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Nurturing transformative participation:A participatory realist review of mental health interventions in low resource settings
Get PDFPurpose The importance of involving people with lived experiences of mental health difficulties and the communities they inhabit, in interventions for them is now widely recognised. However, there is a lack of scrutiny around the theory and practice of how - and to what extent - participation occurs in global mental health interventions. The aim of this review was to examine existing literature and consult with community groups in low and middle income settings in order to understand how, for whom and under what conditions participatory approaches work to lead to positive outcomes for mental health. Methods Informed by a realist approach, we developed a new methodology combining a realist literature synthesis with the experiences of everyday citizens and service users from communities within low and middle income countries. Across a ten-step process we systematically reviewed literature and iteratively conducted focus group discussions, to inform the development of mid-range theories and a programme theory of participation that was reviewed and approved by community members in our LMIC sites. Results Participation in global mental health varies widely across contexts and programmes. We developed a programme theory based on seven principles, to understand how and under what circumstances participation can be meaningful, transformative and lead to improved mental health. The principles were: 1. Interventions and programmes should be built on strong relationships with communities in their localities; 2. Long term engagement in a locality means that services are more responsive; 3. A trusting, supportive and collaborative therapeutic relationship is critical when responding to mental health needs; 4. it is important to integrate existing beliefs, metaphors and traditions into understandings about mental health; 5. Groups and peer support can be important sources of social support leading to changes at individual and group levels; 6. Providing mental health support in spaces which are physically and emotionally safe helps marginalised groups to participate; and 7. Facilitating opportunities for participation and collective action strengthens mental health and social wellbeing. Conclusions Bringing together theory and practice, this realist review underscores the importance of meaningful participation in global mental health. Through this work we develop a programme theory, identifying seven key principles important to facilitating transformative participation
Measurement of the associated production of a top-antitop-quark pair and a Higgs boson decaying into a bb pair in pp collisions at √s = 13 TeV using the ATLAS detector at the LHC
Get PDFHumans in Africa’s wet tropical forests 150 thousand years ago
Get PDFHumans emerged across Africa shortly before 300 thousand years ago (ka)1,2,3. Although this pan-African evolutionary process implicates diverse environments in the human story, the role of tropical forests remains poorly understood. Here we report a clear association between late Middle Pleistocene material culture and a wet tropical forest in southern Côte d’Ivoire, a region of present-day rainforest. Twinned optically stimulated luminescence and electron spin resonance dating methods constrain the onset of human occupations at Bété I to around 150 ka, linking them with Homo sapiens. Plant wax biomarker, stable isotope, phytolith and pollen analyses of associated sediments all point to a wet forest environment. The results represent the oldest yet known clear association between humans and this habitat type. The secure attribution of stone tool assemblages with the wet forest environment demonstrates that Africa’s forests were not a major ecological barrier for H. sapiens as early as around 150 ka
Molecular glues that inhibit deubiquitylase activity and inflammatory signalling
Get PDFDeubiquitylases (DUBs) are crucial in cell signaling and are often regulated by interactions within protein complexes. The BRCC36 isopeptidase complex (BRISC) regulates inflammatory signaling by cleaving K63-linked polyubiquitin chains on type I interferon receptors (IFNAR1). As a Zn²⁺-dependent JAMM/MPN (JAB1, MOV34, MPR1, Pad1 N-terminal) DUB, BRCC36 is challenging to target with selective inhibitors. Here, we discover first-in-class inhibitors, termed BRISC molecular glues (BLUEs), which stabilize a 16-subunit human BRISC dimer in an autoinhibited conformation, blocking active sites and interactions with the targeting subunit, serine hydroxymethyltransferase 2. This unique mode of action results in selective inhibition of BRISC over related complexes with the same catalytic subunit, splice variants and other JAMM/MPN DUBs. BLUE treatment reduced interferon-stimulated gene expression in cells containing wild-type BRISC and this effect was abolished when using structure-guided, inhibitor-resistant BRISC mutants. Additionally, BLUEs increase IFNAR1 ubiquitylation and decrease IFNAR1 surface levels, offering a potential strategy to mitigate type I interferon-mediated diseases. Our approach also provides a template for designing selective inhibitors of large protein complexes by promoting rather than blocking protein–protein interactions
Operating Department Practitioner’s research priorities: A Delphi study
Get PDFWith the 2022 Allied Health Professions’ Research and Innovation Strategy and the College of Operating Department Practitioners joining the Council for Allied Health Professions Research, understanding the Operating Department Practitioner profession’s vision for research and innovation and identifying its research priorities has become important. This Delphi study aimed to establish research priorities for the Operating Department Practitioner profession. Questionnaires were distributed to Operating Department Practitioners using College of Operating Department Practitioners and social media networks. Round 1 saw 49 eligible responses; this reduced to 21 in Round 2 and 17 in Round 3. Thirty-one research priorities were identified by consensus. Priority rank was determined by mean score, percentage agreement, and coefficient of variance. By reaching a consensus, Operating Department Practitioners co-created research priorities and identified several themes that will contribute to professional development and patient care and support funding opportunities. The five key themes were Workforce Transformation, Education, Patient Safety and Experience, Innovation and Technology, and Theatre Culture
Adapting Public Service Media in Belgium: Meeting technology and audience needs in the Age of Platforms
Get PDFPublic service media (PSM) worldwide have consistently been subject to societal and technological changes. Recent years have confronted PSM with radical transformations in media use, competition with transnational streaming services, and the dominance of big tech. New competitors for the attention of citizens have challenged both the PSM mission and values as well as the organization, requiring broadcasters to transform into fully digital, online-first organisations. In this context, we present results from research conducted during the second year of PSM-AP, a large-scale comparative research project analysing ‘Public Service Media in the Age of Platforms’. In this brief, we put forward a series of findings and recommendations on the organisational and cultural challenges facing PSM in the two main language communities of Belgium. This report is based on in-depth interviews with employees (top and middle management) in two PSM organisations: RTBF (French-speaking Community of Belgium) and VRT (Dutch-speaking Community). The collected data was analysed in line with country-specific organisational reports and industry documents
High prevalence of platelet function disorders in women referred for surgical management of refractory heavy menstrual bleeding.
Get PDFINTRODUCTION: Heavy menstrual bleeding (HMB) is a common presenting symptom in women with bleeding disorders, yet haemostatic testing is sometimes overlooked, even when refractory HMB requires surgical intervention. AIM: To determine the prevalence of bleeding disorders in women referred for surgical management of HMB and investigate screening approaches for bleeding disorders in this population.
METHODS: Women with refractory HMB referred for surgical management were enrolled prospectively and underwent a detailed haemostatic investigation. The International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) and PFA-100 assay were interrogated as screening tools for bleeding disorders. Multiplate whole blood impedance aggregometry (WBIA) was compared to the current gold-standard lumiaggregometry testing for platelet dysfunction.
RESULTS: Fifty women underwent laboratory testing. Sixteen percent (95% confidence interval [CI] 7.2%-29.1%) were diagnosed with platelet function defects based on persistently abnormal lumiaggregometry results. No other clinically significant abnormalities were diagnosed. Women were more likely to be diagnosed with platelet dysfunction if they had failed a greater number of prior therapies, particularly prior endometrial ablation. The ISTH-BAT lacked diagnostic accuracy, even at the calculated optimal cutoff value, and PFA-100 assay lacked sensitivity. Multiplate WBIA was inferior to lumiaggregometry for the detection of platelet function disorders, with sensitivity of 62.5% (95% CI 24.5%-91.5%) and specificity of 87.5% (95% CI 73.2%-95.8%).
CONCLUSION: Study findings support platelet function analysis by lumiaggregometry in women with refractory HMB requiring surgery. Accurate diagnosis would allow targeted haemostatic therapy and implementation of additional perioperative safety measures if surgery is still required
Profiling genetic mutations in the DNA damage repair genes of oral squamous cell carcinoma patients from Pakistan
Get PDFHerein, we reported mutations in five DNA Damage Repair (DDR) i.e., TP53, ATR, ATM, CHEK1 and CHEK2 involved in OSCC using NG-WES and their analysis using bioinformatics tools. Out of 42 identified mutations, 16.7% are reported for the 1st time. A total of 28 nonsynonymous SNVs are identified. TP53 harbored the highest number of mutations followed by ATM, ATR, CHEK1 and CHEK2. Nine mutations (TP53p.R43H, TP53p.L125Q, TP53p.R116Q, TP53p.C110Y, TP53p.L62F, ATRp.H120Y, ATMp.P1054R, ATMp.D1853V, ATMp.T2934N) were predicted highly pathogenic. SAAFEQ-SEQ predicted destabilizing effects for all mutations, while ISPRED-SEQ identified 09 IS mutations, 07 on TP53, 01 in ATR and 01 in CHEK1 with no IS mutations predicted for ATM and CHEK2. Among the IS mutations, only SNVs were used in MDS simulations. The gyration radius for all IS SNVs was larger for mutant as compared to the wild type indicating perturbed folding behavior of the mutant proteins. Structural deviations across the carbon back bone were noted by RMSD for mutant and wild type. The TP53 IS mutations include TP53p.R116Q, TP53 p.C110Y, TP53p.R43H, TP53p.E214X, TP53p.R210X, TP53 p.C110Afs*5 and TP53 p,S108Ffs*23 whereas ATR and CHEK1 IS mutations consist of ATRp.M1932T and CHEK1p.E76Kfs*21. ConSurf analysis revealed four SNVs with a high conservation score (9) on TP53 and ATM. TP53p.P33R was predominantly associated with moderately differentiated tumors (84.60%), naswar users (86.60%) and positive family history of cancer (91.60%). The TP53p.P33R, ATRp.M211T and CHEK1p.I437V mutations were found recurrently in 21/27 (77.7%), 20/27 (74.04%), and 27/27 (100%) patients, suggesting its potential biomarker applications in local screening
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