Mortality Patterns and Site Heterogeneity of Severe Malaria in African Children

Background

In this study we aimed to assess site heterogeneity of early, intermediate, and late mortality prediction in children with severe Plasmodium falciparum malaria in sub-Saharan Africa.

Methods

Medical records of 26,036 children admitted with severe Plasmodium falciparum malaria in six hospital research centers between December 2000 to May 2005 were analyzed. Demographic, clinical and laboratory data of children who died within 24 hours (early), between 24 and 47 hours (intermediate) and thereafter (48 hours or later, late mortality) were compared between groups and survivors.

Results

Overall mortality was 4·3% (N = 1,129). Median time to death varied across sites (P<0·001), ranging from 8h (3h–52h) in Lambaréné to 40h (10h–100h) in Kilifi. Fifty-eight percent of deaths occurred within 24 hours and intermediate and late mortality rate were 19% and 23%, respectively. Combining all sites, deep breathing, prostration and hypoglycemia were independent predictors for early, intermediate and late mortality (P<0·01). Site specific independent predictors for early death included prostration, coma and deep breathing at all sites (P<0·001). Site specific independent predictors for intermediate and late death largely varied between sites (P<0·001) and included between 1 and 7 different clinical and laboratory variables.

Conclusion

Site heterogeneity for mortality prediction is evident in African children with severe malaria. Prediction for early mortality has the highest consistency between sites.     

Complex Genetic Effects on Early Vegetative Development Shape Resource Allocation Differences Between Arabidopsis lyrata Populations

Costs of reproduction due to resource allocation trade-offs have long been recognized as key forces in life history evolution, but little is known about their functional or genetic basis. Arabidopsis lyrata, a perennial relative of the annual model plant A. thaliana with a wide climatic distribution, has populations that are strongly diverged in resource allocation. In this study, we evaluated the genetic and functional basis for variation in resource allocation in a reciprocal transplant experiment, using four A. lyrata populations and F₂ progeny from a cross between North Carolina (NC) and Norway parents, which had the most divergent resource allocation patterns. Local alleles at quantitative trait loci (QTL) at a North Carolina field site increased reproductive output while reducing vegetative growth. These QTL had little overlap with flowering date QTL. Structural equation models incorporating QTL genotypes and traits indicated that resource allocation differences result primarily from QTL effects on early vegetative growth patterns, with cascading effects on later vegetative and reproductive development. At a Norway field site, North Carolina alleles at some of the same QTL regions reduced survival and reproductive output components, but these effects were not associated with resource allocation trade-offs in the Norway environment. Our results indicate that resource allocation in perennial plants may involve important adaptive mechanisms largely independent of flowering time. Moreover, the contributions of resource allocation QTL to local adaptation appear to result from their effects on developmental timing and its interaction with environmental constraints, and not from simple models of reproductive costs.     

Generalised Extreme Value Distributions Provide a Natural Hypothesis for the Shape of Seed Mass Distributions

Among co-occurring species, values for functionally important plant traits span orders of magnitude, are uni-modal, and generally positively skewed. Such data are usually log-transformed “for normality” but no convincing mechanistic explanation for a log-normal expectation exists. Here we propose a hypothesis for the distribution of seed masses based on generalised extreme value distributions (GEVs), a class of probability distributions used in climatology to characterise the impact of event magnitudes and frequencies; events that impose strong directional selection on biological traits. In tests involving datasets from 34 locations across the globe, GEVs described log10 seed mass distributions as well or better than conventional normalising statistics in 79% of cases, and revealed a systematic tendency for an overabundance of small seed sizes associated with low latitudes. GEVs characterise disturbance events experienced in a location to which individual species’ life histories could respond, providing a natural, biological explanation for trait expression that is lacking from all previous hypotheses attempting to describe trait distributions in multispecies assemblages. We suggest that GEVs could provide a mechanistic explanation for plant trait distributions and potentially link biology and climatology under a single paradigm.     

