'They're told all the time they're different': how educators understand development of sense of self for autistic pupils

School is a site of critical importance in the development of self yet little is known about the ways in which school affects how autistic pupils come to describe and evaluate themselves. Educators are centrally positioned to support autistic pupils with development of an empowered sense of self. This article reports on a study which captured how staff in four English schools understood development of sense of self for autistic pupils. We found that educators perceived autistic pupils as being affected by both a particular biology and their social encounters with others. Our participants identified the school environment as a significant influencer on sense of self development but seemed uncertain how to make this more enabling. We suggest that one response could be to develop a framework of activism engagement in schools that might enable autistic pupils to work collectively with other autistic people towards a positive sense of self

Stress among UK academics : identifying who copes best?

This paper examined the levels of stress and coping strategies among UK academics. Adopting a positive psychology approach, the influence of the character strengths of hope, optimism, gratitude and self-efficacy, on stress, subjective well-being (SWB), and mental health (GHQ) was examined in 216 academics in a UK university. The study explored the relationship between coping styles and work-coping variables of sense of coherence and work locus of control and stress. No significant differences on the stress, well-being and mental health measures were found for participants' gender, whether in full-time or part-time employment and level of seniority within the university. Participants using problem-focussed coping experienced lower levels of stress while dysfunctional coping was a positive predictor of stress. Hope agency, hope pathway, gratitude, optimism and self-efficacy were the strongest positive predictors of satisfaction with life (SWL), while levels of perceived stress negatively predicted SWL. Gratitude, hope agency and self-efficacy positively predicted positive affect, while stress was a negative predictor. Gratitude, hope agency, self-efficacy and optimism were negative significant predictors of negative affect while stress was a positive predictor. Gratitude positively predicted mental health, while stress was a negative predictor and optimism was a significant moderator of the relationship between stress and mental health. Academics with higher levels of gratitude, self-efficacy, hope and optimism report lower levels of stress at work and higher levels of well-being as measured by higher life satisfaction, higher positive affect and lower negative affect. New approaches to stress management training are suggested based on these findings

Potently neutralizing and protective human antibodies against SARS-CoV-2

The COVID-19 pandemic is a major threat to global health1 for which there are limited medical countermeasures2,3. Moreover, we currently lack a thorough understanding of mechanisms of humoral immunity4. From a larger panel of human monoclonal antibodies (mAbs) targeting the spike (S) glycoprotein5, we identified several that exhibited potent neutralizing activity and fully blocked the receptor-binding domain of S (SRBD) from interacting with human ACE2 (hACE2). Competition-binding, structural, and functional studies allowed clustering of the mAbs into classes recognizing distinct epitopes on the SRBD as well as distinct conformational states of the S trimer. Potent neutralizing mAbs recognizing non-overlapping sites, COV2-2196 and COV2-2130, bound simultaneously to S and synergistically neutralized authentic SARS-CoV-2 virus. In two mouse models of SARS-CoV-2 infection, passive transfer of either COV2-2196 or COV2-2130 alone or a combination of both mAbs protected mice from weight loss and reduced viral burden and inflammation in the lung. In addition, passive transfer of each of two of the most potently ACE2 blocking mAbs (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on SRBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutics

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

Attentional processing of faces in ASD: a dot-probe study

The present study used the Dot-Probe paradigm to explore attentional allocation to faces compared with non-social images in high-functioning individuals with autism spectrum disorder (ASD) and typically developing controls. There was no evidence of attentional bias in either group when stimuli were presented at individually calculated sub-threshold levels. However, at supra-threshold presentation (200 ms), a face bias was found for control participants but not for those with ASD. These results add to evidence of reduced social interest in ASD, relative to controls, and further demonstrate when atypical social processing arises in the attentional time course

Identification and Quantification of 5-Fluoro ADB and the 5-Fluoro ADB Ester Hydrolysis Metabolite in Postmortem Blood Samples by LC–MS/MS

