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Demographic bottlenecks can severely reduce the genetic variation of a population or a species. Establishing whether low genetic variation is caused by a bottleneck or a constantly low effective number of individuals is important to understand a species' ecology and evolution, and it has implications for conservation management. Recent studies have evaluated the power of several statistical methods developed to identify bottlenecks. However, the false positive rate, i.e. the rate with which a bottleneck signal is misidentified in demographically stable populations, has received little attention. We analyse this type of error (type I) in forward computer simulations of stable populations having greater than Poisson variance in reproductive success (i.e., variance in family sizes). The assumption of Poisson variance underlies bottleneck tests, yet it is commonly violated in species with high fecundity.
With large variance in reproductive success (Vk ≥ 40, corresponding to a ratio between effective and census size smaller than 0.1), tests based on allele frequencies, allelic sizes, and DNA sequence polymorphisms (heterozygosity excess, M-ratio, and Tajima's D test) tend to show erroneous signals of a bottleneck. Similarly, strong evidence of population decline is erroneously detected when ancestral and current population sizes are estimated with the model based method MSVAR.
Our results suggest caution when interpreting the results of bottleneck tests in species showing high variance in reproductive success. Particularly in species with high fecundity, computer simulations are recommended to confirm the occurrence of a population bottleneck.
Keywords:Conservation; Heterozygosity excess; M-ratio; MSVAR; FPR; Sweepstakes reproduction; Type I error; Variance in reproductive success
Demographic fluctuations, including changes in population size and growth rate, are common events in natural populations. Severe population size declines (bottlenecks), however, may have detrimental consequences including increased inbreeding, decreased adaptive potential, increased disease susceptibility, lowered fecundity, and disruption in expression of quantitative traits [1-3]. As bottlenecks often affect long-term fitness and population viability, or change the balance of drift and selection, they are key events in a species' evolutionary history, and a principal concern for endangered species [4].
Bottlenecks may leave a population genetic signature, such as decreases in number of alleles and heterozygosity, and loss of rare alleles [5,6]. These signatures can be easily detected when temporal samples are available (e.g. museum specimens or fossil remains), so that contemporary genetic variation can be compared to historic levels. A bottleneck, however, may also leave specific signatures in current genetic variation, distinct from those in populations having a history of small and constant size. Indeed, several methods for detecting genetic bottlenecks in the absence of information about historical sizes and in absence of pre-bottleneck genetic samples exist [7-10]. Genetic methods for bottleneck detection are useful because: (1) historical (and current) census sizes are rarely known; (2) even when census size (Nc) is known, cryptic bottlenecks (change in effective size, Ne, without change in Nc) may occur; and (3) bottleneck outcomes are highly stochastic, meaning that genetic diversity following the bottleneck is somewhat unpredictable even when the demographic history is known [11,12]. It is therefore important to evaluate the statistical performance of these methods, especially as these tests are key components of many evolutionary, molecular ecology, and conservation genetic studies [13-16].
Previous investigations have demonstrated that the statistical power of these tests is highest when the bottleneck is severe or prolonged, and when many loci are used. In addition, factors such as the mutation model and the rate of post-bottleneck recovery may also play an important role [9,13,16-18]. Also, the methods do not always show similar power. For example, the heterozygosity excess test [9] has low power after rapid recovery [17] whereas the M-ratio test [10] remains effective, and the heterozygosity-excess test is weak unless the population is reduced to some tens of individuals [19]. Bottleneck signals are also weakened if the bottleneck occurred gradually, or if the population recovered to its pre-bottleneck population size [16]. Numerous empirical studies have failed to detect a genetic signal even when a moderate or strong demographic bottleneck is known to have occurred [4,11,20], showing empirically that the power of such tests can be limited.
A lack of statistical power in bottleneck tests may result in an underestimation of the extinction risk. On the other hand, identifying bottleneck signatures when they have not occurred may represent a complementary risk [18,21], yet this remains an often overlooked aspect of studies employing these methods. Controlling type I error rate (FPR, False Positive Rate) is important, particularly given that resources towards conservation tend to be limited [22]. Type I error could result in incorrect population protection status or unwarranted, ineffective, or even detrimental in-situ management interventions (e.g., translocations, augmentations). Therefore, an understanding of type I error in realistic situations is essential to properly use and interpret results from these methods.
Investigations of type I error of bottleneck detection methods are few, and have mostly concerned mutation models in microsatellite markers. For example, the probability of type I error can be substantial or extreme (from 40 to 100%) when the wrong mutation model is assumed or when multi-step mutations occur [21]. Also, assuming the wrong population-mutation parameter theta (θ = 4Neμ, where μ is the mutation rate) in the M-ratio test may result in either type I or type II errors, depending on whether the assumed θ is larger or smaller than the actual value [23]. Remarkably, in spite of frequent use of bottleneck tests, and the conservation decisions that are based on them, little is known about their type I error rates when assumptions of the biological model are violated. For example, the influence of mating patterns [13], age structure [14], and reproductive success [21,22] is rarely known.
Here we focus on type I error rates that may arise in bottleneck tests when the variance of reproductive success (hereafter Vk) is larger than the Poisson variance assumed by simple models underlying the bottleneck detection methods. Larger than Poisson Vk could cause strong intergenerational genetic drift, because it introduces additional stochasticity (e.g. unaccounted loss of alleles) when only few parents contribute to the next generation [24]. When extreme, this process has been referred to as Sweepstakes Reproductive Success (SRS), in which many individuals "lose" and produce zero or very few offspring, while one or a few individuals "win" and produce many offspring [25,26]. Such extreme reproductive variance can be caused by complete or near-complete dominance of one pair, or positively correlated sibling survival, in which all offspring of a particular brood survive or perish [24,25]. Variance can also be extreme when only one male contributes offspring [12]. Large Vk reduces the Ne/Nc ratio, which may explain Ne/Nc in the order of 10-2 - 10-3 observed in many amphibians, fish, marine invertebrates, and plants. Even more extreme Ne/Nc ratios, as low as 10-3 to 10-5, have been reported for lobster, cod, red drum, and oyster [27]. "Chaotic" genetic differences at small geographic scale and at different time intervals often observed in marine organisms has been explained as relating to high Vk[26].
Theoretically, the relationship between Vk and the Ne/Nc ratio has been derived under different models [25,28,29], and hence, an increase in Vk can be converted into a predictable reduction in Ne. However, the effect of Vk on the shape of a coalescent tree and on the relationship between different genetic diversity measures (which are the basis for bottleneck testing) have not been investigated [27]. In particular, it remains to be elucidated whether analysis of genetic data from species with large Vk will show signature of small but constant size, or whether large Vk results in a false signal of a genetic bottleneck. Here we investigate this question for different combinations of Ne and Vk values, using simulated data to estimate type I errors in two tests commonly applied to microsatellite data to detect bottlenecks, the M-ratio [10] and the heterozygosity test [9], and when ancestral and current population size are estimated to infer bottlenecks with the MSVAR method [7]. We also consider the effects of Vk on the Tajima's D test [30], which is used to detect selection as well as deviations from demographic stability in DNA sequence polymorphisms. All these tests assume stable populations with Poisson-distributed family sizes, i.e. Vk = 2.
Genetic variation data were generated by simulating demographically stable populations with different effective size (Ne) and different variance in reproductive success (Vk). For each combination of parameters, 100 replicates were generated. Each data set, consisting of 15 microsatellite markers, was analysed with the M-ratio and the heterozygosity excess tests, and with the MSVAR method. The fraction of replicates significantly supporting a bottleneck can be considered as an estimate of the FPR (false positive rate), i.e., the type I error rate. Then a smaller set of simulations was used to analyse two additional markers (microsatellite loci with constrained allelic range and DNA sequence polymorphisms).
Generating the primary set of synthetic data
The software simuPOP [31] was used to generate the virtual data. simuPOP is an individual-based, forward-in-time simulator that uses the flexible scripting language Python to allow operators that control sex ratio, number of offspring produced etc., and is one of few simulators to allow such options [32]. Random mating of individuals and family sizes with different distributions (i.e., Vk) can be simulated straightforwardly. We analysed 16 combinations of Ne (50, 500, 2500 and 5000) and Vk (2, 40, 400, and 2000). Population size was assumed to be constant, and the mean number of offspring per mating was always equal to two. In order to obtain the same Ne for different Vk values, the census sizes required in the simulations were computed using the approximate relationship Ne/Nc = 4/(Vk +2) [25,33]. When Vk =2, family sizes were Poisson distributed (as assumed by most population genetics models) and the ratio Ne/Nc =1. For larger Vk, we used a modified gamma distribution of family sizes with decimal values rounded down to the nearest integer (resulting in a discrete distribution approximating a negative binomial, Figure 1). This choice allowed us to maintain the average number of offspring per mating equal to two while producing a long right tail in the distribution. The Vk values of 40, 400, and 2000 correspond approximately to Ne/Nc equal to 0.1, and 0.01, 0.002, respectively.
