralded advances in girl's sports still haven't changed the attitudes of society toward girls and strength. Componenti di stile sono disponibili in un'ampia selezione, nonch. Web stores do not have any overhead cost and can pass the savings on to you. Fragrances for men are generally referred to as cologne. E Z Rack Color Bar as a Hair Color Organizer has several happy clients who are very happy with its products and its Hair Salon Equipment Sale services. + Monogram Macassar collection, the first LV Monogram Bags Line designed specially for men was introduced on the Louis Vuitton 2009 Fall and Winter Men. como as coisas que voce faz diariamente podem afectar o seu score. If you are brave, try the rather tasty dish, Tripas a moda do Porto, which is made of cattle entrails. nyası ile de yakından ilgili ve deneyimli kişilerdir. - united kingdom online shop features emerged along with something special to give its beautiful ladies. It is so simple to plug your charger into the cigarette lighter section of your car and charge your phone. The Easy-Flex Rubber Sole Resists Slipping 2" Illusion Heel from Moda Spana exudes exquisite elegance with its delicate ankle strap town and a dazzling metallic satin fabric. This gives retail outlets an edge over exclusive outlets of various brands. + There's a much higher consumer awareness for audiophile grade solutions. Nearly all tabletop ethanol fireplace are assembled, just slide the ethanol fireplace burner insert and attach the safety glass. Between her and those expectant faces was an Olympic barbell with plates big as manhole covers at either end, one hundred thirty-five pounds -more than she weighed and certainly not part of her everyday world; she was no jock -didn't even play any sports. These sunglasses are perfect gift for every occasion. - There are records of three in the 17th century, five in the 16th and eight in the 15th. Generally, celebrity men and women act as trendsetters when it comes to style and beauty and young men and women always wish to fill their wardrobe with the latest collection of the costumes introduced by world-known celebrities. All your doubts and queries will be answered in a matter of minutes. To betray someone you purport to love is unconscionable. + There are records of three in the 17th century, five in the 16th and eight in the 15th. While futuristic themes are immediately apparent in the collection, there were tell-tale signs of Andean influences, from the colorful fabric strips on one outfit, to the general style of facial painting and embroidery work on another piece. Top scarpe brands have already started displaying their artifice through fashion shows and in their show rooms it has become easy to provide guide lines. n personal; ten en cuenta que es muy estar siempre bien presentable y a la moda; otro aspecto indispensable es la seguridad, puesto que un hombre t. - Duradera maquillaje no es lo mismo que un tatuaje normal, pasando por las clases puede ayudar a asegurarse de que los que ofrecen el proceso de saber exactamente lo que est. If the stone is not so significant part of the ring, you may sell it for its scrap value to an online buyer. It is better for everybody to shop these kinds of goods on the web along with free delivery service and many other extraordinary features. One such accessory is a pair of stylish sunglasses. + A MELHOR RELIGI''O '' A DO CORA''''O, A MELHOR FILOSOFIA '' DE FAZER O BEM. Also, these headcalls are visually stunning, due to their all-metal and minimalistic pattern. The most recent addition to their line of V-MODA headphones is the Crossfade LP. The shopping trends and desire differ from occasion to occasion, gender to gender, and time to time. | Low | [
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Are really starting to harm the people by not giving them protection from actual pollution. Instead of going after actual pollution, the EPA is too busy going after the bogeyman of CO2, which is a harmless gas that exists naturally on our planet, much unlike the spill in West Virginia which is actually harmful to people. In this instance, we see how the mis-placed priorities of the EPA have actually caused harm to people now. This is proof positive that its time to get rid of the EPA and start over from scratch with an organization that is not going to waste our money on the following frivolous things: 1) Regulating things that are naturally occurring gases that nature emits more of than man. 2) giving lectures to green groups and eco-loons telling them how to sue the Government. 3) Giving away their funds to green lawyers who successfully sue the Government. 4) Going after random industries and giving a pass to others based on political considerations. 5) Arranging secret meetings to discuss with green groups the best way to defraud our Government. Most of this is explicitly illegal, and just like the IRS scandal, its probably going to result in no one going to jail under a corrupt administration that does not believe in sending those guilty to jail. We deserve this Government in the end, and we deserve what it does because we elected a Chicago style politician to office twice. Its no surprise than that corruption like this is so rampant throughout Government, the only question is, what are we going to do about it? Are we the people going to accept a Government involved in RICO violations and a wastage of our money to special interest groups? Or are we going to put a stop to it? A lot of people are criticizing the president over the Syrian conflict and they state that he has no nerve and he will not do what “American needs to do” as if bombing some despot in a third world is what America should be doing. Now granted, doing nothing like he has is sometimes the best course of action. And in so doing nothing, the president has accomplished the following: Not just a blight on the landscape, but the materials used create their own environmental hazards. It could easily have been gas power, using much less land and materials, like the one we have in Broome. An idyll blighted by 18,000 solar panels: Seen from the sky, the reality of alternative energy Row after row, this astonishing array of solar panels has completely engulfed an enormous 30-acre field in the heart of the countryside. As this aerial photograph reveals, acres of beautiful Hampshire countryside have been blighted as a result, by 18,000 solar panels. The solar farm covers a staggering 30 acres of land creating a massive eyesore in the centre of an otherwise picturesque view. The solar farm, Cadland Estate at Fawley in Hampshire, covers a staggering 30 acres of land creating a massive eyesore in the centre of an otherwise picturesque view Yep, its proven that when Obama stated this in his climate change speech on June 23rd: So the question is not whether we need to act. The overwhelming judgment of science — of chemistry and physics and millions of measurements — has put all that to rest. Ninety-seven percent of scientists, including, by the way, some who originally disputed the data, have now put that to rest. They’ve acknowledged the planet is warming and human activity is contributing to it. That 97% number he used comes from the paper written by John Cook of Skeptical Science. I guess I could point out how Cook is not a scientist, but rather a cartoonist, but why waste the fun in seeing who the president of the US listens to on science matters. Recently, we found out that the owner of that blog, John Cook Photoshops himself and his friends into NAZI portraits for fun. The first picture of Cook himself is here: It’s not a bad picture I guess if you enjoy dressing yourself up as a NAZI. But maybe photo-shopping your picture on top of an old nazi uniform does not make you a NAZI. Perhaps in some bizarre creepy fashion show they thought it was funny. Always a possibility, but as of yet we have not heard why they thought this was a good idea, or any justification for that matter, I am not going to state flat-out that we know what Cook is, but the picture HE had on his website originally does show him in a NAZI uniform. What are we supposed to assume by this if he remains silent? I am just baffled that anyone would take advice on science from someone like that I guess. In other words, the leader of the free world takes his advice from a cartoonist from Australia who thinks its fun to photo-shop his picture on top of an old NAZI picture? The more you read into the science of global warming, the more bizarre it gets. I expect loads of more fun as the current stasis of our climate system continues. This question was asked of the British Government recently and here is their reply: RE: Empirical measurement of fossil fuel displacement by wind power Thank you for your Freedom of Information requests received on 1 May 2011. Your requests, received 1 May from Dr John R. Etherington “Has any attempt been made to relate the short term variation of ACTUAL fuel-use by load-following plant to metered wind power feed-in? If so, can the figures be provided, expressed as tonnes of CO2 actually saved per MWh of wind generated electricity? If no such attempt has been made why not, as carbon-fuel displacement is the only justification for deploying expensive, and covertly subsidised wind power?” We have considered your request in accordance with the Environmental Regulations 2004 (EIRs) as the information you sought disclosure of, does in our view, fall within the definition of `environmental information’ as stated in the EIRs. We have now completed searching for the information you requested. In order to determine the relation of the short term variation of actual fuel-use by load-following plant to metered wind power feed-in, we would need to know what fuel use would have occurred in the absence of wind power (i.e. the counterfactual). This counterfactual (the fuel use in the absence of wind power) depends on the proportions of nuclear, CCGT or coal investment that are being displaced by wind power and the effects on their subsequent operation. Such a counterfactual can only be calculated by modelling a world without wind power and by subsequently comparing it to the current data on emissions from the grid. No such analysis has been carried out by DECC. And so we do not actually know the answer to that question. I think this response by the DECC is important for everywhere to realize the truth. No one actually knows the answer on whether wind turbines decrease CO2 emissions and likewise decrease other emissions from normal power plants. In this insane zeal to decrease pollution of all types we have grabbed this delusional thought that we must build the industrial monsters and in the end its nothing but a waste of time and resources. So why do people think they decrease CO2 emissions? That belief comes from the belief that we should only count one side of the equation, namely the side that shows the benefit of Wind Turbines and not look at how it increases emissions as well due to its intermittent nature. The numbers run at the above link indeed show that its likely that adding wind above a certain threshold actually INCREASES CO2 emissions and the best case scenario turns out to be 10% savings assuming everything works perfectly. So somewhere between -10% savings and 10% savings is the probable result of adding wind to the grid in terms of CO2 emissions. In other words, it’s just as likely that we save zero in CO2 emissions than we do not. Until someone actually does the difficult job of figuring out the real result, adding more wind to the grid is a fool’s errand that only accomplishes higher power bills for the poor and tax breaks for the rich. Other than the regressive tax that wind really brings, which is probably good for the rich who buy into these pork barrel products, there is not one good thing to their name. I think its time to answer this question once and for all so that we stop enriching our rich land-owners at the cost of the poor for no reason. The entire concept of being scared of change is what drives and motivates people to be fearful and even paranoid in the modern environmental movement. The reason for this at its heart is that people are fearful of change. And nowhere has society changed more than in modern society where we have gone from an agrarian society to a modern office worker society in just 100 years. This dramatic change has left people without an outlet to discuss each change individually and so these people no longer promote such ideas as conservation and science when they advocate for change. And so these people have turned into fear hustlers and fear promoters who spread their fears to everyone else under the guise of “the environment” or even homeland security. These calls to change the world are based on the simple concepts of fear and paranoia. The only argument left standing is that we should build these monsters because they are pretty. You can talk to any green and they will go on and on about how they admire the aesthetic view of them from afar and how they want to gaze upon their naked faces in the glowing embers of sunset. | Low | [
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Q: Appending images using python and imagemagick Most people recommend "wand" when it comes to imagemagick for python but how can I append images using it in python ? I want to add lables to bottom of images using imagemagick in python : http://www.imagemagick.org/Usage/annotating/ but wand api seems to be very basic and doesn't have lots of imgemagick commands including labels and appending. Is there any other way to use imagemagick in python ? my images are png type and are BytesIO streams inside the python code not files so I can not pass them to imagemagick using command line and can't save them on any temporary file either. A: I'm not really sure what your asking for, but I'm guessing you want to write a label "below" an image. Here's an example with the wand library. from wand.image import Image from wand.compat import nested from wand.color import Color from wand.font import Font with nested(Image(filename='logo:'), Image(filename='null:')) as (source, text): text.font = Font('Impact', 64) text.read(filename='label:Hello world!') largest_width = max(source.width, text.width) offset = (largest_width - min(source.width, text.width)) / 2 with Image(width=largest_width, height=source.height + text.height, background=Color('WHITE')) as dst: dst.composite(source, 0, 0) dst.composite(text, int(offset), source.height) dst.save(filename="output.png") Overview with nested(Image(filename='logo:'), Image(filename='null:')) as (source, text): Create two images. You would be responsible for replacing logo: image with your ByteIO buffer. The null: image is a placeholder for allocating a wand instance. text.font = Font('Impact', 64) text.read(filename='label:Hello world!') This defines the typeface & text to draw. The label: protocol can be replaced with caption: for additional behavior(s?). with Image(width=largest_width, height=source.height + text.height, background=Color('WHITE')) as dst: Create a third "blank" image that is large enough to include both images. dst.composite(source, 0, 0) dst.composite(text, int(offset), source.height) Copy the image data from the source & text to the new image. | Mid | [
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Sports Interactive Community Search [FM12] The complete world encyclopedia of insults shouted at virtual football players If this is your first visit, be sure to check out the forum FAQ and the House Rules and Forum Guidelines. You will have to register before you can post. If you find your registration is rejected, please try again using a different username. To start viewing messages, select the forum that you want to visit from the selection below. [FM12] The complete world encyclopedia of insults shouted at virtual football players Good night ladies and gentlemen, welcome to my first venture into FM12 as I'm literally yet to do a single match - just bought it last Friday and hadn't touched not even the demo before. The interface doesn't look as daunting as you all made it to be, as I've figured out how to browse players and teams by now. After being used to the heights of fame and fortune through the last few seasons of my FM11 adventure, it's time to go back to earth and start from the bottom again, almost certainly I'll despair at how rubbish my new players are compared to the likes of Bagayoko and Duval. However I do not have a clear concept of where I want to go with this career, it's meant to be some sort of journeyman but if I fancy a club I'm free to stick there for 10 seasons if it happens. I don't have any preset tactical ideas I want to implement neither, this time. I'm approaching this with an open mind. Format-wise I'm going to try monthly updates for a while, taking some hints from other careers around, and start from there. I am starting unemployed, automatic experience, an insane amount of leagues loaded (think I got carried around there). Already found myself a club and I will expand on it soon. Look at this, it's got a running track! A HUGE running track! I'm going to have to exert some proper pressure on my vocal chords to get those insults through to the field! I am baffled at how in demand a football manager with no experience whatsoever is these days. I got plenty of offers from many corners in the world. To be honest I could've started lower than in the swiss second tier, the Challenge League with SR Delémont. They've got some fairly handy players already, and it's a professional club. I had loaded stuff like the full scottish or swedish ladder so definitely expected a shittier job to start with. I did have one offer from a 4th tier swedish side but they were mid-season, and leading their league, so it didn't feel right to go there and receive the plaudits for a job already done. Other options were Ukraine were some random club had youngsters valued like 500K€+ already; Brazil to manage Santo André who are way too big and known a club to start with; and Mexico to some club loaded with cash but somehow in the 2nd tier. I've never managed in Switzerland and this looks like a good place as any to start. Now who are Delémont? I only know more than you because I've read the Wikipedia artice. They're a yo-yo club in the french-speaking part of Switzerland who has got promoted and relegated through the last decade more times than I can count. They've briefly been in the top tier but were rubbish, and briefly flirted with the 3rd tier too, which is unplayable in FM. It's not entirely unlikely I may make them fall into there too, because the club is predicted 9th by the media in this 16-team league, and the bottom SIX sides go down. Now that's going to make for an epic relegation battle. Thankfully we already have some talents in our squad to help us escape it, albeit the squad is hilariously unbalanced: Likely key players: Johnny Szlykowicz (AMC) - Wow, that is a much much better player than I'd ever expected to find at this level. The undeniable star of this side. I'm just pissed his name is so unpronounceable because I may have to write it often. Mickaël Rodriguez (ST) - Recent history tells me he's scored 18, 19 and 22 goals in the last 3 seasons for the club. I believe it, he looks handy. Luca Ferro (GK) - Not sure how he'll get on with all the frenchies in the side but that looks a decent goalie. Finances and transfers 52K€ in the bank, they give me 32K€ for transfers, and a monthly wage budget of 64K€ (61.5K€ of it used), which is huge and I can't quite figure out why, where on earth is the money going to come from to pay this lot. I need to bring in lots of players for many positions and this may mean having to sell someone to fund it. A positive thing about this league is that the only foreign players restriction is a maximum of 10 Non-EU players. That's a HUGE freedom compared to most nations I've managed in... Goals for this season I have no idea. Avoid relegation, yes surely. Better than the media prediction of 9th would be good. Gustavo Pinedo (AMR / MR) (1K€) – A better signing than Alic on the other wing but I’m not fully convinced, has serious problems with teamwork, composure and stamina. Transfers (out) Josip Budimir (free), Muharrem Xhaqku (14K€), Sofian Allali (5K€). Fixtures Friendly: Aalst 0-2 Delémont (Macio, Baudry) We had a friendly in my very first day at the job. Set up a 4-2-3-1 based on my FM11 Roma formation, told the assman to choose the players, and off we go. I was quite surprised that it worked! Friendly: Delémont 1-4 Clermont (Chappuis) Or maybe things aren’t going to be that easy. We fell apart in the second half. Friendly: Delémont 4-0 Blue Stars (Rodriguez, Baudry(3)) Just the routine friendly against terrible opposition to boost morale. I already had some of my signings by this point, but it was the 38 year-old winger Baudry who somehow bagged an hat-trick. Challenge League: Kriens 1-2 Delémont (Ochs, Rodriguez) An away win made for a great way to kick off our league campaign. Kriens nearly engineered a comeback from 2-0 down but we held on. Challenge League: Delémont 1-0 Lugano (Szlykowicz) Ermin Alic did miss a penalty early on, but I think we were quite lucky to come out of this with a win against tough opposition. Our star Johnny finally used his talent by scoring the winner, even if it was just a tap-in. 2 wins out of 2 is a nice way to start, albeit I felt we were unconvincing in both matches. Not happy with the squad yet as my tactics rely a lot on wingers and we’re very bad in that department – besides I went mad with wages and am now way over the wage budget already. Challenge League: Delémont 3-0 Chiasso (Szlykowicz, Rodriguez (2)) And suddenly it’s as if nothing had happened, our 2 stars playing to their best on an emphatic win. Good game from new signing Duventru too. Challenge League: Delémont 1-0 St. Gallen (Szlykowicz) An excellent gritty performance and win over the leaders and best side in the league. Player of the Month Coin flip between him and striker Mickael Rodriguez as both have been on magnificent form with 4 goals and 2 assists each this month. Competitions Challenge League: Schweizer Cup: First round is away against lower league side Menzo Reinach next month. Summary A bizarre month where we were both excellent and dreadful, nothing in-between. Thankfully our poor moments did not make us miss the train at the top and we’re fighting for the early lead of the table. Finances-wise I’m following a very bold risky strategy as I’m way over the wage budget and have spent some considerable chunks of money on contract terminations. 347K€ on the red. Venn Touré (DM / MC) (free) – I wasn’t intending to hire more players with the wages being so high already, but with Spilacek being given a leave of absence, and now firmly playing regularly a 2 DM formation, I really needed a 3rd available DM in the squad. Transfers (out) Jules Hamidou (1K€) – I had about 6 players in the pecking order ahead of him, that’s more wages saved. Fixtures Challenge League: Winterthur 2-0 Delémont An uninspired performance in a difficult field facing early season promotion rivals. Challenge League: Wohlen 2-3 Delémont (Bouziane, Pinedo, Germann) We should’ve won this by a bigger margin, nice to see a confident performance away from home. Player of the Month Man of the match against both Menzo Reinach and Wohlen, quite clearly so far my best signing. Competitions Challenge League: Schweizer Cup: Second round opponents are FC Luzern, which isn’t good news as they’re a Super League side. At least the match is at home, next month. Summary A short month in terms of fixtures, but one that spawned a tough test as midfield star Johnny Szlykowicz injured himself in training and the expected stoppage is between 2 and 3 months. Thankfully Bouziane has filled his shoes nicely with 2 goals in his first 2 matches but let’s see if there’s not an impact in the team’s performance in the coming challenges. Challenge League: Delémont 3–2 Stade Nyonnais (Duventru, Djimsiti, Macio) Action-packed, close game, but we scrap an important win over upper midfield challengers – and take the table lead as St. Gallen lose points. Schweizer Cup: Delémont 2–1 FC Luzern (Pinedo, Djimsiti) Awesome result! We pulled an excellent deserved win over a Super League side, albeit they had a man sent off midway through the 2nd half, but we also had 2 men injured after having made all 3 subs, and came back from an equalizer to make it 2-1 late on, in a corner. Unfortunately Gustavo Pinedo’s injury will stop him for 4 to 5 weeks. Challenge League: Brühl 0-2 Delémont (Djimsiti(2)) Better the result than the performance tbh, we should’ve been more convincing against the worst side in the league. Player of the Month 4 goals in 4 matches this month, superb attacking performance from my teenage centre-back. I swear I don’t use any dodgy corner routines, he’s just been inspired. Competitions Challenge League: Schweizer Cup: Very pleased to have beaten a top tier side, next up is fellow Challenge League side Aarau, at home, in the third round (round of 16). Summary Excellent month as the team hits a peak of form, grabs the lead at the top then consolidates it, now with a 3 point gap. Fantastic result in the cup too. I feel we’ve been flattered by the calendar though, that was 3 home matches and a away game against the poorest side in the league. On the other hand, we haven’t felt the absence of our best player Johnny at all which is greatly encouraging. Challenge League: Delémont 1-1 Bienne (Rodriguez) Disappointing result against poor opposition, we were uninspired and even conceded an equalizer against 10 men. Challenge League: Bellinzona 1-1 Delémont (Conteh) The opposition were the better side here, albeit we could’ve won after leading during most of the match. Winterthur overtook us in the table, and we drop to 2nd. Schweizer Cup: Delémont 3–0 Aarau (Rodriguez (2), Duventru) A far far better performance this time, Rodriguez and Duventru both had excellent games and we’re through to the quarter-finals. Player of the Month A brace against Aarau including an excellent solo goal, and another goal against Bienne make him a clear choice in a month where not many players were inspired. Competitions Challenge League: Schweizer Cup: Quarter-finals opponents are Zurich at home, next February. They’re a top tier side but penultimate in the table, we have an outside chance I think. Summary Bit of a form blip here and we lose the table lead, but we’re still firmly in the mix upfront as things are shaping up for a three-way fight between us, Winterthur and St. Gallen. Nice to keep the cup run going, nice outside chance of reaching the semi-finals here which would be a quality achievement. In terms of finances I’m starting to get seriously worried, we’re now a very alarming 800K€ in the red and I may have to sell someone, possibly young centre-back Jimmy Kollar who has potential but is poor in the air and has been moaning about not getting any games. Challenge League: Delémont 8-1 Vaduz (Rodriguez (3), Duventru (2), Szlykowicz, Djimsiti, Bouziane) Wow. An amazing performance as we steamrolled past Liechenstein’s most famous side with by far the season’s best match so far – it’s going to be difficult to top this. Challenge League: Delémont 3-0 Kriens (Rodriguez, Touré, Nogueira) Another very good game, we are on a high here. Unbeaten for 8 games now. Friendly: Delémont 1-4 Basel (Hulmann) The first in a series of home friendlies against bigger sides, in an effort to keep match fitness and get some revenue from attendances during the winter break. More games like this and our confidence may be ruined though. Friendly: Delémont 2-1 Sion (Germann, Szlykowicz) Results are unimportant in these matches but always nice to beat a side from an higher level. Player of the Month Keeping up with his impressively consistent stream of goals, this time got this season’s first hat-trick in official matches for Delémont, then scored again versus Kriens. Is now the top scorer in the league. Competitions Challenge League: Schweizer Cup: Still waiting for the quarter-finals match next February. Summary Short month as we enter the winter break and past the halfway mark of 15 league fixtures, but those were 2 superb performances and results, even if we’re in the same situation we were in before in the table. Next up, no competitive fixtures in January as it’s the winter break. Most definitely a very boring month, the winter break sucks. I tried to sell players to stabilize the finances, but nobody wants them for a decent price so I’m not bothering. Now already 1.1M€ in debt, ouch. Looks like your doing really well so far and some good players in their. Best of luck for the rest of the season! Originally Posted by rancer890 It all seems very easy for you so far. Keep it up! Originally Posted by B.W.G Doing very well so far,hope you can continue through the season with sort of form. Thanks, I'm surprised it has gone this well, the barely changed tactics engine from FM11 has helped me. I'm sort of worried that if we don't get promotion this season the club may collapse financially though. Challenge League: Lugano 1-1 Delémont (Conteh) Dullest match I’ve ever seen in FM, I’m amazed somehow there were two goals. There were only 2 shots the whole of the first half! We lost further ground to Winterthur at the top of the table. Challenge League: Delémont 3-1 Etoile-Carouge (Steinmann, Duventru, Szlykowicz) Could’ve been a total disaster as we found ourselves losing at home and being comprehensively outplayed by the league’s worst team, but we ultimately pulled through. Player of the Month Man of the match and scorer against Etoile-Carouge. Competitions Challenge League: Schweizer Cup: Knocked out in the quarter-finals by Zurich. Summary Things got started again, first with the disappointment of the cup defeat, and losing ground to the leaders in the table, but given that Lugano are one of the best sides in the league it was alright to get a point away. Most importantly, the board injected a mammoth 625K€ into the club’s finances so the accounts look a lot… less bad. Matthew Edile (DL/WBL) (free) – I had to stretch my already stretched wage budget even further, and left-back wasn’t one of my biggest priorities, but an excellent signing who will greatly boost the team filling in for the currently injured Patrick Ochs. Fixtures Challenge League: Delémont 1-3 Locarno (Germann) Ouch, terrible game and result. We can’t afford matches like this if we want to go up. Challenge League: Chiasso 2-1 Delémont (Rodriguez) This month really isn’t going well, the morale has gone down, we thrown away a lead and a golden chance to profit on a couple of slip-ups from former leaders Winterthur – instead we’ve been overtaken by St. Gallen now too. Challenge League: St. Gallen 2-0 Delémont We actually did pretty well in the toughest stadium to visit in the league, but the woodwork, an unbelievable amount of missed one-on-ones by our right winger Pinedo, and clinical finishing from St. Gallen