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Anatomical education in the United Kingdom (UK) and Ireland has long been under scrutiny, especially since the reforms triggered in 1993 by the General Medical Council's "Tomorrow's Doctors." The aim of the current study was to investigate the state of medical student anatomy education in the UK and Ireland in 2019. In all, 39 medical schools completed the survey (100% response rate) and trained 10,093 medical students per year cohort. The teachers comprised 760 individuals, of these 143 were employed on full-time teaching contracts and 103 were employed on education and research contracts. Since a previous survey in 1999, the number of part-time staff has increased by 300%, including a significant increase in the number of anatomy demonstrators. In 2019, anatomy was predominantly taught to medical students in either a system-based or hybrid curriculum. In all, 34 medical schools (87%) used human cadavers to teach anatomy, with a total of 1,363 donors being used per annum. Gross anatomy teaching was integrated with medical imaging in 95% of medical schools, embryology in 81%, living anatomy in 78%, neuroanatomy in 73%, and histology in 68.3%. Throughout their five years of study, medical students are allocated on average 85 h of taught time for gross anatomy, 24 h for neuroanatomy, 24 h for histology, 11 h for living anatomy, and 10 for embryology. In the past 20 years, there has been an average loss of 39 h dedicated to gross anatomy teaching and a reduction in time dedicated to all other anatomy sub-disciplines.

Leukemic relapse remains a major barrier to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aggressive hematologic malignancies. The basis for relapse of advanced lymphoid malignancies remains incompletely understood and may involve escape from the graft-versus-leukemia (GvL) effect. We hypothesized that for patients with chronic lymphocytic leukemia (CLL) treated with allo-HSCT, leukemic cell-intrinsic features influence transplant outcomes by directing the evolutionary trajectories of CLL cells. Integrated genetic, transcriptomic, and epigenetic analyses of CLL cells from 10 patients revealed that the clinical kinetics of post-HSCT relapse are shaped by distinct molecular dynamics. Early relapses after allo-HSCT exhibited notable genetic stability; single CLL cell transcriptional analysis demonstrated a cellular heterogeneity that was static over time. In contrast, CLL cells relapsing late after allo-HSCT displayed notable genetic evolution and evidence of neoantigen depletion, consistent with marked single-cell transcriptional shifts that were unique to each patient. We observed a greater rate of epigenetic change for late relapses not seen in early relapses or relapses after chemotherapy alone, suggesting that the selection pressures of the GvL bottleneck are unlike those imposed by chemotherapy. No selective advantage for human leukocyte antigen (HLA) loss was observed, even when present in pretransplant subpopulations. Gain of stem cell modules was a common signature associated with leukemia relapse regardless of posttransplant relapse kinetics. These data elucidate the biological pathways that underlie GvL resistance and posttransplant relapse.

This article provides an overview of John Rawls' theory of justice, focusing on the concept of a well-ordered society. Rawls argues that in a just society, there will be a diversity of moral and philosophical views, and it is unrealistic to expect complete agreement on a single conception of justice. Instead, he proposes the idea of a well-ordered liberal society, where there is a family of reasonable liberal political conceptions that share certain features, such as equal basic rights and liberties, the priority of these freedoms, and the provision of a social minimum. Rawls also emphasizes the importance of reciprocity and preventing excessive inequalities. The article concludes that justice as fairness is the most reasonable political conception within a well-ordered liberal society. [Extracted from the article]

Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed significant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifications not detected in PT sampling. Lastly, we profiled paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy.Significance: We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profiling of metastatic lesions and/or cfDNA should be systematically evaluated. Cancer Discov; 8(1); 37-48. ©2017 AACR.See related commentary by Sundar and Tan, p. 14See related article by Janjigian et al., p. 49This article is highlighted in the In This Issue feature, p. 1.

Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1. SF3B1 mutation was found to dysregulate multiple cellular functions including DNA damage response, telomere maintenance, and Notch signaling (mediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 transcript, respectively). SF3B1 mutation leads to diverse changes in CLL-related pathways.

The author presents a response to David Blankfein-Tabachnick and Kevin Kordana's criticism of his argument that economic torts in unjust economic systems do not justify John Rawls's difference principle, as well as his contention that the principle requires maximizing the position of the less advantaged to the more advantaged, not their absolute position. He discusses the application of Rawls's difference principle in determining personal tort liability and remedies, including economic torts.