Figure 1. An example of the distribution of offspring per parent in the simulations. The three panels correspond to the distributions obtained in simulations with Vk =2 (top), Vk = 40 (middle), and Vk = 400 (bottom).
Fifteen neutral, independent microsatellites evolving under a strict stepwise mutation model with mutation rate μ=5×10-4 were considered. Mutation-drift equilibrium was obtained by running simulations for Ne generations, starting from individuals with a Dirichelet distribution of allele frequencies. After verifying that the population had reached a stable equilibrium confirmed by the convergence of the number of alleles (K), the expected heterozygosity (He), and the inbreeding coefficient Fis, 50 individuals were randomly sampled and analysed using ARLEQUIN v3.5 [34] for the summary statistics noted above, the M-ratio and the Tajima's D tests, and using BOTTLENECK v.1.2.1 [9] for the heterozygote excess test, and MSVAR v. 1.3 for the estimation of current vs. ancestral population sizes [7].
Additional simulations
Some specific situations were investigated using additional simulations. First we simulated microsatellite markers where the maximum number of alleles is limited to five, to represent expressed (EST) microsatellites which tend to have a limited allelic range; a restricted allele range may affect the M-ratio. Second we simulated DNA sequences of 500 base pairs evolving under an infinite site mutation model with mutation rate μ=10-7 per site per generation. These simulations were conducted to understand whether the spurious signal of a bottleneck produced by Vk > 2 is specific to microsatellites markers, or whether a similar signal would be found when Single Nucleotide Polymorphisms (SNPs) are considered.
Bottleneck tests
Microsatellite data was analysed first with the commonly used M-ratio test [10] and heterozygosity excess test [9]. The M-ratio test is based on the frequency distribution of allelic sizes, which is expected to have gaps after a bottleneck due to stochastic loss of rare alleles. The M-ratio is computed in each data set as simply the ratio of the number of occupied allelic states divided by the number of possible allelic states (e.g. the range). Evidence of deviation from the null hypothesis of demographic stability can be concluded in one of two ways: if the observed value is lower than a simple threshold criteria (M-ratio < 0.68 [10], which is widely used as a "rule of thumb" in conservation genetics) or if the observed value is lower than a critical value, determined by reconstructing the null distribution of M using 1000 coalescent simulations. The coalescent simulations used to generate this null distribution assume by definition Vk = 2. Also we set the parameters Ne and μ to the values used in producing the corresponding data sets. Throughout the paper, we will call M-ratioft test the approach based on the fixed threshold, and M-ratiosim test the approach that uses simulations to compute the critical value. The heterozygosity excess test is based on a relationship between heterozygosity and number of alleles, which is predicted to deviate from theoretical expectations after a bottleneck because the former decreases more slowly than the latter. Statistical significance for this test is computed using the Wilcoxon's signed rank test to compare the expected heterozygosity calculated from the data (He) to an expected heterozygosity based on the number of alleles present (Ha) [9], where Ha is computed by simulation using the program BOTTLENECK [35].
We performed also a more sophisticated analysis which is frequently used to detect changes in population size [7]. This analysis uses a full-likelihood model-based approach called MSVAR to infer current and past population sizes as well as other parameters. The method can be used to infer a bottleneck if the ratio of past to current population size is significantly greater than unity. From each MSVAR analysis, the posterior distribution of the ratio between ancient and current population sizes was estimated, and the data set was considered to support the bottleneck hypothesis if less than 5% of this distribution was smaller than 1. For each data set (1600 in total), we recorded the MCMC (Monte Carlo Markov Chain) output 40,000 times every 10,000 steps. The first 10% of steps were discarded as burn in. Means and variances for priors and hyperpriors are reported in the legend of Table 1. In some cases this approach has been shown to be more powerful than the simpler statistics explained above [11], but it also relies on more assumptions (a particular demographic model).
Table 1. Simulation results for a population with constant size and standard microsatellite mutations
DNA sequences were analysed with the Tajima's D test [30], which is based on the comparison between the average pairwise difference (π) and the number of polymorphic sites (S). If equilibrium is not reached after a demographic event, negative D values are expected under population expansion and positive D values are expected under population decline [30]. Tajima's D is commonly used also to detect deviation from neutrality, i.e. the impact of selection on DNA sequences. Statistical significance is computed by simulations, as implemented in Arlequin [34].
Primary set of simulations
As expected, the average level of genetic variation (expected heterozygosity, He, and number of alleles, K) increased with increasing Ne. The average He observed for Vk=2 is similar to theoretical predictions [36] which are 0.09, 0.42 and 0.78 for Ne values 50, 500, and 5000. The number of alleles does not have a simple expectation under the single-step mutation model, but the observed values are compatible with other results [37]. When Vk increases, we observe a trend of decreased genetic variation within each set of simulations with the same Ne, and this effect is stronger for K than for He. For Vk > 2, populations also appear to deviate from the Hardy-Weinberg equilibrium, with larger observed than expected heterozygosity and consequent negative values of the estimated inbreeding coefficient.
The false positives rate (FPR) clearly increases with Vk. With Vk=2, FPR for the M-ratioft test is either 1% or 0% (indicating probably that this criteria is too conservative) and it varies between 2% and 9% using the M-ratiosim test. For the heterozygosity excess test, the FPR with Vk=2 is around the nominal 5% or less, and varies between 0% and 14% for the MSVAR analysis (this analysis being more permissive with large values of genetic variation). Very different results are obtained for Vk > 2 (Table 1 and Figure 2), especially for Ne equal or larger than 500 (i.e., when level of polymorphisms is not too low). All or almost all replicates analysed with the M-ratiosim test or with the MSVAR analysis support a bottleneck when Vk ≥ 400 and Ne ≥ 500. When the more conservative M-ratioft test or the heterozygosity excess test are applied, the FPR decreases, but never below 21%. For Vk=40, i.e., when the ratio between effective and census size is equal to 0.1, FPR can reach values as high as 93% or 97% in the M-ratiosim test and the MSVAR analysis, respectively. Furthermore, we observe a general trend of FPR to increase with Ne (Table 1 and Figure 3). This pattern, likely related to the overall level of genetic variation available for the tests and to the ratio between the sample size and Ne (which is decreasing when Ne increases), deserves further investigation. In summary, with high variation in reproductive variance, the M-ratio and heterozygosity excess tests produce many false positives, and the probability to detect a spurious bottleneck signal tends to increase with increasing effective population size. MSVAR results are in general similar to those obtained with the M-ratiosim test.
Figure 2. The false positive rate (FPR) as a function of the ratio Ne/ Ncunder different statistical approaches. FPR refers to simulations with Ne = 2500.
Figure 3. The false positive rate (FPR) as a function of the effective population size Neunder different statistical approaches. FPR refers to simulation with Vk =40.
Additional simulations
Constrained allelic size – Simulations with Ne=500 and Vk=2 or 400. When microsatellite alleles exhibit strong size restrictions (only 5 alleles with adjacent number of repeats are possible), the fraction of false positives for the heterozygote excess test increased from 1% to 47% when Vk was increased from 2 to 400. This increase in FPR is similar to that observed in the simulations with size-unconstrained loci. However, none of the replicates with high Vk with constrained loci produced small and significant M-ratios. The likely explanation is that a reduced allelic range prevents the opening of gaps in the allelic size distribution. In other words, the M-ratio test does not tend to suggest a false signal of a bottleneck when analyzing size-constrained EST microsatellites.
DNA sequence polymorphism - Simulations with Ne= 500 and Vk= 400. The Tajima's D distribution, centered around 0 for Vk = 2 in case of constant population size and absence of natural selection, is shifted towards positive values, with a mean of 1.24. The FPR, i.e. the fraction of values significantly larger than 0, is 37%. Thus, the Tajima's D statistics is similarly affected by an increased variance in reproductive success, and would frequently support a population decline or balancing selection when Vk >> 2.
In many organisms with high fecundity, the contribution of each individual or pair to the next generation can be highly skewed, with few "winners" (i.e. those who produce many offspring) and many "losers" who do not contribute to the gene pool of the next generation. Under this scenario of Sweepstakes Reproductive Success (SRS) [38], the variance in reproductive success (Vk) is larger than assumed by the Wright-Fisher model. Population genetics theory predicts that the ratio of Ne (the effective population size) over Nc (the census population size) rapidly decreases from one as Vk increases. The SRS model is thus considered a likely explanation for the empirical observation that many marine organisms have much lower genetic variation (and therefore Ne) than predicted by their very large Nc[39].
While the negative relationship between genetic variation and Vk is well known, the effect of Vk on the gene genealogy shape reconstructed from a sample of DNA fragments is yet unclear. It is possible that large Vk values may introduce distortions in this genealogy, in turn distorting the relationships between genetic variation measures. This is relevant as many statistical analyses for identifying deviations from neutrality and demographic stability assume Vk=2 and are based on the relationships between genetic variation measures.
