‘Stuck in the System’: An Interpretative Phenomenological Analysis of Transmasculine Experiences of Gender Transition in the UK

A gender dysphoria diagnosis is currently required in the UK to access NHS transition-related treatment. However, this approach has been criticised by academics and activists as pathologising, ‘gatekeeping’ transgender identities, and can be viewed by the transgender community as a barrier to necessary medical care. The present research examines transmasculine experiences of gender transition in the UK, focusing on exploring the barriers encountered during identity development and medical transition. Semi-structured interviews were conducted with three individuals, and nine individuals took part in a single focus group. The data were analysed using Interpretative Phenomenological Analysis producing three main themes: ‘Conceptualising Stages of Transition’; ‘NHS Communication and Support’; and ‘Medicalisation, Power and Non-disclosure’. Participants conceptualised access to transition-related treatment as an intrusive and complicated process that negatively impacts identity development. They spoke of barriers such as lack of trans-specific healthcare knowledge, insufficient communication and support from healthcare professionals, and restricted autonomy arising from the pathologisation of trans identities. Results suggest transmasculine individuals may face numerous barriers when trying to access healthcare, and therefore, a move towards the Informed Consent Model could ameliorate many of these barriers and would empower service-users to make informed choices

Development of tumor-reactive T cells after nonmyeloablative allogeneic hematopoietic stem cell transplant for chronic lymphocytic leukemia.

PURPOSE: Allogeneic nonmyeloablative hematopoietic stem cell transplant (NM-HSCT) can result in durable remission of chronic lymphocytic leukemia (CLL). It is thought that the efficacy of NM-HSCT is mediated by recognition of tumor cells by T cells in the donor stem cell graft. We evaluated the development of CTLs specific for CLL after NM-HSCT to determine if their presence correlated with antitumor efficacy. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cells obtained from 12 transplant recipients at intervals after NM-HSCT were stimulated in vitro with CLL cells. Polyclonal T-cell lines and CD8(+) T-cell clones were derived from these cultures and evaluated for lysis of donor and recipient target cells including CLL. The presence and specificity of responses was correlated with clinical outcomes. RESULTS: Eight of the 12 patients achieved remission or a major antitumor response and all 8 developed CD8(+) and CD4(+) T cells specific for antigens expressed by CLL. A clonal analysis of the CD8(+) T-cell response identified T cells specific for multiple minor histocompatibility (H) antigens expressed on CLL in six of the responding patients. A significant fraction of the CD8(+) T-cell response in some patients was also directed against nonshared tumor-specific antigens. By contrast, CLL-reactive T cells were not detected in the four patients who had persistent CLL after NM-HSCT, despite the development of graft-versus-host disease. CONCLUSIONS: The development of a diverse T-cell response specific for minor H and tumor-associated antigens expressed by CLL predicts an effective graft-versus-leukemia response after NM-HSCT

Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association

The adoption and maintenance of physical activity are critical foci for blood glucose management and overall health in individuals with diabetes and prediabetes. Recommendations and precautions vary depending on individual characteristics and health status. In this Position Statement, we provide a clinically oriented review and evidence-based recommendations regarding physical activity and exercise in people with type 1 diabetes, type 2 diabetes, gestational diabetes mellitus, and prediabetes. Physical activity includes all movement that increases energy use, whereas exercise is planned, structured physical activity. Exercise improves blood glucose control in type 2 diabetes, reduces cardiovascular risk factors, contributes to weight loss, and improves well-being (1,2). Regular exercise may prevent or delay type 2 diabetes development (3). Regular exercise also has considerable health benefits for people with type 1 diabetes (e.g., improved cardiovascular fitness, muscle strength, insulin sensitivity, etc.) (4). The challenges related to blood glucose management vary with diabetes type, activity type, and presence of diabetes-related complications (5,6). Physical activity and exercise recommendations, therefore, should be tailored to meet the specific needs of each individual

Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy

Chimeric antigen receptor (CAR) T-cell therapy has produced remarkable anti-tumor responses in patients with B-cell malignancies. However, clonal kinetics and transcriptional programs that regulate the fate of CAR-T cells after infusion remain poorly understood. Here we perform TCRB sequencing, integration site analysis, and single-cell RNA sequencing (scRNA-seq) to profile CD8+ CAR-T cells from infusion products (IPs) and blood of patients undergoing CD19 CAR-T immunotherapy. TCRB sequencing shows that clonal diversity of CAR-T cells is highest in the IPs and declines following infusion. We observe clones that display distinct patterns of clonal kinetics, making variable contributions to the CAR-T cell pool after infusion. Although integration site does not appear to be a key driver of clonal kinetics, scRNA-seq demonstrates that clones that expand after infusion mainly originate from infused clusters with higher expression of cytotoxicity and proliferation genes. Thus, we uncover transcriptional programs associated with CAR-T cell behavior after infusion.Published versio

