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Abstract Background Fluid balance gap (FBgap—prescribed vs. achieved) is associated with hospital mortality. Downtime is an important quality indicator for the delivery of continuous renal replacement therapy (CRRT). We examined the association of CRRT downtime with FBgap and clinical outcomes including mortality. Methods This is a retrospective cohort study of critically ill adults receiving CRRT utilizing both electronic health records (EHR) and CRRT machine data. FBgap was calculated as achieved minus prescribed fluid balance. Downtime, or percent treatment time loss (%TTL), was defined as CRRT downtime in relation to the total CRRT time. Data collection stopped upon transition to intermittent hemodialysis when applicable. Linear and logistic regression models were used to analyze the association of %TTL with FBgap and hospital mortality, respectively. Covariates included demographics, Sequential Organ Failure Assessment (SOFA) score at CRRT initiation, use of organ support devices, and the interaction between %TTL and machine alarms. Results We included 3630 CRRT patient-days from 500 patients with a median age of 59.5 years (IQR 50–67). Patients had a median SOFA score at CRRT initiation of 13 (IQR 10–16). Median %TTL was 8.1% (IQR 4.3–12.5) and median FBgap was 17.4 mL/kg/day (IQR 8.2–30.4). In adjusted models, there was a significant positive relationship between FBgap and %TTL only in the subgroup with higher alarm frequency (6 + alarms per CRRT-day) (β = 0.87 per 1% increase, 95%CI 0.48–1.26). No association was found in the subgroups with lower alarm frequency (0–2 and 3–5 alarms). There was no statistical evidence for an association between %TTL and hospital mortality in the adjusted model with the interaction term of alarm frequency. Conclusions In critically ill adult patients undergoing CRRT, %TTL was associated with FBgap only in the subgroup with higher alarm frequency, but not in the other subgroups with lower alarms. No association between %TTL and mortality was observed. More frequent alarms, possibly indicating unexpected downtime, may suggest compromised CRRT delivery and could negatively impact FBgap.

Abstract Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. Here we determined the prevalence of actionable mutations detectable in ctDNA using a clinically validated cancer gene panel assay in patients with TNBC, without recurrence at the time of study entry. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at much higher risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in neoadjuvant therapy protocols may be identifiable by combining tissue response and sensitive ctDNA detection.

BackgroundSocial media use has potential to facilitate the rapid dissemination of research evidence to busy health and social care practitioners. ObjectiveThis study aims to quantitatively synthesize evidence of the between- and within-group effectiveness of social media for dissemination of research evidence to health and social care practitioners. It also compared effectiveness between different social media platforms, formats, and strategies. MethodsWe searched electronic databases for articles in English that were published between January 1, 2010, and January 10, 2023, and that evaluated social media interventions for disseminating research evidence to qualified, postregistration health and social care practitioners in measures of reach, engagement, direct dissemination, or impact. Screening, data extraction, and risk of bias assessments were carried out by at least 2 independent reviewers. Meta-analyses of standardized pooled effects were carried out for between- and within-group effectiveness of social media and comparisons between platforms, formats, and strategies. Certainty of evidence for outcomes was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. ResultsIn total, 50 mixed-quality articles that were heterogeneous in design and outcome were included (n=9, 18% were randomized controlled trials [RCTs]). Reach (measured in number of practitioners, impressions, or post views) was reported in 26 studies. Engagement (measured in likes or post interactions) was evaluated in 21 studies. Direct dissemination (measured in link clicks, article views, downloads, or altmetric attention score) was analyzed in 23 studies (8 RCTs). Impact (measured in citations or measures of thinking and practice) was reported in 13 studies. Included studies almost universally indicated effects in favor of social media interventions, although effect sizes varied. Cumulative evidence indicated moderate certainty of large and moderate between-group effects of social media interventions on direct dissemination (standardized mean difference [SMD] 0.88; P=.02) and impact (SMD 0.76; P

Summary: Multimorbidity (multiple conditions) and polypharmacy (multiple medications) are increasingly common, yet there is a need to better understand the prevalence of co-occurrence. In this systematic review, we examined the prevalence of multimorbidity and polypharmacy among adults (≥18 years) and older adults (≥65 years) in clinical and community settings. Six electronic databases were searched, and 87 studies were retained after two levels of screening. Most studies focused on adults 65 years and older and were done in population-based community settings. Although the operational definitions of multimorbidity and polypharmacy varied across studies, consistent cut-points (two or more conditions and five or more medications) were used across most studies. In older adult samples, the prevalence of multimorbidity ranged from 4·8% to 93·1%, while the prevalence of polypharmacy ranged from 2·6% to 86·6%. High heterogeneity between studies indicates the need for more consistent reporting of specific lists of conditions and medications used in operational definitions.