We addressed this question by comparing simulated datasets of single populations with different Vk values. Specifically we estimated the impact of large Vk on the results from four statistical tests commonly used to detect population size variation: the M-ratio test, the heterozygote excess test, a test derived from a Bayesian estimate of ancient and current population sizes, and the Tajima's D test. Conceptually, when these tests are applied to neutral markers, the null hypothesis includes demographic stability, no migration and Vk=2. Rejection of this hypothesis may be interpreted as population decline, but may be also due to large Vk in isolated, demographically stable populations. This is relevant in conservation genetics as violation of the assumption of low Vk made by these tests can produce incorrect inference, and may suggest incorrect management interventions.
Our simulations show that high Vk can strongly increase the rate of false positives (FPR = type I error = incorrect inference of population decline) for all the tests. Further, the larger Vk, the larger the rate. FPR is also dependent, to some extent, on Ne (and thus the level of genetic variation), but this relationship appears test-specific. Based on our results, it appears that the MSVAR method is most prone to errors, followed by the M-ratio with the critical threshold computed by simulations (M-ratiosim). The heterozygote excess and M-ratio with the traditional threshold are less prone to false positives when Vk is large and may be preferred for use, if the goal is to reduce type I errors when evidence of large Vk is available. The results we obtained show also that high Vk could cause wrong conclusions when the aim of the analysis is to identify signatures of selection. In particular, the negative Fis values and positive Tajima's D produced in our simulations of neutral markers with large Vk could be misinterpreted as signals of balancing selection.
When Vk is large, a large fraction of siblings is observed every generation. In coalescent terms, several lineages merge in one generation going back in time, producing many short external branches in the gene genealogy and therefore a deviation from the standard Kingman coalescent [27,28]. Allele sharing among individuals will be high and alleles present in one (singletons) or few (rare alleles) individuals will be very low. Considering that bottleneck tests assume the standard Kingman coalescent, or the Wright-Fisher model it approximates, we propose that the excess of short external branches and corresponding deficit of rare alleles could explain the large FPR. In fact, this situation is expected to result in (a) higher heterozygosity than expected based on number of alleles (and thus positive heterozygote excess test and an overall signal of population decline detected by MSVAR), (b) gaps in the microsatellite allele size distribution (and significant M-ratio test) and (c) loss of segregating sites but not substantial reduction in the average pairwise difference (and positive Tajima's D). We also note that the fraction of siblings and the rate of multiple coalescent events rapidly decreases going back in time (since few lineages survive, additional simulation results not shown); thus, one generation of large Vk can generate large FPR. We also note that the constant population size scenario we simulated appears similar, in its effects, to a scenario of a recent and extreme bottleneck in an additional way, with a small recent effective size producing negative Fis values compatible with a population of few individuals [40].
Due to different parameterization of the model of the biological system, our results are not directly comparable with the genetic prediction of recent theoretical models of populations with skewed offspring number and overlapping generations [27,41-45]. These models, which allow for simultaneous multiple coalescent events e.g. [42], suggest that in a "many losers, few winners" situation (high Vk), the chances to obtain star-like genealogies and excess of rare alleles, i.e., signatures of population expansion, is increased compared to the Vk =2 case; this is opposite the result obtained in our study. A possible explanation for the discrepancy is the fact that our simulations considered non-overlapping generations, and overlap in generations may provide a buffer against the effects of drift and consequent high allele sharing caused by high Vk. Additional efforts should be dedicated to make the results produced by theoretical models with multiple merger and those obtained in our study comparable.
Practical applications
Certainly, our results suggest that the genetic signature of a bottlenecks should be interpreted with caution when found in species known to have moderate to large variance in offspring number (as for example in the killer whale, [46]), or where large variance in offspring number is suspected (as for example in many marine species, [26]). In the killer whale example, large variance in offspring number was estimated based on parentage analysis and a demographic bottleneck was inferred from genetic data using the statistical approaches we examined in our study; the authors report that it is unclear whether a bottleneck actually occurred. This work, and our simulations, emphasize that robust, widely applicable, powerful alternative methods of detect a bottleneck are still needed.
An alternative to using the standard bottleneck tests for species with large Vk is using computer simulations [16,32]. Summary statistics from observed data can be compared to a distribution of expected values from simulated data created with forward simulations, in simuPOP, spip [47], Nemo [48], cdpop [49] or other software [32]. The distribution of reproductive success and other aspects of the species' reproductive system can be taken into account in the simulations, allowing the investigator to observe Vk effects on the population genetic signal and, more specifically, generating species-specific null distributions of the bottleneck tests (as the M-ratio statistic) more appropriate for Vk larger than 2. Simulating stable populations, and populations with different intensities of demographic decline, can allow statistical comparison to the observed data (with or without formal approaches like Approximate Bayesian Computation, [50]).
The high FPR we uncover may not present a problem for studies that detect a bottleneck by comparing temporal samples, as comparing a modern sample to museum or ancient samples [23], or comparing to a non-bottlenecked but otherwise similar population [17]. Type I error due to Vk should not be expected to arise because large Vk should affect diversity in both samples. However, this assumes that Vk is constant through time. If census size decreases, Vk may change through time [12], with unknown effects on our ability to detect a bottleneck by comparing ancient and modern genetic variation levels. The increasing use of ancient DNA and prevalence of studies that infer bottlenecks from temporal samples [51], suggests that it will be important to evaluate the effects of high Vk on temporal comparisons.
Finally, considering that our simulations assumed non-overlapping generations, and also considering that effect of drift decreases proportionally to the number of generations that overlap [25,52], we emphasize that our findings should be considered applicable particularly to organisms with non-overlapping generations or short generation times (e.g., annual plants, insects, some fish).
We have shown that high reproductive variance increases the rate of false positives in four widely used bottleneck detection tests. Failing to detect a genuine bottleneck is widely acknowledged as harmful in conservation. However, given the limited resources and myriad of necessary conservation actions that are required to protect vulnerable species and populations [53], accurate tests are required to identify population bottlenecks with low false positive rates so that resources can be applied where they are needed most. The current study highlights the high type I error rate of bottleneck tests and emphasizes the need for more sophisticated analysis to evaluate conservation status of species with high reproductive variance.
Competing interests
The authors declare no competing interests.
Authors' contributions
MM, CVO, and GB conceived and designed the study, MM and AB performed simulations and data analysis, SH drafted the manuscript and GB and OEG worked on it. All authors examined data, discussed results, contributed to manuscript revision and approved the final draft.
Authors' information
All authors are interested in the demographic and genetic dynamics of small or isolated populations, and in the development and testing of statistical approaches to infer population processes from genetic variation data.
Funding was provided by the University of Ferrara, Italy. CvO was funded by the Earth and Life Systems Alliance (ELSA), Norwich Research Park, UK. We thank Lorenzo Zane and Richard Nichols for helpful discussions. GB thanks Camila Mazzoni and Simone Sommer for their hospitality at the at the Berlin Center for Genomics in Biodiversity Research during the revision of this paper.
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Piry S, Luikart G, Cornuet J-M: Computer note. BOTTLENECK: a computer program for detecting recent reductions in the effective size using allele frequency data.
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Hedgecock D: Does variance in reproductive success limit effective population size of marine organisms? In Genetics and evolution of aquatic organisms. Edited by Beaumont A. London: Chapman and Hall; 1994:122-134.
Gaggiotti OE, Vetter R: Effect of life history strategy, environmental variability, and overexploitation on the genetic diversity of pelagic fish populations.
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Philos Trans R Soc B: Biol Sci 2005, 360:1395-1409. Publisher Full Text
Eldon B: Structured coalescent processes from a modified moran model with large offspring numbers.
Theor Popul Biol 2009, 76:92-104. PubMed Abstract | Publisher Full Text
Sargsyan O, Wakeley J: A coalescent process with simultaneous multiple mergers for approximating the gene genealogies of many marine organisms.
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Eldon B: Estimation of parameters in large offspring number models and ratios of coalescence times.
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Ford MJ, Hanson MB, Hempelmann J a, Ayres KL, Emmons CK, Schorr GS, Baird RW, Balcomb KC, Wasser SK, Parsons KM, Balcomb-Bartok K: Inferred paternity and male reproductive success in a killer whale (orcinus orca) population.
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Pertoldi C, Bijlsma R, Loeschcke V: Conservation genetics in a globally changing environment: present problems, paradoxes and future challenges.
Biodivers Conserv 2007, 16:4147-4163. Publisher Full Text


