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IntroductionAcute exacerbation of chronic obstructive pulmonary disease (COPD) is a frequent cause of intensive care unit (ICU) admission. However, data are scarce and conflicting regarding the impact of systemic corticosteroid treatment in critically ill patients with acute exacerbation of COPD. The aim of the study was to assess the impact of systemic corticosteroids on the occurrence of death or need for continuous invasive mechanical ventilation at day 28 after ICU admission.MethodsIn the OutcomeReaTM prospective French national ICU database, we assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of prednisone or equivalent during the first 24 hours ICU stay) on a composite outcome (death or invasive mechanical ventilation) using an inverse probability treatment weighting.ResultsBetween January 1, 1997 and December 31, 2018, 391 out of 1,247 patients with acute exacerbations of COPDs received corticosteroids at ICU admission. Corticosteroids improved the main composite endpoint (OR = 0.70 [0.49; 0.99], p = 0.044. However, for the subgroup of most severe COPD patients, this did not occur (OR = 1.12 [0.53; 2.36], p = 0. 770). There was no significant impact of corticosteroids on rates of non-invasive ventilation failure, length of ICU or hospital stay, mortality or on the duration of mechanical ventilation. Patients on corticosteroids had the same prevalence of nosocomial infections as those without corticosteroids, but more glycaemic disorders.ConclusionUsing systemic corticosteroids for acute exacerbation of COPD at ICU admission had a positive effect on a composite outcome defined by death or need for invasive mechanical ventilation at day 28.

Introduction Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a frequent cause of intensive care unit (ICU) admission. However, data are scarce and conflicting regarding the impact of systemic corticosteroid treatment in critically ill patients with acute exacerbation of COPD. The aim of the study was to assess the impact of systemic corticosteroids on the occurrence of death or need for continuous invasive mechanical ventilation at day 28 after ICU admission. Methods In the OutcomeReaTM prospective French national ICU database, we assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of prednisone or equivalent during the first 24 hours ICU stay) on a composite outcome (death or invasive mechanical ventilation) using an inverse probability treatment weighting. Results Between January 1, 1997 and December 31, 2018, 391 out of 1,247 patients with acute exacerbations of COPDs received corticosteroids at ICU admission. Corticosteroids improved the main composite endpoint (OR = 0.70 [0.49; 0.99], p = 0.044. However, for the subgroup of most severe COPD patients, this did not occur (OR = 1.12 [0.53; 2.36], p = 0. 770). There was no significant impact of corticosteroids on rates of non-invasive ventilation failure, length of ICU or hospital stay, mortality or on the duration of mechanical ventilation. Patients on corticosteroids had the same prevalence of nosocomial infections as those without corticosteroids, but more glycaemic disorders. Conclusion Using systemic corticosteroids for acute exacerbation of COPD at ICU admission had a positive effect on a composite outcome defined by death or need for invasive mechanical ventilation at day 28.

Purpose To compare the characteristics, management, and prognosis of patients admitted to intensive care units (ICU) for coronavirus disease (COVID)-19 during the first two waves of the outbreak and to evaluate the relationship between ICU strain (ICU demand due to COVID-19 admissions) and mortality. Methods In a multicentre retrospective study, 1166 COVID-19 patients admitted to five ICUs in France between 20 February and 31 December 2020 were included. Data were collected at each ICU from medical records. A Cox proportional-hazards model identified factors associated with 28-day mortality. Results 640 patients (55%) were admitted during the first wave (February to June 2020) and 526 (45%) during the second wave (July to December 2020). ICU strain was lower during the second wave (-0.81 [-1.04 –-0.31] vs. 1.18 [-0.34–1.29] SD when compared to mean COVID-19 admission in each center during study period, PConclusion The characteristics and the management of patients varied between the first and the second wave of the pandemic. Rather than the wave, ICU strain was independently associated with 28-day mortality, but not with hospital mortality.

PurposeTo compare the characteristics, management, and prognosis of patients admitted to intensive care units (ICU) for coronavirus disease (COVID)-19 during the first two waves of the outbreak and to evaluate the relationship between ICU strain (ICU demand due to COVID-19 admissions) and mortality.MethodsIn a multicentre retrospective study, 1166 COVID-19 patients admitted to five ICUs in France between 20 February and 31 December 2020 were included. Data were collected at each ICU from medical records. A Cox proportional-hazards model identified factors associated with 28-day mortality.Results640 patients (55%) were admitted during the first wave (February to June 2020) and 526 (45%) during the second wave (July to December 2020). ICU strain was lower during the second wave (-0.81 [-1.04 --0.31] vs. 1.18 [-0.34-1.29] SD when compared to mean COVID-19 admission in each center during study period, PConclusionThe characteristics and the management of patients varied between the first and the second wave of the pandemic. Rather than the wave, ICU strain was independently associated with 28-day mortality, but not with hospital mortality.

PurposeThe purpose of this study was to assess whether the retail food environment, measured by multiple indicators around the home and in activity space, was associated with the nutritional quality of food purchases.MethodsThis cross-sectional study included 462 households from a quota sampling survey conducted in the south of France (Montpellier Metropolitan Area). The revised Healthy Purchase Index was implemented in order to assess the nutritional quality of food purchases. Food environment indicators (presence, number, relative density and proximity of food outlets) were calculated around the home and in activity space using a geographical information system. Six different types of food outlets were studied: supermarkets, markets, greengrocers, bakeries, other specialized food stores (butcher's, fishmonger's and dairy stores) and small grocery stores. Associations between food environment and the nutritional quality of food purchases were assessed using multilevel models, and geographically weighted regressions to account for spatial non-stationarity. Models were adjusted for households' socioeconomic and demographic characteristics.ResultsThe nutritional quality of food purchases was positively associated with the number of greengrocers around the home (1 vs. 0: β = 0.25, 95%CI = [0.01, 0.49]; >1 vs. 0: β = 0.25, 95%CI = [0.00, 0.50]), but negatively associated with the number of markets around the home (1 vs. 0: β = -0.20, 95%CI = [-0.40, 0.00]; >1 vs. 0: β = -0.37, 95%CI = [-0.69, -0.06]). These associations varied across space in the area studied. For lower income households, the number of greengrocers in activity space was positively associated with the nutritional quality of food purchases (1 vs. 0: β = 0.70, 95%CI = [0.12, 1.3]; >1 vs. 0: β = 0.67, 95%CI = [0.22, 1.1]).ConclusionsGreengrocers might be an effective type of food store for promoting healthier dietary behaviors. Further studies, particularly interventional studies, are needed to confirm these results in order to guide public health policies in actions designed to improve the food environment.

Background Heterogeneity in sepsis expression is multidimensional, including highly disparate data such as the underlying disorders, infection source, causative micro-organismsand organ failures. The aim of the study is to identify clusters of patients based on clinical and biological characteristic available at patients’ admission. Methods All patients included in a national prospective multicenter ICU cohort OUTCOMEREA and admitted for sepsis or septic shock (Sepsis 3.0 definition) were retrospectively analyzed. A hierarchical clustering was performed in a training set of patients to build clusters based on a comprehensive set of clinical and biological characteristics available at ICU admission. Clusters were described, and the 28-day, 90-day, and one-year mortality were compared with log-rank rates. Risks of mortality were also compared after adjustment on SOFA score and year of ICU admission. Results Of the 6,046 patients with sepsis in the cohort, 4,050 (67%) were randomly allocated to the training set. Six distinct clusters were identified: young patients without any comorbidities, admitted in ICU for community-acquired pneumonia (n = 1,603 (40%)); young patients without any comorbidities, admitted in ICU for meningitis or encephalitis (n = 149 (4%)); elderly patients with COPD, admitted in ICU for bronchial infection with few organ failures (n = 243 (6%)); elderly patients, with several comorbidities and organ failures (n = 1,094 (27%)); patients admitted after surgery, with a nosocomial infection (n = 623 (15%)); young patients with immunosuppressive conditions (e.g., AIDS, chronic steroid therapy or hematological malignancy) (n = 338 (8%)). Clusters differed significantly in early or late mortality (p < .001), even after adjustment on severity of organ dysfunctions (SOFA) and year of ICU admission. Conclusions Clinical and biological features commonly available at ICU admission of patients with sepsis or septic shock enabled to set up six clusters of patients, with very distinct outcomes. Considering these clusters may improve the care management and the homogeneity of patients in future studies.

BackgroundHeterogeneity in sepsis expression is multidimensional, including highly disparate data such as the underlying disorders, infection source, causative micro-organismsand organ failures. The aim of the study is to identify clusters of patients based on clinical and biological characteristic available at patients' admission.MethodsAll patients included in a national prospective multicenter ICU cohort OUTCOMEREA and admitted for sepsis or septic shock (Sepsis 3.0 definition) were retrospectively analyzed. A hierarchical clustering was performed in a training set of patients to build clusters based on a comprehensive set of clinical and biological characteristics available at ICU admission. Clusters were described, and the 28-day, 90-day, and one-year mortality were compared with log-rank rates. Risks of mortality were also compared after adjustment on SOFA score and year of ICU admission.ResultsOf the 6,046 patients with sepsis in the cohort, 4,050 (67%) were randomly allocated to the training set. Six distinct clusters were identified: young patients without any comorbidities, admitted in ICU for community-acquired pneumonia (n = 1,603 (40%)); young patients without any comorbidities, admitted in ICU for meningitis or encephalitis (n = 149 (4%)); elderly patients with COPD, admitted in ICU for bronchial infection with few organ failures (n = 243 (6%)); elderly patients, with several comorbidities and organ failures (n = 1,094 (27%)); patients admitted after surgery, with a nosocomial infection (n = 623 (15%)); young patients with immunosuppressive conditions (e.g., AIDS, chronic steroid therapy or hematological malignancy) (n = 338 (8%)). Clusters differed significantly in early or late mortality (p < .001), even after adjustment on severity of organ dysfunctions (SOFA) and year of ICU admission.ConclusionsClinical and biological features commonly available at ICU admission of patients with sepsis or septic shock enabled to set up six clusters of patients, with very distinct outcomes. Considering these clusters may improve the care management and the homogeneity of patients in future studies.

