Large-Scale Automatic Feature Selection for Biomarker Discovery in High-Dimensional OMICs Data

The identification of biomarker signatures in omics molecular profiling is usually performed to predict outcomes in a precision medicine context, such as patient disease susceptibility, diagnosis, prognosis, and treatment response. To identify these signatures, we have developed a biomarker discovery tool, called BioDiscML. From a collection of samples and their associated characteristics, i.e., the biomarkers (e.g., gene expression, protein levels, clinico-pathological data), BioDiscML exploits various feature selection procedures to produce signatures associated to machine learning models that will predict efficiently a specified outcome. To this purpose, BioDiscML uses a large variety of machine learning algorithms to select the best combination of biomarkers for predicting categorical or continuous outcomes from highly unbalanced datasets. The software has been implemented to automate all machine learning steps, including data pre-processing, feature selection, model selection, and performance evaluation. BioDiscML is delivered as a stand-alone program and is available for download at https://github.com/mickaelleclercq/BioDiscML

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Outcomes of obstructed abdominal wall hernia: results from the UK national small bowel obstruction audit

Background: Abdominal wall hernia is a common surgical condition. Patients may present in an emergency with bowel obstruction, incarceration or strangulation. Small bowel obstruction (SBO) is a serious surgical condition associated with significant morbidity. The aim of this study was to describe current management and outcomes of patients with obstructed hernia in the UK as identified in the National Audit of Small Bowel Obstruction (NASBO). Methods: NASBO collated data on adults treated for SBO at 131 UK hospitals between January and March 2017. Those with obstruction due to abdominal wall hernia were included in this study. Demographics, co-morbidity, imaging, operative treatment, and in-hospital outcomes were recorded. Modelling for factors associated with mortality and complications was undertaken using Cox proportional hazards and multivariable regression modelling. Results: NASBO included 2341 patients, of whom 415 (17·7 per cent) had SBO due to hernia. Surgery was performed in 312 (75·2 per cent) of the 415 patients; small bowel resection was required in 198 (63·5 per cent) of these operations. Non-operative management was reported in 35 (54 per cent) of 65 patients with a parastomal hernia and in 34 (32·1 per cent) of 106 patients with an incisional hernia. The in-hospital mortality rate was 9·4 per cent (39 of 415), and was highest in patients with a groin hernia (11·1 per cent, 17 of 153). Complications were common, including lower respiratory tract infection in 16·3 per cent of patients with a groin hernia. Increased age was associated with an increased risk of death (hazard ratio 1·05, 95 per cent c.i. 1·01 to 1·10; P = 0·009) and complications (odds ratio 1·05, 95 per cent c.i. 1·02 to 1·09; P = 0·001). Conclusion: NASBO has highlighted poor outcomes for patients with SBO due to hernia, highlighting the need for quality improvement initiatives in this group

Harmonised statistics and maps of forest biomass and increment in Europe.

peer reviewedForest biomass is an essential resource in relation to the green transition and its assessment is key for the sustainable management of forest resources. Here, we present a forest biomass dataset for Europe based on the best available inventory and satellite data, with a higher level of harmonisation and spatial resolution than other existing data. This database provides statistics and maps of the forest area, biomass stock and their share available for wood supply in the year 2020, and statistics on gross and net volume increment in 2010-2020, for 38 European countries. The statistics of most countries are available at a sub-national scale and are derived from National Forest Inventory data, harmonised using common reference definitions and estimation methodology, and updated to a common year using a modelling approach. For those counties without harmonised statistics, data were derived from the State of Europe's Forest 2020 Report at the national scale. The maps are coherent with the statistics and depict the spatial distribution of the forest variables at 100 m resolution

National prospective cohort study of the burden of acute small bowel obstruction

Background Small bowel obstruction is a common surgical emergency, and is associated with high levels of morbidity and mortality across the world. The literature provides little information on the conservatively managed group. The aim of this study was to describe the burden of small bowel obstruction in the UK. Methods This prospective cohort study was conducted in 131 acute hospitals in the UK between January and April 2017, delivered by trainee research collaboratives. Adult patients with a diagnosis of mechanical small bowel obstruction were included. The primary outcome was in‐hospital mortality. Secondary outcomes included complications, unplanned intensive care admission and readmission within 30 days of discharge. Practice measures, including use of radiological investigations, water soluble contrast, operative and nutritional interventions, were collected. Results Of 2341 patients identified, 693 (29·6 per cent) underwent immediate surgery (within 24 h of admission), 500 (21·4 per cent) had delayed surgery after initial conservative management, and 1148 (49·0 per cent) were managed non‐operatively. The mortality rate was 6·6 per cent (6·4 per cent for non‐operative management, 6·8 per cent for immediate surgery, 6·8 per cent for delayed surgery; P = 0·911). The major complication rate was 14·4 per cent overall, affecting 19·0 per cent in the immediate surgery, 23·6 per cent in the delayed surgery and 7·7 per cent in the non‐operative management groups (P < 0·001). Cox regression found hernia or malignant aetiology and malnutrition to be associated with higher rates of death. Malignant aetiology, operative intervention, acute kidney injury and malnutrition were associated with increased risk of major complication. Conclusion Small bowel obstruction represents a significant healthcare burden. Patient‐level factors such as timing of surgery, acute kidney injury and nutritional status are factors that might be modified to improve outcomes

Outcomes following small bowel obstruction due to malignancy in the national audit of small bowel obstruction

Introduction Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction. Methods A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori. Results 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity. Conclusions Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups

Outcomes of obstructed abdominal wall hernia: results from the UK national small bowel obstruction audit

Background Abdominal wall hernia is a common surgical condition. Patients may present in an emergency with bowel obstruction, incarceration or strangulation. Small bowel obstruction (SBO) is a serious surgical condition associated with significant morbidity. The aim of this study was to describe current management and outcomes of patients with obstructed hernia in the UK as identified in the National Audit of Small Bowel Obstruction (NASBO). Methods NASBO collated data on adults treated for SBO at 131 UK hospitals between January and March 2017. Those with obstruction due to abdominal wall hernia were included in this study. Demographics, co‐morbidity, imaging, operative treatment, and in‐hospital outcomes were recorded. Modelling for factors associated with mortality and complications was undertaken using Cox proportional hazards and multivariable regression modelling. Results NASBO included 2341 patients, of whom 415 (17·7 per cent) had SBO due to hernia. Surgery was performed in 312 (75·2 per cent) of the 415 patients; small bowel resection was required in 198 (63·5 per cent) of these operations. Non‐operative management was reported in 35 (54 per cent) of 65 patients with a parastomal hernia and in 34 (32·1 per cent) of 106 patients with an incisional hernia. The in‐hospital mortality rate was 9·4 per cent (39 of 415), and was highest in patients with a groin hernia (11·1 per cent, 17 of 153). Complications were common, including lower respiratory tract infection in 16·3 per cent of patients with a groin hernia. Increased age was associated with an increased risk of death (hazard ratio 1·05, 95 per cent c.i. 1·01 to 1·10; P = 0·009) and complications (odds ratio 1·05, 95 per cent c.i. 1·02 to 1·09; P = 0·001). Conclusion NASBO has highlighted poor outcomes for patients with SBO due to hernia, highlighting the need for quality improvement initiatives in this group

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Inflammabilité et explosivité des nanopoudres : effets-nano ou nano-effets ?

