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Athlete ECG interpretation criteria have been developed and refined from research in athlete populations; however, current guidelines are based on available data primarily from Caucasian and Black athletes. This study aimed to assess the impact of ethnicity on ECG interpretation in athletes. A systematic review was conducted of the MEDLINE, EMBASE, Scopus, SPORTDiscus, and Web of Science databases, for papers that assessed athlete screening ECGs and compared findings on the basis of ethnicity. Fifty-one papers which compared ECGs from various ethnicities were included. Most studies assessed Black athletes against Caucasian athletes and found a greater prevalence of T-wave inversion (TWI) (2.6–22.8% vs. 0–5.0%) and anterior TWI (3.7–14.3% vs. 0.6–2.0%). Black athlete subgroups in Africa had TWI (20–40%) and anterior TWI (4.3–18.7%) at a higher prevalence than other Black athletes. Athletes who were defined as mixed-race, Asian, and Pacific Islander are potentially more like Black athletes than Caucasian athletes. Black ethnicity is known to have an impact on the accurate interpretation of athlete ECGs; however, there is nuance related to origin of both parents. Asian and Pacific Islander origin also may impact athlete ECG interpretation. Further research is required to assist in distinguishing abnormal and normal athlete ECGs in different ethnic populations.

Screening elite athletes for conditions associated with sudden cardiac death is recommended by numerous international guidelines. Current athlete electrocardiogram interpretation criteria recommend the Bazett formula (QTcB) for correcting QT interval. However, other formulae may perform better at lower and higher heart rates (HR). This review aimed to examine the literature on various QT correction methods in athletes and young people aged 14-35 years and determine the most accurate method of calculating QTc in this population. A systematic review of MEDLINE, EMBASE, Scopus, and SportDiscus was performed. Papers comparing at least two different methods of QT interval correction in athletes or young people were included. Quality and risk of bias were assessed using a standardized tool. The search strategy identified 545 papers, of which 10 met the criteria and were included. Nine of these studies concluded that QTcB was least reliable for removing the effect of HR and was inaccurate at both high (>90 beats per min [BPM]) and low (<60 BPM) HRs. No studies supported the use of QTcB in athletes and young people. Alternative QT correction algorithms such as Fridericia (QTcF) produce more accurate correction of QT interval at HRs seen in athletes and young people. QTcB is less accurate at lower and higher HRs. QTcF has been shown to be more accurate in these HR ranges and may be preferred to QTcB for QTc calculation in athletes and young people. However, accurate QTc reference values for discrete HRs using alternative algorithms are not well established and require further research.

To report findings from the High Performance Sport New Zealand cardiac screening programme, including comparisons between sexes and ethnicities. Retrospective cohort study. Elite Olympic-sport athletes were screened (2012–2022) with personal/family history, physical examination, resting 12-lead ECG and followed from the date of first screening until July 2022. An audit reviewed screening records, including demographic data, ECGs, follow-up and diagnoses. Flagged/equivocal ECGs were re-reviewed (International Criteria). 2075 ECGs from 1189 athletes (53 % female, mean age 21 years; 83 % European, 9 % Māori, 5 % Pacific Islander, 3 % other) were included. No athletes retired for cardiac reasons; there were no cardiac deaths or major cardiac incidents (mean follow-up from first screening: 6.1 years (range: 0.6–10.9 years)). Diagnoses included Wolff-Parkinson-White (WPW) syndrome (0.7 %) and cardiomyopathies (0.3 %). Overall, 3.5 % of ECGs were abnormal, with ECGs of females more commonly abnormal (4.4 % vs 2.5 %, p = 0.02) and with a higher proportion of ECGs with abnormal T-wave inversion (TWI) (3.1 % vs 0.9 %, p < 0.001) compared to males. Of the abnormal TWI in females (all aged ≥16 years), 47 % was limited to V1–V3 with no other abnormalities. Abnormality rates were similar between Māori, Pacific Islander and European athlete ECGs. WPW was the most frequent diagnosis, with very little cardiomyopathy found. The proportion of abnormal ECGs was low overall, but higher in females. This was driven by anterior TWI in V1–V3 which was not associated with diagnoses of conditions associated with sudden cardiac death (SCD). There was no difference in the proportion of abnormal ECGs of Māori or Pacific Island athletes compared to European athletes. [Display omitted]

Studying the interactions between nanoengineered materials and biological systems plays a vital role in the development of biological applications of nanotechnology and the improvement of our fundamental understanding of the bio–nano interface. A significant barrier to progress in this multidisciplinary area is the variability of published literature with regards to characterizations performed and experimental details reported. Here, we suggest a ‘minimum information standard’ for experimental literature investigating bio–nano interactions. This standard consists of specific components to be reported, divided into three categories: material characterization, biological characterization and details of experimental protocols. Our intention is for these proposed standards to improve reproducibility, increase quantitative comparisons of bio–nano materials, and facilitate meta analyses and in silico modelling.

