We revisit the classic semiparametric problem of inference on a low dimensional parameter θ_0 in the presence of high-dimensional nuisance parameters η_0. We depart from the classical setting by allowing for η_0 to be so high-dimensional that the traditional assumptions, such as Donsker properties, that limit complexity of the parameter space for this object break down. To estimate η_0, we consider the use of statistical or machine learning (ML) methods which are particularly well-suited to estimation in modern, very high-dimensional cases. ML methods perform well by employing regularization to reduce variance and trading off regularization bias with overfitting in practice. However, both regularization bias and overfitting in estimating η_0 cause a heavy bias in estimators of θ_0 that are obtained by naively plugging ML estimators of η_0 into estimating equations for θ_0. This bias results in the naive estimator failing to be N^(-1/2) consistent, where N is the sample size. We show that the impact of regularization bias and overfitting on estimation of the parameter of interest θ_0 can be removed by using two simple, yet critical, ingredients: (1) using Neyman-orthogonal moments/scores that have reduced sensitivity with respect to nuisance parameters to estimate θ_0, and (2) making use of cross-fitting which provides an efficient form of data-splitting. We call the resulting set of methods double or debiased ML (DML). We verify that DML delivers point estimators that concentrate in a N^(-1/2)-neighborhood of the true parameter values and are approximately unbiased and normally distributed, which allows construction of valid confidence statements. The generic statistical theory of DML is elementary and simultaneously relies on only weak theoretical requirements which will admit the use of a broad array of modern ML methods for estimating the nuisance parameters such as random forests, lasso, ridge, deep neural nets, boosted trees, and various hybrids and ensembles of these methods. We illustrate the general theory by applying it to provide theoretical properties of DML applied to learn the main regression parameter in a partially linear regression model, DML applied to learn the coefficient on an endogenous variable in a partially linear instrumental variables model, DML applied to learn the average treatment effect and the average treatment effect on the treated under unconfoundedness, and DML applied to learn the local average treatment effect in an instrumental variables setting. In addition to these theoretical applications, we also illustrate the use of DML in three empirical examples.


Health care delivery in the Circumpolar North is challenged by a scarcity of culturally relevant health care services, few medical providers trained in cross-cultural care, and high costs of transportation. Community health workers (CHWs) are primarily Indigenous individuals who provide on-the-ground health care and health promotion services in their own communities. The CHWs' scope of work varies from health education to clinical care and often focuses on upstream factors that impact the public's health. Although often overlooked and underutilized, the CHW role is an innovative approach to promoting more sustainable and culturally relevant care within health systems. Investigating and understanding the potential ways that CHW-integrated health care systems support health and wellness could allow for a clearer understanding of how to translate this approach to other regions seeking a transition to sustainability in health and wellness. Drawing on experiences with CHWs in the Circumpolar North, this article introduces a conceptual model summarizing pathways that describe how integrating CHWs supports wellness in their communities. The proposed model includes five pathways for how CHWs could support wellness: (1) the recruitment of CHWs from within a community promotes community capacity and control; (2) the CHW role allows them to advocate to address structural and systemic inequalities that contribute to ill health, if CHWs are supported to organize their communities around wellness; (3) CHWs have the potential to support and empower community members;  (4) CHWs have the potential to develop culturally relevant, feasible, and effective health promotion strategies; and (5) CHWs have the potential to build on community strengths. This model allows for CHW-integrated health care systems to be critically examined to both test and refine this proposed model, and support and empower community health workers as a transition to a more sustainable health care delivery system that reduces inequities and promotes health.


The development of microcrystalline silicon (μc-Si:H) for solar cells has made good progress with efficiencies better than those of amorphous silicon (a-Si:H) devices. Of particular interest is the absence of light-induced degradation in highly crystalline μc-Si:H. However, the highest efficiencies are obtained with material which may still include a-Si:H regions and light-induced changes may be expected in such material. On the other hand, material of high crystallinity is susceptible to in-diffusion of atmospheric gases which, through adsorption or oxidation, affect the electronic transport. Investigations are presented of such effects concerning the stability of μc-Si:H films and solar cells prepared by plasma-enhanced chemical vapour deposition and hot wire chemical vapour deposition.


Abstract:This article explores the relationship between liberal democracy and socioeconomic equality, both on a theoretical and a practical level. It recounts both liberal and non-liberal arguments why democracies should or should not worry about de facto inequality, and then goes through a series of consequentialist arguments about why, alternatively, democracies should either worry about high persistent levels of inequality, or conversely, why attempts to remedy inequality through social policy is likely to have deleterious political or economic effects.


How does political trust affect the competing pressures of policy versus political performance in emergent democracies? Studies suggest that political trust buffers against these pressures, but empirical evidence is lacking in regard to if or how, given the focus in the literature on mature democracies where democratic institutions and practices are unlikely to be upended by either policy or political underperformance. However, in emergent democracies where the risks of democratic reversal loom large, the distinction is highly relevant. This article investigates how political trust matters in emergent democracies, specifically, if political trust buffers against public pressures, and whether it is system-directed versus incumbent-directed, for East and Southeast Asia. The evidence from multiple waves of survey data provides three useful insights: first, it shows that political trust supersedes economic expectations in support for the democratising system; this supports political trust as a buffer for the political system and is system-directed. Second, political trust goes hand-in-hand with economic performance to explain support for the incumbent government. This finding clarifies that political trust does not buffer the government against public pressure for performance. Third, taken together, the results show that economic growth may keep a government in office but institution-building leads to political trust that undergirds the political system, so that institution-building is a priority for stability in emergent democracies. These results expand the political trust literature to underpin democratic progression and consolidation issues that are unique to emergent democracies.


A new, simple, rapid and accurate stability-indicating HPLC method was developed and validated for quantitative determination of carbamazepine (CBMZ) in pure and dosage forms. An isocratic HPLC method, using a C18 reversed phase column (150 mm x4.6 mm i.d., particle size 5 μm) with isocratic binary mobile phase consisting of methanol and water (70:30,V/V), was investigated to separate the drug from its stress degradation products. The flow rate was 1.5 mL min at ambient temperature and photo diode array (PDA) detector was used at 285 nm for detection. The elution time of CBMZ was found to be 2.324±0.003 minutes. The developed method was validated for system suitability, linearity, accuracy, precision, limits of detection and quantitation, specificity, stability and robustness. Stability tests were done through exposure of the analyte solution for five different stress conditions: Reflux with 1.0 mol L hydrochloric acid (HCl), reflux with 1.0 mol L sodium hydroxide (NaOH), reflux with 30% hydrogen peroxide (H2O2), exposure to ultra violet radiation (UV) radiation and heating. The calibration curve was found to be linear with the equationy=0.19677x-0.306, with a correlation coefficient of (R=0.9999) over a concentration range of 2.0-24 μgmL. The limits of detection and quantification were 0.02 and 0.062 μgmL, respectively. The recovery value of this method is 99.80% and the reproducibility is with in 1.23.


Purpose: To discover the geometric features that best identify an anatomically‐similar reference patient from a library of previous treatments to predict achievable dose distributions for automatic IMRT treatment planning of a new patient. Methods: Using a library of previously‐treated patients, two similarity functions are defined in the domain of the dose distributions and geometrical features that match a patient with their most similar member from the cohort. The goal is to attain the same patient matches from these similarity functions, so that when a new patient without dosimetric information is input into the geometric similarity function a similar patient from the library can be identified with good dosimetric predictive power for the new patient. The dosimetric similarity function is defined by a weighted sum of the difference area between two DVHs for all organs and PTV, with the weights tuned to reflect clinical priorities. The generalized geometric similarity function was defined as a nonlinear combination of organ/PTV volume, organ/PTV overlapping volume, and Dice index between a pair of two organs/PTVs/intersections. A genetic‐algorithm‐based learning technique was then employed to find the optimal combination of geometrical features to predict patient similarity. Results: For a database of 10 prostate cancer treated patients, a combination of bladder volume and (PTV, rectum) overlapping Dice index achieved 80% accuracy compared to the DVH similarity function. Validation on a library of 15 patients reduced the accuracy to 60%, implying that other geometric features could be needed. Conclusion: We have developed a method using machine learning to identify the best match of a new patient to the prior patients to guide automatic IMRT planning. Initial results from this feasibility study have modest predictive power but future work will focus in the incorporation of other geometric features, e.g. mutual information and overlap‐volume‐histograms, to increase selection accuracy.


EKREN, S., A. GOKCOL and C. SONMEZ, 2012. Heavy metal contents of Aegean region tobaccos according to quality groups and stalk position. Bulg. J. Agric. Sci., 18: 92-99 The study was carried out in Akhisar district of Ege Region in Turkey where tobacco is very popular in the growing period of 2004-2005. In this research, nine fields which are differences in terms of the quality and efficiency in the villages called Haciosmanlar, Arabacibozkoy, Derekoy, Mecidiye and Suleymanli were selected. Chromium, cobalt, nickel, zinc, arsenic, cadmium and lead contents of the tobaccos were analyzed. All analysis showed that there were significant differences among tobacco samples analyzed in different years, priming and also quality groups. After two years results of the study, arsenic, lead, chromium, cadmium, cobalt, zinc and nickel were measured as 0.18-0.98 ppm, 7.45-38.40 ppm, 4.37-28.60 ppm, 0.05-1.50 ppm, 1.10-5.45 ppm, 43.9-140.9 ppm, 6.00-10.85 ppm, respectively.