International audienceIn the industrial and research fields, nanomaterials provides a growing interest and many industrial applications have already been developed in the last years. However, knowledge about the hazards related to these new materials is currently limited. As safe nanomaterial production cannot be permitted without a deeper evaluation of environmental and occupational hazards, hazards related to nanoparticles have to be evaluated. One often thinks about the potential toxicity of nanoparticles. However, dust fire and explosion should not be neglected when the dusts are combustible, which may often be the case. So far, literature studies concerning the evaluation of explosion and flammability risks of powders were essentially carried out on micron-sized materials and do not enable in fact to evaluate fire and explosion risk probabilities and gravities of nanopowders. The main goal of this work is to study explosion and ignition risks related to nanopowders. In particular, the evaluation of the explosion sensitivity and severity of typical nanomaterials has been studied as well as the validity of the existing analytical and methodological tools designed to evaluate dust ignition and explosion hazards. This work also deals with the methodology applied to a plant and to a laboratory in order to define the best safety barriers which were positioned to ensure the best occupational safety level to all workers and evaluate in a good way the ignition and explosion risks related to the use and production of fluffy nanomaterials. This work will certainly help risk engineers concerned about the handling and the production of combustible nanopowders.Cette étude se propose de répondre aux nombreuses interrogations quant à la réactivité particulière développée par les particules nanométriques. En ce qui concerne la sensibilité à l'inflammation des nanoparticules, deux comportements totalement différents ont été observés en fonction de la nature des poudres. Ainsi, les particules de noir de carbone non poreuses voient leur capacité à être oxydées, diminuer avec l'augmentation de la surface spécifique alors que les particules d'aluminium tendent à s'oxyder plus aisément avec une diminution de la taille des particules. Par ailleurs, nous nous attendions à un accroissement de la sensibilité à l'inflammation par étincelle du nuage de poussières avec la diminution de la taille des particules. Dans le cas de nanopoudres peu réactives comme les nanotubes de carbone ou le noir de carbone, de tels phénomènes ne sont pas perceptibles ; mais au contraire, de telles tendances furent identifiées pour des nanopoudres très réactives comme l'aluminium nanométrique pour lequel des énergies minimales d'inflammation inférieures au millijoule ont été obtenues. Cette évolution rend le risque d'inflammation des nanopoudres supérieur à celui de poudres micrométriques et nécessite des procédures de manipulation adaptées. Le risque d'autoinflammation de tels composés a par ailleurs été déterminé. En ce qui concerne la sévérité des explosions, les noirs de carbone et nanotubes de carbone testés produisent des explosions aussi violentes que celles des noirs de carbone micrométriques, et ce malgré une importante agrégation/agglomération. Dans le cas de l'aluminium nanométrique, on peut donc considérer que la propagation d'une flamme laminaire est essentiellement sous contrôle radiatif, contrairement aux particules micrométriques. Le risque de détonation d'un nuage de nanoparticules d'aluminium semble donc particulièrement élevé. Toutefois, lors des essais réalisés, aucune augmentation dramatique de la sévérité d'explosion n'a été observée. Au contraire, une diminution de la vitesse de la montée en pression a été observée. Par conséquent, il se pourrait que les appareils traditionnels utilisés (notamment la sphère d'explosion de 20 L) ne permettent pas aux phénomènes radiatifs de prendre part significativement à la propagation de la flamme ou tout du moins limitent la radiation. Ce phénomène pourrait participer à la sous-estimation des paramètres de sévérité d'explosion, du moins dans le cas d'un nuage de nanoparticules d'aluminium. Il remet donc en question la validité de la loi cubique utilisée pour le dimensionnement de système de protection (évents, disques de rupture) et impliquerait que les mesures réalisées sur des appareils traditionnels ne seraient alors pas directement extrapolables à d'autres volumes. Enfin, sur la base des travaux cités précédemment, une réflexion a été menée afin de décrire, d'évaluer et de modéliser les dangers et les risques liés à l'utilisation de nanopoudres sur un poste de travail. Cette démarche a pu être menée à bien grâce à l'utilisation du modèle MADS (Méthodologie d'Analyse des Dysfonctionnements dans les Systèmes) et de la méthode MOSAR (Méthode Organisée Systémique d'Analyse des Risques). Elle a permis de modéliser de façon systémique les flux de danger auxquels peuvent être exposés les salariés. Cette étude a conduit à la mise en place d'actions visant à réduire les risques et les impacts des flux de dangers potentiels relatifs aux nanoparticules via la définition de barrières de prévention, de protection et de mitigation adéquates