BackgroundCoagulation disorders are common in patients with hemophagocytic lymphohistiocytosis (HLH), associated with an increased risk of bleeding and death. We aim to investigate coagulation disorders and their outcome implications in critically ill patients with HLH.MethodsWe prospectively evaluated 47 critically ill patients with HLH (median age of 54 years [42-67]) between April 2015 and December 2018. Coagulation assessments were performed at day 1. Abnormal standard coagulation was defined as prothrombin time (PT) ResultsCoagulation disorders and severe bleeding events were frequent, occurring in 30 (64%) and 11 (23%) patients respectively. At day 1, median fibrinogen level was 2∙65g/L [1.61-5.66]. Fibrinolytic activity was high as suggested by increased median levels of D-dimers, fibrin monomers, PAI-1 (plasminogen activator inhibitor) and tPA (tissue plasminogen activator). Forty-one (91%) patients had a decreased ADAMTS13 activity (A Disintegrin-like And Metalloproteinase with ThromboSpondin type 1 repeats, member 13). By multivariable analysis, the occurrence of a severe bleeding (OR 3.215 [1.194-8.653], p = 0∙021) and SOFA score (Sepsis-Related Organ Failure Assessment) at day 1 (OR 1.305 per point [1.146-1.485], pConclusionsHyperfibrinolysis may be the primary mechanism responsible for hypofibrinogenemia and may also participate in ADAMTS13 degradation. Targeting the plasmin system appears as a promising approach in severe HLH-related coagulation disorders.

IntroductionThrombotic thrombocytopenic purpura (TTP) is a diagnostic and therapeutic emergency. Therapeutic plasma exchange (TPE) combined with immunosuppression has been the cornerstone of the initial management. To produce optimal benefits, emerging treatments must be used against a background of best standard of care. Clarifying current uncertainties is therefore crucial.MethodsThe objective of this study was to analyze a large high-quality database (Marketscan) of TTP patients managed between 2005 and 2014, in the pre-caplacizumab era, in order to assess the impact of time to first TPE and use of first-line rituximab on mortality, and whether mortality declines over time.ResultsAmong the 1096 included patients (median age 46 [IQR 35-55], 70% female), 28.8% received TPE before day 2 in the ICU. Hospital mortality was 7.6% (83 deaths). Mortality was independently associated with older age (hazard ratio [HR], 1.024/year; 95% confidence interval [95%CI], [1.009-1.040]), diagnosis of sepsis (HR, 2.360; 95%CI [1.552-3.588]), and the need for mechanical ventilation (HR, 4.103; 95%CI, [2.749-6.126]). Factors independently associated with lower mortality were TPE at ICU admission (HR, 0.284; 95%CI, [0.112-0.717]), TPE within one day after ICU admission (HR, 0.449; 95%CI, [0.275-0.907]), and early rituximab therapy (HR, 0.229; 95% CI, [0.111-0.471]). Delayed TPE was associated with significantly higher costs.ConclusionsImmediate TPE and early rituximab are associated with improved survival in TTP patients. Improved treatments have led to a decline in mortality over time, and alternate outcome variables such as the use of hospital resources or longer term outcomes therefore need to be considered.

To prevent the transmission of damaged genomic material between generations, cells require a system for accommodating DNA repair within their cell cycles. We have previously shown that Escherichia coli cells subject to a single, repairable site-specific DNA double-strand break (DSB) per DNA replication cycle reach a new average cell length, with a negligible effect on population growth rate. We show here that this new cell size distribution is caused by a DSB repair-dependent delay in completion of cell division. This delay occurs despite unperturbed cell size regulated initiation of both chromosomal DNA replication and cell division. Furthermore, despite DSB repair altering the profile of DNA replication across the genome, the time required to complete chromosomal duplication is invariant. The delay in completion of cell division is accompanied by a DSB repair-dependent delay in individualization of sister nucleoids. We suggest that DSB repair events create inter-sister connections that persist until those chromosomes are separated by a closing septum.

OBJECTIVE:To identify food choices allowing the fulfillment of nutritionally adequate diets resembling actual food patterns at the lowest cost achievable for the Brazilian population, stratified by income level. METHODS:Food consumption and prices were obtained from the Household Budget Survey (n = 55,970 households) and National Dietary Survey (n = 32,749 individuals). The sample was stratified into capitals of the states and further by income levels according to the official minimum wage (totaling 108 geographic-economic strata, or GES). Linear programming models were performed for each GES in order to find the lowest cost of diets that meet a set of nutritional constraints. In order to find realistic diets, constraints referring to preferences were introduced in the models allowing optimized food quantities to depart progressively from the current intake for each food and food group. The impact of meeting each target nutrient was assessed by performing models removing each nutrient at the time. RESULTS:The observed and optimized diet costs were US$2.16 and US$2.58 per capita/day. The highest cost increment and the greatest food shifts were observed in the lowest income level. The nutrient adequacy was reached by mainly increasing fruits and vegetables, beans, fish and seafood, dairy, nuts, and eggs; and reducing red and processed meat, chicken, margarine and butter, cookies, cakes, sugar-sweetened beverages, and sauces. As the departure from the current intakes increase, the optimized healthy diet cost reduced. In the lowest income, the lowest cost increment was about US$ 0.10; in the higher income levels, it tended to be cheaper than the observed cost. Calcium was the most expensive nutrient to meet adequacy. CONCLUSION:Nutritionally adequate diets are possible but costlier than the observed.