Patterns in the Evolution of Ungulate Jaw Shape

A survey of biomechanically significant aspects of the jaw apparatusin 13 orders of recent and fossil ungulates indicates that anexpanded angular process evolved independently at least 12 times.Temporal fossa size is reduced inmost ungulatesof modern aspect,but not in many early ungulates. Expansion of the masseter andinternal pterygoid musculature (inferred from the expanded angularprocess) may represent an adaptation for enhanced control ofgrinding action in mastication.     

Coevolution of Quantum and Classical Strategies on Evolving Random Networks

We study the coevolution of quantum and classical strategies on weighted and directed random networks in the realm of the prisoner’s dilemma game. During the evolution, agents can break and rewire their links with the aim of maximizing payoffs, and they can also adjust the weights to indicate preferences, either positive or negative, towards their neighbors. The network structure itself is thus also subject to evolution. Importantly, the directionality of links does not affect the accumulation of payoffs nor the strategy transfers, but serves only to designate the owner of each particular link and with it the right to adjust the link as needed. We show that quantum strategies outperform classical strategies, and that the critical temptation to defect at which cooperative behavior can be maintained rises, if the network structure is updated frequently. Punishing neighbors by reducing the weights of their links also plays an important role in maintaining cooperation under adverse conditions. We find that the self-organization of the initially random network structure, driven by the evolutionary competition between quantum and classical strategies, leads to the spontaneous emergence of small average path length and a large clustering coefficient.     

Local Breast Cancer Spatial Patterning: A Tool for Community Health Resource Allocation to Address Local Disparities in Breast Cancer Mortality

Despite available demographic data on the factors that contribute to breast cancer mortality in large population datasets, local patterns are often overlooked. Such local information could provide a valuable metric by which regional community health resources can be allocated to reduce breast cancer mortality. We used national and statewide datasets to assess geographical distribution of breast cancer mortality rates and known risk factors influencing breast cancer mortality in middle Tennessee. Each county in middle Tennessee, and each ZIP code within metropolitan Davidson County, was scored for risk factor prevalence and assigned quartile scores that were used as a metric to identify geographic areas of need. While breast cancer mortality often correlated with age and incidence, geographic areas were identified in which breast cancer mortality rates did not correlate with age and incidence, but correlated with additional risk factors, such as mammography screening and socioeconomic status. Geographical variability in specific risk factors was evident, demonstrating the utility of this approach to identify local areas of risk. This method revealed local patterns in breast cancer mortality that might otherwise be overlooked in a more broadly based analysis. Our data suggest that understanding the geographic distribution of breast cancer mortality, and the distribution of risk factors that contribute to breast cancer mortality, will not only identify communities with the greatest need of support, but will identify the types of resources that would provide the most benefit to reduce breast cancer mortality in the community.     

Sources and Patterns of Wolverine Mortality in Western Montana

ABSTRACT We instrumented 36 wolverines (Gulo gulo) on 2 study areas in western Montana and one study area on the Idaho-Montana (USA) border: 14 (9 M, 5 F) on the Pioneer study area, 19 (11 M, 8 F) on the Glacier study area, and 3 (2 M, 1 F) on the Clearwater study area. During 2002–2005, harvest from licensed trapping accounted for 9 (6 M, 3 F) of 14 mortalities, including individuals from all 3 study areas. Based on Akaike's Information Criterion adjusted for small sample sizes (AIC_c) rankings of 8 a priori models, a trapping model and a trapping-by-sex interaction model were equally supported (ΔAIC_c < 2) in explaining wolverine survival. Estimated annual survival was 0.80 when we did not consider harvest, whereas additive mortality from harvest reduced annual survival to 0.57. Glacier National Park in the Glacier study area provided some refuge as evidenced by an annual survival rate of 0.77 compared to 0.51 for the Pioneer Mountain study area. We incorporated these survival rates into a simple Lefkovitch stage-based model to examine rates of population change. The finite rate of population change (Λ) for the Glacier study area was 1.1, indicating a stable to slightly increasing population, whereas Λ for the Pioneer study area was 0.7, indicating a 30% annual population decrease during our study. Changes in Λ for both study areas were most sensitive to adult survival. In 2004, we used a Lincoln Index to estimate that 12.8 ± 2.9 (95% CI) wolverines resided in the 4 mountain ranges comprising the Pioneer study area, suggesting that small, island ranges in western Montana supported few individuals. Our results suggest that if wolverines are harvested, they should be managed within individual mountain ranges or small groupings of mountain ranges to limit mortality to within biologically defined limits in recognition of the increased vulnerabilities owing to low fecundity and low population numbers in small mountain ranges. We found that refugia, such as Glacier National Park, were important by reducing trap mortality and providing immigrants to the surrounding population, but even large parks were inadequate to provide complete protection to wolverines from trapping as they ranged outside park borders.     

