Community-associated Methicillin-resistant Staphylococcus aureus in Pediatric Patients

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections increased from 2000 to 2003 in hospitalized pediatric patients in Houston. CA-MRSA was associated with greater illness than was infection with methicillin-susceptible strains. Children with CA-MRSA were younger and mostly African American. Of MRSA isolates, 4.5% had the inducible macrolide-lincosamide-streptogramin B phenotype

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill & Melinda Gates Foundation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Characterization of human regulatory B cells in chronic lymphocytic leukemia

Contexte: La leucémie lymphoïde chronique (LLC) est une hémopathie maligne associée à des anomalies dans les réponses immunitaires. Ce qui contribue à la progression de la maladie. Certains LB peuvent induire une inhibition de la réponse anti-tumorale des LT et ainsi promouvoir la progression des tumeurs. Ces LB appelés LB régulateurs partagent des caractéristiques communes avec les LB de LLC.Objectif: L'objectif principal de ce projet est d'évaluer la fonction régulatrice des LB de LLC, afin d’estimer leur influence sur l'absence de réponses anti-tumorales par les cellules T.Méthode: Des modèles de co-culture in vitro ont été développés pour évaluer la capacité desLB à inhiber la prolifération des LT.Résultats: Nos résultats montrent qu’en absence de stimulation, les LB de LLC sont incapables d’inhiber la prolifération des LT contrairement aux LB de témoins. Cependant, deux groupes de patients ont été identifiés après stimulation du TLR-9 des LB. Dans le premier groupe, les LB présentent des fonctions régulatrices défectueuses par rapport aux LB de témoins. Dans le second groupe, aucune activité inhibitrice n’est détectée. L’expression différentielle des gènes associés à la voie TLR-9 entre les deux groupes de patients semble pouvoir expliquer cette dichotomie de réponse. Une corrélation a par ailleurs été retrouvée entre le doublement lymphocytaire et la faible activité régulatrice des LB de LLC.Conclusion: Pour aller plus loin, il convient d'identifier les mécanismes moléculaires endommageant la voie TLR-9. Ces nouvelles données aideront à la compréhension de l’absence de réponse anti-tumorale et des dysfonctionnements immunitaires retrouvés chez les patients.Background: Chronic lymphocytic leukemia (CLL) is characterized by expansion of CD5+B cells associated with disruption of immune responses, contributing to the immunodeficiency and the disease progression. Regulatory B (Breg) cells may control the anti-tumor responses favoring tumor escape. Intriguingly, CLL B cells share phenotypical characteristics with these cells.Aims: The main focus of this project is to evaluate the regulatory function of CLL B cells, aiming to estimate their influence on the lack of anti-tumor responses mediated by T cells.Methods: In vitro models of co-cultures between T and B cells are used to appraise the regulatory capacity of CLL B cells on T cell proliferation.Results: We determined a defective spontaneous regulatory function for CLL B cells. Two groups of patients have been identified following CpG-ODN stimulation. The first group presents defective regulatory B cell functions compared with control B cells. In the second group, no inhibitory activity is detected. TLR-9 gene expression analysis highlighted differential gene expression between controls and the two groups of CLL patients. Moreover, ours observations indicate that patients with low Breg activity have more aggressive disease.Conclusion: These results suggest alteration of the TLR-9 pathway in CLL B cells. To go further, it will be of interest to identify the molecular mechanisms damaging the TLR-9 pathway. These results would contribute to clarify the lack of anti-tumor immune response found in the CLL patients

Comprendre la physiopathologie des lymphocytes B au cours de la leucémie lymphoïde chronique : role des lymphocytes B régulateurs.

National audienc

Caractérisation des lymphocytes B régulateurs dans la leucémie lymphoïde chronique