Prescribed burning is used for many silvicultural and wildlife management objectives. However, the use of prescribed burning can be constrained due to difficulties in obtaining burning permits, concerns about liability, potential effects of scorch on growth and survival of crop trees, its sometimes ineffective results, limited burning days, and the costs of applying, controlling, and monitoring burns. For some landowners, herbicides offer a cost-effective alternative to prescribed burning for manipulating plant communities and wildlife habitat, especially when the boundaries of application are closely defined and the focus is on individual habitat components. Although the ecological effects of fire and herbicides sometimes differ, when used alone or with other management practices herbicides offer an opportunity to meet many wildlife management objectives. In this paper, we discuss and provide examples of wildlife management objectives that have been met by using herbicides, and factors that should be evaluated when considering use of either prescribed burning or herbicides.


Goldman [Sachs] should matter to outsiders . . . because it stands at the centre of a two-decade-long transformation of the financial markets and a new approach to risk. Business risks that were once seen as a lumpy fact of life are now routinely sliced up and packaged into combinations that generally suit issuers and investors alike. At the heart of this change has been the development of huge markets in swaps, derivatives and other complex and often opaque instruments that allow the transfer of risk from one party to another. From small beginnings in 1987, the face value of contracts in interest-rate and currency derivatives is now more than $200 trillion[,] 16 times America's GDP. A further $17 trillion is outstanding in (even newer) credit-default swaps, which allow bond investors to lay off the risk of issuers defaulting. I. INTRODUCTION Heralded as the "debutante of the suretyship world (pure as the wind-driven snow and virtually unsullied by the foul touch of litigation)," credit default swaps (CDS) have transformed banking.2 Lenders who once found themselves stuck with bundles of indivisible, illiquid risks can now carve out and hedge credit exposure to individual borrowers. And they do it on a massive scale. As last reported by FitchRatings, the notional amount of outstanding CDS stood at $3.5 trillion, representing two-thirds of the entire credit derivatives market and an 86% increase from the prior year's total of $2.8 trillion.3 Yet despite such rapid growth, use of credit derivatives was too small to be either noticed or recorded at any significant levels in 1996.4 As one would expect of a market that has gone from cradle to world phenomenon in less than a decade, CDS have attracted both supporters and detractors. Proponents extol the ability of CDS to spread risk and increase liquidity across credit markets, allowing participants to actively manage and protect credit portfolios.5 Sensational critics warn that a spike in interest rates could trigger a "derivatives tsunami" that would bring all of the major banks to their knees and cause a "blowup" in world credit markets.6 Experience in the past few years has shown that, if used responsibly, CDS have the ability to yield all of the promised benefits with few-if any-of the predicted catastrophes.7 Between the disparagers and the defenders of CDS stand the regulators. But who are the regulators of CDS markets, and what law applies? Since CDS are traded entirely over-the-counter (OTC), one could argue that the true regulators are market participants themselves. Banded together as members of the International Swaps and Derivatives Association (ISDA), derivatives markets participants have created a system of documenting and amending trade relationships that is both flexible and robust. Most members of ISDA are banks or groups of banks. Some outside regulators, however, worry that CDS markets are growing too quickly for any bank or group of banks to control.8 In judging who has authority to step in and govern various aspects of CDS trading, one confronts a crowd of would-be regulators. The CFTC, SEC, Fed, state insurance regulators, and both state and federal courts all have spheres of competence that, depending on circumstances, may or may not affect CDS trading. Letters of guarantee and other analogous surety instruments require their users to focus on merely one body of statutory law-e.g., Article 5 of the Uniform Commercial Code-and its applicable case precedents; CDS, on the other hand, demand that their users at least take account of (and perhaps apply) commodities, securities, banking, and insurance regulation, as well as all applicable case law. Where commodities regulation is concerned, CDS enjoy a blanket exemption under the Commodities Exchange Act.9 The Commodities Exchange Act (the "Act") includes in its definition of "excluded commodity" any "credit risk or measure."10 Building on this definition in a section on "excluded derivative transactions," the Act notes that its terms do not apply to any agreement in an excluded commodity where such agreements are executed between eligible participants-financial institutions, regulated insurance companies, and most investment companies-off of a registered exchange. …


As members of Herbert Marcuse's immediate family, we have been asked for our suggestions as to memorial activities for him. We thought we might best respond in the form of an open letter to Herbert's many personal and political friends, as well as to our own friends. Herbert always felt keenly the importance of preserving and protecting the intimate sphere of the life of the individual. For this reason he had always celebrated the important private events of his life in the intimacy of his family and closest friends. For the same reason we conducted our personal mourning ceremony for him in private, deciding against a public funeral, and had his body cremated, in accordance with his wishes. Herbert Marcuse was a German Jew who was forced out of Germany by a fascist government, and found refuge in the United States. He became an American citizen, and always admired the diversity and acknowledged the relative political freedom that this country provided. Although e was not religious, it was important for him (and it is to us) that he was Jewish. Accordingly, we said Kaddish, the traditional Jewish words of mourning, for him when he died. The aspect of the Jewish tradition with which Herbert most strongly identified isthe importance it places on the struggle for justice in this life, in this world: its insistence on the ongoing effort "to use life to help bring about a better life." While Herbert cherished the intimate spheres of life, he also was deeply convinced that human beings are, in their essence, political beings, and that it belongs to the very nature of a human being to attempt not only to understand the world but also to change it. Politically, he saw continual theoretical work as absolutely vital for an emancipatory socialist practice. He aspired to a very high standard of decency and humanity both in his personal life and in his political role, and his final words, in a political conversation, often were simply: "carry on!" Herbert Marcuse is dead. Neither we nor anyone else can nor should attempt to speak for him. But for those who wish to undertake memorial activities in his honor, it would be our own hope that such activities take place in the tradition of intellectual work and political activity in which Herbert saw himself, and which we have tried to describe briefly in this letter. For those who might wish to make contributions i his memory, gifts to any of the causes which Herbert supported in his lifetime would certainly be welcome. Most recently he was actively involved in the attempt to obtain freedom for Rudolf Bahro, the East German dissident Marxist who was imprisoned for writing the book The Alternative. Contributions to that cause may be sent to the Committee for Rudolf Bahro, c/o Rudi Dutschke, Heibergsgade 25, Aarhus 8200, Denmark.


Spectrin is a membrane skeletal protein best known for its structural role in maintaining cell shape and protecting cells from mechanical damage1-3. Here, we report that spectrin dynamically accumulates and dissolves at the fusogenic synapse, where an attacking fusion partner mechanically invades its receiving partner with actin-propelled protrusions to promote cell-cell fusion4-7. Using genetics, cell biology, biophysics and mathematical modeling, we demonstrate that unlike myosin II that responds to dilation deformation, spectrin exhibits a mechanosensitive accumulation in response to shear deformation, which is highly elevated at the fusogenic synapse. The accumulated spectrin forms an uneven network, which functions as a "sieve" to constrict the invasive fingerlike protrusions, thus putting the fusogenic synapse under high mechanical tension to promote cell membrane fusion. Taken together, our study has revealed a previously unrecognized function of spectrin as a dynamic mechanoresponsive protein that shapes the architecture of intercellular invasion. These findings have general implications for understanding spectrin function in other dynamic cellular processes beyond cell-cell fusion.


Process behaviour in the aluminium smelting industry is typically highly dynamic
and unstable and involves non-linear, highly dimensional relationships among
process parameters. Further, with the presence of noise associated with most of the
measured parameters of the aluminium production technique, process modelling in
the aluminium industry is often a complex task. However, the advancement of both
knowledge and technique has resulted in significant changes to industrial processing
techniques and process control methodologies. One such advancement is the
development of artificial neural networks, which are a well-suited computational
paradigm for use in monitoring and controlling complex dynamic processes. Neural
networks offer a powerful mathematical technique for modelling, control and
optimisation of dynamic processes that are developed using process data, without the
need for a priori knowledge or understanding the associated scientific principles and
underlying relationships among process parameters. Generally, when a neural
network is initially trained for a particular task, some of the features of the training
data will have no significant effect on the networks decision, while other features
will be critical. In addition, there exist many networks for a particular task that may
perform similarly, however, they may use different features of the training data to
make their decision. This work presents an evaluation and empirical performance
comparison of various neural networks in an important and actual application
domain. Such studies are valuable to understanding the strengths and weaknesses of
various problem solving models as well as the characteristics of various application
domains. As neural networks are an advanced control technique that are often used as
an opportunity to maximise corporate revenue, it becomes necessary to develop a set
of selection criteria for selecting a particular neural network that produces optimum
performance when applied to a specific application. Neural network selection can be
completed based on economic considerations, such as cost associated with neural
network accuracy, cost associated with measuring process parameters used as input
variables in the model and cost associated with neural network computation time. In
this work, evaluation of neural networks for three industrial applications, involving
process modelling of reduction cells for aluminium production at Comalco
Aluminium (Bell Bay) Limited, or CABBL, is completed. The performance of six
distinct models of the neural network paradigm is assessed using specific assessment
criteria. The decision of which neural network model is most suitable for a specific
application is complex, requiring quantitative decision logic, particularly as the
assessment criteria are not fundamentally of equal significance. e. It is shown that
optimisation techniques are necessary to select an optimum neural network model for
a specific application. While it is noted that available operations research techniques
are capable of neural network optimisation and selection, such optimisation
techniques are inappropriate for application in this instance. This work reports a
systematic technique that optimises a neural network efficiently on command using
precise mathematical models. It is shown in this work that the influence of each input
parameter on prediction error is analysed to determine an optimum neural network
model for each studied application. Moreover, while a feasible solution for the neural
network model is identified in the first instance, an optimal solution is subsequently
obtained and implemented to achieve maximum economic benefit. It is noted that the
developed optimisation strategy is a unique and novel methodology for neural
network optimisation and selection and has been carefully developed to facilitate its
ease of application in industry.