A Maximum Likelihood Estimator for Shape Parameters of S‐Distributions

The S‐distribution is a four‐parameter distribution that is defined in terms of a differential equation, in which the cumulative is represented as the dependent variable: The article proposes a maximum likelihood estimator for the shape parameters of this distribution.     

基于资源异质性的四川省医师资源公平性研究

目的 基于医师资源异质性假设对2008—2014年四川省医师资源配置公平性进行探讨研究,为进一步优化医师资源配置提供参考。方法 在对医师数量调整的基础上,运用基尼系数和密度指数从人口、地理和经济3个维度评价医师资源配置的公平性。结果 基层医疗机构医师占比逐年下降;四川省卫生资源密度指数高于全国;调整后,按人口和按地理分布的基尼系数值均变大,表明医师素质差异会影响医师资源配置的人口和地理公平性;而受经济分布的影响较小。结论 在医师资源配置中需考虑医师的素质差异,同时兼顾地理和经济因素。     

Resource Allocation and the Evolution of Self-Fertilization in Plants

This article develops a simple evolutionarily stable strategy (ESS) model of resource allocation in partially selfing plants, which incorporates reproductive and sex allocation into a single framework. The analysis shows that, if female fitness gain increases linearly with resource investment, total reproductive allocation is not affected by sex allocation, defined as the fraction of reproductive resources allocated to male function. All else being equal, the ESS total reproductive allocation increases with increasing selfing rate if the fitness of selfed progeny is more than half that of outcrossed progeny, while the ESS sex allocation is always a decreasing function of the selfing rate. Self-fertilization is much more common in annual than in perennial plants, and this association has been commonly interpreted in terms of an effect of life history on mating system. The model in this article shows that self-fertilization can itself cause the evolution of the annual habit. Incorporating the effects of pollen discounting may not have any influence on total reproductive allocation if female fitness gain is a linear function of resource investment, although the evolutionarily stable sex allocation is altered. Evolution of the selfing rate is found to be independent of reproductive and sex allocation under the mass-action assumption that self- and outcross pollen are deposited simultaneously on receptive stigmas and compete for access to ovules.     

试论大型公立医院内部资源配置的优化

当前我国大型公立医院内部资源配置模式存在的弊端主要表现为存在趋利性和粗放性,不适应外部政策导向和自身发展需求。优化内部资源配置是优化运行机制的基础,针对大型公立医院内部资源配置存在的问题结合其资源的特点,从创新发展战略、创新体制机制、加强知识资源管理和对资源科学利用方式探索等方面对优化大型公立医院内部资源配置的相关路径进行探讨并提出相关政策建议。     