EGFR-targeted therapies are efficacious, but toxicity is common and can be severe. Urokinase type plasminogen activator receptor (uPAR)-targeted drugs are only emerging, so neither their efficacy nor toxicity is fully established. Recombinant eBAT was created by combining cytokines EGF and uPA on the same single-chain molecule with truncated Pseudomonas toxin. Its purpose was to simultaneously target tumors and their vasculature in the tumor microenvironment. In prior studies on mice and dogs, the drug proved efficacious. Here, we report the safety of eBAT in normal wildtype, uPAR knockout, and immunoreplete and immunodeficient tumor-bearing mice, as well as in dogs with spontaneous sarcoma that more closely mirror human cancer onset. In immunocompetent mice, tumor-bearing mice, uPAR knockout mice, and mice receiving species-optimized eBAT, toxicities were mild and self-limiting. Likewise, in dogs with life-threatening sarcoma given dosages found to be biologically active, eBAT was well tolerated. In mice receiving higher doses, eBAT was associated with dose-dependent evidence of liver injury, including portal biliary hyperplasia, oval cell proliferation, lymphoplasmacytic inflammation, periportal hepatocellular microvesicular change, hemorrhage, necrosis, and apoptosis. The results support continuing the clinical development of eBAT as a therapeutic agent for individuals with sarcoma and other cancers.

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 124,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in three countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.

Objectives We aimed to explore the psychometric properties of the first known online asynchronous multiple mini-interview (MMI) designed for fairness with subgroup analyses by key characteristics, usability and acceptability.Design Cross-discipline multimethod evaluation.Setting One UK University.Participants Applicants to nursing, midwifery and paramedic science undergraduate programmes during 2021–2022.Primary, secondary outcome measures Psychometric properties (internal consistency, construct validity, dimensionality) were assessed using Cronbach’s alpha (α), parallel analysis (PA), Schmid-Leiman transformation and ordinal confirmatory factor analysis (CFA). Usability and acceptability were evaluated using descriptive statistics and conventional content analysis.Methods The system was configured in a seven question 4 min MMI. Applicants’ videorecorded their answers which were later assessed by interviewers and scores summed. Applicants and interviewers completed online evaluation questionnaires.Results Performance data from 712 applicants determined good-excellent reliability for the asynchronous MMI (mean α 0.72) with similar results across subgroups (gender, age, disability/support needs, UK/non-UK). PA and factor analysis results suggested there were seven factors relating to the MMI questions with an underlying general factor that explained the variance in observed candidate responses. A CFA testing a seven-factor hierarchical model showed an excellent fit to the data (Confirmatory Fit Index=0.99), Tucker Lewis Index=0.99, root mean square error (RMSE) =0.034). Applicants (n=210) viewed the flexibility, relaxed environment and cost savings advantageous. Interviewers (n=65) reported the system to be intuitive, flexible with >70% time saved compared with face-to-face interviews. Reduced personal communication was cited as the principal disadvantage.Conclusions We found that the asynchronous MMI was reliable, time-efficient, fair and acceptable and building fairness in was lost-cost. These novel, insights are applicable across health professions selection internationally informing the future configuration of online interviews to ensure workforces represent the societies they serve.

Abstract Background During vocational general practice training, the content of each trainee’s (in Australia, registrars’) in-consultation clinical experience is expected to entail a breadth of conditions that exemplify general practice, enabling registrars to gain competency in managing common clinical conditions and common clinical scenarios. Prior to the Registrar Clinical Encounters in Training (ReCEnT) project there was little research into the content of registrars’ consultations despite its importance to quality of training. ReCEnT aims to document the consultation-based clinical and educational experiences of individual Australian registrars. Methods ReCEnT is an inception cohort study. It is comprised of closely interrelated research and educational components. Registrars are recruited by participating general practice regional training organisations. They provide demographic information about themselves, their skills, and their previous training. In each of three 6-month long general practice training terms they provide data about the practice where they work and collect data from 60 consecutive patient encounters using an online portal. Analysis of data uses standard techniques including linear and logistic regression modelling. The ReCEnT project has approval from the University of Newcastle Human Research Ethics Committee, Reference H-2009–0323. Discussion Strengths of the study are the granular detail of clinical practice relating to patient demographics, presenting problems/diagnoses, medication decisions, investigations requested, referrals made, procedures undertaken, follow-up arranged, learning goals generated, and in-consultation help sought; the linking of the above variables to the presenting problems/diagnoses to which they pertain; and a very high response rate. The study is limited by not having information regarding severity of illness, medical history of the patient, full medication regimens, or patient compliance to clinical decisions made at the consultation. Data is analysed using standard techniques to answer research questions that can be categorised as: mapping analyses of clinical exposure; exploratory analyses of associations of clinical exposure; mapping and exploratory analyses of educational actions; mapping and exploratory analyses of other outcomes; longitudinal ‘within-registrar’ analyses; longitudinal ‘within-program’ analyses; testing efficacy of educational interventions; and analyses of ReCEnT data together with data from other sources. The study enables identification of training needs and translation of subsequent evidence-based educational innovations into specialist training of general practitioners.

