Supervision, scheduling, satisfaction and shared working: how experiences of junior doctors relate to excess mortality within the NHS.

Background: We sought to explore associations between trainee doctor perception and excess patient mortality.

Methods: Data from two publicly available databases reflecting mortality and components of trainee satisfaction within 81 NHS healthcare institutions between the years 2012 and 2019 were analysed. Pearson's correlation coefficients were calculated.

Between-Sex Differences in Risk Factors for Cardiovascular Disease among Patients with Myocardial Infarction-A Systematic Review.

Between-sex differences in the presentation, risk factors, management, and outcomes of acute myocardial infarction (MI) are well documented. However, as such differences are highly sensitive to cultural and social changes, there is a need to continuously re-evaluate the evidence. The present contemporary systematic review assesses the baseline characteristics of men and women presenting to secondary, tertiary, and quaternary centres with acute myocardial infarction (MI).

Long-term persistence and functionality of adoptively transferred antigen-specific T cells with genetically ablated PD-1 expression.

Engagement of the inhibitory T cell receptor programmed cell death protein 1 (PD-1) associates with dysfunctional states of pathogen- or tumor-specific T cells. Accordingly, systemic antibody-mediated blockade of PD-1 has become a central target for immunotherapies but is also associated with severe toxicities due to loss of peripheral tolerance. Therefore, selective ablation of PD-1 expression on adoptively transferred T cells through direct genetic knockout (KO) is currently being explored as an alternative therapeutic approach.

Hospital Mortality and Trainee Experiences: How General Medical Council Survey Findings Correlate With Summary Hospital-Level Mortality Indicator.

Objectives: This study aimed to investigate whether components of junior doctor satisfaction are associated with patient mortality within the United Kingdom.

Methods: We conducted a cross-sectional study of publicly available data (the General Medical Council [GMC] National Survey and the Summary Hospital-level Mortality Indicator [SHMI]) pertaining to subjective physician trainee satisfaction and patient mortality within 80 United Kingdom-based healthcare institutions. The direction and strength of correlation between components of the GMC National Survey and relative patient mortality as described by the SHMI were calculated.

Signatures of recent activation identify a circulating T cell compartment containing tumor-specific antigen receptors with high avidity.

T cell receptor (TCR) avidity is assumed to be a major determinant of the spatiotemporal fate and protective capacity of tumor-specific T cells. However, monitoring polyclonal T cell responses with known TCR avidities in vivo over space and time remains challenging. Here, we investigated the fate and functionality of tumor neoantigen-specific T cells with TCRs of distinct avidities in a well-established, reductionist preclinical tumor model and human patients with melanoma.

Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events.

Awareness of racial/ethnic disparities represents a key challenge for healthcare systems that attempt to provide effective healthcare and to reduce existing inequalities in the use of and adherence to guideline-recommended cardiovascular drugs to improve clinical outcomes for cardiovascular disease (CVD). In this review, we describe important racial/ethnic differences between and within ethnic groups in the prevalence, risk factors, haemostatic factors, anti-inflammatory and endothelial markers, recurrence, and outcomes of CVD. We discuss important differences in the selection, doses, and response [efficacy and adverse drug reactions (ADRs)] in ethnically diverse patients treated with antithrombotics or lipid-lowering drugs.

Ethnic and Regional Differences in the Management of Angina: The Way Forward.

For decades, there has been great interest in ethnic differences in the management of angina and stable cardiovascular disease. Clinical decisionmaking is known to be both consciously and unconsciously influenced by a patient's demographics, and this is due to in part to differences in clinical guidance and opinion. However, the evidence supporting such decision-making is sparse.

Medical students’ pattern of self-directed learning prior to and during the coronavirus disease 2019 pandemic period and its implications for Free Open Access Meducation within the United Kingdom.

Purpose: Self-directed learning (SDL) has been increasingly emphasized within medical education. However, little is known about the SDL resources medical students use. This study aimed to identify patterns in medical students’ SDL behaviors, their SDL resource choices, factors motivating these choices, and the potential impact of the coronavirus disease 2019 (COVID-19) pandemic on these variables.

Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma.

The reprogramming of a patient's immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractory neuroblastoma with escalating doses of second-generation GD2-directed CAR-T cells and increasing intensity of preparative lymphodepletion.

Paediatric Free Open Access Meducation (FOAM): behaviours, trends and implications.

Introduction: Free Open Access Meducation (FOAM) describes online resources assisting learning in medicine. Little is known about users or their behaviours.

Methods: Using Google Analytics for a popular FOAM site (www.

A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations.

Background: For children with cancer, the clinical integration of precision medicine to enable predictive biomarker-based therapeutic stratification is urgently needed.

Methods: We have developed a hybrid-capture next-generation sequencing (NGS) panel, specifically designed to detect genetic alterations in paediatric solid tumours, which gives reliable results from as little as 50 ng of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue. In this study, we offered an NGS panel, with clinical reporting via a molecular tumour board for children with solid tumours.

Tumor infiltrating lymphocytes expanded from pediatric neuroblastoma display heterogeneity of phenotype and function.

Adoptive transfer of ex vivo expanded tumor infiltrating lymphocytes (TILs) has led to clinical benefit in some patients with melanoma but has not demonstrated convincing efficacy in other solid cancers. Whilst the presence of TILs in many types of cancer is often associated with better clinical prognosis, their function has not been systematically evaluated across cancer types. Responses to immunological checkpoint inhibitors in a wide range of cancers, including those for which adoptive transfer of expanded TILs has not shown clinical benefit, has clearly delineated a number of tumor type associated with tumor-reactive lymphocytes capable of effecting tumor remissions.

Establishment and phenotyping of neurosphere cultures from primary neuroblastoma samples.

: Primary cell culture using serum free media supplemented with growth factors has been used in a number of cancers to propagate primary cells with stem like properties, which form as spherical cellular aggregates. : We systematically evaluated the capacity of freshly disaggregated neuroblastoma tumors to become established as neurospheres in stem cell media using a uniform protocol. 67 primary neuroblastoma samples from patients treated at a single institution were prospectively evaluated for their ability to become established in culture.

Engineered human mesenchymal stem cells for neuroblastoma therapeutics.

Drug-resistant neuroblastoma remains a major challenge in paediatric oncology and novel and less toxic therapeutic approaches are urgently needed to improve survival and reduce the side effects of traditional therapeutic interventions. Mesenchymal stem cells (MSCs) are an attractive candidate for cell and gene therapy since they are recruited by and able to infiltrate tumours. This feature has been exploited by creating genetically modified MSCs that are able to combat cancer by delivering therapeutic molecules.

The presence of Y674/Y675 phosphorylated NTRK1 via TP53 repression of PTPN6 expression as a potential prognostic marker in neuroblastoma.

The tumor suppressor TP53 promotes nerve growth factor receptor (NTRK1) -Y674/Y675 phosphorylation (NTRK1-pY674/pY675) via repression of the NTRK1 phosphatase PTPN6 in a ligand-independent manner, resulting in suppression of breast cancer cell proliferation. Moreover, NTRK1-pY674/pY675 together with low levels of PTPN6 and TP53 expression is associated with favorable disease-free survival of breast cancer patients. We determined whether in neuroblastoma this protein expression pattern impacts relapse-free survival (RFS).

Language lateralisation measured across linguistic and national boundaries.

The visual half-field technique has been shown to be a reliable and valid neuropsychological measurement of language lateralisation, typically showing higher accuracy and faster correct responses for linguistic stimuli presented in the right visual field (RVF) than left visual field (LVF). The RVF advantage corresponds to the well-known dominance of the left hemisphere (LH) in processing language(s). However, clinical and experimental neuroscientists around the globe use different variations of the visual half-field paradigm, making direct comparisons difficult.

Are sleep disturbances causally linked to the presence and severity of psychotic-like, dissociative and hypomanic experiences in non-clinical populations? A systematic review.

The present review aimed to 1) identify what sleep disturbances co-occur alongside psychotic-like, dissociative and hypomanic experiences; 2) assess the strength of potential associations between the severity of sleep disturbances and of the experiences studied; and 3) appraise evidence for a causal link. MedLine and PsycInfo were searched and 44 studies were deemed eligible. Results showed that insomnia was associated with all individual psychotic-like, dissociative and hypomanic experiences reviewed (effect size range: small-to-large).

A Promyelocytic Leukemia Protein-Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma.

Purpose: Neuroblastoma is a childhood malignancy originating from the sympathetic nervous system with a complex biology, prone to metastasize and relapse. High-risk, metastatic cases are explained in part by amplification or mutation of oncogenes, such as MYCN and ALK, and loss of tumor suppressor genes in chromosome band 1p. However, it is fundamental to identify other pathways responsible for the large portion of neuroblastomas with no obvious molecular alterations.

Better than mermaids and stray dogs? Subtyping auditory verbal hallucinations and its implications for research and practice.

The phenomenological diversity of auditory verbal hallucinations (AVH) is not currently accounted for by any model based around a single mechanism. This has led to the proposal that there may be distinct AVH subtypes, which each possess unique (as well as shared) underpinning mechanisms. This could have important implications both for research design and clinical interventions because different subtypes may be responsive to different types of treatment.