Socially structured games

We generalize the concept of a cooperative non-transferable utility game by introducing a socially structured game. In a socially structured game every coalition of players can organize themselves according to one or more internal organizations to generate payoffs. Each admissible internal organization on a coalition yields a set of payoffs attainable by the members of this coalition. The strengths of the players within an internal organization depend on the structure of the internal organization and are represented by an exogenously given power vector. More powerful players have the power to take away payoffs of the less powerful players as long as those latter players are not able to guarantee their payoffs by forming a different internal organization within some coalition in which they have more power.we introduce the socially stable core as a solution concept that contains those payoffs that are both stable in an economic sense, i.e., belong to the core of the underlying cooperative game, and stable in a social sense, i.e., payoffs are sustained by a collection of internal organizations of coalitions for which power is distributed over all players in a balanced way. The socially stable core is a subset and therefore a refinement of the core. We show by means of examples that in many cases the socially stable core is a very small subset of the core.we will state conditions for which the socially stable core is non-empty. In order to derive this result, we formulate a new intersection theorem that generalizes the kkms intersection theorem. We also discuss the relationship between social stability and the wellknown concept of balancedness for ntu-games, a sufficient condition for non-emptiness of the core. In particular we give an example of a socially structured game that satisfies social stability and therefore has a non-empty core, but whose induced ntu-game does not satisfy balancedness in the general sense of billera

Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells

Wnt signalling proteins are essential for culture of human organ stem cells in organoids, but most Wnt protein formulations are poorly active in serum-free media. Here we show that purified Wnt3a protein is ineffective because it rapidly loses activity in culture media due to its hydrophobic nature, and its solubilization requires a detergent, CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate), that interferes with stem cell self-renewal. By stabilizing the Wnt3a protein using phospholipids and cholesterol as carriers, we address both problems: Wnt activity remains stable in serum-free media, while non-toxic carriers allow the use of high Wnt concentrations. Stabilized Wnt3a supports strongly increased self-renewal of organ and embryonic stem cells and the serum-free establishment of human organoids from healthy and diseased intestine and liver. Moreover, the lipophilicity of Wnt3a protein greatly facilitates its purification. Our findings remove a major obstacle impeding clinical applications of adult stem cells and offer advantages for all cell culture uses of Wnt3a protein

Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

Background So far, more than 170 loci have been associated with circulating lipid levels through genomewide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ~60 000 individuals in the discovery stage and ~90 000 samples in the replication stage. Results Our study resu

Association of Factor V Leiden with Subsequent Atherothrombotic Events:A GENIUS-CHD Study of Individual Participant Data

BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I2=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity. CONCLUSIONS: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Serum magnesium and calcium levels in relation to ischemic stroke : Mendelian randomization study

ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 7 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 7 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Cross-border cattle marketing in Sub-Saharan Africa since 1900. Geographical patterns and government induced change

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Astronomical forcing of Northwest African climate and glacial history during the late Messinian (6.5-5.5 Ma)

High-resolution physical, chemical and biological-based climate proxies from the Ain el Beida (AEB) section in Atlantic Morocco reveal the imprint of the three main orbital parameters precession (19–23 kyr), obliquity (41 kyr) and eccentricity (95–125 and 400 kyr) between 6.5 and 5.5 million years before present (Ma). The precession-related variations are most prominently reflected in the color reflectance and chemical composition of the sediment, showing that precession minimum configurations lead to more humid climate conditions in Northwest Africa probably related to the Atlantic system, while more arid climate conditions prevailed during precession maxima. In addition, precession-bound changes in planktonic foraminifera and calcareous nannofossil assemblages indicate that sea surface temperature (SST) increased during the humid phases, while productivity conditions increased during the dry periods. The clear imprint of the short and long-term eccentricity cycles is explained by a non-linear climatic response to the precession forcing with overall more humid climate conditions during eccentricity maxima. The obliquity-controlled variations in SST and aridity conditions concur with glacial–interglacial variability that is conspicuously recorded in both planktonic and benthic δ18O records of AEB. The observed warm and wet climates during interglacial periods most likely reflect the direct ice driven thermal response to the reduced ice sheets and more active Atlantic depressions. Similar as during the Pliocene and Pleistocene, obliquity-controlled variations in the planktonic and benthic carbon isotope (δ13C) records of AEB are inversely related to the oxygen isotope records with more depleted values during glacial stages, although with a small lag. The close correspondence between the δ13C records of AEB and other open ocean sites (i.e., Sites 982 and 926) may therefore point to large-scale glacial-controlled variations in the deep-sea carbon reservoir. Superimposed on the orbital variations, the imprint of the – onset of the – Messinian Salinity Crisis can be traced by a marked ~ 1.0‰ negative excursion in planktonic δ13C at 6.0 Ma, followed by a prominent peak in Ti/Al at ~ 5.97 M