Explore the vast range of titles available.

\"This thrilling volume collects the earliest adventures of the Flash--police scientist Barry Allen, who is the star of the hit TV series The Flash on the CW! These stories, from the late 1950s, relate the origin of the Flash, his discovery of his incredible super-speed, and the introductions of the first of his \"Rogues Gallery\" of super-villains, including Captain Cold, Gorilla Grodd and Weather Wizard, all of whom have been featured on the TV series, as well as the Pied Piper, Mirror Master and Mr. Element. Also in this volume, witness the debut appearances of fellow heroes Kid Flash and the Elongated Man\"-- Provided by publisher.

ObjectiveLower GI bleeding (LGIB) is a common reason for emergency hospital admission, although there is paucity of data on presentations, interventions and outcomes. In this nationwide UK audit, we describe patient characteristics, interventions including endoscopy, radiology and surgery as well as clinical outcomes.DesignMulticentre audit of adults presenting with LGIB to UK hospitals over 2 months in 2015. Consecutive cases were prospectively enrolled by clinical teams and followed for 28 days.ResultsData on 2528 cases of LGIB were provided by 143 hospitals. Most were elderly (median age 74 years) with major comorbidities, 29.4% taking antiplatelets and 15.9% anticoagulants. Shock was uncommon (58/2528, 2.3%), but 666 (26.3%) received a red cell transfusion. Flexible sigmoidoscopy was the most common investigation (21.5%) but only 2.1% received endoscopic haemostasis. Use of embolisation or surgery was rare, used in 19 (0.8%) and 6 (0.2%) cases, respectively. 48% patients underwent no inpatient investigations. The most common diagnoses were diverticular bleeding (26.4%) and benign anorectal conditions (16.7%). Median length of stay was 3 days, 13.6% patients rebled during admission and 4.4% were readmitted with bleeding within 28 days. In-hospital mortality was 85/2528 (3.4%) and was highest in established inpatients (17.8%, p<0.0001) and in patients experiencing rebleeding (7.1%, p<0.0001).ConclusionsPatients with LGIB have a high burden of comorbidity and frequent antiplatelet or anticoagulant use. Red cell transfusion was common but most patients were not shocked and required no endoscopic, radiological or surgical treatment. Nearly half were not investigated. In-hospital mortality was related to comorbidity, not severe haemorrhage.

Recent progress has been made in the identification and implementation of best transfusion practices on the basis of evidence-based clinical trials, published clinical practice guidelines, and process improvements for blood use and clinical patient outcomes. However, substantial variability persists in transfusion outcomes for patients in some clinical settings—eg, patients undergoing cardiothoracic surgery. This variability could be the result of insufficient understanding of published guidelines; different recommendations of medical societies, including the specification of a haemoglobin concentration threshold to use as a transfusion trigger; the value of haemoglobin as a surrogate indicator for transfusion benefit, even though only changes in concentration and not absolute red cell mass of haemoglobin can be identified; and disagreement about the validity of the level 1 evidence for clinical practice guidelines. Nevertheless, institutional experience and national databases suggest that a restrictive blood transfusion approach is being increasingly implemented as best practice.

In a large study using registry data from Britain, overall cancer incidence was not increased among children born after assisted conception. Assisted conception was associated with an increased risk of hepatoblastoma and rhabdomyosarcoma, but the absolute risks were small. Since the introduction of in vitro fertilization (IVF) in 1978, the number and proportion of children born after assisted conception have increased annually, and currently there are more than 5 million such persons worldwide. 1 Well-recognized perinatal complications in this population include low birth weight, prematurity, and congenital malformations. 2 – 4 However, there remains a dearth of population-based studies investigating important but rare health outcomes. The possibility of an increased risk of cancer in this population has been suggested previously. 5 – 9 This concern is supported by the discovery of altered epigenetic patterns in human embryos, 10 , 11 cord blood, 12 and placentas 12 , 13 after . . .

