Project description:GigaScience is now 5 years old, having been launched at the 2012 Intelligent Systems for Molecular Biology conference. Anyone who has attended what is the largest computational biology conference since then has had the opportunity to join us for each birthday celebration-and receive 1 of our fun T-shirts as a party prize. Since launching, we have pushed our agenda of openness, transparency, reproducibility, and reusability. Here, we look back at our first 5 years and what we have done to forward our open science goals in scientific publishing. Our mainstay has been to create a process that allows the availability and publication of as many "research objects" as possible to create a more complete way of communicating how the research process is done.
Project description:Over the past 20 years, there has been tremendous progress in retinal gene therapy. The safety and efficacy results in one early-onset severe blinding disease may lead to the first gene therapy drug approval in the United States. Here, we review how far the field has come over the past two decades and speculate on the directions that the field will take in the future.
Project description:BackgroundAvailable evidence concerning the association between air pollution and preeclampsia is limited, and specific associations with early- and late-onset preeclampsia have not been assessed.ObjectivesWe investigated the association, if any, between preeclampsia (all, early-, and late-onset) and exposure to nitrogen dioxide, nitrogen oxides, particulate matter with aerodynamic diameter ? 2.5 ?m (PM2.5; fine particles), ? 10 ?m, and 2.5-10 ?m, and PM2.5 light absorption (a proxy for elemental carbon) during the entire pregnancy and during the first, second, and third trimesters.MethodsThis study was based on 8,398 pregnancies (including 103 cases of preeclampsia) among women residing in Barcelona, Spain (2000-2005). We applied a spatiotemporal exposure assessment framework using land use regression models to predict ambient pollutant levels during each week of pregnancy at the geocoded residence address of each woman at the time of birth. Logistic and conditional logistic regression models were used to estimate unadjusted and adjusted associations.ResultsWe found positive associations for most of our evaluated outcome-exposure pairs, with the strongest associations observed for preeclampsia and late-onset preeclampsia in relation to the third-trimester exposure to fine particulate pollutants, and for early-onset preeclampsia in relation to the first-trimester exposure to fine particulate pollutants. Among our investigated associations, those of first- and third-trimester exposures to PM2.5 and third-trimester exposure to PM2.5 absorbance and all preeclampsia, and third-trimester PM2.5 exposure and late-onset preeclampsia attained statistical significance.ConclusionWe observed increased risk of preeclampsia associated with exposure to fine particulate air pollution. Our findings, in combination with previous evidence suggesting distinct pathogenic mechanisms for early- and late-onset preeclampsia, support additional research on this topic.
Project description:Implications In this commentary, we describe the evidence-based approach used to identify the primary cause of EVALI and to curb the 2019 outbreak. We also discuss future research opportunities and public health practice considerations to prevent a resurgence of EVALI.
Project description:The field of Alzheimer disease (AD) prevention has been a culmination of basic science, clinical, and translational research. In the past three years since the new 2011 AD diagnostic guidelines, large-scale collaborative efforts have embarked on new clinical trials with the hope of someday preventing AD. This review will shed light on the historical and scientific contexts in which these trials were based on, as well as discuss potential challenges these trials may face in the coming years. Primary preventive measures, such as lifestyle, multidomain, medication, and supplemental interventions, will be analyzed. Secondary prevention as represented by disease-modifying interventions, such as antiamyloid therapy and pioglitazone, will also be reviewed. Finally, hypotheses on future directions for AD prevention trials will be proposed.
Project description:Covid Act Now (CAN) developed an epidemiological model that takes various non-pharmaceutical interventions (NPIs) into account and predicts viral spread and subsequent health outcomes. In this study, the projections of the model developed by CAN were back-tested against real-world data, and it was found that the model consistently overestimated hospitalizations and deaths by 25%-100% and 70%-170%, respectively, due in part to an underestimation of the efficacy of NPIs. Other COVID models were also back-tested against historical data, and it was found that all models generally captured the potential magnitude and directionality of the pandemic in the short term. There are limitations to epidemiological models, but understanding these limitations enables these models to be utilized as tools for data-driven decision-making in viral outbreaks. Further, it can be valuable to have multiple, independently developed models to mitigate the inaccuracies of or to correct for the incorrect assumptions made by a particular model.
Project description:In commemoration of the centennial of the 1918 influenza pandemic, the American Journal of Epidemiology has convened a collection of 12 articles that further illuminate the epidemiology of that pandemic and consider whether we would be more prepared if an equally deadly influenza virus were to emerge again. In the present commentary, we place these 12 articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. We also highlight persisting mysteries in the origins and severity of the 1918 pandemic and the need to preserve rapidly decaying information that may provide treasure troves for future generations.
Project description:Halogen bonding has emerged at the forefront of advances in improving ligand: receptor interactions. In particular the newfound ability of this extant non-covalent-bonding phenomena has revolutionized computational approaches to drug discovery while simultaneously reenergizing synthetic approaches to the field. Here we survey, via examples of classical applications involving halogen atoms in pharmaceutical compounds and their biological hosts, the unique advantages that halogen atoms offer as both Lewis acids and Lewis bases.
Project description:Although ambient air pollution may increase hypertension risk through endothelial damage and oxidative stress, evidence is inconsistent regarding its effect on hypertension in pregnancy. Prior research has evaluated a limited scope of pollution species and often not differentiated preeclampsia, which may have a placental origin, from gestational hypertension. Among 49?607 women with at least 2 singleton deliveries in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Consecutive Pregnancies Study (2002-2010), we estimated criteria pollutant and volatile organic compound levels during pregnancy using Community Multiscale Air Quality models and abstracted gestational hypertension and preeclampsia diagnoses from medical records. Generalized estimating equations accounted for repeat pregnancies and adjusted for ambient temperature and maternal age, race/ethnicity, body mass index, smoking, alcohol, parity, insurance, marital status, and asthma. Air pollution levels were low to moderate (eg, median 41.6 ppb [interquartile range, 38.9-43.7 ppb] for ozone and 35.1 ppb [28.9-40.3 ppb] for nitrogen oxides). Higher levels of most criteria pollutants during preconception and the first trimester were associated with lower preeclampsia risk, while higher second-trimester levels were associated with greater gestational hypertension risk. For example, an interquartile increase in first-trimester carbon monoxide was associated with a relative risk of 0.88 (95% CI, 0.81-0.95) for preeclampsia and second-trimester carbon monoxide a relative risk of 1.14 (95% CI, 1.07-1.22) for gestational hypertension. Volatile organic compounds, conversely, were not associated with gestational hypertension but consistently associated with higher preeclampsia risk. These findings further suggest air pollution may affect the development of hypertension in pregnancy, although differing causes of preeclampsia and gestational hypertension may alter these relationships.
Project description:The family environment, with all its complexity and diverse components, plays a critical role in shaping neurodevelopmental outcomes in children. Herein we review several domains of the family environment (family socioeconomic status, family composition and home environment, parenting behaviors and interaction styles, parental mental health and functioning, and parental substance use) and discuss how these domains influence neurodevelopment, with particular emphasis on mental health outcomes. We also highlight a new initiative launched by the National Institutes of Health, the Environmental influences on Child Health Outcomes (ECHO) program. We discuss the role that ECHO will play in advancing our understanding of the impact of the family environment on children's risk for psychiatric outcomes. Lastly, we conclude with important unanswered questions and controversies in this area of research, highlighting how ECHO will contribute to resolving these gaps in our understanding, clarifying relationships between the family environment and children's mental health.