text: Jacob Volkov | IBDB: The official source for Broadway Information IBDB: The official source for Broadway Information Official Broadway League sites: - sites - broadway.org broadwayleague.com broadwayfanclub.com kidsnightonbroadway.com stagespecs.org tonyawards.com Quick Search For: In This Category: All Show People/Org. Theatre Season Jacob Volkov Writer Male Productions ProductionsDate of ProductionsThe Suicide[Play, Comedy, Original] Translated by Jacob Volkov Oct 09, 1980 - Nov 30, 1980 Find out where Jacob Volkov and are credited together © 2001-2015, The Broadway League, All Rights Reserved. (Copyright and Disclaimer)

subset: commoncrawl


text:
Pregnancy: After Loss Community
Congratulations on your pregnancy! Join our community for those who are ... more
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My Communities
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Soooo..... I have to get a BP cuff for home. It was pretty normal today but I feel fine today. I explained to her how I feel when I think it is high and she thinks it is definitely my BP. I told her about how I have gone to the store and used the store machines and it was a bit elevated but she said that the store machines are horrible and it could have actually been higher than the store machines were reading so she wants me to have a good quality BP cuff of my own that I can take in and compare its #'s with her #'s to check it's accuracy. Then I have to start checking it daily. I am happy to do this, now I won't worry so much about it if I actually know what my BP is rather than just feeling like it is high and wondering if I should call the doctor. Once I have the BP cuff I will know if I need to call the doctor or not. Takes the guess-work out of it.
She felt my hands and feet and she thinks I am going to have a problem with swelling . There was no protein in my urine, but she thinks that I need to start watching my salt intake and to only eat fresh veggies (no canned), add no extra salt to food, eat no processed meats, etc... I am eating super healthy and I weigh myself every night before bed. Within 1 day, I am serious 1 day (last Friday), I gained 7lbs and it has stuck with me. My weight didn't go back down, the extra weight and swelling is still on me. She said that is not weight gain, that is water weight. It is making it harder for me to get around, that is for sure! I gained 12 lbs total since my last appt 5 weeks ago! After she felt my feet she thinks that about 85% of that is water weight. She is concerned about such a large amount of swelling in such a short period of time. I just figured it was normal, since I was preg with Gwen in the winter, I figured I would swell more in the summer. She agreed with that, but she said not this rapidly within 1 month.
She said that I have to stop doing my mile+ walks outside, I have to start walking on our treadmill. Hello BORING walks. She thinks that when I am getting warm (not even really hot) on my walks it is making me swell and probably not helping my BP. I really enjoy going on long walks with Gwen but the past few days I feel like my body is telling me to be horizontal. I asked her about that too, because in the pregnancy book they gave me it says that walking can help BP and swelling and asked if she thought that I should push through on those days I am feeling bloated and walk anyway or listen to my body telling me to slow down. She said to listen to my body.
I start going every 2 weeks now. I wish we lived closer to the doctors office, oh well though. Yay for a great appointment for Reese! Oye, on the news about me and the swelling.
View Thread
If it eases your mind, my niece was born at 36 weeks and she is a very smart, gorgeous, and talkative 3 year old now.View Thread
TRIGGERS: I asked her about my placenta and she said that as of right now, (based on what she has seen on the ultrasound) she would have me try and labor and see how much I bleed out. If I have excessive bleeding then she will rush me in for an emergency c-section. Does this sound like normal procedure for partial placenta previa? I had concerns about "calls" that my doctor made during my labor with Gwen so this concerns me. I do not want to end up with a hysterectomy if I could have just had a planned c-section, KWIM? Sure, I would prefer vaginal over c-section, but honestly vaginal childbirth is not THAT important to me to be talking about possibly bleeding out and talking about possible hysterectomies at worst case scenario. I know she has to make me aware of all of the possibilities, but really, I feel like if the "H" word is even a thought, why risk it?
I would change doctors but I am so afraid of change sometimes. I feel like I know this doctor and every doctor is probably going to have things that I don't like about them, so why change. I think I am going to stick with her because she knows my history and she delivered my daughter. Have any of you not really liked your doctor all that much? Just curious...
Just a bit concerned about the placenta subject, but otherwise everything looks great!View Thread
I ended up losing my job due to the bed rest. They had to lay me off because there were only 2 of us running the office so they really did have to replace me otherwise the whole place would have shut down. Unfortunately since the company was so small, FMLA did not protect me, so after I had Gwen I had no job to go back to. I have been been a SAHM ever since because I can't get a job now. $$ is super tight. When I lost my job that was a whole new low for me. I felt like everything that made me "me" was fading away.
Due to the extreme bed rest I ended up gaining almost 80lbs. I was in my 120's when I became pregnant and I exceeded 200 when I had Gwen. It was so hard on my body to gain the weight so quickly. It was so depressing to not be able to even walk around my house, let alone exercise. I am soooooooooo extremely sorry that you are going through this too! You said that you do laundry, so hopefully you are not on as strict of bed rest as I was. I can tell you that now that Gwen is here, looking back, it seems like my pregnancy with her flew by. At the time I was pregnant, it seemed like it was taking forever. I hope you can find some new hobbies that you can become interested in. Do you know how to crochet? You could make blankets or scarves for your loved ones for Christmas? Just a thought. I think I made 5 very large king sized croched blankets, and about 20 scarves! LOL! Everyone loved the hand made gifts.
Sending tons of (((HUGS))). Do not feel bad about venting about this. This board was literally one of the only things that kept my sanity. I felt like I LIVED on this board with my pregnancy with Gwen, I desperately needed the support. (((HUGS)))!View Thread
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text:
Kulluk Headed Back to Unalaska
Tuesday, February 12 2013
Update 02/13: The Unified Command has released additional information about the Kulluk's tow plan. You can find it here.
In the latest setback to Shell's Arctic drilling plans for this summer, the company says it's sending both of its drilling rigs to Asia for dry dock repairs. The Noble Discoverer needs an engine overhaul and the Kulluk needs major repairs to its internal electrical systems and hull after running aground near Kodiak on New Year's Eve. Shell spokesperson Curtis Smith says the Kulluk was damaged inside when seawater came through open hatches, and that the hull was "compromised" in some areas.
"We felt that dry dock in Asia was the best place to really get a good look at the underside of the hull, make a better analysis about the next steps and a timeline for the next steps," Smith said.
Smith says the company is planning to tow the Kulluk to Unalaska, and then put the rig on a larger heavy lift vessel for the rest of the trip to Asia. That vessel will pull up next to the Kulluk and dip down into the water to scoop the drill rig up onto its deck.
"So imagine if somebody was floating on the surface of a swimming pool and you went underneath them and were taller than them, of course, and you went underneath them and stood up, at that point they would be on your shoulders or on top of you, and that's sort of what happens in this dry tow scenario," Smith said.
For the trip to Unalaska, the Kulluk will be towed by three tugs. Only one tug was towing it during the reverse trip, when its towline broke in rough seas. Smith says the fuel onboard won't be removed until it gets to port. That troubles environmental activist Rick Steiner. He says he doesn't understand why the Kulluk's substantial fuel load hasn't already been offloaded.
"It's clearly unacceptable that they would be willing to tow the Kulluk with the 150,000 gallons of fuel on board, along the Alaska Peninsula through Unimak pass over to Dutch Harbor with any kind of a risk of the vessel breaking loose again and grounding or foundering and sinking. They should clearly get the fuel off now, before they take it out of Kiliuda Bay," Steiner said.
Steiner is also concerned that Shell and the Unified Command haven't released more information on the condition of the Kulluk. Shell says it hopes the Coast Guard will approve its tow plan in a few days and expects it could have the vessel in Unalaska in about two weeks. He says the company doesn't know yet how this will affect the 2013 drilling season in the Arctic.


text:
National Museum of the Marine Corps to Open Late Friday
If you have a trip planned to the The National Museum of the Marine Corps in Triangle this Friday, you'll have to get a later start.
The Museum, its parking lot and the grounds will be closed to the general public until 1:00 p.m., while staff gets ready to host the opening ceremonies of the DOD Warrior Games. The Games are a Paralympic-style military sports competition for wounded, ill, and injured service members and veterans. More than 250 are expected in the region, through next Sunday.


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Capital Markets
Company Overview of California Public Employees' Retirement System
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The Obama administration is close to finalizing a massive $1-billion bailout for the increasingly totalitarian Muslim Brotherhood regime ruling over Egypt, according to U.S. government officials cited in news reports. The move is already drawing fierce criticism from opponents arguing that bailing out the new Islamist ruler, who is already working to bolster Egyptian ties with the communist Chinese dictatorship while becoming increasingly despotic at home, would be a mistake on multiple levels.
In addition to forgiving the $1 billion in Egyptian government debt, almost a third of its total burden, the administration is also working with the International Monetary Fund (IMF) — largely funded by American taxpayers — to secure a $5-billion loan for the regime. On top of that, U.S. officials are in the process of creating multiple funds and programs worth almost $500 million to help politically connected U.S. and Egyptian businesses.
All of that taxpayer money — presumably to be printed by the Federal Reserve or borrowed from the communist Chinese dictatorship — would be in addition to the regular "security" and "foreign aid" packages. The long-standing U.S. government assistance to Egypt's rulers, set to continue indefinitely, has amounted to around $1.5 billion annually for the past several decades under the deposed dictatorship of Hosni Mubarak.
The plan to bail out the new Egyptian regime was originally announced over a year ago. However, opposition on Capitol Hill and the prosecution of U.S. government-funded "democracy activists" operating in Egypt had temporarily soured relations between the two governments. It seems the scheme is now back on track.
Click here to read the entire article.
Photo: Egyptian President Mohammed Morsi speaks to reporters during a joint news conference with Tunisian President Moncef Marzouki, unseen, at the Presidential palace in Cairo, July 13, 2012: AP Images