Background: Chronic lymphocytic leukemia (CLL) is characterized by expansion of CD5+B cells associated with disruption of immune responses, contributing to the immunodeficiency and the disease progression. Regulatory B (Breg) cells may control the anti-tumor responses favoring tumor escape. Intriguingly, CLL B cells share phenotypical characteristics with these cells.Aims: The main focus of this project is to evaluate the regulatory function of CLL B cells, aiming to estimate their influence on the lack of anti-tumor responses mediated by T cells.Methods: In vitro models of co-cultures between T and B cells are used to appraise the regulatory capacity of CLL B cells on T cell proliferation.Results: We determined a defective spontaneous regulatory function for CLL B cells. Two groups of patients have been identified following CpG-ODN stimulation. The first group presents defective regulatory B cell functions compared with control B cells. In the second group, no inhibitory activity is detected. TLR-9 gene expression analysis highlighted differential gene expression between controls and the two groups of CLL patients. Moreover, ours observations indicate that patients with low Breg activity have more aggressive disease.Conclusion: These results suggest alteration of the TLR-9 pathway in CLL B cells. To go further, it will be of interest to identify the molecular mechanisms damaging the TLR-9 pathway. These results would contribute to clarify the lack of anti-tumor immune response found in the CLL patients.Contexte: La leucémie lymphoïde chronique (LLC) est une hémopathie maligne associée à des anomalies dans les réponses immunitaires. Ce qui contribue à la progression de la maladie. Certains LB peuvent induire une inhibition de la réponse anti-tumorale des LT et ainsi promouvoir la progression des tumeurs. Ces LB appelés LB régulateurs partagent des caractéristiques communes avec les LB de LLC.Objectif: L'objectif principal de ce projet est d'évaluer la fonction régulatrice des LB de LLC, afin d’estimer leur influence sur l'absence de réponses anti-tumorales par les cellules T.Méthode: Des modèles de co-culture in vitro ont été développés pour évaluer la capacité desLB à inhiber la prolifération des LT.Résultats: Nos résultats montrent qu’en absence de stimulation, les LB de LLC sont incapables d’inhiber la prolifération des LT contrairement aux LB de témoins. Cependant, deux groupes de patients ont été identifiés après stimulation du TLR-9 des LB. Dans le premier groupe, les LB présentent des fonctions régulatrices défectueuses par rapport aux LB de témoins. Dans le second groupe, aucune activité inhibitrice n’est détectée. L’expression différentielle des gènes associés à la voie TLR-9 entre les deux groupes de patients semble pouvoir expliquer cette dichotomie de réponse. Une corrélation a par ailleurs été retrouvée entre le doublement lymphocytaire et la faible activité régulatrice des LB de LLC.Conclusion: Pour aller plus loin, il convient d'identifier les mécanismes moléculaires endommageant la voie TLR-9. Ces nouvelles données aideront à la compréhension de l’absence de réponse anti-tumorale et des dysfonctionnements immunitaires retrouvés chez les patients

Accompagner des enseignants dans le développement individuel et collectif de pratiques de feedbacks propres à optimiser l’apprentissage des étudiants de 1ère année d’une même Faculté. Lignes de force d’un dispositif mis en œuvre à l’Université de Liège en Sciences appliquées.

peer reviewedNée à l’Université de Liège d’un partenariat entre le Centre de Didactique Supérieure (CDS) et le Service Guidance Etude (SGE) de l’Administration de l’Enseignement et des Etudiants, initié par l’Institut de Formation et de Recherche en Enseignement Supérieur (IFRES), la phase pilote d’un projet visant à promouvoir et optimiser les pratiques de feedbacks formatifs en 1ère année sur base d’un dispositif d’accompagnement intégré a été implémentée en Faculté des Sciences appliquées. Cette communication présente le positionnement du projet au sein de l’Institution, son orientation thématique, les fondements théoriques de sa méthodologie, ainsi que les étapes de développement mises en œuvre à ce stade. La seconde partie se penche sur la réception du projet par le collège d’enseignants impliqués en première ligne, et examine les initiatives pédagogiques individuelles et collectives adoptées avec le soutien d’une équipe d’accompagnateurs détachée sur le terrain

Comprendre la physiopathologie des lymphocytes B au cours de la leucmie lymphoïde chronique : role des lymphocytes B régulateurs.

International audienc

Monitoring Shallow Infiltration in Sandy Soil Using GPR Groundwave Techniques

Color poster with text, diagrams, images, and tables.Characterizing the near-surface soil water content distribution is important for precision agriculture and groundwater remediation applications. Measuring soil water content over large areas is often difficult, as conventional point measurement and remote sensing techniques are often insufficient to characterize water content heterogeneity at the field scale. Ground penetrating radar (GPR) groundwaves are an electromagnetic geophysical technique that can be used to estimate water content quickly over large areas. The objective of this field-scale research is to explore the potential of multi-frequency GPR groundwave data for detecting changes in soil moisture at different depths as water moves through the near-surface soil.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs; National Research Initiative of the USDA Cooperative State Research, Education and Extension Servic