Evolution of the Selfing Rate and Resource Allocation Models

Abstract First, evolutionary theories of selfing of terrestrial plants are reviewed briefly. The evolution of the selfing rate is controlled mainly by (1) the benefit of enhanced genetic relatedness to seeds and (2) the cost of lowered fitness of selfed offspring (inbreeding depression), being modified by (3) fertility assurance under pollen limitation, (4) reduced performance as pollen donor, (5) reduced expenditure to male function, and (6) lowered genetic recombination. Models of the joint evolution of selfing and inbreeding depression predict either strong outcrossing or predominant selfing. Although wind-pollinated plants fit the prediction, some animal-pollinated species have intermediate selfing rates, refuting the theory.
Second, three resource allocation models are analyzed, in which an individual plant optimally allocates limited resources to outcrossed seeds, selfed seeds, and to energy reserves for the next year. The first model explains how the number of outcrossed and selfed offspring change with plant size when they differ in dispersal distance. The second model predicts that, in a disturbed habitat, the plant is likely to be annual and to produce both selfed and outcrossed seeds; in contrast, in a stable habitat, the plant tends to be perennial and to abort selfed seeds selectively. Hand pollination may increase seed production for perennials but not for annuals. The third model explains the observed difference between animal and wind pollinated plants in the out-crossing rate pattern by the difference in the way pollen acquisition increases with investment.     

Compositional Heterogeneity and Patterns of Molecular Evolution in the Drosophila Genome

The rates and patterns of molecular evolution in many eukaryotic organisms have been shown to be influenced by the compartmentalization of their genomes into fractions of distinct base composition and mutational properties. We have examined the Drosophila genome to explore relationships between the nucleotide content of large chromosomal segments and the base composition and rate of evolution of genes within those segments. Direct determination of the G + C contents of yeast artificial chromosome clones containing inserts of Drosophila melanogaster DNA ranging from 140-340 kb revealed significant heterogeneity in base composition. The G + C content of the large segments studied ranged from 36.9% G + C for a clone containing the hunchback locus in polytene region 85, to 50.9% G + C for a clone that includes the rosy region in polytene region 87. Unlike other organisms, however, there was no significant correlation between the base composition of large chromosomal regions and the base composition at fourfold degenerate nucleotide sites of genes encompassed within those regions. Despite the situation seen in mammals, there was also no significant association between base composition and rate of nucleotide substitution. These results suggest that nucleotide sequence evolution in Drosophila differs from that of many vertebrates and does not reflect distinct mutational biases, as a function of base composition, in different genomic regions. Significant negative correlations between codon-usage bias and rates of synonymous site divergence, however, provide strong support for an argument that selection among alternative codons may be a major contributor to variability in evolutionary rates within Drosophila genomes.     

Competition and the Effect of Spatial Resource Heterogeneity on Evolutionary Diversification

A model is presented to explore how the form of selection arising from competition for resources is affected by spatial resource heterogeneity. The model consists of a single species occupying two patches connected by migration, where the two patches can differ in the type of resources that they contain. The main goal is to determine the conditions under which competition for resources results in disruptive selection (i.e., selection favoring a polymorphism) since it is this form of selection that will give rise to the evolutionary diversification of resource exploitation strategies. In particular, comparing the conditions giving rise to disruptive selection when the two patches are identical to the conditions when they contain different resources reveals the effect of spatial resource heterogeneity. Results show that when the patches are identical, the conditions giving rise to disruptive selection are identical to those that give rise to character displacement in previous models. When the patches are different, the conditions giving rise to disruptive selection can be either more or less stringent depending upon demographic parameters such as the intrinsic rate of increase and the migration rate. Surprisingly, spatial resource heterogeneity can actually make forms of evolutionary diversification such as character displacement less likely. It is also found that results are dependent on how the resource exploitation strategies and the spatial resource heterogeneity affect the population dynamics. One robust conclusion however, is that spatial resource heterogeneity always has a disruptive effect when the migration rate between patches is low.     