•Behaviorally people assigned less positivity to the authentic (vs. presented) self.•P1 showed a preference for threatening information about the presented self.•N170 showed a preference for favorable information about the presented self.•People engaged in more elaborate processing about the authentic self later (LPP).•Though authenticity is aligned with positivity, it still allows room for negativity. Authenticity has captivated scholars. But what is it? An emerging view considers it exaggerated favorability (self-enhancement), whereas traditional views regard it as self-accuracy and self-consistency. We tested these theoretical views by contrasting the authentic self with the presented self, a highly desirable representation. Behaviorally, participants ascribed less positivity to the authentic self: They endorsed more negative traits and were faster to admit having them; also, they endorsed fewer positive traits and were slower to admit having them. Neurally, participants manifested preferential processing of threatening information (P1), followed by preferential processing of favorable information (N170), about the presented self (than authentic self), indicating its brittleness. At a later stage (LPP), participants engaged in more elaborate processing of threatening and favorable information about the authentic self, indicating its subjective importance. Authenticity, albeit mostly positive, allows room for negativity.

Aims/hypothesisApparent type 2 diabetes is increasingly reported in lean adult individuals in sub-Saharan Africa. However, studies undertaking robust clinical and metabolic characterisation of lean individuals with new-onset type 2 diabetes are limited in this population. This cross-sectional study aimed to perform a detailed clinical and metabolic characterisation of newly diagnosed adult patients with diabetes in Uganda, in order to compare features between lean and non-lean individuals.MethodsSocio-demographic, clinical, biophysical and metabolic (including oral glucose tolerance test) data were collected on 568 adult patients with newly diagnosed diabetes. Participants were screened for islet autoantibodies to exclude those with autoimmune diabetes. The remaining participants (with type 2 diabetes) were then classified as lean (BMI <25 kg/m2) or non-lean (BMI ≥25 kg/m2), and their socio-demographic, clinical, biophysical and metabolic characteristics were compared.ResultsThirty-four participants (6.4%) were excluded from analyses because they were positive for pancreatic autoantibodies, and a further 34 participants because they had incomplete data. For the remaining 500 participants, the median (IQR) age, BMI and HbA1c were 48 years (39–58), 27.5 kg/m2 (23.6–31.4) and 90 mmol/mol (61–113) (10.3% [7.7–12.5]), respectively, with a female predominance (approximately 57%). Of the 500 participants, 160 (32%) and 340 (68%) were lean and non-lean, respectively. Compared with non-lean participants, lean participants were mainly male (60.6% vs 35.3%, p<0.001) and had lower visceral adiposity level (5 [4–7] vs 11 [9–13], p<0.001) and features of the metabolic syndrome (uric acid, 246.5 [205.0–290.6] vs 289 [234–347] μmol/l, p<0.001; leptin, 660.9 [174.5–1993.1] vs 3988.0 [1336.0–6595.0] pg/ml, p<0.001). In addition, they displayed markedly reduced markers of beta cell function (oral insulinogenic index 0.8 [0.3–2.5] vs 1.6 [0.6–4.6] pmol/mmol; 120 min serum C-peptide 0.70 [0.33–1.36] vs 1.02 [0.60–1.66] nmol/l, p<0.001).Conclusions/interpretationApproximately one-third of participants with incident adult-onset non-autoimmune diabetes had BMI <25 kg/m2. Diabetes in these lean individuals was more common in men, and predominantly associated with reduced pancreatic secretory function rather than insulin resistance. The underlying pathological mechanisms are unclear, but this is likely to have important management implications.

Background Microangiopathy in type 2 diabetes (T2D) is associated with cardiovascular disease (CVD), but most relevant studies were performed > 10 years ago. CVD risk factor management has since improved. The aim of this study was to determine whether diabetic retinopathy (DR) and its severity increases stroke and myocardial infarction (MI) risk in a contemporary cohort. Methods Fremantle Diabetes Study Phase II participants with T2D had DR graded from fundus photography at baseline between 2008 and 2011. Subsequent hospitalizations and mortality for MI or stroke were ascertained through validated data linkage to end-2016. Cox regression modelling identified predictors of first stroke and MI including DR presence and severity. Results The 1521 participants with T2D and known DR status (mean age 65.6 years, 52.1% males, median diabetes duration 9.0 years) were followed for a mean of 6.6 years. After excluding those with prior MI/stroke, there were 126 incident MIs among 1393 eligible participants and 53 incident strokes in 1473 eligible participants, respectively. Moderate non-proliferative DR (NPDR) or worse was significantly and independently associated with an increased risk of incident stroke (adjusted hazard ratio 2.55 (95% CI 1.19, 5.47), p  = 0.016). Retinopathy presence and severity increased the risk of incident MI in unadjusted models ( p  ≤ 0.001), but these associations were no longer statistically significant after adjusting for other risk factors. Conclusions Moderate NPDR or worse was associated with an increased risk of first stroke in Australians with T2D. Intensified CVD risk factor management should be considered for patients with at least moderate NPDR.