The United States Environmental Protection Agency (US EPA) has developed a set of annual North American emissions data for multiple air pollutants across 18 broad source categories for 2002 through 2017. The sixteen new annual emissions inventories were developed using consistent input data and methods across all years. When a consistent method or tool was not available for a source category, emissions were estimated by scaling data from the EPA's 2017 National Emissions Inventory with scaling factors based on activity data and/or emissions control information. The emissions datasets are designed to support regional air quality modeling for a wide variety of human health and ecological applications. The data were developed to support simulations of the EPA's Community Multiscale Air Quality model but can also be used by other regional scale air quality models. The emissions data are one component of EPA's Air Quality Time Series Project which also includes air quality modeling inputs (meteorology, initial conditions, boundary conditions) and outputs (e.g., ozone, PM2.5 and constituent species, wet and dry deposition) for the Conterminous US at a 12 km horizontal grid spacing.

Abstract Background Prolidase deficiency (PD) is an autosomal recessive inborn multisystemic disease caused by mutations in the PEPD gene encoding the enzyme prolidase D, leading to defects in turnover of proline-containing proteins, such as collagen. PD is categorized as a metabolic disease, but also as an inborn error of immunity. PD presents with a range of findings including dysmorphic features, intellectual disabilities, recurrent infections, intractable skin ulceration, autoimmunity, and splenomegaly. Despite symptoms of immune dysregulation, only very limited immunologic assessments have been reported and standard therapies for PD have not been described. We report twin females with PD, including comprehensive immunologic profiles and treatment modalities used. Case presentation Patient 1 had recurrent infections in childhood. At age 13, she presented with telangiectasia, followed by painful, refractory skin ulcerations on her lower limbs, where skin biopsy excluded vasculitis. She had typical dysmorphic features of PD. Next-generation sequencing revealed pathogenic compound heterozygous mutations (premature stop codons) in the PEPD gene. Patient 2 had the same mutations, typical PD facial features, atopy, and telangiectasias, but no skin ulceration. Both patients had imidodipeptiduria. Lymphocyte subset analysis revealed low-normal frequency of Treg cells and decreased frequency of expression of the checkpoint molecule CTLA-4 in CD4+ TEM cells. Analysis of Th1, Th2, and Th17 profiles revealed increased inflammatory IL-17+ CD8+ TEM cells in both patients and overexpression of the activation marker HLA-DR on CD4+ TEM cells, reflecting a highly activated proinflammatory state. Neither PD patient had specific antibody deficiencies despite low CD4+CXCR5+ Tfh cells and low class-switched memory B cells. Plasma IL-18 levels were exceptionally high. Conclusions Immunologic abnormalities including skewed frequencies of activated inflammatory CD4+ and CD8+ TEM cells, decreased CTLA-4 expression, and defects in memory B cells may be a feature of immune dysregulation associated with PD; however, a larger sample size is required to validate these findings. The high IL-18 plasma levels suggest underlying autoinflammatory processes.

We report the case of a 19-month-old girl with late-onset ornithine transcarbamylase (OTC) deficiency initially referred to gastroenterology for intermittent vomiting lasting a year and abnormal liver enzymes (AST 730 U/L [reference range 26–55 U/L]; ALT 1213 U/L [reference range 11–30 U/L]) without hepatomegaly. While the patient was hospitalized for liver biopsy, intermittent tremors of the upper extremities with varying severity were noted. The patient was presumed to have hyperammonemia secondary to acute liver failure and was discharged after 5 days; follow-up monitoring led to readmission 7 days later. A brain MRI showed nonspecific bilateral pericallosal and bifrontal white matter FLAIR hyperintensities. These findings raised suspicion for a metabolic disease and prompted a genetics consultation. After inconclusive biochemical testing and worsening clinical status, rapid whole genome sequencing results were obtained identifying a novel, de novo, likely pathogenic, variant c.608C > T (p.Ser203Phe) in the OTC gene. The patient was promptly started on an oral nitrogen scavenger, citrulline supplementation, and protein restriction. Ammonia and glutamine levels normalized within 1 month of treatment and have stayed within the goal ranges with continued tailoring of treatment. Her parents noted resolution of vomiting and improved mood stability. Liver enzymes normalized after 2 months of treatment. The tremor, identified as asterixis, improved and a repeat brain MRI 3 months after the initial imaging showed near-complete resolution of previous white matter hyperintensities.