1 Abstract MR fluids are smart materials that respond to a magnetic field by changing their rheological properties. This change in the yield shear stress of MR fluids is proportional to the magnetic field applied. Dampers with MR fluid as the working fluid have a damping response comparable to conventional synthetic oil dampers. The smart nature of MR fluid enables real time semi-active control of damping, which makes them particularly suitable for motorcycle steering. This project involves the study of MR fluid, its application as a shock absorbing device and the total design and manufacture of an MR fluid steering damper for a motorcycle. Motorcycle steering and the causes of erratic steering motions are investigated and a comparison between a manually adjustment damper and the proposed MR damper are discussed. The design principles are discussed and applied to optimize the design of the MR valve using finite element analysis. A full chapter is dedicated to a total bottom-up design of an MR fluid steering damper, while the chapter on design covers every aspect of the design, including the concept, the selection of material and components, design embodiment, the design of structural members, and technical production drawings. The testing stage enabled the working range and functionality of the completed damper to be established and documented, and served to investigate any shortcomings in the design and lay the groundwork for further improvement in areas such as the damping force range, optimization of the MR valve, size and weight reduction, and reliability. Finally, the project was concluded on an understanding that this design can be used as a foundation for future work with the aim of a commercial damper design that is effective (as an controllable damper in semi-active suspension systems), lightweight, aesthetically appealing, reliable, and at the same time be commercially viable by having a low production cost.


Abstract Quartz-rich sedimentary rocks are commonly assumed to be the eroded products of cratons or recycled orogens. However, active or eroded acidic volcanic regions can also be an important, but commonly overlooked, source of quartz. Cenozoic sandstones from East Java, Indonesia, illustrate this point. They are rich in quartz, and it has long been assumed that they are the product of erosion of a continental source. However, new work using a variety of provenance indicators shows that the sandstones contain a significant, previously overlooked, volcanic component. A number of factors have contributed to their character: quartz-rich source regions, eruptive volcanic processes, and tropical weathering. Ternary discriminant diagrams, such as QFL plots which use the ratios of quartz, feldspars, and lithic grains to interpret provenance from cratonic, volcanic, and recycled orogen hinterland, may mislead, particularly in tropical volcanic settings. The quartz from acidic volcanic sources is commonly overlooked because it is commonly assumed that quartz has a continental crustal source. Volcanic eruptive processes can lead to crystal enrichment in rapidly eroded ash and sediments. Intense chemical weathering can have considerable impact on the composition of sedimentary rocks by selectively removing labile minerals and lithic grains. The resulting deposits may be texturally immature but compositionally mature, and rich in resistant minerals such as quartz and zircon. In tropical settings the widely held view that quartz-rich sandstones are mature sediments representing multiple phases of recycling may in many cases be incorrect.


Bootstrap percolation is a type of cellular automaton which has been used to model various physical phenomena, such as ferromagnetism. For each natural number $r$, the $r$-neighbour bootstrap process is an update rule for vertices of a graph in one of two states: `infected' or `healthy'. In consecutive rounds, each healthy vertex with at least $r$ infected neighbours becomes itself infected. Percolation is said to occur if every vertex is eventually infected. Usually, the starting set of infected vertices is chosen at random, with all vertices initially infected independently with probability $p$. In that case, given a graph $G$ and infection threshold $r$, a quantity of interest is the critical probability, $p_c(G,r)$, at which percolation becomes likely to occur. In this paper, we look at infinite trees and, answering a problem posed by Balogh, Peres and Pete, we show that for any $b \geq r$ and for any $\epsilon > 0$ there exists a tree $T$ with branching number $\operatorname{br}(T) = b$ and critical probability $p_c(T,r) 0$ such that if $T$ is a Galton- Watson tree with branching number $\operatorname{br}(T) = b \geq r$ then $$p_c(T,r) > \frac{c_r}{b} e^{-\frac{b}{r-1}}.$$  We also show that this bound is sharp up to a factor of $O(b)$ by giving an explicit family of Galton--Watson trees with critical probability bounded from above by $C_r e^{-\frac{b}{r-1}}$ for some constant $C_r>0$.


Abstract Dinosaur tracks and trackways yield invaluable information as to the identity, size, and gait of the trackmaker and the conditions of the media (=substrate) it traversed. Correctly interpreting tracks requires consideration of their three-dimensional morphology. Laboratory-controlled simulations were conducted to investigate the subsurface track morphology formed from differently shaped feet, as the shape of the footprint deteriorates with depth. A circular, triangular, and a tridactyl dinosaur foot-shaped template, or indenter, were indented vertically into two types of sand, with four moisture contents—dry, 10%, 20%, and saturated. The morphology of all three indenters was preserved most accurately in the moist sand. Tracks in dry and saturated sand were distorted by a greater degree of media deformation. Digit imprints of tridactyl tracks were only clearly discernible in near-surface layers and were deformed by shear zones or inward movement of sediment in dry and saturated sand. The long digits of the template produced the greatest degree of outward displacement, and tracks became wider with depth and deepest in the heel region. This was most distinct in dry sand, where extensive shear zones in cross section demonstrated the outward and upward movement of sediment. All tracks in saturated sand were characterized by considerable downward displacement of sediment and features related to the upward pull of sediment as the templates were withdrawn. These diagnostic features allow vertebrate tracks to be differentiated from nonbiogenic, soft-sediment deformation. Fossil tracks studied from the Middle Jurassic succession of the Cleveland Basin, Yorkshire, demonstrate affinities to the experimental tracks formed in saturated sand.


The purpose of this paper was to assess the quality of groundwater in Behshahr (Iran) based on water quality index (WQI). Sixteen water samples from this coastal aquifer were collected and analyzed to study physico-chemical parameters such as pH, hardness, chloride (Cl), electrical conductivity (EC) and total dissolved solids (TDS). The results showed that the annual average of TDS value increased by 343 mg/l between 1999 and 2015 due to anthropogenic activities. According to WQI, it was concluded that the groundwater quality degraded over the last sixteen-year period so that the percentage of samples identified as "good water" decreased by 18.5% and on the other hand, alas, the percentage of "poor water" quality soared by nearly 12.5%. Correspondence of WQI distribution diagram with that of chloride-bicarbonate ratio attests to the significant contribution of saltwater intrusion to groundwater quality deterioration in this area.


Lower respiratory tract infection (LRTI) is one of the leading reasons for consulting in primary care. Today, a general practitioner faces the challenge of distinguishing between patients with a mild self-limiting disease to whom antibiotics would do more harm than good and those who would benefit from antibiotic treatment and should be monitored closely. Two categories are generally considered relevant with regard to the diagnosis and treatment of LRTI, i.e. bacterial LRTI and pneumonia. However, the current management of LRTIs is often inadequate and involves the unnecessary prescription of antibiotics, which drives antimicrobial resistance. To contribute to the rational management of LRTIs in adults, three main topics – for which currently evidence is lacking – are discussed in this thesis: the diagnostic workup and disease course of bacterial LRTI in primary care, the effects of antibiotics on uncomplicated pneumonia and the clinical relevance of resistance in bacterial LRTIs. We analysed data on 3,104 adult primary care patients with acute cough (≤ 28 days) in 12 European countries. All of the patients underwent clinical examination, measurement of C-reactive protein and procalcitonin in blood, and chest radiography. Bacterial infection was determined by conventional culture, polymerase chain reaction and serology, and positive results were defined by the presence of Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Bordetella pertussis or Legionella pneumophila. All patients recorded symptoms in a diary for four weeks. The main results were as follows. Firstly,signs and symptoms turned out to have limited clinical value for identifying a bacterial cause in primary care patients who are not severely ill and in those who present with clinically unsuspected pneumonia. C-reactive protein measurement added little to the clinical assessment and procalcitonin added no information to the diagnostic workup of these patients. Moreover, we found that Bordetella pertussis infection was not that common among adults presenting with acute cough (3%) and that symptoms had limited diagnostic value when it came to detecting pertussis in these patients. In general, the disease course of bacterial LRTI in outpatients without pneumonia was mild, uncomplicated and self-limiting; no different from that of non-bacterial LRTI, with the exception that B. pertussis infection showed a prolonged disease course, especially regarding cough. However, in subjects with radiologically proven but not clinically suspected pneumonia bacterial aetiology seems to matter since antibiotics (oral amoxicillin) improved symptom duration and symptom severity in this subset of patients. Finally, bacterial resistance was not related to disease course. Based on these results, we concluded that in outpatients with non-severe LRTI without risk factors, the detection of bacterial pathogens is not helpful when it comes to deciding which patients should receive antibiotic treatment. Moreover information about antimicrobial resistance does not contribute. Indications for the antibiotic treatment of LRTI are related to disease severity and the patient's vulnerability. For elderly patients, there is still insufficient evidence on bacterial infections in LRTI to withhold antibiotics with confidence. Future studies could help determine the diagnostic and prognostic value of point-of-care inflammatory tests.