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5–46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells. Genetic and phenotypic analysis reveals expression quantitative trait loci in human induced pluripotent stem cell lines associated with cancer and disease. Mapping variations in human induced pluripotent stem cells The Human Induced Pluripotent Stem Cells Initiative (HipSci) has resulted in the generation, genotyping and phenotyping of more than 700 human induced pluripotent stem (iPS) cell lines derived from 300 healthy individuals. Although analysis of these data indicates that most of the variations in phenotypes between cells arise from variations between individuals, the authors also assess the consequences of the rare genetic defects that are recurrently seen in iPS cells after reprogramming and provide a map of the common regulatory variants that can change the transcriptome of human pluripotent cells. This resource will be useful for genetic studies of complex traits and cancer.

Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system 1 . We have previously shown that the disialoganglioside GD2 is highly expressed on H3K27M-mutated glioma cells and have demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells 2 , providing the rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR T cell-induced brainstem inflammation can result in obstructive hydrocephalus, increased intracranial pressure and dangerous tissue shifts, neurocritical care precautions were incorporated. Here we present the clinical experience from the first four patients with H3K27M-mutated DIPG or spinal cord DMG treated with GD2-CAR T cells at dose level 1 (1 × 10 6 GD2-CAR T cells per kg administered intravenously). Patients who exhibited clinical benefit were eligible for subsequent GD2-CAR T cell infusions administered intracerebroventricularly 3 . Toxicity was largely related to the location of the tumour and was reversible with intensive supportive care. On-target, off-tumour toxicity was not observed. Three of four patients exhibited clinical and radiographic improvement. Pro-inflammatory cytokine levels were increased in the plasma and cerebrospinal fluid. Transcriptomic analyses of 65,598 single cells from CAR T cell products and cerebrospinal fluid elucidate heterogeneity in response between participants and administration routes. These early results underscore the promise of this therapeutic approach for patients with H3K27M-mutated DIPG or spinal cord DMG. A phase I dose-escalation trial of GD2-CAR T cells in children and young adults with diffuse midline gliomas to assess the feasibility of manufacturing, safety and tolerability, and to preliminarily assess efficacy.

This study aimed to investigate the frequency of islet autoantibody positivity in adult patients with recently diagnosed diabetes in Uganda and its associated characteristics. Autoantibodies to glutamic acid decarboxylase-65 (GADA), zinc transporter 8 (ZnT8-A), and tyrosine phosphatase (IA-2A) were measured in 534 adult patients with recently diagnosed diabetes. Islet autoantibody positivity was defined based on diagnostic thresholds derived from a local adult population without diabetes. The socio-demographic, clinical, and metabolic characteristics of islet autoantibody-positive and negative participants were then compared. The differences in these characteristics were analysed using the x2 test for categorical data and the Kruskal Wallis test for continuous data. Multivariate analysis was performed to identify predictors of islet autoantibody positivity. Thirty four (6.4%) participants were positive for ≥1 islet autoantibody. GADA, IA-2A and ZnT8-A positivity was detected in 17 (3.2%), 10 (1.9%), and 7 (1.3%) participants, respectively. Compared with those negative for islet autoantibodies, participants positive for islet autoantibodies were more likely to live in a rural area (n = 18, 52.9% Vs n = 127, 25.5%, p = 0.005), to be initiated on insulin therapy (n = 19, 55.9% Vs n = 134, 26.8%, p<0.001), to have a lower median waist circumference (90 [80-99] cm Vs 96 [87-104.8], p = 0.04), waist circumference: height ratio (0.55 [0.50-0.63] vs 0.59 [0.53-0.65], p = 0.03), and fasting C-peptide concentration (0.9 [0.6-1.8] Vs 1.4 [0.8-2.1] ng/ml, p = 0.01). On multivariate analysis, living in a rural area (odds ratio or OR 3.62, 95%CI 1.68-7.80, p = 0.001) and being initiated on insulin therapy (OR 3.61, 95% CI 1.67-7.83, p = 0.001) were associated with islet autoantibody positivity. The prevalence of islet autoantibody positivity was relatively low, suggesting that pancreatic autoimmunity is a rare cause of new-onset diabetes in this adult Ugandan population. Living in a rural area and being initiated on insulin therapy were independently associated with islet autoantibody positivity in this study population.