Explore the vast range of titles available.

Background The rising prevalence of adolescent mild depression in the UK and the paucity of evidence-based interventions in non-specialist sectors where most cases present, creates an urgent need for early psychological interventions. Randomised controlled trials (RCTs) are considered the gold standard for obtaining unbiased estimates of intervention effectiveness. However, the complexity of mental health settings poses great challenges for effectiveness evaluations. This paper reports learning from an embedded process evaluation of the ICALM RCT which tested the feasibility of delivering Interpersonal Counselling for Adolescents (IPC-A) plus Treatment as Usual (TAU) versus TAU only for adolescent (age 12–18) mild depression by non-qualified mental health professionals in non-specialist sectors. Methods A qualitative mixed methods process evaluation, drawing on Bronfenbrenner’s socioecological model to investigate key influences on trial delivery across macro-(e.g. policy), meso-(e.g. service characteristics) and micro-(e.g. on-site trial processes) contextual levels. Data collection methods included 9 site questionnaires, 4 observations of team meetings, policy documents, and 18 interviews with stakeholders including therapists, heads of service and managers. Thematic analysis focused on understanding how contextual features shaped trial implementation. Results The ICALM trial concluded in 2022 having only randomised 14 out of the target 60 young people. At a macro-level, trial delivery was impacted by the COVID-19 pandemic, with services reporting a sharp increase in cases of (social) anxiety over low mood, and backlogs at central referral points which prolonged waiting times for mild cases (e.g. low mood). An interaction between high demand and lack of capacity at a meso-service level led to low prioritisation of trial activities at a micro-level. Unfamiliarity with research processes (e.g. randomisation) and variation in TAU support also accentuated the complexities of conducting an RCT in this setting. Conclusions Conducting a RCT of IPC-A in non-specialist services is not feasible in the current context. Failure to conduct effectiveness trials in this setting has clinical implications, potentially resulting in escalation of mild mental health problems. Research done in this setting should adopt pragmatic and innovative recruitment and engagement approaches (e.g. creating new referral pathways) and consider alternative trial designs, e.g. cluster, stepped-wedge or non-controlled studies using complex systems approaches to embrace contextual complexity. Trial registration ISRCTN registry, ISRCTN82180413. Registered on 31 December 2019.

Background Depression is a common health problem during adolescence and is associated with adverse academic, social and health outcomes. To meet the demand for treatment for adolescent depression, there is a need for evidence-based interventions suitable for delivery outside of specialist Child and Adolescent Mental Health Services (CAMHS). Interpersonal Counselling for Adolescents (IPC-A) is a brief manualised intervention for adolescent depression suitable for delivery by staff who are not qualified health professionals following participation in a brief training course. While initial piloting within Local Authority services has generated promising results, the effectiveness and cost-effectiveness of IPC-A has yet to be established. This study aims to assess the feasibility of a randomised controlled trial (RCT), evaluating the effectiveness and cost-effectiveness of IPC-A delivered by staff without core professional training in comparison to current provision. Method Feasibility RCT with process evaluation using ethnographic methodology. Eligible young people ( n = 60) will be randomised in a 1:1 ratio to receive either IPC-A or treatment as usual (TAU). Participants will be assessed pre-randomisation (baseline) and followed up at 5, 10 and 23 weeks post-randomisation. A parallel process evaluation will generate understanding of intervention implementation across services and explore the acceptability of the intervention from the perspective of young people and other key stakeholders. Participants Young people aged 12–18 years presenting to non-specialist services with symptoms of depression. Youth workers, young people and stakeholders will participate in the process evaluation. Discussion The need for effective and accessible interventions for young people with mild/sub-threshold depression who, in most cases, do not meet the threshold for mainstream mental health services is long overdue. The primary output of this feasibility trial will be the design of the subsequent full-scale trial. If the results of the current study indicate that this would be feasible, we intend to progress to a multi-site, assessor-blind, superiority RCT of the effectiveness and cost-effectiveness of IPC-A in comparison to TAU for adolescents presenting to non-specialist services with depressive symptoms. If satisfactory solutions to any problems encountered cannot be identified, alternative research designs will be considered. If proven effective, an IPC-A training programme could be implemented. Trial registry ISRCTN registry, ISRCTN82180413 , Registered 31 December 2019.