Heterogeneity in Individual Mortality Risk and Its Importance for Evolutionary Studies of Senescence

Mortality was simulated under the assumption of heterogeneity in individual age-specific mortality risk. Heterogeneity was modeled by assigning each individual its own Gompertz mortality function. Means and variances of the Gompertz intercept and slope parameters were based on published data for Drosophila melanogaster. Simulations of large cohorts reproduced mortality plateaus similar to those observed for actual cohorts of flies. Catastrophic late-age mortality was not observed except when heterogeneity was very low and rates of senescence were very high. A second set of simulations was designed to mimic experiments that have investigated age-specific patterns of genetic variance in mortality rates. Within-genotype heterogeneity in mortality risk resulted in a decline in genetic variance of mortality rates at old ages. That result suggests that the decline in genetic variance at old ages that has been observed in some experiments is an artifact of heterogeneity. Mortality rate plateaus, decrease in genetic variance of mortality rates at old ages, and absence of catastrophic late-age mortality all appear to contradict predictions of the evolutionary theory of senescence. Heterogeneity in mortality risk may explain those contradictions.     

依法推进医疗卫生资源优化配置战略的实施

文章以依法推进我国医疗卫生资源优化配置为主线,分别从依法明确公立医院功能定位,依法规划公立医院的规模、数量与布局,依法建立以人为中心的医疗卫生系统,依法充分发挥社会办医的作用,以及依法推进医疗卫生资源配置规划的编制与实施五个方面论述了资源配置战略,旨在为制订好“十三五”期间公立医院规模、数量与布局的规划提供了理论支撑。     

Effects of Resource Allocation on Behavioural Strategies: A Comparison of Red Junglefowl (Gallus gallus) and Two Domesticated Breeds of Poultry

Three different breeds of poultry, representing different degrees of domestication, were observed in semi-natural conditions in order to study differences in foraging behaviour, activity levels and social behaviours which could be caused by correlated responses to selection for increased production. The breeds used were: (i) red junglefowl ( Gallus gallus ); (ii) Swedish bantam, which is a domestic breed that has not undergone selection for production traits; and (iii) Hy-Line, a White leghorn laying hybrid, selected mainly for food conversion efficiency. The birds were offered ad libitum food simultaneously from sites where the food was freely available and from sites where the birds had to search and scratch for food which was mixed with wood-shavings. The behaviour was observed three times per day (48 min/d), 3 d per week in eight groups (four birds per group) of each breed between 7 and 18 wks of age. Junglefowl and bantam obtained a significantly higher proportion of their food from the site that required effort. The opposite case was true for the Hy-Line. Overall, bantams performed significantly more foraging behaviour than Hy-Lines. The Hy-Line breed was more inactive and less involved in social interactions than the junglefowl and the bantam. The results support the idea that selection for high production results in modified behavioural strategies. Behaviours that are of high energetic cost, such as extensive foraging and social interactions, were of lower in frequency in the laying hens compared to junglefowl and bantam, allowing the laying hens to save energy that can be reallocated to production traits.     

资源异质性环境中三种匍匐茎草本植物克隆内资源共享和分株功能特化

研究了3种来自中国北方林下、草地和碱化草甸匍匐茎型克隆草本植物绢毛匍匐委陵菜 (Potentilla reptans L. var. sericophylla Franch.)、鹅绒委陵菜 (P. anserina L.) 和金戴戴 (Halerpestes ruthenica (Jacq.) Qvcz.) 对由高光照低养分斑块和低光照高养分斑块组成的资源交互斑块性生境的适应性对策.当生长于高光照低养分条件下分株 (HL分株) 与生长于低光照高养分条件下分株 (LH分株) 之间的匍匐茎连接时, 3种克隆植物HL分株、LH分株以及整个分株对系统 (HL分株 + LH分株) 的生物量均得到显著提高.同时, LH分株根冠比显著增加, 而HL分株根冠比显著下降.这表明, 当互连分株置于由低光照高养分斑块和高光照低养分斑块组成的异质性环境中时, 3种植物克隆分株均发生了环境诱导的功能特化.克隆内资源共享以及克隆内不同分株的功能特化有利于整个分株系统对局部丰富资源的获取, 从而能够缓解资源交互斑块性生境对克隆植物的不利影响.