Abstract Introduction A high BMI during and after pregnancy is linked to poor pregnancy outcomes and contributes to long-term maternal obesity, hypertension, and diabetes. Evidence of feasible, effective postnatal interventions is lacking. This randomised controlled trial will assess the feasibility of conducting a future definitive trial to determine effectiveness and cost-effectiveness of lifestyle information and access to Slimming World® (Alfreton, UK) groups for 12 weeks commencing from 8 to 16 weeks postnatally, in relation to supporting longer-term postnatal weight management in women in an ethnically diverse inner city population. Methods/analysis Women will be recruited from one maternity unit in London. To be eligible, women will be overweight (BMI 25–29.9 kg/m2) or obese (BMI ≥ 30 kg/m2) as identified at their first antenatal contact, or have a normal BMI (18.5–24.9 kg/m2) at booking but gain excessive gestational weight as assessed at 36 weeks gestation. Women will be aged 18 and over, can speak and read English, expecting a single baby, and will not have accessed weight management groups in this pregnancy. Women will be randomly allocated to standard care plus lifestyle information and access to Slimming World® (Alfreton, UK) groups or standard care only. A sample of 130 women is required. Feasibility trial objectives reflect those considered most important inform a decision about undertaking a definitive future trial. These include estimation of impact of lifestyle information and postnatal access to Slimming World® (Alfreton, UK) on maternal weight change between antenatal booking weight and weight at 12 months postbirth, recruitment rate and time to recruitment, retention rate, influence of lifestyle information and Slimming World® (Alfreton, UK) groups on weight management, diet, physical activity, breastfeeding, smoking cessation, alcohol intake, physical and mental health, infant health, and health-related quality of life 6 and 12 months postnatally. An embedded process evaluation will assess acceptability of study processes and procedures to women. Ethics/dissemination London–Camberwell St Giles Research Ethics Committee, reference: 16/LO/1422. Outcomes will be disseminated in peer-reviewed journals and presentations at national and international conferences. Trial registration Trial registration number: ISRCTN 39186148. Protocol version number: v7, 13 August 17. Trial sponsor: King’s College London.

Background NHS Practitioner Health is the England wide programme providing mental health and addiction healthcare to doctors and dentists. Outcomes are assessed using five measures. Aims To contribute to a service evaluation of NHS Practitioner Health. To determine responsiveness to change and compare outcome measures. Method Measures were completed at baseline and 6 months: Generalized Anxiety Disorder Assessment (GAD-7), Perceived Stress Scale (PSS), Patient Health Questionaire-9 (PHQ-9), Warwick-Edinburgh Mental Wellbeing scale (WEMWBS), Psychological Outcome Profiles (PSYCHLOPS). Responsiveness to change was determined using effect size with improvement threshold ≥0.80. Instruments were compared using Bland–Altman plots. Results Our sample, n = 402; with 14 (3.5%) excluded for missing data; final sample, n = 388. All measures showed strong mean effect sizes: PSYCHLOPS 1.86 (95%CI 1.73–1.99), 75.8% ≥0.80; PSS 1.48 (1.34–1.62), 64.4% ≥0.80; WEMWBS 1.24 (1.13–1.35), 58.2% ≥0.80; GAD-7 1.07 (0.96–1.18), 52.8% ≥0.80; PHQ-9 0.86 (0.76–0.96), 52.8% ≥0.80. Findings were largely unchanged after stratification by diagnosis, presenting problem or therapy type. Fifty (12.9%) participants did not reach the threshold for improvement on any instrument. Bland–Altman plots indicated generally strong agreement between measures; combining PSYCHLOPS with WEMWBS maximised capture of improvement with only 3.6% of patients lying outside limits of agreement; GAD-7 was most likely to duplicate recovery scores of other measures. Conclusions Patients attending the NHS Practitioner Health service demonstrated high levels of improvement in mental health scores. The patient-generated instrument produced higher change scores than standardised instruments. Combining PSYCHLOPS and WEMWBS captured 96% of patients with above threshold improvement; GAD-7 added little to overall recovery measurement.

The mechanisms contributing to excessive fibronectin in preeclampsia, a pregnancy-related disorder, remain unknown. Herein, we investigated the role of JMJD6, an O2- and Fe2+-dependent enzyme, in mediating placental fibronectin processing and function. MALDI-TOF identified fibronectin as a novel target of JMJD6-mediated lysyl hydroxylation, preceding fibronectin glycosylation, deposition, and degradation. In preeclamptic placentae, fibronectin accumulated primarily in lysosomes of the mesenchyme. Using primary placental mesenchymal cells (pMSCs), we found that fibronectin fibril formation and turnover were markedly impeded in preeclamptic pMSCs, partly due to impaired lysosomal degradation. JMJD6 knockdown in control pMSCs recapitulated the preeclamptic FN phenotype. Importantly, preeclamptic pMSCs had less total and labile Fe2+ and Hinokitiol treatment rescued fibronectin assembly and promoted lysosomal degradation. Time-lapse imaging demonstrated that defective ECM deposition by preeclamptic pMSCs impeded HTR-8/SVneo cell migration, which was rescued upon Hinokitiol exposure. Our findings reveal new Fe2+-dependent mechanisms controlling fibronectin homeostasis/function in the placenta that go awry in preeclampsia.