The size of oocytes was previously reported to be smaller in obese women with polycystic ovary syndrome (PCOS). In the present prospective cohort study, we sought to determine whether oocyte size and morphology are associated with patient characteristics in non-PCOS women. Oocyte and oolemmal diameter were measured, enlarged perivitelline space (PVS) and ooplasmic granulation were assessed in 308 MII oocytes from 77 IVF/ICSI couples. Statistical analysis was undertaken using SAS version 9.4 (SAS institute Inc., USA). Continuous values are presented as mean ± SD and compared using a two-sample t-test or Mann-Whitney U test as appropriate. Categorical parameters are presented as proportions and compared using a Fisher exact test. Logistic and linear regression models were used to control for the effect of age for categorical and continuous variables respectively. P-value < 0.05 was considered statistically significant. Patients presented with a mean age of 40.3±5.0 years, had a BMI of 25.1±6.1 kg/m2, median AMH levels of 0.6 ng/ml and produced a median of 4 oocytes. Mean total oocyte diameter was 163.2±7.4 μm (range 145.8-182.1 μm), while oolemmal diameter was 109.4±4.1 μm (range 98.5-122.3 μm). After adjusting for age and ovarian reserve increasing BMI was associated with decreased total oocyte diameter (p

Low FMR1 variants (CGGn

Reducing the consumption of meat and other animal-based products is widely advocated to improve the sustainability of diets in high-income countries. However, such reduction may impair nutritional adequacy, since the bioavailability of key nutrients is higher when they come from animal- vs plant-based foods. Meat reduction may also affect the balance between foods co-produced within the same animal production system.The objective was to assess the impact of introducing nutrient bioavailability and co-production links considerations on the dietary changes needed - especially regarding meat ‒ to improve diet sustainability.Diet optimization with linear and non-linear programming was used to design, for each gender, three modeled diets departing the least from the mean observed French diet (OBS) while reducing by at least 30% the diet-related environmental impacts (greenhouse gas emissions, eutrophication, acidification): i) in the nutrition-environment (NE) model, the fulfillment of recommended dietary allowances for all nutrients was imposed; ii) in the NE-bioavailability (NEB) model, nutritional adequacy was further ensured by accounting for iron, zinc, protein and provitamin A bioavailability; iii) in the NEB-co-production (NEB-CP) model, two links between co-produced animal foods (milk-beef and blood sausage-pork) were additionally included into the models by proportionally co-constraining their respective quantities. The price and environmental impacts of individual foods were assumed to be constant.'Fruit and vegetables' and 'Starches' quantities increased in all modeled diets compared to OBS. In parallel, total meat and ruminant meat quantities decreased. Starting from 110g/d women's OBS diet (168g/d for men), total meat quantity decreased by 78%, 67% and 32% for women (68%, 66% and 62% for men) in NE, NEB and NEB-CP diets, respectively. Starting from 36g/d women's OBS diet (54g/d for men), ruminant meat quantity dropped severely by 84% and 87% in NE and NEB diets for women (80% and 78% for men), whereas it only decreased by 27% in NEB-CP diets (38% for men). The share of energy and proteins of animal origin was similar for the 3 modeled diets (approximately 1/5 of total energy, and 1/2 of protein) and lower than in OBS diet (approximately 1/3 of total energy, and 2/3 of protein).Decreasing meat content was strictly needed to achieve more sustainable diets for French adults, but the reduction was less severe when nutrient bioavailability and co-production links were taken into account.

The impact of prevention strategies and risk factors for early-onset (EOP) versus late-onset (LOP) ventilator-associated pneumonia (VAP) are still debated.To evaluate, in a multicenter cohort, the risk factors for EOP and LOP, as the evolution of prevention strategies.7,784 patients with mechanical ventilation (MV) for at least 48 hours were selected into the multicenter prospective OUTCOMEREA database (1997-2016). VAP occurring between the 3rd and 6th day of MV defined EOP, while those occurring after defined LOPs. We used a Fine and Gray subdistribution model to take the successful extubation into account as a competing event.Overall, 1,234 included patients developed VAP (EOP: 445 (36%); LOP: 789 (64%)). Male gender was a risk factor for both EOP and LOP. Factors specifically associated with EOP were admission for respiratory distress, previous colonization with multidrug-resistant Pseudomonas aeruginosa, chest tube and enteral feeding within the first 2 days of MV. Antimicrobials administrated within the first 2 days of MV were all protective of EOP. ICU admission for COPD exacerbation or pneumonia were early risk factors for LOP, while imidazole and vancomycin use within the first 2 days of MV were protective factors. Late risk factors (between the 3rd and the 6th day of MV) were the intra-hospital transport, PAO2-FIO2

