MeCP2 binds to methylated DNA independently of phase separation and heterochromatin organisation.

Correlative evidence has suggested that the methyl-CpG-binding protein MeCP2 contributes to the formation of heterochromatin condensates via liquid-liquid phase separation. This interpretation has been reinforced by the observation that heterochromatin, DNA methylation and MeCP2 co-localise within prominent foci in mouse cells. The findings presented here revise this view. MeCP2 localisation is independent of heterochromatin as MeCP2 foci persist even when heterochromatin organisation is disrupted. Additionally, MeCP2 foci fail to show hallmarks of phase separation in live cells. Importantly, we find that mouse cellular models are highly atypical as MeCP2 distribution is diffuse in most mammalian species, including humans. Notably, MeCP2 foci are absent in Mus spretus which is a mouse subspecies lacking methylated satellite DNA repeats. We conclude that MeCP2 has no intrinsic tendency to form condensates and its localisation is independent of heterochromatin. Instead, the distribution of MeCP2 in the nucleus is primarily determined by global DNA methylation patterns.

Adequate menstrual suppression in adolescents with inherited bleeding disorders often requires multiple treatment changes: Retrospective cohort study of a multidisciplinary clinic.

Heavy menstrual bleeding (HMB) is often the presenting symptom for females with inherited bleeding disorders (IBD). Multidisciplinary clinics leverage the expertise of hematologists and women's health specialists. This study characterizes the complexity of HMB management for adolescents with IBDs from a large multidisciplinary clinic. Adolescents often required multiple different menstrual suppression treatments, with only about 20% achieving acceptable suppression with their first treatment. Adolescents switched therapy most often for uncontrolled bleeding, followed by adverse effects, and patient preference. Given the difficulty in achieving adequate menstrual suppression, multidisciplinary clinics offer necessary expertise in accomplishing bleeding control with minimal adverse effects.

How to discuss transferability of qualitative research in health professions education.

Transferability is commonly identified as a quality criterion for qualitative research. This criterion was introduced by Lincoln and Guba to describe the degree to which a study's findings can be transferred to other contexts, settings or respondents. In this How To paper, we present a more nuanced, multidimensional view of transferability and explain relevant concepts, reflexive approaches and specific techniques to guide researchers in discussing transferability. We identify three dimensions of transferability for use in many approaches to qualitative research: applicability, resonance and theoretical engagement. Transferability as applicability relates to providing sufficient information for readers to evaluate the relevance of findings to other contexts. Transferability as resonance requires the researcher to present the research in a way that evokes a sense of familiarity or shared experience. Transferability as theoretical engagement refers to ways the researcher uses theory to frame a problem, connects findings to existing constructs and/or proposes a model or theory that could explain a process or phenomenon. We encourage researchers to consider all three dimensions of transferability when developing and presenting their work, keeping in mind that some dimensions may be more relevant than others based on study methodology and project goals.

Procedural outcomes in children with mild type 1 von Willebrand disease.

Background: In patients with mild type 1 von Willebrand disease (VWD), treatment guidelines suggest individualization of surgical management. However, these conditional recommendations are based on very low-certainty evidence due to limited data on surgical outcomes in this population. Objectives: To characterize procedural bleeding prophylaxis strategies and outcomes in children with mild type 1 VWD. Methods: This is a retrospective cohort study that included patients aged between 0 and 21 years with mild type 1 VWD (defined as von Willebrand factor antigen and/or an activity of 30-50 IU/dL) who underwent a procedure from July 1, 2017, to July 1, 2022. Demographic, surgical, medication, and bleeding data were collected by manual chart review. Results: A total of 161 procedures were performed in 108 patients. The population was primarily female (75%), White (77.8%), and non-Hispanic (79.6%). Median age was 15.8 years (IQR, 8.2-17.6). Fifty-nine surgeries were classified as major, 66 as minor, and 36 as dental. For most procedures, patients received only antifibrinolytics for bleeding prophylaxis (n = 128, 79.5%); desmopressin was used in 17 (10.6%) procedures, and von Willebrand factor concentrate was used in 12 (7.5%) procedures. Bleeding complications occurred in 8 (5.0%) procedures: these included 1 major, 4 clinically relevant nonmajor, and 3 minor bleeding events. No patient required blood transfusion or an additional procedure to achieve hemostasis. Most bleeding complications were seen following intrauterine device (IUD) placement (5/8). Nearly 30% of patients who underwent IUD placement reported bleeding. Conclusion: Pediatric patients with mild type 1 VWD can safely undergo procedures using a tailored approach. Bleeding complications were uncommon, with the majority following IUD placement.

Surface Deformation and Seismicity Linked to Fluid Injection in the Raton Basin.