Background: Increasing numbers of UK women have overweight or obese body mass index scores when they become pregnant, or gain excessive weight in pregnancy, increasing their risk of adverse outcomes. Failure to manage postnatal weight is linked to smoking, non-healthy dietary choices, lack of regular exercise and poorer longer-term health. Women living in areas of higher social deprivation are more likely to experience weight management problems postnatally. Objectives: The objectives were to assess the feasibility of conducting a definitive randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of lifestyle information and access to a commercial weight management group focusing on self-monitoring, goal-setting and motivation to achieve dietary change commencing 8–16 weeks postnatally to achieve and maintain weight management and positive lifestyle behaviour. Design: The design was a randomised two-arm feasibility trial with a nested mixed-methods process evaluation. Setting: The setting was a single centre in an inner city setting in the south of England. Participants: Participants were women with body mass index scores of > 25 kg/m2 at antenatal ‘booking’ and women with normal body mass index scores (18.0–24.9 kg/m2) at antenatal booking who developed excessive gestational weight gain as assessed at 36 weeks’ gestation. Main outcome measures: Recruitment, retention, acceptability of trial processes and identification of relevant economic data were the feasibility objectives. The proposed primary outcome was difference between groups in weight at 12 months postnatally, expressed as percentage weight change and weight loss from antenatal booking. Other proposed outcomes included assessment of diet, physical activity, smoking, alcohol consumption, body image, maternal esteem, mental health, infant feeding and NHS costs. Results: Most objectives were achieved. A total of 193 women were recruited, 98 allocated to the intervention arm and 95 to the control arm. High follow-up rates (> 80%) were achieved to 12 months. There was an 8.8% difference in weight loss at 12 months between women allocated to the intervention arm and women allocated to the control arm (13.0% vs. 4.2%, respectively; p = 0.062); 47% of women in the intervention arm attended at least one weight management session, with low risk of contamination between arms. The greatest benefit was among women who attended ≥ 10 sessions. Barriers to attending sessions included capability, opportunity and motivation issues. Data collection tools were appropriate to support economic evaluation in a definitive trial, and economic modelling is feasible to quantify resource impacts and outcomes not directly measurable within a trial. Limitations: The trial recruited from only one site. It was not possible to recruit women with normal body mass index scores who developed excessive pregnancy weight gain. Conclusions: It was feasible to recruit and retain women with overweight or obese body mass index scores at antenatal booking to a trial comparing postnatal weight management plus standard care with standard care only and collect relevant data to assess outcomes. Approaches to recruit women with normal body mass index scores who gain excessive gestational weight need to be considered. Commercial weight management groups could support women’s weight management as assessed at 12 months postnatally, with probable greater benefit from attending ≥ 10 sessions. Process evaluation findings highlighted the importance of providing more information about the intervention on trial allocation, extended duration of time to commence sessions following birth and extended number of sessions offered to enhance uptake and retention. Results support the conduct of a future randomised controlled trial. Trial registration: Current Controlled Trials ISRCTN39186148. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 8, No. 9. See the NIHR Journals Library website for further project information.

Abstract Background In settings where abortion is legally restricted, or permitted but not widely accessible, women face significant barriers to abortion access, sometimes leading them to seek services outside legal facilities. The advent of medication abortion has further increased the prevalence of informal sector abortion. This study investigates the reasons for attempting self-induction, methods used, complications, and sources of information about informal sector abortion, and tests a specific recruitment method which could lead to improved estimates of informal sector abortion prevalence among an at-risk population. Methods We recruited women who have sought informal sector abortion services in Cape Town, South Africa using respondent driven sampling (RDS). An initial seed recruiter was responsible for initiating recruitment using a structured coupon system. Participants completed face-to-face questionnaires, which included information about demographics, informal sector abortion seeking, and safe abortion access needs. Results We enrolled 42 women, nearly one-third of whom reported they were sex workers. Thirty-four women (81%) reported having had one informal sector abortion within the past 5 years, 14% reported having had two, and 5% reported having had three. These women consumed home remedies, herbal mixtures from traditional healers, or tablets from an unregistered provider. Twelve sought additional care for potential warning signs of complications. Privacy and fear of mistreatment at public sector facilities were among the main reported reasons for attempting informal sector abortion. Most women (67%) cited other community members as their source of information about informal sector abortion; posted signs and fliers in public spaces also served as an important source of information. Conclusions Women are attempting informal sector abortion because they seek privacy and fear mistreatment and stigma in health facilities. Some were unaware how or where to seek formal sector services, or believed the cost was too high. Many informal methods are ineffective and unsafe, leading to potential warning signs of complications and continued pregnancy. Sex workers may be at particular risk of unsafe abortion. Based on these results, it is essential that future studies sample women outside of the formal health sector. The use of innovative sampling methods would greatly improve our knowledge about informal sector abortion in South Africa.