text:
Search goes on for ferry boy
Posted: January 04, 2013|
AN EXTENSIVE search was launched on New Year's Eve after a 16-year-old jumped from the Torpoint ferry into the bitterly cold River Tamar.
As the Cornish Guardian went to press, Jordan Cobb from Plymouth had not been found.
Detective Inspector Nick West, leading the search, said police, the RNLI and the coastguard were still looking for Jordan.
"It's a tragic incident for the family. We're supporting them as best we can.
"We're keeping an open mind and hoping he's managed to get to shore," he said.
Jordan was seen to leap from the ferry as it neared the Cornish side of the river at around 9.15pm.
A coastguard spokesman said it was thought he had been involved in "high jinks" with friends, celebrating the final hours of 2012.
The river was bitterly cold at this time of year and there would have been a current of about 4 knots, about 4.5mph, on the Torpoint side, heading towards sea, as the tide was going out.
About 30 to 40 members of the public turned up on the Tamar Bridge to help with the search effort on Wednesday morning.
Mr West urged people to take care if conducting searches along the river and to be aware of the tides.
Anyone with any information is being asked to call the police on 101.
More than 5,000 people have liked a Facebook page set up to share information about Jordan.
At Stoke Damerel Community College, where he was in Year 11, staff and governors said their thoughts were with his distraught family.
Principal Carol Hannaford said: "Jordan is a popular member of Year 11 and has been a source of strength for his younger brother, who also attends the school."
The Reverend Gordon Cryer, a governor at the school and former rector of Stoke Damerel, said: "We're very prayerful for the family.
"It's very sad, particularly at this time of year and when someone so young has been lost."


text:
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Blackfoot Reservation fishing
I am interested in flyfishing some of the small rivers on the Blackfoot reservation (Badger, etc.). Does anybody have any information on this area. . . .where to get a tribal permit? cost of a tribal permit? types of flies used, etc. Any information would be appreciated.
i went to browning (city) this spring to fish and the pemit there was about 65 for the season and about half that for three days..they were selling them at the grocery store.. i dont know if browning is on the blackfoot res or not.. but they shouldnt vary too much from that.. fly fishing is a science to its own.. i dont know your skills but ill give a quick rundown.. when you arrive at an unknown stream you take a fine mesh screen with two sticks on each end about 2x2 feet is plenty and hold it in the current and see what bugs are coming down stream.. try one that looks like it on the bottom bouncing and in the film on top, or use the fly copying those that are comming off the surface. match color and size and you dont want to have any drag on the fly making it look unatural.. when you catch a fish you can use a stomack pump to see what theyare eating and match that from your fly box or get some that match up at a store near there.. .. its a never ending thing, im always being amazed that the little buggers are eating something ive never heard of before.. only professional fly shops have some of the best fly for certain days in thier area.. other days plain caddis work great.. talk to guys you see fishing there and go buy what he or she is using.. presentation of the fly properly with the right color and size is quite important, and do not scare the fish.. always wade upstream for instance... dave...
Last edited by ffffg : 07-18-2006 at 08:13 PM.
Fly fishing the Blackfeet Indian Reservation
fffg is right - you can pick up a tribal permit in Browning - the largest city on the reservation. You can also probably - but not necessarily - pick one up in St. Mary too, at one of the grocery stores up there. Last but not least, I know you can pick up a permit at the little general store up on Duck Lake.
Be prepared for wind - the Blackfeet Reservation, like other areas on the Rocky Mountain Front - is notoriously windy at times. Maybe you'll get lucky and hit one of the calm days, but don't count on it!
I really have no idea what the trout fishing is like on the little creeks/streams that meander their way through the reservation itself, though. I know Duck Lake has excellent fishing, but you really need a boat to fish that. The other river that looks like it holds promise is the St. Mary River, downstream a bit from the lake.
Anyways, good luck and let us know how you do.
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Injection of Cyanoacrylate+Lipiodol vs Cyanoacrylate+Lauromacrogol in Gastric Varices
Recruitment status was Recruiting
- Full Text View
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- No Study Results Posted
- Disclaimer
- How to Read a Study Record
The purpose of this randomized study to compare effect of endoscopic injection of a mixture of cyanoacrylate and lipiodol versus cyanoacrylate and lauromacrogol in gastric varices.
Gastric Varices
Portal Hypertension
Drug: Lipiodol
Drug: Lauromacrogol
|Study Type:
|Study Design:
|Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:
|A Randomized Study to Compare Effect of Endoscopic Injection of a Mixture of Cyanoacrylate and Lipiodol Versus Cyanoacrylate and Lauromacrogol in Gastric Varices
- bleeding rate of the puncture site [ Time Frame: time period since the beginning of the injection, until up to 24 hours after the procedure ] [ Designated as safety issue: Yes ]We tend to observe the immediate puncture site bleed on the injection of cyanoacrylate and lipiodol or lauromacrogol and withdrawal of needle catheter during endoscopic treatment of gastric varices.
- Rebleeding rate after endoscopic treatment [ Time Frame: 6 months from the date of enrollment ] [ Designated as safety issue: No ]Patients were followed up for 6 months to see if they experience relapse of bleeding, presenting melena, haematemesis or both.
- incidence rate of ulcer formation [ Time Frame: 2 months after the initial endoscopic treatment ] [ Designated as safety issue: No ]The patients will be assessed if ulceration is formed on the site of the injection when they have gastroscopy review in 2 months after the initial endoscopic treatment.
- eradication rate of gastric varices [ Time Frame: 2 months after the initial endoscopic treatment ] [ Designated as safety issue: No ]Patients will be evaluated if gastric varices are eradicated when they have gastroscopy review in 2 months after the initial endoscopic treatment.
- incidence rate of complications [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]Participants will be followed for up to 6 months starting from the date of enrollment.Complications associated with endoscopic treatments include transient fever, transient dysphagia, transient arrhythmias, ulceration, perforation, stricture, rebleeding, aspiration pneumonia, sepsis, peritonitis and chest pain.
|Estimated Enrollment:
|Study Start Date:
|April 2013
|Estimated Study Completion Date:
|December 2013
|Estimated Primary Completion Date:
|December 2013 (Final data collection date for primary outcome measure)
|Assigned Interventions
Active Comparator: NBCA-lipiodol
Patients will receive injection of a mixture of cyanoacrylate and lipiodol to treat gastric varices
Drug: Lipiodol
endoscopic injection of lipiodol + cyanoacrylate + lipiodol for gastric varices
Experimental: NBCA-lauromacrogol
Patients will receive injection of the mixture of cyanoacrylate and lauromacrogol to treat gastric varices
Drug: Lauromacrogol
endoscopic injection of lauromacrogol + cyanoacrylate + lauromacrogol for gastric varices
Detailed Description:
Gastroesophageal variceal bleeding is known as one of the most frequent death causes of patients with portal hypertension. When a patient has a bleeding episode, if no further prophylactic treatments is given, it's very likely that he/she will develop another rebleeding event in the future and maybe a terminal event. Gastric varices occur in 18-70% of patients with portal hypertension, which appear to be more severe, to require more transfusion and to have a higher mortality rate than esophageal variceal bleeding, with a high rate of rebleeding(38-89%). It has been recommended to use endoscopic cyanoacrylate injection as the first line treatment for hemostasis and secondary prophylaxis for gastric varices by general consensus. However, the efficacy and prevalence of complications between mixture of cyanoacrylate + lipiodol and cyanoacrylate + lauromacrogol have not yet been explored and reported. We conducted this study to evaluate the effect of endoscopic injection of a mixture of cyanoacrylate and lipiodol versus cyanoacrylate and lauromacrogol in gastric varices.
|Ages Eligible for Study:
|18 Years to 80 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Inclusion Criteria:
- Patients presented to our hospital with acute gastric variceal bleeding, with or without liver cirrhosis.
- The age of the patients range from 18 to 80 years old.
Exclusion Criteria:
- Patients who have contraindications for cyanoacrylate, lipiodol or lauromacrogol therapy.
- Patients who have abnormal portosystemic shunt according to the imaging results.
- Patients who have no previous upper gastrointestinal bleeding history.
- Patients who have multiple endoscopic treatments for esophagogastric varices before.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01923064
|Contact: Shiyao CHEN, MD
|Contact: Jie CHEN, MD
|China, Shanghai
|Zhongshan Hospital
|Shanghai, Shanghai, China, 0086200032
|Contact: Shiyao CHEN, MD 8613601767319 email@example.com
|Contact: Jie Chen, MD 8613764633539 firstname.lastname@example.com
|Principal Investigator: Shiyao CHEN, MD
|Sub-Investigator: Jie CHEN, MD
|Sub-Investigator: Xiaoqing ZENG, MD
|Study Director:
|Shiyao Chen, MD
|Zhongshan Hospital, Shanghai
No publications provided
|Responsible Party:
|Shiyao Chen, professor, Shanghai Zhongshan Hospital
|ClinicalTrials.gov Identifier:
|NCT01923064 History of Changes
|Other Study ID Numbers:
|Study First Received:
|August 7, 2013
|Last Updated:
|August 13, 2013
|Health Authority:
|China: Ministry of Health
Additional relevant MeSH terms:
Esophageal and Gastric Varices
Hypertension, Portal
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Liver Diseases
Ethiodized Oil
Antineoplastic Agents
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions
Therapeutic Uses
ClinicalTrials.gov processed this record on October 09, 2015


