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CORPORATE LAW IN THE UNITED STATES INVOLVES DUAL REGULATION. ALTHOUGH STATE AND FEDERAL CORPORATE LAW TYPICALLY FUNCTION WITHOUT MUTUAL INTERFERENCE, THE LAST THIRTY YEARS HAVE REVEALED POTENTIAL CONFLICTS CHIEFLY IN TWO SITUATIONS. ONE INVOLVES CIVIL REMEDIES FOR INVESTORS UNDER FEDERAL SECURITIES STATUTES; THE OTHER IS STATE ANTI-TAKEOVER REGULATION AND ITS RELATIONSHIP TO THE FEDERAL WILLIAMS ACT. THE AUTHORS ARGUE THAT THE CORE INTERPRETIVE TASK IN FEDERAL SECURITIES LAW IS PRESERVATIN OF BOTH REGIMES TO MAXIMUM EFFECT, BECAUSE THE CONGRESS HAS EXPRESSLY DECLARED THAT STATE AUTHORITY SHOULD CONTINUE ADJACENT TO FEDERAL REGULATION.

ObjectiveThe current observational research literature shows extensive publication bias and contradiction. The Observational Health Data Sciences and Informatics (OHDSI) initiative seeks to improve research reproducibility through open science.MethodsOHDSI has created an international federated data source of electronic health records and administrative claims that covers nearly 10% of the world's population. Using a common data model with a practical schema and extensive vocabulary mappings, data from around the world follow the identical format. OHDSI's research methods emphasize reproducibility, with a large-scale approach to addressing confounding using propensity score adjustment with extensive diagnostics; negative and positive control hypotheses to test for residual systematic error; a variety of data sources to assess consistency and generalizability; a completely open approach including protocol, software, models, parameters, and raw results so that studies can be externally verified; and the study of many hypotheses in parallel so that the operating characteristics of the methods can be assessed.ResultsOHDSI has already produced findings in areas like hypertension treatment that are being incorporated into practice, and it has produced rigorous studies of COVID-19 that have aided government agencies in their treatment decisions, that have characterized the disease extensively, that have estimated the comparative effects of treatments, and that the predict likelihood of advancing to serious complications.ConclusionsOHDSI practices open science and incorporates a series of methods to address reproducibility. It has produced important results in several areas, including hypertension therapy and COVID-19 research.

INTRODUCTION: In the EASEL study of patients with type 2 diabetes and high cardiovascular risk, initiation of sodium glucose co‐transporter 2 inhibitors (SGLT2i) was associated with lower risk of cardiovascular events and mortality and higher risk of below‐knee lower extremity (BKLE) amputation versus non‐SGLT2i therapies. This analysis further examined risk of cardiovascular events, cardiovascular and noncardiovascular death and BKLE amputation with the SGLT2i canagliflozin versus non‐SGLT2i. METHODS: New user cohorts were constructed from Department of Defense Military Health System patients initiating canagliflozin or non‐SGLT2i (4/1/2013‐12/31/2016). Propensity score matching (1:1) controlled for imbalances in baseline covariates. Incidence rates, hazard ratios and 95% confidence intervals for time to first composite outcome of all‐cause mortality (ACM) and hospitalization for heart failure (HHF), composite major adverse cardiovascular events (MACE) and individual components were evaluated using conditional Cox models. The National Death Index was used to differentiate cardiovascular from noncardiovascular death. The exploratory safety end‐point was BKLE amputation. RESULTS: After propensity matching, 15 394 patients with well‐balanced baseline covariates were followed for a median of 2.03 years (intent‐to‐treat). Canagliflozin showed significant benefit for ACM and HHF (P < .0001), MACE (P = .0001), cardiovascular death (P < .0001) and noncardiovascular death (P = .0018). No significant difference in risk of BKLE amputation was observed (P = .20), though few events were observed. Results were generally consistent in on‐treatment analyses. CONCLUSIONS: In this high cardiovascular risk cohort studied in routine clinical practice, canagliflozin was associated with lower risk of cardiovascular events, cardiovascular death and all‐cause mortality with no significant increase in BKLE amputation risk versus non‐SGLT2i.

