Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy

Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case-control sample, the low-producing lymphotoxin-alpha (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases.     

A hierarchical multiple criteria model for eliciting relative preferences in conflict situations

A multiple criteria decision analysis(MCDA) approach is designed for capturing the relative preference information of a decision maker involved in a conflict.More specifically,an MCDA approach based on the outranking method,ELECTRE III,is employed for ranking states or possible scenarios in the conflict from most to least preferred,where ties are allowed,for a decision maker according to his or her value system.To demonstrate how this preference elicitation methodology can be conveniently implemented in practice within the framework of the Graph Model for Conflict Resolution,it is applied to a real world water supply crisis which occurred in the town of North Battleford,located in the Canadian province of Saskatchewan.     

射频仿真系统的误差分析与可信度评估研究

首次将统计方法应用于射频仿真系统的可靠性分析中，总结出其应采用的一般方法。采用Grubbs准则对校准系统测得的实验数据中的粗大数据进行滤除，接着分别采用数据比较法和阿贝检验法对定值和变值两种系统误差是否显著进行检验，如果系统误差显著，则应采用实验比对的方法消除之，使随机性成为数据的主导因素。采用x^2-分析法确定数据概率分布，对合格区间进行概率密度的积分以确定可信度。这种方法易于通过编程实现，并由校准系统自动完成可信度评估。给出了它的算法描述与应用效果实例。     

Helmholtz's Kant revisited (Once more). The all-pervasive nature of Helmholtz's struggle with Kant's Anschauung

In this analysis, the classical problem of Hermann von Helmholtz's (1821–1894) Kantianism is explored from a particular vantage point, that to my knowledge, has not received the attention it deserves notwithstanding its possible key role in disentangling Helmholtz's relation to Kant's critical project. More particularly, we will focus on Helmholtz's critical engagement with Kant's concept of intuition [Anschauung] and (the related issue of) his dissatisfaction with Kant's doctrinal dualism. In doing so, it soon becomes clear that both (i) crucially mediated Helmholtz's idiosyncratic appropriation and criticism of (certain aspects of) Kant's critical project, and (ii) can be considered as a common denominator in a variety of issues that are usually addressed separately under the general header of (the problem of) Helmholtz's Kantianism. The perspective offered in this analysis can not only shed interesting new light on some interpretive issues that have become commonplace in discussions on Helmholtz's Kantianism, but also offers a particular way of connecting seemingly unrelated dimensions of Helmholtz's engagement with Kant's critical project (e.g. Helmholtz's views on causality and space). Furthermore, it amounts to the rather surprising conclusion that Helmholtz's most drastic revision of Kant's project pertains to his assumption of free will as a formal condition of experience and knowledge.     

Common variants near MC4R are associated with fat mass, weight and risk of obesity

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.     

Heterogeneous Forecast Adjustment

There is ample empirical evidence that expert‐adjusted model forecasts can be improved. One way to potential improvement concerns providing various forms of feedback to the sales forecasters. It is also often recognized that the experts (forecasters) might not constitute a homogeneous group. This paper provides a data‐based methodology to discern latent clusters of forecasters, and applies it to a fully new large database with data on expert‐adjusted forecasts, model forecasts and realizations. For the data at hand, two clusters can clearly be identified. Next, the consequences of having clusters are discussed. Copyright © 2016 John Wiley & Sons, Ltd.