BackgroundNational guidance cautions against low-intensity interventions for people with personality disorder, but evidence from trials is lacking.AimsTo test the feasibility of conducting a randomised trial of a low-intensity intervention for people with personality disorder.MethodSingle-blind, feasibility trial (trial registration: ISRCTN14994755). We recruited people aged 18 or over with a clinical diagnosis of personality disorder from mental health services, excluding those with a coexisting organic or psychotic mental disorder. We randomly allocated participants via a remote system on a 1:1 ratio to six to ten sessions of Structured Psychological Support (SPS) or to treatment as usual. We assessed social functioning, mental health, health-related quality of life, satisfaction with care and resource use and costs at baseline and 24 weeks after randomisation.ResultsA total of 63 participants were randomly assigned to either SPS (n = 33) or treatment as usual (n = 30). Twenty-nine (88%) of those in the active arm of the trial received one or more session (median 7). Among 46 (73%) who were followed up at 24 weeks, social dysfunction was lower (−6.3, 95% CI −12.0 to −0.6, P = 0.03) and satisfaction with care was higher (6.5, 95% CI 2.5 to 10.4; P = 0.002) in those allocated to SPS. Statistically significant differences were not found in other outcomes. The cost of the intervention was low and total costs over 24 weeks were similar in both groups.ConclusionsSPS may provide an effective low-intensity intervention for people with personality disorder and should be tested in fully powered clinical trials.

Next-generation RNA-sequencing is an incredibly powerful means of generating a snapshot of the transcriptomic state within a cell, tissue, or whole organism. As the questions addressed by RNA-sequencing (RNA-seq) become both more complex and greater in number, there is a need to simplify RNA-seq processing workflows, make them more efficient and interoperable, and capable of handling both large and small datasets. This is especially important for researchers who need to process hundreds to tens of thousands of RNA-seq datasets. To address these needs, we have developed a scalable, user-friendly, and easily deployable analysis suite called RMTA (Read Mapping, Transcript Assembly). RMTA can easily process thousands of RNA-seq datasets with features that include automated read quality analysis, filters for lowly expressed transcripts, and read counting for differential expression analysis. RMTA is containerized using Docker for easy deployment within any compute environment [cloud, local, or high-performance computing (HPC)] and is available as two apps in CyVerse's Discovery Environment, one for normal use and one specifically designed for introducing undergraduates and high school to RNA-seq analysis. For extremely large datasets (tens of thousands of FASTq files) we developed a high-throughput, scalable, and parallelized version of RMTA optimized for launching on the Open Science Grid (OSG) from within the Discovery Environment. OSG-RMTA allows users to utilize the Discovery Environment for data management, parallelization, and submitting jobs to OSG, and finally, employ the OSG for distributed, high throughput computing. Alternatively, OSG-RMTA can be run directly on the OSG through the command line. RMTA is designed to be useful for data scientists, of any skill level, interested in rapidly and reproducibly analyzing their large RNA-seq data sets.

Mass spectrometry (MS) is an emerging method to determine the accurate concentration of immunogenic gluten peptides. It is of interest to quantify specific peptides within the gluten peptidome due to the role they play in the activation of the celiac immune cascade. Celiac disease is an autoimmune disorder triggered in genetically susceptible individuals by the presence of specific gluten peptides that resist digestion in the gastrointestinal tract. The protocol detailed within this paper can accurately quantify (label-free) the concentration of six immunogenic gluten peptides (including the 33mer) released from a food matrix using the INFOGEST in vitro digestion protocol. This method can be used to monitor small changes in the concentration of these marker peptides in response to exogenous factors such as plant-breeding, fermentation or food processing.

Background: Evidence suggests that investing in specialist eating disorders services for young people with anorexia nervosa could have important implications for the NHS, with the potential to improve health outcomes and reduce costs through reductions in the number and length of hospital admissions. Objectives: The primary objectives were to evaluate the costs and cost-effectiveness of alternative community-based models of service provision for young people with anorexia nervosa and to model the impact of potential changes to the provision of specialist services. Design: Observational surveillance study using the Child and Adolescent Psychiatry Surveillance System. Setting: Community-based secondary or tertiary child and adolescent mental health services (CAMHS) in the UK and the Republic of Ireland. Participants: A total of 298 young people aged 8–17 years in contact with CAMHS for a first episode of anorexia nervosa in accordance with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria. Interventions: Community-based specialist eating disorders services and generic CAMHS. Main outcome measures: Children’s Global Assessment Scale (CGAS) score (primary outcome) and percentage of median expected body mass index (BMI) for age and sex (%mBMI) (secondary outcome) were assessed at baseline and at 6 and 12 months. Data sources: Data were collected by clinicians from clinical records. Results: Total costs incurred by young people initially assessed in specialist eating disorders services were not significantly different from those incurred by young people initially assessed in generic CAMHS. However, adjustment for baseline covariates resulted in observed differences favouring specialist services (costs were lower, on average) because of the significantly poorer clinical status of the specialist group at baseline. At the 6-month follow-up, mean %mBMI was significantly higher in the specialist group, but no other significant differences in outcomes were evident. Cost-effectiveness analyses suggest that initial assessment in a specialist service has a higher probability of being cost-effective than initial assessment in generic CAMHS, as determined by CGAS score and %mBMI. However, no firm conclusion can be drawn without knowledge of society’s willingness to pay for improvements in these outcomes. Decision modelling did not support the hypothesis that changes to the provision of specialist services would generate savings for the NHS, with results suggesting that cost per 10-point improvement in CGAS score (improvement from one CGAS category to the next) varies little as the percentage of participants taking the specialist or generic pathway is varied. Limitations: Follow-up rates were lower than expected, but the sample was still larger than has been achieved to date in RCTs carried out in this population in the UK, and an exploration of the impact of missing cost and outcome data produced very similar results to those of the main analyses. Conclusions: The results of this study suggest that initial assessment in a specialist eating disorders service for young people with anorexia nervosa may have a higher probability of being cost-effective than initial assessment in generic CAMHS, although the associated uncertainty makes it hard to draw firm conclusions. Although costs and outcomes were similar, young people in specialist services were more severely ill at baseline, suggesting that specialist services were achieving larger clinical effectiveness gains without the need for additional expenditure. The results did not suggest that providing more specialist services would save money for the NHS, given similar costs and outcomes, so decisions about which service type to fund could be made with reference to other factors, such as the preferences of patients and carers. Future work: Data on measures of quality of life capable of generating quality-adjusted life-years are needed to confirm the cost-effectiveness of specialist services. Trial registration: Current Controlled Trials ISRCTN12676087. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 7, No. 37. See the NIHR Journals Library website for further project information.