pretty much killed our promotion dreams. Challenge League: Wil 0-3 Delémont (Duventru(2), Djimsiti) A team meeting that went very well boosted our spirits into getting this much needed superb result. This game was originally postponed due to snow, first time I’ve seen this happening since the days FM was still CM. Challenge League: Delémont 3-2 Winterthur (Pinedo, Duventru, Conteh) A spectacular match and a very important win over promotion rivals. They pulled level from 2-0 down just before the break, but centre-back Conteh still managed to score the winner for us in a 2nd half corner. Deserved winner, too. Player of the Month It's Dylan yet again on very good form, man of the match in both our wins versus Wil and Winterthur, with 3 goals in those games. Competitions Challenge League: Schweizer Cup: Knocked out in the quarter-finals by Zurich. Summary A disastrous month as we nearly fell for good from the fight at the top with 3 consecutive defeats, thankfully we bounced back nicely with a win away to very difficult opponents, then beating one of our main rivals to come within 1 point of the playoff place again. We’re in a considerably worse position now than last month, but it’s still wide open with 7 fixtures to go. Challenge League: Delémont 2-1 Wohlen (Duventru, Szlykowicz) Tougher than expected, we went into half-time losing by 1-0, but ultimately got the win. Challenge League: Stade Nyonnais 1-2 Delémont (Pinedo, Edile) Despite playing with 10 men we got a crucial last-minute winner from my recently signed left-back, and again boost past Winterthur in the table as they lose to St. Gallen. Challenge League: Aarau 1-1 Delémont (Garat (og)) I’m happy to get an away point in what was a fairly poor performance from us. Challenge League: Delémont 1-0 Brühl (Djimsiti) Decent showing, we could and should’ve scored more against a team already relegated. Player of the Month Another good month from our loanee teenage centre-back, scoring the winner against Brühl. Competitions Challenge League: Schweizer Cup: Knocked out in the quarter-finals by Zurich. Summary We were pretty much unconvincing in every match, but got 10 points from 12 possible so I can’t complain – particularly with Winterthur doing us a massive favor by imploding out of contention, almost mathematically so. 3 fixtures to go which will decide everything now between us and the mighty St. Gallen, if we don’t get direct promotion I don’t see us going up as we’d face Sion who are much better than us. It's pretty much equivalent, 2 away games, 1 at home, 2 to relegated or near-relegated sides, 1 to mid-table opponents. Though something unexpected just happened, St. Gallen lost their home match and we barged through to 1st place with 2 games to go! Challenge League: Bienne 1-3 Delémont (Duventru, Pinedo, Rodriguez) As clinical as it gets as we score 3 in our first 5 shots. We guarantee at least a playoff spot, and remarkably St. Gallen lose at home to Wohlen gifting us the table lead! Challenge League: Delémont 4-0 Bellinzona (Pinedo, Bouziane, Djimsiti, Touré) An emphatic win with 4 different goalscorers, what an excellent way to build confidence and morale into the final decisive fixture. Challenge League: Vaduz 1-5 Delémont (Djimsiti (2), Germann, Pinedo(2)) So it all came down to a crazy finale in a trip to Liechtenstein. We needed a win or at least a result as good as St. Gallen’s, but found ourselves losing by the 3rd minute and it remained 1-0 all the way until half time, as St Gallen were 0-0. It was looking like a massive choke from us, but then Djimsiti tied the game. Not enough – St Gallen were now winning at Aarau. Then to my delight Germann scored and completed the comeback. Or so I thought, we had an amazing second half and scored 3 more goals, whereas Aarau turned their game too! We have just been promoted to the Axpo Super League! Amusingly, this game relegated Vaduz, we had already been very mean to them with a 8-1 win a few months ago… Player of the Month Amazing end of season form from the bolivian winger as he scores 4 in 3 games. Competitions Challenge League: I’m amazed Winterthur managed to drop so badly in the end that they finished 12 points behind us! Eventually St. Gallen beat Sion in the playoff and went up too. Schweizer Cup: Knocked out in the quarter-finals by Zurich. Thun beat Servette in the final. Summary That was an awesome season, it looked like we had thrown the league a couple of times – particularly after those 3 consecutive defeats in early March – but we came good at the right time and found the mental strength to overcome what could’ve been a catastrophic choke in the Liechtenstein finale. I didn’t sign for the club expecting to get promotion on the first season, and it’s going to be pretty difficult in the Super League as it seems much more competitive. I took our finances into a pretty shambolic state so it’s going to be hard to sign players good enough for that level, but I suppose it’s also going to give us more income than another year here, so it’s always nice to go up. Thanks folks, I think I'll need some luck next season, looks like quite a step up, specially given the finances. I'd consider buggering off into another club already but it wouldn't be fair to Delémont, I want to sort them out first. This is the formation and instructions we used for most of the season, nothing out of the ordinary, fluid and with an emphasis on pace, balls on the ground, and passing into the runs of the mobile forward and the wingers – but also a balanced formation with 2 DMs. Usual shouts: “run at defence” and “work ball into box”. An alternative formation for tougher matches pushed the AMR and AML into MR, ML positions with “Counter” strategy and a little less fluidity; whereas there was also a version of the 4-2-3-1 with one of the DMs moved into the MC slot but I rarely used this. Also used: “attacking” strategy when losing, and “retain possession” shout when winning in the final minutes of a game. Squad These are the numbers that the Delémont players set: Top 5 key players of the season 5. Gustavo Pinedo (AMR) – Took a while to impress, but came really good at the end of the season, I thought his very bad teamwork and composure would cause problems but he added value to our attack. 3. Mickaël Rodriguez (ST) – Our top scorer on 16 goals, unfortunately starting to get a bit old, not sure he’ll be good enough at the top level next season. 2. Berat Djimsiti (DC) – This young centre-back will have a stellar future for sure, I’d like to renew his loan but doubt I’ll pull it off. 11 goals was a superb tally, certainly his performance in set pieces was important for us. 1. Dylan Duventru (AML) – Definitely our best signing as the French winger terrorized defenders all season long in the league. 11 goals and 17 assists says it all. Match of the season No doubt our better performance as we helped sink the morale of Liechtenstein’s top side – the 5-1 of the final fixture, again versus Vaduz, wasn’t bad neither. Awards Challenge League Manager of the Season – Cláudio Alegria (1st) Challenge League Team of the Season – Berat Djimsiti, Gustavo Pinedo, Dylan Duventru, Johnny Szlykowicz, Mickaël Rodriguez Challenge League Young Player of the Year – Berat Djimsiti (2nd) Challenge League Midfielder of the Season – Dylan Duventru (1st), Gustavo Pinedo (2nd) Challenge League Striker of the Season – Mickaël Rodriguez (1st) A lot of contracts ran out, I agreed mutual termination, released or sold by 0€ to other clubs quite a few players so this is a very long list: Sebastião Nogueira, Pape Sarr, Sid Bouziane, Kewullay Conteh, Radek Spilacek, Abdul Iddi, Garry Germann, Florian Hengel, Ermin Alic, Luca Ferro, Cédric Hulmann, Dylan Choulat, Gaetan Frund and Macio. Also the loans of Berat Djimsiti and Dominik Stadlbauer ended. A few of those were first team players, particularly the centre-backs Conteh and Djimsiti, the latter of which a huge part of our promotion success, let’s see if we don’t miss him. FixturesFriendly: Kapfenberger 0-3 Delémont (Duventru(2), Jarosch) I forgot to set up the friendlies myself and ended up with a nonsense schedule. Got it going started well though. Friendly: Cambuur 1-0 Delémont Not quite as good. Friendly: Austria Lustenau 3-0 Delémont Even worse. Friendly: Veendam 1-1 Delémont (Lowinsky) Already the final friendly, and not the morale-booster I usually set up. Super League: Delémont 1-0 St. Gallen (Rodriguez) A good start with a win despite playing with 10 men for a while as Jarosch got himself sent off, but this is one of the easiest fixtures of the year, at home against our former Challenge League rivals. Super League: Young Boys 1-0 Delémont Good showing in one of the toughest fixtures of the season, we were unlucky to lose. Player of the Month Good start to his life in Switzerland from my new Spanish centre-back. Competitions Axpo Super League: Schweizer Cup: First round to be drawn late August. Summary The squad’s looking better than I imagined, we got a lot of talented signings and I’m now cautiously optimistic of avoiding relegation, particularly with a decent start in the league. Finances look settled, still 770K€ in the red but this league gives rather good TV revenue, I think the news item said something like 1.5M€ through the season. Super League: Thun 0-0 Delémont Plenty of chances for both sides, we even hit the bar in injury time, but it’s the first 0-0 of my career. Super League: Lausanne 1-1 Delémont (Roberts) We did well to equalize late on, if we had lost Lausanne would’ve caught us from last place. Player of the Month Starting to come good, scored 3 of the team’s 5 goals this month. Competitions Super League: Schweizer Cup: First opponents are lower league side Chippis, away. Summary Looking good, it’s awesome to be in 3rd place, but in this extremely tight league we’re only a mere 3 points above the dreaded 10th place which gives relegation. It all promises to be a very exciting season. Super League: Delémont 1-0 Grasshoppers (Pinedo) Lucky to scrap a late winner in a corner in a dull uninspired game. Super League: St. Gallen 2-4 Delémont (Szlykowicz, Sani(3)) Wow. We were playing awfully and being comprehensively outplayed, even briefly losing by 2-0, when Emmanuel Sani decided to have a blinding game scoring an hat-trick, one of his 3 goals a sublime lob. Super League: Luzern 5-2 Delémont (Szlykowicz, Sani) Wild goalfest as we paid the price for trying to play an open game. A very abrupt end to a great run. Moreover Gilson Silva picked up a 10 month injury… oh dear. Super League: Delémont 1-1 Young Boys (Rigo) Good to get a point against a top team, not so good to throw away a lead against 10 men. Player of the Month Could’ve been Emmanuel Sani for that astonishing performance versus St. Gallen, but Johnny scored and/or assisted in every league match this month. Competitions Super League: Schweizer Cup: Next up are FC Wabern. Who? Summary I’m quite pleased with how things are going, despite being well aware that 16 points in 11 games isn’t a tally that would usually give us 3rd place. We’re benefitting from the fact no team in this league other than Basel gets a decent consistent run of form. Super League: Delémont 0-0 Servette We were lucky to get out of this with a point after a dreadful home performance against a team that dropped to dead last with this result. Player of the Month Not sure whether I should be happy he’s outperforming my theoretical better forwards, or worried that we seem to be relying on a third-choice 32 year old striker and his… hints of pace. Either way, 4 goals this month. Competitions Super League: Schweizer Cup: Third round opponents are Bellinzona who we faced last year in the Challenge League. Summary Boring month with only 3 competitive matches. Plenty of the season to come up yet and I believe we need to cling on to that 3rd place for as long as possible, scrapping as many points as possible from every match, as we may really need them later on. The whole league feels like a giant relegation battle – and then Basel. I released on a free the veteran midfielder Anthony Sirufo, who was about to retire at the end of the season anyway. Fixtures Super League: Basel 3-0 Delémont I didn’t even bother to attack to avoid being battered. It didn’t work. Super League: Delémont 2-1 Thun (Szlykowicz, Jarosch) Quite pleased to grab a league win again, it’s been a while. Particularly against the 2nd placed in the table. A team meeting helped to motivate the team for this very scrappy game. Super League: Delémont 1-0 Lausanne (Ortlechner(og)) Another lucky win in an extremely tight game – we benefitted from an early owngoal. I’ll take the 3 points. Player of the Month Everyone was very average this month so better pick my top class but unspectacular player who was suspended for the Basel shambles, and then did well in the other two matches. Competitions Super League: Schweizer Cup: Bellinzona away right up ahead in the 1st of December. Summary Well the trouncing at Basel was to be expected, otherwise the 2 wins were a great boost even if we were quite lucky in both games. The field is starting to spread apart a little in the league and while it’s still early days, the top 5 places give European qualification, even the 2nd place goes to the Champions League. I’m daring to starting to think of it a bit. Mirko Barbero (DM / MC) – I needed a backup DM after releasing Sirufo on a free and this kid fills that role, whilst also having 4* of PA. Juan Albín (AMC / AML, ST) – I sort of bankrupted the club with the loyalty bonus and agent fee to bring him in, but it’s got to be worth it, he’s easily the most talented played in my whole squad now. 5* of CA… Fixtures Schweizer Cup: Bellinzona 2-3 Delémont (Sani(2), Duventru) I’d like to thank our opponents for opening up highways for Emmanuel Sani. Nice to see Duventru scoring his first of the season too, he’s been underwhelming compared to last year. Super League: Delémont 1-4 Luzern (Pinedo) Would be the understatement of the century to say everything that could’ve gone wrong, went wrong. By 10 minutes we were losing 2-0, and they’ve only had had one shot – Guillaume Katz scored in his own goal the other one. Then 20 minutes later he scores another owngoal. Awesome. Super League: Grasshoppers 0-0 Delémont Superkeeper bug. Thankfully the superkeeper played for us – Sebastién Robert. I can’t believe we went out of this without conceding, it got to a point it was funny, they even hit the woodwork twice in succession. Friendly: Delémont 0-2 Basel First of the winter break friendlies – and it’s not like I thought we’d win this one. Player of the Month Emmanuel is amazing on his day, it’s just a shame his days come once every 3 months or so. It came against Bellinzona with a brace and MOM performance. Competitions Super League: Schweizer Cup: Still waiting for the St. Gallen game in the quarter-finals. Summary Not a very positive month, we were amazingly bad against Luzern, wildly lucky to get a point from the hoppers, barely scrapped the win against lower league Bellinzona in the cup. And dropped a bit off the pace at the top of the table, now down to 4th. The good news is we seem clear from relegation at this stage, we’re at the halfway mark still but looking much closer to Europe than to a return to the Challenge League. I’m on holidays this week and looking forward to play a little faster, hopefully finish this season. I’m playing this career very slowly due to lack of time and I don’t want that to kill my motivation because what I really fancy in FM is going way into the future. Super League: Delémont 1-1 St. Gallen (Ammari) Slightly unlucky not to win this but we were not convincing. We lose Pinedo to an injury for at least 7 weeks – when he was on blindingly good form and there’s no other decent right winger. Super League: Young Boys 1-2 Delémont (Rigo, Duventru) A great win in a difficult stadium even if Young Boys may be struggling. Player of the Month Magnificent game against Young Boys with 2 assists, given a 9.0 rating. Competitions Super League: Forgot to take a screenie. 4th place. Schweizer Cup: Still waiting for the St. Gallen game in the quarter-finals. Summary The winter break sucks arse and feels like a waste of time playing, no progress in over 2 months basically. I think FM’s a bit too slow so have removed a bunch of lower leagues from a couple nations that I don’t think I’ll be visiting at that low a level. Schweizer Cup: Delémont 1-1 St. Gallen (a.e.t.) (4-2 pens.) (Sani) Took us 120 minutes, but we’re in the semi-finals. We got an extra-time lead through Emmanuel Sani but Matthew Edile nearly thrown it all away for us as he got a red card and then St. Gallen equalized from the free-kick. We held on for the remaining 10 minutes, it went to penalties, and despite Roberts missing the first one, we scored all the others and beat St. Gallen. Super League: Delémont 0-3 Grasshoppers Another disaster. No wonder, we had about half of our team injured or suspended, and the other half exhausted from the mid-week cup marathon. Player of the Month Couple of very impressive defensive performances from the young midfielder this month. Competitions Super League: Schweizer Cup: The semi-final is away, and against Thun. Summary We’re falling apart. Champions League? Yeah right. This is still quite a positive season, but if I stick with this club for next season (and at this moment I’m leaning towards that), I’ll look into making a large reevaluation of the squad. Looks like Laussanne is going down, 10 points adrift. Maybe make a push for EL? you;re only 3 points away. Yes, it's remarkable just how bad Lausanne suddenly have become, 3 points in the last 10 games, so that's relegation settled. Europa League is closer than that, we're in 5th and 5th gives qualification depending on the Cup winner, 4th gives qualification for sure. Originally Posted by deltablue More than positive. Well, thanks. I know it's been good, what's p*ssing me off is that when we're bad we're very bad, some heavy defeats lately so that's why I sound so negative. Also the league's midfield is still really tight, 2 points separate 4th from 8th, I think in a normal season our points tally wouldn't have been enough to be sitting 5th. Super League: Luzern 3-0 Delémont Ouch. The team was still very tired and we put in another abysmal performance. We’re in very bad form at the moment. Super League: St. Gallen 0-1 Delémont (Lowinsky) I tried a tactical twist, Szlykowicz on a MC position and Albín as playmaker on AMC, telling the team to hold the ball as much as possible. It worked remarkably well and we grabbed an important result to boost morale, whilst putting in a performance like I hadn’t seen in a very long time. Super League: Delémont 0-1 Young Boys Very disappointing, I thought we’d build up on the result of the previous match. Schweizer Cup: Thun 3-1 Delémont (Pinedo) I usually would be frustrated that the cup run ended so close to the final, but this was another very bad performance from us and Thun deserved to go through. Super League: Delémont 1-3 Servette FC (Sani) A team meeting went horribly wrong and it shown on the pitch. Super League: Delémont 0-4 Thun 3 goals down on the first half, 1 player sent off, another player injured after all subs were over, it doesn’t get any more depressing than this. Player of the Month By player of the month I mean least sh*t player of the month, remarkably Dylan has come out of this shambles with some credibility. Competitions Super League: Schweizer Cup: Lost in the semi-final to Thun. Summary Well now it’s all really fallen apart. I always knew there was a danger of this happening despite the very strong beginning to the season, but we’ve entered a poor morale/poor results spiral of doom and can’t seem to get away from it. I didn’t help neither with a disastrous team meeting. We’re still fulfilling the minimum goal of not going back down to the Challenge League, and added to it a nice cup run, but I’m now thinking of leaving the club at the end of the season when the contract runs out. I think it’s best for both me and the club, they need a morale injection from somewhere. Super League: Delémont 2-0 Lausanne (Rigo, Roberts) Trust Lausanne to allow us to get a win, we really needed it, however Roberts was sent off and then Jarosch got injured which meant we ended the game on 9 men! Super League: Grasshoppers 2-2 Delémont (Albín, Katz) So close to a great win, we led this game twice and had more chances than them. 2 assists this month playing as AMR, against Grasshoppers and Lausanne. Competitions Super League: Schweizer Cup: Lost in the semi-final to Thun. Summary A much better month but we couldn’t improve the league position, and finish the season in 9th. I’m really torn here on whether I should leave the club or ask for a new contract (and they want me to stay, offered contracts twice, I rejected both). This season got depressing on its final stages, and we’re 1M€ on the red in terms of finances so there’s good reasons to move and look for a new challenge. On the other hand, straightening this club and settling it on the top tier is a big challenge as well, and we have some really exciting youngsters. Opinions? Slightly different now as I’ve moved one of the DMs to MC, given playmaking duties to our AMC, and given up on the target man. This 11 was the most usual starting lineup albeit I’ve tried billions of combinations. Squad Here’s some numbers, stats and sh*t, yo: Top 5 key players of the season 5. Matthew Edile (DL) – I could’ve done without the 2 red cards, and with a much better ability to tackle (or defend in general), but somehow he was our best defender. 4. Dylan Duventru (AML) – 2 goals and 4 assists looks very bad compared to what he did last season, but he still was one of our most convincing players. 3. Sidi Keita (DMC) – I could’ve picked any of our 3 usual DMs as they’re all reliable but Sidi’s got an extra level of class about him. My new job is in Belgium, and my team plays in the rather ugly/boxy-looking Het Kuipje: I could’ve gone to the English League Two to manage Shrewsbury, or to the Liga Orangina in Portugal to manage the recently relegated Beira-Mar, but I took KVC Westerlo in Belgium instead. I wanted to try another country I’ve never managed in before, and staying in a top tier was almost obligatory given that was where I was with Delémont. Westerlo are a settled mid-table Jupiler Pro League, and have been there hopping between 6th and 14th place for the past 16 seasons – so that’s the opposite of yo-yo Delémont all over the place. They have qualified for Europe a couple times but been pretty much rubbish each time, best result was in the 2011/2012 season (already within my FM world) when they beat Split and PAOK in the qualifying rounds then lost to Schalke before the groups. Westerlo are well off financially with 1.1M€ on the bank (albeit also a loan debt of 400K€), indeed I have a luxurious 331K€/month wage budget – of which 244K€/month are in use – and even a transfer budget of 277K€. It’s all a huge increase from what I had in Switzerland. Goals for this season The Belgian league has a funny format where it’s all divided in mini-groups mid-season, I’m aiming at just about making the championship group (top 6), or be among the best in the following group who fight for an European spot. The media only predicts a 15th place however, so I may be a little optimistic. The board puzzlingly only wants me to “learn from the experience of playing in the Jupiler Pro League”. I removed the Belgian league third tier recently (before even dreaming I’d take this job), I hope I didn’t mess anything up here with that. Wim De Decker (DM) (free) – I didn’t really need another DM but this Belgian international is better than all of the many I had in my squad. Transfers (out) Jonas Bogaerts (40K€) and Wouter Scheelen (35K€) were sold, Arnaud De Greef was loaned for a 3K€ fee, and Stig Engelen released on a free. Fixtures Jupiler Pro League: AA Gent 4-2 Westerlo (Bordagaray, Yulu-Matondo) Hectic start to the season! We did well to have more chances than them in a difficult away fixture, but still lost and didn’t take a 1 man advantage after they had their full-back sent off. Bordagaray scored a great goal on debut. 4 goals, 1 assists, 1 MOM award, despite being very annoyed with me because I won’t let him move to a bigger club. Competitions Jupiler Pro League: Cofidis Cup: I still have no idea in which round we’ll enter. Summary Very pleased with this start! We’re playing an expansive, flowing version of football with 2 robust DMs to cover the highly attacking front 4 and my two superb full-backs (Mathiás Abero and the unpronounceable Günther Vanaudenaerde) bombing from the back. It’s all very positive stuff and pleasing to watch. Fredy Montero (ST) (free) – Probably irresponsible to hire a ST when I already had 3, plus 2 other players who can do the position, plus a ST lined up to join in January. And I usually play a lineup with only 1 striker! But I couldn’t let go such an amazing player! Fixtures Jupiler Pro League: Westerlo 0-3 Genk No resemblance whatsoever to the last few matches, we caused no danger and they were incredibly efficient. Jupiler Pro League: OH Leuven 1-0 Westerlo We slowly took control of the match, then conceded one when we didn’t deserve it, and couldn’t turn it around. Jupiler Pro League: Westerlo 2-1 KV Kortrijk (Yulu-Matondo, Kumedor(og)) I played an attacking 4-4-2 wide diamond and dominated the whole game, we should’ve won by a bigger margin. Jupiler Pro League: Lokeren 0-0 Westerlo Tried a much more defensive approach to this match and we held on to the draw – just. Had a few scares late in the game… Player of the Month Not many players shone this month, but our Chinese playmaker had a very good game against Kortrijk (MOM in fact, with an assist), and held his own in the other matches. Jupiler Pro League: Westerlo 2-1 Anderlecht (Zheng Zhi, Yulu-Matondo) What a match, I’m so proud of my players. I played a very defensive version of my 4-2-3-1 but put lots of emphasis in trying to hold onto the ball as much as possible and play out of defence. The result was that we frustrated Anderlecht for most of the game, whilst also having most of the ball and eventually making use of it to win the game. Cofidis Cup: Westerlo 3-0 La Louviére Centre (Montero (2), Al-Suwaileh) We set out to steamroll the minnows and met the expectations. Fredy Montero scores his first 2 for the club, ending a lengthy goal drought that had started in his previous club. Player of the Month Has been a very successful signing so far, can’t recall a poor performance yet, MOM and goal scorer against Mons this month. Competitions Jupiler Pro League: Cofidis Cup: I don’t know who the next opponents will be yet. Summary A positive month, really enjoyed the win over Anderlecht and have now developed a set of varied tactics that I tweak according to the opposition and the way the games evolve. Currently constantly switching between a game-controlling 4-2-3-1, a gung-ho 4-4-2 wide diamond and a very defensive version of the 4-2-3-1. Am also using a varied array of shouts. Jupiler Pro League: Standard 1-3 Westerlo (Yulu-Matondo, Abero, Bordagaray) Brilliant, brilliant result, winning by 2 goals away at the league leaders is just superb (and it was their first defeat), Zheng Zhi even missed a penalty too! Jupiler Pro League: Westerlo 1-1 Club Brugge (De Decker) We tried to pull the same stunt we used to beat Anderlecht and Standard, but the game plan nearly went to hell when we conceded a goal in the very first minute. A late penalty gave us the equalizer, and another great result. Cofidis Cup: Westerlo 3-1 KV Mechelen (Montero (2), Caballero) Took us a while to get the hang of this game but we pulled it off with a determined display in the 2nd half. Fredy Montero becoming a bit of a cup specialist with another brace. Jupiler Pro League: Westerlo 0-0 Zulte Waregem Very poor performance, not at all on par with what we’ve been doing lately. 20-3 for the opposition on shots… Jupiler Pro League: Westerlo 2-2 AA Gent (Montero, Abero) Bloody hell, so close to another great win over a top side, unfortunately they bounced back from 2 behind to equalize already in injury time. Montero was amazing for us, a magnificent goal and a superb assist. Player of the Month What a player, he’s been very good as a left-back and even better as a defensive winger in the big games. On stellar form at the moment, goals and brilliant exhibitions against Standard and Gent this month. Competitions Jupiler Pro League: Cofidis Cup: Now into the quarter-finals where we’ll meet KV Kortrijk in a two-legged round in January. Summary Considering just how tough the fixtures for this month were, I’m very, very pleased with what we did. Only worry is that we don’t seem as good at controlling a match when we must set out to win, than when given the underdog tag - we’re much more comfortable sitting deep and frustrating the opposition. Mid-season still, but we’re currently well on course for a top 6 finish which would qualify us for the Championship Group. Jupiler Pro League: Genk 1-0 Westerlo Tough to take, we put up a fight but a goalkeeping error by Verbauwhede ruined it all. Player of the Month With the attacking players gone missing, the defensive have shone and Caballero continues on brilliant form, MOM in the 0-0s against Antwerp and Charleroi. Competitions Jupiler Pro League: Cofidis Cup: Waiting for the quarter-finals against KV Kortrijk. Summary Not a good month, maybe I’ve become too cautious with our tactics but we forgot how to score goals. I’ve been playing with ML/MRs every game, maybe time to use AMR/AMLs again. The loss to Genk may prove to be costly, we lost the top 6 position to them. Championship will probably be out of reach, but you can fight for the third place. Keep up! Tks, I really don't think we can get into the actual championship fight, those teams up there have far more resources than us, what I'm aiming at is a top 6 position which qualifies us for the title deciding mini-league (and a few european spots). Diego Penny (GK) (free) – With Verbauwhede having a great season, I probably could’ve done without him but he’s our best keeper in theory, in practice will start as 2nd choice. Luis Perea (ST) (free) – Transfer agreed a long time ago, before hiring Fredy Moreno, nevertheless a very good forward. Jacob Nielsen (DC, DMC / MC) (loan) – Our parent club Chelsea decided to send him our way and I was delighted to receive him, in fact I had already tried this loan in the Summer but they didn’t agree to it then. Transfers (out) Loaned out a few players: Forward Ahmed Al-Suwaileh went to NAC Breda so I could save on his extortionate wages, youngsters Stefaan Roef and Jente Van Gucht went to clubs where they can get some first team football. Fixtures Cofidis Cup Quarter-Finals 1st Leg: KV Kortrijk 1-2 Westerlo (Wils, Perea) About bloody time we got a win again, our new signings Céspedes and Perea pulling the strings, albeit it took a goal in injury time. Jupiler Pro League: Westerlo 4-0 OH Leuven (Córdoba, Lenaerts (og), Yulu-Matondo, Wille(og)) We benefitted from two own-goals and some above-average finishing, but still one of the best matches of the season, excellent win. Cofidis Cup Quarter-Finals 2nd Leg: Westerlo 1-1 KV Kortrijk (Perea) Not as comfortable a game as I’d have liked, we trailed for most of the game, but we’re through to the semi-finals. Player of the Month 3 assists and 3 MOM mentions in the 3 games he’s played for the club in the starting 11. An excellent arrival to Belgium! Won the Player of the Month award. Competitions Jupiler Pro League: Cofidis Cup: Semi-final opponents are Sint-Truiden, I think we’ve got a genuine big chance of reaching the final here! Summary I decided to play a much more expansive branch of football this month, and it paid off, with 2 league wins and the qualification for the cup’s semi-finals. We’re still 7th but fighting strongly to reach our goal of 6th. Unfortunately the remaining 7 fixtures of the league are quite difficult, they include consecutive games against Anderlecht, Standard and Club Brugge. Oh and it was a reference to how Napoleon 'met his waterloo'. It was either that or quoting 'Abba' (who won Eurovision with a song called 'Waterloo') and this didn't seem the right crowd for that sort of thing. Oh and it was a reference to how Napoleon 'met his waterloo'. It was either that or quoting 'Abba' (who won Eurovision with a song called 'Waterloo') and this didn't seem the right crowd for that sort of thing. Jupiler Pro League: Mons 2-1 Westerlo (Córdoba) A little unlucky but no excuses for losing to the last placed in the league. Jupiler Pro League: Westerlo 1-1 Sint-Truiden (Córdoba) Decent rehearsal for the cup match but they were probably a little more dangerous than us. Cofidis Cup Semi-Final 1st Leg: Sint-Truiden 2-0 Westerlo Oh dear, that’s the cup dream over most likely. Very harsh result IMO, it was an even game. Jupiler Pro League: Anderlecht 2-1 Westerlo (Liliu) Not a terrible effort but we couldn’t engineer an upset this time. Jupiler Pro League: Westerlo 0-1 Standard Started pretty well but then De Decker got sent off stupidly and that didn’t help us. Player of the Month No-one shone this month but I’ll pick Glenn for his MOM performance against Sint-Truiden in the league match. Competitions Jupiler Pro League: Cofidis Cup: Hanging on in the semi-final against Sint-Truiden but it’s very unlikely we’ll turn it around. Summary A poor month – even considering the very difficult calendar – takes us out mathematically of my goal of a top 6 position, and Sint-Truiden also open up a gap for 7th spot. The last 2 fixtures are pretty much meaningless as the 8th position is almost certain, we should be focusing now on the European Places Playoff which will come after that. Injuries to my three 'bero's - Caballero, Abero and Montero - who are key players, haven't helped. Vanderbergh has a long way to go but 4.5 stars is very exciting, everyone in the club agrees he's going to be a star. Also signed Gómez and Linetty. Talking about youngsters, I haven't mentioned Hugo Horemans yet. This is a player I inheritted at the club already but looks superb for a 16 y.o., including full 5 stars potential recommendation from the assman, and I'm starting to give him the odd first team chance. Westerlo looks like a great breeding ground for strikers, even if they seem to come lacking in finishing - but that can be trained. Jupiler Pro League: Club Brugge 3-1 Westerlo (Yulu-Matondo) I really could’ve done without Farssi deciding to get a daft red card on the 6th minute, but we held on remarkably to go into half-time 0-0, then even equalized with 10 men but Club Brugge scored 2 in the final 10 minutes. I gave the hugely exciting 16 year old Hugo Horemans a first team chance and he became Westerlo’s youngest ever player – whilst making the assist to the goal! Jupiler Pro League: Zulte Waregem 1-2 Westerlo (Caballero, Córdoba) We set out to have some fun in the final match of the regular season and it turned out to be lots of fun indeed! 7 clear cut chances and Jorge Córdoba scoring a superb solo goal. Jupiler Pro League Euro Playoffs Grp B: Lokeren 0-0 Westerlo Not a very good start to the playoffs, we were lucky to come away from this with a point. Cofidis Cup Semi-Final 2nd Leg: Westerlo 2–0 Sint-Truiden (aet) (2-3 p.k.) (Céspedes, Bordagaray) Awesome, what a fantastic match! We ultimately lost on penalties but I can be very proud of my players. Despite Stef Wils being sent off, we scored 2 in the final 10 minutes and tied the semi-final dramatically. We so nearly made the final… Jupiler Pro League Euro Playoffs Grp B: Westerlo 3-2 Beerschot AC (Horemans, Córdoba, Lucas Silva) I decided to play ultra-attacking all game long and it turned out to be a thriller, we could’ve hammered them but the finishing wasn’t all that. Hugo Horemans breaks another club record becoming the youngest ever goalscorer (and the Belgian league’s youngster ever scorer), plus he got another assist too. Player of the Month We’ve not had reliable goalscorers this season but Córdoba lately has been the closest thing to it, goals against Zulte Waregem and Beerschot this month. Competitions Jupiler Pro League: Those were the regular stage final standings, whereas this is how the Euro Playoffs are looking like: Cofidis Cup: Defeated on penalties in the Semi-Final versus Sint-Truiden Summary I’d say things are looking on the up again, but the chances of making it to the Europa League are still slim because only one team from the 8 in the playoffs gets to play in the final for that spot, and even then you have to play one team from the Championship Playoff. Gutted that we nearly pulled a miracle and made the Cup final but just about missed out. Jupiler Pro League Euro Playoffs Grp B: Westerlo 1–1 Lokeren (Montero) Bloody hell, we didn’t deserve to concede the late equalizer. Fredy Montero scored a monster of a volley in his first match returning from a long-term injury. Jupiler Pro League Euro Playoffs Grp B: Beerschot AC 3-1 Westerlo (Lucas Silva) Another game with tons of chances, they were luckier than us and turned the game around after we got the first goal. We drop the 1st place in the group to Lokeren with 1 match remaining. Player of the Month Remarkable game against Charleroi including a goal. Competitions Jupiler Pro League: Cofidis Cup: Defeated on penalties in the Semi-Final versus Sint-Truiden Summary 1 fixture to go, we need to win at Charleroi and hope Lokeren doesn’t win at Beerschot, to keep going in the competition. Disappointing, even more so because if it wasn’t for the undeserved late equalizer at home to Lokeren we’d be through. Jupiler Pro League Euro Playoffs Grp B: Charleroi 2-2 Westerlo (Céspedes, Yulu-Matondo) We had the lead but we conceded a late equalizer (yet again) from long range, and it didn’t matter anyway as a 10-men Lokeren won at Beerschot. Player of the Month MOM in this month’s only game, with an assist. Competitions Jupiler Pro League: Cofidis Cup: Defeated on penalties in the Semi-Final versus Sint-Truiden. Summary That’s it, season over already – at the start of May! I think it’s been highly fun at times but also very frustrating: being on target for the top 6 finish then crumbling apart at the wrong time of the season; coming from the dead in the cup semi-final only to lose on penalties; playing very well in the Euro Playoffs but watching our opponents take their chances. Ultimately I’d say it was a good season but not particularly remarkable, I’m sticking for another year at least, but I’ve got a big job to do as I screwed up the finances this season and we’re 1.3M€ in the red. I'd like some tips from whoever's reading this on the career format, I'm going to far more detail than my previous venture into FMCU, but haven't generated much interest. Thinking of doing updates every 3 months instead of every month maybe, albeit I'm enjoying this. | Low | [
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A qualitative evaluation of a citywide Community Health Partnership program. While there have been numerous community-based programs in Baltimore, Maryland, aimed at helping patients access medical treatments and services, they historically were underutilized and did not operate synergistically. For that reason, sanofi-aventis, along with key stakeholders in Baltimore, developed the Community Health Partnership (CHP) to educate, empower, and connect patients to community health resources to enable patients to be more proactive about their health. The CHP utilizes a community health liaison (CHL) and a community health action team (CHAT) consisting of community health leaders who are hands-on activists and health care workers who coordinate activities and provide guidance for the CHP. The goal of the program is to foster community collaboration to raise awareness of the need to improve health in the community and to identify and connect patients to existing resources and services that can help. A qualitative evaluation of the Baltimore CHP was conducted through focus group and key informant interviews with members of the CHAT and CHP. Results suggest that the CHP program has enhanced patient-provider relationships, brought together a wealth of resources, and made people more aware of health information. The CHP facilitated providers' ability to help patients find resources and empowered patients in the community to better manage their health conditions. In parallel, physicians requested additional culturally sensitive resources on medical conditions that addressed the health literacy of their diverse patients. Through stakeholder engagement, many more communities beyond Baltimore can become better networked to help patients navigate the health care system and improve their health. | High | [
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Man of War: Charles V, Holy Roman Emperor Charles V Charles V Charles V Charles V Equipment of Charles V Charles V Charles V Charles V Charles V Charles V Charles V Charles V Charles V Conclusion Charles V An article by Chad Arnow Politically-motivated marriages have been a mainstay of the nobility throughout the ages, as rulers and other powerful figures sought to solidify and increase their holdings. In, we see one of the peaks of this system in a monarch who ruled large portions of Europe and oversaw some of the explorations to the New World.The futurewas born February 24th of 1500. His grandparents were Ferdinand II, King of Aragon, Isabella I, Queen of Castile, Mary of Burgundy and Maximilian I, Holy Roman Emperor. Charles was born in Ghent in family territories in Burgundy, and grew up influenced by the many cultures from which he descended. He was said to have been able to speak at least a little French, Dutch, German, Spanish, and Italian throughout the course of his life. Early in his life, he was tutored by the future Pope Adrian VI.With the death of his father Philip the Handsome in late 1506, the very young Charles became titular ruler of the family's Burgundian territories, inherited through his grandmother Mary. In reality, the territories were under the rule of the appointed regent, his aunt, until 1515. Throughout his life, he expanded the Burgundian territories and strengthened their ties with the Holy Roman Empire.With the death of his maternal grandfather, Ferdinand II, the teen-agebecame the first ruler of a united Spain, bringing together Aragon and Castile. This united kingdom included the old kingdom of Navarre, bordering the western Pyrenees Mountains, the city of Granada, Naples, the two largest islands in the Mediterranean Sea, Sicily and Sardinia, and all the Castilian territories in the New World. Though considered by many to be a foreigner, Charles spent most of his life in Spain after his succession to the Spanish throne.The death of Maximilian I in 1519 gave Charles control of the Habsburg lands, extending his rule into Austria. His lineage and holdings made him an obvious candidate to succeed Maximilian as Holy Roman Emperor. His main rival for the position was France's Francis I, who would conflict with Charles throughout his life. Charles prevailed and was elected in June of 1519, around six months after his grandfather's death. Francis and Charles would spend years in conflict over the sovereign rule of Burgundy (held by Francis), as well as territories in Italy. Charles eventually gained control of Milan, and conquered Rome. When not fighting France directly, Charles fought against the Ottoman Empire, a threat to his Habsburg holdings, which was known to ally itself with France.Charles's lifetime saw the rise of Protestantism in Europe. Martin Luther's theses were written shortly before Charles was elected Holy Roman Emperor. Charles, as emperor, outlawed Protestantism, which led to conflict in his German lands. His capture of Rome kept Pope Clement VII from issuing an annulment to Henry VIII's marriage to Catherine of Aragon, Charles's aunt. This was one of the steps toward the eventual souring of Anglo-Spanish relations and towards the establishment of the Church of England.In 1556, bothered by ill health and gout, passed control of his Spanish and his Burgundian territories to his son Philip II. His German lands and the Holy Roman Empire were passed to his brother Ferdinand, who had been given increasing control over them as Charles had fought in Italy and against the Ottomans. Charles spent his late years at the monastery of Yuste in Extremadura, a western province of Spain. Though not in control any more, he did communicate with those in power and remained interested in the fate of the empire. Charles died September 21, 1558. His remains were permanently interred over two decades later at the newly-built(Royal Monastery of Saint Lawrence of El Escorial). It was built by Philip II to house the remains of Spanish monarchs in its Royal Pantheon.It should be no surprise that a monarch with Charles's wealth and political reach should have left behind a plethora of fine examples of arms and armour . Charles had access not only to the fine armourers of Germany like the Helmschmids and Konrad Seusenhofer (favorites of Maximilian I), but also to the finest Italian armourers, like the Negroli family. This trove includes many full harnesses, many other armour pieces, firearms, and other weapons with ties to Charles.The earliest surviving items attributed toare two "costume" harnesses made for him as a child by Innsbruck armourers, probably commissioned by Maximilian I. The earlier one was made in circa 1512 by H. (Hans?) Rabeiler, the later one between 1512 and 1514 by Konrad Seusenhofer. Both are of a design calledand were made to follow fashion popular at the time, especially among theemployed by the Holy Roman Empire. The later harness, with its skirt (tonlet), features pierced bands of gilded silver over violet velvet. Both harnesses are housed in Kunsthistorisches Museum in Vienna.In Madrid's Real Armería rests a harness for man and horse that dates to circa 1520. It is said to date from 1518 when Charles visited his Spanish kingdom for the first time. The harness is obviously built for the tournament, as it is reinforced on the left side to receive lance blows. The helm is of the shape we now call frog-mouthed. The harness for the man has etched bands of foliage surrounding plain ones on its larger plates. Some of these bands are echoed as decoration on the smaller pieces, as on the helm, gauntlets, and arms defenses. The bard (horse armour) features roped decorations and more etched bands, and removable lion's head decorations, as well as scenes depicting battles from the Bible. It is attributed to the Augsburg armourer Kolman Helmschmid.Also in Madrid is a splendid garniture known as the "KD" garniture or the(armour with diamond-studded borders). It is also attributed to Kolman Helmschmid and dates to circa 1525. It is a complete harness with pieces of exchange. Harnesses of this type could be used both in battle or in various forms of tournament combat by exchanging pieces and adding reinforcing defenses. This magnificent harness gets one of its names from the raised decorative bands that feature raised diamond shapes. The bands are surrounded by etched and gilt bands and by raised roped bands. The "KD" nomenclature comes from the ornately engraved initials on the haute piece of the left pauldron, said to signify(Divine Charles), an imperial title. The harness can be worn in a variety of combinations and includes both and armet and a burgonet.A third harness attributed to Kolman Helmschmid survives in the Real Armería. Known as the "Hunt Tonlet" it is a harness configured for combat on foot in a tournament. Its skirt-like tonlet has a removable band that features animals from the hunt on an etched and gilt background, giving it its name. The tonlet covers the upper part of the fully-enclosing, articulated breaches that now lacks its codpiece. All joints are completely protected by laminated plates, even the inside of the elbows and backs of the knees. As is typical of Helmschmid, the decoration, though ornate and complex with etched and gilt bands and roped sections, is broken up by expanses of plain steel, giving it a look that is elegant and functional.Charles's dealings in Italy left us with fine examples of pieces crafted for him the by great Negroli family of Milan. The earliest of these is a parade helmet and shield dated to 1533. The helm's skull is embossed and gilded to look like curls of hair, with a laurel wreath encircling the brow. The bearded bevor, though similar, is not original. The decoration on its lower edge doesn't match the rest of the helm. The shield is embossed and gilt with a lion's head as its boss. Both burgonet and shield are signed and dated by Filippo Negroli and reside in the Real Armería.Another helm ofsculpted to appear as if with curly hair survives in Vienna, but was originally part of the "Palm-branch" armour whose pieces are in Madrid and in the Higgins Armory Museum in Worcester, Massachusetts.Yet another harness survives in the Real Armería, this one by Desiderius Helmschmid, Kolman's son. This harness was assembled from armour pieces attributed to, many of them made by Desiderius in the 1530s. The pieces come from a combination of field and tournament harnesses.Another Desiderius Helmschmid harness survives in Madrid, this one designed for the field. It was commissioned not long after the outbreak of conflict between Protestants of the Schmalkaldic League and Catholics, and was presumably used during those military efforts. This example, which features etched and gilt bands surrounded by roped borders, echoes some of the braided trim decoration popular in Spanish courtly dress at the time.From 1541 dates another parade helmet and shield, also by the Negroli family. Resting in Vienna, it consists of an embossed and gilt burgonet with a pivoting visor in the form of a lion's mask. Given to Charles by his brother after Charles's successful African campaign, it features commemorations to heroes of ancient Rome's conquests in Africa. The round shield is also embossed and gilt and features the head of Medusa at its center.A second Medusa-head parade shield of the Negrolis resides in Madrid. It is also damascened, embossed, etched and gilt. Its Medusa head appear to be slightly more complex. It also dates to 1541.From 1545 survives an embossed parade burgonet, made by Filippo and Francesco Negroli. The comb is shaped as a bound Turk rising from a column, while it is also decorated with the allegorical figures of Fame and Victory. Similarly decorated burgonets reside in the Musée de l'Armée in Paris and in The Metropolitan Museum of Art , New York.Dating to 1546 is one of Charles's more unique parade armours. Made by Bartolomeo Campi in Pesaro, it is known as the Alla Romana parade harness for its Romanesque look. This harness was a gift of the Duke of Urbino, Guidobaldo II, who hoped to curry favor withafter his successes in Italy. It is inscribed with the armourer's name, Guidobaldo II's, and a note about how it was commissioned by the Duke and completed within two months. The harness's cuirass is muscled to represent classical Greek and Roman armour, and is accompanied by boots that imitate the thong lacing of Roman sandals, with embossed toes to complete the look.In addition to these, there are other pieces of armour and armoured saddles belonging tothat survive to this day. In the Kunsthistorisches Museum Vienna reside two burgonets attributed to. Both are by Desiderius Helmschmid and date from around 1540. Both feature roping, raised circles, and etched decorations. Also by Desiderius Helmschmid is a three-quarter harness dating from 1543.While we have many examples of armour known to have belonged to, it is not often as easy to find weapons that can specifically be attributed to him. There are many surviving pieces that were given as gifts to Charles and even more records of such examples, but it's somewhat difficult to know how they were received or what was done with them.There is a sword located in Madrid’s Real Armería that has matching ornamentation to the "damascened garniture" shown above. It is dated circa 1546 and came out of the Negroli workshop in Milan. While the attribution to Charles V is somewhat speculative, signs seem to indicate that the sword was commissioned with the armour.Another surviving weapon is a pistol dated to 1540-45, made by Peter Pech of Munich. The barrel is etched and gilt, as are both lock mechanisms. The spirally-carved stock is of cherry wood. The barrels are stacked, and the double locks allow for two shots to be fired. This particular example resides in The Metropolitan Museum of Art, but several others attributed toreside in Madrid's Real Armería.was a man of wealth and power whose influence reached from Western Europe, through Italy, the Mediterranean, and Spain and into the New World. As the first ruler of a united Spain and a backer of Spanish explorers, he played an important part in creating the world we know today. As Holy Roman Emperor he witnessed the beginnings of Protestant Reformation. Charles lived during a period of upheaval and change, and was an important figure in many events of the day. The arms and armour he left behind show evidence of both his great wealth and the awesome power he wielded. | Mid | [
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Documentaries about films and filmmaking have a special place in the heart of most film devotees. Though largely confined to television and DVD special features, every now and then we get treated to a feature-length exploration of a filmmaker or key period of movie history. In recent years we've had The Kid Stays in the Picture (a portrait of legendary producer Robert Evans), Overnight (a cautionary tale of sidden movie success), Lost in La Mancha (a sobering look at how quickly a major film project can fall apart), This Film is Not Yet Rated (an exposé of the workings of the American movie ratings board), Not Quite Hollywood (a celebration of Australian exploitation movies) and Inside Deep Throat (well, you can work that one out for yourself), to name but a few. Two in the Wave (Deux de la Vague) is the story of a friendship and estrangement involving to of the key figures of French New Wave cinema. Jean-Luc Godard was born in 1930; François Truffaut two years later. Love of movies brings them together. They write in the same magazines, Cahiers du Cinema and Arts. When the younger of the two becomes a filmmaker with The 400 Blows, which triumphs in Cannes in 1959, he helps his older friend shift to directing, offering him a screenplay which already has a title, A bout de souffle, or Breathless. Through the 1960s the two loyally support each other. History and politics separate them in 1968 and afterwards – when Godard plunges into radical politics but Truffaut continues his career as before. Between the two of them, the actor Jean-Pierre Léaud is torn like a child caught between two separated and warring parents. Their friendship and their break-up embody the story of French cinema. Exploring the letters, personal archives and films of the two New Wave directors, Emmanuel Laurent's Two in the Wave takes us back to a prodigious decade that transformed the world of cinema. Two in the Wave will be released on UK DVD on 11th April 2011 by New Wave Films at the RRP of £15.99. The only included extra is a trailer. | High | [
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Dirty Bob to Refund XRCO Sponsorship From ICM Registry CHATSWORTH, Calif.—X-Rated Critics Organization (XRCO) chairman "Dirty" Bob Krotts has decided, following an outcry of protest from several adult industry figures, to return the sponsorship funds for this year's XRCO Awards Show provided to the organization by .XXX domain registration outfit ICM Registry. Over the past several days, Krotts received intense scrutiny on various adult forums from such industry observers as Mike South and original XRCO member William Margold over his choice to accept sponsorship funds from the much-maligned ICM. Krotts claimed in response that he was unaware at the time he accepted the funds that ICM was the body overseeing the registration of .XXX domains. ADVERTISEMENT In addition to the online flack, Krotts got wind that such major participants as Digital Playground (whose contract stars Kayden Kross and Jesse Jane are, respectively, co-hosting the ceremony and going into the Hall of Fame) were considering pulling their presence from the show. A few individuals from the adult community have stepped up to help replenish the funds ICM had provided, Krotts disclosed in the following formal statement: "ICM Registry LLC, aka .XXX, agreed to our request today to withdraw as a sponsor for the upcoming XRCO Awards Show. I would like to thank them for graciously bowing out upon our request; their sponsorship donation will be refunded in full. I would further like to thank the many people who supported us and are helping to make up for part of the loss of ICM Registry, LLC's sponsorship donation—with special thanks to Jeff Mullen, Axel Braun, and another XRCO benefactor who wishes to remain anonymous. This outpouring of industry support renews my faith in the business and also assures us of another great industry-only awards party when the XRCO celebrates its 28th annual XRCO Awards Show on April 12th at the Hollywood Highlands." | Mid | [