Sudden changes in microfossils and lithologies in Holocene sediments of a former tidal inlet on the Hikurangi subduction margin provide evidence of 10 large earthquakes. Studies were focused in three former embayments where intertidal shelly sediment interfingers with freshwater and salt-marsh peat. Paleoelevation histories were reconstructed using the modern analogue technique with foraminiferal assemblages. Land elevation record analysis indicates 8−9 m of mid- to late Holocene tectonic subsidence occurred prior to 1.5 m of uplift during the A.D. 1931 Hawkes Bay earthquake. Chronologies of displacement events were constrained using 50 radiocarbon dates and three widespread air-fall tephras. We infer the following earthquakes: earthquake 1: 7.3−7.0 ka (−1.1 ± 0.3 m), earthquake 2: 5.6−5.1 ka (+0.4 ± 0.4 m), earthquake 3: 5.2−4.9 ka (−0.5 ± 0.5 m), earthquake 4: 4.4−3.8 ka (−0.6 ± 0.5 m), earthquake 5: 2.8−2.4 ka (−0.9 ± 0.5 m), earthquake 6: 1.73−1.70 ka (−1.0 ± 0.3 m), earthquake 7: 1.5−1.3 ka (−0.7 ± 0.5 m), earthquake 8: 1.04−0.89 ka (−1.2 ± 0.4 m), earthquake 9: 0.60−0.44 ka (−0.8 ± 0.6 m), and earthquake 10: A.D. 1931 (+1.5 ± 0.3 m). A further 1.6−2.6 m of subsidence could have occurred by gradual aseismic slip or in smaller earthquakes. The age ranges of four of the recognized earthquakes (earthquakes 1, 6, 8, and 9) overlap with other documented displacement events onshore along 250−600 km of the Hikurangi subduction margin, and with turbidites offshore 100−300 km to the north. These four are considered strong candidates for large subduction-interface earthquakes. The other five inferred earthquakes are less strongly correlated with along-margin displacement events and offshore turbidites. These could have been caused by upper-plate fault ruptures (like historic earthquake 10), but subduction-interface sources cannot be ruled out. This evidence for repeated coseismic vertical deformation suggests large coseismic slip on a part of the subduction interface beneath Hawkes Bay that is currently dominated by aseismic creep processes, such as transient slow-slip events. This clearly indicates multiple slip processes are possible in a single location on a subduction interface.


Disinterestedness, a comparatively recent concept in aesthetics, is commonly held to be one of the characteristics of an appropriate response to art, but can be understood in a number of senses. Three varieties are distinguished: a strong form which confines attention exclusively to the internal relations of the work of art; a moderate variety which links internal and external features of the work but solely within the cognitive domain; and a weak form which permits the appreciator to draw on a wide range of external referents but proscribes purely idiosyncratic responses. An illustration is given of the confusion which can arise from failure to respect these differences. Only the weak form of disinterestedness appears to be viable, and it is discussed in more detail.


Initiation and promotion in mouse skin carcinogenesis produce multiple benign tumors, squamous papillomas, but only a few squamous cell carcinomas. The spontaneous conversion from the benign to the malignant phenotype occurs over many months and in stages, but induced malignant conversion can be accomplished more rapidly by exposure of papilloma-bearing mice to mutagens or by transfection of papilloma cell lines with specific oncogenes. The analysis of genetic targets responsible for carcinogen-induced neoplastic progression would be facilitated by the development of in vitro models where the process is rapid, focal, and quantitative. To this end, primary newborn mouse keratinocytes were initiated in vitro by the introduction of the v-rasHa oncogene via a defective retrovirus. Recipient cells produce squamous papillomas and have a high proliferation rate in culture medium with 0.05 mM Ca2+, but fail to grow in medium with 0.5 mM Ca2+ which is permissive for growth of malignant keratinocytes. When v-rasHa-keratinocytes were exposed to mutagens in vitro, proliferative foci emerged after culture in 0.5 mM Ca2+ for 4 weeks. These foci stained intensely red with rhodamine stain, could be easily quantitated, and readily incorporated bromodeoxyuridine. Dose-response studies with several mutagens indicated that the number of foci increased with concentration to the point where excessive cytotoxicity developed. Mutagens varied in potency for producing foci in the following order: cis-diamminedichloroplatinum greater than or equal to benzo(a)pyrene diolexpoxide I greater than N-methyl-N'-nitro-N-nitrosoguanidine greater than or equal to 4-nitroquinoline-N-oxide greater than N-acetoxy-acetyl- aminofluorene. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate was inactive in the assay. A subset of cell lines derived from foci produced malignant tumors in vivo, while others were not tumorigenic. Analysis of DNA from cell lines and tumors revealed that most tumorigenic cell lines maintained the v-rasHa genome, whereas the viral sequences were deleted in nontumorigenic cell lines. Immunohistochemical analysis indicated that proliferative foci and quiescent v-rasHa keratinocytes expressed keratin 8, a marker of v-rasHa expression in cultured keratinocytes. Cells in foci, but not v-rasHa control cells, expressed keratin 13, a marker which is strongly associated with the malignant progression of skin tumors in vivo. This in vitro assay provides a quantitative model to study chemically induced focal neoplastic progression at the cellular level and to identify agents which may be selective for enhancing malignant conversion.


This paper focuses on the implications of the negotiations on industrial tariffs for longer term industrialization in developing countries. It begins with a brief overview of the NAMA framework that is followed by a review of the historical experience of todays advanced countries regarding the use of tariffs in the course of their industrialization, and compares and contrasts it with the actual situation prevailing in developing countries today and the proposals put forward. Then it discusses the sectoral pattern and evolution of tariffs that may be needed in the course of industrial development in comparison with the constraints that would result from the proposals made by developed countries, and advances a simple alternative formula that can help reconcile policy flexibility with multilateral discipline. This is followed by an evaluation of various estimates of benefits of tariff cuts to developing countries. There the paper turns to the question of reciprocity from a broad developmental perspective. It is concluded with a brief summary of the key points on how the negotiations could accommodate both the immediate needs and longer-term interests of developing countries.


Surfaces exposed to atmospheric cold temperature and humid environments are prone to ice accretion. Airplanes, electrical power transmission cables, and wind turbines are typical examples for which icing has to be considered. The measurement of the resulting ice shapes is a challenging process. While macroscopic characteristics of the ice geometry can be observed using photography and optical scanning techniques, microscopic measurements are difficult to conduct because grooved surface partially occludes the geometry of chasms. To overcome this optical inaccessibility, we propose a method to carry out detailed high‐resolution measurements of the accretion surface with micro‐computed tomography. This approach provides a unique visualization of the empty spaces in the feather region. The information obtained by this technique can improve the understanding of ice accretion physics and its computational modeling.


Entanglement distribution is key to the success of secure communication schemes based on quantum mechanics, and there is a strong need for an ultimate architecture able to overcome the limitations of recent proposals such as those based on entanglement percolation or quantum repeaters. In this work we provide a broad theoretical background for the development of such technologies. In particular, we investigate the question of whether entanglement distribution is more efficient if some amount of entanglement—or some amount of correlations in general—is available prior to the transmission stage of the protocol. We show that in the presence of noise the answer to this question strongly depends on the type of noise and on the way the entanglement is quantified. On the one hand, subadditive entanglement measures do not show an advantage of preshared correlations if entanglement is established via combinations of single-qubit Pauli channels. On the other hand, based on the superadditivity conjecture of distillable entanglement, we provide evidence that this phenomenon occurs for this measure. These results strongly suggest that sending one half of some pure entangled state down a noisy channel is the best strategy for any subadditive entanglement quantifier, thus paving the way to a unified approach for entanglement distribution which does not depend on the nature of noise. We also provide general bounds for entanglement distribution involving quantum discord and present a counterintuitive phenomenon of the advantage of arbitrarily little entangled states over maximally entangled ones, which may also occur for quantum channels relevant in experiments.


Each mobile network architecture able to meet the traffic requirements of future 5G services comes with its own set of benefits vs. requirements for the radio and the transport segments. This paper focuses on the energy performance of four mobile network architectures, each one with different splitting options for the baseband processing functions. The radio segment under exam is based on a new radio access technology referred to as 5G-NX, while the transport segment is based on wavelength division multiplexing (WDM). The energy consumption of each mobile network architecture is weighted against (i) the benefits for the radio segment as a function of the level of centralization of the baseband processing resources and (ii) the required transport capacity and consequently the power consumption levels needed to accommodate the backhaul, midhaul, and/or fronthaul traffic generated at each base station. Our results show that a fully centralized radio access network (C-RAN) with centralization of all the baseband functions is not a practical approach for 5G mobile networks, while a partially centralized C-RAN architecture in which the physical layer baseband processing is performed at the base station site represents a promising solution.


In 2017, CVC sold its target company, ista to a Chinese infrastructure investor after an investment period of 14 years. This transaction was the largest private equity exit from a German target company up to date. The authors investigate the transaction structuring and financing as well as CVC's impact on the financial performance and business development of the target company. The analysis shows that ista grew steady regarding revenue and EBITDA, employed more people, and performed comprehensible internationalization and business area extension decisions. However, the company also seems to be condemned to success. With each new transaction cycle, the level of liabilities and interest payment obligations increased. ista had to grow and increase efficiency continuously to meet the expectations of debt, mezzanine and equity capital providers. This article provides a holistic overview of the investment phase, enabling the reader to form an opinion about CVC's long-term involvement and to adopt the strategies used in this practical application.


Anyone can become a victim of abuse online, but it is apparent that certain behaviours are gender specific. For instance, women are more likely to have comments aimed at them threatening rape and other forms of sexual violence.

This is particularly the case for women in the public eye. For example, Gina Miller (the claimant in R (Miller) v The Secretary of State for Exiting the European Union [2016] EWHC 2768) has found herself at the centre of a campaign of online abuse. Abusive comments of sexual violence have been aimed at her. Comments like these are increasingly being used when it comes to the trolling of women online.