Abstract 5-Fluoro ADB, also known as 5-fluoro MDMB-PINACA, is a potent synthetic cannabinoid that is an agonist to the human cannabinoid CB1 and CB2 receptors. Adverse physiological and psychological effects that have resulted in hospitalization and/or death have been associated with 5-Fluoro ADB use. In addition, analytical confirmation of 5-Fluoro ADB use has been reported in both forensic human performance toxicology and postmortem cases. An analytical method for the identification and quantification of 5-fluoro ADB and the 5-fluoro ADB ester hydrolysis metabolite in human blood samples by liquid chromatography–tandem mass spectrometry was created and validated. The linear range of this assay was determined to be 0.01–10 ng/mL for 5-fluoro ADB and 10–500 ng/mL for the 5-fluoro ADB ester hydrolysis metabolite. The method met both precision and accuracy requirements. Endogenous and exogenous interferences were not observed. Ion suppression exceeding 25% was observed for 5-fluoro ADB. However, additional experiments were performed to ensure that the observed suppression did not affect other method validation parameters such as limit of detection and accuracy. Blood samples from 36 postmortem cases were analyzed utilizing this methodology. The average blood concentration of 5-fluoro ADB was 0.29 ng/mL in central blood specimens and 0.05 ng/mL in peripheral blood specimens. The average blood concentration of the 5-fluoro ADB ester hydrolysis metabolite was 49 ng/mL in central blood specimens and 21 ng/mL in peripheral blood specimens. A serum sample was also analyzed and had a serum concentration of 0.12 ng/mL for 5-fluoro ADB and 42 ng/mL for the 5-fluoro ADB ester hydrolysis metabolite. As the concentration of the 5-fluoro ADB ester hydrolysis metabolite was found at a greater concentration than that of 5-fluoro ADB, this metabolite may be a useful marker to monitor in an attempt to confirm 5-fluoro ADB use in toxicological investigations

LC-MS-MS vs ELISA: Validation of a Comprehensive Urine Toxicology Screen by LC-MS-MS and a Comparison of 100 Forensic Specimens

Toxicology laboratories commonly employ immunoassay methodologies to perform an initial drug screen on urine specimens to direct confirmatory testing. Due to limitations of immunoassay testing and the need to screen for a broader range of drugs with lower limits of detection at a lower cost, mass spectrometry screening techniques have gained favor in the toxicology field. A liquid chromatography-tandem mass spectrometry (LC-MS-MS) urine screening panel was developed and validated for 52 drugs and metabolites. A simple dilute-and-shoot with enzymatic hydrolysis technique was utilized to prepare the urine specimens for analysis. Limit of detection, interference, ionization suppression/enhancement, carryover and stability of processed specimens were assessed during validation. To evaluate the toxicological results obtained from utilizing the LC-MS-MS in comparison with the laboratory's current enzyme-linked immunosorbent assay (ELISA) panel, 100 authentic urine specimens from suspected driving under the influence and drug-facilitated crime cases were analyzed using both methodologies and the results were compared. In addition, the cost of each methodology was evaluated and compared. The validated LC-MS-MS method had limits of detection that were equal to or lower than the concentrations validated for ELISA cutoffs, had fewer exogenous interferences, and the cost of screening per specimen was reduced by ~70% when compared to ELISA. Comparing the toxicology results of forensic urine specimens demonstrated that by only using ELISA, the laboratory was unable to detect benzoylecgonine in 26%, lorazepam in 33% and oxymorphone in 60% of the positive specimens. Additional analytes detected using the LC-MS-MS method were zolpidem and/or metabolite, gabapentin, tramadol and metabolite, methadone and metabolite, meprobamate and phentermine. The results of the validation, the toxicological result comparison and the cost comparison showed that the LC-MS-MS screening method is a simple, sensitive and cost-effective alternative to ELISA screening methods for urine specimens