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Ataxia–telangiectasia Ataxia–telangiectasia (AT or A–T), also referred to as ataxia–telangiectasia syndrome or Louis–Bar syndrome, is a rare, neurodegenerative, autosomal recessive disease causing severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease. A–T affects many parts of the body: It impairs certain areas of the brain including the cerebellum, causing difficulty with movement and coordination. It weakens the immune system, causing a predisposition to infection. It prevents repair of broken DNA, increasing the risk of cancer. Symptoms most often first appear in early childhood (the toddler stage) when children begin to sit or walk. Though they usually start walking at a normal age, they wobble or sway when walking, standing still or sitting. In late pre-school and early school age, they develop difficulty moving their eyes in a natural manner from one place to the next (oculomotor apraxia). They develop slurred or distorted speech, and swallowing problems. Some have an increased number of respiratory tract infections (ear infections, sinusitis, bronchitis, and pneumonia). Because not all children develop in the same manner or at the same rate, it may be some years before A–T is properly diagnosed. Most children with A–T have stable neurologic symptoms for the first 4–5 years of life, but begin to show increasing problems in early school years. A–T is caused by a defect in the ATM gene, which is involved in the recognition and repair of damaged DNA. The prevalence of A–T is estimated to be as high as 1 in 40,000 to as low as 1 in 300,000 people. Symptoms There is substantial variability in the severity of features of A–T among affected individuals, and at different ages. The following symptoms or problems are either common or important features of A–T: Ataxia (difficulty with control of movement) that is apparent early but worsens in school to pre-teen years Oculomotor apraxia (difficulty with coordination of head and eye movement when shifting gaze from one place to the next) Involuntary movements Telangiectasia (dilated blood vessels) over the white (sclera) of the eyes, making them appear bloodshot. These are not apparent in infancy and may first appear at age 5–8 years. Telangiectasia may also appear on sun-exposed areas of skin. Problems with infections, especially of the ears, sinuses and lungs Increased incidence of cancer (primarily, but not exclusively, lymphomas and leukemias) Delayed onset or incomplete pubertal development, and very early menopause Slowed rate of growth (weight and/or height) Drooling particularly in young children when they are tired or concentrating on activities Dysarthria (slurred, slow, or distorted speech sounds) Diabetes in adolescence or later Premature changes in hair and skin Many children are initially misdiagnosed as having cerebral palsy. The diagnosis of A–T may not be made until the preschool years when the neurologic symptoms of impaired gait, hand coordination, speech and eye movement appear or worsen, and the telangiectasia first appear. Because A–T is so rare, doctors may not be familiar with the symptoms, or methods of making a diagnosis. The late appearance of telangiectasia may be a barrier to the diagnosis. It may also take some time before doctors consider A–T as a possibility because of the early stability of symptoms and signs. Ataxia and other neurologic problems The first indications of A–T usually occur during the toddler years. Children start walking at a normal age, but may not improve much from their initial wobbly gait. Sometimes they have problems standing or sitting still and tend to sway backward or from side to side. In primary school years, walking becomes more difficult, and children will use doorways and walls for support. Children with A–T often appear better when running or walking quickly in comparison to when they are walking slowly or standing in one place. Around the beginning of their second decade, children with the more severe ("classic") form of A–T start using a wheelchair for long distances. During school years, children may have increasing difficulty with reading because of impaired coordination of eye movement. At the same time, other problems with fine-motor functions (writing, coloring, and using utensils to eat), and with slurring of speech (dysarthria) may arise. Most of these neurologic problems stop progressing after the age of about 12 – 15 years, though involuntary movements may start at any age and may worsen over time. These extra movements can take many forms, including small jerks of the hands and feet that look like fidgeting (chorea), slower twisting movements of the upper body (athetosis), adoption of stiff and twisted postures (dystonia), occasional uncontrolled jerks (myoclonic jerks), and various rhythmic and non-rhythmic movements with attempts at coordinated action (tremors). Telangiectasia Prominent blood vessels (telangiectasia) over the white (sclera) of the eyes usually occur by the age of 5–8 years, but sometimes appear later or not at all. The absence of telangiectasia does not exclude the diagnosis of A–T. Potentially a cosmetic problem, the ocular telangiectasia do not bleed or itch, though they are sometimes misdiagnosed as chronic conjunctivitis. It is their constant nature, not changing with time, weather or emotion, that marks them as different from other visible blood vessels. Telangiectasia can also appear on sun-exposed areas of skin, especially the face and ears. They occur in the bladder as a late complication of chemotherapy with cyclophosphamide, have been seen deep inside the brain of older people with A–T, and occasionally arise in the liver and lungs. Immune problems About two-thirds of people with A–T have abnormalities of the immune system. The most common abnormalities are low levels of one or more classes of immunoglobulins (IgG, IgA or IgE subclasses), not making antibodies in response to vaccines or infections, and having low numbers of lymphocytes (especially T-lymphocytes) in the blood. Some people have frequent infections of the upper (colds, sinus and ear infections) and lower (bronchitis and pneumonia) respiratory tract. All children with A–T should have their immune systems evaluated to detect those with severe problems that require treatment to minimize the number or severity of infections. Some people with A–T need additional immunizations (especially with pneumonia and influenza vaccines), antibiotics to provide protection (prophylaxis) from infections, and/or infusions of immunoglobulins (gamma globulin). The need for these treatments should be determined by an expert in the field of immunodeficiency or infectious diseases. Cancer People with A–T have a highly increased incidence (approximately 25% lifetime risk) of cancers, particularly lymphomas and leukemia, but other cancers can occur. When possible, treatment should avoid the use of radiation therapy and chemotherapy drugs that work in a way that is similar to radiation therapy (radiomimetic drugs), as these are particularly toxic for people with A–T. The special problems of managing cancer are sufficiently complicated that treatment should be done only in academic oncology centers and after consultation with physicians who have specific expertise in A–T. Unfortunately, there is no way to predict which individuals will develop cancer. Because leukemia and lymphomas differ from solid tumors in not progressing from solitary to metastatic stages, there is less need to diagnose them early in their appearance. Surveillance for leukemia and lymphoma is thus not helpful, other than considering cancer as a diagnostic possibility whenever possible symptoms of cancer (e.g. persistent swollen lymph glands, unexplained fever) arise. Women who are A–T carriers (who have one mutated copy of the ATM gene), have approximately a two-fold increased risk for the development of breast cancer compared to the general population. This includes all mothers of A–T children and some female relatives. Current consensus is that special screening tests are not helpful, but all women should have routine cancer surveillance. Skin A–T can cause features of early aging such as premature graying of the hair. It can also cause vitiligo (an auto-immune disease causing loss of skin pigment resulting in a blotchy “bleach-splashed” look), and warts which can be extensive and recalcitrant to treatment. A small number of people develop a chronic inflammatory skin disease (granulomas). Lung disease Chronic lung disease develops in more than 25% of people with A–T. Three major types of lung disease can develop: (1) recurrent and chronic sinopulmonary infections; (2) lung disease caused by ineffective cough, swallowing dysfunction, and impaired airway clearance; and (3) restrictive interstitial lung disease. It is common for individuals with A–T to have more than one of these lung conditions. Chronic lung disease can occur because of recurrent lung infections due to immunodeficiency. Individuals with this problem are at risk of developing bronchiectasis, a condition in which bronchial tubes are permanently damaged, resulting in recurrent lower airway infections. Gamma globulin for people with antibody deficiency and/or chronic antibiotic treatment may reduce the problems of infection. Other individuals with A–T have difficulty with taking deep breaths and may have an ineffective cough, making it difficult to clear oral and bronchial secretions. This can lead to prolonged respiratory symptoms following common viral respiratory illnesses. Techniques that allow clearance of mucus can be helpful in some individuals during respiratory illnesses. Some people will develop swallowing problems as they age, increasing their risk of aspiration pneumonia. Recurrent injury to the lungs caused by chronic infections or aspiration may cause lung fibrosis and scarring. This process may be enhanced by inadequate tissue repair in ATM-deficient cells. A small number of individuals develop interstitial lung disease. They have decreased pulmonary reserve, trouble breathing, a need for supplemental oxygen and chronic cough in the absence of lung infections. They may respond to systemic steroid treatment or other drugs to reduce inflammation. Lung function tests (spirometry) should be performed at least annually in children old enough to perform them, influenza and pneumococcal vaccines given to eligible individuals, and sinopulmonary infections treated aggressively to limit the development of chronic lung disease. Feeding, swallowing, and nutrition Feeding and swallowing can become difficult for people with A–T as they get older. Feeding refers to all aspects of eating and drinking, including getting food and liquids to the mouth; swallowing refers to ingestion or what happens after food or liquids enter the mouth. Primary goals for feeding and swallowing are safe, adequate, and enjoyable mealtimes. Involuntary movements may make feeding difficult or messy and may excessively prolong mealtimes. It may be easier to finger feed than use utensils (e.g., spoon or fork). For liquids, it is often easier to drink from a closed container with a straw than from an open cup. Caregivers may need to provide foods or liquids so that self-feeding is possible, or they may need to feed the person with A–T. In general, meals should be completed within approximately 30 minutes. Longer meals may be stressful, interfere with other daily activities, and limit the intake of necessary liquids and nutrients. If swallowing problems (dysphagia) occur, they typically present during the second decade of life. Dysphagia is common because of the neurological changes that interfere with coordination of mouth and pharynx (throat) movements that are needed for safe and efficient swallowing. Coordination problems involving the mouth may make chewing difficult and increase the duration of meals. Problems involving the pharynx may cause liquid, food, and saliva to be inhaled into the airway (aspiration). People with dysphagia may not cough when they aspirate (silent aspiration). Swallowing problems and especially swallowing problems with silent aspiration may cause lung problems due to inability to cough and clear food and liquids from the airway. Warning signs of a swallowing problem Choking or coughing when eating or drinking Poor weight gain (during ages of expected growth) or weight loss at any age Excessive drooling Mealtimes longer than 40 – 45 minutes, on a regular basis Foods or drinks previously enjoyed are now refused or difficult Chewing problems Increase in the frequency or duration of breathing or respiratory problems Increase in lung infections Eye and vision Most people develop telangiectasia (prominent blood vessels) in the membrane that covers the white part (sclera) of the eye. Vision (ability to see objects in focus) is normal. Control of eye movement is often impaired, affecting visual functions that require fast, accurate eye movements from point to point (e.g. reading). Eye misalignments (strabismus) are common, but may be treatable. There may be difficulty in coordinating eye position and shaping the lens to see objects up close. Orthopedics Many individuals with A–T develop deformities of the feet that compound the difficulty they have with walking due to impaired coordination. Early treatment may slow progression of this deformity. Bracing or surgical correction sometimes improves stability at the ankle sufficient to enable an individual to walk with support, or bear weight during assisted standing transfers from one seat to another. Severe scoliosis is relatively uncommon, but probably does occur more often than in those without A–T. Spinal fusion is only rarely indicated. Genetics A–T is caused by mutations in the ATM (ATM serine/threonine kinase or ataxia–telangiectasia mutated) gene, which was cloned in 1995. ATM is located on human chromosome 11 (11q22.3) and is made up of 69 exons spread across 150kb of genomic DNA. The mode of inheritance for A–T is autosomal recessive. Each parent is a carrier, meaning that they have one normal copy of the A–T gene (ATM) and one copy which is mutated. A–T occurs if a child inherits the mutated A–T gene from each parent, so in a family with two carrier parents, there is 1 chance in 4 that a child born to the parents will have the disorder. Prenatal diagnosis (and carrier detection) can be carried out in families if the errors (mutation) in an affected child's two ATM genes have been identified. The process of getting this done can be complicated and, as it requires time, should be arranged before conception. Looking for mutations in the ATM gene of an unrelated person (for example, the spouse of a known A–T carrier) presents significant challenges. Genes often have variant spellings (polymorphisms) which do not affect function. In a gene as large as ATM, such variant spellings are likely to occur and doctors cannot always predict whether a specific variant will or will not cause disease. Genetic counseling can help family members of an A–T patient understand what can or cannot be tested, and how the test results should be interpreted. Carriers of A–T, such as the parents of a person with A–T, have one mutated copy of the ATM gene and one normal copy. They are generally healthy, but there is an increased risk of breast cancer in women. This finding has been confirmed in a variety of different ways, and is the subject of current research. Standard surveillance (including monthly breast self-exams and mammography at the usual schedule for age) is recommended, unless additional tests are indicated because the individual has other risk factors (e.g., family history of breast cancer). Pathophysiology How does loss of the ATM protein create a multisystem disorder? A–T has been described as a genome instability syndrome, a DNA repair disorder and a DNA damage response (DDR) syndrome. ATM, the gene responsible for this multi-system disorder, encodes a protein of the same name which coordinates the cellular response to DNA double strand breaks (DSBs). Radiation therapy, chemotherapy that acts like radiation (radiomimetic drugs) and certain biochemical processes and metabolites can cause DSBs. When these breaks occur, ATM stops the cell from making new DNA (cell cycle arrest) and recruits and activates other proteins to repair the damage. Thus, ATM allows the cell to repair its DNA before the completion of cell division. If DNA damage is too severe, ATM will mediate the process of programmed cell death (apoptosis) to eliminate the cell and prevent genomic instability. Cancer and radiosensitivity In the absence of the ATM protein, cell-cycle check-point regulation and programmed cell death in response to DSBs are defective. The result is genomic instability which can lead to the development of cancers. Irradiation and radiomimetic compounds induce DSBs which are unable to be repaired appropriately when ATM is absent. Consequently, such agents can prove especially cytotoxic to A–T cells and people with A–T. Delayed pubertal development (gonadal dysgenesis) Infertility is often described as a characteristic of A–T. Whereas this is certainly the case for the mouse model of A–T, in humans it may be more accurate to characterize the reproductive abnormality as gonadal atrophy or dysgenesis characterized by delayed pubertal development. Because programmed DSBs are generated to initiate genetic recombinations involved in the production of sperm and eggs in reproductive organs (a process known as meiosis), meiotic defects and arrest can occur when ATM is not present. Immune system defects and immune-related cancers As lymphocytes develop from stem cells in the bone marrow into mature lymphocytes in the periphery, they rearrange special segments of their DNA [V(D)J recombination process]. This process requires them to make DSBs, which are difficult to repair in the absence of ATM. As a result, most people with A–T have reduced numbers of lymphocytes and some impairment of lymphocyte function (such as an impaired ability to make antibodies in response to vaccines or infections). In addition, broken pieces of DNA in chromosomes involved in the above-mentioned rearrangements have a tendency to recombine with other genes (translocation), making the cells prone to the development of cancer (lymphoma and leukemia). Progeric changes Cells from people with A–T demonstrate genomic instability, slow growth and premature senescence in culture, shortened telomeres and an ongoing, low-level stress response. These factors may contribute to the progeric (signs of early aging) changes of skin and hair sometimes observed in people with A–T. For example, DNA damage and genomic instability cause melanocyte stem cell (MSC) differentiation which produces graying. Thus, ATM may be a “stemness checkpoint” protecting against MSC differentiation and premature graying of the hair. Telangiectasia The cause of telangiectasia or dilated blood vessels in the absence of the ATM protein is not yet known. Increased alpha-fetoprotein (AFP) levels Approximately 95% of people with A–T have elevated serum AFP levels after the age of two, and measured levels of AFP appear to increase slowly over time. AFP levels are very high in the newborn, and normally descend to adult levels over the first year to 18 months. The reason for why individuals with A–T have elevated levels of AFP is not yet known. Neurodegeneration A–T is one of several DNA repair disorders which result in neurological abnormalities or degeneration. Arguably some of the most devastating symptoms of A–T are a result of progressive cerebellar degeneration, characterized by the loss of Purkinje cells and, to a lesser extent, granule cells (located exclusively in the cerebellum). The cause of this cell loss is not known, though many hypotheses have been proposed based on experiments performed both in cell culture and in the mouse model of A–T. Current hypotheses explaining the neurodegeneration associated with A–T include the following: Defective DNA damage response in neurons which can lead to Failed clearance of genomically damaged neurons during development Transcription stress and abortive transcription including topoisomerase 1 cleavage complex (TOP1cc) dependent lesions Aneuploidy Defective response to oxidative stress characterized by elevated ROS and altered cellular metabolism Mitochondrial dysfunction Defects in neuronal function: Inappropriate cell cycle re-entry of post-mitotic (mature) neurons Synaptic/vesicular dysregulation HDAC4 dysregulation Histone hypermethylation and altered epigenetics Altered protein turnover These hypotheses may not be mutually exclusive and more than one of these mechanisms may underlie neuronal cell death when there is an absence or deficiency of ATM. Further, cerebellar damage and loss of Purkinje and granule cells do not explain all of the neurologic abnormalities seen in people with A–T. The effects of ATM deficiency on the other areas of the brain outside of the cerebellum are being actively investigated. Radiation exposure People with A–T have an increased sensitivity to ionizing radiation (X-rays and gamma rays). Therefore, X-ray exposure should be limited to times when it is medically necessary, as exposing an A–T patient to ionizing radiation can damage cells in such a way that the body cannot repair them. The cells can cope normally with other forms of radiation, such as ultraviolet light, so there is no need for special precautions from sunlight exposure. Diagnosis The diagnosis of A–T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with telangiectasia and sometimes increased infections, and confirmed by specific laboratory abnormalities (elevated alpha-fetoprotein levels, increased chromosomal breakage or cell death of white blood cells after exposure to X-rays, absence of ATM protein in white blood cells, or mutations in each of the person's ATM genes). A variety of laboratory abnormalities occur in most people with A–T, allowing for a tentative diagnosis to be made in the presence of typical clinical features. Not all abnormalities are seen in all patients. These abnormalities include: Elevated and slowly increasing alpha-fetoprotein levels in serum after 2 years of age Immunodeficiency with low levels of immunoglobulins (especially IgA, IgG subclasses, and IgE) and low number of lymphocytes in the blood Chromosomal instability (broken pieces of chromosomes) Increased sensitivity of cells to x-ray exposure (cells die or develop even more breaks and other damage to chromosomes) Cerebellar atrophy on MRI scan The diagnosis can be confirmed in the laboratory by finding an absence or deficiency of the ATM protein in cultured blood cells, an absence or deficiency of ATM function (kinase assay), or mutations in both copies of the cell's ATM gene. These more specialized tests are not always needed, but are particularly helpful if a child's symptoms are atypical. Differential diagnosis There are several other disorders with similar symptoms or laboratory features that physicians may consider when diagnosing A–T. The three most common disorders that are sometimes confused with A–T are: Cerebral palsy Friedreich's ataxia Cogan oculomotor apraxia Each of these can be distinguished from A–T by the neurologic exam and clinical history. Cerebral palsy (CP) describes a non-progressive disorder of motor function stemming from malformation or early damage to the brain. CP can manifest in many ways, given the different manner in which brain can be damaged; in common to all forms is the emergence of signs and symptoms of impairment as the child develops. However, milestones that have been accomplished and neurologic functions that have developed do not deteriorate in CP as they often do in children with A–T in the late pre-school years. Most children with ataxia caused by CP do not begin to walk at a normal age, whereas most children with A–T start to walk at a normal age even though they often "wobble" from the start. Pure ataxia is a rare manifestation of early brain damage or malformation, however, and the possibility of an occult genetic disorder of brain should be considered and sought for those in whom ataxia is the chief manif estation of CP. Children with ataxic CP will not manifest the laboratory abnormalities associated with A–T. Cogan occulomotor apraxia is a rare disorder of development. Affected children have difficulty moving their eyes only to a new visual target, so they will turn their head past the target to “drag” the eyes to the new object of interest, then turn the head back. This tendency becomes evident in late infancy and toddler years, and mostly improves with time. This contrasts to the oculomotor difficulties evident in children with A–T, which are not evident in early childhood but emerge over time. Cogan's oculomotor apraxia is generally an isolated problem, or may be associated with broader developmental delay. Friedreich ataxia (FA) is the most common genetic cause of ataxia in children. Like A–T, FA is a recessive disease, appearing in families without a history of the disorder. FA is caused by mutation in the frataxin gene, most often an expansion of a naturally occurring repetition of the three nucleotide bases GAA from the usual 5–33 repetitions of this trinucleotide sequence to greater than 65 repeats on each chromosome. Most often the ataxia appears between 10 and 15 years of age, and differs from A–T by the absence of telangiectasia and oculomotor apraxia, a normal alpha fetalprotein, and the frequent presence of scoliosis, absent tendon reflexes, and abnormal features on the EKG. Individuals with FA manifest difficulty standing in one place that is much enhanced by closure of the eyes (Romberg sign) that is not so apparent in those with A–T – even though those with A–T may have greater difficulty standing in one place with their eyes open. There are other rare disorders that can be confused with A–T, either because of similar clinical features, a similarity of some laboratory features, or both. These include: Ataxia–oculomotor apraxia type 1 (AOA1) Ataxia–oculomotor apraxia type 2 (AOA2 also known as SCAR1) Ataxia–telangiectasia like disorder (ATLD) Nijmegen breakage syndrome (NBS) Ataxia–oculomotor apraxia type 1 (AOA1) is an autosomal recessive disorder similar to A–T in manifesting increasing problems with coordination and oculomotor apraxia, often at a similar age to those having A–T. It is caused by mutation in the gene coding for the protein aprataxin. Affected individuals differ from those with A–T by the early appearance of peripheral neuropathy, early in their course manifest difficulty with initiation of gaze shifts, and the absence of ocular telangiectasia, but laboratory features are of key importance in the differentiation of the two. Individuals with AOA1 have a normal AFP, normal measures of immune function, and after 10–15 years have low serum levels of albumin. Genetic testing of the aprataxin gene can confirm the diagnosis. There is no enhanced risk for cancer. Ataxia–oculomotor apraxia type 2 (AOA2) is an autosomal recessive disorder also similar to A–T in manifesting increasing problems with coordination and peripheral neuropathy, but oculomotor apraxia is present in only half of affected individuals. Ocular telangiectasia do not develop. Laboratory abnormalities of AOA2 are like A–T, and unlike AOA1, in having an elevated serum AFP level, but like AOA1 and unlike A–T in having normal markers of immune function. Genetic testing of the senataxin gene (SETX) can confirm the diagnosis. There is no enhanced risk for cancer. Ataxia–telangiectasia like disorder (ATLD) is an extremely rare condition, caused by mutation in the hMre11 gene, that could be considered in the differential diagnosis of A–T. Patients with ATLD are very similar to those with A–T in showing a progressive cerebellar ataxia, hypersensitivity to ionizing radiation and genomic instability. Those rare individuals with ATLD who are well described differ from those with A–T by the absence of telangiectasia, normal immunoglobulin levels, a later onset, and a slower progression of the symptoms. Because of its rarity, it is not yet known whether or not ATLD carries an increased risk to develop cancer. Because those mutations of Mre11 that severely impair the MRE11 protein are incompatible with life, individuals with ATLD all have some partial function of the Mre11 protein, and hence likely all have their own levels of disease severity. Nijmegen breakage syndrome (NBS) is a rare genetic disorder that has similar chromosomal instability to that seen in people with A–T, but the problems experienced are quite different. Children with NBS have significant microcephaly, a distinct facial appearance, short stature, and moderate cognitive impairment, but do not experience any neurologic deterioration over time. Like those with A–T, children with NBS have enhanced sensitivity to radiation, disposition to lymphoma and leukemia, and some laboratory measures of impaired immune function, but do not have ocular telangiectasia or an elevated level of AFP. The proteins expressed by the hMre11 (defective in ATLD) and Nbs1 (defective in NBS) genes exist in the cell as a complex, along with a third protein expressed by the hRad50 gene. This complex, known as the MRN complex, plays an important role in DNA damage repair and signaling and is required to recruit ATM to the sites of DNA double strand breaks. Mre11 and Nbs1 are also targets for phosphorylation by the ATM kinase. Thus, the similarity of the three diseases can be explained in part by the fact that the protein products of the three genes mutated in these disorders interact in common pathways in the cell. Differentiation of these disorders is often possible with clinical features and selected laboratory tests. In cases where the distinction is unclear, clinical laboratories can identify genetic abnormalities of ATM, aprataxin and senataxin, and specialty centers can identify abnormality of the proteins of potentially responsible genes, such as ATM, MRE11, nibrin, TDP1, aprataxin and senataxin as well as other proteins important to ATM function such as ATR, DNA-PK, and RAD50. Management Ataxia and other neurologic problems There is no treatment known to slow or stop the progression of the neurologic problems. Treatment of A–T is symptomatic and supportive. Physical, occupational and speech therapies and exercise may help maintain function but will not slow the course of neurodegeneration. Therapeutic exercises should not be used to the point of fatigue and should not interfere with activities of daily life. Certain anti-Parkinson and anti-epileptic drugs may be useful in the management of symptoms, but should be prescribed in consultation with a neurologist. Immune problems All individuals with A–T should have at least one comprehensive immunologic evaluation that measures the number and type of lymphocytes in the blood (T-lymphocytes and B-lymphocytes), the levels of serum immunoglobulins (IgG, IgA, and IgM) and antibody responses to T-dependent (e.g., tetanus, Hemophilus influenzae b) and T-independent (23-valent pneumococcal polysaccharide) vaccines. For the most part, the pattern of immunodeficiency seen in an A–T patient early in life (by age five) will be the same pattern seen throughout the lifetime of that individual. Therefore, the tests need not be repeated unless that individual develops more problems with infection. Problems with immunity sometimes can be overcome by immunization. Vaccines against common bacterial respiratory pathogens such as Hemophilus influenzae, pneumococci and influenza virus (the “flu”) are commercially available and often help to boost antibody responses, even in individuals with low immunoglobulin levels. If the vaccines do not work and the patient continues to have problems with infections, gamma globulin therapy (IV or subcutaneous infusions of antibodies collected from normal individuals) may be of benefit. A small number of people with A–T develop an abnormality in which one or more types of immunoglobulin are increased far beyond the normal range. In a few cases, the immunoglobulin levels can be increased so much that the blood becomes thick and does not flow properly. Therapy for this problem must be tailored to the specific abnormality found and its severity. If an individual patient's susceptibility to infection increases, it is important to reassess immune function in case deterioration has occurred and a new therapy is indicated. If infections are occurring in the lung, it is also important to investigate the possibility of dysfunctional swallow with aspiration into the lungs (see above sections under Symptoms: Lung Disease and Symptoms: Feeding, Swallowing and Nutrition.) Most people with A–T have low lymphocyte counts in the blood. This problem seems to be relatively stable with age, but a rare number of people do have progressively decreasing lymphocyte counts as they get older. In the general population, very low lymphocyte counts are associated with an increased risk for infection. Such individuals develop complications from live viral vaccines (measles, mumps, rubella and chickenpox), chronic or severe viral infections, yeast infections of the skin and vagina, and opportunistic infections (such as pneumocystis pneumonia). Although lymphocyte counts are often as low in people with A–T, they seldom have problems with opportunistic infections. (The one exception to that rule is that problems with chronic or recurrent warts are common.) The number and function of T-lymphocytes should be re-evaluated if a person with A–T is treated with corticosteroid drugs such as prednisone for longer than a few weeks or is treated with chemotherapy for cancer. If lymphocyte counts are low in people taking those types of drugs, the use of prophylactic antibiotics is recommended to prevent opportunistic infections. If the tests show significant abnormalities of the immune system, a specialist in immunodeficiency or infectious diseases will be able to discuss various treatment options. Absence of immunoglobulin or antibody responses to vaccine can be treated with replacement gamma globulin infusions, or can be managed with prophylactic antibiotics and minimized exposure to infection. If antibody function is normal, all routine childhood immunizations including live viral vaccines (measles, mumps, rubella and varicella) should be given. In addition, several “special” vaccines (that is, licensed but not routine for otherwise healthy children and young adults) should be given to decrease the risk that an A–T patient will develop lung infections. The patient and all household members should receive the influenza (flu) vaccine every fall. People with A–T who are less than two years old should receive three (3) doses of a pneumococcal conjugate vaccine (Prevnar) given at two month intervals. People older than two years who have not previously been immunized with Prevnar should receive two (2) doses of Prevnar. At least 6 months after the last Prevnar has been given and after the child is at least two years old, the 23-valent pneumococcal vaccine should be administered. Immunization with the 23-valent pneumococcal vaccine should be repeated approximately every five years after the first dose. In people with A–T who have low levels of IgA, further testing should be performed to determine whether the IgA level is low or completely absent. If absent, there is a slightly increased risk of a transfusion reaction. “Medical Alert” bracelets are not necessary, but the family and primary physician should be aware that if there is elective surgery requiring red cell transfusion, the