The first year of university is a particularly stressful period and can impact academic performance and students' health. The aim of this study was to evaluate the health and lifestyle of undergraduates and assess risk factors associated with psychiatric symptoms.Between September 2012 and June 2013, we included all undergraduate students who underwent compulsory a medical visit at the university medical service in Nice (France) during which they were screened for potential diseases during a diagnostic interview. Data were collected prospectively in the CALCIUM database (Consultations Assistés par Logiciel pour les Centres Inter-Universitaire de Médecine) and included information about the students' lifestyle (living conditions, dietary behavior, physical activity, use of recreational drugs). The prevalence of psychiatric symptoms related to depression, anxiety and panic attacks was assessed and risk factors for these symptoms were analyzed using logistic regression.A total of 4,184 undergraduates were included. Prevalence for depression, anxiety and panic attacks were 12.6%, 7.6% and 1.0%, respectively. During the 30 days preceding the evaluation, 0.6% of the students regularly drank alcohol, 6.3% were frequent-to-heavy tobacco smokers, and 10.0% smoked marijuana. Dealing with financial difficulties and having learning disabilities were associated with psychiatric symptoms. Students who were dissatisfied with their living conditions and those with poor dietary behavior were at risk of depression. Being a woman and living alone were associated with anxiety. Students who screened positively for any psychiatric disorder assessed were at a higher risk of having another psychiatric disorder concomitantly.The prevalence of psychiatric disorders in undergraduate students is low but the rate of students at risk of developing chronic disease is far from being negligible. Understanding predictors for these symptoms may improve students' health by implementing targeted prevention campaigns. Further research in other French universities is necessary to confirm our results.

OBJECTIVE:To explore the dietary changes needed to achieve nutritional adequacy across income levels at constant energy and diet cost. MATERIALS AND METHODS:Individual diet modelling was used to design iso-caloric, nutritionally adequate optimised diets for each observed diet in a sample of adult normo-reporters aged ≥20 years (n = 1,719) from the Individual and National Dietary Survey (INCA2), 2006-2007. Diet cost was estimated from mean national food prices (2006-2007). A first set of free-cost models explored the impact of optimisation on the variation of diet cost. A second set of iso-cost models explored the dietary changes induced by the optimisation with cost set equal to the observed one. Analyses of dietary changes were conducted by income quintiles, adjusting for energy intake, sociodemographic and socioeconomic variables, and smoking status. RESULTS:The cost of observed diets increased with increasing income quintiles. In free-cost models, the optimisation increased diet cost on average (+0.22 ± 1.03 euros/d) and within each income quintile, with no significant difference between quintiles, but with systematic increases for observed costs lower than 3.85 euros/d. In iso-cost models, it was possible to design nutritionally adequate diets whatever the initial observed cost. On average, the optimisation at iso-cost increased fruits and vegetables (+171 g/day), starchy foods (+121 g/d), water and beverages (+91 g/d), and dairy products (+20 g/d), and decreased the other food groups (e.g. mixed dishes and salted snacks), leading to increased total diet weight (+300 g/d). Those changes were mostly similar across income quintiles, but lower-income individuals needed to introduce significantly more fruit and vegetables than higher-income ones. CONCLUSIONS:In France, the dietary changes needed to reach nutritional adequacy without increasing cost are similar regardless of income, but may be more difficult to implement when the budget for food is lower than 3.85 euros/d.

Food-Based Dietary Guidelines (FBDGs) are developed to promote healthier eating patterns, but increasing food prices may make healthy eating less affordable. The aim of this study was to design a range of cost-minimized nutritionally adequate health-promoting food baskets (FBs) that help prevent both micronutrient inadequacy and diet-related non-communicable diseases at lowest cost.Average prices for 312 foods were collected within the Greater Copenhagen area. The cost and nutrient content of five different cost-minimized FBs for a family of four were calculated per day using linear programming. The FBs were defined using five different constraints: cultural acceptability (CA), or dietary guidelines (DG), or nutrient recommendations (N), or cultural acceptability and nutrient recommendations (CAN), or dietary guidelines and nutrient recommendations (DGN). The variety and number of foods in each of the resulting five baskets was increased through limiting the relative share of individual foods.The one-day version of N contained only 12 foods at the minimum cost of DKK 27 (€ 3.6). The CA, DG, and DGN were about twice of this and the CAN cost ~DKK 81 (€ 10.8). The baskets with the greater variety of foods contained from 70 (CAN) to 134 (DGN) foods and cost between DKK 60 (€ 8.1, N) and DKK 125 (€ 16.8, DGN). Ensuring that the food baskets cover both dietary guidelines and nutrient recommendations doubled the cost while cultural acceptability (CAN) tripled it.Use of linear programming facilitates the generation of low-cost food baskets that are nutritionally adequate, health promoting, and culturally acceptable.