Background: In persons suffering from rheumatoid arthritis (RA), the metacarpophalangeal (MCP) joints are commonly affected, resulting in inflammation, pain, joint instability, diminished grip strength and difficulties with function. However, the effectiveness of Kinesio Taping® of the MCP joints in alleviating the symptoms has not been established. Aim: To determine the effectiveness of bilateral Kinesio Taping® of the MCP joints on pain, range of motion, grip strength and hand function in elderly individuals previously diagnosed with RA. Methods: A repeated measure, experimental design was used over a 7-week period with the Kinesio Taping group (n = 30) receiving bilateral space correction Kinesio Taping® of the MCP joints with a joint protection (JP) group (n = 31) participating in JP workshops. The Kinesio Tape® was worn for 3 days a week with four applications during the data collection process. For the control group, 2-hour JP educational–behavioural workshops were run weekly for 4 weeks. Weekly assessments were completed for grip strength, ulnar deviation and pain (VAS), and two pre-intervention assessments and one post-intervention assessment was completed for the Michigan Hands Outcomes Questionnaire (MHQ). Results: Kinesio Taping® of the MCP joints showed a significant decrease in pain (p = 0.001) and improved range of motion (p = 0.001 bilaterally). JP was found to have a significant improvement in grip strength (p = 0.001 bilaterally) and in the work (p = 0.01) and activities of daily living (ADL) (p = 0.01) sections of the MHQ. No significant difference was found between groups after intervention in the majority of outcomes (p = 0.24) except for grip strength where a significant difference was found. Conclusion: Kinesio Taping® of the MCP joints is an effective conservative intervention to improve pain and MCP ulnar deviation in individuals with RA. Significance of the work: Kinesio Taping® of the MCP joints of individuals with RA showed a significant decrease in pain (p = 0.00) and improved range of motion (p = 0.001 bilaterally). JP was found to significantly improve grip strength (p = 0.001 bilaterally) and in the work (p = 0.01) and ADL (p = 0.01) sections of the MHQ. No significant difference was found between groups after intervention in the majority of outcomes (p = 0.24) except for grip strength where a significant difference was found (p = 0.001).

Background: Identification of permanent hearing impairment at the earliest possible age is crucial to maximise the development of speech and language. Universal newborn hearing screening identifies the majority of the 1 in 1000 children born with a hearing impairment, but later onset can occur at any time and there is no optimum time for further screening. A universal but non-standardised school entry screening (SES) programme is in place in many parts of the UK but its value is questioned. Objectives: To evaluate the diagnostic accuracy of hearing screening tests and the cost-effectiveness of the SES programme in the UK. Design: Systematic review, case–control diagnostic accuracy study, comparison of routinely collected data for services with and without a SES programme, parental questionnaires, observation of practical implementation and cost-effectiveness modelling. Setting: Second- and third-tier audiology services; community. Participants: Children aged 4–6 years and their parents. Main outcome measures: Diagnostic accuracy of two hearing screening devices, referral rate and source, yield, age at referral and cost per quality-adjusted life-year. Results: The review of diagnostic accuracy studies concluded that research to date demonstrates marked variability in the design, methodological quality and results. The pure-tone screen (PTS) (Amplivox, Eynsham, UK) and HearCheck (HC) screener (Siemens, Frimley, UK) devices had high sensitivity (PTS ≥ 89%, HC ≥ 83%) and specificity (PTS ≥ 78%, HC ≥ 83%) for identifying hearing impairment. The rate of referral for hearing problems was 36% lower with SES (Nottingham) relative to no SES (Cambridge) [rate ratio 0.64, 95% confidence interval (CI) 0.59 to 0.69; p