cells should be washed to decrease the risk of an allergic reaction. People with A–T also have an increased risk of developing autoimmune or chronic inflammatory diseases. This risk is probably a secondary effect of their immunodeficiency and not a direct effect of the lack of ATM protein. The most common examples of such disorders in A–T include immune thrombocytopenia (ITP), several forms of arthritis, and vitiligo. Lung disease Recurrent sinus and lung infections can lead to the development of chronic lung disease. Such infections should be treated with appropriate antibiotics to prevent and limit lung injury. Administration of antibiotics should be considered when children and adults have prolonged respiratory symptoms (greater than 7 days), even following what was presumed to have been a viral infection. To help prevent respiratory illnesses from common respiratory pathogens, annual influenza vaccinations should be given and pneumococcal vaccines should be administered when appropriate. Antibiotic treatment should also be considered in children with chronic coughs that are productive of mucous, those who do not respond to aggressive pulmonary clearance techniques and in children with muco-purulent secretions from the sinuses or chest. A wet cough can also be associated with chronic aspiration which should be ruled out through proper diagnostic studies, however aspiration and respiratory infections are not necessarily exclusive of each other. In children and adults with bronchiectasis, chronic antibiotic therapy should be considered to slow chronic lung disease progression. Culturing of the sinuses may be needed to direct antibiotic therapy. This can be done by an Ear Nose and Throat (ENT) specialist. In addition, diagnostic bronchoscopy may be necessary in people who have recurrent pneumonias, especially those who do not respond or respond incompletely to a course of antibiotics. Clearance of bronchial secretions is essential for good pulmonary health and can help limit injury from acute and chronic lung infections. Children and adults with increased bronchial secretions can benefit from routine chest therapy using the manual method, an a cappella device or a chest physiotherapy vest. Chest physiotherapy can help bring up mucous from the lower bronchial tree, however an adequate cough is needed to remove secretions. In people who have decreased lung reserve and a weak cough, use of an insufflator-exsufflator (cough-assist) device may be useful as a maintenance therapy or during acute respiratory illnesses to help remove bronchial secretions from the upper airways. Evaluation by a Pulmonology specialist however, should first be done to properly assess patient suitability. Children and adults with chronic dry cough, increased work of breathing (fast respiratory rate, shortness of breath at rest or with activities) and absence of an infectious process to explain respiratory symptoms should be evaluated for interstitial lung disease or another intrapulmonary process. Evaluation by a Pulmonologist and a CT scan of the chest should be considered in individuals with symptoms of interstitial lung disease or to rule other non-infectious pulmonary processes. People diagnosed with interstitial lung disease may benefit from systemic steroids. Feeding, swallowing and nutrition Oral intake may be aided by teaching persons with A–T how to drink, chew and swallow more safely. The propriety of treatments for swallowing problems should be determined following evaluation by an expert in the field of speech-language pathology. Dieticians may help treat nutrition problems by recommending dietary modifications, including high calorie foods or food supplements. A feeding (gastrostomy) tube is recommended when any of the following occur: A child cannot eat enough to grow or a person of any age cannot eat enough to maintain weight; Aspiration is problematic; Mealtimes are stressful or too long, interfering with other activities. Feeding tubes can decrease the risk of aspiration by enabling persons to avoid liquids or foods that are difficult to swallow and provide adequate calories without the stress and time commitment of prolonged meals. Gastrostomy tubes do not prevent people from eating by mouth. Once a tube is in place, the general goal should be to maintain weight at the 10–25th percentile. Education and socialization Most children with A–T have difficulty in school because of a delay in response time to visual, verbal or other cues, slurred and quiet speech (dysarthria), abnormalities of eye control (oculomotor apraxia), and impaired fine motor control. Despite these problems, children with A–T often enjoy school if proper accommodations to their disability can be made. The decision about the need for special education classes or extra help in regular classes is highly influenced by the local resources available. Decisions about proper educational placement should be revisited as often as circumstances warrant. Despite their many neurologic impairments, most individuals with A–T are very socially aware and socially skilled, and thus benefit from sustained peer relationships developed at school. Some individuals are able to function quite well despite their disabilities and a few have graduated from community colleges. Many of the problems encountered will benefit from special attention, as problems are often related more to “input and output” issues than to intellectual impairment. Problems with eye movement control make it difficult for people with A–T to read, yet most fully understand the meaning and nuances of text that is read to them. Delays in speech initiation and lack of facial expression make it seem that they do not know the answers to questions. Reduction of the skilled effort needed to answer questions, and an increase of the time available to respond, is often rewarded by real accomplishment. It is important to recognize that intellectual disability is not regularly a part of the clinical picture of A–T although school performance may be suboptimal because of the many difficulties in reading, writing, and speech. Children with A–T are often very conscious of their appearance, and strive to appear normal to their peers and teachers. Life within the ataxic body can be tiring. The enhanced effort needed to maintain appearances and increased energy expended in abnormal tone and extra movements all contribute to physical and mental fatigue. As a consequence, for some a shortened school day yields real benefits. General recommendations All children with A–T need special attention to the barriers they experience in school. In the United States, this takes the form of a formal IEP (Individualized Education Program). Children with A–T tend to be excellent problem solvers. Their involvement in how to best perform tasks should be encouraged. Speech-language pathologists may facilitate communication skills that enable persons with A–T to get their messages across (using key words vs. complete sentences) and teach strategies to decrease frustration associated with the increase time needed to respond to questions (e.g., holding up a hand and informing others about the need to allow more time for responses). Rarely helpful are traditional speech therapies that focus on the production of specific sounds and strengthening of the lip and tongue muscles. Classroom aides may be appropriate, especially to help with scribing, transportation through the school, mealtimes and toileting. The impact of an aide on peer relationships should be monitored carefully. Physical therapy is useful to maintain strength and general cardiovascular health. Horseback therapy and exercises in a swimming pool are often well tolerated and fun for people with A–T. However, no amount of practice will slow the cerebellar degeneration or improve neurologic function. Exercise to the point of exhaustion should be avoided. Hearing is normal throughout life. Books on tape may be a useful adjunct to traditional school materials. Early use of computers (preschool) with word completion software should be encouraged. Practicing coordination (e.g. balance beam or cursive writing exercises) is not helpful. Occupational therapy is helpful for managing daily living skills. Allow rest time, shortened days, reduced class schedule, reduced homework, modified tests as necessary. Like all children, those with A–T need to have goals to experience the satisfaction of making progress. Social interactions with peers are important, and should be taken into consideration for class placement. For everyone long-term peer relationships can be the most rewarding part of life; for those with A–T establishing these connections in school years can be helpful. Treatment No curative medication has been approved for the treatment of inherited cerebellar ataxias, including Ataxia-Telangiectasia. The treatment of A-T remains based in medical management (of immunodeficiencies and sinopulmonary infections, neurologic dysfunction, and malignancy) and neurorehabilitation (physical, occupational, and speech/swallowing therapy; adaptive equipment; and nutritional counseling). N-Acetyl-Leucine N-Acetyl-Leucine is an orally administered, modified amino acid that is being developed as a novel treatment for multiple rare and common neurological disorders by IntraBio Inc (Oxford, United Kingdom). N-Acetyl-Leucine has been granted multiple orphan drug designations from the U.S. Food & Drug Administration (FDA)and the European Medicines Agency (EMA)for the treatment of various genetic diseases, including Ataxia-Telangiectasia. N-Acetyl-Leucine has also been granted Orphan Drug Designations in the US and EU for related inherited cerebellar ataxias, such as Spinocerebellar Ataxias. U.S. Food & Drug Administration (FDA) and the European Medicines Agency (EMA). Published case series studies have demonstrated the positive clinical benefit of treatment with N-Acetyl-Leucine various inherited cerebellar ataxias. Additional compassionate use studies in patients with Ataxia Telangiectasia have shown the symptomatic, and disease-modifying potential of the treatment. These studies further demonstrated that the treatment is well tolerated, with a good safety profile. A multinational clinical trial investigating N-Acetyl-L-Leucine for the treatment Ataxia-Telangiectasia began in 2019. IntraBio is also conducting two parallel clinical trials with N-Acetyl-L-Leucine for the treatment Niemann-Pick disease type C and GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease) Future opportunities to develop N-Acetyl-Leucine include Lewy Body Dementia, Amyotrophic lateral sclerosis, Restless Leg Syndrome, Multiple Sclerosis, and Migraine. Prognosis The life expectancy of people with A–T is highly variable. The average is approximately 25 years, but continues to improve with advances in care. The two most common causes of death are chronic lung disease (about one-third of cases) and cancer (about one-third of cases). Epidemiology Individuals of all races and ethnicities are affected equally. The incidence worldwide is estimated to be between 1 in 40,000 and 1 in 100,000 people. Research directions An open-label Phase II clinical trial studying the use of red blood cells (erythrocytes) loaded with dexamethasone sodium phosphate found that this treatment improved symptoms and appeared to be well tolerated. This treatment uses a unique delivery system for medication by using the patient's own red blood cells as the delivery vehicle for the drug. Given the other immunologic deficits present in individuals with A–T, there remains a need to evaluate the therapeutic potential of steroids further, particularly with respect to the duration of any benefit and its long-term safety. References External links About A–T from the NINDS Orphanet for A–T GeneReviews for ataxia–telangiectasia Replication-Independent Double-Strand Breaks (DSBs) Discusses importance of the ATM kinase Category:Chromosome instability syndromes Category:Genodermatoses Category:Systemic atrophies primarily affecting the central nervous system Category:Neurodegenerative disorders Category:IUIS-PID table 3 immunodeficiencies Category:DNA replication and repair-deficiency disorders Category:Syndromes affecting the nervous system Category:Syndromes with tumors | High | [
0.691056910569105,
31.875,
14.25
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13 Evaluate ((-28)/(-1890))/((-7)/35). -2/27 (-4)/(-40) - 1159/190 -6 What is ((-3)/51)/((-29)/(-2) + -14)? -2/17 What is (8/32)/((-7)/(453 + -5))? -16 What is the value of (16 - -20)/(-108)*72? -24 What is 2375/500*3/((-3)/(-4))? 19 Calculate (-257 - -271)*((-158)/(-28) + -3). 37 (-4 - -10)*(1648/96 - 14) 19 What is ((144/30)/3)/((-96)/1920)? -32 Calculate (8/20)/(18/1260) + 5 + -9. 24 What is (-286)/26*112/88? -14 What is the value of (-1 - -16) + -12 + (-39)/6? -7/2 What is (61 + 11000/(-180))/((-2)/450)? 25 338/(-26) - 3/15*0 -13 Calculate 14/(-4) + 39/((-126360)/(-17676)) - 2. -2/45 (-20 + (-3366)/(-165))*10*(-2)/(-16) 1/2 What is the value of (-19)/76*((4 - 2) + -94)? 23 What is the value of ((-3336)/2780)/((-1)/5 - 0)? 6 (-5)/(38 - (-227)/(-6)) -30 Evaluate (-163)/(-652) + 1/(-36). 2/9 Evaluate (-1 - -2)*(-1216)/(-4864)*(-12)/22. -3/22 What is the value of 10/(-140) + 14/196 + (-4)/(-6)? 2/3 Calculate (-893)/(-470) - 6/(-60). 2 Evaluate (-40)/4 + 1 + 16120/1768. 2/17 Calculate (-4230)/(-32430) + 3/(-23). 0 Calculate -2*(-9)/(-6)*81/(-243)*-17. -17 What is (43/258)/((-1)/66)? -11 Calculate (70/(-49))/(-10) - (-110)/14. 8 Evaluate (6/120*-5)/(-4 - 1835/(-460)). 23 (-1)/2*(-245)/196 5/8 (16/2)/2 - 5 - 60/6 -11 Calculate -13 + (-2 - -26) + 2. 13 Calculate 14/(-910)*-13 - (39/(-40))/(-3). -1/8 What is 1 - -33 - ((-40)/(-15))/(23/69)? 26 What is (17 - 11) + 5/(-7)*(-490)/(-60)? 1/6 -14 - -16 - 4/(7 + -6) -2 Evaluate (-154)/(-77) - (-27)/(-12). -1/4 What is 180/(-162) - 2546/171? -16 Calculate (-11)/(1320/(-72)) - (286/10 - 3). -25 Evaluate 14091/854*(-2)/3. -11 Evaluate 8151/(-234) + 34 + (-95)/30. -4 What is the value of 9/6 + (-2 - (-4 + (-138)/(-36)))? -1/3 Calculate 9828/214839 - (-8)/(-292). 2/109 Calculate ((-2586)/7327)/((-6)/136). 8 What is (16/(-28))/(4/(1 + -108 - -9))? 14 Evaluate 3 + ((-88)/264)/((-2)/24). 7 What is the value of 140/20 - (-1)/(-1)? 6 Evaluate -15 + ((-31)/(465/12))/((-4)/30). -9 What is the value of (-32)/(4*((-1007)/76 - -13))? 32 ((-56)/(-108))/((-1)/(-12)) - 120/20 2/9 What is (36/15)/((-18)/(-33) + (-9028)/6105)? -18/7 Calculate (-6)/10 + 1 - ((-902)/615)/(-22). 1/3 -7*1 - (-39)/27*5 2/9 Evaluate 2790/(-465)*(5 - 1). -24 1076/(-1614) + 2*(-4)/(-2) 10/3 Evaluate 2 - -1*(-6 + 57/6)*2. 9 50/(-15)*(279/310)/((-2)/4) 6 What is (-14)/(-9) + (-360)/270? 2/9 Evaluate (3 - (-14)/(350/(-55)))/(14/(-5)). -2/7 What is the value of (-1120)/(-110) - (-5 + (-114)/(-22))? 10 Calculate 1848/1496 + (2/(-12) - (-50)/(-60)). 4/17 Calculate -1 - (2 - -10 - 2) - 6. -17 5 + (-102)/9 + (-4)/(-12) -6 (5/(-20))/((-14)/(-56)) -1 What is (-1)/8 - ((-15096)/(-4032))/(-17)? 2/21 Evaluate 8*(-9 + 287/28). 10 Calculate (-17)/((-11 - (40*-3)/12)*1). 17 What is 5175/270 + (-200)/10? -5/6 958/(-5269) + (-207)/11 -19 What is the value of (6/(3 + -33))/(34/(-3740))? 22 Calculate (-1)/((-3)/(-2)) + 340/15 + -21. 1 What is (-22)/(-4)*(-21)/(-924)? 1/8 Evaluate ((-20493)/1587 + (-6)/69)/((-4)/(-12)). -39 Calculate (-8)/(-18)*(-70335)/3126. -10 What is the value of (-1)/5*(5 - 0) - (9 + -9)? -1 What is ((-3)/(-6))/(-10 + 261/26)? 13 Calculate (-793)/3843 - (-6)/(-27). -3/7 Evaluate (-22)/((-19)/(342/(-108))). -11/3 (-220)/(-50)*(20 + 285/(-19)) 22 What is (-20*(-16)/176)/(22/121)? 10 Evaluate (-3 - -2)/(9/((-72)/80) + 13). -1/3 ((-35)/2)/(1092/(-936)) 15 What is ((-63)/(-216) + (-12)/32)/(1/(-3))? 1/4 What is ((-17)/(-51)*30*(4 - 2))/2? 10 What is the value of 0 - -75*(-54)/3645? -10/9 (-22)/132*36/3 -2 166944/7548 + 1*-22 2/17 ((-182)/(-93) - 2)/((-1448)/2172) 2/31 Evaluate 3 - (-52)/(-14) - (-3689)/(-7595). -6/5 What is the value of -5*(-36)/(-15 + 27)? 15 Calculate 35 + 2813/(-87) - -8*12/(-9). -8 What is (-234)/(-1365) + 15/(-25)? -3/7 Calculate ((-1452)/10)/(-11) + -12. 6/5 What is the value of 4/2*((-1)/(-5))/(904/(-565))? -1/4 Calculate 166/(-22) - ((-91)/(-13) - 14). -6/11 Calculate (54/(-4))/3*(-9)/(-108). -3/8 What is the value of ((-4)/3)/(505/303)? -4/5 What is (-2)/(-15)*(-300)/180 - (-98)/360? 1/20 Calculate (-450)/300*4/(-10). 3/5 What is ((-7)/14)/((-235)/(-94))? -1/5 Calculate (45 + -51 + (-33)/(-6))/(2/20). -5 (-209 - -212) + (-24)/14 9/7 Calculate (-30)/(-5)*(-6)/(-9)*(-1353)/164. -33 Evaluate (83 - -1)/3 - (-234 + 250). 12 (1825/(-375) - -5) + ((-32)/(-30) - 1) 1/5 Calculate -5*(-5)/(-50)*18. -9 Evaluate ((-6)/(-3564)*9)/(13/78). 1/11 (-4)/(-10)*(-860)/(-86) 4 282/(-235)*(-25)/9 10/3 (((-12)/16)/((-33)/(-11)))/((-15)/(-12)) -1/5 Evaluate (-142)/10 + (-10136)/3620. -17 What is 9/((-675)/20)*(-12)/56? 2/35 What is the value of -5*(11/(55/20))/(-5)? 4 (-15)/((-2520)/(-16))*-1 2/21 Evaluate (((-108)/(-18))/(-6))/(3/24). -8 5/4*(-392)/1715 -2/7 6/(-5)*-6*1010/606 12 (12/(-30))/((-4)/((-7)/28*-70)) 7/4 Calculate (13/(-2))/(13780/(-2120)). 1 Calculate 5 + (-568)/120 - (-10)/25. 2/3 What is 1*(11*(4 - 5) + 0/2)? -11 Calculate 10/(60/18)*66/(-11). -18 (-14)/5 - 42/504*-12 -9/5 What is the value of ((-4)/(-185))/(-18 - 1104/(-60))? 2/37 Calculate 1133/721 - (-9)/21. 2 Evaluate ((-2)/1)/(2748/(-26106)). 19 (-1610)/(-391) - 2/17 4 Calculate (119/28 + -5)*(-2)/(-3). -1/2 What is (16/280)/(-9 - (-352)/56)? -2/95 Calculate (45/(-10))/(9 + (-300)/24). 9/7 What is the value of (-171)/912 - (-660)/(-576)? -4/3 What is (3/(-2))/(13 + (-2464)/160)? 5/8 Calculate (-3 + 2 - -8) + (-836)/133. 5/7 Calculate (-28 + 22)*(-4)/48*-8. -4 Calculate (-4)/(-10) - (249/9628)/((-60)/(-688)). 3/29 Calculate (-3)/(21/((-315)/80) + 5). 9 What is ((-1919)/190 + 10)/1? -1/10 ((-4)/(-10) - (-506)/10)/(1152 + -1155) -17 12/78*(-17 + 2664/16) 23 Evaluate (-1450)/(-348) - (-322)/(-69). -1/2 ((-6)/(-8))/((-60)/(-112)) 7/5 What is 167/275 + (-2430)/(-20250)? 8/11 Evaluate 2/(-12)*-2*(90 + -46 - 41). 1 Evaluate (5/5)/((-9)/12*(-2)/6). 4 -9*90/(-81) + 2 12 Calculate ((-3749)/161 - -1) + 21. -9/7 What is the value of ((-1)/4)/(20/1120)? -14 What is the value of (-4)/14 + 282/(-1316)? -1/2 Evaluate -13 + 45 - -2 - 18. 16 Evaluate (-27)/((-270)/350)*3/(-15)*-2. 14 What is 42/24*((-1760)/2660)/(-11)? 2/19 Calculate (1/(-64 - -65))/(-1 + 90/87). 29 Evaluate ((-378)/36 - -10)*(-2)/7. 1/7 What is -20 + 1026/51 - ((-173)/(-170) - 1)? 1/10 Evaluate 78/104 + 30/(-8) + 264/24. 8 Evaluate 32 - 16 - 19416/1212. -2/101 Evaluate (-11 - -17) + (228/40)/(-1). 3/10 1/(4/18 + 18425/(-495)) -1/37 2418/(-162) - (-30)/(-405) -15 Evaluate (-272)/119*(-14)/4. 8 What is the value of 66/(-17) - (650/(-255) - 56/(-21))? -4 What is the value of -5*8/(-220) + 276/2673*-2? -2/81 What is the value of 87/174 - 5/(-2)? 3 9 + 7 + -4 + (1 - 4) + -21 -12 What is the value of ((-184)/6*(-2)/(-8))/(183/549)? -23 Evaluate 10/2*284/(-12070). -2/17 What is 184/(-1656)*(-27)/3? 1 Calculate 0/(-2)*300/1500. 0 Evaluate (-674)/32 - (-71)/1136. -21 Calculate 1/(-265*6/225 + 7). -15 What is the value of ((-92)/(-6))/(-23) - (-32)/9? 26/9 -6 + (((-1408)/(-96))/(-22) - 70/3) -30 -1 + (-16)/32 + 15*3/(-6) -9 (24/(-9) + -2)*29/580*-6 7/5 Evaluate 39/(-143) + 438/33. 13 Evaluate 11 - 2457/196 - 10/(-8). -2/7 What is (-3)/((-504)/(-284)) - (-180)/216? -6/7 Calculate (2 - 0)/((-106)/1007). -19 What is 3088/193 + (15/6)/((-1)/(-2))? 21 Evaluate -2 + (-2)/30*(-39 + 11). -2/15 Calculate (-1)/(-3) + (-512)/(-192). 3 Calculate 1*(-14*3/6 + 10). 3 (-105)/(-5)*((-220)/(-66) + (-2 - 2)) -14 Evaluate (-630)/48*(-328)/123. 35 8 - (5/(-10) - (-5 + (-49)/(-2))) 28 What is (-2)/4*(117/3 - 9)? -15 Calculate 2816/3744 - 24/54. 4/13 What is the value of 2276/(-1320) + (-70)/(-84) - 2/10? -12/11 What is the value of ((-6)/10)/(12/300*3)? -5 What is (-1)/248*-171 + 1844/(-28582)? 5/8 0/((14 + -19)/(-5)) 0 What is 9 - (-117)/(-13)*2? -9 Evaluate (-704)/33 + 28 + -6. 2/3 Calculate (-4)/5 - (-190)/225. 2/45 Calculate (20*40/2000)/(4/190). 19 Evaluate (27*(-5)/15 - -10)*-5. -5 What is 17/119 + 12/(-21)? -3/7 78/15*(-665)/(-266) 13 Evaluate 22 - 24 - ((-9)/((-2844)/940) - 5). 2/79 Calculate (-189)/(-308)*(-320)/(-24) + -8. 2/11 Evaluate (72/14)/((-5656)/98 + 58). 18 6/(-52) - 318859/(-19786) 16 Calculate (-6 - -7)/(5*(-10)/700). -14 What is ((-588)/112)/((-6)/(-16))? -14 Calculate ((2 + -1)/((-255)/102))/((-4)/(-22)). -11/5 Evaluate 23/(1288/42) + 63/12. 6 Calculate -12 + -1 - ((-785)/15 + 38). 4/3 What is the value of (-76)/(-437) + 12662/(-598)? | Mid | [
0.54047619047619,
28.375,
24.125
] |
Top 5 Things to Do in Phoenix This Weekend Chris Tucker @ Celebrity Theatre Go ahead and call it a comeback. After effectively dropping off the face of the earth following the release of 2007's massively successful Rush Hour 3, comedian Chris Tucker is relaunching his career. His stand-up tour stops in the Valley Friday, March 22. | Low | [
0.35406698564593303,
18.5,
33.75
] |
Arkadiusz Moryto Arkadiusz Moryto (born 31 August 1997) is a Polish handball player who plays for PGE Vive Kielce and the Polish national team. He participated at the 2017 World Men's Handball Championship. References Category:1997 births Category:Handball players Category:Living people Category:Sportspeople from Kraków Category:Polish male handball players Category:Vive Kielce players | High | [
0.73449920508744,
28.875,
10.4375
] |
Haseeb Hameed and Ben Duckett look to be the likely beneficiaries of the decision by Alex Hales and Eoin Morgan to miss the tour of Bangladesh, as England's selectors prepare to name their Test and ODI squads. A recall for off-spinner Gareth Batty, who will be 39 by the time the Test series starts, is also anticipated, as well as his Surrey team-mate, Zafar Ansari. Duckett, who has enjoyed an outstanding season with Northants, looks set to come into the limited-overs squad, while Hameed has emerged as the likely replacement for Hales as Alastair Cook's opening partner in the Test squad. Other uncapped players with a chance of a call-up include the left-arm spinner Jack Leach, as well as Durham's opening batsman Keaton Jennings and the Surrey wicketkeeper, Ben Foakes. England's potential new faces Haseeb Hameed 1129 fc runs @ 51.31, 4x100 Keaton Jennings 1522 fc runs @69.18, 7x100 Ben Foakes 739 fc runs @43.47, 1x100 Gareth Batty 41 fc wkts @ 32.31 Ben Duckett 2706 runs in all formats this season England look set to name an unusually large 17-man squad for the two-Test series, plus a 15-man squad for the three-match ODI series in Bangladesh. And, while the tour moves straight into a Test series in India without warm-up games, the ECB have specified that this squad will cover the Bangladesh segment only. The most contentious decisions ahead of the announcement of the Test squad (at 10am on Friday) focus on the identity of Cook's new opening partner, the identity of the reserve wicketkeeper and the identity of the side's third (and perhaps fourth) spin bowler. While Moeen Ali and Adil Rashid are sure to be named as the two main spinners in the squad, the battle for the remaining places is intriguing. Batty, despite his age, is expected to return as an experienced pro, with Ansari a strong possibility despite an injury-ravaged year. Jack Leach may have to be content with a Lions tour despite 58 Championship wickets at a cost of 22.60 this season. Liam Dawson, who has claimed only 15 Championship wickets at an average of 46.80 this season but is seen as a good controlling bowler, is expected to miss out, as is Ollie Rayner who has claimed 50 Championship wickets this season. The selectors have a similarly tricky decision to make over the opening position. While Sam Robson has looked in good touch this season - Warwickshire believe he played Jeetan Patel, Division One's leading wicket-taker, better than anyone - it seems Hameed is the one who has made the biggest impression on the selectors. Haseeb Hameed looks set to be named as Alastair Cook's new opening partner Getty Images Aged just 19 and with fewer than 20 first-class games behind him, his selection would, in some ways, constitute a gamble. But he has impressed with his tight technique and unflustered temperament - his director of cricket at Lancashire, Ashley Giles, compares his hatred of losing his wicket as similar to that of Jonathan Trott's - and England's head coach, Trevor Bayliss, is understood to have been impressed by the footage he has seen of him in action. Jennings' success this season is hard to ignore, though. Nobody in the top division of the County Championship has scored more runs - he has made 1,522 at 69.18 - or as many centuries (seven). Having just qualified for England (he is the son of Ray Jennings, the former South Africa wicketkeeper), he has made a compelling case for selection. Mark Wood looks sure to return, while James Vince looks set to miss out. Gary Ballance is another who faces an anxious wait, though he may well have done just enough. The choice of reserve wicketkeeper comes down to a choice between Foakes and Jos Buttler. Foakes has only had one full season as first-choice keeper, but is clearly a special talent, while Buttler has, at this stage, played only one red-ball game since he was dropped from the Test team last October. His record against spin isn't wonderful, either, though his talent is unquestioned and his appointment as stand-in ODI captain demonstrates the management's faith in his character. There was a time when the selectors suggested that nobody would be selected for England unless they had previously come through the Lions system. There is some sense in that stance, too, as it gives the management an idea of how their players will react in a new environment and, often, at a slightly higher level. But that isn't an option this time. The ECB did not arrange any red-ball cricket for the Lions over the winter of 2015-16 or over the summer of 2016, so there has been no chance to see how Jennings or Hameed might cope. To be fair, both have developed from relative obscurity and would have been unlikely candidates for a Lions tour this time last year. This winter, the Lions are hoping to play two four-day games (and five limited-overs games) in Sri Lanka and, subject to agreements, a three-day game against Afghanistan in Dubai before Christmas. The squad for those tours will be named on Monday. While Duckett is a pretty clear choice for the ODI squad - it is by no means impossible that a successful debut would render Eoin Morgan's return problematic - there may well be opportunities for several other fringe players (the likes of Sam Billings and Dawid Malan, among them) if, as expected, England rest the likes of Joe Root and Moeen from the limited-overs section of the tour. | Mid | [
0.6477541371158391,
34.25,
18.625
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/*
* Copyright (C) 2006 TopCoder Inc., All Rights Reserved.
*/
package com.topcoder.uml.actions.model.sequence.accuracytests;
import com.topcoder.uml.actions.model.sequence.AddObjectAction;
import com.topcoder.uml.model.collaborations.collaborationinteractions.Collaboration;
import com.topcoder.uml.model.collaborations.collaborationinteractions.CollaborationImpl;
import com.topcoder.uml.model.commonbehavior.instances.ObjectImpl;
import com.topcoder.uml.modelmanager.UMLModelManager;
import com.topcoder.uml.projectconfiguration.ProjectConfigurationManager;
/**
* <p>
* Accuracy test for <code>{@link AddObjectAction}</code> class.
* </p>
*
* @author FireIce
* @version 1.0
*/
public class AddObjectActionAccuracyTests extends BaseTestCase {
/**
* <p>
* Represents the <code>AddObjectAction</code> instance used in tests.
* </p>
*/
private AddObjectAction addObjectAction;
/**
* <p>
* Accuracy test for
* <code>{@link AddObjectAction#AddObjectAction(Stimulus, Collaboration, UMLModelManager)}</code>
* constructor.
* </p>
*/
public void testAddObjectActionAccruracy() {
addObjectAction = new AddObjectAction(new ObjectImpl(), new CollaborationImpl(), new UMLModelManager());
assertNotNull("object not created", addObjectAction);
}
/**
* <p>
* Accuracy test for <code>{@link AddObjectAction#execute()}</code>
* method.
* </p>
*
* @throws Exception pass any unexpected exception to JUnit.
*/
public void testExecuteAccuracy() throws Exception {
UMLModelManager umlModelManager = new UMLModelManager();
umlModelManager.setProjectConfigurationManager(new ProjectConfigurationManager(umlModelManager));
addObjectAction = new AddObjectAction(new ObjectImpl(), new CollaborationImpl(), umlModelManager);
addObjectAction.execute();
assertFalse("should not logged.", confirmFileContents("WARN"));
}
/**
* <p>
* Accuracy test for <code>{@link AddObjectAction#undo()}</code> method.
* </p>
*
* @throws Exception pass any unexpected exception to JUnit.
*/
public void testUndoAccuracy1() throws Exception {
UMLModelManager umlModelManager = new UMLModelManager();
umlModelManager.setProjectConfigurationManager(new ProjectConfigurationManager(umlModelManager));
addObjectAction = new AddObjectAction(new ObjectImpl(), new CollaborationImpl(), umlModelManager);
addObjectAction.die();
addObjectAction.undo();
assertTrue("should logged warn as can not undo.", confirmFileContents("WARN"));
}
/**
* <p>
* Accuracy test for <code>{@link AddObjectAction#undo()}</code> method.
* </p>
*
* @throws Exception pass any unexpected exception to JUnit.
*/
public void testUndoAccuracy2() throws Exception {
UMLModelManager umlModelManager = new UMLModelManager();
umlModelManager.setProjectConfigurationManager(new ProjectConfigurationManager(umlModelManager));
addObjectAction = new AddObjectAction(new ObjectImpl(), new CollaborationImpl(), umlModelManager);
addObjectAction.execute();
addObjectAction.undo();
assertFalse("should not logged warn as can undo.", confirmFileContents("WARN"));
}
/**
* <p>
* Accuracy test for <code>{@link AddObjectAction#redo()}</code> method.
* </p>
*
* @throws Exception pass any unexpected exception to JUnit.
*/
public void testRedoAccuracy1() throws Exception {
UMLModelManager umlModelManager = new UMLModelManager();
umlModelManager.setProjectConfigurationManager(new ProjectConfigurationManager(umlModelManager));
addObjectAction = new AddObjectAction(new ObjectImpl(), new CollaborationImpl(), umlModelManager);
addObjectAction.die();
addObjectAction.redo();
assertTrue("should logged warn as can not undo.", confirmFileContents("WARN"));
}
/**
* <p>
* Accuracy test for <code>{@link AddObjectAction#redo()}</code> method.
* </p>
*
* @throws Exception pass any unexpected exception to JUnit.
*/
public void testRedoAccuracy2() throws Exception {
UMLModelManager umlModelManager = new UMLModelManager();
umlModelManager.setProjectConfigurationManager(new ProjectConfigurationManager(umlModelManager));
addObjectAction = new AddObjectAction(new ObjectImpl(), new CollaborationImpl(), umlModelManager);
addObjectAction.execute();
addObjectAction.undo();
addObjectAction.redo();
assertFalse("should not logged warn as can redo.", confirmFileContents("WARN"));
}
/**
* <p>
* Accuracy test for
* <code>{@link AddObjectAction#getPresentationName()}</code> method.