Introduction: Vaccination during pregnancy protects both the mother and the foetus from vaccine-preventable diseases. However, uptake of the recommended vaccines (influenza, pertussis, COVID-19) by pregnant women remains low in Europe and the USA. Understanding the reasons for this is crucial to inform strategies to increase vaccination rates in pregnant women. This qualitative systematic review aimed to identify the barriers and facilitators to vaccination against influenza, pertussis/whooping cough and COVID-19 during pregnancy and identify possible strategies to increase vaccination rates. Methods: We conducted a comprehensive search of electronic databases, including Medline, PsycINFO, CINAHL, Web of Science, WHO database, Embase and grey literature to identify qualitative studies that explored barriers and facilitators to vaccine uptake among pregnant women (PROSPERO CRD42023399488). The search was limited to studies published between 2012 and 2022 conducted in high-income countries with established vaccination programmes during pregnancy. Studies were thematically analysed and underwent quality assessment using the Joanna Briggs Institute validated critical appraisal tool for qualitative research. Results: Out of 2681 articles screened, 28 studies (n = 1573 participants) were eligible for inclusion. Five overarching themes emerged relating to personal, provider and systemic factors. Barriers to vaccine uptake included concerns about vaccine safety and efficacy, lack of knowledge about vaccines' benefits and necessity, fear of adverse effects on the foetus or mother and low perception of disease severity. Facilitators included recommendations from trusted healthcare providers, easy access to vaccination, clear communication on the benefits and safety of vaccination, and positive social influences from family and friends. Strategies for increasing vaccination uptake included strong and proactive vaccine recommendations by trusted healthcare professionals, provision of vaccines during routine antenatal care, and clear and consistent communication about vaccines addressing pregnant women's concerns. Conclusion: This review highlights the need for interventions that address the identified barriers to vaccine uptake among pregnant women. Recommendation from a healthcare provider can play a significant role in promoting vaccine uptake, as can clear risk/benefit communication and convenient access to vaccination. Addressing concerns about vaccine safety and providing accurate information about vaccines is also important. [ABSTRACT FROM AUTHOR]

Objective: To assess Australian and New Zealand emergency clinicians' attitudes towards the use of artificial intelligence (AI) in emergency medicine. Methods: We undertook a qualitative interview‐based study based on grounded theory. Participants were recruited through ED internal mailing lists, the Australasian College for Emergency Medicine Bulletin, and the research teams' personal networks. Interviews were transcribed, coded and themes presented. Results: Twenty‐five interviews were conducted between July 2021 and May 2022. Thematic saturation was achieved after 22 interviews. Most participants were from either Western Australia (52%) or Victoria (16%) and were consultants (96%). More participants reported feeling optimistic (10/25) than neutral (6/25), pessimistic (2/25) or mixed (7/25) towards the use of AI in the ED. A minority expressed scepticism regarding the feasibility or value of implementing AI into the ED. Multiple potential risks and ethical issues were discussed by participants including skill loss from overreliance on AI, algorithmic bias, patient privacy and concerns over liability. Participants also discussed perceived inadequacies in existing information technology systems. Participants felt that AI technologies would be used as decision support tools and not replace the roles of emergency clinicians. Participants were not concerned about the impact of AI on their job security. Most (17/25) participants thought that AI would impact emergency medicine within the next 10 years. Conclusions: Emergency clinicians interviewed were generally optimistic about the use of AI in emergency medicine, so long as it is used as a decision support tool and they maintain the ability to override its recommendations. This qualitative study found that emergency clinicians in Australia and New Zealand were generally optimistic about the use of artificial intelligence (AI)‐enabled decision support tools in EDs. A number of issues were raised that require attention before full acceptance. AI‐enabled tools must operate as decision support only, be locally validated, be effectively integrated into existing workflows and take ethical concerns into consideration. [ABSTRACT FROM AUTHOR]

Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

This policy brief discusses the key dimensions of military expenditure transparency and assesses them in relation to China. While spending transparency relates most obviously to the availability, reliability, detail, and comprehensiveness of information, it cannot be completely separated from broader defense policy formation issues. China has a robust framework for developing, implementing, and monitoring defense policy, budgeting, and expenditure, and producing readily-accessible budget and expenditure data in English and Chinese; however, these processes are largely carried out behind closed doors.