Phylogenetic analyses of mode of larval development

Phylogenies based on morphological or molecular characters have been used to provide an evolutionary context for analysis of larval evolution. Studies of gastropods, bivalves, tunicates, sea stars, sea urchins, and polychaetes have revealed massive parallel evolution of similar larval forms. Some of these studies were designed to test, and have rejected, the species selection hypothesis for evolutionary trends in the frequency of derived larvae or life history traits. However, the lack of well supported models of larval character evolution leave some doubt about the quality of inferences of larval evolution from phylogenies of living taxa. Better models based on maximum likelihood methods and known prior probabilities of larval character state changes will improve our understanding of the history of larval evolution.     

Estimation in a Cox proportional hazards cure model

Some failure time data come from a population that consists of some subjects who are susceptible to and others who are nonsusceptible to the event of interest. The data typically have heavy censoring at the end of the follow-up period, and a standard survival analysis would not always be appropriate. In such situations where there is good scientific or empirical evidence of a nonsusceptible population, the mixture or cure model can be used (Farewell, 1982, Biometrics 38, 1041-1046). It assumes a binary distribution to model the incidence probability and a parametric failure time distribution to model the latency. Kuk and Chen (1992, Biometrika 79, 531-541) extended the model by using Cox's proportional hazards regression for the latency. We develop maximum likelihood techniques for the joint estimation of the incidence and latency regression parameters in this model using the nonparametric form of the likelihood and an EM algorithm. A zero-tail constraint is used to reduce the near nonidentifiability of the problem. The inverse of the observed information matrix is used to compute the standard errors. A simulation study shows that the methods are competitive to the parametric methods under ideal conditions and are generally better when censoring from loss to follow-up is heavy. The methods are applied to a data set of tonsil cancer patients treated with radiation therapy.     

Divergence genetics analysis reveals historical population genetic processes leading to contrasting phylogeographic patterns in co-distributed species

Coalescent samplers are computational time machines for inferring the historical demographic genetic processes that have given rise to observable patterns of spatial genetic variation among contemporary populations. We have used traditional characterizations of population structure and coalescent‐based inferences about demographic processes to reconstruct the population histories of two co‐distributed marine species, the frilled dog whelk, Nucella lamellosa, and the bat star, Patiria miniata. Analyses of population structure were consistent with previous work in both species except that additional samples of N. lamellosa showed a larger regional genetic break on Vancouver Island (VI) rather than between the southern Alexander Archipelago as in P. miniata. Our understanding of the causes, rather than just the patterns, of spatial genetic variation was dramatically improved by coalescent analyses that emphasized variation in population divergence times. Overall, gene flow was greater in bat stars (planktonic development) than snails (benthic development) but spatially homogeneous within species. In both species, these large phylogeographic breaks corresponded to relatively ancient divergence times between populations rather than regionally restricted gene flow. Although only N. lamellosa shows a large break on VI, population separation times on VI are congruent between species, suggesting a similar response to late Pleistocene ice sheet expansion. The absence of a phylogeographic break in P. miniata on VI can be attributed to greater gene flow and larger effective population size in this species. Such insights put the relative significance of gene flow into a more comprehensive historical biogeographic context and have important implications for conservation and landscape genetic studies that emphasize the role of contemporary gene flow and connectivity in shaping patterns of population differentiation.     

深圳市社区公共卫生服务包运行的成本结构分析

目的 了解深圳市社区公共卫生服务包运行成本的总体情况及财政投入的参考标准。方法 在人力成本、基本支持与保障成本测算的基础上,结合社康中心普查资料与统计年鉴,分析服务包运行中各要素成本及其占财政支出的比例。结果 完成服务包基本项目时,按每万服务人口计,服务包运行成本为64.67万元,其中人力成本占70%,此时服务包成本占同年财政一般性的比例约为1%。结论 深圳市有实力也有必要进一步加大对社区卫生服务的投入,特别是保证人员经费的投入。     

Estimating Wind Turbine-Caused Bird Mortality

ABSTRACT Mortality estimates are needed of birds and bats killed by wind turbines because wind power generation is rapidly expanding worldwide. A mortality estimate is based on the number of fatalities assumed caused by wind turbines and found during periodic searches, plus the estimated number not found. The 2 most commonly used estimators adjust mortality estimates by rates of searcher detection and scavenger removal of carcasses. However, searcher detection trials can be biased by the species used in the trial, the number volitionally placed for a given fatality search, and the disposition of the carcass on the ground. Scavenger removal trials can be biased by the metric representing removal rate, the number of carcasses placed at once, the duration of the trial, species used, whether carcasses were frozen, whether carcasses included injuries consistent with wind turbine collisions, season, distance from the wind turbines, and general location. I summarized searcher detection rates among reported trials, and I developed models to predict the proportion of carcasses remaining since the last fatality search. The summaries I present can be used to adjust previous and future estimates of mortality to improve comparability. I also identify research directions to better understand these and other adjustments needed to compare mortality estimates among wind farms.     