Solution Geochemistry of the Water of Limestone Terrains

Limestone groundwater flows mainly in openings it has solutionally enlarged, thus an understanding of the water\u27s state of saturation relative to calcite (the principal mineral component of limestone) is fundamental to an understanding of the nature and evolution of the limestone aquifer. This study investigated the Mammoth Cave-Sinkhole Plain (MCSP) and Cave Hollow (CH) aquifers in Kentucky, both in Missippian limestones. Both aquifers were always undersaturated with calcite. Except for completely ventilated vadose flows (usually) and some vadose seepage (occasionally), all recharges sampled (sinking streams, vadose flows, and vadose seepage) were also undersaturated. The lack of saturation in the MCSP aquifer was due to the introduction of carbon dioxide into the water in amounts difficult to explain by the carbon dioxide content of the above recharges. In both vadose flows and seepage, undersaturatlon tended to correlate directly with flow volume, and there was an inverse correlation between the amount of carbon dioxide and calcite saturation in most of the waters sampled. In vadose seepage this relationship was so strong as to suggest seasonal invariance of carbon dioxide content of the water prior to out gassing. Results suggest solutional enlargement is greatest near recharge points in ventilated aquifers (CH) but the carbon dioxide introduction phenomenon (MCSP) allows solution over wide areas in unventilated aquifers

National Cancer Institute’s First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Summary and Recommendations from the Organizing Committee

The National Cancer Institute’s First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation was organized and convened to identify, prioritize, and coordinate future research activities related to relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Each of the Workshop’s 6 Working Committees has published individual reports of ongoing basic, translational, and clinical research and recommended areas for future research related to the areas of relapse biology, epidemiology, prevention, and treatment. This document summarizes each committee’s recommendations and suggests 3 major initiatives for a coordinated research effort to address the problem of relapse after allo-HSCT: (1) to establish multicenter correlative and clinical trial networks for basic/translational, epidemiologic, and clinical research; (2) to establish a network of biorepositories for the collection of samples before and after allo-HSCT to aid in laboratory and clinical studies; and (3) to further refine, implement, and study the Workshop-proposed definitions for disease-specific response and relapse and recommendations for monitoring of minimal residual disease. These recommendations, in coordination with ongoing research initiatives and transplantation organizations, provide a research framework to rapidly and efficiently address the significant problem of relapse after allo-HSCT

Social marketing and healthy eating : Findings from young people in Greece

This document is the Accepted Manuscript version. The final publication is available at Springer via http://dx.doi.org/10.1007/s12208-013-0112-xGreece has high rates of obesity and non-communicable diseases owing to poor dietary choices. This research provides lessons for social marketing to tackle the severe nutrition-related problems in this country by obtaining insight into the eating behaviour of young adults aged 18–23. Also, the main behavioural theories used to inform the research are critically discussed. The research was conducted in Athens. Nine focus groups with young adults from eight educational institutions were conducted and fifty-nine participants’ views towards eating habits, healthy eating and the factors that affect their food choices were explored. The study found that the participants adopted unhealthier nutritional habits after enrolment. Motivations for healthy eating were good health, appearance and psychological consequences, while barriers included lack of time, fast-food availability and taste, peer pressure, lack of knowledge and lack of family support. Participants reported lack of supportive environments when deciding on food choices. Based on the findings, recommendations about the development of the basic 4Ps of the marketing mix, as well as of a fifth P, for Policy are proposedPeer reviewe

Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies

Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical trials include the inability of animal models to recapitulate the human disease, variations in breeding and colony maintenance, lack of standards in design, conduct and analysis of animal trials, and publication bias due to under-reporting of negative results in the scientific literature. The quality of animal model research on novel therapeutics can be improved by bringing the rigor of human clinical trials to animal studies. Research communities in several disease areas have developed recommendations for the conduct and reporting of preclinical studies in order to increase their validity, reproducibility, and predictive value. To address these issues in the AD community, the Alzheimer's Drug Discovery Foundation partnered with Charles River Discovery Services (Morrisville, NC, USA) and Cerebricon Ltd. (Kuopio, Finland) to convene an expert advisory panel of academic, industry, and government scientists to make recommendations on best practices for animal studies testing investigational AD therapies. The panel produced recommendations regarding the measurement, analysis, and reporting of relevant AD targets, th choice of animal model, quality control measures for breeding and colony maintenance, and preclinical animal study design. Major considerations to incorporate into preclinical study design include a priori hypotheses, pharmacokinetics-pharmacodynamics studies prior to proof-of-concept testing, biomarker measurements, sample size determination, and power analysis. The panel also recommended distinguishing between pilot 'exploratory' animal studies and more extensive 'therapeutic' studies to guide interpretation. Finally, the panel proposed infrastructure and resource development, such as the establishment of a public data repository in which both positive animal studies and negative ones could be reported. By promoting best practices, these recommendations can improve the methodological quality and predictive value of AD animal studies and make the translation to human clinical trials more efficient and reliable