Women\u27s Professional Sports: A Case Study on Practices that Could Increase Their Profitability

Women’s professional sports leagues have often been considered a risky business endeavor. Critics cite low attendance, lack of sponsorships, lack of media rights deals, and numerous other reasons for why women’s professional sports leagues are not profitable. In analyzing the current landscape of women’s professional sport leagues, this paper uses a case study approach to develop a strategy that will highlight lessons learned from past women’s professional sports leagues, current professional sports leagues, sponsorship agreements, fans, social, digital, and mobile marketing strategies, and management practices to show how the business of women’s sports could be made into a more profitable endeavor

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Artificial intelligence for dementia—applied models and digital health

The use of applied modelling in dementia risk prediction, diagnosis, and prognostics will have substantial public health benefit, particularly as ‘deep phenotyping’ cohorts with multi-omics health data become available. This narrative review synthesizes understanding of applied models and digital health technologies, in terms of dementia risk prediction, diagnostic discrimination, prognosis and progression. Machine learning approaches show evidence of improved predictive power compared to standard clinical risk-scores in predicting dementia, and the potential to decompose large numbers of variables into relatively few critical predictors. This review focusses on key areas of emerging promise including: emphasis on easier, more transparent data sharing and cohort access, integration of high-throughput biomarker and electronic health record data into modelling, and progressing beyond primary prediction of dementia to secondary outcomes e.g., treatment response and physical health. Such approaches will benefit also from improvements in remote data measurement, whether cognitive (e.g. online), or naturalistic (e.g. watch-based accelerometry).This paper was the product of a DEMON Network state of the science symposium entitled “Harnessing Data Science and AI in Dementia Research” funded by Alzheimer’s Research UK. AK is supported in part by the NIHR AI Award (AI_AWARD02183). CL is funded by Alzheimer’s Society and Alzheimer’s Research UK. ELH is supported by the Cambridge British Heart Foundation Centre of Research Excellence (RE/18/1/34212). MHI is supported by the UK Research and Innovation-funded DATAMIND project (MR/W014386/1). ET (National Institute for Health Research (NIHR) Clinical Lectureship) is funded by the NIHR. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care. JMR and DJL are supported by Alzheimer’s Research UK and the Alan Turing Institute/Engineering and Physical Sciences Research Council (EP/N510129/1). DJL also receives funding from the Medical Research Council (MR/X005674/1), National Institute for Health Research (NIHR) Applied Research Collaboration South West Peninsula, National Health and Medical Research Council (NHMRC), and National Institute on Aging/National Institutes of Health (RF1AG055654)

Artificial intelligence for dementia-Applied models and digital health.

INTRODUCTION: The use of applied modeling in dementia risk prediction, diagnosis, and prognostics will have substantial public health benefits, particularly as "deep phenotyping" cohorts with multi-omics health data become available. METHODS: This narrative review synthesizes understanding of applied models and digital health technologies, in terms of dementia risk prediction, diagnostic discrimination, prognosis, and progression. Machine learning approaches show evidence of improved predictive power compared to standard clinical risk scores in predicting dementia, and the potential to decompose large numbers of variables into relatively few critical predictors. RESULTS: This review focuses on key areas of emerging promise including: emphasis on easier, more transparent data sharing and cohort access; integration of high-throughput biomarker and electronic health record data into modeling; and progressing beyond the primary prediction of dementia to secondary outcomes, for example, treatment response and physical health. DISCUSSION: Such approaches will benefit also from improvements in remote data measurement, whether cognitive (e.g., online), or naturalistic (e.g., watch-based accelerometry).This paper was the product of a DEMON Network state of the science symposium entitled “Harnessing Data Science and AI in Dementia Research” funded by Alzheimer’s Research UK. AK is supported in part by the NIHR AI Award (AI_AWARD02183). CL is funded by Alzheimer’s Society and Alzheimer’s Research UK. ELH is supported by the Cambridge British Heart Foundation Centre of Research Excellence (RE/18/1/34212). MHI is supported by the UK Research and Innovation-funded DATAMIND project (MR/W014386/1). ET (National Institute for Health Research (NIHR) Clinical Lectureship) is funded by the NIHR. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care. JMR and DJL are supported by Alzheimer’s Research UK and the Alan Turing Institute/Engineering and Physical Sciences Research Council (EP/N510129/1). DJL also receives funding from the Medical Research Council (MR/X005674/1), National Institute for Health Research (NIHR) Applied Research Collaboration South West Peninsula, National Health and Medical Research Council (NHMRC), and National Institute on Aging/National Institutes of Health (RF1AG055654)

Artificial intelligence for dementia - applied models and digital health

No abstract available