"Sisters of the Capital": White Women in Richmond, Virginia, 1860-1880

This dissertation examines the effects of the Civil War and Reconstruction on elite, middle-, and working-class white women in Richmond, Virginia. Anne Firer Scott has written that the Civil War was a historical watershed that enabled southern women's movement into broader social, economic, and political roles in southern society. Suzanne Lebsock and George Rable have observed that claims about white Southern women's gains must be measured against the conservatism of Southern society as the patriarchy reasserted itself in the postwar decades. This study addresses this historiographical debate by examining changes in white Richmond women's roles in the workforce, in organizational politics, and the churches. It also analyzes the war's impact on marriage and family relations. Civil War Richmond represented a two-edged sword to its white female population. As the Confederate capital, it provided them with employment opportunities that were impossible before the war began. By 1863, however, Richmond's population more than doubled as southerners emigrated to the city in search of work or to escape Union armies. This expanding population created extreme shortages in food and housing; it also triggered the largest bread riot in the confederacy. With Confederate defeat, many wartime occupations disappeared, although the need for work did not. Widespread postwar poverty led to the emergence of different occupations. Women had formed a number of charitable organizations before the war began. During the war, they developed new associations that stressed women's patriotism rather than their maternity. In the churches, women's wartime work led to the emergence of independent missionary associations that often were in conflict with male-dominated foreign mission boards. Although change occurred, this study concludes that white women's experiences of the Civil War and Reconstruction in Richmond, Virginia, were far more complex than Scott's notion of a historical watershed indicates. The wartime transformation in women's lives was often fraught with irony. Many changes were neither sought nor anticipated by Richmond women. Several came precisely as a direct result of Confederate defeat. Others tended to reinforce patriarchal notions about white women's subordinate status in Southern society

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

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele