Adolescents with sexually inappropriate behaviours : background, characteristics and approaches to intervention

The incidence of sexually inappropriate behaviour in adolescents is increasing. Understanding of the nature, incidence and characteristics of the perpetrators of such behaviours is growing; however a validated and conclusive aetiology of sexually inappropriate behaviour in adolescents remains elusive. A specialist project for adolescents with sexually inappropriate behaviours was accessed as a component of a national evaluation project, from where the research developed. It was the first aim of the research to explore the characteristics of a British sample of adolescents with sexually inappropriate behaviours attending a specialised intervention project. A retrospective analysis of case file records of young people was undertaken. A number of characteristics common to previous research were found as were a number contrary. A number of differences were observed between young people convicted and those alleged to have committed sexually inappropriate acts. Intervention for adolescent offenders has seen considerable growth. However, offending continues and adolescents continue to re-offend despite receiving intervention. As a consequence, the second and third aims of the research were to psychometrically assess a sample of adolescents with sexually inappropriate behaviours. The validity of a proposed model of sexually inappropriate behaviour was tested and the efficacy of a specialist intervention project was assessed. Sexually inappropriate young people, non-sexual offenders and non-offenders were comparatively assessed. A small number of statistically significant xi differences were found between the groups. However there were no statistically significant differences found in the majority of assessed areas. The adolescents who participated in the research were a heterogeneous group with differing characteristics and needs. No support was found for the tested model of sexually inappropriate behaviours in adolescents. Comparative analyses of the score results compared at two points in time showed no significant differences in scores after intervention by the specialist intervention project. Research has also acknowledged the need to look beyond the content of offending intervention to how it is delivered. Psychological therapy research has recognised the role and importance of the working alliance between a professional and patient and the concept has began to be explored within research and intervention with adult sexual offenders. The role of the working alliance within youth offending research has received limited research attention. Therefore it was the last aim of the research to explore the concept of a working alliance in youth offending intervention and its impact on successful outcomes. Interviews were conducted with youth offending professionals and young offenders and grounded theory analyses were completed to produce a model of interpretations of the role of the working alliance. The findings suggest that a working alliance exerts some influence on the success of youth offending interventions

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

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu