Effects due to overlapping large impact basins on Mars

Many ancient, highly degraded large impact basins exist on Mars. In many cases these basins overlap or are overlapped by more easily observed, presumably younger, impact basins. While impact basin overlap is becoming more recognized, the effects of such overlap have only occassionally been described. Such effects will depend on a variety of factors including the absolute and relative size of the basins, the degree of overlap, the state of the lithosphere and its thermal gradient at the time of impact, and the time between impacts. There now exists enough evidence for overlapping basins of different sizes that some of these can be discussed. This paper highlights some examples of the obvious effects of basin overlap

The relationship between personal and interpersonal mental health experiences and stigma-related outcomes in Hong Kong

Background Previous research indicates that personal mental health experiences (e.g. one's current mental health status) and interpersonal mental health experiences (e.g. one's familiarity with someone with mental illness) are associated with stigma-related outcomes. These outcomes include knowledge, attitudes and desire for social distance from people with mental illness. Aims To explore the extent to which current personal mental health status and familiarity with mental illness predict stigma-related outcomes in Hong Kong. Method Data were drawn from a larger research project examining mental well-being in Hong Kong citizens. Citizens (N = 1010) aged ≥18 years were surveyed between August and September 2021. Results Multiple regression analyses revealed that immediate family and friends showed better attitudinal outcomes and lower desire for social distance compared with people who did not know anyone with mental illness (all β > 1.00, all P < 0.05), whereas people with personal experience of mental illness showed higher prejudicial attitudes compared with people who did not know anyone with mental illness (β = −0.744, P = 0.016). Better current personal mental health predicted lower prejudicial attitudes (β = 0.488, P < 0.001) and mixed outcomes on different realms of mental health knowledge. Conclusions Cultural concerns surrounding ‘saving face’ and emphasis on collectivistic values may explain the nonlinear relationship between personal and interpersonal mental health experiences and stigma-related outcomes. Future anti-stigma interventions should tailor their approaches to the needs of people with different levels of familiarity with mental illness and include efforts to support the mental health of the overall population

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

Preventing Respiratory Viral Illness Invisibly (PRiVII): protocol for a pragmatic cluster randomized trial evaluating far-UVC light devices in long-term care facilities to reduce infections

Abstract Background Respiratory viral illness (RVI)—e.g., influenza, COVID-19—is a serious threat in long-term care (LTC) facilities. Standard infection control measures are suboptimal in LTC facilities because of residents’ cognitive impairments, care needs, and susceptibility to loneliness and mental illness. Further, LTC residents living with high degrees of frailty who contract RVIs often develop the so-called atypical symptoms (e.g., delirium, worse mobility) instead of typical cough and fever, delaying infection diagnosis and treatment. Although far-UVC (222 nm) light devices have shown potent antiviral activity in vitro, clinical efficacy remains unproven. Methods Following a study to assay acceptability at each site, this multicenter, double-blinded, cluster-randomized, placebo-controlled trial aims to assess whether far-UVC light devices impact the incidence of RVIs in LTC facilities. Neighborhoods within LTC facilities are randomized to receive far-UVC light devices (222 nm) or identical placebo light devices that emit only visible spectrum light (400–700 nm) in common areas. All residents are monitored for RVIs using both a standard screening protocol and a novel screening protocol that target atypical symptoms. The 3-year incidence of RVIs will be compared using intention-to-treat analysis. A cost-consequence analysis will follow. Discussion This trial aims to inform decisions about whether to implement far-UVC light in LTC facilities for RVI prevention. The trial design features align with this pragmatic intent. Appropriate additional ethical protections have been implemented to mitigate participant vulnerabilities that arise from conducting this study. Knowledge dissemination will be supported through media engagement, peer-reviewed presentations, and publications. Trial registration ClinicalTrials.gov NCT05084898. October 20, 2021

Pembrolizumab alone and pembrolizumab plus chemotherapy in previously treated, extrapulmonary poorly differentiated neuroendocrine carcinomas

BackgroundTo date, single-agent immune checkpoint inhibitor (CPI) therapy has proven to be ineffective against biomarker-unselected extrapulmonary poorly differentiated neuroendocrine carcinomas (EP-PDNECs). The efficacy of CPI in combination with chemotherapy remains under investigation.MethodsPatients with advanced, progressive EP-PDNECs were enrolled in a two-part study of pembrolizumab-based therapy. In Part A, patients received pembrolizumab alone. In Part B, patients received pembrolizumab plus chemotherapy.Primary endpointobjective response rate (ORR). Secondary endpoints: safety, progression-free survival (PFS) and overall survival (OS). Tumours were profiled for programmed death-ligand 1 expression, microsatellite-high/mismatch repair deficient status, mutational burden (TMB), genomic correlates. Tumour growth rate was evaluated.ResultsPart A (N = 14): ORR (pembrolizumab alone) 7% (95% CI, 0.2-33.9%), median PFS 1.8 months (95% CI, 1.7-21.4), median OS 7.8 months (95% CI, 3.1-not reached); 14% of patients (N = 2) had grade 3/4 treatment-related adverse events (TRAEs). Part B (N = 22): ORR (pembrolizumab plus chemotherapy) 5% (95% CI, 0-22.8%), median PFS 2.0 months (95% CI, 1.9-3.4), median OS 4.8 months (95% CI, 4.1-8.2); 45% of patients (N = 10) had grade 3/4 TRAEs. The two patients with objective response had high-TMB tumours.DiscussionTreatment with pembrolizumab alone and pembrolizumab plus chemotherapy was ineffective in advanced, progressive EP-PDNECs.Clinical trial registrationClinicalTrials.gov NCT03136055

Additional file 1 of Preventing Respiratory Viral Illness Invisibly (PRiVII): protocol for a pragmatic cluster randomized trial evaluating far-UVC light devices in long-term care facilities to reduce infections

Additional file 1. Sample Size Estimation