Examining Youth Camping Outcomes Across Multiple States: the National 4-H Camping Research Consortium (NCRC)

The impact of residential camp participation is needed for camps focused on a variety of outcomes including education, summer fun, prevention, and youth development. One system, the Cooperative Extension Service, conducts 4-H residential camps in most states nationwide every year. These camps, though offering educational enhancement and fun activities, are focused on youth development, incorporating a framework called the essential elements of positive youth development. The National 4-H Camping Research Consortium (NCRC), a group of Extension specialists and county-level educators, designed and piloted assessment tools for 4-H camps that can be used at any camp that focuses on youth development. The camp context questionnaire measures three essential elements of youth development: relationship with a caring adult, self-determination and mastery, and safe and inclusive environments. The life skill questionnaire measures three life skills: accepting self and others, accomplishing goals, and taking responsibility. Logic models and evaluation guidelines help camp directors plan camps that work for youth

TST positivity in household contacts of tuberculosis patients : a case-contact study in Malawi

This work was supported by a Wellcome Trust Fellowship awarded to DJ Sloan (086757/Z/08/A) a Malawi Liverpool Wellcome Trust (MLW) Core grant awarded by the Wellcome Trust and by a grant from the European Union Action for Diseases of Poverty Program (Sante–2006–105-061).Background:  Screening household contacts of active tuberculosis (TB) patients is recommended for TB control. Due to resource constraints this rarely occurs in lower income countries. Demographic and clinical features of index cases may influence the likelihood of onwards TB transmission. It has also been proposed that accumulation of intracellular lipid bodies within M. tuberculosis cells may also enhance bacterial transmissibility. This study explored whether clinical and bacteriological observations recorded at baseline in TB cases in Malawi could help identify those with the highest risk of onwards transmission, to prioritise contact tracing. Methods:  In this case-contact study, data on clinical presentation, sputum bacterial load and the percentage of lipid body positive acid-fast bacilli (%LB + AFB) on sputum smears were recorded in adults with sputum smear and culture positive pulmonary TB before initiation of therapy. The Tuberculin Skin Test (TST) was used to detect infection with M. tuberculosis amongst household contacts under the age of 15 years. TST positivity of the child contacts was related to characteristics of the index case. Results:  Thirty four index cases brought 56 contacts (median: 1, range: 1–4 contacts each). 37 (66%) of contacts had a positive TST. Cavities or a high percentage of lung affected on index patient CXRs were associated with TST positivity. Multivariate analysis of non-radiological factors showed that male sex, HIV-negative status and raised peripheral blood white blood count (WBC) in index patients were also independent risk factors of TST positivity. Lower %LB + AFB counts were associated with TST positivity on univariate analysis only. Conclusion:  TST positivity is common amongst household contacts of sputum smear positive adult TB patients in Malawi. Contact tracing in this high risk population could be guided by prioritising index cases with CXR cavities and extensive radiological disease or, in the absence of CXRs, those who are HIV-negative with a raised WBC.Publisher PDFPeer reviewe

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Functional interdependence of BRD4 and DOT1L in MLL leukemia.

Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation, we found that native BRD4 and DOT1L exist in separate protein complexes. Genetic disruption or small-molecule inhibition of BRD4 and DOT1L showed marked synergistic activity against MLL leukemia cell lines, primary human leukemia cells and mouse leukemia models. Mechanistically, we found a previously unrecognized functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in proximity to superenhancers. DOT1L, via dimethylated histone H3 K79, facilitates histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide new insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this disease with poor prognosis

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

Social impacts of electronic mail in organizations: a review of the research literature

E-mail is a communication network operating on a computer network that supports social networks. It combines iocatiornl flexibility, rapid transmission to muitiple others across time and spa.ce, and the ability to store and process information. We review research into how e-mail shapes - and is shaped by - organizational structures and processes. Although social phenomeru strongly affect the use of e-mail, many discussions of media use have treated it as a voluntary, individual act of matching task to media. They have paid less attention to the influence of organizational power, group perceptions, and social network relations. E-mail provides fewer cues than FTF communication about interactions, physical context or social roles. As this fosters status equalization, there is less awareness of group members' organizational niche and power, or ascribed characteristics. People are more uninhibited, non-conformist and conflictual when using email; groups are more polarized and take longer to reach consensus. However, groups using e-mail tend to produce more diverse opinions and better decisions. E-mail increases access to new people; weakens spatial, temporal and status barrien; and provides access to information that would otherwise be unavailable. Whm people conmunicate electronically, work groups become more fluid. People can participate actively in more groups, and those on the periphery get more involved.Centre for Urban and Community Studies, UofT Ontario Telepresence Projec