BACKGROUND:Assisted Reproductive Technology (ART) reports generated by the Centers for Disease Control and Prevention (CDC) exclude embryo banking cycles from outcome calculations. METHODS:We examined data reported to the CDC in 2013 for the impact of embryo banking exclusion on national ART outcomes by recalculating autologous oocyte ART live birth rates. Inflation of reported fresh ART cycle live birth rates was assessed for all age groups of infertile women as the difference between fresh cycle live births with reference to number of initiated fresh cycles (excluding embryo banking cycles), as typically reported by the CDC, and fresh cycle live births with reference to total initiated fresh ART cycles (including embryo banking cycles). RESULTS:During 2013, out of 121,351 fresh non-donor ART cycles 27,564 (22.7%) involved embryo banking. The proportion of banking cycles increased with female age from 15.5% in women 44 years. Concomitantly, the proportion of thawed cycles decreased with advancing female age (P 44. The inflation of live birth rates in thawed cycles could not be calculated from the publically available CDC data but appears to be even greater. CONCLUSIONS:Utilization of embryo banking increased during 2013 with advancing female age, suggesting a potential age selection bias. Exclusion of embryo banking cycles from national ART outcome reports significantly inflated national ART success rates, especially among older women. PRÉCIS:Exclusion of embryo banking cycles from US National Assisted Reproductive Technology outcome reports significantly inflates reported success rates especially in older women.

There is a lack of standardized country-specific environmental data to combine with nutritional and dietary data for assessing the environmental impact of individual diets in epidemiology surveys, which are consequently reliant on environmental food datasets based on values retrieved from a heterogeneous literature. The aim of this study was to compare and assess the relative strengths and limits of a database of food greenhouse gas emissions (GHGE) values estimated with a hybrid method combining input/output and LCA approaches, with a dataset of GHGE values retrieved from the literature. France is the geographical perimeter considered in this study, but the methodology could be applied to other countries. The GHGE of 402 foodstuffs, representative of French diet, were estimated using the hybrid method. In parallel, the GHGE of individual foods were collected from existing literature. Median per-food-category GHGE values from the hybrid method and the reviewed literature were found to correlate strongly (Spearman correlation was 0.83), showing similar rankings of food categories. Median values were significantly different for only 5 (out of 29) food categories, including the ruminant meats category for which the hybrid method gave lower estimates than those from existing literature. Analysis also revealed that literature values came from heterogeneous studies that were not always sourced and that were conducted under different LCA modeling hypotheses. In contrast, the hybrid method helps build reliably-sourced, representative national standards for product-based datasets. We anticipate this hybrid method to be a starting point for better environmental impact assessments of diets.

ObjectivesFeed efficiency and its digestive component, digestive efficiency, are key factors in the environmental impact and economic output of poultry production. The interaction between the host and intestinal microbiota has a crucial role in the determination of the ability of the bird to digest its food and to the birds' feed efficiency. We therefore investigated the phenotypic and genetic relationships between birds' efficiency and the composition of the cecal microbiota in a F2 cross between broiler lines divergently selected for their high or low digestive efficiency.MethodsAnalyses were performed on 144 birds with extreme feed efficiency values at 3 weeks, with feed conversion values of 1.41±0.05 and 2.02±0.04 in the efficient and non-efficient groups, respectively. The total numbers of Lactobacillus, L. salivarius, L. crispatus, C. coccoides, C. leptum and E. coli per gram of cecal content were measured.ResultsThe two groups mainly differed in larger counts of Lactobacillus, L. salivarius and E. coli in less efficient birds. The equilibrium between bacterial groups was also affected, efficient birds showing higher C. leptum, C. coccoides and L. salivarius to E. coli ratios. The heritability of the composition of microbiota was also estimated and L. crispatus, C. leptum, and C. coccoides to E. coli ratios were moderately but significantly heritable (0.16 to 0.24). The coefficient of fecal digestive use of dry matter was genetically and positively correlated with L. crispatus, C. leptum, C. coccoides (0.50 to 0.76) and negatively with E. coli (-0.66). Lipid digestibility was negatively correlated with E. coli (-0.64), and AMEn positively correlated with C. coccoides and with the C. coccoides to Lactobacillus ratio (0.48 to 0.64). We also detected 14 Quantitative Trait Loci (QTL) for microbiota on the host genome, mostly on C. leptum and Lactobacillus. The QTL for C. leptum on GGA6 was close to genome-wide significance. This region mainly includes genes involved in anti-inflammatory responses and in the motility of the gastrointestinal tract.

In online social media networks, individuals often have hundreds or even thousands of connections, which link these users not only to friends, associates, and colleagues, but also to news outlets, celebrities, and organizations. In these complex social networks, a 'community' as studied in the social network literature, can have very different meaning depending on the property of the network under study. Taking into account the multifaceted nature of these networks, we claim that community detection in online social networks should also be multifaceted in order to capture all of the different and valuable viewpoints of 'community.' In this paper we focus on three types of communities beyond follower-based structural communities: activity-based, topic-based, and interaction-based. We analyze a Twitter dataset using three different weightings of the structural network meant to highlight these three community types, and then infer the communities associated with these weightings. We show that interesting insights can be obtained about the complex community structure present in social networks by studying when and how these four community types give rise to similar as well as completely distinct community structure.

