The size, concentration, and growth of biodiversity-conservation nonprofits

Nonprofit organizations play a critical role in efforts to conserve biodiversity. Their success in this regard will be determined in part by how effectively individual nonprofits and the sector as a whole are structured. One of the most fundamental questions about an organization’s structure is how large it should be, with the logical counterpart being how concentrated the whole sector should be. We review empirical patterns in the size, concentration, and growth of over 1700 biodiversity-conservation nonprofits registered for tax purposes in the United States within the context of relevant economic theory. Conservation-nonprofit sizes vary by six to seven orders of magnitude and are positively skewed. Larger nonprofits access more revenue streams and hold more of their assets in land and buildings than smaller or midsized nonprofits do. The size of conservation nonprofits varies with the ecological focus of the organization, but the growth rates of nonprofits do not

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

Is there a difference between hospital-verified and self-reported self-harm? Implications for repetition

OBJECTIVE: Repeated intentional self-harm (SH) is associated with economic costs and increased risk of suicide. Estimates of repetition vary according to method of data capture and are limited by short periods of follow-up observation. Some sources use hospital records and others self-reported SH (SRSH). Our aim was to examine the relationship between SRSH and hospital-verified SH (HVSH) and later repetition of SH (predictive validity). We also aimed to examine whether rates of SH repetition differ between first-time presenters and non-first-time presenters using either definition of SH. METHOD: We conducted a large prospective study tracking SH attempts through an Accident and Emergency (A&E) department within the United Kingdom. We took a representative sample of 774 patients (30% of total who reported SH) and followed them for 5.6 years on average. The index episode of SH was recorded at the time of referral to staff in A&E. Prior episodes of SH were determined from an electronic search of A&E patient database, and in addition, recollection of prior SH as reported by the patient to their clinician at the time of index presentation was recorded. RESULTS: Across the whole sample 32.0% of patients repeated SH within 1 year, which rose to 54.1% at completion of follow-up. Repetition rates were considerably higher in patients with a prior SH history than those presenting with a first SH episode after 1 year (47.9% vs. 19.6%) and by the end of follow-up (73.8% vs. 39.4%) (P<.001). Of 411 with self-reported first presentations, 45.2% repeated over the study period. In terms of predictive validity, 65.2% of those with previous SRSH repeated vs. 73.8% with previous HVSH (P<.001). There was low agreement between SRSH and HVSH (Kappa=0.353, 95% confidence interval 0.287-0.419, low). CONCLUSIONS: We found relatively poor agreement between hospital-defined and self-reported SH. A total of 62.8% of those who denied SH actually had a hospital-verified previous episode. Patients with recorded prior SH and those who recall previous SH have significantly higher rates of repetition, but the two samples imprecisely overlap and predictive validity is stronger for HVSH

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway