Symmetry is related to sexual dimorphism in faces: data across culture and species

BACKGROUND: Many animals both display and assess multiple signals. Two prominently studied traits are symmetry and sexual dimorphism, which, for many animals, are proposed cues to heritable fitness benefits. These traits are associated with other potential benefits, such as fertility. In humans, the face has been extensively studied in terms of attractiveness. Faces have the potential to be advertisements of mate quality and both symmetry and sexual dimorphism have been linked to the attractiveness of human face shape. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that measurements of symmetry and sexual dimorphism from faces are related in humans, both in Europeans and African hunter-gatherers, and in a non-human primate. Using human judges, symmetry measurements were also related to perceived sexual dimorphism. In all samples, symmetric males had more masculine facial proportions and symmetric females had more feminine facial proportions. CONCLUSIONS/SIGNIFICANCE: Our findings support the claim that sexual dimorphism and symmetry in faces are signals advertising quality by providing evidence that there must be a biological mechanism linking the two traits during development. Such data also suggests that the signalling properties of faces are universal across human populations and are potentially phylogenetically old in primates

Identifying key health system components associated with improved outcomes to inform the reconfiguration of services for adults with rare autoimmune rheumatic diseases : a mixed methods study.

Open Access via the Elsevier agreementPeer reviewe

Targeted Physical Therapy Combined with Spasticity Management Changes Motor Development Trajectory for a 2- Year-Old with Cerebral Palsy

Therapies for children with cerebral palsy (CP) often fail to address essential components of early rehabilitation: intensity, child initiation, and an embodied approach. Sitting Together And Reaching To Play (START-Play) addresses these issues while incorporating intensive family involvement to maximize therapeutic dosage. While START-Play was developed and tested on children aged 7–16 months with motor delays, the theoretical construct can be applied to intervention in children of broader ages and skills levels. This study quantifies the impact of a broader STARTPlay intervention combined with Botulinum toxin-A (BoNT-A) and phenol on the developmental trajectory of a 24 month-old child with bilateral spastic CP. In this AB +1 study, A consisted of multiple baseline assessments with the Gross Motor Function Measure-66 and the Assessment of Problem Solving in Play. The research participant demonstrated a stable baseline during A and changes in response to the combination of BoNT-A/phenol and 12 START-Play sessions during B, surpassing the minimal clinically important difference on the Gross Motor Function Measure-66. The followup data point (+1) was completed after a second round of BoNT-A/phenol injections. While the findings suggest the participant improved his gross motor skills with BoNT-A/phenol and STARTPlay, further research is needed to generalize these findings

Identifying key health system components associated with improved outcomes to inform the reconfiguration of services for adults with rare autoimmune rheumatic diseases: a mixed methods study

Background Adults with rare autoimmune rheumatic diseases face unique challenges and struggles to navigate health-care systems designed to manage common conditions. Evidence to inform an optimal service framework for their care is scarce. Using systemic vasculitis as an exemplar, we aimed to identify and explain the key service components underpinning effective care for rare diseases. Methods In this mixed-methods study, data were collected as part of a survey of vasculitis service providers across the UK and Ireland, interviews with patients, and from organisational case studies to identify key service components that enable good care. The association between these components and patient outcomes (eg, serious infections, mortality) and provider outcomes (eg, emergency hospital admissions) were examined in a population-based data linkage study using routine health-care data obtained from patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis from national health datasets in Scotland. We did univariable and multivariable analyses using Bayesian poisson and negative binomial regression to estimate incident rate ratios (IRRs), and Cox proportional hazards models to estimate hazard ratios (HRs). People with lived experiences were involved in the research and writing process. Findings Good care was characterised by service components that supported timely access to services, integrated care, and expertise. In 1420 patients with ANCA-associated vasculitis identified from national health datasets, service-reported average waiting times for new patients of less than 1 week were associated with fewer serious infections (IRR 0·70 [95% credibility interval 0·55–0·88]) and fewer emergency hospital admissions (0·78 [0·68–0·92]). Nurse-led advice lines were associated with fewer serious infections (0·76 [0·58–0·93]) and fewer emergency hospital admissions (0·85 [0·74–0·96]). Average waiting times for new patients of less than 1 week were also associated with reduced mortality (HR 0·59 [95% credibility interval 0·37–0·93]). Cohorted clinics, nurse-led clinics, and specialist vasculitis multi-disciplinary team meetings were associated with fewer serious infections (IRR 0·75 [0·59–0·96] for cohorted clinics; 0·65 [0·39–0·84] for nurse-led clinics; 0·72 [0·57–0·90] for specialist vasculitis multi-disciplinary team meetings) and emergency hospital admissions (0·81 [0·71–0·91]; 0·75 [0·65–0·94]; 0·86 [0·75–0·96]). Key components were characterised by their ability to overcome professional tensions between specialties. Interpretation Key service components associated with important health outcomes and underpinning factors were identified to inform initiatives to improve the design, delivery, and effectiveness of health-care models for rare autoimmune rheumatic diseases