Experimental studies suggest that intra-abdominal infection (IAI) induces biological alterations that may affect the risk of lung infection.To investigate the potential effect of IAI at ICU admission on the subsequent occurrence of ventilator-associated pneumonia (VAP).We used data entered into the French prospective multicenter Outcomerea database in 1997-2011. Consecutive patients who had severe sepsis and/or septic shock at ICU admission and required mechanical ventilation for more than 3 days were included. Patients with acute pancreatitis were not included.Of 2623 database patients meeting the inclusion criteria, 290 (11.1%) had IAI and 2333 (88.9%) had other infections. The IAI group had fewer patients with VAP (56 [19.3%] vs. 806 [34.5%], P

Whether diabetes mellitus increases the risk of acute kidney injury (AKI) during sepsis is controversial.We used a case-control design to compare the frequency of AKI, use of renal replacement therapy (RRT), and renal recovery in patients who had severe sepsis or septic shock with or without diabetes. The data were from the Outcomerea prospective multicenter database, in which 12 French ICUs enrolled patients admitted between January 1997 and June 2009.First, we compared 451 patients with severe sepsis or septic shock and diabetes to 3,277 controls with severe sepsis or septic shock and without diabetes. Then, we compared 318 cases (with diabetes) to 746 matched controls (without diabetes). Diabetic patients did not have a higher frequency of AKI (hazard ratio [HR], 1.18; P = 0.05]) or RRT (HR, 1.09; P = 0.6). However, at discharge, diabetic patients with severe sepsis or septic shock who experienced acute kidney injury during the ICU stay and were discharged alive more often required RRT (9.5% vs. 4.8%; P = 0.02), had higher serum creatinine values (134 vs. 103 µmoL/L; P

DNA damage checkpoints exist to promote cell survival and the faithful inheritance of genetic information. It is thought that one function of such checkpoints is to ensure that cell division does not occur before DNA damage is repaired. However, in unicellular organisms, rapid cell multiplication confers a powerful selective advantage, leading to a dilemma. Is the activation of a DNA damage checkpoint compatible with rapid cell multiplication? By uncoupling the initiation of DNA replication from cell division, the Escherichia coli cell cycle offers a solution to this dilemma. Here, we show that a DNA double-strand break, which occurs once per replication cycle, induces the SOS response. This SOS induction is needed for cell survival due to a requirement for an elevated level of expression of the RecA protein. Cell division is delayed, leading to an increase in average cell length but with no detectable consequence on mutagenesis and little effect on growth rate and viability. The increase in cell length caused by chronic DNA double-strand break repair comprises three components: two types of increase in the unit cell size, one independent of SfiA and SlmA, the other dependent of the presence of SfiA and the absence of SlmA, and a filamentation component that is dependent on the presence of either SfiA or SlmA. These results imply that chronic checkpoint induction in E. coli is compatible with rapid cell multiplication. Therefore, under conditions of chronic low-level DNA damage, the SOS checkpoint operates seamlessly in a cell cycle where the initiation of DNA replication is uncoupled from cell division.

Species diversity in large herbivore communities is often explained by niche segregation allowed by differences in body mass and digestive morphophysiological features. Based on large number of gut samples in fall and winter, we analysed the temporal dynamics of diet composition, quality and interspecific overlap of 4 coexisting mountain herbivores. We tested whether the relative consumption of grass and browse differed among species of different rumen types (moose-type and intermediate-type), whether diet was of lower quality for the largest species, whether we could identify plant species which determined diet quality, and whether these plants, which could be "key-food-resources" were similar for all herbivores. Our analyses revealed that (1) body mass and rumen types were overall poor predictors of diet composition and quality, although the roe deer, a species with a moose-type rumen was confirmed as an "obligatory non grazer", while red deer, the largest species, had the most lignified diet; (2) diet overlap among herbivores was well predicted by rumen type (high among species of intermediate types only), when measured over broad plant groups, (3) the relationship between diet composition and quality differed among herbivore species, and the actual plant species used during winter which determined the diet quality, was herbivore species-specific. Even if diets overlapped to a great extent, the species-specific relationships between diet composition and quality suggest that herbivores may select different plant species within similar plant group types, or different plant parts and that this, along with other behavioural mechanisms of ecological niche segregation, may contribute to the coexistence of large herbivores of relatively similar body mass, as observed in mountain ecosystems.

