Sick of the sick role: narratives of what ‘recovery’ means to people with chronic fatigue syndrome/myalgic encephalomyelitis

Little is known about what recovery means to those with chronic fatigue syndrome/myalgic encephalomyelitis, a poorly understood, disabling chronic health condition. To explore this issue, semi-structured interviews were conducted with patients reporting improvement (n=9) and deterioration (n=10) after a guided self-help intervention, and analysed via “constant comparison”. The meaning of recovery differed between participants - expectations for improvement and deployment of the sick role (and associated stigma) were key influences. Whilst some saw recovery as complete freedom from symptoms, many defined it as freedom from the ‘sick role’, with functionality prioritized. Others redefined recovery, reluctant to return to the lifestyle that may have contributed to their illness, or rejected the concept as unhelpful. Recovery is not always about eliminating all symptoms. Rather, it is a nexus between the reality of limited opportunities for full recovery, yet a strong desire to leave the illness behind and regain a sense of ‘normality’

Guided graded exercise self-help for chronic fatigue syndrome: Patient experiences and perceptions

Purpose: This study explored patient experiences of Guided graded Exercise Self-help delivered as part of a randomised controlled trial for people with chronic fatigue syndrome/myalgic encephalomyelitis, which found that Guided graded Exercise Self-help was better than specialist medical care at reducing fatigue and improving physical functioning. Methods: Semi-structured interviews were conducted with patients reporting improvement (n=9) and deteriorated (n = 10), and analysed using a thematic “constant comparison”. Results: The improved group described more facilitators to doing Guided graded Exercise Self-help, and were more likely to describe high levels of self-motivation, whilst the deteriorated group described more barriers to Guided graded Exercise Self-help (including worse exacerbation of symptoms after Guided graded Exercise Self-help, greater interference from comorbid conditions and obstacles to Guided graded Exercise Self-help in their lives), and had been ill for longer. Having the capacity to do Guided graded Exercise Self-help was important; of note, those with relatively lower levels of functioning sometimes had more time and space in their lives to support their Guided graded Exercise Self-help engagement. We identified an important ‘indeterminate phase’ early on, in which participants did not initially improve. Conclusions: Guided graded Exercise Self-help may be improved by targeting those most likely to improve, and education about the indeterminate phase

Men, trans/masculine, and non-binary people's experiences of pregnancy loss: an international qualitative study.

Growing numbers of men, trans/masculine, and non-binary people are becoming gestational parents, yet very little is known about experiences of pregnancy loss among this diverse population. The study employed a cross sectional design. Interviews were undertaken with a convenience sample of 51 trans/masculine and non-binary people who had undertaken at least one pregnancy, living in either Australia, the United States, Canada, or the European Union (including the United Kingdom). Participants were recruited by posts on Facebook and Twitter, via researcher networks, and by community members. 16 (31.2%) of the participants had experienced a pregnancy loss and are the focus of this paper. Thematic analysis was used to analyse interview responses given by these 16 participants to a specific question asking about becoming pregnant and a follow up probe question about pregnancy loss. Thematic analysis of interview responses given by the 16 participants led to the development of 10 themes: (1) pregnancy losses count as children, (2) minimizing pregnancy loss, (3) accounting for causes of pregnancy loss, (4) pregnancy loss as devastating, (5) pregnancy loss as having positive meaning, (6) fears arising from a pregnancy loss, (7) experiences of hospitals enacting inclusion, (8) lack of formal support offered, (9) lack of understanding from family, and (10) importance of friends. The paper concludes by outlining specific recommendations for clinical practice. These include the importance of focusing on the emotions attached to pregnancy loss, the need for targeted support services for men, trans/masculine, and non-binary people who undertake a pregnancy (including for their partners), and the need for ongoing training for hospital staff so as to ensure the provision of trans-affirming medical care

Graded Exercise Therapy Guided Self-Help Trial for Patients with Chronic Fatigue Syndrome (GETSET): Protocol for a Randomized Controlled Trial and Interview Study

Background: Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is characterized by chronic disabling fatigue and other symptoms, which are not explained by an alternative diagnosis. Previous trials have suggested that graded exercise therapy (GET) is an effective and safe treatment. GET itself is therapist-intensive with limited availability. Objective: While guided self-help based on cognitive behavior therapy appears helpful to patients, Guided graded Exercise Self-help (GES) is yet to be tested. Methods: This pragmatic randomized controlled trial is set within 2 specialist CFS/ME services in the South of England. Adults attending secondary care clinics with National Institute for Health and Clinical Excellence (NICE)-defined CFS/ME (N=218) will be randomly allocated to specialist medical care (SMC) or SMC plus GES while on a waiting list for therapist-delivered rehabilitation. GES will consist of a structured booklet describing a 6-step graded exercise program, supported by up to 4 face-to-face/telephone/Skype™ consultations with a GES-trained physiotherapist (no more than 90 minutes in total) over 8 weeks. The primary outcomes at 12-weeks after randomization will be physical function (SF-36 physical functioning subscale) and fatigue (Chalder Fatigue Questionnaire). Secondary outcomes will include healthcare costs, adverse outcomes, and self-rated global impression change scores. We will follow up all participants until 1 year after randomization. We will also undertake qualitative interviews of a sample of participants who received GES, looking at perceptions and experiences of those who improved and worsened. Results: The project was funded in 2011 and enrolment was completed in December 2014, with follow-up completed in March 2016. Data analysis is currently underway and the first results are expected to be submitted soon. Conclusions: This study will indicate whether adding GES to SMC will benefit patients who often spend many months waiting for rehabilitative therapy with little or no improvement being made during that time. The study will indicate whether this type of guided self-management is cost-effective and safe. If this trial shows GES to be acceptable, safe, and comparatively effective, the GES booklet could be made available on the Internet as a practitioner and therapist resource for clinics to recommend, with the caveat that patients also be supported with guidance from a trained physiotherapist. The pragmatic approach in this trial means that GES findings will be generalizable to usual National Health Service (NHS) practice

Harnessing large language models (LLMs) for candidate gene prioritization and selection.

BACKGROUND: Feature selection is a critical step for translating advances afforded by systems-scale molecular profiling into actionable clinical insights. While data-driven methods are commonly utilized for selecting candidate genes, knowledge-driven methods must contend with the challenge of efficiently sifting through extensive volumes of biomedical information. This work aimed to assess the utility of large language models (LLMs) for knowledge-driven gene prioritization and selection. METHODS: In this proof of concept, we focused on 11 blood transcriptional modules associated with an Erythroid cells signature. We evaluated four leading LLMs across multiple tasks. Next, we established a workflow leveraging LLMs. The steps consisted of: (1) Selecting one of the 11 modules; (2) Identifying functional convergences among constituent genes using the LLMs; (3) Scoring candidate genes across six criteria capturing the gene\u27s biological and clinical relevance; (4) Prioritizing candidate genes and summarizing justifications; (5) Fact-checking justifications and identifying supporting references; (6) Selecting a top candidate gene based on validated scoring justifications; and (7) Factoring in transcriptome profiling data to finalize the selection of the top candidate gene. RESULTS: Of the four LLMs evaluated, OpenAI\u27s GPT-4 and Anthropic\u27s Claude demonstrated the best performance and were chosen for the implementation of the candidate gene prioritization and selection workflow. This workflow was run in parallel for each of the 11 erythroid cell modules by participants in a data mining workshop. Module M9.2 served as an illustrative use case. The 30 candidate genes forming this module were assessed, and the top five scoring genes were identified as BCL2L1, ALAS2, SLC4A1, CA1, and FECH. Researchers carefully fact-checked the summarized scoring justifications, after which the LLMs were prompted to select a top candidate based on this information. GPT-4 initially chose BCL2L1, while Claude selected ALAS2. When transcriptional profiling data from three reference datasets were provided for additional context, GPT-4 revised its initial choice to ALAS2, whereas Claude reaffirmed its original selection for this module. CONCLUSIONS: Taken together, our findings highlight the ability of LLMs to prioritize candidate genes with minimal human intervention. This suggests the potential of this technology to boost productivity, especially for tasks that require leveraging extensive biomedical knowledge

