The Shocking Impact of Corporate Scandal on Directors\u27 and Officers\u27 Liability

Directors and officers liability (hereinafter D&O) serves as a deterrent to corporate wrongdoing. Recent cycles of corporate scandal have impacted the tools used to manage the risk that D&O liability creates. The impact of these scandals is a shock, which is a sudden event that alters the market profoundly. Market alteration has counter intuitively resulted in increased availability of D&O insurance at a lower price, despite an increase in D&O liability. With increased D&O coverage offerings at lower costs, the market has become soft, making coverage readily available. Carriers are competing for insureds and there is now a risk of undermining the deterrent effect that D&O liability provides. This paper explores whether D&O liability\u27s deterrent effect has been jeopardized in this soft D&O insurance marke

Using near-term forecasts and uncertainty partitioning to improve predictions of low-frequency cyanobacterial events

Near-term ecological forecasts provide resource managers advance notice of changes in ecosystem services, such as fisheries stocks, timber yields, or water and air quality. Importantly, ecological forecasts can identify where uncertainty enters the forecasting system, which is necessary to refine and improve forecast skill and guide interpretation of forecast results. Uncertainty partitioning identifies the relative contributions to total forecast variance (uncertainty) introduced by different sources, including specification of the model structure, errors in driver data, and estimation of initial state conditions. Uncertainty partitioning could be particularly useful in improving forecasts of high-density cyanobacterial events, which are difficult to predict and present a persistent challenge for lake managers. Cyanobacteria can produce toxic or unsightly surface scums and advance warning of these events could help managers mitigate water quality issues. Here, we calibrate fourteen Bayesian state-space models to evaluate different hypotheses about cyanobacterial growth using data from eight summers of weekly cyanobacteria density samples in an oligotrophic (low nutrient) lake that experiences sporadic surface scums of the toxin-producing cyanobacterium, Gloeotrichia echinulata. We identify dominant sources of uncertainty for near-term (one-week to four-week) forecasts of G. echinulata densities over two years. Water temperature was an important predictor in calibration and at the four-week forecast horizon. However, no environmental covariates improved over a simple autoregressive (AR) model at the one-week horizon. Even the best fit models exhibited large variance in forecasted cyanobacterial densities and often did not capture rare peak density occurrences, indicating that significant explanatory variables in calibration are not always effective for near-term forecasting of low-frequency events. Uncertainty partitioning revealed that model process specification and initial conditions uncertainty dominated forecasts at both time horizons. These findings suggest that observed densities result from both growth and movement of G. echinulata, and that imperfect observations as well as spatial misalignment of environmental data and cyanobacteria observations affect forecast skill. Future research efforts should prioritize long-term studies to refine process understanding and increased sampling frequency and replication to better define initial conditions. Our results emphasize the importance of ecological forecasting principles and uncertainty partitioning to refine and understand predictive capacity across ecosystems.Accepted manuscrip

Early participation in a prenatal food supplementation program ameliorates the negative association of food insecurity with quality of maternal-infant interaction.

Food insecurity is detrimental to child development, yet little is known about the combined influence of food insecurity and nutritional interventions on child development in low-income countries. We proposed that women assigned to an early invitation time to start a prenatal food supplementation program could reduce the negative influence of food insecurity on maternal-infant interaction. A cohort of 180 mother-infant dyads were studied (born between May and October 2003) from among 3267 in the randomized controlled trial Maternal Infant Nutritional Interventions Matlab, which was conducted in Matlab, Bangladesh. At 8 wk gestation, women were randomly assigned an invitation time to start receiving food supplements (2.5 MJ/d; 6 d/wk) either early (~9 wk gestation; early-invitation group) or at the usual start time (~20 wk gestation; usual-invitation group) for the government program. Maternal-infant interaction was observed in homes with the use of the Nursing Child Assessment Satellite Training Feeding Scale, and food-insecurity status was obtained from questionnaires completed when infants were 3.4-4.0 mo old. By using a general linear model for maternal-infant interaction, we found a significant interaction (P = 0.012) between invitation time to start a prenatal food supplementation program and food insecurity. Those in the usual-invitation group with higher food insecurity scores (i.e., more food insecure) had a lower quality of maternal-infant interaction, but this relationship was ameliorated among those in the early-invitation group. Food insecurity limits the ability of mothers and infants to interact well, but an early invitation time to start a prenatal food supplementation program can support mother-infant interaction among those who are food insecure

A Global Census of Fission Yeast Deubiquitinating Enzyme Localization and Interaction Networks Reveals Distinct Compartmentalization Profiles and Overlapping Functions in Endocytosis and Polarity

Proteomic, localization, and enzymatic activity screens in fission yeast reveal how deubiquitinating enzyme localization and function are tuned

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Risk Factors for SARS-CoV-2 Infection Among US Healthcare Personnel, May-December 2020

To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case-control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living

Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery

Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoingcardiac surgery may be especially vulnerable to the adverse effects of transfusion

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570