REQUITE: A prospective multicentre cohort study of patients undergoing radiotherapy for breast, lung or prostate cancer

Purpose: REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. Methods: An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially curable radiotherapy. Radiotherapy was prescribed according to local regimens, but centres used standardised data collection forms. Pre-treatment blood samples were collected. Patients were followed for a minimum of 12 (lung) or 24 (breast/prostate) months and summary descriptive statistics were generated. Results: The study recruited 2069 breast (99% of target), 1808 prostate (86%) and 561 lung (51%) cancer patients. The centralised, accessible database includes: physician-(47,025 forms) and patient-(54,901) reported outcomes; 11,563 breast photos; 17,107 DICOMs and 12,684 DVHs. Imputed genotype data are available for 4223 patients with European ancestry (1948 breast, 1728 prostate, 547 lung). Radiation-induced lymphocyte apoptosis (RILA) assay data are available for 1319 patients. DNA (n = 4409) and PAXgene tubes (n = 3039) are stored in the centralised biobank. Example prevalences of 2-year (1-year for lung) grade >= 2 CTCAE toxicities are 13% atrophy (breast), 3% rectal bleeding (prostate) and 27% dyspnoea (lung). Conclusion: The comprehensive centralised database and linked biobank is a valuable resource for the radiotherapy community for validating predictive models and biomarkers. Patient summary: Up to half of cancer patients undergo radiation therapy and irradiation of surrounding healthy tissue is unavoidable. Damage to healthy tissue can affect short-and long-term quality-of-life. Not all patients are equally sensitive to radiation "damage" but it is not possible at the moment to identify those who are. REQUITE was established with the aim of trying to understand more about how we could predict radiation sensitivity. The purpose of this paper is to provide an overview and summary of the data and material available. In the REQUITE study 4400 breast, prostate and lung cancer patients filled out questionnaires and donated blood. A large amount of data was collected in the same way. With all these data and samples a database and biobank were created that showed it is possible to collect this kind of information in a standardised way across countries. In the future, our database and linked biobank will be a resource for research and validation of clinical predictors and models of radiation sensitivity. REQUITE will also enable a better understanding of how many people suffer with radiotherapy toxicity

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Développement de prodrogues glycérolipidiques en vue de l'amélioration de la biodisponibilité orale de la didanosine

La didanosine est un analogue nucléosidique largement utilisé dans le traitement de l infection par le VIH. Elle a une faible biodisponibilité per os en raison de son faible passage de la membrane intestinale et un fort effet de premier passage hépatique. Deux prodrogues glycérolipidiques de la didanosine ont été conçues afin d améliorer la diffusion à travers la membrane des entérocytes, et d éviter l effet de premier passage hépatique de la didanosine en favorisant son passage lymphatique. Au final, la biodisponibilité orale doit être fortement améliorée. Après la synthèse des deux prodrogues, leur caractérisation physico-chimique a révélé une organisation similaire à celle des triglycérides, un caractère amphiphile et une faible solubilité dans l eau et les huiles. Ces prodrogues ont pu être incorporées au sein de liposomes. Le biomimétisme des prodrogues a été établi après incubation dans de la pancréatine de porc et analyse des métabolites par spectrométrie de masse couplée à l HPLCDidanosine is a nucleoside analogue largely used for the HIV treatment. Because of its poor membrane absorption and high hepatic first pass metabolism, it suffers from a poor bioavailability. Two didanosine glycerolipidic prodrugs were synthesized to increase diffusion through enterocytes and avoid hepatic first pass metabolism, in order to enhance didanosine bioavailability. After the synthesis of these 2 prodrugs, their physico-chemical characterization revealed a typical triglycerides organization, an amphiphilic character and a low solubility in water, or oil. They could be efficiently incorporated in liposomes. Their biomimetism was established after incubation with porc pancreatin and metabolism evaluation with HPLC tandem mass spectrometry.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Study of cleavage fracture in ferritic stainless steels Part II: Cleavage micro-mechanisms and critical stresses

International audienceCleavage fracture and the mechanisms involved in different ferritic steel model microstructures are investigated according to grain sizes, precipitates and solute atoms in the matrix. For each case, one of these parameters is varied. Estimation of the critical stress for cleavage was investigated and discussed: it is shown to be determined from a simple Griffith inspired analysis or by employing the Smith's description. The description to adopt depends on careful analysis of the involved mechanisms. This aims at better understanding the governing parameters of the Ductile to Brittle Transition Temperature (DBTT) and to suggest routes for alloys processing to reduce the DBTT in ferritic steels

Study of cleavage fracture in ferritic stainless steels. Part I: Development and characterization of model microstructures

International audienceA major drawback in ferritic steels production and usage is their mechanical brittleness at temperatures close to ambient temperature. Precipitation and grain size appear as two major parameters in such cleavage brittle behavior. This is why six model microstructures have been elaborated from the same base of chemical composition, but with different elements additions and thermal treatments. The base composition is 18% chromium and 2% molybdenum to ensure an entirely ferritic matrix at any temperature even with 0.015% of both carbon and nitrogen. The addition of titanium or niobium changed the nature, size and location of the carbides and nitrides, while carefully chosen heat treatments varied the size of the grains. Microstructure characterizations down to very fine scales (TEM, SANS) combined with thermodynamics and diffusion modeling allowed analyzing precipitates formation as well as remaining interstitial elements (carbon and nitrogen) in solution in the ferritic matrix. This multi-scale analysis of the microstructures is important to understand the mechanical behavior of the alloys, which will be presented in a companion paper

La France, puissance industrielle : une nouvelle politique industrielle par les territoires : réseaux d'entreprises, vallées technologiques, pôles de compétitivité

L'élargissement de l'Europe, l'internationalisation de l'économie et la décentralisation ont conduit le Gouvernement à repenser la politique d'aménagement du territoire. Les nouvelles orientations, arrêtées lors du Comité interministériel d'aménagement et de développement du territoire (Ciadt) du 13 décembre 2002, visent ainsi à favoriser l'attractivité de la France et la compétitivité de nos territoires afin de contribuer à la création de nouvelles richesses. Bien que la France soit la cinquième puissance industrielle mondiale, son potentiel est encore aujourd'hui concentré sur un trop petit nombre de pôles de rayonnement international. La politique d'aménagement du territoire doit y remédier en impulsant et en accompagnant une stratégie territoriale qui favorise la création et le renforcement de pôles de compétitivité regroupant les entreprises, les réseaux technologiques conjuguant la recherche publique et privée, ainsi que les établissements d'enseignement et de recherche. L'objectif de ce rapport n'est évidemment pas de conclure. Il vise au contraire à Lancer Le débat