The success of global treatment as prevention (TasP) efforts for individuals living with HIV/AIDS (PLWHA) is dependent on successful implementation, and therefore the appropriate contribution of social and behavioral science to these efforts. Understanding the psychosocial context of condomless sex among PLWHA could shed light on effective points of intervention. HPTN 063 was an observational mixed-methods study of sexually active, in-care PLWHA in Thailand, Zambia, and Brazil as a foundation for integrating secondary HIV prevention into HIV treatment. From 2010-2012, 80 qualitative interviews were conducted with PLWHA receiving HIV care and reported recent sexual risk. Thirty men who have sex with women (MSW) and 30 women who have sex with men (WSM) participated in equal numbers across the sites. Thailand and Brazil also enrolled 20 biologically-born men who have sex with men (MSM). Part of the interview focused on the impact of HIV on sexual practices and relationships. Interviews were recorded, transcribed, translated into English and examined using qualitative descriptive analysis. The mean age was 25 (SD = 3.2). There were numerous similarities in experiences and attitudes between MSM, MSW and WSM across the three settings. Participants had a high degree of HIV transmission risk awareness and practiced some protective sexual behaviors such as reduced sexual activity, increased use of condoms, and external ejaculation. Themes related to risk behavior can be categorized according to struggles for intimacy and fears of isolation, including: fear of infecting a sex partner, guilt about sex, sexual communication difficulty, HIV-stigma, and worry about sexual partnerships. Emphasizing sexual health, intimacy and protective practices as components of nonjudgmental sex-positive secondary HIV prevention interventions is recommended. For in-care PLWHA, this approach has the potential to support TasP. The overlap of themes across groups and countries indicates that similar intervention content may be effective for a range of settings.

ObjectiveOne in six young adults presents with at least one mental health problem. However, so far, little attention has been directed to the mental health needs and the efficacy of therapeutic interventions for young adults. We conducted a systematic review and meta-analysis of the type, quality and efficacy of psychoanalytic psychotherapy for young people.MethodWe searched the PsycInfo, PubMed, Embase, and Cochrane databases to identify all the published randomized controlled trials (RCT), and naturalistic and observational studies of psychodynamic or psychoanalytic psychotherapies. We calculated the standardized mean difference in scores of psychodynamic interventions versus control conditions, adopting a random effects model (Hedges’ g).ResultsWe identified 22 eligible studies, including 14 RCTs, and 8 naturalistic studies. Statistical analyses showed no significant difference between psychodynamic psychotherapy and other comparison treatments (psychotherapy or pharmacological interventions) for young adults (Hedges’g − 0.34 [95% CI: −0.991;-0.309], p = 0.304). Nevertheless, there was a significant effect of psychodynamic psychotherapy when compared with control conditions (waiting list or treatment as usual) for target symptoms (Hedges’g − 1.24 [95% CI: −1.97;-0.51], p

Summary: Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges for targeted clinical interventions due to prevalent KRAS mutations, rendering PDAC resistant to RAF and MEK inhibitors (RAFi and MEKi). In addition, responses to targeted therapies vary between patients. Here, we explored the differential sensitivities of PDAC cell lines to RAFi and MEKi and developed an isogenic pair comprising the most sensitive and resistant PDAC cells. To simulate patient- or tumor-specific variations, we constructed cell-line-specific mechanistic models based on protein expression profiling and differential properties of KRAS mutants. These models predicted synergy between two RAFi with different conformation specificity (type I½ and type II RAFi) in inhibiting phospho-ERK (ppERK) and reducing PDAC cell viability. This synergy was experimentally validated across all four studied PDAC cell lines. Our findings underscore the need for combination approaches to inhibit the ERK pathway in PDAC.

Objectives Generation Scotland (GS) is a family-based genetic epidemiology study. Initial recruitment was ~24,000 adult volunteers from across Scotland in 2006-11 with consent for medical record linkage and re-contact. In 2022 we began recruiting another 20,000, with consent extended to administrative records, with age range now 12+. Methods People join the study and complete a questionnaire online, with postal saliva sample collection for DNA. Initially, the consent process required a parent/guardian to join GS, confirm their 12-15 year-old’s capacity for enduring consent and invite their child to join. After launch, parents and young people fed back that the communication and consent methods had a negative effect on the ability of young people to join GS - impacting their autonomy, as they were unable join GS independently of their parents. Results The GS Team designed a new sign-up process for 12–15 year-olds that allowed the teenager to sign up first and request that their parent agree they have capacity to consent. Creating this process was done in collaboration with the new GS YPAG. This new sign-up process was launched in September 2023. We also enabled sign-up using a mobile phone number instead of an email address. Conclusion Co-design of GS recruitment with young people and parents has greatly improved the sign-up process, making GS the first UK longitudinal study where people aged 12-15 can provide enduring consent online with parental confirmation of their capacity. This provides young people with greater ownership over their ability to take part in health research.