Abstract
Oxidative potential (OP) is a toxicologically relevant metric that integrates features like mass concentration and chemical composition of particulate matter (PM). Although it has been extensively explored as a metric for the characterization of environmental particles, this is still an underexplored application in the occupational field. This study aimed to estimate the OP of particles in two occupational settings from a construction trades school. This characterization also includes the comparison between activities, sampling strategies, and size fractions. Particulate mass concentrations (PM4-Personal, PM4-Area, and PM2.5-Area) and number concentrations were measured during three weeks of welding and construction/bricklaying activities. The OP was assessed by the ascorbate assay (OPAA) using a synthetic respiratory tract lining fluid (RTLF), while the oxidative burden (OBAA) was determined by multiplying the OPAA values with PM concentrations. Median (25th–75th percentiles) of PM mass and number concentrations were 900 (672–1730) µg m–3 and 128 000 (78 000–169 000) particles cm–3 for welding, and 432 (345–530) µg m–3 and 2800 (1700–4400) particles cm–3 for construction. Welding particles, especially from the first week of activities, were also associated with higher redox activity (OPAA: 3.3 (2.3–4.6) ρmol min–1 µg–1; OBAA: 1750 (893–4560) ρmol min–1 m–3) compared to the construction site (OPAA: 1.4 (1.0–1.8) ρmol min–1 µg–1; OBAA: 486 (341–695) ρmol min–1 m–3). The OPAA was independent of the sampling strategy or size fraction. However, driven by the higher PM concentrations, the OBAA from personal samples was higher compared to area samples in the welding shop, suggesting an influence of the sampling strategy on PM concentrations and OBAA. These results demonstrate that important levels of OPAA can be found in occupational settings, especially during welding activities. Furthermore, the OBAA found in both workplaces largely exceeded the levels found in environmental studies. Therefore, measures of OP and OB could be further explored as metrics for exposure assessment to occupational PM, as well as for associations with cardiorespiratory outcomes in future occupational epidemiological studies.

Looks at all aspects of the pivotal intellectual relationship between two key figures of the EnlightenmentThis collection brings together an international and interdisciplinary group of Adam Smith and Jean-Jacques Rousseau scholars to explore the key shared concerns of these two great thinkers in politics, philosophy, economics, history and literature.Rousseau (1712–78) and Smith (1723–90) are two of the foremost thinkers of the European Enlightenment. They both made seminal contributions to moral and political philosophy and shaped some of the key concepts of modern political economy. Among Smith's first published works was a letter to the Edinburgh Review where he discusses Rousseau's Discourse on the Origin of Inequality. Smith continued to engage with Rousseau's work and to explore many shared themes such as sympathy, political economy, sentiment and inequality. Though we have no solid evidence that they met in person, we do know that they shared many friends and interlocutors. In particular, David Hume was Smith's closest intellectual associate and was also the one who arranged for Rousseau's stay in England in 1766.ContributorsTabitha Baker, University of Warwick, UK.Christel Fricke, University of Oslo, Norway.Charles L. Griswold, Boston University, USA.Ryan Patrick Hanley, Marquette University, USA.Mark Hill, London School of Economics, UK.Mark Hulliung, Brandeis University, USA.Jimena Hurtado, Universidad de los Andes, Columbia.John McHugh, Denison University, USA.Jason Neidleman, University of La Verne, USA.Maria Pia Paganelli, Trinity University, USA.Dennis C. Rasmussen, Tufts University, USA. Neil Saccamano, Cornell University, USA. Michael Schleeter, Pacific Lutheran University, USA.Adam Schoene, Cornell University, USA. Craig Smith, University of Glasgow, UK

