The impact of free cash flow and dividend policy on stock abnormal returns.

Agency costs arise when both parties to a contract, under which there is delegation of authority for decision-making from the principal to the agent performing some service, are both utility-maximizers. Monitoring expenditures are incurred by the principal and bonding expenditures by the agent.Master of Business Administratio

Comparison of mental-physical comorbidity, risk of death and mortality among patients with mental disorders - a retrospective cohort study

Aim: To compare the risk of death, the prevalence of comorbid chronic physical illness and mortality among an Asian population of patients with mental disorders. Methods: This was a retrospective data analysing of medical records of patients with schizophrenia, depression, anxiety, bipolar disorder, alcohol use disorder (AUD) or substance use disorder and the comorbid chronic physical illnesses. The hazard risk of death was calculated with Cox regression and compared between patients with and without comorbid chronic physical illness(es). Odds ratios of specific comorbid chronic physical illness were calculated with logistic regression and mean crude death rate was calculated for patients with different mental disorders. Results: A total of 56,447 patients with mental disorders were included in the analysis. Compared to patients without comorbid physical illness, patients with mental-physical comorbidity were associated with a higher risk of death [2.36 (2.22–2.52); hazard ratio (95% CI)] and less estimated survival days [2157 (2142–2172) vs 2508 (2504–2513)]. Compared to other mental disorders, those with AUD had the highest prevalence of two or more comorbid chronic physical illnesses and associated with the highest odds of comorbid hypertension, diabetes mellitus, stroke, nephritis, chronic kidney disease, and cancer. The highest one-year crude death rate was similarly observed in patients with AUD. Conclusions: Mental-physical comorbidity was associated with a higher risk of death compared to patients with mental disorders only. The highest prevalence of mental-physical comorbidity and mortality were observed in patients with AUD. More attention and resources may be needed to tackle the burden of AUD

A five-safes approach to a secure and scalable genomics data repository

Summary: Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud. Additionally, regulators are mandating data access patterns and specific security protocols for the storage and use of genomic data. While CSP provides tools for security and regulatory compliance, building the necessary controls required for cloud solutions is not trivial. Research Assets Provisioning and Tracking Online Repository (RAPTOR) by the Genome Institute of Singapore is a cloud-native genomics data repository and analytics platform that implements a “five-safes” framework to provide security and governance controls to data contributors and users, leveraging CSP for sharing and analysis of genomic datasets without the risk of security breaches or running afoul of regulations

Analysis of clinically relevant variants from ancestrally diverse Asian genomes.

10.1038/s41467-022-34116-9Nat Commun1316694

The Singapore national precision medicine strategy

Precision medicine promises to transform healthcare for groups and individuals through early disease detection, refining diagnoses and tailoring treatments. Analysis of large-scale genomic-phenotypic databases is a critical enabler of precision medicine. Although Asia is home to 60% of the world's population, many Asian ancestries are under-represented in existing databases, leading to missed opportunities for new discoveries, particularly for diseases most relevant for these populations. The Singapore National Precision Medicine initiative is a whole-of-government 10-year initiative aiming to generate precision medicine data of up to one million individuals, integrating genomic, lifestyle, health, social and environmental data. Beyond technologies, routine adoption of precision medicine in clinical practice requires social, ethical, legal and regulatory barriers to be addressed. Identifying driver use cases in which precision medicine results in standardized changes to clinical workflows or improvements in population health, coupled with health economic analysis to demonstrate value-based healthcare, is a vital prerequisite for responsible health system adoption.Agency for Science, Technology and Research (A*STAR)Ministry of Health (MOH)National Medical Research Council (NMRC)National Research Foundation (NRF)We thank all investigators, staf members and study participants of the contributing cohorts and studies: (1) the HELIOS study at the Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; (2) the GUSTO study jointly hosted by the National University Hospital, KK Women’s and Children’s Hospital, the National University of Singapore and the Singapore Institute for Clinical Sciences, the Agency for Science Technology and Research (A*STAR); (3) the SEED cohort at the Singapore Eye Research Institute; (4) the MEC, National University of Singapore; (5) the PRISM cohort; and (6) the TTSH Personalised Medicine Normal Controls cohort. We also thank the National Supercomputing Centre, Singapore (https://www.ncss.sg) for computation resources. The SG10K_Health project is funded by the Industry Alignment Fund (Pre-Positioning) (IAF-PP, H17/01/a0/007); the project made use of participating study cohorts supported by the following funding sources: (1) the HELIOS study by grants from a Strategic Initiative at Lee Kong Chian School of Medicine, the Singapore MOH under its Singapore Translational Research Investigator Award (NMRC/STaR/0028/2017) and the IAF-PP (H18/01/a0/016); (2) the GUSTO study by the Singapore National Research Foundation under its Translational and Clinical Research Flagship Program and administered by the Singapore MOH’s National Medical Research Council Singapore (NMRC/TCR/004-NUS/2008, NMRC/ TCR/012-NUHS/2014) with additional funding support available through the A*STAR and the IAF-PP (H17/01/a0/005); (3) the SEED study by NMRC/CIRG/1417/2015, NMRC/CIRG/1488/2018 and NMRC/OFLCG/004/2018; (4) the MEC by individual research and clinical scientist award schemes from the Singapore National Medical Research Council (including MOH-000271-00) and the Singapore Biomedical Research Council, the Singapore MOH, the National University of Singapore and the Singapore National University Health System; (5) the PRISM cohort study by NMRC/CG/ M006/2017_NHCS, NMRC/STaR/0011/2012, NMRC/STaR/0026/2015, the Lee Foundation and the Tanoto Foundation; and (6) the TTSH cohort study by NMRC/CG12AUG2017 and CGAug16M012. This research is also supported by the National Research Foundation Singapore under its NPM program Phase II funding (MOH-000588) and administered by the Singapore MOH’s National Medical Research Council

Analysis of clinically relevant variants from ancestrally diverse Asian genomes

Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent variants and identify individuals with variants specific to ancestries discordant to their self-reported ethnicity, mostly due to cryptic admixture. About 27% of severe recessive disorder genes with appreciable carrier frequencies in Asians are missed by carrier screening panels, and we estimate 0.5% Asian couples at-risk of having an affected child. Prevalence of medically-actionable variant carriers is 3.4% and a further 1.6% harbour variants with potential for pathogenic classification upon additional clinical/experimental evidence. We profile 23 pharmacogenes with high-confidence gene-drug associations and find 22.4% of Asians at-risk of Centers for Disease Control and Prevention Tier 1 genetic conditions concurrently harbour pharmacogenetic variants with actionable phenotypes, highlighting the benefits of pre-emptive pharmacogenomics. Our findings illuminate the diversity in genetic disease epidemiology and opportunities for precision medicine for a large, diverse Asian population.</p

Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore

Because of Singapore's unique history of immigration, whole-genome sequence analysis of 4,810 Singaporeans provides a snapshot of the genetic diversity across East, Southeast, and South Asia.</p