text:
Book your room at Kantary House Hotel & Serviced Apartments
Get an overview of this hotelFamily-friendly Bangkok hotel in Ramkhamhaeng with free breakfast
This family-friendly Bangkok hotel is located near the airport, within 1 mi (2 km) of Tawanna Night Bazaar and Happyland Center. Ramkhamhaeng University and Samitivej Srinakarin Hospital are also within 2 mi (3 km).
Hotel Features
Along with an outdoor pool, this smoke-free hotel has a health club and a bar/lounge. Free buffet breakfast and free self parking are also provided. Additionally, a coffee shop/café, a snack bar/deli, and a spa tub are onsite.
Room Amenities
All 187 individually decorated rooms feature WiFi and DVD players. Guests can enjoy deep soaking tubs, and other standard amenities include kitchenettes with refrigerators and microwaves.Information missing or incorrect? Tell us!
Hotel Amenities
Hotel Amenities
In addition to an outdoor pool, Kantary House Hotel & Serviced Apartments provides a health club, a spa tub, and a sauna. Dining options at the hotel include a coffee shop/café and a snack bar/deli. A bar/lounge is on site where guests can unwind with a drink. Guests can enjoy a complimentary breakfast each morning. Public areas are equipped with high-speed wired and wireless Internet access (surcharge).
Business-related amenities at this 3.5-star property consist of a business center and a meeting room. This family-friendly hotel also offers a steam room, an arcade/game room, and multilingual staff. For a surcharge, a roundtrip airport shuttle (available on request) is offered to guests. Limited complimentary onsite parking is available on a first-come, first-served basis.
Kantary House Hotel & Serviced Apartments is a smoke-free property.
- 24-hour front desk
- Airport transportation (surcharge)
- Arcade/game room
- Babysitting or childcare
- Bar/lounge
- Business center
- Coffee shop or café
- Elevator/lift
- Pool umbrellas
- Billiards or pool table
- Grocery/convenience store
- Total number of rooms - 187
- Number of floors - 11
- Multilingual staff
- Porter/bellhop
- Safe-deposit box at front desk
- Number of restaurants - 1
- Free self parking
- Sauna
- Free newspapers in lobby
- Free breakfast
- Dry cleaning/laundry service
- Health club
- WiFi (surcharge)
- Wired (high-speed) Internet access - surcharge
- One meeting room
- Parking (limited spaces)
- Year Built 1992
- Snack bar/deli
- Smoke-free property
- Number of buildings/towers - 2
- Spa tub
- Steam room
- Outdoor pool
Family Friendly Amenities
- Family Hotel
- Outdoor pool
- Kitchenette
- Grocery/convenience store
- Snack bar/deli
- Babysitting or childcare
- Arcade/game room
- Separate dining area
- Refrigerator
- Microwave
- DVD player
Available in all rooms: Wireless internet access ( 200 THB per 24-hour period )
Available in some public areas: WiFi (surcharge) , Wired (high-speed) Internet access - surcharge
Free self parking, Parking (limited spaces)
Room Amenities
- Room service (limited hours)
- DVD player
- Air conditioning
- Phone
- Kitchenette
- Microwave
- Refrigerator
- Hair dryer
- Balcony
- Lanai
- Separate sitting area
- Climate control
- Free bottled water
- Daily housekeeping
- Private bathroom
- Free toiletries
- Deep soaking bathtub
- Bidet
- Separate bathtub and shower
- Desk
- In-room safe
- Cookware, dishware, and utensils
- Cable TV service
- Flat-panel TV
- WiFi (surcharge)
- Separate dining area
- Blackout drapes/curtains
- Individually furnished
- Individually decorated
Where to Eat
Guests are offered a complimentary buffet breakfast each morning.
The Orchard - Onsite restaurant.
Room service (during limited hours) is available.
Nearby Things to Do
An outdoor pool and a spa tub are on site. Other recreational amenities include a health club, a sauna, and a steam room.
Hotel Policies
Check-in time starts at 2 PM
Check-out time is noon
Payment types
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
No pets or service animals allowed
- Fee for in-room wireless Internet: THB 200 per 24-hour period (rates may vary)
- Rollaway bed fee: THB 668 per night
We should mention
This property offers transfers from the airport (surcharges may apply). Guests must contact the property with arrival details before travel, using the contact information on the booking confirmation. One child 3 years old or younger stays free when occupying the parent or guardian's room, using existing bedding. Children may not be eligible for complimentary breakfast. No pets and no service animals are allowed at this property.


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A clean and simple set of sliders that uses little details to differentiate.Posted in Interface → Element
A couple of beautiful app icons that use colour very effectively.Posted in Interface → iPhone App
A beautiful re-imagining of the Tweetbot icon for iOS 7. I love the way this design retains the character of the icon, all while simplifying the design.Posted in Branding → Logo
The Mac App Store icon for Memoir. I really like the custom "m" and the use of colour.Posted in Interface → Element
Website for the Loyalty Program 360 Rewards for Standard Chartered Bank Singapore. Plenty of modern visual effects as you scroll through the design examples here, and I love the consistent interface feel throughout the site.Visualizers VisualizersPosted in Web Design → Corporate
Fantastic icon designs that have a real sense of consistency and style.Posted in Interface → Other
A minimal site for a web app designed to help with project and task collaboration. I like the intuitive layout and focussed use of colour.Posted in Web Design → Software
A beautiful portfolio site designed by and for Mustafa Demirkent, a backend and frontend developer at R/GA London. I love the intuitive tile-design and the supremely minimal layout.Posted in Web Design → Portfolio
A simply blog design that features some really clean social icons.Posted in Web Design → Blog
A slick interface for an iPhone app that helps you discover new places to go. I particularly like the bright design aesthetic and the use of colour.Posted in Interface → iPhone App
A superb button design that's distinctive and clean.Posted in Interface → Element
Lightweight, mobile-first, flexible responsive portfolio site.Alec RustPosted in Web Design → Portfolio
This simple logo mark that represents the water cycle is concise and neatly designed using almost too appropriate colours.Posted in Branding → Logo
An interesting design for an icon that goes right for the flat aesthetic.Posted in Interface → iPhone App
This is the new version of my portfolioBorja GonzálezPosted in Web Design → Portfolio
A neat little map icon that uses well recognised symbols and simple colours to create a certain aesthetic.Posted in Interface → Element
Black Pearl is a unique and powerful theme that is simple, modern, and easy-to-use.Posted in Web Design → Design
A detailed badge complimented with some beautiful ribbon.Posted in →
A superb set of icons derived from the component pieces of a skateboard. I like the attention to detail and the sense of realism.Posted in Interface → Element
Dark and simple menus to be used for any application or website. I like the selection colour and the simple symmetry.Posted in Interface → Element