It is suggested that in addition to seismicity deep fluid injection may cause surface uplift and subsidence in oil and gas-producing regions. This study uses the Raton Basin as an example to investigate the hydromechanical processes of surface uplift and subsidence during wastewater injection. The Raton Basin, in southern central Colorado and northern central New Mexico, has experienced wastewater injection related to coalbed methane and gas production starting in 1994. In this study, we estimate the extent and magnitude of total vertical deformation in the Raton Basin from 1994 to 2020 and incremental deformation between the years 2017 to 2020. Results indicate a modeled uplift as much as 15 cm occurring between 1994 and 2020. Between 2017 and 2020, up to 3 cm of uplift occurred, largely near the northwestern injection wells. Most modeled uplift between 1994 and 2020 occurred near the southern wells, where the greatest cumulative volume of wastewater was injected. However, modeled subsidence occurred around the southern and eastern wells between 2017 and 2020, after the rate of injection decreased. Modeling indicates that while the magnitude of modeled uplift corresponds to cumulative injection volume and maximum rate in the long-term, short-term incremental deformation (uplift or subsidence) is controlled by changes in the rate of injection. The number of yearly earthquake events follows periods of rapid modeled uplifting throughout the Basin, suggesting that measurable surface deformation may be caused by the same injection-induced pore pressure perturbations that initiate seismicity.

The Promise and Perils of Artificial Intelligence in Health Professions Education Practice and Scholarship.

ABSTRACT: Artificial intelligence (AI) methods, especially machine learning and natural language processing, are increasingly affecting health professions education (HPE), including the medical school application and selection processes, assessment, and scholarship production. The rise of large language models over the past 18 months, such as ChatGPT, has raised questions about how best to incorporate these methods into HPE. The lack of training in AI among most HPE faculty and scholars poses an important challenge in facilitating such discussions. In this commentary, the authors provide a primer on the AI methods most often used in the practice and scholarship of HPE, discuss the most pressing challenges and opportunities these tools afford, and underscore that these methods should be understood as part of the larger set of statistical tools available.Despite their ability to process huge amounts of data and their high performance completing some tasks, AI methods are only as good as the data on which they are trained. Of particular importance is that these models can perpetuate the biases that are present in those training datasets, and they can be applied in a biased manner by human users. A minimum set of expectations for the application of AI methods in HPE practice and scholarship is discussed in this commentary, including the interpretability of the models developed and the transparency needed into the use and characteristics of such methods.The rise of AI methods is affecting multiple aspects of HPE including raising questions about how best to incorporate these models into HPE practice and scholarship. In this commentary, we provide a primer on the AI methods most often used in HPE and discuss the most pressing challenges and opportunities these tools afford.

How to support others in developing a career in clinical education research.

The Incubator for Clinical Education Research (ClinEdR) is a UK-wide network, established with support from the National Institute for Health Research, to lead initiatives to build capacity in the field. A key barrier identified by this group is that many experienced educators, clinicians, and researchers, who may be committed to supporting others, have little guidance on how best to do this. In this "How to …" paper, we draw on relevant literature and our individual and collective experiences as members of the National Institute for Health Research ClinEdR incubator to offer suggestions on how educators can support others to develop successful careers involving ClinEdR. This article offers guidance and inspiration for all professionals whose role involves research and scholarship and who encounter aspiring or developing clinical education researchers in the course of their work. It will also be of interest to researchers who are starting out and progressing in the field.

The interprofessional education of medical students and physician associate students during the COVID-19 pandemic.

Background: Due to the potential for improved team working and patient care, interprofessional education (IPE) is increasingly recognized as a core competency within the education of health-care professionals. Methods: In response to cancellation of the physician associate (PA) acute medicine clinical placement at our institution following COVID-19, a technology-focused, case-based IPE course between medical and PA students was implemented. The course consisted of 6 weekly seminars involving an average of 16 PA students, two medical students, and two supervising general practitioners. Course evaluation was mixed methods, comprising pre/postcourse questionnaires, weekly feedback forms, and postcourse e-mail interviews. Results: The course improved the confidence and perceived knowledge base of all participating students across every clinical topic covered, while promoting interprofessional collaboration and understanding. Discussion: To our knowledge, this represents one of the first IPE courses implemented between medical and PA students alone and has highlighted the need for further IPE courses between both professions. We show that successful IPE is feasible during a global pandemic, and that initiatives relying on technology alone are successful. Weekly written feedback was overwhelmingly positive, and based on the success of this course, faculty have planned further IPE opportunities between both professions.

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides.

2,2'-Bis(4-dimethylaminophenyl)- and 2,2'-dicyclohexyl-1,1',3,3'-tetramethyl-2,2',3,3'-tetrahydro-2,2'-bibenzo[d]imidazole ((N-DMBI)2 and (Cyc-DMBI)2) are quite strong reductants with effective potentials of ca. -2 V vs ferrocenium/ferrocene, yet are relatively stable to air due to the coupling of redox and bond-breaking processes. Here, we examine their use in accomplishing electron transfer-induced bond-cleavage reactions, specifically dehalogenations. The dimers reduce halides that have reduction potentials less cathodic than ca. -2 V vs ferrocenium/ferrocene, especially under UV photoexcitation (using a 365 nm LED). In the case of benzyl halides, the products are bibenzyl derivatives, whereas aryl halides are reduced to the corresponding arenes. The potentials of the halides that can be reduced in this way, quantum-chemical calculations, and steady-state and transient absorption spectroscopy suggest that UV irradiation accelerates the reactions via cleavage of the dimers to the corresponding radical monomers.

Medical students impacted by discrimination: a qualitative study into their experiences of belonging and support systems at medical schools in the UK.

OBJECTIVE: To better understand the broader experience of medical students impacted by discrimination and the support systems they engage with. DESIGN: Qualitative study using semi-structured interviews. SETTING: Four medical schools based in the UK. PARTICIPANTS: 17 medical students were recruited using volunteer and snowball sampling: all students self-identified as being impacted by discrimination. RESULTS: 5 themes were identified: feelings of isolation, imposter syndrome and exclusion; a lack of representation and positive role modelling; the importance of peer support; issues relating to the accessibility of support; building support networks through shared experiences and attempts to foster a sense of inclusion through peer and institutionally led initiatives. CONCLUSIONS: The findings of this study suggest medical schools could do more to recognise the importance of acknowledging the multiple identities at risk of discrimination held by students, perpetuating feelings of isolation and exclusion. Our research highlights the need for practical systemic initiatives to improve the sense of belonging of medical students who are impacted by discrimination. Medical educators and institutions should consider formal and informal provisions, such as creating time and space for students to meet and share experiences, access support and reporting networks, to foster a greater sense of belonging.

Beyond the bedside: protocol for a scoping review exploring the experiences of non-practicing healthcare professionals within health professions education.

BACKGROUND: The number of healthcare professionals leaving clinical practice and transitioning to alternative careers in health professions education is increasing. Among these non-practicing healthcare professionals, concerns have been reported regarding tensions in relation to identity, role, and credibility in their new field. There are suggestions that this is a particularly pressing issue for minoritised professionals who make this transition. Support is critical to attract and retain diverse talent within health professions education teaching and research. The purpose of this scoping review is to explore the career experiences of non-practicing healthcare professionals who work in health professions education internationally. METHODS: Arksey and O'Malley's framework has been utilised to guide the design of this scoping review process and will be used throughout the course of the review. A comprehensive search of seven electronic databases and limited search of Google Scholar will be conducted, as well as a hand search of eligible article reference lists. Two reviewers will independently screen all articles based on inclusion criteria, with conflicts resolved by a third reviewer. Data from included articles will be charted, collated, and analysed thematically. Meta-data will be summarised quantitatively. DISCUSSION: This scoping review aims to explore the role and experiences of non-practicing healthcare professionals working within health professions education. The review will follow established scoping review guidelines and will include studies from various regions and languages, provided an English translation is available. The study remit will be broad, including both quantitative and qualitative studies, as well as reviews and opinion papers. Limitations may include the exclusion of non-English articles and potential difficulty of identifying papers which discuss the experiences of non-practicing clinicians. However, the review will provide insight into the current knowledge on what it is like to be a non-practicing clinician working within health professions education and identify gaps for both future research, and future support for those making this career transition. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework Registration  https://doi.org/10.17605/OSF.IO/485Z3.

Mapping Effectiveness Studies of Occupational Therapy in Africa: A Scoping Review.

Background: Contextual relevance is an important consideration for evidence-based practice, especially in low- and middle-income countries where the nature of practice may differ from high-income countries. Resources and access to rehabilitation are constrained, and service-users face a range of intersecting challenges to activity and participation. Aim: To evaluate the body of evidence for the effectiveness of occupational therapy in Africa, and to determine if systematic reviews with meta-analysis and/or meta-synthesis are feasible. Methods and Analysis. We conducted a systematic scoping review of published and grey literature by following PRISMA-ScR guidelines across 13 databases and through personal contact with occupational therapists across Africa. Covidence software was used to manage a blind review process by at least three reviewers per included article. The McMaster Quantitative Review Form, NHMRC levels of evidence, the Cochrane PROGRESS-Plus health equity criteria, and the TIDieR checklist informed data extraction using Microsoft Forms. Results: The search yielded 4199 articles, of which 45 were included. Evidence in six fields of practice included paediatrics, mental health, physical rehabilitation, hand therapy, work practice, and community development, although the evidence was largely limited to South Africa (93% studies). Levels of evidence varied but included 13 RCTs. In all, 1957 participants were included, ranging in age from 25 days to 99 years, with a wide range of health conditions. Most studies reported a positive outcome for occupational therapy. Conclusion: Findings suggest a moderate body of evidence to support occupational therapy in Africa. Systematic review with meta-analysis, assessment of risk of bias, and in-depth analysis of specific areas of practice are now required. All effectiveness studies in occupational therapy should include measures of occupational performance or participation, minimum reporting standard checklists should be used more consistently, and effect sizes should be consistently calculated and reported in effectiveness research.