The law of the United Kingdom has started to respond to online abuse. Legislation has been adapted to cover online behaviour. Despite this, the law's response to serious online abuse directed at women has often seemed inadequate. For instance, Caroline Criado-Perez was subjected to extreme threats of sexual violence in 2014 via social media; several individuals were prosecuted for sending what was deemed "grossly offensive" comments. Yet, the conduct of Peter Nunn, in sending abusive messages to Ms Criado-Perez, and to the Labour MP Stella Creasey, might be thought to be more serious than the crime for which he was convicted – sending indecent, obscene or menacing messages – for which he received a six week custodial sentence. Rather, it might be thought that his actions amounted to harassment or stalking. If so, this suggests that the potential of the law to protect women from online abuse is not being used to the full.

This paper will propose that women are subjected to a unique form of abuse online, where threats of sexual violence are used to intimidate women. The paper will critically evaluate the law's response and make suggestions for how women may be better protected online.


This text explains the use of compressed air for energy storage and efficient pneumatic applications. Chapters cover the elementary physical and engineering principles related to compressed air, including compression and expansion characteristics, adiabatic, polytropic, and isothermal phenomena, and energy content within a given volume. The author also discusses the advantages and drawbacks of pneumatic technology and presents innovative ways to increase the energy efficiency of pneumatic actuators. A key highlight of the book is the introduction of a method to enhance efficiency by incorporating expansion work alongside constant pressure displacement. The author presents an analysis of various cylinder assemblies where energy efficiency is notably improved compared to conventional pneumatic actuators. The book serves as a primary reference for mechanical engineering students and as a handbook for engineers designing efficient pneumatic devices.

Key Features:

 Fundamental and advanced information about actuators and their pneumatic applications

 Focus on energy efficiency testing

 Systematic chapter order for effective learning progression, with a working example to support comprehension

 References for further reading

 Appendices providing additional insights and resources .


For GaN-based microcavity light emitters, such as vertical-cavity surface-emitting lasers (VCSELs) and resonant cavity light emitting diodes (RCLEDs) in the blue-green wavelength regime, achieving a high reflectivity wide bandwidth feedback mirror is truly challenging. The material properties of the III-nitride alloys are hardly compatible with the conventional distributed Bragg reflectors (DBRs) and the newly proposed high-contrast gratings (HCGs). Alternatively, at least for the top outcoupling mirror, dielectric materials offer more suitable material combinations not only for the DBRs but also for the HCGs. HCGs may offer advantages such as transverse mode and polarization control, a broader reflectivity spectrum than epitaxially grown DBRs, and the possibility to set the resonance wavelength after epitaxial growth by the grating parameters. In this work we have realized an air-suspended TiO2 grating with the help of a SiO2 sacrificial layer. The deposition processes for the dielectric layers were fine-tuned to minimize the residual stress. To achieve an accurate control of the grating duty cycle, a newly developed lift-off process, using hydrogen silesquioxan (HSQ) and sacrificial polymethyl-methacrylate (PMMA) resists, was applied to deposit the hard mask, providing sub-10 nm resolution. The finally obtained TiO2/air HCGs were characterized in a micro-reflectance measurement setup. A peak power reflectivity in excess of 95% was achieved for TM polarization at the center wavelength of 435 nm, with a reflectivity stopband width of about 80 nm (FWHM). The measured HCG reflectance spectra were compared to corresponding simulations obtained from rigorous coupled-wave analysis and very good agreement was found.


Visually appealing and vivid simulations of deformable solids represent an important aspect of physically based computer animation. For the temporal discretization, it is customary in computer animation to use first‐order accurate integration methods, such as Backward Euler, due to their simplicity and robustness. Although there is notable research on second‐order methods, their use is not widespread. Many of these well‐known methods have significant drawbacks such as severe numerical damping or scene‐dependent time step restrictions to ensure stability. In this paper, we discuss the most relevant requirements on such methods in computer animation and motivate the interest beyond first‐order accuracy. Keeping these requirements in mind, we investigate several promising methods from the families of diagonally implicit Runge‐Kutta (DIRK) and Rosenbrock methods which currently do not appear to have considerable popularity in this field. We show that the usage of such methods improves the visual quality of physical animations. In addition, we demonstrate that they allow distinctly more control over damping at lower computational cost than classical methods. As part of our theoretical contribution, we review aspects of simulations that are often considered more intricate with higher‐order methods, such as contact handling. To this end, we derive an implicit linearized contact model based on a predictor‐corrector approach that leads to consistent behavior with higher‐order integrators as predictors. Our contact model is well suited for the simulation of stiff, nonlinear materials with the integration methods presented in this paper and more common methods such as Backward Euler alike.


The hydrazine molecule is one of the most prolific far-infrared (FIR) laser sources. We present a complete list of its 268 observed FIR laser emissions excited by the ^12 C ^16 O2 laser. For each line we report all the available data on the CO2 pump line, the frequency measurement when available, the wavelength, the optimum operating pressure, the relative intensity, the polarization relative to the pump radiation, and the absorption offset from the CO2 line center. In spite of the large amount of experimental research performed on the hydrazine laser, only a few papers have reported the assignments of the levels involved in the laser systems. In fact, a systematic assignment of the IR hydrazine absorption spectrum is only at a preliminary stage owing to the complexity of the Hamiltonian of this molecule. We have investigated the possible assignments for all the reviewed FIR laser emissions by comparison with an N2H4 absorption spectrum. We can confirm the assignments for only 37 FIR laser lines belonging to 20 laser systems.


The paper presents undergraduate, graduate and postgraduate engineering programs of the Kuban State Technological University redesigned as "engineering triads" based on the CDIO Standards, as well as on the FCDI and FFCD models, developed as a result of the CDIO approach evolution. The methodology for developing the FCDI and FFCD models is based on the specifics of engineering activities of the MSc and PhD program graduates. In the continuation and extension of the CDIO model mostly focused on complex engineering activity of the BEng program graduates, the FCDI and FFCD models consider innovative engineering activity and research engineering activity as priorities for MSc and PhD program graduates, respectively. The CDIO Standards and newly developed FCDI and FFCD Standards were used for the design of undergraduate, graduate and postgraduate engineering programs ensuring the consistency and continuity of the 3 cycles of graduate training for complex, innovative and research engineering activities.


Context. Particle acceleration consequences from fluctuating electric fields superposed on an X-type magnetic field in collisionless solar plasma are studied. Such a system is chosen to mimic generic features of dynamic reconnection, or the reconnective dissipation of a linear disturbance. Aims. We explore numerically the consequences for charged particle distributions of fluctuating electric fields superposed on an X-type magnetic field. Methods. Particle distributions are obtained by numerically integrating individual charged particle orbits when a time varying electric field is superimposed on a static X-type neutral point. This configuration represents the effects of the passage of a generic MHD disturbance through such a system. Different frequencies of the electric field are used, representing different possible types of wave. The electric field reduces with increasing distance from the X-type neutral point as in linear dynamic magnetic reconnection. Results. The resulting particle distributions have properties that depend on the amplitude and frequency of the electric field. In many cases a bimodal form is found. Depending on the timescale for variation of the electric field, electrons and ions may be accelerated to different degrees and often have energy distributions of different forms. Protons are accelerated to γ-ray producing energies and electrons to and above hard X-ray producing energies in timescales of 1 s. The acceleration mechanism is possibly important for solar flares and solar noise storms but is also applicable to all collisionless plasmas.


Study Design: Retrospective cohort study. Objectives: Describe the rate of dural tears (DTs) in adult spinal deformity (ASD) surgery. Describe the risk factors for DT and the impact of this complication on clinical outcomes. Methods: Patients with ASD undergoing surgery between 2008 and 2014 were separated into DT and non-DT cohorts; demographics, operative details, radiographic, and clinical outcomes were compared. Statistical analysis included t tests or χ2 tests as appropriate and a multivariate analysis. Results: A total of 564 patients were identified. The rate of DT was 10.8% (n = 61). Patients with DT were older (61.1 vs 56.5 years, P = .005) and were more likely to have had prior spine surgery (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.2-3.3, P = .007). DT patients had higher pelvic tilt, lower lumbar lordosis, and greater pelvic-incidence lumbar lordosis mismatch than non-DT patients (P < .05). DT patients had longer operative times (424 vs 375 minutes, P = .008), were more likely to undergo interbody fusions (OR = 2.0, 95% CI = 1.1-3.6, P = .021), osteotomies (OR = 2.2, 95% CI = 1.1-4.0, P = .012), and decompressions (OR = 2.3, 95% CI = 1.3-4.3, P = .003). In our multivariate analysis, only decompressions were associated with an increased risk of DT (OR = 3.2, 95% CI = 1.4-7.6, P = .006). There were no significant differences in patient outcomes at 2 years. Conclusions: The rate of DT was 10.8% in an ASD cohort. This is similar to rates of DT reported following surgery for degenerative pathology. A history of prior spine surgery, decompression, interbody fusion, and osteotomies are all associated with an increased risk of DT, but decompression is the only independent risk factor for DT.


Programmers employ a multitude of languages to build systems. Some are general-purpose languages. Others are specific to individual domains. These assist programmers with at least three different tasks: domain modeling, system validation and representing the structure of their general purpose program. As a result, programming languages have become key factors in the software engineering process. They are, however, rarely codified into the process and treated systematically.
My dissertation develops a framework to treat programming languages as software engineering artifacts. In this framework, languages are identifiable, reusable entities that programmers can compose and link to produce larger languages; furthermore, languages themselves meet the properties of software components. Programmers can augment this lateral growth of languages with vertical growth, by producing languages that synthesize languages. Thus, software construction becomes a multi-phase process. In later phases, programmers use languages to build programs; in earlier phases, they employ languages to construct languages. This treatment of languages as artifacts addresses several open questions.