Pre-emptive pharmacogenomic (PGx) testing of a panel of genes may be easier to implement and more cost-effective than reactive pharmacogenomic testing if a sufficient number of medications are covered by a single test and future medication exposure can be anticipated. We analysed the incidence of exposure of individual patients in the United States to multiple drugs for which pharmacogenomic guidelines are available (PGx drugs) within a selected four-year period (2009-2012) in order to identify and quantify the incidence of pharmacotherapy in a nation-wide patient population that could be impacted by pre-emptive PGx testing based on currently available clinical guidelines. In total, 73 024 095 patient records from private insurance, Medicare Supplemental and Medicaid were included. Patients enrolled in Medicare Supplemental age > = 65 or Medicaid age 40-64 had the highest incidence of PGx drug use, with approximately half of the patients receiving at least one PGx drug during the 4 year period and one fourth to one third of patients receiving two or more PGx drugs. These data suggest that exposure to multiple PGx drugs is common and that it may be beneficial to implement wide-scale pre-emptive genomic testing. Future work should therefore concentrate on investigating the cost-effectiveness of multiplexed pre-emptive testing strategies. ; Reagan-Udall Foundation for the FDA [RUF-IMEDSSA_0017]; Austrian Science Fund (FWF) [P25608-N15]; European Union's Horizon research and Innovation programme [668353]; US ational Institute on Aging [K01AG044433]; National Library of Medicine [1R01LM011838-01]; National Center for the Advancing Translation Sciences [KL2TR000146] ; This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.

peer-reviewed ; Objectives: Irish adolescents have one of the highest rates of suicide and self-harm in the European Union. Although primary care has been identified as an opportune environment in which to detect and treat mental health problems in adolescents, lack of training among primary care professionals (PCPs) is a barrier to optimum identification and treatment. We describe the development and evaluation of an educational intervention on youth mental health and substance misuse for PCPs. Methods: Thirty general practitioners and other PCPs working in the Mid-West region participated in an educational session on youth-friendly consultations, and identification and treatment of mental ill-health and substance use. Learning objectives were addressed through a presentation, video demonstration, small-group discussions, role play, question-and-answer sessions with clinical experts, and an information pack. Following the session, participants completed an evaluation form assessing knowledge gain and usefulness of different components of the session. Results: 71% of participants were involved in the provision of care to young people. 55% had no previous training in youth mental health or substance abuse. Participants rated knowledge gains as highest with regard to understanding the importance of early intervention, and primary care, in youth mental health. The components rated as most useful were case studies/small group discussion, the 'question-and-answer session' with clinical experts, and peer interaction. Conclusions: The educational session outlined in this pilot was feasible and acceptable and may represent an effective way to train professionals to help tackle the current crisis in youth mental health.

Purpose Quantify and examine the racial fairness of two widely used childhood asthma predictive precision medicine algorithms: the asthma predictive index (API) and the pediatric asthma risk score (PARS). Design Apply the API and PARS and evaluate model performance overall and when stratified by race. Setting Cincinnati, OH, USA. Subjects A prospective birth cohort of 590 children with clinically measured asthma diagnosis by age seven. Measures Model diagnostic criteria included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Analysis Significant differences in model performance between Black and white children were considered to be present if the P-value associated with a t-test based on 100 bootstrap replications was less than .05. Results Compared to predictions for white children, predictions for Black children using the PARS had a higher sensitivity (.88 vs .57), lower specificity (.55 vs .83), higher PPV (.42 vs .33), but a similar NPV (.93 vs .93). Within the API and compared to predictions for white children, predictions for Black children had a higher sensitivity (.63 vs .53), similar specificity (.81 vs .80), higher PPV (.54 vs .28), and lower NPV (.86 vs .92). Conclusions Overall, racial disparities in model diagnostic criteria were greatest for sensitivity and specificity in the PARS, but racial disparities existed in three of the four criteria for both the PARS and the API.