Transfusion thresholds for acute upper gastrointestinal bleeding are controversial. So far, only three small, underpowered studies and one single-centre trial have been done. Findings from the single-centre trial showed reduced mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess whether a multicentre, cluster randomised trial is a feasible method to substantiate or refute this finding. In this pragmatic, open-label, cluster randomised feasibility trial, done in six university hospitals in the UK, we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding, irrespective of comorbidity, except for exsanguinating haemorrhage. We randomly assigned hospitals (1:1) with a computer-generated randomisation sequence (random permuted block size of 6, without stratification or matching) to either a restrictive (transfusion when haemoglobin concentration fell below 80 g/L) or liberal (transfusion when haemoglobin concentration fell below 100 g/L) RBC transfusion policy. Neither patients nor investigators were masked to treatment allocation. Feasibility outcomes were recruitment rate, protocol adherence, haemoglobin concentration, RBC exposure, selection bias, and information to guide design and economic evaluation of the phase 3 trial. Main exploratory clinical outcomes were further bleeding and mortality at day 28. We did analyses on all enrolled patients for whom an outcome was available. This trial is registered, ISRCTN85757829 and NCT02105532. Between Sept 3, 2012, and March 1, 2013, we enrolled 936 patients across six hospitals (403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy). Recruitment rate was significantly higher for the liberal than for the restrictive policy (62% vs 55%; p=0·04). Despite some baseline imbalances, Rockall and Blatchford risk scores were identical between policies. Protocol adherence was 96% (SD 10) in the restrictive policy vs 83% (25) in the liberal policy (difference 14%; 95% CI 7–21; p=0·005). Mean last recorded haemoglobin concentration was 116 (SD 24) g/L for patients on the restrictive policy and 118 (20) g/L for those on the liberal policy (difference −2·0 [95% CI −12·0 to 7·0]; p=0·50). Fewer patients received RBCs on the restrictive policy than on the liberal policy (restrictive policy 133 [33%] vs liberal policy 247 [46%]; difference −12% [95% CI −35 to 11]; p=0·23), with fewer RBC units transfused (mean 1·2 [SD 2·1] vs 1·9 [2·8]; difference −0·7 [–1·6 to 0·3]; p=0·12), although these differences were not significant. We noted no significant difference in clinical outcomes. A cluster randomised design led to rapid recruitment, high protocol adherence, separation in degree of anaemia between groups, and non-significant reduction in RBC transfusion in the restrictive policy. A large cluster randomised trial to assess the effectiveness of transfusion strategies for acute upper gastrointestinal bleeding is both feasible and essential before clinical practice guidelines change to recommend restrictive transfusion for all patients with acute upper gastrointestinal bleeding. NHS Blood and Transplant Research and Development.

Background This nationwide study investigated associations between paternal occupational exposure and childhood bone tumours and soft- tissue sarcomas. Methods The UK National Registry of Childhood Tumours provided cases of childhood sarcomas born and diagnosed in Great Britain, 1962–2010. Control births, unaffected by childhood cancer, were matched on sex, birth period and birth registration sub-district. Fathers’ occupations were assigned to one or more of 33 exposure groups and coded for occupational social class. Results We analysed 5,369 childhood sarcoma cases and 5380 controls. Total bone tumours, total soft-tissue sarcomas and the subgroups osteosarcoma, rhabdomyosarcoma and Ewing Sarcoma Family of Tumours (ESFT) were considered separately. Significant positive associations were seen between rhabdomyosarcoma and paternal exposure to EMFs (odds ratio = 1.67, CI = 1.22–2.28) and also for ESFT and textile dust (1.93, 1.01–3.63). There were putative protective effects on total bone tumours of paternal dermal exposure to hydrocarbons, metal, metal working or oil mists. Conclusions Despite the large size and freedom from bias of this study, our results should be interpreted with caution. Many significance tests were undertaken, and chance findings are to be expected. Nevertheless, our finding of associations between ESFT and paternal exposure to textile dust may support related suggestions in the literature.

Background This nationwide study investigates associations between paternal occupational exposure and childhood lymphoma. Methods The UK National Registry of Childhood Tumours provided cases of childhood lymphoma born and diagnosed in Great Britain 1962–2010. Control births, unaffected by childhood cancer, were matched on sex, birth period and birth registration sub-district. Fathers’ occupations were assigned to one or more of 33 exposure groups and also coded for occupational social class. Results We analysed 5033 childhood lymphoma cases and 4990 controls. Total lymphoma and the subgroups Hodgkin, Burkitt and non-Hodgkin lymphoma were considered separately. No one exposure was significantly associated with increased risk within all subgroups and for total lymphoma. However, exposure to “ceramics and glass” was significantly associated with increased risk of total lymphoma, Hodgkin and non-Hodgkin lymphoma. Paternal lead exposure was associated with Burkitt lymphoma and exposure to metal fumes was associated with Hodgkin lymphoma. Conclusions This study provides no support for previous suggestions of an association between childhood lymphoma and paternal occupational exposure to pesticides, solvents/hydrocarbons or infections potentially transmitted by father’s social contacts. An association with exposure to “ceramics and glass” was noted for the two major lymphoma subtypes together comprising 80% of total lymphoma.

