Feasibility and acceptability of autism adapted safety plans: an external pilot randomised controlled trial.

Autistic people are a high-risk group for self-harm and suicide. There are no evidence-based suicide prevention interventions developed specifically for autistic people. We undertook a pilot feasibility randomised controlled trial of autism adapted safety plans (AASP) to reduce self-harm and suicide for autistic people. This study took place in the United Kingdom and followed a randomised, two-arm, controlled design. Autistic adults (n=53, mean age=39, gender=49% female, 29% not male or female) were recruited via third sector organisations and self-referral between 11.8.21 and 19.10.22. Participants were randomised without stratification to usual care with or without AASP. The AASP was completed by the autistic adults together with someone trained to support them. Research staff who completed follow-up assessments were blind to participant allocation. Primary outcomes were feasibility and acceptability. Participants were assessed at baseline, 1 and 6 months. Primary data were analysed under the intention to treat principle. Study protocol is published. The trial is closed to new participants. This study is registered with the ISRCTN registry, ISRCTN70594445. 53 participants consented, 49 were randomised to either AASP with usual care (n=25) or usual care (n=24). 68% of participants in the AASP arm were satisfied with the AASP and 41% rated it as useable. Feedback on the AASP and research methods were positive with suggested adaptations to some outcome measures. Retention and completion of outcomes measures in both arms was excellent, as was fidelity of delivery of the AASP. Study progression criteria were met, suggesting that the parameters of a future definitive trial of clinical and cost effectiveness of AASP to reduce self-harm and suicide in autistic adults are achievable, with minor recommended adaptions to outcome measures and AASP. Future research should explore the use of AASP in routine clinical practice. This study is funded by the NIHR [Public Health Research Programme (NIHR129196)]. [Abstract copyright: © 2024 The Authors.

Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection

Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasite Trypanosoma brucei and induces profound reactivity of glial cells and neuroinflammation when the parasites colonise the central nervous system. However, the transcriptional and functional responses of the brain to chronic T. brucei infection remain poorly understood. By integrating single cell and spatial transcriptomics of the mouse brain, we identify that glial responses triggered by infection are readily detected in the proximity to the circumventricular organs, including the lateral and 3rd ventricle. This coincides with the spatial localisation of both slender and stumpy forms of T. brucei. Furthermore, in silico predictions and functional validations led us to identify a previously unknown crosstalk between homeostatic microglia and Cd138+ plasma cells mediated by IL-10 and B cell activating factor (BAFF) signalling. This study provides important insights and resources to improve understanding of the molecular and cellular responses in the brain during infection with African trypanosomes

Adapting safety plans for autistic adults with involvement from the autism community

Background: Autistic adults are at greater risk of self-harm and suicide than the general population. One promising intervention in the general population is safety planning. We aimed to seek advice from autistic adults and others in the autism community on how to adapt safety plans for autistic adults. Methods: We conducted focus groups with autistic adults (n = 15), family members (n = 5), and service providers (n = 10), about their views of the Autism Adapted Safety Plan (AASP). We also conducted interviews about the acceptability of the AASP with autistic adults who had developed an AASP (n = 8) and with service providers who had supported them (n = 8). We analyzed the focus group and interview transcripts using thematic analysis. Results: Theme 1 highlights conditions needed to make the process of creating the AASP acceptable for autistic adults. This included creating the AASP with someone they could trust and at the right place and time, when they were not in distress or in crisis. Theme 2 describes how safety planning needed to be a creative, flexible, and iterative process. Autistic adults may need help in expressing their emotions and identifying coping strategies, which can be supported through visual resources and suggestions from the service provider. To ensure that the AASP is accessible in times of crisis, it needs to meet the autistic adults' preferences in terms of formatting and how it is stored (i.e., hard copy or electronic). Conclusions: The AASP is a potentially valuable intervention for autistic adults, provided that the process of creating it is flexible and sensitive to individual needs. Further testing of the AASP to assess its clinical effectiveness in reducing suicidal behavior could provide a life-saving intervention for autistic adults

Die Notverordnungen des kroatischen Präsidenten aus den Jahren 1991 und 1992

U radu se razmatraju uredbe iz nužde koje je donio predsjednik Republike Franjo Tuđman u drugoj polovici 1991. i početkom 1992. godine u vrijeme otvorene agresije na Republiku Hrvatsku. Glavnina uredbi donesena je 10. rujna 1991., a do kraja 1991. godine donesene su gotovo sve uredbe iz nužde. Uredbama su regulirani klasični državni resori poput pravosuđa, unutarnjih poslova i vojske, no velik dio uredbi regulirao je i javne službe te gospodarstvo.At the beginning, this paper gives a brief notional historical overview of emergency decrees, after which follows a reconstruction of events in 1990 that led to the introduction of articles 17 and 101 of the Constitution of the Republic of Croatia as Constitutional decrees relating to states of emergency. The central part of the paper deals with emergency decrees passed by the Croatian President Franjo Tuđman at the time of the open aggression against the Republic of Croatia in the second half of 1991 and the beginning of 1992. In this section, using sources, especially the minutes of the Commission for Constitutional Matters of the Croatian Partliament and the minutes of the plenary sessions of the Croatian Parliament, and also relevant literature, the paper sheds light on the circumstances under which the decrees were passed and approved by the Croatian Parliament, and thus provides a new interpretation of the decrees. After discussing the circumstances under which the decrees were passed, the author deals with various aspects of the decrees\u27 content, first noting the basic characteristics of the decrees, and then classifying them according to fields, such as: internal affairs, defense and justice, and also those covering public services and the economy. While discussing particular decrees the author sets out only the main provisions of the decrees with a view to presenting their basic characteristics, such as the limitation of constitutional rights and the centralisation of public services and of the economy. In the last part of the paper, the author analyzes the constitutionality of the decrees and their lifting. The question of whether the Parliament could convene is paramount in considering the constitutionality of the decrees, since this is important in establishing whether the President of the Republic had the power to pass decrees limiting constitutional rights. The author also considers the decision of the Constitutional Court to approve the constitutionality of the decrees. The lifting of the decrees is analyzed with special consideration given to the circumstances leading to this.Am Anfang dieser Arbeit wird eine kurze begriffshistorische Übersicht über die Notverordnungen präsentiert, wonach rekonstruiert wird, wie die den Ausnahmezustand regelnden Artikel 17 und 101 der Verfassung der Republik Kroatien von 1990 zustande kamen. Der zentrale Teil dieser Arbeit befasst sich mit den Notverordnungen, die der damalige kroatische Staatspräsident Franjo Tuđman während des offenen Angriffskrieges gegen die Republik Kroatien in der zweiten Hälfte des Jahres 1991 und Anfang 1992 erließ. Dabei wird versucht, anhand des Quellenstudiums, vor allem der Niederschriften zur Arbeit der parlamentarischen Kommission für Verfassungsfragen, der Protokolle zu den Plenarsitzungen des Parlaments der Republik Kroatien (Sabor), aber auch unter Rückgriff auf die entsprechende Literatur die Umstände des Erlasses der Notverordnungen sowie ihrer Bestätigung durch den Sabor zu beleuchten und auf diese Weise einen Beitrag zur Reinterpretation der betreffenden Verordnungen zu leisten. Nach einer dementsprechenden Klärung werden die inhaltlichen Aspekte der Verordnungen dargestellt, indem zunächst deren Hauptmerkmale bestimmt werden und danach eine Zuordnung zum Bereich des Inneren, der Verteidigung und der Justiz beziehungsweise zum Bereich der öffentlichen Aufgaben und der Wirtschaft erfolgt. Innerhalb der Darstellung einzelner Verordnungen versuchen wir, lediglich ihre wesentlichen Bestimmungen zu präsentieren, an denen die wichtigsten Merkmale wie die Beschränkung der Verfassungsrechte und die Zentralisierung der öffentlichen Aufgaben und der Wirtschaft deutlich werden. Im letzten Teil der Arbeit werden die Verfassungskonformität der Verordnungen und das Ende ihrer Gültigkeit analysiert. Die Verfassungsmäßigkeit der Verordnungen wird in erster Linie unter dem Aspekt untersucht, ob das Parlament hätte zusammentreten können, wovon schließlich die Zuständigkeit des Präsidenten der Republik für das Erlassen von verfassungsrechtsbeschränkenden Verordnungen abhing. Ebenfalls wird die Entscheidung des Verfassungsgerichts besprochen, in der es den Verordnungen Verfassungsmäßigkeit bescheinigt. Die Aufhebung der Verordnungen wird hinsichtlich der dafür verantwortlichen Umstände analysiert

A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860

Measured ambulation and self-reported health status following total joint replacement for the osteoarthritic knee

This paper describes the use of an ambulatory activity monitor to record patients over a 24 hour period as a quantitative outcome measure of activity and function to assess therapeutic intervention. The study builds on previous research by Chandler to develop mechanisms of activity monitoring

Defining the learning curve of point-of-care ultrasound for confirming endotracheal tube placement by emergency physicians

Abstract Background Unrecognized esophageal intubations are associated with significant patient morbidity and mortality. No single confirmatory device has been shown to be 100 % accurate at ruling out esophageal intubations in the emergency department. Recent studies have demonstrated that point-of-care ultrasound (POCUS) may be a useful adjunct for confirming endotracheal tube placement; however, the amount of practice required to become proficient at this technique is unclear. The purpose of this study is to determine the amount of practice required by emergency physicians to become proficient at interpreting ultrasound video clips of esophageal and endotracheal intubations. Methods Emergency physicians and emergency medicine residents completed a baseline interpretation test followed by a 10 min online tutorial. They then interpreted POCUS clips of esophageal and endotracheal intubations in a randomly selected order. If an incorrect response was provided, the participant completed another practice session with feedback. This process continued until they correctly interpreted ten consecutive ultrasound clips. Descriptive statistics were used to summarize the data. Results Of the 87 eligible physicians, 66 (75.9 %) completed the study. The mean score on the baseline test was 42.9 % (SD 32.7 %). After the tutorial, 90.9 % (60/66) of the participants achieved proficiency after one practice attempt and 100 % achieved proficiency after two practice attempts. Six intubation ultrasound clips were misinterpreted, for a total error rate of 0.9 % (6/684). Overall, the participants had a sensitivity of 98.3 % (95 % CI 96.3–99.4 %) and specificity of 100 % (95 % CI 98.9–100 %) for detecting correct tube location. Scans were interpreted within an average of 4 s (SD 2.9 s) of the intubation. Conclusions After a brief online tutorial and only two practice attempts, emergency physicians were able to quickly and accurately interpret ultrasound intubation clips of esophageal and endotracheal intubations