* </p>
*/
public void testGetPresentationNameAccuracy() {
addObjectAction = new AddObjectAction(new ObjectImpl(), new CollaborationImpl(), new UMLModelManager());
assertEquals("incorrect presentation name", "Add Object", addObjectAction.getPresentationName());
}
}
| Low | [
0.50179211469534,
35,
34.75
] |
class SuperAdminPermit < CanTango::RolePermit def initialize ability super end def static_rules can :manage, :all end end | Low | [
0.5125858123569791,
28,
26.625
] |
Q: Chain promises while condition is true I'm trying to get all pages requsted via XHR using JS Promise. For me it's relatively trivial to get this with recursive callbacks, but how I can achieve this with promises? Simplified example without promises: class Foo { getPages(callback, pagesCount) { if (typeof(pagesCount) === 'undefined') { pagesCount = 0; } // Let's say its async XHR window.setTimeout(() => { ++pagesCount; // Let's say that in 90% of cases we will get a full page if (Math.random() < 0.9) { console.log('Page received!'); this.getPages(callback, pagesCount); } else { console.log('Last page received!'); callback(pagesCount); } }, 1000); } doStuff(pagesCount) { console.log('Total pages: ' + pagesCount); } run() { this.getPages(this.doStuff); } } (new Foo()).run(); And I'm trying to achieve something like: class Foo { getPages() { ... } doStuff(pagesCount) { console.log('Total pages: ' + pagesCount); } run() { this.getPages().then(this.doStuff); } } (new Foo()).run(); A: Before the advent of async/await recursive promises were indeed impossible. You'd have to convert the promise into a callback friendly code and do your recursion using callbacks. However, async/await allows you to do what you want: async getPages(pagesCount) { if (typeof(pagesCount) === 'undefined') { pagesCount = 0; } // Let's say its async XHR while () { // Call promisified XHR like this: // xhrResult = await XHR(); // Call callback based XHR like this: // xhrResult = await new Promise(function(ok,err){ // XHR(function (error, result) { // if (error) { // err(error) // } else { // ok(result) // } // }); if (Math.random() < 0.9) { console.log('Page received!'); return await getPages(pagesCount); } else { console.log('Last page received!'); return pagesCount; } }; } Note: all functions marked async return promises. So now you can do: getPages(100).then(count => console.log(count + ' pages left')) | Mid | [
0.637096774193548,
29.625,
16.875
] |
Neural synchrony indexes impaired motor slowing after errors and novelty following white matter damage. In humans, action errors and perceptual novelty elicit activity in a shared frontostriatal brain network, allowing them to adapt their ongoing behavior to such unexpected action outcomes. Healthy and pathologic aging reduces the integrity of white matter pathways that connect individual hubs of such networks and can impair the associated cognitive functions. Here, we investigated whether structural disconnection within this network because of small-vessel disease impairs the neural processes that subserve motor slowing after errors and novelty (post-error slowing, PES; post-novel slowing, PNS). Participants with intact frontostriatal circuitry showed increased right-lateralized beta-band (12-24 Hz) synchrony between frontocentral and frontolateral electrode sites in the electroencephalogram after errors and novelty, indexing increased neural communication. Importantly, this synchrony correlated with PES and PNS across participants. Furthermore, such synchrony was reduced in participants with frontostriatal white matter damage, in line with reduced PES and PNS. The results demonstrate that behavioral change after errors and novelty result from coordinated neural activity across a frontostriatal brain network and that such cognitive control is impaired by reduced white matter integrity. | High | [
0.673684210526315,
32,
15.5
] |
37 Wn. App. 295 (1984) 680 P.2d 439 KENART & ASSOCIATES, Appellant, v. SKAGIT COUNTY, ET AL, Respondents. No. 10737-2-I. The Court of Appeals of Washington, Division One. April 9, 1984. As amended by order April 16, 1984. Kenneth J. Evans, for appellant. C. Thomas Moser, Prosecuting Attorney, and John R. Moffat, Chief Civil Deputy, for respondents. [As amended by order of the Court of Appeals April 16, 1984.] JOHNSEN, J.[*] Kenart & Associates (Kenart) owns land in Skagit County which it wished to develop. The Board of County Commissioners denied Kenart's application for a Planned Unit Development (PUD) and Kenart sought review by way of writ of review. The Superior Court affirmed the decision of the Board and Kenart has appealed. The findings of fact, which are not challenged, are as follows: 1. Plaintiff Kenart and Associates filed an application with defendant Skagit County for a preliminary plat of Kenart Estates, an 80 lot, 79.5 acre Planned Unit Development located approximately three miles north of Sedro *297 Woolley, Skagit County, Washington. 2. This matter was referred to the Skagit County Planning Commission which held a public hearing on June 23, 1980, at which the applicant, the County and other interested citizens had an opportunity to present their views on a proposal; at the conclusion of the public hearing, the Planning Commission voted to continue the matter until July 14, 1980. 3. On July 14, the Planning Commission voted to deny the application for preliminary plat approval of Kenart Estates P.U.D. 4. The recommendation of the Planning Commission was then referred to the Skagit County Board of Commissioners. 5. The Board considered the matter at public meetings on July 29 and August 6, 1980. 6. On August 6, 1980, the Board of County Commissioners voted to remand the matter to the Skagit County Planning Commission for the preparation of findings of fact to support the recommendation previously made by the Planning Commission. 7. On August 11, 1980, the Skagit County Planning Commission adopted findings denying the Kenart Estates P.U.D. The Planning Commission recommended denial of the proposal for the following reasons: 1. The soils on the subject property have been identified prime agricultural soils. Approval of the P.U.D. would contribute incrementally to the loss of agricultural lands and potential agricultural lands; 2. The P.U.D. would increase traffic levels on SR 9 by significant amounts. This concern is substantiated in the D.E.I.S.; 3. Potential drainage problems associated with known periodical flooding of creeks which flow through the subject property; 4. Potential adverse impact on existing domestic water sources; 5. Lack of adequate services such as fire protection, police protection, potential capacity problems of schools, particularly Samish Elementary; 6. Potential disruption of existing rural life styles; 7. No evidence to substantiate the need for the creation of additional lots; 8. The public interest will not be served by approval of *298 this P.U.D. 8. On August 26, 1980, the Board of County Commissioners unanimously voted to accept the recommendation of the Planning Commission to deny the Kenart Estates P.U.D.... The court concluded that the record contained sufficient evidence to support and validate the findings made below and that the decision of the Board of County Commissioners was not arbitrary, capricious or unreasoning. The court further concluded that the Board's referral back to the Planning Commission for the entry of findings was not error, that denial of the plat was not an unconstitutional taking of property, and that there was no requirement for a county legislative body to advise the applicant either orally or in writing of what steps he should take in order to have the application approved at a later date. The court then entered an order affirming the Board's decision. Error has been assigned to the court's decision upholding the Board and to the court's refusal to direct the Board to determine what changes in the plat were required in order to obtain approval or specify what conditions precluded any possibility of approval. Prior to its acquisition by Kenart, this 79.5-acre property had been zoned as residential, that is, one residence was allowed for each 12,500 square feet. Later the acreage was rezoned as residential reserve, which required a full acre for each residence. Kenart's proposal is for a PUD of 80 lots on 79.5 acres with 39 acres of clustered residential development, 30 acres of open space and 10 acres for a gravel pit. [1] A request for approval of a planned unit development is treated as a request for a rezone. Lutz v. Longview, 83 Wn.2d 566, 520 P.2d 1374 (1974); Johnson v. Mount Vernon, 37 Wn. App. 214, 679 P.2d 405 (1984). An appellate court will overturn a governmental body's decision on a rezone only if the decision is arbitrary or capricious. Lechelt v. Seattle, 32 Wn. App. 831, 650 P.2d 240 (1982); RCW 58.17.180. Arbitrary and capricious action has been defined as *299 willful and unreasoning action, without consideration and in disregard of facts and circumstances. Where there is room for two opinions, action is not arbitrary and capricious even though one may believe an erroneous conclusion has been reached. (Citations omitted.) State v. Rowe, 93 Wn.2d 277, 284, 609 P.2d 1348 (1980). The party alleging that an action is arbitrary and capricious bears the burden of so showing. Pierce Cy. Sheriff v. Civil Serv. Comm'n, 98 Wn.2d 690, 658 P.2d 648 (1983). Kenart argues that the Board's findings are not supported by the record and further argues that the Board must tell Kenart how to correct the application so it will be approved or if there are factors which would prohibit approval under any circumstances. Kenart also argues that the process as conducted here violated the "appearance of fairness" doctrine and amounts to an unconstitutional taking of property without compensation. The criteria for approving or disapproving the preliminary plat of a proposed subdivision are stated in RCW 58.17.110, which reads in relevant part as follows: The city, town, or county legislative body shall inquire into the public use and interest proposed to be served by the establishment of the subdivision and dedication. It shall determine if appropriate provisions are made for, but not limited to, the public health, safety, and general welfare, for open spaces, drainage ways, streets, alleys, other public ways, water supplies, sanitary wastes, parks, playgrounds, sites for schools and schoolgrounds, and shall consider all other relevant facts and determine whether the public interest will be served by the subdivision and dedication. If it finds that the proposed plat makes appropriate provisions for the public health, safety, and general welfare and for such open spaces, drainage ways, streets, alleys, other public ways, water supplies, sanitary wastes, parks, playgrounds, sites for schools and schoolgrounds and that the public use and interest will be served by the platting of such subdivision, then it shall be approved. If it finds that the proposed plat does not make such appropriate provisions or that the public use and interest will not be served, then *300 the legislative body may disapprove the proposed plat. In Loveless v. Yantis, 82 Wn.2d 754, 513 P.2d 1023 (1973), the Supreme Court reversed a superior court judgment granting preliminary approval to a plat because the county commissioners' refusal to grant approval was arbitrary and capricious. In the course of its opinion, that court made the following observations: It is true that a purpose of a preliminary plat is to secure approval of the street layout and location "design" of a proposal. Essentially, the plat provides information not specified in ordinance regulations. 3 A. Rathkopf, The Law of Planning and Zoning, ch. 71, § 5 (1972). The importance of this preliminary approval procedure is indicated by Rathkopf at page 71-34: Where this two-step procedure is in effect, consideration of the preliminary plat must result either in its approval as submitted, or a statement that it will be approved if it is modified in the manner specified by the planning board, or in its disapproval where conditions or infirmities appear or exist that would preclude any possibility of approval. The planning board cannot modify the preliminary plat and then disapprove a final plat conforming to the plat modified as prescribed by the board. Loveless v. Yantis, supra at 761. Both parties also cite the case of Department of Natural Resources v. Thurston Cy., 92 Wn.2d 656, 601 P.2d 494 (1979). There the county commissioners denied a preliminary plat application in order to preserve an eagle habitat. In sustaining that decision, the court made this observation at page 669. Of crucial importance in this case is the fact that the Commissioners' decision to deny the plat leaves open the possibility of approving a less dense development of Wood Point. The Commissioners have consistently maintained they would entertain an application for a plat which provided an adequate buffer zone for protection of the eagles' preferred perching and feeding areas. It should be noted that the Commissioners did not find any adverse impact from development of 11 of the proposed lots. Moreover, the findings provide specific guidelines *301 for planning a buffer zone the Commissioners would find acceptable. Finally the decision left open the possibility of an alternate cluster configuration for the development a configuration specifically favored by the County's Comprehensive Plan. The distinguishing characteristics of this case are that specific guidelines were contained in the commissioners' findings so that their decision suggested an alternate which might be acceptable, and their objections might be met. Buchsieb/Danard, Inc. v. Skagit Cy., 31 Wn. App. 489, 643 P.2d 460 (1982) lends some support to the trial court's decision but is distinguishable on its facts. In Buchsieb/Danard the County received applications for both a rezone and a preliminary plat approval. The plat provided for the subdivision of approximately 98 acres into 326 lots for single family and duplex residential use and the reclassification of other residential zoned property for industrial and multi-family use. The planning commission recommended approval of the preliminary plat to the extent of one phase of the proposed residential development, consisting of 118 lots on 37 acres. The county commissioners denied approval of both the rezone and the preliminary plat. Upon review this court affirmed the decision, noting, among other concerns, that the board was confronted with plans for a high density development which would turn a previously unused area into the fourth largest town in Skagit County. [2] The most recent opinion on the subject of plats is Johnson v. Mount Vernon, supra. There the developer had applied for approval of a preliminary development plan for a 69-acre mobile home subdivision. The planning commission approved the plat; the city council disapproved. Upon review the Superior Court examined the reasons for disapproval of the application, and although the court had the benefit of the discussion of the issue by council members, there were no specific findings and conclusions which would permit this court to evaluate the council's decision. This court held that there must be both findings and an adequate record to review adjudicatory proceedings. Johnson *302 v. Mount Vernon, supra. The reasons for this requirement are to provide a basis for review and guidance to the developer. We turn now to the findings of the planning commission which were incorporated in the Board's decision to deny the PUD application. The finding that a PUD would contribute to the loss of agricultural lands is supported but conflicts directly with the Comprehensive Plan which dictates residential rather than agricultural use of the area in question. The finding that increased traffic levels would result on SR 9 is supported but whether Kenart's proposed solution to this problem is adequate is not addressed. The finding that potential drainage problems exist is not sufficiently precise to explain a denial in the face of a contrary opinion by the Public Works Department. The Health Department conditionally approved the water supply and, contrary to the finding of the Commission, fire and police protection were determined to be adequate by the appropriate reviewing agencies within the county. School capacity is always a legitimate concern but, taken alone, any development could be halted solely on this ground. If no solution exists, then perhaps no further development is appropriate. But the mere fact that more houses mean more children and more children mean greater school capacity is needed, is not the end of the inquiry. Any finding that existing rural lifestyles might be disrupted by the proposed use is insufficient to support denial of the plat in view of a comprehensive plan which authorizes the population density requested by the developer. Finally, the Commission found that there was no need for platting additional lots and that the public interest would not be served by approving the proposed plat. These recitals, unless supported by other findings, are not "facts". RCW 58.17.110 requires the legislative body to inquire into the public use and interest proposed to be served and properly so. But once appropriate provision is made for the enumerated factors and the Board wishes to consider "other relevant facts", such as loss of agricultural lands, *303 potential disruption of rural lifestyles, and the need for additional lots, the Board must specify why the proposed use of land already zoned for residential use will reduce the quantity of land available for agriculture, how the proposed use will disrupt existing rural lifestyles, why there is not a need for a subdivision creating additional lots in the community and why these factors are relevant. Our concern in this case is that the planning commission may have denied approval of the PUD as a result of community displeasure rather than for the reasons stated. In every instance the developer either satisfied, or offered a change to satisfy, the concerns raised; yet its application was denied based on findings which are virtually unreviewable. Loss of agricultural land which has been zoned residential does not impress us as a logical reason for denial. We also have difficulty understanding, without more explanation, why disruption of existing rural lifestyles and a surplus of lots in the community are valid reasons for denial. The findings in this case neither provide guidance to the developer nor permit meaningful appellate review. We therefore reverse the trial court's order and remand to the Board of County Commissioners for further hearing and clarification of its findings. We do not adopt Kenart's proposal that there be a requirement that the Board specifically advise an applicant what must be done to obtain approval of a plat. Because of our disposition, we do not address the "appearance of fairness" issue or any claim that denial of this application was a taking of property without compensation. Reversed and remanded. SWANSON and SCHOLFIELD, JJ., concur. Review denied by Supreme Court June 8, 1984. NOTES [*] Judge Oluf Johnsen is serving as a judge pro tempore of the Court of Appeals pursuant to RCW 2.06.150. | Mid | [
0.618955512572533,
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Introduction {#Sec1} ============ Rapamycin, an immunosuppressant with an anti-proliferative ability, inhibits the mammalian target of rapamycin (mTOR) serine/threonine kinase that is related to the phosphatidylinositol 3-kinase (PI3K) family and the cellular integration center for controlling cell growth and proliferation and for sensing nutrients as well as hormonal signals, including insulin released from pancreatic beta cells \[[@CR1]\]. Binding of insulin to its tyrosine kinase receptor leads to the phosphorylation of the insulin receptor substrate (IRS) and the activation of the downstream PI3K/Akt kinase pathway as well as the mTOR signaling pathway to mediate insulin actions in liver and other tissues \[[@CR2]\]. Rapamycin treatment could therefore have broad impact in glucose homeostasis. Recent studies suggest that rapamycin and its derivatives may be used as therapeutic agents for treating cancers, diabetes, and Alzheimer's disease \[[@CR3], [@CR4]\]. Moreover, Harrison et al. \[[@CR5]\] reported that rapamycin extends the median and maximal life span of both male and female mice and noted that "disease patterns of rapamycin-treated mice did not differ from those of control mice," thereby raising the prospect of human clinical trials of rapamycin to treat aging and age-related diseases \[[@CR6], [@CR7]\]. However, the potential side effects of rapamycin such as glucose intolerance---a significant risk factor for diabetes and cardiovascular diseases \[[@CR8]--[@CR11]\] as well as cognitive impairments \[[@CR12]\]---warrant further investigation. There are conflicting reports of rapamycin effects on glucose homeostasis. On the one hand, hyperinsulinemia and hyperglycemia activates mTOR, raising the possibility that rapamycin inhibition of mTOR may reduce the risk of diabetes \[[@CR3]\]. Moreover, activated mTOR causes the phosphorylation of downstream effectors such as S6 kinase (S6K), the ribosomal protein S6, and the eukaryotic initiation factor 4E binding protein (4EBP) \[[@CR1]\]. S6K may also phosphorylate IRS to promote IRS deactivation and degradation, thereby causing insulin resistance \[[@CR13], [@CR14]\]. Consistent with this notion, S6K1 knockout mice are resistant to diet-induced obesity (DIO) and diabetes \[[@CR15]\]. On the other hand, chronic rapamycin treatment increases the risk of diabetes of human kidney transplant recipients \[[@CR16]\]. Other preclinical studies have also shown that rapamycin causes diabetes in obese sand rats (*Psammomys obesus*) \[[@CR17]\], lean rats \[[@CR18]\], and DIO mice \[[@CR19]\]. In this study, we show that aged mice fed with the same mouse chow with encapsulated rapamycin that extends life span \[[@CR5]\] became glucose-intolerant. We further show that chronic exposure to rapamycin caused glucose intolerance in mice due to a reduction in beta cell mass and insulin production as well as insulin resistance. Materials and methods {#Sec2} ===================== Animals {#Sec3} ------- This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and used protocol approved by the Institutional Animal Care and Use Committee of the University of California San Francisco (approved protocol ID: AN079064-03D). Inbred male C57B/L6 mice were from Jackson Laboratory (Bar Harbor, ME). The aged mice were from National Institute of Aging (Bethesda, MD). Mice (three to five per cage) housed in the animal facility were fed with PicoLab Mouse Diet \#5058 (Lab Diet, Brentwood, MO) and subjected to a standard 12-h light/dark cycle. Rapamycin (Apollo Scientific, UK or LC Laboratories, Boston, MA) was dissolved in DMSO (Sigma, St. Louis, MO) and then diluted in PBS before injection. For encapsulated rapamycin diet, rapamycin was micro-encapsulated and incorporated into Purina 5LG6 diet (Southwest Research Institute, San Antonio, TX). Intraperitoneal glucose tolerance test {#Sec4} -------------------------------------- Glucose tolerance tests were performed after a 16-h fasting period (6 [pm]{.smallcaps} to 10 [am]{.smallcaps}) with free access to water. Each mouse received an intraperitoneal injection of glucose (1.5 g/kg body weight). Blood samples were obtained from the tail and the whole blood glucose level determined using an OneTouch Ultra glucometer (LifeScan, Milpitas, CA). Insulin sensitivity test {#Sec5} ------------------------ Starting at 7 [am]{.smallcaps}, mice were fasted for 4 h with free access to water and then injected intraperitoneally with bovine insulin (1 U/kg body weight, Sigma). Blood samples were obtained from the tail and the whole blood glucose level determined using an OneTouch Ultra glucometer. Plasma insulin and C-peptide measurement {#Sec6} ---------------------------------------- Starting at 7 [am]{.smallcaps}, mice were fasted for 4 h with free access to water and then injected intraperitoneally with glucose (1.5 g/kg body weight). Blood samples were first collected into an ethylene glycol tetraacetic acid (EGTA)-coated tube (Sarstedt, Germany) and plasma was isolated by low-speed centrifugation. Plasma insulin concentration was determined using an ultrasensitive insulin and C-peptide ELISA assay (Alpco, Salem, NH). The HOMA-IR index was calculated as (fasting plasma insulin × fasting plasma glucose)/(22.5 × 18) \[[@CR20]\]. Insulin secretion from isolated islets {#Sec7} -------------------------------------- Mice were treated with either rapamycin or vehicle only for 3 weeks (five mice per group). At the end of the third week, mice were euthanized and pancreatic islets were isolated according to published protocol \[[@CR21]\]. For each sample, ten islets were pooled together and exposed to low (2.5 mM) glucose for 20 min followed by high (12.5 mM) glucose stimulation for 20 min; all the islets were saved for total insulin and DNA quantification. Insulin level in supernatants was determined using a High Range ELISA insulin plate (Alpco) and normalized to total DNA. Electrophysiology {#Sec8} ----------------- Pancreatic slices (100 μm thick) were prepared as described previously \[[@CR22]\]. Slices were incubated in the extracellular solution (in millimolars): 126 NaCl, 21.4 NaHCO~3~, 2.5 glucose, 5 KCl, 1.25 NaH~2~PO~4~, 1.2 MgCl~2~, 2 CaCl~2~, equilibrated with 95% O~2~/5% CO~2~. Beta cells were identified with infrared DIC optics. An Axon200B amplifier (Molecular Devices Corp., Sunnyvale, CA) was used to measure membrane potentials and membrane capacitance in the standard whole-cell patch-clamp configuration. Data were acquired at 5 kHz with Clampex10 software (Molecular Devices Corp.). Data with series resistances higher than 20 MΩ were excluded from further analysis. The intracellular solution contained (in millimolars): 150 KCl, 10 HEPES, 5 Mg~2~ATP, 1 Na~3~GTP, 10 sodium phosphocreatine, 0.05 EGTA; pH was adjusted to 7.2 with KOH. All the experiments were performed at room temperature. Immunostaining {#Sec9} -------------- Mice were anesthetized (Avertin, 0.25 g/kg, i.p. injection) and perfused transcardially with 4% paraformaldehyde. Pancreases were removed and post-fixed overnight in 4% paraformaldehyde then cryoprotected overnight in saline containing 30% sucrose. Tissue sections (20 μm) that were 200 μm apart from one another were mounted onto gelatin-coated slides. Sections were washed in blocking medium containing 0.1% Triton X-100 and 5% donkey serum (Jackson Immunoresearch Laboratories, West Grove, PA) and incubated overnight (4°C) with primary antibodies against insulin (guinea pig, 1:100; DAKO) and Ki67 (rabbit, 1:500; Thermo Scientific) followed by Alexa dye-tagged secondary antibodies (donkey, 1:500; Invitrogen, Eugene, OR). The slides were mounted using Fluoromount G mounting medium containing DAPI (Southern Biotech) and the images acquired using a Nikon fluorescent microscope equipped with a CCD camera. TUNEL apoptosis detection kit (Millipore, Billerica, MA) was used to identify apoptotic beta cells. Western blot analysis {#Sec10} --------------------- Mice fasted for 4 h were injected intraperitoneally with insulin (1 U/kg body weight). Ten minutes after injection, mice were euthanized and liver tissues were harvested. Western blot analysis was performed as described previously \[[@CR23]\]. Phospho-S6 (Ser235/6), Phospho-4EBP (Thr70), Phospho-Akt (Ser473), S6, 4EBP, and Akt antibodies were purchased from Cell Signaling. Statistical analyses {#Sec11} -------------------- Statistical analyses were performed with Prism software (Graphpad Software, San Diego, CA) or R (The R Foundation for Statistical Computing, Vienna, Austria) using two-way repeated measures ANOVA with Bonferroni post hoc test, Mann--Whitney *U* test, or Student's *t* test for pairwise comparisons. A *p* \< 0.05 was considered statistically significant. Barnard's exact test or Fisher's exact test was used to evaluate the significance of contingency data. Area under the curve (AUC) of intraperitoneal glucose tolerance test (IPGTT) was calculated using the trapezoidal rule method. Dose-dependent curves were constructed using the following equation to determine $\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ Y = {E_{\text{baseline}}} + \left( {{E_{{{ \max }}}} - {E_{\text{baseline}}}} \right)/[{1} + \left( {X/{\text{E}}{{\text{C}}_{{{5}0}}}} \right) $$\end{document}$\], where *E*~baseline~ is the AUC value from DMSO-treated mice, *E*~max~ is the AUC value from mice receiving the highest dose of rapamycin treatment (5 mg/kg), *Y* is the AUC value at *X* dose, and EC~50~ is the estimated half-maximum dose. Results {#Sec12} ======= Low-dose rapamycin induces glucose intolerance in aged mice {#Sec13} ----------------------------------------------------------- The remarkable finding that encapsulated rapamycin ingestion even commenced from midlife can extend life span in aged mice \[[@CR5]\] has raised the prospect for human clinical trials \[[@CR6], [@CR7]\]. To examine the effect of this rapamycin treatment on glucose homeostasis, we obtained two strains of aged hybrid mice, BD6F1 and B6D2F1, and fed them Purina 5LG6 diet with or without encapsulated rapamycin. Remarkably, these aged mice developed glucose intolerance within 4 weeks on rapamycin diet (*p* \< 0.05, Fig. [1a](#Fig1){ref-type="fig"}, [b](#Fig1){ref-type="fig"}). Using a criterion of glucose intolerance as a blood glucose level above 10 mM (180 mg/dl) at 120 min post-intraperitoneal glucose injection, we found that a significant fraction of mice on rapamycin diet showed glucose intolerance (*p* \< 0.05, Fig. [1c](#Fig1){ref-type="fig"}). This rapamycin-induced impairment of glucose homeostasis was associated with hypoinsulinemia: mice on rapamycin diet had plasma insulin levels lower than control values both before and after glucose injection (Fig. [1d](#Fig1){ref-type="fig"}), indicative of impaired beta cell function since the rapamycin diet did not cause insulin resistance in these aged mice (Fig. [1e](#Fig1){ref-type="fig"}).Fig. 1Aged mice fed with diet containing rapamycin showed impaired glucose homeostasis. **a** Rapamycin-induced glucose intolerance in aged mice (*p* \< 0.05, two-way repeated measures ANOVA, *n* = 47 and 40 for control and rapamycin groups, respectively). **b** Rapamycin-fed aged mice had a significantly higher AUC than control group (*p* \< 0.05, Mann--Whitney *U* test). **c** More aged mice in the rapamycin-fed group showed glucose intolerance than in control group (*p* \< 0.05, Barnard's exact test). **d** Rapamycin significantly reduced plasma insulin level (*p* \< 0.01 for 0 min and *p* \< 0.05 for 30 min after glucose injection, Mann--Whitney *U* test, *n* = 35 and 29 for control and rapamycin groups, respectively). **e** Rapamycin diet did not alter insulin sensitivity in aged mice (*p* \> 0.05, two-way repeated measures ANOVA, *n* = 50 and 45 for control and rapamycin group, respectively) Chronic rapamycin treatment causes hyperglycemia and hypoinsulinemia in young mice {#Sec14} ---------------------------------------------------------------------------------- Having found that low-dosage rapamycin caused glucose intolerance in a subset of aged mice with a hybrid genetic background, we decided to explore the possible pathophysiologic mechanism by studying C57B/L6 mice, the most widely used inbred mouse line to reduce possible variability due to genetic background. We administrated rapamycin by intraperitoneal injection to have better dosage control and reduce the variability due to differences in diet ingestion. Similar to the aged hybrid mice, 1-year-old C57B/6 mice developed glucose intolerance when injected with rapamycin intraperitoneally (Fig. [2a](#Fig2){ref-type="fig"}). Next, we asked whether this rapamycin-induced glucose intolerance is age-dependent, given that the turnover rate of pancreatic beta cells in aged mice is slower \[[@CR24]\]. We found that 3 weeks of intraperitoneal administration of rapamycin also caused glucose intolerance in young (2 months old) mice (Fig. [2b](#Fig2){ref-type="fig"}). Interestingly, both young and old mice regained glucose sensitivity 2 weeks after termination of the rapamycin regimen (Fig. [2a--c](#Fig2){ref-type="fig"}). The sensitivity to rapamycin was comparable between young and old mice, with EC~50~ of 0.28 and 0.26 mg/kg for 2-months-old and 1-year-old mice, respectively (Fig. [2d](#Fig2){ref-type="fig"}). We found that intraperitoneal rapamycin injection for 3 weeks did not affect the bodyweight of both young and old mice (Fig. [2e](#Fig2){ref-type="fig"}, [f](#Fig2){ref-type="fig"}). Since similar rapamycin-induced glucose intolerance was observed in mice of different ages and strains, we focused on young healthy male C57B/6 mice to study the underlying physiological and biochemical mechanism. We chose the paradigm of daily intraperitoneal injection for 3 weeks of either DMSO-only as control or 0.5 mg/kg rapamycin since this dose is within the effective therapeutic concentration for immunosuppression in mammals \[[@CR25]\] and is effective in inducing glucose intolerance in mice (Fig. [2d](#Fig2){ref-type="fig"}).Fig. 2Intraperitoneal rapamycin injection caused glucose intolerance in both young and old mice. **a** Old mice (1 year old) treated with different rapamycin dosages. Each group of mice (*n* = 10 for each dose) received a particular dose of rapamycin (*from left to right*): DMSO vehicle control, 0.05, 0.5, and 5 mg/kg; for each graph, the IPGTT curves before (baseline, *solid black line*), 3 weeks after rapamycin treatment (treatment, *red line*), and 2 weeks after stopping rapamycin treatment (recovery, *dash black line*) were plotted together. **b** Young (2 months old) mice (*n* = 10 for each