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FHP: Driver was traveling north in southbound lanes on U.S. 1 in Indian River County
INDIAN RIVER COUNTY — A Vero Beach woman traveling north in the southbound lanes of U.S. 1 collided with another car Sunday, leaving both drivers in critical condition, the Florida Highway Patrol said.
The crash happened at 8:45 p.m. Sunday near the St. Lucie County line. Carol Garcia, 37, of Vero Beach was driving her Chevrolet Blazer north in the southbound lanes, troopers said. The Blazer struck a southbound Honda Element driven by Michelle Lynn Morey, 27, of Fort Pierce.
The women were being treated at Lawnwood Regional Medical Center & Heart Institute in Fort Pierce.
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Sure, he resembles Phil Hartman's Unfrozen Caveman Lawyer and speaks in the kind of scattershot English that Frankenstein's monster croaked out. But a monster he is not.
So how does The Room live among midnight-movie classics like Plan 9 From Outer Space, The Rocky Horror Picture Show, Troll 2 and Pink Flamingos?
We'll have the chance to ask the singular Wiseau that very question when he hits Cinema 21 on Friday and Saturday for The Room's 10-year anniversary—though it's almost certain even he doesn't know the answer. From its sub-Skinemax opening sex scene to Wiseau's final monologue of sputtered consonants, The Room is so bad that Wiseau has been declared the Ed Wood of romantic dramas, a title that insults Wood's legacy. After all, Plan 9 at least featured a fading star in Bela Lugosi and some hackneyed yet inventive special effects that paved the way for everything from Night of the Lepus to Sharknado. The Room, conversely, exists in a creative vacuum. People go to The Room not to worship an outsider artist but to laugh at the incompetence of a man who thought he was making something special.
But here's the thing: The Room is no worse than most ultra-indie movies. Ninety-nine percent of them are twice as self-serious as The Room, equally incompetent and nowhere near as hilarious. If the directors of those films were to endure such ridicule, they'd crumble. Wiseau, though, has harnessed that mean-spirited rubbernecking into cult status. He's translated most filmmakers' nightmares into a dream…or at least into free hotel rooms whenever he wants to show up at a screening. He plays village idiot to people who wouldn't have the balls even to attempt their dream projects, standing proudly in front of his creation as it's eviscerated.
No, Wiseau isn't a midnight-movie monster. He's a goddamn saint in a baggy suit. Cinema 21. 10:45 pm Friday-Saturday, Dec. 6-7.
Also Showing:
- Whether you—like most cinephiles—melt at the very mention of Christopher Marker or—like me—wince at the pretentiousness, a meticulous restoration of the 1963 "direct cinema" (read: boring) documentary Le Joli Mai by the film's original cinematographer is cause for excitement…even if you're (read: I'm) rolling your (read: my) eyes. NW Film Center's Whitsell Auditorium. 7 pm Thursday, Dec. 5.
- Every time Tim Burton and Johnny Depp team up to take a big, steaming crap on something like Alice in Wonderland, take a deep breath and remember that their first collaboration was the beautiful, heartbreaking and hilarious Edward Scissorhands. Then wonder what the fuck happened. Hollywood Theatre. Dec. 6-9, 11-12.
- In Planes, Trains & Automobiles, Steve Martin plays an insufferable, self-important dickhead. John Candy plays a lovable idiot. They're stuck together for the holidays. I can't think of a more apt analogy for most Christmas dinners. Laurelhurst Theater. Dec. 6-12.
- The Cascade AIDS Project takes over the Clinton with a series of eye-opening documentaries such as United in Anger and Miss HIV. But, in an effort not to be depressing, it caps things off with a sing-along to Rent, a feel-good musical about…oh, wait. Clinton Street Theater. Dec. 6-8.
- Before she got (in this writer's opinion) befuddling praise for Lost in Translation and stumbled in Marie Antoinette, Sofia Coppola made her best film, an adaptation of Jeffrey Eugenides' The Virgin Suicides. 5th Avenue Cinema. Dec. 6-8.
- Because you won't be able to watch TV this month without thinking, "God, the Christmas shit I watched as a kid was so much better than this," Animated Christmas 2 is back with a collection of rare 16 mm and VHS cartoons that will prove your childhood taste was crappier than you remember. Hollywood Theatre. 2:30 pm Saturday, Dec. 7.
- Arnold Schwarzenegger's contribution to Christmas cinema, Jingle All the Way, teaches the valuable lesson that, no matter what obstacles or Sinbads you face, you should go to any extreme to get your stupid kid some stupid toy. Hecklevision, do your damage. Hollywood Theatre. 7:30 pm Saturday, Dec. 7.
- Hollywood Theatre programmer Dan Halsted seems to be in a pissing contest of one-upmanship with himself in order to make each entry in the Kung Fu Theater series weirder. Kid With the Golden Arms continues that tradition with metal-limbed melees set in what is described as an "18th-century disco" and looks like it was shot from Timothy Leary's POV. Hollywood Theatre. 7:30 pm Tuesday, Dec. 10.


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WNO Commentary: The Force of Destiny 7 of 7: Act Four: Scene One: At the monastery. Scene Two: At a nearby grotto (audio only)
Loading the player...
Musicologist Saul Lilienstein offers his commentary on The Force of Destiny, featuring insights about the music and history. Musical excerpts used courtesy of EMI Classics.


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Frank Rodney Reed
Position: DB
Height: 5-11 Weight: 193 lbs.
Born: May 13, 1954 in Seattle, WA
High School: Oliver M. Hazen
College: Washington (school history)
Drafted by the Atlanta Falcons in the 8th round (219th overall) of the 1976 NFL Draft.
Weighted Career AV (100-95-...): 22 (4371st overall since 1950)
Promote your website or business by sponsoring this page for $5 on Pro-Football-Reference.com. Your message will replace this ad.


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Have you ever had a teacher who has changed your life and made you want to learn? Now you can give something back to that someone who has given you so much! During select weeks in the school year, a Midlands Teacher will be rewarded as someone who has gone above and beyond the call of duty and will be recognized on a Tuesday evening during WLTX's "Friends @ Five". The winning teacher will receive a basket of apples.
Download and print a nomination form - Click here.
After you complete the nomination form, please send it to:
'Teacher Of The Week'
6027 Garners Ferry Rd.
Columbia, SC 29209


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A bill that would overhaul Oklahoma's workers' compensation court and replace it with an administrative system that sped through the Senate will be slowed down in the House of Representatives for a closer look, House Speaker T.W. Shannon said.
House to take close look at workers' compensation bill
Shannon, R-Lawton, said he generally supports the measure, but the House will take its time with Senate Bill 1062 to look at how the bill would reduce compensation benefits available to injured workers.
"Our main concern is that injured workers are not penalized and that the company that provides the benefits is able to do so in an affordable manner and that it doesn't become a hindrance to doing business in Oklahoma," Shannon said. "I haven't seen the Senate bill to know exactly, but I think I like a lot of what I've heard about it. What I like about it the most is that it goes to an administrative system."
SB 1062, a 260-page bill, was unveiled nearly two weeks ago by Senate leaders. A Senate committee passed it 8-2 and last week the Senate passed it 34-12.
"We'll have a lot more time to vet the bill than happened in the Senate," Shannon said. "That will give us a lot more opportunities to make it even stronger.
"We'll get it over to the House," he said. "We'll make some modifications to it and hopefully make it an even stronger workers' compensation bill."
If changes are made to the bill in the House, it would have to return to the Senate for consideration.
Thursday was the deadline for House and Senate bills to be heard and passed out of each chamber's committees. For the next two weeks, lawmakers will spend time in session to meet a March 14 deadline of getting House-originated bills out of the House and Senate-originated bills out of the Senate.
Backers say SB 1062 would bring system costs and compensation benefits in line with neighboring states. The State Chamber said Oklahoma ranks as the sixth-highest in workers' compensation benefits awarded to injured workers. Opponents say it would reduce employer liability and make significant cuts to a program intended to protect workers.
If the bill becomes law, workers' comp claims would be heard and decided by a panel of administrative law judges who are appointed by a trio of commissioners. The commissioners would be appointed by the governor, subject to Senate approval. It would make Oklahoma only the second state to allow qualified employers to opt out of the workers' compensation system entirely as long as they can develop their own replacement program. It also would establish a method for employee-employer disputes to be mediated outside of a courtroom.
Oklahoma, one of two states with a judicial system handling cases of workers hurt on the job, has 10 workers' compensation judges. Each judge hears disputed workers' compensation issues, which may be resolved informally at a prehearing or settlement conference, or by a trial. Written orders of the trial judge are final unless appealed to a three-judge review panel of the workers' compensation court, or to the Oklahoma Supreme Court.
House Minority Leader Scott Inman, D-Del City, said he agrees changes are needed in the system, but it's too early to make a major overhaul. Changes passed by legislation two years ago that were intended to reduce costs are just now taking effect, he said. Costs also could be reduced by working to control the rising costs of medical procedures and care within the system, he said.
Continue reading this story on the...


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Healthy Cats
Hyperthyroidism (Thyroid Cancer) in Cats
In this article
Hyperthyroidism in cats is almost always associated with a cancer-a benign adenoma (more common) or a malignant adenocarcinoma. These cancers tend to occur in older cats and the major effect is the increased thyroid hormone production they stimulate. Exposure to secondhand cigarette smoke may be a factor. Himalayans and Siamese have a lower risk for this problem.
The first signs may be dramatic. The increase in thyroid hormones tends to cause an increase in appetite-the finicky eater now wolfs everything down and may even open cupboards looking for more-and an increase in activity. The sedate older cat who used to spend his days soaking in the sun on his window seat is now flying around the house like a wild kitten. Weight loss, vomiting, and panting may all be noted. Careful palpation of the area under the chin when the head is lifted may reveal a small lump. Thyroid tumors may appear only on one side, but they can be bilateral.
Blood work is important to see if thyroid hormone levels are truly elevated. It is important to check kidney function, because the increased metabolic rate may hide kidney failure. It is also important to thoroughly evaluate the heart, which can be damaged from the increased metabolic rate. High blood pressure or hypertension is often seen in hyperthyroid cats.
Treatment tends to start with an oral medication called methimazole, which lowers hormone production. This must be given daily and manufacturers are working on palatable and easy-to-administer forms for cats, including a compounded version that is applied to the ear and absorbed through the skin. Medical treatment enables your veterinarian to evaluate the cat's kidney and cardiac status prior to the more definitive treatment of surgery or radioactive iodine.
Surgery is another option, with the cancerous gland removed. Care must be taken not to damage or remove the parathyroid glands that regulate calcium metabolism. If both thyroid glands are removed, the cat will need supplemental thyroid for the rest of his life.
A third and popular option is to use radioactive iodine to destroy the cancerous tissue. Cats who undergo this therapy must stay at a treatment center for 7 to 25 days while the radioactivity shed in the cat's urine and feces decreases to a safe level. These cats may need supplemental thyroid for the rest of their lives.


