Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics

Club Enlargement: Early Versus Late Admittance

We develop an incomplete contract model to analyse the enlargement strategy of a club. An applicant is characterized by his wealth and the degree of conformity with the club standard. The club gains only from a fully reformed new member, but reform is costly. The club chooses between early admittance, where it can enforce reform through its partial control power, and late admittance, where entry is conditional on completed reform. Under the optimal enlargement strategy of the club, wealthy applicants pay an entrance fee and enter early, and poor applicants enter in reversed order: A less advanced member is admitted early, and a more advanced one, late. Moreover, poor applicants extract rents that increase in the ratio of reform distance to wealth. If the club can impose a deadline for late entry, it can eliminate all rents with stage financing. In the dynamic game, renegotiation undermines the viability of the late admittance strategy. In the finite game, the applicant's rent from a late offer is non-monotonic in his reform distance and the ability to deteriorate his reform status strategically need not be detrimental to the club.Club Theory; Governance; Incomplete Contracts; Reform Incentives

Skin Health in Dance Focusing on Professional Dance and Latin American Formation Dance during Periods of Different Training Loads

Up to the present, there has been a lack of studies on the skin health of professional and recreational dancers. Dancers are at risk of skin diseases due to contact with allergenic or irritating substances and working in humid environments. The aim of the present study was, therefore, to examine skin health in two different dance styles and training periods. Methods: Physical dermatological examination of professional dancers (PD; n = 35) and Latin American formation dancers (LD; n = 79) after a 4-week period of recovery (T0) and a period of high training or work load (T1). Results: PD are significantly more frequently affected by skin dermatoses than LD (T0, p = 0.004) (frontal traction alopecia, hair loss, facial seborrhoea, xerosis cutis of the trunk and extremities, and facial folliculitis). The following significant differences between the sexes were observed in the LD: more folliculitis of the trunk in male subjects (T0 and T1, p = 0.009), more frequent xerosis cutis of the extremities (p < 0.001) and perioral dermatitis in female subjects (T1, p = 0.043). Subjects with skin lesions trained more frequently, performed more times per year, and had longer dance experience. Discussion: Based on the findings, preventive measures for skin protection (especially informing dancers about skin health) are necessary. At the same time, further studies on this topic are important

LAS ENTRAÑAS DEL PODER: UNA AUTOPSIA MICHOACANA DEL SIGLO XVIII

\u3cp\u3eIdentifying player motivations such as curiosity could help game designers analyze player profiles and substantially improve game design. However, research on player profiling focuses on generalized personality traits, not specific aspects of motivation. This study examines how player behaviour indicates constructs of curiosity-related motivation. It contributes a more discriminating operationalization of game-related curiosity. We derive a curiosity measure from established self-report survey methodologies relating to social capital, behavioural activation, obsessive/harmonious passion, and BrainHex player types. We present the results of a cross-sectional study with data from 1,745 players of Destiny - A popular shared-world first-person shooter (FPS) game. Behaviour metrics were paired with four curiosity factors: 'social' curiosity, 'sensory/cognitive' curiosity, 'novelty-seeking' curiosity, and 'explorative' curiosity. Our findings provide key insights into the relationships between players curiosity and their in-game behaviour. We infer curiosity-related motivational profiles from behaviour metrics, and discuss how this may impact game design and player-computer interaction.\u3c/p\u3