Aging in the Right Place

Background: This project builds upon a pilot study that documented innovative shelter/housing solutions that have not undergone rigorous evaluation but hold the promise of supporting “aging in the right place” for older persons (50+) with experiences of homelessness (OPEH) in Montreal, Calgary, and Vancouver. “Aging in the right place” means older adults remain in their homes and communities supported by housing, health, social services responsive to their unique lifestyles and needs. While our pilot study identified innovative shelter/housing solutions that support OPEH to establish and maintain a home and work towards aging in the right place, there remains a knowledge gap regarding what works, why it works, and for whom it works. Methods/Design: Through a community-based participatory research approach, we will conduct evaluations of 11 different promising shelter/housing practices to determine the types of practices that appear most useful in supporting aging in the right place, and the groups of OPEH for whom the promising practices work based on intersections of risk (e.g., age, gender, sexual orientation, race/ethnicity, disability, Indigenous status, and immigrant status). Our overall goal is to improve the shelter/housing options to meet the unique and complex health and social needs of OPEH across Canada. Discussion: Program evaluations will offer practice-based evidence of ways in which promising practices of shelter/housing might serve as best practices for supporting OPEH to establish and maintain a home and work towards aging in the right place. Project findings will inform housing, homelessness, health, and social service providers’ design and delivery of programs for OPEH to improve the sustainability of community housing, build provider capacity, and ensure supports that promote aging in the right place are sustained

Aging in the Right Place

Background: This project builds upon a pilot study that documented innovative shelter/housing solutions that have not undergone rigorous evaluation but hold the promise of supporting “aging in the right place” for older persons (50+) with experiences of homelessness (OPEH) in Montreal, Calgary, and Vancouver. “Aging in the right place” means older adults remain in their homes and communities supported by housing, health, social services responsive to their unique lifestyles and needs. While our pilot study identified innovative shelter/housing solutions that support OPEH to establish and maintain a home and work towards aging in the right place, there remains a knowledge gap regarding what works, why it works, and for whom it works. Methods/Design: Through a community-based participatory research approach, we will conduct evaluations of 11 different promising shelter/housing practices to determine the types of practices that appear most useful in supporting aging in the right place, and the groups of OPEH for whom the promising practices work based on intersections of risk (e.g., age, gender, sexual orientation, race/ethnicity, disability, Indigenous status, and immigrant status). Our overall goal is to improve the shelter/housing options to meet the unique and complex health and social needs of OPEH across Canada. Discussion: Program evaluations will offer practice-based evidence of ways in which promising practices of shelter/housing might serve as best practices for supporting OPEH to establish and maintain a home and work towards aging in the right place. Project findings will inform housing, homelessness, health, and social service providers’ design and delivery of programs for OPEH to improve the sustainability of community housing, build provider capacity, and ensure supports that promote aging in the right place are sustained

Cinacalcet reverses short QT Interval in familial hypocalciuric hypercalcemia type 1

Context: Familial hypocalciuric hypercalcemia type 1 (FHH-1) defines an autosomal dominant disease, related to mutations in the CASR gene, with mild hypercalcemia in most cases. Cases of FHH-1 with a short QT interval have not been reported to date. Objective: Three family members presented with FHH-1 and short QT interval (< 360 ms), a condition that could lead to cardiac arrhythmias, and the effects of cinacalcet, an allosteric modulator of the CaSR, in rectifying the abnormal sensitivity of the mutant CaSR and in correcting the short QT interval were determined. Methods: CASR mutational analysis was performed by next-generation sequencing and functional consequences of the identified CaSR variant (p.Ile555Thr) and effects of cinacalcet were assessed in HEK293 cells expressing wild-type and variant CaSRs. A cinacalcet test consisting of administration of 30 mg cinacalcet (8am) followed by hourly measurement of serum calcium, phosphate, and PTH during 8 hours, and an ECG was performed. Results: The CaSR variant (p.Ile555Thr) was confirmed in all three FHH-1 patients and was shown to be associated with a loss of function that was ameliorated by cinacalcet. Cinacalcet decreased PTH by >50% within two hours, and decreases in serum calcium and increases in serum phosphate occurred within 8 hours, with rectification of the QT interval, which remained normal after 3 months of cinacalcet treatment. Conclusion: Our results indicate that FHH-1 patients should be assessed for a short QT interval, and a cinacalcet test used to select patients who are likely to benefit from this treatment

GEO-6 assessment for the pan-European region

Through this assessment, the authors and the United Nations Environment Programme (UNEP) secretariat are providing an objective evaluation and analysis of the pan-European environment designed to support environmental decision-making at multiple scales. In this assessment, the judgement of experts is applied to existing knowledge to provide scientifically credible answers to policy-relevant questions. These questions include, but are not limited to the following:• What is happening to the environment in the pan-European region and why?• What are the consequences for the environment and the human population in the pan-European region?• What is being done and how effective is it?• What are the prospects for the environment in the future?• What actions could be taken to achieve a more sustainable future?<br/

Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth

The A20 protein is a known inhibitor of apoptosis that here is shown to be a novel cancer stem cell-promoting factor associated with poor glioma patient survival

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

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

Exchange of Sacrifices: West Africa in the Medieval World of Goods

Although excluded from Abu-Lughod’s description of the medieval world system, West Africa nevertheless played a central role in this economic network via the trans-Saharan routes linking the Mediterranean with Africa south of the Sahara. In the thirteenth century, these links were extended and strengthened under the Empire of Mali, which structured trade between trans-Saharan entrepôts and the Savannah regions where prized African elephants thrived. The carved ivories produced in contemporary Europe would not have been possible without these networks, which also supplied local communities with the materials they themselves prized, some of which were regional products, some of which were imported from northwestern Europe. In particular, works of art produced at the Savannah-Forest interface in modern Nigeria demonstrate sub-Saharan Africa’s connection to the world system in the years around 1300

La VAE : un outil au service du projet professionnel et de la carrière des individus ?

International audienc