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Artisan Santa Fe wants to help grow a young artist.
The organization is offering a Budding Artist Fellowship for students from any learning situation ages 13-17.
The fellowship awards a young artist with $100 worth of art supplies every month for a year. Young artists between the ages of 13 and 17 from all public schools, charter schools, private, parochial and Indian schools and home-schooled young people are encouraged to apply.
Artists apply by submitting three artworks and a statement of intent for consideration.
Artists must be confident that they are sincere that this fellowship will become part of their regular school work. Submissions for 2013 and registration are due by May 15.
Winner will be announced in the Artisan-Santa Fe's June 2013 e-newsletter.
The Budding Artist Fellowship is open to the first 100 applicants.
The Artisan Staff will be judging the field of applicants and act as resources for the winner.
Artisan Santa Fe store will issue a gift card and be adding to the credit each month. Staff will help the winner navigate supply questions and choices.
Some of the winner's artworks may eventually be hung in the Santa Fe store.
Our web master will help put a web presence for the winner on the Artisan web site.
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Katherine "Kati" Key, 83, of Alexandria, died Feb. 5, 2013, at Judson Care Center in Cincinnati.
She was a waitress for Hathaway's downtown Cincinnati.
Her husband, William Cogel Key Jr., died previously.
Survivors include her daughters, Deborah Veirs of Butler, Kim Stitt of Morning View, and Teresa Hunt of Clarkston, Mich.; sons, William Key, III, of Sharpsburg and James Key of Alexandria; 17 grandchildren; 21 great-grandchildren; and two great-great-grandchildren.
Visitation will be 11 a.m.-1 p.m., Friday, Feb. 8, at Dobbling, Muehlenkamp-Erschell Funeral Home in Bellevue. Funeral ceremony will be 1 p.m. Friday, Feb. 8, 2013, at the funeral home. Burial will be at Evergreen Cemetery in Southgate.
Memorials: Alzheimer's Association, 644 Linn St., Suite 1026, Cincinnati, OH 45203.


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At this point in her career, actress Milla Jovovich is perhaps best known for playing action heroes. She kicks a significant amount of ass in the Resident Evil films, and first rose to prominence with her role alongside Bruce Willis in The Fifth Element. She has a slew of movie roles lined up for the next several months, including a part in the upcoming film The Three Musketeers.
A word from Milla: "I used to ride my bicycle around for hours in the garage of our apartment building singing 'Material Girl.'"
Consider posting a comment.


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Art Show Focuses on Garment Workers
New York, NY —
At one time, New York City had hundreds of thousands of workers churning out much of this country's clothing. Today, there are about eighty-thousand blue-collar garment workers left in the city. A recent art installation focused on some of them.
This past weekend, an old, empty Liz Claiborne store at the South Street Seaport was turned into a gallery for a few days, reflecting the lives and jobs of people like Joe Raco, a cutter for the past 40 years, and president of Local 10, the cutter's union.
RACO: I cut quality garments made in New York—made in New York. If you were to buy a garment that's let's say a plaid, now you look at this garment, and you see all the lines lining up on the front and the back, I bet you never gave it much thought about how it got that way—well it gets there by an expert cutter.
In an alcove where clothing was once displayed, a video screen showed Raco miming a cutting motion with his middle and forefingers, cutting out invisible patterns, picking up invisible pieces of fabric and putting them in a pile.
Similar images ran throughout the former retail space. In the videos, cutters, sewers, and sample makers mimic the actions of their jobs and talk about what they do—mostly in Cantonese. Local 23-25, one of two unions the artists worked with, estimates that more than half of its members are Chinese.
[Chinese chorus]
That's Solidarity Forever, sung in Cantonese by the Chinese chorus of Local 23-25. The singers were smiling, and not surprisingly, sharply dressed and wearing white caps with the UNITE HERE union logo.
The exhibition was part of a project called CAKE—Collecting Action and Knowledge about the Everyday. It was created by choreographer Ann Carlson and video artist Mary Ellen Strom, along with a team of six other artists. Carlson says it started with a pair of jeans.
CARLSON: We went to Mexico, we got into a jeans factory, and we saw a pair of Gap jeans being built from the ground up.
Then they turned their attention to New York.
CARLSON: A lot of the workers that are building Guess dresses and things that you see all over here, even in the Seaport, are being made just over in Chinatown. So it's not all outsourced. There's neighborhood workers that are laboring every day to make the dress you buy at guess. And we're not looking at it from a heavy-handed, like, you shouldn't be buying that dress, just, who makes it?
The artists spent about four hours with each worker, videotaping them and helping them shape the movements of their jobs.
CARLSON: They're sort of personal dances in a way. We were thinking about 19th Century portraiture, like a combination of a visual formality, as well as a kind of the casual everyday-ness of gesture.
Ching Hang Lee, a seamstress who came here from Hong Kong 14 years ago, explained through a translator that she also teaches T'ai Chi.
LEE: So when she's at work she almost feels like the movement is like practicing her T'ai Chi, so you'll see in her film how the movement of pushing the material through the sewing machine is almost like pushing in T'ai Chi.
JOE RACO: They've taken an entire industry and put a face on it.
Cutter's union president Joe Raco.
RACO: We needed that to give us some of our pride back. Not that we've ever lost it skill-wise, but we've been beaten down pretty bad lately.
Since federal import quotas expired in January, cotton imports from Chinas jumped fifteen hundred percent. The situation is so extreme that the government announced last week that it is considering bringing quotas back.
The project is a work-in-progress. Carlson and Strom are hoping to mount another installation in about year using a lot of the material shown at the Seaport, and taking a look at the past and the future of the city's garment industry.
For WNYC, I'm Alicia Zuckerman.
[Chinese union Chorus](CAKE was sponsored by the Lower Manhattan Cultural Council and Mix NYC.)


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Letter: All downhill
Scott Mansell, Naples
All downhill
The tipping point has been passed, even though more of the map was red than blue.
We now have more voters concerned about their government goodies than our Constitution or the fiscal mess that will now consume us. After all, you don't vote against "Baracka Claus."
I do not refer to seniors collecting Social Security. You paid an awful lot into that Ponzi scheme; you are owed some of it back. Realize, you won't get back anywhere near what you put into it. People my age, in their mid 30s and 40s, are realizing it likely won't be there when we get there.
The scary part is the number of voters who could name all past "American Idol" judges, but can't name one Supreme Court judge. They're more interested in the next episode of the "Jersey Shore."
The Dow lost about 450 points in the days following the election. By the end of the year, it will get worse.
We are stuck with the unaffordable Obamacare. Its devastating effect on our economy will be seen soon. Small companies will not hire that 50th employee. Companies with 55 employees will be trimming down to 49. Big companies will be announcing layoffs and reduction in hours for part-time workers.
You can kiss your employer-provided health insurance buh-bye. It's cheaper to pay the Obamacare fine (I mean tax!) than it is to provide your company insurance benefit.
Last Christmas card for your family doctor too. More and more doctors are already not accepting new Medicare patients because of Obamacare. Good luck, new retirees.
The fundamental transformation of our country is now unstoppable. Welcome to the new DSA — Divided States of Amerikstan.
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Police ID body found in river as missing man
ROSEBURG, Ore. -- Police have identified the body found in the South Umpqua river as that of a missing Roseburg man.
A follow up investigation by the Oregon State Medical Examiner's Office led to the identification of the body as that of Levi Paul Jones of Roseburg.
Jones was reported missing to the Roseburg Police Department on January 3, having last been seen leaving a home on SE Pine St. on the evening of December 30, 2012.
The Medical Examiner's Office determined that Jones' death was by drowning, and that foul play is not suspected.


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Every Wednesday Susan from A Southern Daydreamer is hosting Outdoor Wednesday. I actually wrote a post today , but when I saw the lovely posts...well, I just had to join in too and write another.
I am dreaming of Spring,
and Daffodils.
Pots and pots of Daffodils...
I know a garden,
not too far from here,
Where hundreds,
and hundreds,
of Daffodils
will soon be in bloom.
Today, if you click HERE,
you will be lead down the garden paths to Outdoor Wednesday,
hosted by the lovely Susan. And if you are so inclined, you can add your name to the growing list.
The song for this post is Just The Way You Are. A love song for the awaited Daffodil


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Ellen Trout Zoo Welcomes Another Rare Baby Antelope
Halloween Events Planned in Lufkin
Here are a few ideas about events happening around Lufkin around Halloween, so you and the kids can plan accordingly. Don't miss out!
The last week of October is always a busy one for trick-or-treaters, and parents have to make choices about which organized events to attend; or mix some of those events in while also taking the kids house-to-house for candy in the neighborhood.
Ellen Trout Zoo Welcomes A Baby Antelope
Worker Escapes A Lion At The Dallas Zoo
Having a job working with animals at a zoo has to be sort of similar to a security guard watching security cameras all day. Most of the time everything is calm and serene and just fine, and very little happens. But then there's that one moment when things get tense, and it's time to act!
A worker was cornered by a lion at the Dallas Zoo a few days ago, and had to be treated at the hospital after the attack. Here's what led up to it.