Impact of Type and Shape of Microplastics on the Transport in Column Experiments.

The pervasive nature of plastic and the longevity of plastics leaves a legacy of microplastics (MPs) that contaminate our environment, including drinking water sources. Although MPs have been documented in every environmental setting, a paucity of research has focused on the transport and fate of MPs in groundwater. Previous field and laboratory studies have shown that MPs can migrate through aquifer material and are influenced by environmental factors. This study used controlled column experiments to investigate the influence of polymer type (polyamide, polyethylene, polypropylene, and polyester) and particle shape (fragment, fiber, and sphere) on MP retardation and retention. The results showed that all individual MP types investigated were retarded compared to the NaCl tracer, with a retardation factor ranging from 1.53 to 1.75. While hypothesized that presence of multiple types and shapes could change mobility, the results indicate that this hypothesis is not correct for the conditions tested. This study provides new insights into MP transport in groundwater systems based on the characteristics of MP particles. In addition, this study demonstrates the need for further research on types of MPs and under more conditions, especially in the presence of a mixture of types and shapes of MPs to gauge what is occurring in natural systems where many MPs are present together.

A qualitative evaluation of the impact of a medical student school outreach project on both medical students and school pupils.

OBJECTIVE: To explore medical student and school pupil experiences of an outreach school teaching project. SETTING: Community engagement is increasingly commonplace within medical school. Secondary schools offer ample opportunities for community engagement as medical students teach and engage in service learning. There is a lack of research regarding the impact of school community engagement projects and the impact on pupils, as critical stakeholders in the service medical students provide. In this qualitative study, we explore the perspectives of medical students and school pupils involved in a school teaching project. PARTICIPANTS: Ten medical students participated in individual interviews, and 17 school pupils across three schools participated in group interviews. Data were analysed using thematic analysis and the concept of service learning. RESULTS: For medical students, the project fostered communication and teaching skills, but a lack of reflection hampered further benefit. For school pupils, experiences varied - learning about careers in medicine could be inspiring, but content pitched at the incorrect level disengaged some pupils. The conflict between session timing and medical students' exams negatively influenced engagement. CONCLUSIONS: To shift the focus of community engagement projects that promote service-learning towards mutual benefit, designing in partnership with relevant community stakeholders and integrating opportunities to reflect on these experiences are critical.

Genomic Variation, Population History, and Long-Term Genetic Adaptation to High Altitudes in Tibetan Partridge (Perdix hodgsoniae).

Species residing across elevational gradients display adaptations in response to environmental changes such as oxygen availability, ultraviolet radiation, and temperature. Here, we study genomic variation, gene expression, and long-term adaptation in Tibetan Partridge (Perdix hodgsoniae) populations residing across the elevational gradient of the Tibetan Plateau. We generated a high-quality draft genome and used it to carry out downstream population genomic and transcriptomic analysis. The P. hodgsoniae populations residing across various elevations were genetically distinct, and their phylogenetic clustering was consistent with their geographic distribution. We identified possible evidence of gene flow between populations residing in <3,000 and >4,200 m elevation that is consistent with known habitat expansion of high-altitude populations of P. hodgsoniae to a lower elevation. We identified a 60 kb haplotype encompassing the Estrogen Receptor 1 (ESR1) gene, showing strong genetic divergence between populations of P. hodgsoniae. We identified six single nucleotide polymorphisms within the ESR1 gene fixed for derived alleles in high-altitude populations that are strongly conserved across vertebrates. We also compared blood transcriptome profiles and identified differentially expressed genes (such as GAPDH, LDHA, and ALDOC) that correlated with differences in altitude among populations of P. hodgsoniae. These candidate genes from population genomics and transcriptomics analysis were enriched for neutrophil degranulation and glycolysis pathways, which are known to respond to hypoxia and hence may contribute to long-term adaptation to high altitudes in P. hodgsoniae. Our results highlight Tibetan Partridges as a useful model to study molecular mechanisms underlying long-term adaptation to high altitudes.