Optimal Operation of Batch Processes with Multiple Inputs and Constraints B. Srinivasan, S. Palanki, and D. Bonvin Optimal operation of batch processes has become increasingly important in recent years in the face of increased competition and also due to the trend towards building small, flexible plants n e a r the markets of consumption. Traditionally, batch processes have been operated with rudimentary control loops, which hinders the implementation of best operating policies in t h e face of uncertainty. This results in substantial losses in both quality and productivity. In this paper, a theoretical framework for on-line optimization o f batch processes with multiple inputs and constraints is developed. It is shown that the optimal solution consists o f several discontinuous input intervals; however, the inputs are a n a l y t i c in between discontinuities. Some combinations the i n p u t s push the system towards the constraints of the p r o b l e m , while other combinations exploit the intrinsic compromises present in the system. A procedure is developed t o separate these two combinations of inputs. This c h a r a c t e r i z a t i o n of the optimal solution can be utilized t o develop an efficient numerical procedure for computing the n o m i n a l optimal solution. Furthermore, the characterization also helps develop a measurement-based optimization scheme t h a t is highly efficient in the presence of uncertainties. The benefits of this scheme are illustrated via the simulation of a non-isothermal semi-batch reactor.


Abstract Conflict over water allocations and the need to adapt to climate change in Australia's Murray-Darling Basin has resulted in decision makers choosing engineering interventions to use water more efficiently for wetlands conservation. We review a range of policy and infrastructure adaptation measures implemented in the Basin by governments. The water supply and demand "environmental works and measures" adopted in the Coorong and Lower Lakes region, as well as along the River Murray, are assessed and compared with the opportunity costs for ecosystem-based adaptation. The results suggest that risks of disruption to ecological processes, desiccation of wetland areas and institutional failure with infrastructure-led adaptation measures are little appreciated. Further, ecosystem-based measures to maintain a more diverse range of ecological processes that would spread risk and conserve a more diverse range of biota have not been identified or adopted by governments. We conclude that as a primary adaptation to climate change environmental works and measures may represent overly-narrow or mal-adaptation that can reduce the resilience of wetland ecosystems.


Abstract Acute kidney injury (AKI) is a serious complication in the perioperative period and is consistently associated with increased morbidity and case fatality rate. This has been best studied in the cardiac surgery setting where it has been shown that up to 11.5–86.0% of patients exposed to cardiopulmonary bypass (CPB) will develop AKI, with 2.0–18.9% requiring renal replacement therapy (RRT). A prospective uncontrolled cohort study was conducted between 2011 and 2015, in which 93 children with various congenital heart lesions undergoing CPB were enrolled. Serum creatinine (SCr) level was determined by Jaffé's method (Cobas 6000 analyser, Roche). Postoperative fluid balance was estimated as the difference between fluid intake and output. Data for further processing were retrieved from anaesthesia and intensive care data management system flowsheets (IntelliView, Philips). AKI developed in 42 patients (45.6%) by meeting at least KDIGO (Kidney Disease: Improving Global Outcomes) stage I criteria (with SCr rise by more than 50% from the baseline). Thirty eight patients complied with the 1st stage of AKI, three with 2nd stage and two with 3rd stage, according the KDIGO classification and staging system. One patient having severity stage II and two patients having severity stage III of AKI required initiation of RRT using peritoneal dialysis. Two patients from the RRT group survived, one died. The median intraoperative urine output was 2.32 ml/kg/h, (range from 0.42–5.87 ml/kg/h). Median CPB time was 163 min., median aortic cross-clamping time was 97.9 min., cooling during CPB to 29.5 °C. The diagnosis of AKI using SCr was delayed by 48 hours after CPB. Median fluid balance (FB) on the first postoperative day in non-AKI patients was 13.58 ml/kg (IQR 0–37.02) vs 49.38 ml/kg (IQR 13.20–69.32) in AKI patients, p < 0.001. AKI is a frequent complication after open heart surgery in children with congenital heart lesions. From 93 patients included in the study, 42 (45.2%) met at least KDIGO Stage I criteria for AKI. FB is a sensitive marker of kidney dysfunction. Median FB in the 1st postoperative day significantly differed between AKI patients: 49.38 ml/kg (13.20–69.32) versus 13.58 ml/kg in patients with intact kidney function (AUC = 0.84; p = 0.001). Thus it can be used as a marker of AKI.


Summary: This study examined the role of cardiac β-adrenergic receptors and cardiac sympathetic and vagal nerves in the cardiotoxicity of 3-β-0-(4-amino-4.6-dideoxyβ-D-glucopyranosyl), digitoxigenin hydrochloride (ASI-254). Vagally intact dogs received a constant-rate intravenous infusion of either digoxin or ASI-254 in the presence and absence of practolol. Practolol pretreatment increased the dose of digoxin required to produce arrhythmias and markedly altered the pattern of toxicity. but did not alter the lethal dose. The terminal event was cardiac standstill rather than ventricular tibrillation as seen in digoxin control dogs. Practolol did not alter the toxic dose of ASI-254 and produced little change in the pattern of cardiotoxicity: both control and practolol-treated dogs died in cardiac standstill. Surgical sympathectomy did not alter the toxic dose of ASI-254. the character of toxicity. or the lethal dose compared to neurally intact dogs. However, vagal innervation may play a role in determining the type of cardiotoxicity produced by ASI-254. Vagotomy alone did not alter the toxic or the lethal dose of ASI-254: vagotomy did, however, alter the character of cardiotoxicity and terminal event. Our results indicate that ASI-254 infused intravenously does not interact with sites, central or peripheral, which activate the sympathetic nervous system. ASI-254 administered into the lateral ventricles produced signs of increased cardiac sympathetic nervous system activity. Tachycardia and arrhythmias produced by ICV ASI-254 appear to be neurally mediated since ganglionic blockade blunted these effects. These results suggest that ASI-254 is capable of interacting with central sympathetic nervous system structures, but in contrast to digoxin, access to these structures from intravenous administration is limited.


The photo effect of gap-gate type hydrogenated amorphous silicon thin-film transistor (a-Si:H TFT) has been studied to be employed as light sensors owing to its outstanding photosensitivity. It can be operated in on region to provide a higher current level as the sensing signal. However, the gap-gate a-Si:H TFT suffers from some problems such as the photo-current degradation resulted from illuminations and the disturbance of the backlight source when it is used as the sensor in display panel. A new method is proposed to overcome the above issues, which gives a feasible way for this kind of TFT to be used in TFT LCD panel. In this paper, the operation of the sensing method is fully described.


In-Situ Resource Utilization (ISRU) has always been suggested for ambitious space endeavours; and asteroids and comets in particular are generally agreed to be ideal sources, both in terms of its accessibility and wealth. The future utilisation of asteroid resources is here revisited by, firstly, providing an estimate of the total amount of accessible resources in the Earth's neighbourhood and, secondly, by envisaging a series of missions in order to retrieve resources from the most accessible objects known today. An analytical multi-impulsive transfer model is proposed in order to define the region in Keplerian space from which resources are accessible, and mapped subsequently into a near-Earth asteroid model, to understand the availability of material. This estimate shows a substantial amount of resources can be accessible at relatively low energy-cost; on the order of 1014 kg of material could potentially be accessed at an energy cost lower than that required to access the resources in the Moon. Most of this material is currently undiscovered, but the current surveyed population of near-Earth asteroid provides a good starting point for a search for future capture opportunities. The possibility of capturing, i.e., placing the asteroid into an orbit in permanent close proximity to Earth, a small-size NEO or a segment from a larger object would be of great scientific and technological interest in the coming decades. A systematic search of capture candidates among catalogued NEOs is presented, which targets the L2 region as the destination for the captured material. A robust methodology for systematic pruning of candidates and optimisation of capture trajectories through the stable manifold of planar Lyapunov orbits around L2 has been implemented and tested. Five possible candidates for affordable asteroid retrieval missions have been identified among known NEOs, and the transfers to the L2 region calculated. These transfers enable the capture of bodies with 2-8 meters diameter with modest propellant requirements. Because of the optimal departure dates, two of them have been identified as attractive targets for capture missions in the 2020-2030 time frame.


Abstract Heavy metals are present in low concentrations in reservoirs, but seasonal anthropogenic activities usually elevate the concentrations to a level that could become a health hazard. The dry season concentrations of cadmium, copper, iron, lead, mercury, nickel and zinc were assessed from three sites for 12 weeks in Oyun reservoir, Offa, Nigeria. Triplicate surface water samples were collected and analysed using atomic absorption spectrophotometry. The trend in the level of concentrations in the three sites is site C > B > A, while the trend in the levels of the concentrations in the reservoir is Ni > Fe > Zn > Pb > Cd > Cu > Hg. Ni, Cd, Pb and Hg were found to be higher than the WHO guidelines for the metals in drinking water. The high concentration of these metals was from anthropogenic watershed run-off of industrial effluents, domestic sewages and agricultural materials into the reservoir coming from several human activities such as washing, bathing, fish smoking, especially in site C. The health effects of high concentration of these metals in the reservoir were highlighted. Methods for the treatment and removal of the heavy metals from the reservoir during water purification such as active carbon adsorption, coagulation-flocculation, oxidation-filtration, softening treatment and reverse osmosis process were highlighted. Other methods that could be used include phytoremediation, rhizofiltration, bisorption and bioremediation. Watershed best management practices (BMP) remains the best solution to reduce the intrusion of the heavy metals from the watershed into the reservoir.


