Search

Traumatic abdominal wall hernia is a rare presentation, most commonly reported in the context of motor vehicle accidents and associated with blunt abdominal injuries and handlebar injuries in the pediatric population. A 13-year-old boy presented with multiple traumatic injuries and hemodynamic instability after a high-speed motor vehicle accident. His injuries consisted of massive traumatic abdominal wall hernia (grade 4) with bowel injury and perforation, blunt aortic injury, a Chance fracture, hemopneumothorax, and a humeral shaft fracture. Initial surgical management included partial resection of the terminal ileum, sigmoid colon, and descending colon. Laparostomy was managed with negative pressure wound therapy. The patient underwent skin-only primary closure of the abdominal wall and required multiple returns to theatre for debridement, dressing changes, and repair of other injuries. Various surgical management options for abdominal wall closure were considered. In total, he underwent 36 procedures. The multiple injuries had competing management aims, which required close collaboration between specialist clinicians to form an individualized management plan. The severity and complexity of this injury was of a scale not previously experienced by many clinicians and benefited from intrahospital and interhospital specialist collaboration. The ideal aim of primary surgical repair was not possible in this case of a giant abdominal wall defect.

Introduction Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and participants’ genetic profiles.Methods and analysis EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will be given a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent to the study to access pre-existing clinical data. Participants will be added to the EAGER registry and data will be shared externally through established AIMS-2-TRIALS mechanisms.Ethics and dissemination To date, EAGER has received full ethical approval for 11 out of the 13 sites in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023), Spain (HCB/2023/0038, PIC-164-22), Sweden (Dnr 2023-06737-01), Ireland (230907) and Italy (CET_62/2023, CEL-IRCCS OASI/24-01-2024/EM01, EM 2024-13/1032 EAGER). Findings will be disseminated via scientific publications and conferences but also beyond to participants and the wider community (eg, the AIMS-2-TRIALS website, stakeholder meetings, newsletters).

Summary: Background: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. Methods: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant's virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074. Findings: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference −0.6%, 95% CI −3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period. Interpretation: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded. Funding: The National Institute for Health Research Health Technology Assessment programme.

Abstract Background What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). Method The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. Results A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. Discussion UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training.

Abstract Background Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors. Method Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail. Results Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p

This study described the developmental and behavioral characteristics of children identified with idiopathic sensory processing disorder (SPD) as well as the relations among specific types of SPD as proposed by the nosology presented by Miller et al. (2007), adaptive behavior profiles, and behaviors associated with mental functioning. A retrospective, non-experimental design applying descriptive and correlational analyses was used. Data were obtained from clinic medical records of 78 children ages 2 to 7 years who were identified with sensory processing problems affecting daily life, but who did not meet criteria for any other neurodevelopmental or mental disorders following a comprehensive diagnostic evaluation. Results revealed that all SPD types as described by current typologies were well represented with the most common being the over-responsivity sensory modulation subtype. Within the sample, 53% of the children displayed more than one SPD type. Atypical externalizing and internalizing behavior scores associated with various mental disorders as measured by the child behavior checklist (CBCL) fell in the borderline dysfunctional range. Adaptive behavior for all developmental domains was below average, and the severity of SPD symptoms moderately and positively correlated with behaviors associated with mental disorders, and with lower adaptive behavior performance. It was concluded that symptoms characteristic of the various types of idiopathic SPD overlap substantially suggesting that current typologies may include more types/subtypes than are necessary or clinically useful. Children with SPD share similar, but often less severe pathological behaviors associated with other mental or related neurodevelopmental disorders. Psychometrically sound measures of SPD are needed, and further study of the neural mechanisms involved in sensory processing deficits is vital for validating idiopathic SPD as its own diagnostic entity.

Intimate partner violence and sexual assault are under-researched experiences in autistic people's lives. Recent research, however, has shown that autistic people are more likely to have been victimized than non-autistic people. This research, therefore, sought to explore the firsthand accounts of a range of autistic people about intimate partner violence and sexual assault. Twenty-four autistic adults with lived experience (6 male, 15 female, 3 non-binary) aged 25-61 years took part in semi-structured interviews online. They were asked about their experiences of intimate partner violence and sexual assault, whether and how they felt being autistic interacted with those experiences, and what recommendations they would have for improving education in the future. Almost all participants had repeated experiences of intimate partner violence and sexual assault, regardless of gender, and there were clear similarities in their stories. Six themes with subthemes were identified. These were "'experiences of abuse'", "'autism used against you'", "'poor family models'", "'impact of/on friendships'", "'handling trauma'", and "'recommendations for future practice'". Autistic people experience many of the same patterns of abuse as non-autistic people do, but there are unique autism-related vulnerabilities and outcomes. We found that there were a variety of responses to these experiences, and call for greater understanding so that autistic victims can be better supported.

Abstract Recent work demonstrated that 3D fibrin scaffolds function as an effective substrate for engineering tissues from pluripotent stem cells. However, the rapid degradation rate of fibrin remains a major limitation when differentiating human pluripotent stem cells for tissue engineering applications. The addition of crosslinking agents, such as genipin, during the polymerization process increases scaffold stability while decreasing the degradation rate of fibrin. Genipin crosslinking alters the physical characteristics of the fibrin scaffolds, which influences the behaviour of the differentiating cells seeded inside. It also possesses neuritogenic and neuroprotective properties, making it particularly attractive for engineering neural tissue from pluripotent stem cells. Here we show that genipin enhances neuronal differentiation of neural progenitors derived from human induced pluripotent stem cells (hiPSCs) in 2D culture and genipin concentration influences the morphological and mechanical properties of 3D fibrin scaffolds. These mechanically stable genipin-crosslinked fibrin scaffolds support hiPSC-derived neural aggregates and induce neurite outgrowth while remaining intact for 2 weeks as opposed to 5 days for unmodified fibrin scaffolds.

The purpose of this study is to explore the views of autistic adults on randomised controlled trials, specifically on processes such as randomisation and blinding, to understand the barriers and facilitators for recruiting autistic people to randomised controlled trials involving medications. We conducted one-to-one interviews with 49 autistic adults. Interviews were audio-recorded and analysed thematically. The participants found randomised controlled trial processes acceptable and linked positive attitudes towards randomised controlled trial participation to autistic peoples' heightened sense of fairness and preference for evidence-driven knowledge. However, randomised controlled trial designs may be incompatible with a (1) preference for a controlled predictable world, (2) perceived vulnerability at physical and mental health levels and (3) history of misunderstanding and exclusion, crucially from healthcare professionals. Suggestions that emerged from our findings include efforts to co-produce research to nurture trust and adapting communication practices to improve access to trials. Autistic people are a highly motivated group to work with research teams to mitigate barriers to randomised controlled trial participation. We explored what psychosocial determinants play a role in the acceptability of randomised controlled trials to test interventions to improve quality of life and mental health in autistic adults. The study provides useful information that may help the design and conduct of more accessible trials with and for the autistic community.

Background and study aims Capsule endoscopy(CE) is a well-established investigation for iron deficiency anemia (IDA) and melena, usually following negative upper and lower endoscopy. We aimed to study the effect of earlier CE in the investigative pathway for inpatients with IDA or melena at a large tertiary referral centre. Patients and methods We analyzed inpatients undergoing CE for IDA or melena from 2005 to 2017, without signs/symptoms suggesting lower gastrointestinal tract pathology. Patients underwent CE following negative upper and lower gastrointestinal endoscopy (Group 1), or negative upper gastrointestinal endoscopy (UGIE) only (Group 2). Results One hundred and seventy inpatients underwent CE for IDA (n = 44) and melena (n = 126). In Group 1, 46/95 (48.4%) patients had small bowel (SB) findings. CE found 16/95 (16.8 %) gastric and 12/95 (12.6 %) colon findings. Three of 12 patients with colon findings required repeat colonoscopy. One hundred and three colon investigations were carried out for 95 admissions. In Group 2, 33/75 (44.0%) patients had SB findings. There were 12/75 (16.0 %) gastric and 11/75 (14.7 %) colon findings. In patients with positive CE, significant colonic findings led to colonoscopy in 10 of 39 patients (diagnostic yield 6/10). Thirty-six patients had negative CE; 15 underwent colonoscopy (diagnostic yield 9/15). The remaining 21 of 36 patients with no further colonoscopy did not develop adverse outcomes related to colonic pathology. Twenty-six colon investigations were carried out in 75 admissions. Patients in Group 2 had shorter mean times from admission to CE (5.08 ± 3.80 vs. 6.38 ± 3.80 days; P = 0.02) and hospital stays (10.5 ± 9.58 vs. 12.5 ± 11.4 days; P = 0.04) compared to Group 1. Conclusion Earlier use of CE in inpatients with melena or IDA, no signs of lower gastrointestinal pathology and negative UGIE resulted in shortened hospital stays, significant DY from both small bowel and upper gastrointestinal tract, and two-thirds less unnecessary colon investigations without affecting clinical outcomes.