Under-smoothed kernel confidence intervals for the hazard ratio based on censored data

In cancer clinical trials, it is often of interest in estimating the ratios of hazard rates at some specific time points during the study from two independent populations. In this paper, we consider nonparametric confidence interval procedures for the hazard ratio based on kernel estimates for the hazard rates with under-smoothing bandwidths. Two methods are used to derive the confidence intervals: one based on the asymptotic normality of the ratio of the kernel estimates for the hazard rates in two populations and another through Fieller's Theorem. The performances of the proposed confidence intervals are evaluated through Monte-Carlo simulations and applied to the analysis of data from a clinical trial on early breast cancer.     

Gene flow between species of Lake Victoria haplochromine fishes

The haplochromine cichlid fishes of Lake Victoria (LV), East Africa, are a textbook example of adaptive radiation-a rapid divergence of multiple morphologically distinguishable forms from a few founding lineages. The forms are generally believed to constitute a "flock" of several hundred reproductively isolated species in a dozen or so genera. This belief has, until now, not been subjected to a test, however. Here, we compare genetic variation at 11 loci in 10 haplochromine populations of 6 different species. Although the genetic diversity in the populations is quite high, using a variety of statistical tests, we find no evidence of genetic differentiation among the populations of LV haplochromines. On genetic distance trees, populations of the same species intermingle with those of different species. At the molecular level, the species are indistinguishable from one another. Genetic comparisons with closely related species in 2 crater lakes indicate that the species within LV continue exchanging genes. These observations have important implications for phylogenetic reconstruction. The approach used in this study is applicable to other instances of adaptive radiation.     

Model misspecification confounds the estimation of rates and exaggerates their time dependency

While welcoming the comment of Ho et al. ( 2015 ), we find little that undermines the strength of our criticism, and it would appear they have misunderstood our central argument. Here we respond with the purpose of reiterating that we are (i) generally critical of much of the evidence presented in support of the time‐dependent molecular rate (TDMR) hypothesis and (ii) specifically critical of estimates of μ derived from tip‐dated sequences that exaggerate the importance of purifying selection as an explanation for TDMR over extended timescales. In response to assertions put forward by Ho et al. ( 2015 ), we use panmictic coalescent simulations of temporal data to explore a fundamental assumption for tip‐dated tree shape and associated mutation rate estimates, and the appropriateness and utility of the date randomization test. The results reveal problems for the joint estimation of tree topology, effective population size and μ with tip‐dated sequences using beast . Given the simulations, beast consistently obtains incorrect topological tree structures that are consistent with the substantial overestimation of μ and underestimation of effective population size. Data generated from lower effective population sizes were less likely to fail the date randomization test yet still resulted in substantially upwardly biased estimates of rates, bringing previous estimates of μ from temporally sampled DNA sequences into question. We find that our general criticisms of both the hypothesis of time‐dependent molecular evolution and Bayesian methods to estimate μ from temporally sampled DNA sequences are further reinforced.     

Construction of a robust and sensitive arginine biosensor through ancestral protein reconstruction

Biosensors for signaling molecules allow the study of physiological processes by bringing together the fields of protein engineering, fluorescence imaging, and cell biology. Construction of genetically encoded biosensors generally relies on the availability of a binding “core” that is both specific and stable, which can then be combined with fluorescent molecules to create a sensor. However, binding proteins with the desired properties are often not available in nature and substantial improvement to sensors can be required, particularly with regard to their durability. Ancestral protein reconstruction is a powerful protein-engineering tool able to generate highly stable and functional proteins. In this work, we sought to establish the utility of ancestral protein reconstruction to biosensor development, beginning with the construction of an l-arginine biosensor. l-arginine, as the immediate precursor to nitric oxide, is an important molecule in many physiological contexts including brain function. Using a combination of ancestral reconstruction and circular permutation, we constructed a Förster resonance energy transfer (FRET) biosensor for l-arginine (cpFLIPR). cpFLIPR displays high sensitivity and specificity, with a K_d of ∼14 µM and a maximal dynamic range of 35%. Importantly, cpFLIPR was highly robust, enabling accurate l-arginine measurement at physiological temperatures. We established that cpFLIPR is compatible with two-photon excitation fluorescence microscopy and report l-arginine concentrations in brain tissue.     

Lack of support for the time‐dependent molecular evolution hypothesis

There is increasing momentum surrounding the hypothesis that rates of molecular evolution between individuals within contemporary populations are high, and that these rates decrease as a function of time, perhaps over several millions of years, before reaching stationarity. The implications of this are powerful, potentially reshaping our view of how climate history impacts upon both species distribution patterns and the geographic structuring of genetic variation within species. However, our assessment of the hypothesis reveals a lack of theoretical support and empirical evidence for hypothesized magnitudes of time‐dependent rates of molecular evolution, with much of the apparent rate changes coming from artefacts and biases inherent in the methods of rate estimation. Our assessment also reveals a problem with how serial sampling is implemented for mutation rate estimation using ancient DNA samples, rendering published estimates unreliable.