Using the space above desktop input devices adds a rich new input channel to desktop interaction. Input in this elevated layer has been previously used to modify the granularity of a 2D slider, navigate layers of a 3D body scan above a multitouch table and access vertically stacked menus. However, designing these interactions is challenging because the lack of haptic and direct visual feedback easily leads to input errors. For bare finger input, the user's fingers needs to reliably enter and stay inside the interactive layer, and engagement techniques such as midair clicking have to be disambiguated from leaving the layer. These issues have been addressed for interactions in which users operate other devices in midair, but there is little guidance for the design of bare finger input in this space. In this paper, we present the results of two user studies that inform the design of finger input above desktop devices. Our studies show that 2 cm is the minimum thickness of the above-surface volume that users can reliably remain within. We found that when accessing midair layers, users do not automatically move to the same height. To address this, we introduce a technique that dynamically determines the height at which the layer is placed, depending on the velocity profile of the user's initial finger movement into midair. Finally, we propose a technique that reliably distinguishes clicking from homing movements, based on the user's hand shape. We structure the presentation of our findings using Buxton's three-state input model, adding additional states and transitions for above-surface interactions. Author


The majority of the vertebrate genome sequence is not coding for proteins. In recent years, the evolution of this noncoding fraction of the genome has gained interest. These studies have been greatly facilitated by the availability of full genome sequences. The aim of this thesis is to study evolution of the noncoding vertebrate genome through bioinformatic analysis of large-scale genomic datasets.In a first analysis we addressed the use of conservation of sequence between highly diverged genomes to infer function. We provided evidence for a turnover of the patterns of negative selection. Hence, measures of constraint based on comparisons of diverged genomes might underestimate the functional proportion of the genome.In the following analyses we focused on length variation as found in small-scale insertion and deletion (indel) polymorphisms and microsatellites. For indels in chicken, replication slippage is a likely mutation mechanism, as a large proportion of the indels are parts of tandem-duplicates. Using a set of microsatellite polymorphisms in chicken, where we avoid ascertainment bias, we showed that polymorphism is positively correlated with microsatellite length and AT-content. Furthermore, interruptions in the microsatellite sequence decrease the levels of polymorphism.We also analysed the association between microsatellite polymorphism and recombination in the human genome. Here we found increased levels of microsatellite polymorphism in human recombination hotspots and also similar increases in the frequencies of single nucleotide polymorphisms (SNPs) and indels. This points towards natural selection shaping the levels of variation. Alternatively, recombination is mutagenic for all three kinds of polymorphisms. Finally, I present the program ILAPlot. It is a tool for visualisation, exploration and data extraction based on BLAST.Our combined results highlight the intricate connections between evolutionary phenomena. It also emphasises the importance of length variability in genome evolution, as well as the gradual difference between indels and microsatellites.


Background: The Progress in International Reading Literacy Study (PIRLS), and similar international assessments, have consistently shown South African intermediate phase learners' performance to be among the lowest worldwide. Of particular concern is the Curriculum and Assessment Policy Statement (CAPS) for Home Language in the Intermediate Phase and, specifically, the document's treatment of the assessment of reading comprehension. Objectives: In this study, the CAPS requirements for assessing reading comprehension were examined, with the aim of laying the groundwork for an improved policy framework. Method: The research design of the study involved evaluating the assessment of reading comprehension in the CAPS document, using a social realist approach to uncover its underlying structures and mechanisms. Results: The study found that a principled approach to the assessment of reading comprehension was lacking, which had a cumulative effect across the CAPS document, resulting in random, yet highly prescriptive, requirements. Conclusion: The study concluded that CAPS does not provide adequate guidance for improving reading comprehension and, moreover, that the prescribed programme of assessment is not supported by the research literature on reading comprehension. The study recommends that better, more evidence-informed and consultative policies and guidelines be introduced to support teachers in the assessment – and, ultimately, the improvement – of intermediate phase learners' reading comprehension.


The purpose of this study was to develop an instrument for appraising educational apps in mathematics education. The instrument allows mathematics related apps to be analysed based on the three aspects of the TPACK (technological pedagogical content knowledge) model, namely, content, technology and pedagogy. Four sub-scales were created with the first one examining the app role according to the type of task promoted: explorative, productivity and/or instructive. The second sub-scale appraises the degree of cognitive involvement when a learner interacts with the app. The third and fourth sub-scale deals with general pedagogical and operational affordance. The instrument framework was piloted and subsequently trialled with ten school teachers and mathematics educators to ensure content validity. It was further endorsed with examples of educational apps currently available in the context of the secondary curriculum.


This book analyses the evolution of the French model of capitalism in relation to the instability of socio-political compromises. In the 2010s, France was in a situation of systemic crisis, namely, the impossibility for political leadership to find a strategy of institutional change, or more generally a model of capitalism, that could gather sufficient social and political support. This book analyses the various attempts at reforming the French model since the 1980s, when the left tried briefly to orient the French political economy in a social-democratic/socialist direction before changing course and opting for a more orthodox macroeconomic and structural policy direction. The attempts of governments of the right to implement a radically neo-liberal structural policy also failed in the face of a significant social opposition. The enduring French systemic crisis is the expression of contradictions between the economic policies implemented by the successive left and right governments, and the existence of a dominant, social bloc, that is, a coalition of social groups that would politically support the dominant political strategy. Since 1978, both the right and the left have failed to find a solution to the contradictions between the policies they implemented and the expectations of their respective social bases, which are themselves inhabited by tensions and contradictions that evolve with the structural reforms that gradually transformed French capitalism.


ABSTRACT A well-established postgraduate researcher development program has existed at De Montfort University for many years. Library and Learning Services include modules on literature searching skills and critical appraisal. However, we recognized that researchers seemed to be disengaged with the services on offer. This concern informed a research project that considered the ways we could communicate better with researchers based on their needs. This paper explores the essential components of successful communication, such as context, timeliness and communication channels. An action-research approach was taken including focus groups and online surveys. The outcomes highlighted three significant crisis points, emphasizing the key times when researchers might need some intervention. The findings of this research identified the distinct needs of Postgraduate Researchers (PGRs) and how relevant and timely communication from the library can meet these needs. It also considers the impact of how communication has improved with researchers as a result of some of our interventions.


Social Media involve many shared items, such as photos, which may concern more than one user. The challenge is that users' individual privacy preferences for the same item may conflict, so an approach that just merges in some way the users' privacy preferences may provide unsatisfactory results. Previous proposals to deal with the problem were either time-consuming or did not consider compromises to solve these conflicts (e.g., by considering unilaterally-imposed approaches only). We propose a negotiation mechanism for users to agree on a compromise for the conflicts found. The second challenge we address in this paper relates to the exponential complexity of such a negotiation mechanism. To address this, we propose heuristics that reduce the complexity of the negotiation mechanism and show how substantial benefits can be derived from the use of these heuristics through extensive experimental evaluation that compares the performance of the negotiation mechanism with and without these heuristics. Moreover, we show that one such heuristic makes the negotiation mechanism produce results fast enough to be used in actual Social Media infrastructures with near-optimal results.


UNLABELLED
Magnetic Resonance Imaging is an essential diagnostic imaging technique. The complexity of interpreting MRI images is often compounded by the presence of a wide range of artifacts which are often challenging to identify and eliminate. Ontology permits the construction of a knowledge database with which users can interact given an appropriate interface. The goal of this work is to create an interactive tool for the ontology of MRI artifacts that will allow a radiologist to compare any given MRI artifact image with those contained in the ontology.

MATERIAL AND METHOD
Using Protégé 4, we have constructed the ontology with input from an expert in MRI artifacts and utilizing images exemplifying such artifacts. The graphical user interface has been built in Java and the linkage with the ontology made with Owl API.

RESULTS
Using the tool, users can compare imaging artifacts encountered in daily practice to those in the database. Once a user has identified the image the most similar to their own, they then have instantaneous access to the knowledge contained in the ontology about the artifact. Individual users can also submit images and have access to DICOM data.


Abstract. In the current work we present six hindcast WRF (Weather Research and Forecasting model) simulations for the EURO-CORDEX (European Coordinated Regional Climate Downscaling Experiment) domain with different configurations in microphysics, convection and radiation for the time period 1990–2008. All regional model simulations are forced by the ERA-Interim reanalysis and have the same spatial resolution (0.44°). These simulations are evaluated for surface temperature, precipitation, short- and longwave downward radiation at the surface and total cloud cover. The analysis of the WRF ensemble indicates systematic temperature and precipitation biases, which are linked to different physical mechanisms in the summer and winter seasons. Overestimation of total cloud cover and underestimation of downward shortwave radiation at the surface, mostly linked to the Grell–Devenyi convection and CAM (Community Atmosphere Model) radiation schemes, intensifies the negative bias in summer temperatures over northern Europe (max −2.5 °C). Conversely, a strong positive bias in downward shortwave radiation in summer over central (40–60%) and southern Europe mitigates the systematic cold bias over these regions, signifying a typical case of error compensation. Maximum winter cold biases are over northeastern Europe (−2.8 °C); this location suggests that land–atmosphere rather than cloud–radiation interactions are to blame. Precipitation is overestimated in summer by all model configurations, especially the higher quantiles which are associated with summertime deep cumulus convection. The largest precipitation biases are produced by the Kain–Fritsch convection scheme over the Mediterranean. Precipitation biases in winter are lower than those for summer in all model configurations (15–30%). The results of this study indicate the importance of evaluating not only the basic climatic parameters of interest for climate change applications (temperature and precipitation), but also other components of the energy and water cycle, in order to identify the sources of systematic biases, possible compensatory or masking mechanisms and suggest pathways for model improvement.