Unemployment and underemployment is a significant problem effecting the lives of the disabled. This dissertation uses a variety of qualitative techniques to examine the experiences of eleven mentally retarded young adults enrolled in a work transition program based on a Support Employment model as they move from school to the workplace. Observation, participant observation, interviewing and records reviews are used to understand their experiences, lives and views of the move to the workplace. This information is presented in series of participant biographies which permits comparison of experiences and the establishment of parallel influences on success. Significant individual influences included: past education programming and the degree to which participants were able to develop solutions to problems in the work setting, the role of families in developing confidence and social interaction abilities, individual ability to manage life issues and the degree to which each participant had a view of their future. Significant program influences identified included: the need for committed and interactive job coaching, comprehensive and detailed job analysis particularly the development of an understanding of the total environment of work and careful matching of participant skills to workplace requirements.

Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 μg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV−like Sarbecovirus vaccine development.

Bacterial pneumonia in neonates can cause significant morbidity and mortality when compared to other childhood age groups. To understand the immune mechanisms that underlie these age-related differences, we employed a mouse model of Escherichia coli pneumonia to determine the dynamic cellular and molecular differences in immune responsiveness between neonates (PND 3–5) and juveniles (PND 12–18), at 24, 48, and 72 hr. Cytokine gene expression from whole lung extracts was also quantified at these time points, using quantitative RT-PCR. E. coli challenge resulted in rapid and significant increases in neutrophils, monocytes, and γδT cells, along with significant decreases in dendritic cells and alveolar macrophages in the lungs of both neonates and juveniles. E. coli -challenged juvenile lung had significant increases in interstitial macrophages and recruited monocytes that were not observed in neonatal lungs. Expression of IFNγ-responsive genes was positively correlated with the levels and dynamics of MHCII-expressing innate cells in neonatal and juvenile lungs. Several facets of immune responsiveness in the wild-type neonates were recapitulated in juvenile MHCII −/− juveniles. Employing a pre-clinical model of E. coli pneumonia, we identified significant differences in the early cellular and molecular dynamics in the lungs that likely contribute to the elevated susceptibility of neonates to bacterial pneumonia and could represent targets for intervention to improve respiratory outcomes and survivability of neonates.

Abstract The integration of transcriptomic and proteomic data from lung tissue with chronic obstructive pulmonary disease (COPD)–associated genetic variants could provide insight into the biological mechanisms of COPD. Here, we assessed associations between lung transcriptomics and proteomics with COPD in 98 subjects from the Lung Tissue Research Consortium. Low correlations between transcriptomics and proteomics were generally observed, but higher correlations were found for COPD-associated proteins. We integrated COPD risk SNPs or SNPs near COPD-associated proteins with lung transcripts and proteins to identify regulatory cis-quantitative trait loci (QTLs). Significant expression QTLs (eQTLs) and protein QTLs (pQTLs) were found regulating multiple COPD-associated biomarkers. We investigated mediated associations from significant pQTLs through transcripts to protein levels of COPD-associated proteins. We also attempted to identify colocalized effects between COPD genome-wide association studies and eQTL and pQTL signals. Evidence was found for colocalization between COPD genome-wide association study signals and a pQTL for RHOB and an eQTL for DSP. We applied weighted gene co-expression network analysis to find consensus COPD-associated network modules. Two network modules generated by consensus weighted gene co-expression network analysis were associated with COPD with a false discovery rate lower than 0.05. One network module is related to the catenin complex, and the other module is related to plasma membrane components. In summary, multiple cis-acting determinants of transcripts and proteins associated with COPD were identified. Colocalization analysis, mediation analysis, and correlation-based network analysis of multiple omics data may identify key genes and proteins that work together to influence COPD pathogenesis.

Iron from haemolysed blood is implicated in secondary injury after intracerebral haemorrhage. We aimed to assess the safety of the iron chelator deferoxamine mesylate in patients with intracerebral haemorrhage and to establish whether the drug merits investigation in a phase 3 trial. We did a multicentre, futility-design, randomised, placebo-controlled, double-blind, phase 2 trial at 40 hospitals in Canada and the USA. Adults aged 18–80 years with primary, spontaneous, supratentorial intracerebral haemorrhage were randomly assigned (1:1) to receive deferoxamine mesylate (32 mg/kg per day) or placebo (saline) infusions for 3 consecutive days within 24 h of haemorrhage onset. Randomisation was done via a web-based trial-management system centrally in real time, and treatment allocation was concealed from both participants and investigators. The primary outcome was good clinical outcome, which was defined as a modified Rankin Scale score of 0–2 at day 90. We did a futility analysis: if the 90% upper confidence bound of the absolute risk difference between the two groups in the proportion of participants with a good clinical outcome was less than 12% in favour of deferoxamine mesylate, then to move to a phase 3 efficacy trial would be futile. Primary outcome and safety data were analysed in the modified intention-to-treat population, comprising only participants in whom the study infusions were initiated. This trial is registered with ClinicalTrials.gov, number NCT02175225, and is completed. We recruited 294 participants between Nov 23, 2014, and Nov 10, 2017. The modified intention-to-treat population consisted of 144 patients assigned to the deferoxamine mesylate group and 147 assigned to the placebo group. At day 90, among patients with available data for the primary outcome, 48 (34%) of 140 participants in the deferoxamine mesylate group, and 47 (33%) of 143 patients in the placebo group, had modified Rankin Scale scores of 0–2 (adjusted absolute risk difference 0·6% [90% upper confidence bound 6·8%]). By day 90, 70 serious adverse events were reported in 39 (27%) of 144 patients in the deferoxamine mesylate group, and 78 serious adverse events were reported in 49 (33%) of 147 patients in the placebo group. Ten (7%) participants in the deferoxamine mesylate and 11 (7%) in the placebo group died. None of the deaths were judged to be treatment related. Deferoxamine mesylate was safe. However, the primary result showed that further study of the efficacy of deferoxamine mesylate with anticipation that the drug would significantly improve the chance of good clinical outcome (ie, mRS score of 0–2) at day 90 would be futile. US National Institutes of Health and US National Institute of Neurological Disorders and Stroke.

Intersectional feminist work around digital archiving can productively develop stack models to address questions concerning the location, site, and materiality of possible and effective feminist intervention. Developing this proposition, we draw on two DH research projects undertaken between the UK and Ireland (2020 and on-going) focussing on work around community archives at a moment of their radical transformation. Asking what feminist DH can be in relation to these archives, we engage with the hollowing out of intersectional feminism – noting that it at times becomes a reached for category rather than a useful signifier, while also recognizing that theorizing forms of intersection between categories and groups experiencing discrimination is essential to grappling with issues including new forms of institutionalization, context dependency, and privacy. An exploration of various forms of Critical Race Theory (CRT) and of more historically materialist thinking around intersectionality enables us to develop a feminist-informed stack approach able to grapple with the complicated stakes of archiving histories of trauma – including those undertaken by those in different situated positions. We use this to inform a discussion of where feminism should act and develop an argument that stack models – echoing in theory what is found in material infrastructure – can be useful as guides to think about appropriate and expanded sites for feminist intervention in DH.

The Spitzer Survey of Stellar Structure in Galaxies ([inline image]) is an Exploration Science Legacy Program approved for the Spitzer post-cryogenic mission. It is a volume-, magnitude-, and size-limited (d < 40 Mpc,

The characteristics of patients with coronavirus disease 2019 (COVID-19) have primarily been described in hospitalized adults. Characterization of COVID-19 in ambulatory care is needed for a better understanding of its evolving epidemiology. Our aim is to provide a description of the demographics, comorbidities, clinical presentation, and social factors in confirmed SARS-CoV-2-positive non-hospitalized adults. We conducted a retrospective medical record review of 208 confirmed SARS-CoV-2-positive patients treated in a COVID-19 virtual outpatient management clinic established in an academic health system in Georgia. The mean age was 47.8 (range 21–88) and 69.2% were female. By race/ethnicity, 49.5% were non-Hispanic African American, 25.5% other/unknown, 22.6% non-Hispanic white, and 2.4% Hispanic. Nearly 70% had at least one preexisting medical condition. The most common presenting symptoms were cough (75.5%), loss of smell or taste (63%), headache (62%), and body aches (54.3%). Physician or advanced practice provider assessed symptom severity ranged from 51.9% mild, 30.3% moderate, and 1.4% severe. Only eight reported limitations to home care (3.8%), 55.3% had a caregiver available, and 93.3% reported initiating self-isolation. Care needs were met for 83.2%. Our results suggest the demographic and clinical characteristics of COVID-19 illness in non-hospitalized adults differ considerably from hospitalized patients and warrant greater awareness of risk among younger and healthier individuals and consideration of testing and recommending self-isolation for a wider spectrum of clinical symptoms by clinicians. Social factors may also influence the efficacy of preventive strategies and allocation of resources toward the SARS-CoV-2 pandemic.