dose) had comparable responses to intraperitoneal injection of rapamycin for the same range of doses and regimen. **c** Representative time course of young mice treated with rapamycin (0.5 mg/kg). After 1 week of rapamycin treatment, mice became glucose-intolerant (*p* \< 0.001, two-way ANOVA with Bonferroni post hoc test), and it took about 2 weeks to restore the glucose sensitivity after termination of the rapamycin treatment that lasted for 3 weeks (*n* = 10 for each group). **d** Rapamycin dose dependence curves of old (*open circle*) and young (*solid circle*) mice. The EC~50~ were 0.28 and 0.26 mg/kg for young (2 months old) and old (1 year old) mice, respectively. Three weeks of 0.5 mg/kg rapamycin injection did not affect mouse bodyweight from young (**e**) or old (**f**) mice. Bodyweights were normalized to the starting value prior to rapamycin treatment Having found that rapamycin diet caused glucose intolerance by reducing plasma insulin level (Fig. [1d](#Fig1){ref-type="fig"}), we further showed that intraperitoneal rapamycin treatment also caused a significant reduction of plasma insulin level (Fig. [3a](#Fig3){ref-type="fig"}). Moreover, the plasma insulin level of rapamycin-treated mice failed to rise following intraperitoneal glucose administration (*p* \< 0.05, Fig. [3a](#Fig3){ref-type="fig"}). As reduced plasma insulin may arise from either decreased insulin secretion from the pancreatic beta cells or increased hepatic insulin clearance, we measured the plasma level of C-peptide, which accompanies insulin release with longer half-life in the plasma due to low hepatic clearance. We found that glucose injection also failed to raise C-peptide levels in the same plasma samples from rapamycin-treated mice (*p* \< 0.05, Fig. [3b](#Fig3){ref-type="fig"}) without altering the plasma insulin/C-peptide ratio (Fig. [3c](#Fig3){ref-type="fig"}), suggesting that insulin secretion from pancreatic beta cells is impaired in rapamycin-treated mice. Indeed, although islets isolated from both DMSO- and rapamycin-treated mice still responded to high (12.5 mM) glucose stimulation (*p* \< 0.05), islets from rapamycin-treated mice exhibited much less glucose-induced insulin release (*p* \< 0.05, Fig. [3e](#Fig3){ref-type="fig"}), which was associated with a reduction in the total insulin content in islets (*p* \< 0.05, Fig. [3f](#Fig3){ref-type="fig"}), suggesting that the suppression of insulin production by chronic rapamycin treatment led to impaired glucose homeostasis.Fig. 3Rapamycin reduced glucose-stimulated insulin secretion in vivo and ex vivo. **a** Plasma insulin level was assessed before (0 min) and 30 min (30 min) after intraperitoneal glucose injection (1.5 g glucose/kg). Rapamycin blunted glucose-induced insulin secretion (30 min) in vivo (*p* \< 0.05, paired *t* test). Each group had six to ten animals. **b** Analyses of the same plasma samples revealed that rapamycin also blunted glucose-induced C-peptide secretion (30 min) in vivo (*p* \< 0.05, paired *t* test). **c** Rapamycin treatment did not alter the plasma insulin/C-peptide ratio with or without glucose stimulation. **d** Rapamycin treatment increased HOMA-IR index (*p* \< 0.05, Mann--Whitney *U* test). **e** Pancreatic islets isolated from rapamycin-treated mice showed a decreased insulin secretion upon glucose stimulation. Insulin level was normalized to total protein extract from the isolated islets (*p* \< 0.05, paired *t* test). **f** Three weeks of rapamycin treatment reduced total insulin content in islets (*p* \< 0.05, unpaired *t* test). For experiments using isolated islets (**d--f**), each data point was for five to seven sets of ten islets pooled from five mice Glucose induces insulin secretion by closing K~ATP~ channels to depolarize the beta cell and induce action potential firing, which in turn causes calcium influx to trigger exocytosis \[[@CR26]\]. To ask whether chronic rapamycin treatment impairs the stimulus--secretion coupling for glucose-induced insulin release, we performed patch-clamp recording from beta cells in pancreatic slices. Since beta cells form a syncytium within the islet of Langerhans, whole-cell recording from the intact islet preparation can monitor the membrane potential changes of the entire islet that maintains electrical coupling through gap junctions \[[@CR22], [@CR27]\]. Like beta cells from control mice (Fig. [4a](#Fig4){ref-type="fig"}), beta cells from rapamycin-treated mice responded to glucose stimulation with depolarization and action potential firing (Fig. [4b](#Fig4){ref-type="fig"}). We also measured the increase of membrane capacitance following fifty 3-Hz depolarization pulses from −70 to 0 mV for 100 ms, a stimulation mimicking action potential firing induced by glucose stimulation \[[@CR22], [@CR26]\]. This membrane capacitance measurement revealed that the depolarization pulses caused similar increases in the cell surface area of beta cells from rapamycin-treated mice and control mice (Fig. [4d](#Fig4){ref-type="fig"}). Thus, rapamycin did not alter the glucose stimulus--excitation coupling or the exocytotic machinery of beta cells.Fig. 4Rapamycin does not alter glucose stimulus--secretion coupling in beta cells. DMSO-treated (**a**) and rapamycin-treated (**b**) mice had beta cells that responded similarly to a rise of glucose in the extracellular solution from 2.5 to 12.5 mM with membrane depolarization and action potential firing. **c** Beta cells from DMSO- or rapamycin-treated mice had similar membrane capacitance, indicating that the cell size was comparable (*p* \> 0.05, unpaired *t* test). **d** A train of 100-ms pulses from −70 to 0 mV delivered at 3 Hz for 50 s caused similar capacitance increases in beta cells from DMSO- and rapamycin-treated mice (*p* \> 0.05, unpaired *t* test). Each group had six to eight cells from three animals Rapamycin reduces beta cell mass in pancreatic islets by decreasing beta cell proliferation {#Sec15} ------------------------------------------------------------------------------------------- As a previous study has shown that rapamycin reduces beta cell mass in the islets of obese sand rats \[[@CR17]\], we examined the beta cell mass in these lean C57B/L6 mice and found that the pancreatic islets from rapamycin-treated mice were significantly reduced in size (*p* \< 0.05, Fig. [5a--c](#Fig5){ref-type="fig"}) while the beta cell density remains unchanged (Fig. [5d](#Fig5){ref-type="fig"}). Moreover, using membrane capacitance as a surrogate measure for cell size, we found that the surface area of beta cells from rapamycin-treated mice was normal (Fig. [4c](#Fig4){ref-type="fig"}). A reduction of beta cell mass could be caused by reducing beta cell proliferation, increasing beta cell apoptosis, or both \[[@CR17], [@CR28]\]. We found that the pancreatic islets from rapamycin-treated mice had a reduction of Ki67-positive cells and insulin-positive cells (0.1% for the DMSO group and 0.03% for the rapamycin group, *p* \< 0.05, Fisher's exact test; Fig. [6](#Fig6){ref-type="fig"}), but TUNEL staining of a cell apoptotic marker did not reveal any difference (data not shown). This result indicates that rapamycin treatment reduced islet size by inhibiting beta cell proliferation rather than increasing beta cell apoptosis.Fig. 5Rapamycin reduced islet size. Representative images of pancreatic sections from DMSO-treated (**a**) or rapamycin-treated (**b**) mice, with beta cell mass outlined by insulin-positive cells. Rapamycin significantly reduced islet size (**c**) (*p* \< 0.05 unpaired *t* test), but not the average insulin-positive cell area that was determined by measuring the area of insulin staining for each islet normalized by the total cell number measured by DAPI counts (**d**)Fig. 6Rapamycin reduced beta cell proliferation. Immunostaining of pancreatic islets from control mice (**a**) or mice treated with rapamycin for 3 weeks (**b**). Beta cells were identified by insulin (*green*, *top panel*) and proliferating cells were marked by Ki67, a cell proliferation marker (*red*, *middle panel*). *Bottom panels* showed merged images of both insulin and Ki67. Proliferating beta cells can be seen in control islets (*white arrows*) (**a**), but not in islets from rapamycin-treated mice (**b**). *Scale bars*, 50 μm Rapamycin reduces insulin sensitivity {#Sec16} ------------------------------------- Given that mTOR is a key molecule in the insulin signaling pathway \[[@CR2], [@CR29]\], rapamycin inhibition of mTORC1 may cause not only hypoinsulinemia but also other effects such as reduced insulin sensitivity, as observed in sand rats \[[@CR17]\]. Although the low dosage of encapsulated rapamycin in the diet did not alter insulin sensitivity of the aged mice, daily injection of lean C57B/L6 mice with rapamycin at 0.5 mg/kg for 3 weeks increased the homeostatic model assessment of insulin resistance (HOMA-IR) index (*p* \< 0.005, Fig. [3d](#Fig3){ref-type="fig"}), indicating that chronic rapamycin treatment could cause insulin resistance. Indeed, in the intraperitoneal insulin tolerance test, rapamycin-treated mice showed a moderate but significant reduction of insulin sensitivity (*p* \< 0.05, Fig. [7a](#Fig7){ref-type="fig"}).Fig. 7Rapamycin reduced insulin signaling and caused insulin resistance in lean mice. **a** After a 4-h fasting followed with 1 U/kg bovine insulin injection, the blood glucose measured at the designated time points from these mice revealed a reduction of insulin sensitivity in rapamycin-treated mice (*p* \< 0.05, two-way ANOVA repeat measurement). Blood glucose levels were normalized to the initial value (*t* = 0 min). Each group had 12--16 mice. **b** Representative Western blot of mTOR, S6, and Akt in liver samples from mice treated for 3 weeks with either rapamycin or DMSO. **c** Phospho-mTOR/total mTOR (*p* \< 0.005, unpaired *t* test). **d** Total mTOR/total actin (*p* \< 0.005, unpaired *t* test). **e** Phospho-S6/total S6 (*p* \< 0.005, unpaired *t* test). **f** Total S6/total actin (*p* \< 0.05, unpaired *t* test). **g** Phospho-4EBP/total 4EBP (*p \>* 0.05, unpaired *t* test). **h** Total 4EBP/total actin (*p* \< 0.01, unpaired *t* test). **i** Phospho-Akt/total Akt (*p* \> 0.05, unpaired *t* test). **j** Total Akt/total actin (*p* \< 0.005, unpaired *t* test). *n* = 3 for each group To determine how rapamycin treatment might reduce insulin sensitivity, we examined liver protein extracts from rapamycin-treated mice and control mice (Fig. [7b](#Fig7){ref-type="fig"}). Chronic rapamycin treatment reduced the extent of phosphorylated mTOR (Ser2448) and phosphorylated S6 (Ser235/6, *p* \< 0.005) but not phosphorylated 4EBP (Thr70) after normalization with the respective protein level (Fig. [7c](#Fig7){ref-type="fig"}, [e](#Fig7){ref-type="fig"}, [g](#Fig7){ref-type="fig"}). We also found lower levels of mTOR (*p* \< 0.005, Fig. [7d](#Fig7){ref-type="fig"}), S6 (*p* \< 0.05, Fig. [7f](#Fig7){ref-type="fig"}), and 4EBP (*p* \< 0.01, Fig. [7h](#Fig7){ref-type="fig"}) proteins in the liver from rapamycin-treated mice. Whereas there was no significant alteration of the extent of phosphorylated Akt (Ser473) after normalization with the total Akt protein level (Fig. [7i](#Fig7){ref-type="fig"}), rapamycin treatment did cause a significant reduction of the Akt protein level (*p* \< 0.005, Fig. [7j](#Fig7){ref-type="fig"}) so that the amount of phosphorylated Akt was actually lower in the liver from rapamycin-treated mice. This reduction of mTOR signaling as well as Akt activity could compromise insulin signaling \[[@CR30]\]. Discussion {#Sec17} ========== We found that the low-dose rapamycin treatment that increases life span in aged mice \[[@CR5]\] caused glucose intolerance by reducing plasma insulin levels before and after glucose stimulation. In lean C57B/L6 mice, a higher dose of rapamycin treatment not only reduced plasma insulin and plasma C-peptide levels but also caused insulin resistance accompanied with compromised hepatic mTOR and insulin signaling. We further characterized the impairment in insulin secretion of pancreatic islets from rapamycin-treated mice, showing that it likely arose from a reduction in beta cell mass and insulin content. Previous studies report that chronic rapamycin treatment raises plasma insulin of DIO mice \[[@CR19]\] and of rats displaying impaired hepatic insulin clearance \[[@CR18]\]. In our study, we show that chronic rapamycin treatment of young as well as old mice causes glucose intolerance in a dose-dependent and reversible manner (Fig. [2](#Fig2){ref-type="fig"}). Under standard rapamycin regimen (0.5 mg/kg), it took about 2 weeks to fully develop glucose intolerance, and glucose tolerance was restored 2 weeks after stopping the rapamycin regimen (Fig. [2c](#Fig2){ref-type="fig"}). Given that the beta cell proliferation rate is very slow, we suspect that a reduction of insulin content upon rapamycin treatment may contribute significantly to a faster onset and offset of glucose intolerance (Fig. [3e](#Fig3){ref-type="fig"}, [f](#Fig3){ref-type="fig"}). Previous studies have shown that insulin turnover rate is about 48--72 h in rodents \[[@CR31]\]. Since both the insulin secretory machinery and the excitation--secretion coupling are not affected, rapamycin may slow down the de novo synthesis of insulin without affecting preexisting insulin in the secretory granules. This way, it may take a few days, if not weeks, to deplete the preexisting insulin pool even if rapamycin halts the synthesis of insulin. Also, we suspect that during the first few days after stopping rapamycin treatment, the residual rapamycin in the system might still be effective in suppressing insulin production and inhibiting beta cell proliferation so that the recovery is delayed until rapamycin level is reduced below its pharmacological effective concentration. Indeed, in vivo pharmacokinetic analysis has revealed that rapamycin has a relatively long half-life (5--12 h), larger volume of distribution, and extensive tissue binding \[[@CR32]\]. Rapamycin treatment of lean C57B/L6 mice reduces the glucose-stimulated insulin secretion in both in vivo and ex vivo conditions (Fig. [3](#Fig3){ref-type="fig"}). Our electrophysiological recordings revealed no alterations in glucose stimulus--excitation coupling and the exocytotic machinery of beta cells from rapamycin-treated mice (Fig. [4](#Fig4){ref-type="fig"}). Therefore, the impaired insulin secretion is likely due to a reduction of the total insulin content by 70% (Fig. [3f](#Fig3){ref-type="fig"}) and of the average beta cell mass by 50% in rapamycin-treated mice (Fig. [5](#Fig5){ref-type="fig"}). Since both the insulin-positive cell area (Fig. [5e](#Fig5){ref-type="fig"}) and the membrane capacitance of beta cells were normal in islets from rapamycin-treated mice, these mice most likely have fewer beta cells. Indeed, we found a reduction in dividing cells as well as insulin-containing cells in islets from rapamycin-treated mice (Fig. [6](#Fig6){ref-type="fig"}), consistent with previous studies \[[@CR17], [@CR28]\]. Nir et al. \[[@CR33]\] have demonstrated the regenerative capacity of mouse pancreatic beta cells after diabetogenic injury, and they have also shown that immunosuppressants such as rapamycin and tarcolimus used in the Edmonton protocol, a pancreatic islet transplantation procedure for treating type I diabetes in patients, prevents beta cell proliferation. Our study has important clinical implications, given that long-term rapamycin (sirolimus) exposure is required to prolong life span or treat illnesses such as Alzheimer's disease, organ transplant, and cancer \[[@CR3]--[@CR5]\] and given the consideration of rapamycin in human clinical trials \[[@CR6], [@CR7]\]. Our findings raise the concern that chronic low-dose rapamycin regimen has the potential to disrupt glucose homeostasis, thereby elevating the risk for hyperglycemia, which could lead to diabetes. A reduction in circulating insulin causing glucose intolerance could be a double-edged sword: lowering the insulin level impairs glucose homeostasis, extending life span, but also likely compromising the quality of life. How can the conflicting reports of rapamycin effects be reconciled? On the one hand, overactivation of the mTOR-S6K pathway may be diabetogenic in mammals. For example, in a short-term in vivo study on human subjects, rapamycin ameliorates glucose intolerance caused by nutrient abundance of amino acids \[[@CR34]\]. Additionally, deleting S6K1 alleviates insulin resistance and improves beta cell survival under conditions of chronic hyperglycemia \[[@CR15]\], and rapamycin injection prevents the onset of insulin dependent diabetes in non-obese diabetic mice \[[@CR35]\]. Conversely, other studies have suggested that rapamycin is diabetogenic: a retrospective study has shown that kidney transplant patients taking rapamycin have a significantly higher risk of developing diabetes \[[@CR16]\]; rapamycin also induces diabetes in DIO sand rats \[[@CR17]\] and mice \[[@CR19]\]. Our study has further uncovered the diabetogenic effects of rapamycin in young and old lean inbred C57B/L6 mice. One way to reconcile these conflicting findings is to consider that the effects of rapamycin are different depending on the duration of the treatment: short-term rapamycin treatment seems to alleviate the metabolic symptoms \[[@CR34]\], whereas chronic rapamycin treatment reduces insulin secretion and decreases insulin sensitivity; hence, chronic rapamycin treatment is diabetogenic and causes deterioration of metabolic symptoms in mice of different ages and strains (Figs. [1](#Fig1){ref-type="fig"} and [2](#Fig2){ref-type="fig"}). In summary, our study shows that chronic rapamycin is diabetogenic in mice. Chronic inhibition of mTORC1 with rapamycin impairs insulin secretion and causes insulin resistance. It would be prudent to monitor glucose homeostasis in patients treated with rapamycin or other mTOR inhibitors to minimize the risk of developing metabolic syndromes. We thank members of the Xu and Vaisse laboratories (Diabetes Center, UCSF) for discussions. We thank Greg Zsot for excellent technical support (Diabetes Center, UCSF). This work was supported by NIH grant R37MH065334 and the American Diabetes Association Mentor-Based Fellowship 7-06-MN-29 (to S.B.Y.). Y.N.J. and L.Y.J. are investigators of the Howard Hughes Medical Institute. Disclosure of potential conflict of interests {#d29e1234} ============================================= The authors declare no conflict of interests related to this study. Open Access {#d29e1239} =========== This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. | High | [
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Tyler Cowen and Kevin Grier are both economists. They are also both basketball fans. Here’s their take on the NBA lockout. The Golden Rule: He who has the gold, rules Fundamental Rule of Negotiation: He who cares the least wins In the NBA, it’s the owners who have the gold and care the least. What do the owners have to lose? Net revenues from the lost games and any decline in the value of their franchises due to fan alienation and depreciation of assets — namely the players they have under contract. What do players have to lose? Salaries from lost games and time cut off from already short career windows. Why do owners have leverage? They have deeper pockets and alternative sources of income. The next most lucrative financial option for players is far worse than the owners’ lowest offer. Why do players have leverage? Only a handful of star players have leverage. The owners’ product without the top 20-30 players in the league would stink for at least a few years. Rank-and-file players are more easily replaced and have almost no leverage at all. Why are labor disputes in sports so weird? The bosses control the whole sector and face little competition when it comes to hiring labor. Since the merger with the ABA in 1976, the NBA is a monopoly and operates in a manner (it monopolizes!) that would be illegal outside the sports world. Unlike in Silicon Valley, there are no NBA “start-ups.” You cannot create a new NBA team without permission of the incumbent owners. The league also has to approve changes in teams’ location and ownership. What does this mean? The owners can get together and agree to jointly cut expenses, that is, the player salaries. Players have limited opportunities to play professional basketball in other countries, but realistically, if you are a world-class professional basketball player, you probably want to be in the NBA. The star players are the only counterweight to management’s power. To a large extent, they ARE the NBA’s product. Because of this, the owners aren’t talking about using replacement players, and some stars are getting decent offers to play overseas during the lockout. These factors are a cause for concern for the owners and put limits on how much they can extract from the players. Why have past CBAs been so favorable to the players? In the past, traditional NBA owners were in the game for the fun, the control, and the bragging rights. They made money through franchise appreciation; there was less emphasis on maximizing short-run operating profits. The newer group of owners bought high, are more corporate in orientation, and the financial crisis renewed their sense of vulnerability. They’ve poured a lot of money into those teams and they aren’t comfortable with seeing red on their balance sheets year after year. Why don’t the players settle? Perhaps because they have done so well in the past, it’s hard for the players to accept that the owners are dead set on hammering them this time. They feel, correctly, that they have been making all the concessions. Imagine trying to redo your “chores deal” with your spouse, with one side giving in on every negotiating point. As human beings, we are programmed to reject one-sided deals, even when surrender might be the rational choice. How far apart are the two sides? The split on BRI (Basketball Related Income) is supposedly the biggest point of contention. Players want 52.5 percent (down from 57 in the previous contract). Owners are “adamant” on 50 percent and started with an initial lowball offer of 37. Take the NBA’s 2009-10 BRI estimate of $3.6 billion; 2.5 percent of that is $90 million. Let’s say the life of the contract is 6 years. The total value of that over six years, with reinvestment, is around $500 million. Is it economically worthwhile for the players to hold out for $500 million? No. Total NBA salaries last year were over $1.5 billion, about three times the amount they are fighting over. Canceling a third of the current season would wipe out the gain of winning the extra 2.5 percent of BRI over the life of the new collective bargaining agreement. Canceling the whole season over 2.5 percent of BRI is insane for the players. Of course there are other issues relating to the salary cap, like the length of contracts, but the BRI split seems to be the sticking point. What’s the bottom line? Can the owners afford to give the players a better deal? Yes. Forbes magazine estimates that the Knicks franchise, the NBA’s most profitable, is worth about $655 million. The Milwaukee Bucks, the least profitable franchise according to Forbes, still is worth $258 million, and the Clippers, often considered the worst-run team, have a net value of $305 million. The value of the Knicks alone could more than cover what the players are asking for. Can the players stop the owners from getting a deal that is much worse for them than the previous Collective Bargaining Agreement? No. What the players are willing to agree to is already materially worse than before. The only question that remains is how bad it will get. Does the players’ line in the sand over 2.5 percent of BRI make economic sense? No, not if they miss many games to achieve it. Is the owners’ offer fair? Not really. Should the players take it? Yes. Will the owners give in and up the ante? Very unlikely. Will the players be rational and take what is on the plate? We can only hope so. Follow Grantland on Twitter or check out Grantland’s Facebook page. Read more of The Triangle, Grantland’s sports blog. Contact us at [email protected] | Mid | [
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Are Cardiac Anomalies and Persistent Fetal Circulation a Risk Factor for Cardiovascular Events During Minimally Invasive Surgery in Neonates? Introduction: Minimally invasive surgery (MIS) in neonates is progressively performed. The aim of this study was to evaluate the risk for cardiovascular events during endoscopic surgery in neonates and to analyze the influence of persistent fetal circulation and/or cardiac anomalies. Materials and Methods: This is a retrospective single institution study including all neonates undergoing MIS. The charts were reviewed for intraoperative cardiovascular events and operative procedure was performed. Special attention was paid to cardiac anomalies and persistent fetal circulation. In addition, a review of the literature was performed. Results: Between January 2004 and December 2012, 108 neonates underwent MIS at our institution. Laparoscopic surgery was performed in 91 (84.3%) and thoracoscopy in 17 (15.7%) babies. None of these 108 patients developed a cardiovascular event during endoscopic surgery (0.0%). Persistent fetal circulation and/or cardiac anomalies were evaluated in 50 of 108 (46.3%) neonates. In the additionally performed review of the literature, four single case reports were identified. All 4 authors published a major cardiovascular event during laparoscopic surgery in neonates. In all 4 patients, gas embolism through a patent umbilical vein was assumed to be responsible for the cardiovascular event. Conclusions: In our opinion, the main risk factor for the development of a major cardiovascular event during MIS in neonates is vascular injury of a persistent umbilical vein. Persistent fetal circulation and/or cardiac anomalies seem to be less important. In case of injury of a persistent umbilical vein, the risk of gas embolism has to be respected and conversion to the open approach has to be considered. | High | [
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Adickes was a critical empiricist, or moderate Kantian, and he wrote important works on Kant, including in 1895 a Kantian bibliography in German. An opponent of Ernst Haeckel, Adickes in his Kant contra Haeckel wrote I have no more belief than he in a personal extra-mundane God, a creation of the world by him, or an immaterial soul separated from the body. He is also known for introducing in 1907, his concept of Four World-Views: Dogmatic (or Doctrinaire), Agnostic (or skeptical), Traditional, and Innovative, which would help shape personality theory in the 20th century. | High | [
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Q: Qstring to LPCWSTR LPCWSTR path; void WinApiLibrary::StartProcess(QString name) { path = name.utf16(); CreateProcess(path, NULL, NULL, NULL, FALSE, 0, NULL, NULL, &si, &pi); } C:\kursovaya\smc\winapilibrary.cpp:21: error: invalid conversion from 'const ushort* {aka const short unsigned int*}' to 'LPCWSTR {aka const wchar_t*}' [-fpermissive] path = name.utf16(); This code worked in the Qt 4.8, but now i have Qt 5.2 and this code isn't working. What's wrong with this guy? A: I had the same issue (I'm using Qt 5.3), this is how I fixed it: QString strVariable1; LPCWSTR strVariable2 = (const wchar_t*) strVariable1.utf16(); A: QString::utf16() returns const ushort*, which is different from const wchar_t*, so you have the compile error. You are probably compiling with /Zc:wchar_t. If you change it to /Zc:wchar_t- it should work, as wchar_t type becomes typedef to 16-bit integer in this case. In Visual Studio: Project Properties->Configuration Properties->C/C++->Treat WChar_t As Built in Type->No. Or just add reinterpret_cast<LPCWSTR>. A: I'm using Qt 5.2 and I had the same issue. This is how I fixed it: QString sPath = "C:\\Program File\\MyProg"; wchar_t wcPath[1024]; int iLen = sPath.toWCharArray(wcPath); | Mid | [
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## ## Socket Mode ## # # Require this file if you wish to run your server and/or client RPC # with the raw socket handlers. This is the default run mode for bin/rpc_server. # # To run with rpc_server either omit any mode switches, or explicitly pass `socket`: # # rpc_server myapp.rb # rpc_server --socket myapp.rb # # To run for client-side only override the require in your Gemfile: # # gem 'protobuf', :require => 'protobuf/socket' # require 'protobuf' require 'protobuf/rpc/servers/socket/server' require 'protobuf/rpc/connectors/socket' ::Protobuf.connector_type_class = ::Protobuf::Rpc::Connectors::Socket | Mid | [
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"Carlos Romero." "Marta Rubial." "Mar Garcia." "Pablo Guerrero." "Mary of the Mountains Enriquez?" "You have a very good CV, Mary of the Mountains." "Thank you." "What would you do first in the firm if we hired you?" "Well, get to work on time." "A market study, including all the social networks, the main targets, and focus resources on the prime target." "What type of person are you?" "A... normal person." "And what's a normal person?" "A normal person is someone... with a job," "a home, a partner," "hobbies, a social life," "family life..." "Hello?" "Merry Christmas." "...and... and who's happy" "Do you think you fulfil all these requisites?" "JOB, HOME, PARTNER, SOCIAL LIFE, HOBBIES, FAMILY LIFE, BE HAPPY" "All of them." "Certainly." "My name's Mary of the Mountains and my life is a mess." "500,000 children were born in Spain in 1985." "I was one of them." "I cried a lot, non-stop, until they put on my ID bracelet." "They are different shapes and colours, but all with the same purpose, to label you." "I guess knowing who I was gave me some peace." "And this is me now." "I have no ID bracelet now, beyond being an unemployed thirty-something who thought she'd conquer the world when she graduated... and didn't." "With a degree in advertising, an online English course and a masters in advertising, my greatest achievement is an unemployment card, though I think it's expired now." "Why am I loaded down with bags?" "No, I'm not going on a trip." "I wish!" "I got thrown out of my flat for not paying the rent." "Sure, I did owe them three months." "So I'm going back to the last place I'd want to go back to, my mother's place." "Sis!" "Bro!" "So glad to see you!" "You look skinnier!" "And you look outer!" "Wait, I'll open up!" "This is Alex, my brother." "He's always been more sure about things than me." "At 7 he told us he was gay and at 18 he already had a job." "And he was just re-elected president of the Twilight Fan Club." " Hey, handsome!" " Hi!" "So...?" "Mum's going to be so happy you're back home!" "It's temporary, Alex, just till I find a job, then I'm going." "Isn't she home?" "No, there's a meeting of Thermomix salespeople." "5 years selling Thermomixes!" "I can't believe how time's flown." "Believe it!" "I beat my own record this year, 10 machines in one month!" "Yes, but you haven't reached Maria Eugenia's 20." "What excuse will I give my husband tomorrow?" "See?" "That's why I don't have one." "Excuse me." "Alex, honey." "Hi, Mum." "I've got news." "Mary's back home." " Is she alright?" " Sure, she's fine." "Did she seem strange?" "No way." "The things you say, Mum." "Shall I put her on?" "No, don't put her on." "I'll be back soon." "Big kiss." "This is my mum, Barbara." "We haven't spoken in a while." "Since she was widowed she's sold Thermomixes." "She likes classical music, playing Solitaire and..." "I don't know much more about her." "The last time we spoke was because my phone dialled by accident." "Tell me, what type of person do you consider yourself to be?" "REQUIREMENTS TO BE A NORMAL PERSON" "HOME" "JOB" "PARTNER" "FAMILY LIFE" "SOCIAL LIFE" "HOBBIES" "BE HAPPY" "REQUIREMENTS TO BE A NORMAL PERSON" "Morning!" "Wake up, we have to go see my boss." "Don't forget your CV." "And don't go back to sleep!" "First requisite, have a job." "JOB" "Look, I've got your CV here." "You'd better send it off via the website too." "Okay." " See you later!" " See you later!" "I did marketing, but you can consider me for any position." " Anything, don't worry." " Thank you." "Great, see you. 'Bye, Alex." "'Bye, Paula." "You look pretty." " Thanks!" "I hope they call you." "Why don't we have lunch together?" " Okay." "Do they sell light bulbs here?" " Of course, sis'." "Hello." "Need anything?" "No." " Sure?" " Yes, I'm fine, thanks." "Are you sure I can't help you?" "Well, I'm looking for a bulb for my desk lamp, but I'm not sure what light these give off exactly." "Exactly... 