Modelling relationships between individuals is a classical question in social sciences and clustering individuals according to the observed patterns of interactions allows us to uncover a latent structure in the data. The stochastic block model is a popular approach for grouping individuals with respect to their social comportment. When several relationships of various types can occur jointly between individuals, the data are represented by multiplex networks where more than one edge can exist between the nodes. We extend stochastic block models to multiplex networks to obtain a clustering based on more than one kind of relationship. We propose to estimate the parameters—such as the marginal probabilities of assignment to groups (blocks) and the matrix of probabilities of connections between groups—through a variational expectation–maximization procedure. Consistency of the estimates is studied. The number of groups is chosen by using the integrated completed likelihood criterion, which is a penalized likelihood criterion. Multiplex stochastic block models arise in many situations but our applied example is motivated by a network of French cancer researchers. The two possible links (edges) between researchers are a direct connection or a connection through their laboratories. Our results show strong interactions between these two kinds of connection and the groups that are obtained are discussed to emphasize the common features of researchers grouped together.


We present a novel method for generating performance-driven, "hand-drawn" animation in real-time. Given an annotated set of hand-drawn faces for various expressions, our algorithm performs multi-way morphs to generate real-time animation that mimics the expressions of a user. Our system consists of a vision-based tracking component and a rendering component. Together, they form an animation system that can be used in a variety of applications, including teleconferencing, multi-user virtual worlds, compressed instructional videos, and consumer-oriented animation kits.This paper describes our algorithms in detail and illustrates the potential for this work in a teleconferencing application. Experience with our implementation suggests that there are several advantages to our hand-drawn characters over other alternatives: (1) flexibility of animation style; (2) increased compression of expression information; and (3) masking of errors made by the face tracking system that are distracting in photorealistic animations.


The results of three surveys are presented. The first survey was carried out in four large cities in Japan, and the findings were analyzed by factor analysis and cluster analysis. The second survey was carried out in Seoul, Korea and Tokyo, Japan to determine color preference in the two countries, focusing on the preference for white. The last survey compared color preference in Taipei and Tokyo, also with emphasis on the preference for white. In these successive studies on color preference in Japan and other Asian cities, the subjects were mainly asked to choose from a color chart the three colors they liked most and the three they liked least, and to state the reasons for their choices. The results of Survey 1 showed that color preference could be influenced by differences in age, sex, and geographical region. Also factor analysis and cluster analysis indicated some relation between color preference and the subjects' life styles. Dual scaling analysis of the results of Surveys 2 and 3 indicated that each Asian area has unique color preference tendencies and that there are statistically significant differences in the frequency of selection of colors of certain hues and tones. However, a high preference for white was common to all areas, along with preferences for some other colors. These results thus demonstrated a common strong preference for white in three neighboring Asian areas. The reasons given for the choices suggested that besides the factors of age and sex, associative images based on environmental and cultural aspects may be an important factor influencing color preference. © 1996 John Wiley & Sons, Inc.


Neoclassical growth theory is the dominant perspective for explaining economic growth. At its core are four implicit assumptions: 1) economic output can become decoupled from energy consumption; 2) economic distribution is unrelated to growth; 3) large institutions are not important for growth; and 4) labor force structure is not important for growth. Drawing on a wide range of data from the economic history of the United States, this book tests the validity of these assumptions and finds no empirical support. Instead, connections are found between the growth in energy consumption and such disparate phenomena as economic redistribution, corporate employment concentration, and changing labor force structure. The integration of energy into an economic growth model has the potential to offer insight into the future effects of fossil fuel depletion on key macroeconomic indicators, which is already manifested in stalled or diminished growth and escalating debt in many national economies. This book argues for an alternative, biophysical perspective to the study of growth, and presents a set of 'stylized facts' that such an approach must successfully explain. Aspects of biophysical analysis are combined with differential monetary analysis to arrive at a unique empirical methodology for investigating the elements and dependencies of the economic growth process.


The Lectures series on Campus Fm 103.7 is a transmission of public lectures, mostly but not exclusively, held at the University of Malta. These include lectures from the Works in Progress Seminar Series, Language Planning and Lights on Theatre Traffic.


This thesis is a contribution towards modelling extended defects in nuclear graphite. Programmatic tools have been created which allow the implementation of displacement fields for basal and prismatic dislocations in graphite using the anisotropic elastic equations. These dislocation displacements have also been used to accommodate other defects which may be represented using dislocation formalisms. Structures such as prismatic loops, dislocation dipoles, folds, surface ridges and turbostratic graphite have been created for the purpose of generating structures for modelling.

We have investigated the X-ray diffraction simulations resulting from the various structures containing defects and compared these directly with experimental results from samples of neutron irradiated graphite. We have shown that some of the line defects, such as the ruck and tuck fold, reproduce characteristic diffraction phenomena as seen in the literature, providing evidence for the existence of such defects in the relevant temperature range. Powder diffraction patterns also show diffraction peaks at small angles, in line with what is expected from long range disorder. With the use of molecular modelling software with interatomic potentials, we have shown that the spiro interstitial defect, which binds adjacent layers, may not be a sufficient barrier to prevent the glide of partial basal dislocations past one another, especially when the shear constant for graphite is reduced by the presence of disregistry or stacking faults. In addition, we have shown that basal dislocations with large Burgers vectors (superedge dislocations) give rise to delamination across the glide plane, whereas a 90° partial basal dislocation does not.

Finally we treat graphene as a continuum membrane, performing calculations of the formation energy due to free bending, and compared the results for the nanotube with Density Fucntional Theory (DFT) calculations with good agreement. As such, the same method has been applied to other, more exotic structures for layer deformations, such as a buckles, folds and a wave packet like structure representing a local ripple in a layer, thought to occur when dislocation motion is inhibited and in-plane strain is relieved as out-of-plane deformations.


Ivanova, T. and E. RaIchEva, 2015. Wool production and some wool properties from ewes from Synthetic population Bulgarian milk. Bulg. J. Agric. Sci., 21: 1076–1079 The aim of the present study was to determine the wool production and some wool properties from ewes from Synthetic population Bulgarian milk. The study was carried out with 25 ewes at age of 18 months and 25 ewes at 2.5 years reared in Institute of animal Science – Kostinbrod. The wool samples were taken from the sides of ewes for laboratory assessment of the fiber thickness. The thickness of the wool was measured for 100 fibres from each nonfat wool sample, in µm, by Lanimetre MP 3, PZo, Poland with enlargement 20. During the shearing of sheep, it was measured the individual quantity of grease wool with accuracy up to 100 g. Samples were taken from different parts of the body in amount of 300 g for determining the yield and preparation of the samples for measurement of the wool's whiteness. on base of the information for the individual wool production and yield it was calculated the quantity of clean fiber. The whiteness was assessed by photometric methods with Spekol 11 - Carl Zeiss Yena on the base of the measurements of red (X), green (Y) and blue (Z) components of the reflected light from the wool sample. The degree of whiteness, the degree of yellowing and index of yellowing were calculated. The obtained information was analyzed by methods of variation statistics, the effect of age was established by one-way anova. The significance of the influence of the studied factor was established by F-criterion of Fisher. The significance of the differ ences between means of the studied traits was evaluated by t-criterion of Student. The age of ewes had significant influence on the yield, clean fiber, thickness and whiteness of wool (P < 0.05) (P < 0.001). It was established negative, considerable high, significant correlation coefficients (r = - 0.51** ÷ - 0.65***) between the whiteness, degree of yellowing and index of yellow ing. The ewes with 48 quality of wool had the highest percentage (over 50%).


The effects of random environmental impacts on optimal exploitation of a fish population are investigated using both optimization and simulation, based on a discrete-time age-structured bioeconomic model. The optimization problem is solved as a non-linear programming problem in GAMS. First, a basic model structure and 6 different scenarios, dealing with two interactions between fish and environment, are introduced. Based on the simplest scenario, eight different parameter combinations are tested. Then the optimization problem is solved for each of the 6 scenarios for a period of 100 years in order to gain long term insights. The main finding is that higher volatility from the environment leads to higher net profits but together with a lower probability of actually hitting the mean values. Simulations are conducted with different fixed fishing mortality levels under 6 scenarios. It seems that a constant fishing mortality around 0.06 is optimal. In the end, a comparison is made between historical and optimal harvest for a period of 40 years. It turns out that in more than 70% of the time, the optimal exploitation offered by our optimization model dominates the historical one, leading to 43% higher net profit and 34% lower fishing cost on average.


Lingzhi (Ganoderma lucidum) is a woody mushroom highly regarded in traditional medicine and is widely consumed in the belief that it promotes health and longevity, lowers the risk of cancer and heart disease and boosts the immune system. However, objective scientific validation of the putative health benefits of Lingzhi in human subjects is lacking, and issues of possible toxicity must be addressed. The present double-blinded, placebo-controlled, cross-over intervention study investigated the effects of 4 weeks Lingzhi supplementation on a range of biomarkers for antioxidant status, CHD risk, DNA damage, immune status, and inflammation, as well as markers of liver and renal toxicity. It was performed as a follow-up to a study that showed that antioxidant power in plasma increased after Lingzhi ingestion, and that 10 d supplementation was associated with a trend towards an improved CHD biomarker profile. In the present study, fasting blood and urine from healthy, consenting adults (n 18; aged 22-52 years) was collected before and after 4 weeks supplementation with a commercially available encapsulated Lingzhi preparation (1.44 g Lingzhi/d; equivalent to 13.2 g fresh mushroom/d) or placebo. No significant change in any of the variables was found, although a slight trend toward lower lipids was again seen, and antioxidant capacity in urine increased. The results showed no evidence of liver, renal or DNA toxicity with Lingzhi intake, and this is reassuring. The present study of the effects in healthy, well-nourished subjects provides useful, new scientific data that will support controlled intervention trials using at-risk subjects in order to assess the therapeutic effect of Lingzhi in the promotion of healthy ageing.