Charlson index scores from administrative data and case-note review compared favourably in a renal disease cohort

Background: The Charlson index is a widely used measure of comorbidity. The objective was to compare Charlson index scores calculated using administrative data to those calculated using case-note review (CNR) in relation to all-cause mortality and initiation of renal replacement therapy (RRT) in the Grampian Laboratory Outcomes Mortality and Morbidity Study (GLOMMS-1) chronic kidney disease cohort. Methods: Modified Charlson index scores were calculated using both data sources in the GLOMMS-1 cohort. Agreement between scores was assessed using the weighted Kappa. The association with outcomes was assessed using Poisson regression, and the performance of each was compared using net reclassification improvement. Results: Of 3382 individuals, median age 78.5 years, 56% female, there was moderate agreement between scores derived from the two data sources (weighted kappa 0.41). Both scores were associated with mortality independent of a number of confounding factors. Administrative data Charlson scores were more strongly associated with death than CNR scores using net reclassification improvement. Neither score was associated with commencing RRT. Conclusion: Despite only moderate agreement, modified Charlson index scores from both data sources were associated with mortality. Neither was associated with commencing RRT. Administrative data compared favourably and may be superior to CNR when used in the Charlson index to predict mortality

Development of Risk Prediction Equations for Incident Chronic Kidney Disease

IMPORTANCE ‐ Early identification of individuals at elevated risk of developing chronic kidney disease  could improve clinical care through enhanced surveillance and better management of underlying health  conditions.  OBJECTIVE – To develop assessment tools to identify individuals at increased risk of chronic kidney  disease, defined by reduced estimated glomerular filtration rate (eGFR).  DESIGN, SETTING, AND PARTICIPANTS – Individual level data analysis of 34 multinational cohorts from  the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected  from April, 1970 through January, 2017. A two‐stage analysis was performed, with each study first  analyzed individually and summarized overall using a weighted average. Since clinical variables were  often differentially available by diabetes status, models were developed separately within participants  with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external  cohorts (N=2,253,540). EXPOSURE Demographic and clinical factors.  MAIN OUTCOMES AND MEASURES – Incident eGFR <60 ml/min/1.73 m2.  RESULTS – In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there were  660,856 incident cases of reduced eGFR during a mean follow‐up of 4.2 years. In 781,627 participants  with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean follow‐up of 3.9 years. Equations for the 5‐year risk of reduced eGFR included age, sex, ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participants  with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction  between the two. The risk equations had a median C statistic for the 5‐year predicted probability of  0.845 (25th – 75th percentile, 0.789‐0.890) in the cohorts without diabetes and 0.801 (25th – 75th percentile, 0.750‐0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%) study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was  similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. CONCLUSIONS AND RELEVANCE – Equations for predicting risk of incident chronic kidney disease developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination and  variable calibration in diverse populations

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk