Langerhans cell precursors acquire RANK/CD265 in prenatal human skin

AbstractThe skin is the first barrier against foreign pathogens and the prenatal formation of a strong network of various innate and adaptive cells is required to protect the newborn from perinatal infections. While many studies about the immune system in healthy and diseased adult human skin exist, our knowledge about the cutaneous prenatal/developing immune system and especially about the phenotype and function of antigen-presenting cells such as epidermal Langerhans cells (LCs) in human skin is still scarce. It has been shown previously that LCs in healthy adult human skin express receptor activator of NF-κB (RANK), an important molecule prolonging their survival. In this study, we investigated at which developmental stage LCs acquire this important molecule. Immunofluorescence double-labeling of cryostat sections revealed that LC precursors in prenatal human skin either do not yet [10–11 weeks of estimated gestational age (EGA)] or only faintly (13–15 weeks EGA) express RANK. LCs express RANK at levels comparable to adult LCs by the end of the second trimester. Comparable with adult skin, dermal antigen-presenting cells at no gestational age express this marker. These findings indicate that epidermal leukocytes gradually acquire RANK during gestation – a phenomenon previously observed also for other markers on LCs in prenatal human skin

Clinical stakeholders' opinions on the use of selective decontamination of the digestive tract in critically ill patients in intensive care units : an international Delphi study

Peer reviewedPublisher PD

Clinical components and associated behavioural aspects of a complex healthcare intervention : Multi-methods study of selective decontamination of the digestive tract in critical care

Copyright © 2013 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.Peer reviewedPostprin

Neurodevelopmental disorders and neurodiversity: Definition of terms from Scotland's National Autism Implementation Team [Editorial]

From PubMed via Jisc Publications RouterAdults with neurodevelopmental disorders frequently present to, but fit uneasily into, adult mental health services. We offer definitions of important terms related to neurodevelopmental disorders through unifying research data, medical and other viewpoints. This may improve understanding, clinical practice and development of neurodevelopmental disorder pathways within adult mental health services.aheadofprintaheadofprin

Mental health in autistic adults: a rapid review of prevalence of psychiatric disorders and umbrella review of the effectiveness of interventions within a neurodiversity informed perspective

Eleanor Curnow - ORCID: 0000-0001-9332-8248 https://orcid.org/0000-0001-9332-8248Marion Rutherford - ORCID: 0000-0002-2283-6736 https://orcid.org/0000-0002-2283-6736Donald Maciver - ORCID: 0000-0002-6173-429X https://orcid.org/0000-0002-6173-429XItem updated 2023-07-14 to include VoR.Background Autistic adults have high risk of mental ill-health and some available interventions have been associated with increased psychiatric diagnoses. Understanding prevalence of psychiatric diagnoses is important to inform the development of individualised treatment and support for autistic adults which have been identified as a research priority by the autistic community. Interventions require to be evaluated both in terms of effectiveness and regarding their acceptability to the autistic community. Objective This rapid review identified the prevalence of psychiatric disorders in autistic adults, then systematic reviews of interventions aimed at supporting autistic adults were examined. A rapid review of prevalence studies was completed concurrently with an umbrella review of interventions. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed, including protocol registration (PROSPERO#CRD42021283570). Data sources MEDLINE, CINAHL, PsycINFO, and Cochrane Database of Systematic Reviews. Study eligibility criteria English language; published 2011–2022; primary studies describing prevalence of psychiatric conditions in autistic adults; or systematic reviews evaluating interventions for autistic adults. Appraisal and synthesis Bias was assessed using the Prevalence Critical Appraisal Instrument and AMSTAR2. Prevalence was grouped according to psychiatric diagnosis. Interventions were grouped into pharmacological, employment, psychological or mixed therapies. Strength of evidence for interventions was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Autistic researchers within the team supported interpretation. Results Twenty prevalence studies were identified. Many included small sample sizes or failed to compare their sample group with the general population reducing validity. Prevalence of psychiatric diagnoses was variable with prevalence of any psychiatric diagnosis ranging from 15.4% to 79%. Heterogeneity was associated with age, diagnosis method, sampling methods, and country. Thirty-two systematic reviews of interventions were identified. Four reviews were high quality, four were moderate, five were low and nineteen critically low, indicating bias. Following synthesis, no intervention was rated as ‘evidence based.’ Acceptability of interventions to autistic adults and priorities of autistic adults were often not considered. Conclusions There is some understanding of the scope of mental ill-health in autism, but interventions are not tailored to the needs of autistic adults, not evidence based, and may focus on promoting neurotypical behaviours rather than the priorities of autistic people.pubpu

Selective decontamination of the digestive tract in critically ill patients treated in intensive care units: a mixed-methods feasibility study (the SuDDICU study)

Background: Hospital-acquired infections (HAIs) are a major cause of morbidity and mortality. Critically ill patients in intensive care units (ICUs) are particularly susceptible to these infections. One intervention that has gained much attention in reducing HAIs is selective decontamination of the digestive tract (SDD). SDD involves the application of topical non-absorbable antibiotics to the oropharynx and stomach and a short course of intravenous (i.v.) antibiotics. SDD may reduce infections and improve mortality, but has not been widely adopted in the UK or internationally. Hence, there is a need to identify the reasons for low uptake and whether or not further clinical research is needed before wider implementation would be considered appropriate. Objectives: The project objectives were to (1) identify and describe the SDD intervention, (2) identify views about the evidence base, (3) identify acceptability of further research and (4) identify feasibility of further randomised controlled trials (RCTs). Design : A four-stage approach involving (1) case studies of two ICUs in which SDD is delivered including observations, interviews and documentary analysis, (2) a three-round Delphi study for in-depth investigation of clinicians' views, including semi-structured interviews and two iterations of questionnaires with structured feedback, (3) a nationwide online survey of consultants in intensive care medicine and clinical microbiology and (4) semistructured interviews with international clinical triallists to identify the feasibility of further research. Setting : Case studies were set in two UK ICUs. Other stages of this research were conducted by telephone and online with NHS staff working in ICUs. Participants : (1) Staff involved in SDD adoption or delivery in two UK ICUs, (2) ICU experts (intensive care consultants, clinical microbiologists, hospital pharmacists and ICU clinical leads), (3) all intensive care consultants and clinical microbiologists in the UK with responsibility for patients in ICUs were invited and (4) international triallists, selected from their research profiles in intensive care, clinical trials and/or implementation trials. Interventions : SDD involves the application of topical non-absorbable antibiotics to the oropharynx and stomach and a short course of i.v. antibiotics. Main outcome measures: Levels of support for, or opposition to, SDD in UK ICUs; views about the SDD evidence base and about barriers to implementation; and feasibility of further SDD research (e.g. likely participation rates). Results : (1) The two case studies identified complexity in the interplay of clinical and behavioural components of SDD, involving multiple staff. However, from the perspective of individual staff, delivery of SDD was regarded as simple and straightforward. (2) The Delphi study (n = 42) identified (a) specific barriers to SDD implementation, (b) uncertainty about the evidence base and (c) bimodal distributions for key variables, e.g. support for, or opposition to, SDD. (3) The national survey (n = 468) identified uncertainty about the effect of SDD on antimicrobial resistance, infection rates, mortality and cost-effectiveness. Most participants would participate in further SDD research. (4) The triallist interviews (n = 10) focused largely on the substantial challenges of conducting a large, multinational clinical effectiveness trial. Conclusions : There was considerable uncertainty about possible benefits and harms of SDD. Further large-scale clinical effectiveness trials of SDD in ICUs may be required to address these uncertainties, especially relating to antimicrobial resistance. There was a general willingness to participate in a future effectiveness RCT of SDD. However, support was not unanimous. Future research should address the barriers to acceptance and participation in any trial. There was some, but a low level of, interest in adoption of SDD, or studies to encourage implementation of SDD into practice

Has the gender gap in voter turnout really disappeared?

According to conventional wisdom, the traditional gender gap in voting has disappeared or even reversed in most established democracies. Drawing on the existing literature on sex differences in political engagement and on pioneering voter turnout theories, this article questions the conventional assumption and hypothesises that women still participate at lower rates in less important elections. It systematically tests this hypothesis by exploring the impact of sex on voter turnout in different electoral arenas. The empirical analyses of two cross-national datasets (Making Electoral Democracy Work and the European Election Study) demonstrate that although there is generally no gender gap in first-order elections, women tend to vote less than men in second-order contests. This reflects women’s weaker interest in politics and their lower levels of knowledge about politics in second-order electoral arenas

The views of health care professionals about selective decontamination of the digestive tract: An international, theoretically informed interview study

Purpose: Selective Decontamination of the Digestive tract (SDD) as a prophylactic intervention improves hospital-acquired infection and survival rates. Uptake of SDD is low and remains controversial. This study applied the Theoretical Domains Framework (TDF) to assess ICU clinicians’ views about SDD in regions with limited or no adoption of SDD. Materials and Methods: Participants were health professionals with ‘decisional authority’ for the adoption of SDD. Semistructured interviews were conducted as the first round of a Delphi study. Views about SDDadoption, delivery and further SDD research were explored. Directed content analysis of interview data identified sub-themes which informed item development for subsequent Delphi rounds. Linguistic features of interview data were also explored. Results: 141 participants provided interview data. Fifty-six sub-themes were identified; 46 were common across regions. Beliefs about consequences was the most widely elaborated theme. Linguistic features of how participants discussed SDD included caution expressed when discussing the risks and benefits and words such as worry, anxiety and fear when discussing potential antibiotic resistance associated with SDD. Conclusions: We identified salient beliefs, barriers and facilitators to SDD adoption and delivery. What participants said about SDD and the way in which they said it demonstrated the degree of clinical caution, uncertainty and concern that SDD evokes

Development of a pathway for multidisciplinary neurodevelopmental assessment and diagnosis in children and young people

Marion Rutherford - ORCID: 0000-0002-2283-6736 https://orcid.org/0000-0002-2283-6736Donald Maciver - ORCID: 0000-0002-6173-429X https://orcid.org/0000-0002-6173-429XThere is a variable standard of access to quality neurodevelopmental assessment and diagnosis. People may have negative experiences, encountering lengthy waiting times, and inconsistent practices. Practitioners need guidance on standards and practices for assessment and diagnosis matched to new ways of working. In this paper, we present a new pathway and recommendations for multidisciplinary neurodevelopmental assessment and diagnosis for children and young people (<19 years), developed by the Scottish Government funded National Autism Implementation Team (NAIT). Our research used the Medical Research Council guidance for the development of complex interventions and included several iterative stages. Stage 1: n = 44 stakeholders attended an event on developing new practices for diagnosis and assessment. Stage 2: a literature synthesis was completed by the research team of clinical guidelines and diagnosis and assessment tools. Stage 3: an event with n = 127 stakeholders included discussion and debate of the data from stages 1 and 2. Recommendations and a draft pathway were written. Stage 4: successive drafts of recommendations and the pathway documentation were circulated among an advisory group, including multidisciplinary clinical experts and people with lived experience, until the final pathway was agreed upon. The finalised pathway includes guidance on terminology, assessment, diagnosis, triage, time standards and engagement of people with lived experience. The new pathway has been adopted by the Scottish Government. The pathway and associated documentation are freely available online for use by others.This research was funded by the Scottish Government.https://doi.org/10.3390/children81110338pubpub1

Pulmonary Vascular Resistance as Assessed by Bicycle Stress Echocardiography in Patients With Atrial Septal Defect Type Secundum

Background-Volume overload of the pulmonary circulation in patients with atrial septal defect (ASD)-type secundum causes pulmonary vascular disease over a long period of time. This study aimed at (1) evaluating pulmonary vascular resistance (PVR) and (2) investigating the relation between PVR and exercise capacity in patients with open and closed ASD.status: publishe