BackgroundOptimal chemotherapy with minimal toxicity is the main determinant of complete remission in patients with newly diagnosed hematological malignancies. Acute organ dysfunctions may impair the patient's ability to receive optimal chemotherapy.Design and methodsTo compare 6-month complete remission rates in patients with and without acute kidney injury (AKI), we collected prospective data on 200 patients with newly diagnosed high-grade malignancies (non-Hodgkin lymphoma, 53.5%; acute myeloid leukemia, 29%; acute lymphoblastic leukemia, 11.5%; and Hodgkin disease, 6%).ResultsAccording to RIFLE criteria, 137 (68.5%) patients had AKI. Five causes of AKI accounted for 91.4% of cases: hypoperfusion, tumor lysis syndrome, tubular necrosis, nephrotoxic agents, and hemophagocytic lymphohistiocytosis. Half of the AKI patients received renal replacement therapy and 14.6% received suboptimal chemotherapy. AKI was associated with a lower 6-month complete remission rate (39.4% vs. 68.3%, PConclusionAKI is common in patients with newly diagnosed high-grade malignancies and is associated with lower complete remission rates and higher mortality.

BACKGROUND: This study aimed to determine the prevalence of genetic and environmental vascular risk factors in non diabetic patients with premature peripheral arterial disease, either peripheral arterial occlusive disease or thromboangiitis obliterans, the two main entities of peripheral arterial disease, and to established whether some of them are specifically associated with one or another of the premature peripheral arterial disease subgroups. METHODS AND RESULTS: This study included 113 non diabetic patients with premature peripheral arterial disease (diagnosis

Immune cell infiltration of expanding adipose tissue during obesity and its role in insulin resistance has been described and involves chemokines. However, studies so far have focused on a single chemokine or its receptor (especially CCL2 and CCL5) whereas redundant functions of chemokines have been described. The objective of this work was to explore the expression of chemokines in inflamed adipose tissue in obesity. Human and mouse adipocytes were analyzed for expression of chemokines in response to inflammatory signal (TNF-α) using microarrays and gene set enrichment analysis. Gene expression was verified by qRT-PCR. Chemokine protein was determined in culture medium with ELISA. Chemokine expression was investigated in human subcutaneous adipose tissue biopsies and mechanism of chemokine expression was investigated using chemical inhibitors and cellular and animal transgenic models. Chemokine encoding genes were the most responsive genes in TNF-α treated human and mouse adipocytes. mRNA and protein of 34 chemokine genes were induced in a dose-dependent manner in the culture system. Furthermore, expression of those chemokines was elevated in human obese adipose tissue. Finally, chemokine expression was reduced by NF-κB inactivation and elevated by NF-κB activation. Our data indicate that besides CCL2 and CCL5, numerous other chemokines such as CCL19 are expressed by adipocytes under obesity-associated chronic inflammation. Their expression is regulated predominantly by NF-κB. Those chemokines could be involved in the initiation of infiltration of leukocytes into obese adipose tissue.

Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder occurring in the progeny of a single bull. Its clinical spectrum includes polledness (complete agenesis of horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, and variable neurological and cardiac anomalies. PMS is also characterized by a deviation of the sex-ratio, suggesting male lethality during pregnancy. Using Mendelian error mapping and whole-genome sequencing, we identified a 3.7 Mb deletion on the paternal bovine chromosome 2 encompassing ARHGAP15, GTDC1 and ZEB2 genes. We then produced control and affected 90-day old fetuses to characterize this syndrome by histological and expression analyses. Compared to wild type individuals, affected animals showed a decreased expression of the three deleted genes. Based on a comparison with human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation. Finally sperm-FISH, embryo genotyping and analysis of reproduction records confirmed somatic mosaicism in the founder bull and male-specific lethality during the first third of gestation. In conclusion, we identified a novel locus involved in bovid horn ontogenesis and suggest that epithelial-to-mesenchymal transition plays a critical role in horn bud differentiation. We also provide new insights into the pathogenicity of ZEB2 loss of heterozygosity in bovine and humans and describe the first case of male-specific lethality associated with an autosomal locus in a non-murine mammalian species. This result sets PMS as a unique model to study sex-specific gene expression/regulation.

The fur of common rabbits is constituted of 3 types of hair differing in length and diameter while that of rex animals is essentially made up of amazingly soft down-hair. Rex short hair coat phenotypes in rabbits were shown to be controlled by three distinct loci. We focused on the "r1" mutation which segregates at a simple autosomal-recessive locus in our rabbit strains. A positional candidate gene approach was used to identify the rex gene and the corresponding mutation. The gene was primo-localized within a 40 cM region on rabbit chromosome 14 by genome scanning families of 187 rabbits in an experimental mating scheme. Then, fine mapping refined the region to 0.5 cM (Z = 78) by genotyping an additional 359 offspring for 94 microsatellites present or newly generated within the first defined interval. Comparative mapping pointed out a candidate gene in this 700 kb region, namely LIPH (Lipase Member H). In humans, several mutations in this major gene cause alopecia, hair loss phenotypes. The rabbit gene structure was established and a deletion of a single nucleotide was found in LIPH exon 9 of rex rabbits (1362delA). This mutation results in a frameshift and introduces a premature stop codon potentially shortening the protein by 19 amino acids. The association between this deletion and the rex phenotype was complete, as determined by its presence in our rabbit families and among a panel of 60 rex and its absence in all 60 non-rex rabbits. This strongly suggests that this deletion, in a homozygous state, is responsible for the rex phenotype in rabbits.