We describe a method to evaluate an uncertainly budget for the in situ Ocean Colour Radiometric measurements. A Monte Carlo approach is chosen to propagate the measurement uncertainty inputs through the measurements model. The measurement model is designed to address instrument characteristics and uncertainty associated with them. We present the results for a particular example when the radiometers were fully characterised and then use the same data to show a case when such characterisation is missing. This, depending on the measurement and the wavelength, can increase the uncertainty value significantly; for example, the downwelling irradiance at 442.5 nm with fully characterised instruments can reach uncertainty values of 1%, but for the instruments without such characterisation, that value could increase to almost 7%. The uncertainty values presented in this paper are not final, as some of the environmental contributors were not fully evaluated. The main conclusion of this work are the significance of thoughtful instrument characterisation and correction for the most significant uncertainty contributions in order to achieve a lower measurements uncertainty value.

Decision makers need accessible robust evidence to introduce new policies to mitigate and adapt to climate change. There is an increasing amount of environmental information available to policy makers concerning observations and trends relating to the climate. However, this data is hosted across a multitude of websites often with inconsistent metadata and sparse information relating to the quality, accuracy and validity of the data. Subsequently, the task of comparing datasets to decide which is the most appropriate for a certain purpose is very complex and often infeasible. In support of the European Union’s Copernicus Climate Change Service (C3S) mission to provide authoritative information about the past, present and future climate in Europe and the rest of the world, each dataset to be provided through this service must undergo an evaluation of its climate relevance and scientific quality to help with data comparisons. This paper presents the framework for Evaluation and Quality Control (EQC) of climate data products derived from satellite and in situ observations to be catalogued within the C3S Climate Data Store (CDS). The EQC framework will be implemented by C3S as part of their operational quality assurance programme. It builds on past and present international investment in Quality Assurance for Earth Observation initiatives, extensive user requirements gathering exercises, as well as a broad evaluation of over 250 data products and a more in-depth evaluation of a selection of 24 individual data products derived from satellite and in situ observations across the land, ocean and atmosphere Essential Climate Variable (ECV) domains. A prototype Content Management System (CMS) to facilitate the process of collating, evaluating and presenting the quality aspects and status of each data product to data users is also described. The development of the EQC framework has highlighted cross-domain as well as ECV specific science knowledge gaps in relation to addressing the quality of climate data sets derived from satellite and in situ observations. We discuss 10 common priority science knowledge gaps that will require further research investment to ensure all quality aspects of climate data sets can be ascertained and provide users with the range of information necessary to confidently select relevant products for their specific application.

Anastasios Koulaouzidis, Sarah DouglasCentre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Edinburgh, UKAbstract: Until recently, the small bowel was considered a ‘no man’s land’ as the imaging modalities available for its investigation were laborious, invasive, costly, or involve significant radiation exposure. Wireless capsule endoscopy (WCE) has changed the field dramatically, over the last eight years. The established indications for small bowel WCE are obscure gastrointestinal bleed/anemia, Crohn’s disease, hereditary polyposis syndromes, and to a lesser extent, evaluation of side effects of nonsteroidal anti-inflammatory medications and coeliac disease. We herein present an overview of the capsule examination, which seems to be a quickly improving area.Keywords: capsule, imaging, small bowel, Crohn’s, celiac, GI bleed

Background and study aims: SmartPill® (Given Imaging Corp.,Yoqneam,Israel) is an ingestible, non-imaging capsule that records physiological data including contractions and pH throughout the gastrointestinal tract. There are scarce data looking at SmartPill® assessment of patients with known/suspected small-bowel Crohn’s Disease (CD). This pilot study aims to investigate feasibility and safety of SmartPill® to assess gut motility in this group. Patients and methods: Over 1 year, patients with known/suspected CD, referred for small-bowel capsule endoscopy (SBCE), were invited to participate and 12 were recruited (7 female, 5 male, mean age 44.2 ± 16.6 years). They underwent hydrogen breath test to exclude small-bowel bacterial overgrowth, patency capsule (Agile®), and provided stool samples for fecal calprotectin (FC). Patients ingested PillCam®SB2 and SmartPill® 4 hours apart. Using unpublished data, 33 healthy controls also were identified for the study. P