Medical uncertainty and reproduction of the “normal”: decision-making around testosterone therapy in transgender pregnancy

No abstract available

New Ways of Being a Man: "Positive" Hegemonic Masculinity in Meditation-based Communities of Practice

Connell’s concept of hegemonic masculinity is often reduced to a singular construct, consisting of “toxic” traits viewed as detrimental to well-being. However, the concept allows for variation in hegemony, including the possibility of forms more conducive to well-being. Through in-depth interviews with thirty male meditators in the United Kingdom, we explored the social dimensions of meditation practice to examine its potential implications for well-being. Most participants became involved with “communities of practice” centered on meditation that promoted new local hegemonies, and these included ideals experienced as conducive to well-being, like abstinence. However, social processes associated with hegemony, like hierarchy and marginalization, were not overturned. Moreover, participants faced challenges enacting new practices in relation to the broader system of hegemonic masculinity—outside these communities—reporting censure. Our findings are cautionary for professionals seeking to encourage well-being behaviors: that is, there is potential for adaptation in men, yet complex social processes influence this change

Traction Forces of Endothelial Cells under Slow Shear Flow

Endothelial cells are constantly exposed to fluid shear stresses that regulate vascular morphogenesis, homeostasis, and disease. The mechanical responses of endothelial cells to relatively high shear flow such as that characteristic of arterial circulation has been extensively studied. Much less is known about the responses of endothelial cells to slow shear flow such as that characteristic of venous circulation, early angiogenesis, atherosclerosis, intracranial aneurysm, or interstitial flow. Here we used a novel, to our knowledge, microfluidic technique to measure traction forces exerted by confluent vascular endothelial cell monolayers under slow shear flow. We found that cells respond to flow with rapid and pronounced increases in traction forces and cell-cell stresses. These responses are reversible in time and do not involve reorientation of the cell body. Traction maps reveal that local cell responses to slow shear flow are highly heterogeneous in magnitude and sign. Our findings unveil a low-flow regime in which endothelial cell mechanics is acutely responsive to shear stress

High precision astrometry mission for the detection and characterization of nearby habitable planetary systems with the Nearby Earth Astrometric Telescope (NEAT)

(abridged) A complete census of planetary systems around a volume-limited sample of solar-type stars (FGK dwarfs) in the Solar neighborhood with uniform sensitivity down to Earth-mass planets within their Habitable Zones out to several AUs would be a major milestone in extrasolar planets astrophysics. This fundamental goal can be achieved with a mission concept such as NEAT - the Nearby Earth Astrometric Telescope. NEAT is designed to carry out space-borne extremely-high-precision astrometric measurements sufficient to detect dynamical effects due to orbiting planets of mass even lower than Earth's around the nearest stars. Such a survey mission would provide the actual planetary masses and the full orbital geometry for all the components of the detected planetary systems down to the Earth-mass limit. The NEAT performance limits can be achieved by carrying out differential astrometry between the targets and a set of suitable reference stars in the field. The NEAT instrument design consists of an off-axis parabola single-mirror telescope, a detector with a large field of view made of small movable CCDs located around a fixed central CCD, and an interferometric calibration system originating from metrology fibers located at the primary mirror. The proposed mission architecture relies on the use of two satellites operating at L2 for 5 years, flying in formation and offering a capability of more than 20,000 reconfigurations (alternative option uses deployable boom). The NEAT primary science program will encompass an astrometric survey of our 200 closest F-, G- and K-type stellar neighbors, with an average of 50 visits. The remaining time might be allocated to improve the characterization of the architecture of selected planetary systems around nearby targets of specific interest (low-mass stars, young stars, etc.) discovered by Gaia, ground-based high-precision radial-velocity surveys.Comment: Accepted for publication in Experimental Astronomy. The full member list of the NEAT proposal and the news about the project are available at http://neat.obs.ujf-grenoble.fr. The final publication is available at http://www.springerlink.co