We investigated whether an observed reduction in overall childhood cancer risk (<15 years of age) in twins has been sustained, and how this extends into young adulthood. We searched for English language publications reporting childhood cancer risk in twins, obtained unpublished data directly from some authors, and updated a meta-analysis. We used the Swedish Multigeneration Register to investigate the age to which the reduced overall risk of childhood cancer (observed previously using that Swedish dataset and in this and earlier meta-analyses) persisted into the teenage/young adult years, and which specific tumors accounted for the overall risk reduction beyond childhood. Our meta-analysis of studies of aggregate childhood cancer risk in twins confirmed their approximate 15% reduction in cancer mortality and incidence. Further analysis of Swedish Multigeneration Register data for 1958 to 2002 suggested these reduced risks of cancer (particularly leukaemias and renal tumors) extended from childhood to young adult ages. Reduced risks of these and some other specific tumor types occurring across childhood/teenage/young adult years appeared to account for most of the overall risk reduction. Our results suggest a persistent reduction of overall childhood cancer risk in twins and that this extends into young adulthood. Risk reductions for several specific tumors might account for this and, although there are several potential explanations, intrauterine growth patterns of twins might be a major contributor.

Background Anaemia significantly affects health outcomes and quality of life. While blood transfusion remains a common intervention, alternative treatments, such as iron supplementation and erythropoiesis‐stimulating agents (ESAs), offer potential to mitigate transfusion‐associated costs. However, robust evidence on their cost‐effectiveness remains limited. Objective This review assesses the cost‐effectiveness of anaemia treatments, aiming to inform UK healthcare policy and practice. Methods A systematic review was conducted following PRISMA guidelines, identifying economic evaluations published between 2015 and 2025. Study quality was appraised using the Drummond checklist and NICE reference case criteria. Data were synthesised using the Hierarchical Decision Matrix framework. Results Of 5496 records screened, 14 studies met inclusion criteria; 11 were included in the final synthesis, with three excluded due to low methodological quality. Restrictive transfusion strategies were cost‐saving (£35.50–£75 per patient), reduced red blood cell utilisation by ∼21%, shortened length of stay by 0.5 to 3 days, and yielded modest QALY gains (0.01 to 0.02). ESAs reduced transfusion risk (RR 0.61 to 0.87) but incurred substantial incremental costs (£1859–£3060) with limited evidence of QALY gains. Transfusion of fresher blood in ICU settings increased costs without a measurable clinical or economic advantage. Preoperative erythropoietin and ferric carboxymaltose reduced transfusion incidence but were high‐cost interventions with limited evidence on QALY gains. Patient Blood Management (PBM), particularly intravenous iron, was cost‐saving (£30.80–1166 saved per patient), reduced transfusion rates (RR 0.61), but with limited evidence on QALY gains. Conclusion Restrictive transfusion thresholds and PBM interventions, especially intravenous iron, demonstrate favourable cost‐effectiveness and potential for NHS cost savings. In contrast, the cost‐effectiveness of ESAs remains uncertain due to high costs and limited utility evidence. Further research is needed to capture long‐term outcomes and generate UK‐specific economic data. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