15 watts." "Right, 15 watts, and how much light is that?" "Turn it on and off." "Yes, but..." "See?" "You can't really see the difference." "So to tell we should be in darkness here, right?" "I mean, all the lamps should be off and we turn it on and off to tell the difference." " You never thought about that?" " No." "That's alright." " Need anything else?" " No." "Okay." "Do you know if Mum uses Dad's car?" " Yes, but not to drive." " No?" "No, but when she's sad, she goes to the car to think." "Gee." " Can I ask you a question?" " Sure." "How do you know if someone likes you or not?" "Iguess".because"." "when you're with them..." " Do you like somebody?" " I think so." "I can't remember the last time I really liked someone." "That was me in primary school with Guillermo Conde Sánchez." "I know, it was a long time ago." "He'd always ask for my notes and I'd blush every time." "Once I dared to put a heart and "I like you" on my math notes, and I don't know why, but he never asked me again." "That day I understood that love confessions are not my forte." "JOB" "Don't tell me your life story." "The economic report was for today!" "PARTNER" "BEING HAPPY IS EASY" "LIVING HAPPY" "I WANT A CHANGE" "SELF-HELP" "I'm sorry!" "Excuse me!" "This..." "This..." "THE JUICE DIET" "These aren't for me." "And these aren't for me..." "SLIMMING IS EASY ...obviously." "Obviously." ""Smile, It Works"," ""The Power is in You"," ""Living Happy"." "And what's happiness?" "I don't know." "At least you're thin." " Your weight doesn't make you happy." " Typical thin girl answer." "SLIMMING IS EASY" "THE JUICE DIET" "QUALITY CALORIES" "You don't know what it's like to diet all the time." "Carrot cake with extra cream here, coffee..." "Can you bring some saccharine?" "To Compensate." "Not going to answer it?" "Mum?" "Yes." "No, I won't be at dinner." "Because I..." "I ran into a friend." "What friend?" "You, right?" "Do you want to go to dinner?" " If it's a salad, yes." " Okay." "No, I won't be at dinner, I'm going out with Borja." "Well... a friend." " What bulb did you get in the end?" " The 15." "Oh, okay." "Tell me what the light's like." " I will, when I see it in the dark." " Of course." "What?" "Are you taking the piss out of me?" "No, no way." "Just your obsession with turning the lamps on and off." " It's an obsession that works." " It depends." "Where'd you read that list?" "I didn't read it." "They asked me about it at a job interview." "I'd never thought about it before." " I only Satisfy half the list." " Then you're half normal." "That's not bad." "What about you?" "I don't Satisfy any of it." "Nothing?" "Nothing." "Bugger all." "There are people, like the Pope for example, that don't Satisfy the list." "But the Pope's the Pope, he doesn't need to be normal." " If you look at it like that..." " Sure." "Though he's married to God, so one of them..." "No, nuns are married to God." "Not the Pope." " And why not?" " I don't know." "Ask him." "You'll love this place." "We'll get a table, for sure." " Here?" " Right?" "Mary, Gagandeep." " Nice to meet you." " Same here." "The pizza's delicious." "Yeah." "So, to help you with your list, you want me to find you a flat." " Yes." "A studio flat will do." " Okay." "A little one." "A job." "Not as a trainee, please." " A boyfriend." " Yes." " How do you want him?" " Normal." " Normal." " Supernormal." "If he's normal, like on your list, he'll have a partner." "Oh, right." "Then he's to Satisfy 80% of the list." "Okay." "So?" "Do you think you can turn me into a normal person?" "Yeah." "Do you think you can make me thin?" "Sure." "Yeah." "Have we got a pact?" "Quid pro quo." "Quid pro quo." "Right, Mary of the Mountains." "Let's start our quid pro quo." "Point one:" "SOCIAL LIFE." "I don't feel like doing this one." "Come on, you must have some friend from university." "I did it by correspondence." "Then from high school or matriculation classes?" "I was in the first year of the new system." " You done?" " I did the last year of the old one." "Really?" "They say you're better educated." "Absolutely." "Don't change the subject." "Come on, someone from high school." "I don't keep in touch with anyone." " Nobody?" " No." "I'm going to do something." "What?" "What?" "I'll look at your contacts, and phone at random." "No, no." "Cristina Pi." " No, not Cristina Pi!" " It's ringing, take it!" " Mary?" "Cristina?" " Who?" "No, I'm Mary..." " This is Mary Enriquez Conde." " Who?" " From Sant Jordi." " From school?" " Yes." " Well!" " Do you remember me?" " No,Id0nT" "We were in the same class." "Give me more clues, or..." "Remember the end-of-year dances?" "There was a number by Vicky Larraz?" "Who's Vicky Larraz?" "Who's Vicky Larraz?" "The singer in OIé Olé, not Marta Sánchez, the real one, the first one." " Never mind, in Vicky's number..." " Yes." "There was an accident with a katana..." "The Samurai!" " Yes, that's me." " Oh, great!" "I was thinking, "I wonder what Cristina's up to." "I'll call her."" "I've got your number from the students reunion which I didn't got to." " How are you?" " Great!" "Do you feel like meeting up next week?" "Yes, I'd love to." "I was thinking of taking the kids to Montjuic Gardens." "I love gardens." " Perfect, shall we write?" " Okay." "What's your Facebook name?" "I'll add you." " My Facebook name..." " Tell her." " I don't have one." " What?" "Make one up!" "Mary Carrot." "Mary Carrot, that's original." " I'll write to you." " Okay." " Big kiss." " Big kiss." "My grandmother's on Facebook!" "And I've got a friends afternoon with Cristina Pi." "First objective, make contact." " What'll we talk about?" " You'll see." "I won't have any conversation topics." " What happened at the school party?" " I don't know what you mean." "Tell me what happened." " Tell me, please." " Nothing happened." " Did you kill someone?" " No, no." "Tell me, Mary Carrot, please!" " Now your quid pro quo." " Tell me." "Let's get started." "Look." "Stairs." "Come on, Borja!" "One, two, one, two!" "RUTH!" "This is more my level." " That's how it is." " It's not a package." "It's vertical." " What's it for?" " It's a ball of energy." "Borja, did you bring yourjunk food?" "That's it?" "That's all the stuff you've got?" "Yes." " Sure you don't have anything else?" " I'm sure." "I'd rather go to your place and check." "My place?" "I share a place, and without warning..." "Thanks for the cupcakes, grandma!" "Yes, homemade, very nice, but your grandson has to eat healthy!" "When she wants her space, she takes out her hearing aid." " Who can say no to her?" " To a grandma?" "Nobody." "Want to see the place?" "This is the recreation area." "Let's hit the kitchen first." "My turn." "Let's do the easy one:" "HOBBIES." "Playing an instrument." "Painting." "Origami?" "Knitting." "Cooking." "Puzzles." "Swimming." "Cycling." "Running." "Knitting!" "Sex." "No way." "I've got it!" "Watching Venezuelan soaps with my grandma." "HOBBIES" "LIVING HAPPY" "Mary?" "Coming!" "I'm going to bed, I don't feel so good." "See you tomorrow." "Good night." "What are up to this afternoon?" "Will you come with me to look at a flat?" "Wait, the little ball was in front of us." "No, you're the little ball." "Isn't that the destination?" "There are two balls!" "Look!" "If I spin around the ball changes colour!" "It's here." "Here it says "pet shop"." "The lady said it was next to a pet shop." "You sure?" "Wait for me!" "The loft is separate, but access is through the shop." "And if it's closed?" "Don't worry, I'll give you a key." "What do you do?" "It's just for the forms, for the rent of the flat." "Marketing and advertising, but right now I'm in professional transition." "Here, it won't take long to see it." "Right, a loft means no separating partitions, but if you had another budget you could rent the flat my daughter Desi vacated." "It's 60 sq. metres, two rooms, if you want kids..." " No, we're not..." " No, it's for me." "Go on!" "I can see it in your eyes." "Even if I wanted to, I couldn't afford it." "I'm actually unemployed." "Weren't you in advertising?" "Well, I think I have a job for you." " When can I start?" " Whenever you like, right now." "JOB" "What do I have to do?" "New vanilla flavour, your dog will be over the moon!" "New vanilla flavour, your dog..." "Look, he'll be over the moon." "Biscuit?" "Would you like a biscuit?" "New vanilla flavour, your dog will be..." "It's for dogs, eh?" " Mind if I take a photo?" " No." "Sure." "Daddy, take my photo with the biscuit!" "Hey,bum" "New biscuits!" "If I tell you the watts the bulb has, it doesn't matter because we've got no perspective on the light." "The watts don't matter." "We have no idea." "Because we have no perspective, understand?" "We'd have to turn out all the lights in Ikea to remotely understand its light, understand?" "Biscuits!" "Fresh made today, sir!" "Sir!" "Sir!" "But..." "Get off!" "What the...?" "Get off!" "Dumbass!" "Dirty doggie!" "Dirty!" "I'm going to tell my mum!" "Mateo!" "I told you, I don't like you Chasing Chicho!" " Sorry, did he bother you?" " No." "No." "Mary?" " Mary of the Mountains!" " Cristina!" "That's amazing!" "What a coincidence!" "We spoke the other day and now we run into each other!" "You're..." "I'm doing a study to see the effect on a brand of product representation." "Great." "Yes, we marketing people are kind of..." "I know, my husband's in advertising, I know what you mean." "I'm off to the club nearby." "Will they let get away, 15 minutes?" "I don't know..." " Like a biscuit?" " No, thanks." "Did you eat...?" "I was going to sign him up forjudo, but I chose tennis because it's less violent, and he loves Rafa Nadal." " Sure." " Excuse me." "Yes, honey." "They can't after all." "Have it before the vitamins go." "That way I can rest up." "Okay, big kiss." "I love you, too. 'Bye." "Sorry." "My HUSBAND'S opening an ART GALLERY he's starting with some FRIENDS, my parents can't mind the KIDS, and the poor man was worried I'd forgotten about it." "I've started a new JOB working from HOME and I'm a bit stressed, but never mind, I'm HAPPY." "You can tell." "Chicho!" "Stop!" "Sorry, he's turned out so virile, he latches on to the first thing he can." "Behave yourself or no date with Smurf a." " Smurf a is..." " His girlfriend." "He's got a girlfriend and everything." "He's very sporty too." "Sometimes he acts as a ballboy!" "He's so cute!" "The King of the house." "Sorry, I'm going on about myself." "What about you?" "Do you live around here?" "Partner?" "Kids?" "Javi!" "We're training next week!" " How's your love life?" " Not right now..." " No?" " No." "How are your parents?" "My father died." " Oh, I'm sorry." " It's okay." "And your mother?" "No, my mother didn't." "Honey?" "Yes, I sent the invitations." "Gustavo's as well." "Gustavo's coming alone, isn't he?" "No reason." "I'm going, I'm with a friend." "I was thinking..." "Do you like blind dates?" "BE HAPPY" "(WITH AN ARGENTINIAN ACCENT) Let's breathe, relax your abdomens." "Let go, let your mind go, your emotions as well, they have to come out..." " Borja." " What?" " We put ourselves in therapy." " So?" "That's what people with problems do." "No!" "Normal people go to therapy." "You should put that on your list." "I want to laugh to be happy!" "After me!" "I want to laugh to be happy!" " I ran into Cristina Pi yesterday." " And?" "Great, super normal." "She's got a lovely husband, parents that babysit her boy Mateo." "The vocal laugh with abdominal thrust is the most contagious." "She's going to introduce me to a guy, Gustavo, he's charming." "Let's try it." "One, two, three, four..." "Here are the balloons." "For the next time, I want you to do an exercise:" "Blow them up, get a marker pen, write down everything that makes you anxious, sad, sorrowful... right?" "Put it on the balloons, tie them up and toss them into the air." "Is that clear?" " Excuse me." " Yes?" "Can I get two bags?" "Of course." "Why not?" "I thought at 30 my life would be different." " Different to what?" " To what it is now." "You didn't?" "No." "I didn't think at 30 I'd be back at my mum's house." "I live with my grandma, so..." "we're even." "But you get along with her." "It's impossible not to get along with her." "There's no credit in that." "Come on, you know what's next:" "FAMILY LIFE" "Start with Ludo, close families do it." "Do you want to play Ludo?" "Hallö, Hemnes, Hilver, Hövet..." "I'll need two more, in the name of Pàmies and Barroso." "The same street, yes." "When's delivery?" "Two weeks?" "Do you think we become copies of our parents?" "No." "Because my father and my brother are thin." "And your mother?" "Her too." "Maybe you're adopted." "Switch." "My mother's a mystery to me." "I never really know what she's feeling or thinking." "Why don't you talk to her?" "Do you have deep conversations with your parents?" "We're Galicians." "You never really know what we're talking about." "Right." "And what about your father?" "Switch." "I remember the day we took this photo, on a trip to Montserrat." "We ate hamburgers and Alex and I were allowed to eat sweets." "On the way back my parents argued, for a change." "They could argue about anything, the weather, food, what was on TV, banks, a blown light bulb, shoelaces, a skirt that was too short, an overdone steak, a badly ironed shirt, "you're a bad mother," "you're worthless, useless, an idiot..."" "After every argument, my father went into his office and my mother locked herself in the car." "Hi!" "What?" " I was doing my Swedish classes." " How come?" "In case I get a job at central office in Stockholm." "Stockholm." " There's one exchange every year." " Cool." " Did you talk to your mother?" " I haven't had time yet." "For the exercise today I brought the console." "No console, no way!" "Give it here." "You design my avatar and I'll do yours." " How's the Sausage job?" " It's a biscuit." " How is it?" " Fine." "Where's your grandma?" " I wanted to talk to you about that." " What happened?" "She's not my grandma." "What?" "One day I helped her carry up her shopping, I was flat-hunting, she asked me if I wanted to stay, one thing led to another, and now... she thinks I'm her grandson." "Are you serious?" "I save on rent money by cleaning the house, making the food, doing the shopping," "I shower her..." "It's quid pro quo, like us, right?" "Let's piav." "You shower her every day?" "I don't want to talk about it." "Hey, I'm not that fat!" " And my head's not that huge!" " Sure it isn't." " Are you insinuating something?" " No, your tits are perfect." "You looked at my tits!" "If we're discussing your tits, I'll look at your tits." "If we're discussing your feet, I'll look at your feet." "You did it again!" "Can we stop talking about your tits and talk about the screen?" "We can." "Though your feet are pretty too, I must say." "What do you like more, my tits or my feet?" "Your head." "And your ass." "Okay, I swallowed and breathed in, but revenge is best served on a cold plate." " It doesn't go like that." " Yes, it does." "No, it's "revenge is a dish best served cold"." " Revenge is the dish." " That's what I just said." " No, you're mixing me up." " Yes!" "No, revenge is a dish, it's the dish..." "It's the dish you serve cold." "No, revenge is the dish and you put it in the fridge." "What?" "The fridge?" "What's up, lovebirds?" "Why are you spying on your sister?" "I'm checking that she's dating handsome guys like you." "Cutie!" " This isn't a date, Alex." " It looks like it." " Working tomorrow?" " Yes, so are you." "Then we'll talk tomorrow." "The Swedish jobs registrations come out tomorrow." " Yes!" "Get to sleep!" "'Bye!" "'Bye!" "This isn't a date, is it?" "This?" " I don't know." " No." "We spent all evening playing video games." "That's true." " Not much of a date." " No, no." " Shall we meet tomorrow?" " Tomorrow." "Okay." "We'll talk." " Quid pro quo." " Quid pro quo." "'Bye." "'Bye." " You just made that up." " No." "It's the typical thing that everyone does, but won't admit to it." "I don't know, Borja." "You've done it." " No." " Admit it." " No!" " You've done it, admit it." "Okay, right..." "Maybe one time, just after the deed itself," "I did this with the duvet..." "And?" "And the smell reached me and it didn't bother me." "You..." "I liked it a little bit!" "A lot!" "You liked it a lot!" "I bet you breathed deep." "It's a "Dutch oven", everyone does it." "You know what a "Dutch oven" is?" "You fart, cover yourself with the duvet and make a microclimate." " There you go." " Welcome to the club." "Thanks." " I'll just get your card..." " Thanks." "...and you can sign it." " And we'll fart to seal it." " That's how you sign it." " Oh, thanks." " What's this?" " A surprise." "From Gagandeep and me." "Take that!" " But...?" " You can skip your diet today." " Really?" " Sure." "A message from Gustavo, Cristina Pi's friend." "He doesn't waste any time." "Hi, Mary, it's Gustavo." "Are you coming at 9 to Pablo's gallery opening?" "I'd love to meet you." "Big kiss." " Now what do I do?" " Say yes." "But that's in an hour." "Say yes." "Let me..." "Send me the address and I'll be there, looking cute." " Don't put that!" " I didn't." "Big kiss." "And an emoticon." " You like emoticons." " Very much." "Well." "You've got it." "You'll be late." "You have to go home, get yourself pretty, even prettier than now." "Thanks." "Put on earrings, perfume..." "Leave the plaits, you look cute with them." " I look good in plaits?" " Yes." "Go on." "You're my champ, you can do it." "Another point on the list." "Come on." "You're doing your duty." " Go on!" "'Bye!" ""Bye." "PARTNER" "...extremely beautiful, but with a disconcerting depth." "What?" "I am the artwork." "She's the artwork." "Very interesting... very good..." "Gustavo," "I'm in front of a painting..." "I suppose it's a uterus, in theory, but..." "I'm in a white dress, with straps," "I'm in plaits..." "And it all looks great on you." "Hi!" " Sorry." "I saw you here..." " That's okay." " Gustavo, right?" "Of course." " Yes." " How are you?" " Great." " Nice space." " Isn't it?" "Yes." "Pablo chose the place well." "It was hard for him to decide, but he got it right in the end." " Do you know...?" " It just opened, didn't it?" "No, I mean Pablo, Cris' husband." "Oh, sure." "No, I don't know him." "He's a charming guy." "Except when you beat him at tennis." "We've got an amateur CHAMPIONSHIP, a few FRIENDS after WORK, a few games, it does us the world of GOOD." "At some courts near HOME." "My BROTHER lives nearby and sometimes he comes too." "He's an ace, I mean it." "I'm talking too much." "I'm a bit nervous." "It's my first blind date." " Really?" " Yes." " Mine too." " Really?" " Yes." " How about that!" "It's a tie." " Well, deuce." " What?" " Deuce, like in tennis." " Deuce, of course." " Shall we take a look?" " Okay." "Tell me about yourself." "Brothers and sisters?" " This is my favourite." " Nice." "What's the plant?" "The sword oi Sam Aarch." " Very nice." " And this?" "A new plant, my mother's." "Mari." "Isn't your mother called Luisa?" "No, Mari is the plant!" "Shall we get the Sandwiches from the kitchen?" " Yes, sandwiches first!" " Let's go!" "And get met a Fanta!" "I'll put on the movie and get the Costumes." "Marta, how do you know if you really like someone?" " Do you want me to tell you?" " Keep your voice down!" "Okay, if you really like someone if that person makes you feel like David the Gnome." "But David the Gnome is tiny." "But he's 7 times stronger than you!" "Juanj0's mum's plant." "I wonder if it's the one the hippies smoked in the 60s." "The artist wished to show the void of the siren as a reflection of our times." "The absence of the uterus is the key to the artwork, her hysterectomy a symbol of vacuous, superficial Western consumerism." "Precisely." "You can see the influence of François Mauvellet." "Correct." "If you'll accompany me, we shall further appreciate..." "I think the..." "I didn't get it at all." "You didn't?" "Me neither!" " I don't get any of it." " I see a fishbowl." "Sure, I'm nodding away, and acting interested, but..." "Excuse me." "No, we were just discussing Mauvellet." "Sorry, I didn't mean to interrupt." "Let me introduce you." "Mary, Pablo." " I don't know if you know each other." " Hi." "How are you?" " How are you?" " You're Cris' Pablo?" "The very same." "Nice to meet you." "Sorry, I need to take him away for a second, if you don't mind." "Of course." "I just need your help with a buyer about tax deductions, what you told me the other day, I just don't understand it." "Mind if I go?" "That's fine, I'll stay here with the uteruses..." " Learn a lot, then tell me later." " Okay." " Don't go away." " Yes." "Just a second, okay?" "One, two, three..." "The uterus." "(TWILIGHT SCENE" "This is about absence, only smoke remains." "And the verticality is the abyss." "Excuse us." "No!" "That's the artwork!" "Sure, if you look at it separately..." "Mary, I'm here now." "Did they bring out the canapés?" "May I?" " Delicious!" " Yes." "It's got a dash of something..." "Can't you taste it?" " Thanks for walking me." " No trouble." "Thank you for coming." "It was fun in the end, wasn't it?" "Yes, it was good." "We learnt some things." "As well." "About uteruses, where they are..." "Maybe you knew better than I did." "Yes, especially my own." "It's here." "Oh, it's nice." " You've got a singing neighbour." " My brother." " Really?" "He sings well." " Doesn't he?" " Hi there!" " Hi." "Let me introduce a friend." " How are you?" "I'm Gustavo." " I'm Alex." "Nice to meet you." "Can I get your MP3?" "Okay, in my night table, in the drawer." " By the way, how was your dinner?" " Great, thanks!" "Cool." "Alex, great to meet you." "I hope we see each other again." "Maybe." " Nice guy." " He is nice, yes." "Your brother's very nice." "Yes, he's really happy I'm staying for a few days." "No wonder." "Big sister at home." "Yes." "Well, I don't know, Mary..." "I'd love to see you again." "I don't know if you..." "Me too." " Really?" " Yes, of course, yes." "We could go to Cris and Pablo's baby shower, or..." "'Yes'?" "Yes." "Well, they didn't mention it to me..." "No, you're coming with me, don't worry." "Check, check, check, check..." "I Satisfy them all." " What are you looking at?" " Is this list on the level?" "I don't know, I think so." "Why do you want to be normal?" "That's what everyone wants." "I don't." "Well... to fit in." "You fit in here." "Sure, with you, but..." "By the way, I know when you really like someone." " Oh, yeah?" " Yeah." "It's when they make you feel like David the Gnome." "What?" "7 times stronger." "7 times?" " Sure!" " Come on." " On three." "One, two, three!" "Quick, quick!" "Quick!" "Take that!" "Point!" "Don't get too excited, we're on 6-17-1." "Let's go over your list." "You've now got hobbies." "Bagpipes and puzzles..." "I'm not so sure." "Playing with the console is a hobby." "You've got a social life, Cristina Pi, you go to galleries, you've got a job." " Temporary job." " Temporary is normal." "What you don't have is a partner." "Gustavo's around." " But did anything happen?" " A shag?" "No way!" "Until the third date, no partner." "But he might be." "Not until the third date." "It's a universal law." "I'm meeting him this week." "That'll be our second date." "Take that!" " No." " Yes, a bet's a bet." " You can't do this to me." " Yes, yes I can." " It's filthy." " Yes, I can." "Be a man and get in there." "Go on." " Now?" " Wait!" " I'm bored." "3, 2, 1..." "Dutch oven!" " That's gross!" " Hang on, we said 10 seconds." " It's disgusting." "I want to get out!" " No." " It's horrible!" "What did you eat?" " Carrots." " Gross!" " It's part of your diet." "This is the most intimate moment I've had with anybody." "What are you doing?" " No, no..." " Yes." " God!" " Now you hang on!" "'Ha"9 on!" " No!" "I ate tons of stuff!" " God, you've got Hell in there." " I know." "If there's a Hell, you have it inside you." "Thanks." " If my kids catch me, I'll die." " Aren't they working?" "Quiet, it's starting." "Get it out." " Here." " A bit here, no?" "A bit more?" " No, he said..." " This is very expensive." "That puts my teeth on edge." "Now." "Oh, he's got two kinds." "It's impossible, I keep on dropping the filter." "If John from Prescott, Arkansas, can do it, so can we." "I've got an idea." "JAMAICAN BROWNIES" "INGREDIENTS" "BUTTER" "FLOUR" "SUGAR" "EGGS" "CHOCOLATE" "W ALNUT S" "MARIJUANA" "Butter, flour, eggs, chocolate, walnuts..." "That's it." "Now a little grass..." "More, put in more." " Will we get high?" " Put it all in!" "Sabina!" "Sabina, Serrat." "Serrat, Sabina." "I think Serrat and Sabina are the same person." "I think before I'm 60 I want to get it off with a black guy, like the guy from "The Intouchables", very firm, very black." "Black." " But with really white teeth." " White." "Who was the actor in "The Intouchables"?" "I'll look it up in my multimedia device..." " Look, your boyfriend's name is Omar." " What boyfriend?" "Omar, your black boyfriend." " Omar Sy, I can't say it." " Omar Sharif f!" " Why not?" " Omar Sy." "How nice." "What about you?" "You're not saying anything." " Me?" " Your wishes, Barbara." "What do you wish for?" "To tell my kids I'm sorry for being a bad mother." "This marijuana is..." "Vanilla biscuits, they'll be over the moon!" "This girl won't make me rich." "Gustavo!" "Hi, how are you?" "I'm so tied up here..." "Cristina's baby shower was today?" "No, sure I remember." "Just kidding." "I got a present, it's just gorgeous." "No, it's a surprise." "Okay, see you later." "Big hug, "bye." " Have we got anything for babies?" " Well..." "Shall I buy you this outfit?" "Thank you so much." "You didn't have to." " It's lovely." " Isn't it?" "It's like..." " We love it, don't we?" " We love it!" " Thanks a lot." " It's a trifle." "She chose it, she's just being modest." "I've never seen one this shape before." "The things they make for babies these days, it's amazing." "Listen, a toast to the cooks." "I brought a fabulous wine." " Here." " Let's do it." "Cheers!" "SOCIAL LIFE" "So, what do you do?" "I work in marketing." "A biscuit company." "Teo tried them and he loves them." " They're for dogs." " They're for dogs?" "No!" "I mean, yes and no." "They're biscuits for both human and canine consumption." " Since the dog is man's best friend..." " Sure." "And Teds med them?" " Y es." "It's all the rage." "They give kids dog biscuits." "Dog biscuits aren't for dogs, they're for dogs and kids." "The slogan is "Biscuits for everyone"." " I love it." " Yes." "My firm?" "Prats-McDougall." "Prats was my grandfather, and McDougall a Scot who drank a ton of whisky." "I've always thought the mood in the FIRM is so good because we're like FAMILY." "We travel, play sport TOGETHER..." "I don't know if Gustavo told you, we play tennis." "You must come one day, you'd LOVE it." "We do Pilates TOGETHER, it's amazing, your "power house", they show you how to breathe, to do this thing with your arms, you get rid of WORK stress, you feel better and you can do it at HOME, right, honey?" "Yes, I had no nausea, my HUSBAND was delighted, and I worked up until a month before the birth." "Actually, I didn't want to get pregnant, then my PARENTS helped me out so much, they're essential." "I'm going to make some Cocktails with an imported gin I got." "Delicious, you'll see." " Like that?" " Yes!" " Do you know where it all is?" " Yes." " Your schoolmate." " Who?" "You always tell that anecdote aboutherdance, some choreography for the end-of-year dance, and bam!" " Bam?" " She cut off a student's finger!" "Yes!" "You don't know, you weren't there." "You've told me 20 times." " Cut off a finger with what?" " Sliced it with a katana!" "No one would dance with her, so they got two primary schoolers, she looked like Snow White and two dwarves..." " Isn't it a terrific story?" " Terrific." "What did you call her?" "Wait, wait..." "The Samurai." "The Samurai, yes." "Got any dill?" "I don't know..." "Never mind, I'll make gin and tonics with cardamom and a little..." "Peppen" "Where's the bathroom?" " On the left, down the end." " Okay." "Are you alright?" "What is it?" "What?" "What's wrong?" " No!" " Quiet." " No!" " What is it?" "She's The Samurai." " No." " I swear." " That's it." " Fucking hell." "TRANSFER REQUEST" "HUGE PARTY" "Wes?" "'B°Ua?" "Mary, I can't hear you, I'm at a party." "I didn't know you had a party." "Yes, with some people from work." "I'll go outside a moment." "Be right back, guys!" "If it's a bother, I'll call later." " I can't hear you well." " If it's..." "We're at a birthday party for a girlfriend of a guy at work, all her girl friends are here, it's a huge party." "Oh, okay." "How's your date?" "It's not a date, it's some friends meeting up, remembering old times, having fun." "Right." "I'm having lots of fun too." "In fact, it's been ages since I had so much fun." "It's been months since I had this much fun." "Years for me." "Like 10 years, for me." "I think it's the greatest night of my life." "Shall we do something tomorrow?" "I can't, I've got... this thing." "Okay." "Alright." " Alright." " Okay." " We'll talk." " Right then." ""Bye." ""Bye." "I'm an idiot." "You really cut off his finger?" "Bone and everything?" "The whole digit." "Well..." "I hope if I misbehave, you won't do the same to me." "No, of course not." "Which finger was it?" "This one." "What do you do with this?" "Nothing." "You can't point, but..." " But you've got more." " Four more." "You can't touch, that's true." "Like this." "Good evening." "Hey, champ." "You're bothering the neighbours." "It's late!" "Alex!" "Is he annoyed about something?" "I don't know." "Well..." " Sorry." " No, it's okay." "Do I call you?" "Shall we meet up this week?" "Okay." " Great." " Yes." " Anyway, sleep well." " You too." " Give your brother a kiss." " Okay." "CAN YOU TALK?" "REQUEST, TRANSFER TO STOCKHOLM" "VALIDATE" "Your attention." "This centre opens in 10 minutes." "Your friend brought you some balloons." "What are you doing here?" "What are you doing here?" "I'd go if I were you." "Wait." "Are you angry with me?" "No, I'm busy with the Stockholm thing." "You're going?" "If they choose me." "There's nothing the matter?" "It's great you found helium." "We had lots of balloons to blow up." "Now what do we do?" "What the Argentine teacher said." "What was that?" "Get a marker pen and write down everything that annoys you about your life." "What if nothing annoys you?" "Nothing annoys you?" "That's lucky." "Shall we do it?" "Go on." "Okay." "LONELINESS" "FEAR" "FAT" "REJECUON" "SHOUTING" "BLOWS" "GUILT" "I'm sorry." "I love you so much." "Are you alright?" "Yes." "If you go to Stockholm, I'll miss you." "SONGS FOR WHEN MUM IS SAD" "Almost at the end of side B." "Super Secret Radio 9.0 here." "For a special listener who came on a spaceship." "Älex, Mom didn't come on a spaceship." "For a special listener, she's cool in the pool!" "1, 2, 3, we love you, Mum!" "I love you, Mum." "I love you too, my girl." "Sorry I was a bad daughter and didn't help you with Dad." "It was my fault for loving him and staying in love with him." "You look lovely with your hair down." "What are you doing here?" "I was looking for you!" "FAMILY LIFE" "We were talking." "About time, that's great." "What about you?" " I want to tell you something." " What?" "I've got a boyfriend." "Really?" " What's his name?" " Juanjo." "Juanjo?" " When do we meet him?" " I don't know." "Let's go have dinner, the three of us." " Now?" " Yes." "I can't, I'm meeting someone." "30th?" "Before working with the carbonics we have to cool the glass." "Oh, sorry." "No problem." "Does anyone know the basic component of tonic?" "Quinine." "Tonic's basic component is quinine, which appear during the English Colonization of India." "The best is yet to come." "Taste it!" "Alcohol doesn't sit right with me." "It's time to start the tasting." "Start with the first mix." "You've put in the pepper?" "Try a tiny sip" "The pepper lodges in the upper palate, spicy at first, then diluting in the palate." "It gives it a freshness, doesn't it?" "Now the third, with the ginger." "Okay." "Don't swallow!" "I want you to feel the freshness, to see how the ginger..." "JOB" "HOME" "PARTNER" "SOCIAL LIFE" "HOBBIES" "FAMILY LIFE" "BE HAPPY" "Excuse me a moment!" " Can I ask a favour?" " Yes." "Can you stand here?" "Look." "JOB" "HOME" "PARTNER" "SOCIAL LIFE" "HOBBIES" "FAMILY LIFE" "BE HAPPY" "Is this list on the level?" "I don't think so." "So, dill, Cucumber, right?" " Ginger." " Ginger." "And depending on if you put in cardamom..." "Gustavo." "Do you have fun with me?" "Of course I have fun." "Even though I don't perceive the floral nuances?" "Well, it's your first class." "Our first time was..." "And if I say we bought Cristina's son a Chihuahua outfit?" "And I like farting under the blanket?" "Yes, yes!" "That's fine, Mary." "It's just... everyone's looking at us a bit strangely and..." "Sorry, what was your name?" " Manuel." " You look familiar." "Weren't you Argentinean?" "Yes, the laughter therapy's a second job." "I get paid more as an Argentinean." "And a great teacher, I'm sure." "Gustavo, you're so nice." "You're like the perfect guy, the kind of guy a normal girl would dream of." "Well..." "But I'm The Samurai." "At 15 I cut off the finger of a primary schooler with a katana." "My mentally handicapped brother knows more about life than me." "It's taken me 10 years to tell my mum I love her, and I'm in love with a fat redhead who lives with his grandma, who's not even his grandma, and I fart under blankets with him." "That's nice." "Thanks for everything, Gustavo." "You too, for coming and..." "No, you even more." "You can taste the cardamom." "Chihuahua..." "Weirdo." "Borja Santaolalla, your presence is required in the kitchen section, please." "I WANT A THIRD DATE." "I want a third date with you, and if you like, I'd love a pizza with you here." "But if I had to go to Stockholm, I wouldn't mind," "I'd catch a plane, go and eat Swedish pizza, buy anoraks with those duck feathers." "I've seen them, they're fantastic." " A bit expensive, but good." " Sorry..." "Can you... repeat... what you said?" " Which part?" " The beginning." "The pizza thing?" "I said pizza because the first day we had... the day we met we had a date." "Was it a date?" "Yes." "Then on our first date we had pizza and..." "I've realized how much I like you." "How long do we have before you go to Stockholm?" "I'm not going." " Alex told me they chose you." " But I'm not going." "I'm staying." "Come on." "I want to show you something." "Remember the day we met?" "I'm looking for a bulb for my desk lamp, but I'm not sure what light these give off exactly." "So to tell we should be in darkness here, right?" "I mean, all those lamps should be off and we turn it on and off to tell the difference." "Do you know what I mean?" " How about this one?" " It's my favourite." " Really?" " Yes." "Then it's yours." "REQUIREMENTS TO BE A NORMAL PERSON" "READ IN SWEDISH" "EAT ICE CREAM" "DANCE" "HAVE GIGGLE ATTACKS" "DO A STRIPTEASE" "Take it all off!" | Low | [
0.513698630136986,
37.5,
35.5
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