Forty‐Three Fatalities Involving the Synthetic Cannabinoid, 5‐Fluoro‐ADB: Forensic Pathology and Toxicology Implications

Forty‐three fatalities involving the potent synthetic cannabinoid, 5‐Fluoro‐ADB, are summarized. For each case, a description of the terminal event, autopsy findings, cause of death, qualitative identification of 5‐Fluoro‐ADB and its ester hydrolysis metabolite, 5‐Fluoro‐ADB metabolite 7, in urine, and the quantitative values obtained in the blood specimens are outlined. Central blood concentrations ranged from 0.010 to 2.2 ng/mL for 5‐Fluoro‐ADB and 2.0 to 166 ng/mL for 5‐Fluoro‐ADB metabolite 7. Peripheral blood concentrations ranged from 0.010 to 0.77 ng/mL and 2.0 to 110 ng/mL for 5‐Fluoro‐ADB and 5‐Fluoro‐ADB metabolite 7, respectively. The majority of cases resulted in central to peripheral blood concentration ratios greater than 1 for 5‐Fluoro‐ADB (58%) and 5‐Fluoro‐ADB metabolite 7 (71%) suggesting that postmortem redistribution occurs to some extent. Combining the increased cardiac weight and/or gastric volume and toxicology data identifying 5‐Fluoro‐ADB, it is hypothesized that abuse of this substance may precipitate a dysrhythmia and cause sudden death

The relationship between substance use, prior trauma history, and risk of developing post-traumatic stress disorder in the immediate aftermath of civilian trauma

Many reports have documented the relationship between post-traumatic stress disorder (PTSD) and substance use. Substance use is commonly comorbid with PTSD and is a risk factor for trauma exposure. The aim of this study was to prospectively examine how recent substance use, abuse, or dependence influenced the development of PTSD in the context of a prior trauma history, including child abuse, and the severity of initial trauma reactions. Participants (N = 81) were recruited and assessed at the emergency department of a large urban hospital in Miami and serum levels of common drugs of abuse were measured. Although substance use appeared to be a risk factor for trauma exposure, neither self-reported nor blood toxicology influenced the development of PTSD. Positive toxicology screens were more likely to be associated with a diagnosis of substance abuse or dependence, χ2 (1) = 4.11, p = .04. Participants with a history of physical abuse were more likely to have a positive toxicology screen, χ2 (1) = 4.03, p = .05. The majority of our trauma-exposed subjects (66%) were found to be positive for one or more illicit substances at presentation at the ED. The current findings provide support for the “high risk” hypothesis in which substance use is associated with increased trauma exposure

Acute Effects of Cheddar Cheese Consumption on Circulating Amino Acids and Human Skeletal Muscle

Cheddar cheese is a protein-dense whole food and high in leucine content. However, no information is known about the acute blood amino acid kinetics and protein anabolic effects in skeletal muscle in healthy adults. Therefore, we conducted a crossover study in which men and women (n = 24; ~27 years, ~23 kg/m2) consumed cheese (20 g protein) or an isonitrogenous amount of milk. Blood and skeletal muscle biopsies were taken before and during the post absorptive period following ingestion. We evaluated circulating essential and non-essential amino acids, insulin, and free fatty acids and examined skeletal muscle anabolism by mTORC1 cellular localization, intracellular signaling, and ribosomal profiling. We found that cheese ingestion had a slower yet more sustained branched-chain amino acid circulation appearance over the postprandial period peaking at ~120 min. Cheese also modestly stimulated mTORC1 signaling and increased membrane localization. Using ribosomal profiling we found that, though both milk and cheese stimulated a muscle anabolic program associated with mTORC1 signaling that was more evident with milk, mTORC1 signaling persisted with cheese while also inducing a lower insulinogenic response. We conclude that Cheddar cheese induced a sustained blood amino acid and moderate muscle mTORC1 response yet had a lower glycemic profile compared to milk