Correspondence to Dr Gaurav Bhaskar Nigam, University of Oxford Oxford Translational Gastroenterology Unit, Oxford, UK; gaurav.nigam@nhs.net Key messages Machine learning can help to predict the risk of adverse outcomes and need for intervention in patients with acute gastrointestinal bleeding, allowing clinicians to intervene earlier and improve patient outcomes Use of machine learning in this context is still in its early stages, and further research is needed to refine and validate prediction models Interpretability and transparency of machine learning models are essential to gain the trust of clinicians and ensure that models are used appropriately in clinical practice Collaboration between clinicians and data scientists is critical to the successful implementation of machine learning in the management of acute gastrointestinal bleeding Integration of machine learning has the potential to transform the management of acute gastrointestinal bleeding, but a transparent and collaborative approach will be key, argue Gaurav Nigam and colleagues Introduction Acute gastrointestinal bleeding, which can affect both the upper and lower gastrointestinal tracts, poses a global healthcare challenge. Incidence rates for acute upper gastrointestinal bleeding have been reported to range from 15.0 to 172.0 per 100 000 person years, whereas rates for acute lower gastrointestinal bleeding have ranged from 20.5 to 87.0 per 100 000 person years.1 The UK has had a pioneering role in improving acute gastrointestinal bleeding patient care through national audits and novel risk score development for both acute upper and lower gastrointestinal bleeding.2–4 Results from a 2007 audit involving 6750 patients with acute upper gastrointestinal bleeding showed a high overall in-hospital mortality of 10%, with a striking 26% mortality among established inpatients who developed acute upper gastrointestinal bleeding.2 Similarly, a 2015 audit of 2528 patients with acute lower gastrointestinal bleeding reported a 3.4% overall in-hospital mortality and 18% mortality among established inpatients who developed acute lower gastrointestinal bleeding, often attributable to comorbidities rather than from severe haemorrhage.3 Recent years have seen efforts to enhance acute gastrointestinal bleeding management, encompassing changes in clinical practices, the development of new risk assessment scores, and improved medical and endoscopic treatments.5 Notably, interim results from a 2022 re-audit of acute upper gastrointestinal bleeding in the UK suggest a decline in overall in-hospital mortality to 8.2% (5.2% in new admissions and 19% in established inpatients) despite a more comorbid population compared with 2007.6 Patients with acute gastrointestinal bleeding often present with diverse comorbidities and bleeding causes, necessitating individualised management plans. Table 1 Descriptions of machine learning models and their suitability in prediction of acute gastrointestinal bleeding risk Model Description Advantages Suitability Decision trees Tree-like structure where internal nodes represent feature attributes, branches represent decisions, and leaves represent outcomes or labels Easy to interpret and visualise, suitable for both classification and regression tasks Appropriate when transparency and interpretability are essential, useful for initial insights into data Gradient boosting model (XGBoost) Ensemble learning technique that combines predictions of multiple weaker models (usually decision trees) to create a stronger predictive model Excellent predictive performance, handles missing data effectively, provides feature importance rankings High predictive accuracy in risk prediction tasks k-nearest neighbors Non-parametric, instance based learning method that classifies data points based on the majority class among their k-nearest neighbors Simple to understand and implement, effective for small to medium sized datasets Suitable for tasks where data points share similar characteristics, eg, patient risk assessment Regularised Cox regression Survival analysis method used for time-to-event prediction, considering both covariates and event times Accounts for censoring, handles survival data, can incorporate covariate information Particularly useful for predicting critical outcomes with time-to-event dependencies, eg, rebleeding Random survival forests Survival analysis technique using random forests to analyse survival data and estimate survival probabilities Reduces overfitting risk compared with individual trees, handles high dimensional data Beneficial for analysing survival data in patients with acute gastrointestinal bleeding and estimating time dependent risks Neural networks Deep learning models inspired by the human brain, composed of interconnected layers of artificial neurons Captures complex, non-linear relationships, suitable for large datasets and diverse data types Excels in tasks with intricate underlying patterns and substantial data requirements Support vector Machines Classification technique aiming to find an optimal hyperplane to separate data points into different classes Effective for high dimensional data and adept at capturing complex associations Valuable when dealing with complex, high dimensional data in risk prediction of acute gastrointestinal bleeding Current application of machine learning for acute gastrointestinal bleeding Risk prediction and outcome analysis Various risk scores have been developed for patients with acute gastrointestinal bleeding; for example, Glasgow Blatchford score, full or pre-endoscopy Rockall score, AIMS65, Progetto Nazionale Emorragia Digestive score, Oakland score, and the more recently developed ABC score.4 11 These risk scores have been developed to assist clinical decision making and prediction of relevant clinical outcomes that include hospital based interventions (eg, need for transfusion, endoscopic treatment, interventional radiology, and surgery), rebleeding, and mortality. [...]these risk scores exhibit variable performance, and a single score cannot predict all relevant outcomes.12 13 A systematic review of 14 observational studies that developed machine learning based models on acute gastrointestinal bleeding showed event prevalence of 2-20% for mortality, 11-21% for rebleeding, and 12-76% for need of intervention; each study included 147 to 2380 participants, with four to 50 variables (ie, demographic, laboratory, and clinical characteristics at presentation).14 These models performed well for predicting rebleeding, need for intervention, and mortality in patients with acute gastrointestinal bleeding.