New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Epidémiologie, traitement et survie du cancer du pancréas dans le département du Calvados entre 1978 et 2001

CAEN-BU Médecine pharmacie (141182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Pancreatic cancer: Incidence, treatment and survival trends - 1175 cases in Calvados (France) from 1978 to 2002.

International audienceAIM: To assess the trends in incidence, therapeutic modalities and survival of pancreatic cancer between 1978 and 2002 in a well-defined population, as recorded in the Calvados digestive cancer registry database. PATIENTS AND METHODS: All patients living in Calvados with a diagnosis of pancreatic cancer were registered. Clinical data and treatment modalities were prospectively recorded. This 25-year database was divided into five 5-year periods. Data were compared using log-rank tests and the Cox model. RESULTS: A total of 1175 cases of pancreatic cancer (617 men, 558 women) were registered. Its incidence increased with an average annual coefficient of +2.8% in men and +5.1% in women. Therapeutic modalities changed over the five time periods: surgical resection increased from 6.8 to 13.4% (median survival 15 months) while radiation therapy and/or chemotherapy also increased from 5.5 to 13.2%. Palliative surgery decreased from 54.6 to 32.0% and favored interventional endoscopic techniques. Postoperative mortality decreased significantly. Survival increased significantly over the five time periods, although the median survival time remained stable (4 months). CONCLUSION: From 1978 to 2002, pancreatic cancer incidence increased in Calvados (France). Therapeutic modalities changed, with endoscopic treatments preferred over palliative surgery. The improvement in survival could be explained by the decrease in postoperative mortality

Climate-driven fluxes of organic-bound uranium to an alpine lake overthe Holocene

International audienceUranium (U) isotopic signatures and concentration in sediments are widely used as paleo-redox proxies, as the behavior of U is often controlled by bottom water oxygenation. Here, we investigated the processes controlling U accumulation in the sediments of Lake Nègre (Mediterranean Alps, South-East France) over the past 9200 years. Exceptionally high natural U concentrations (350-1250 μg.g-1) allowed the measurement of U along with other elements by high-resolution X-Ray Fluorescence core-scanning. Weathering and erosion proxies (Ti content, Zr/Al and K/Ti ratios) indicate that sedimentary inputs were controlled by Holocene climatic variations. After a period of low erosion during the Holocene Climatic Optimum, a major regime shift was recorded at 4.2 kyr BP when terrigenous fluxes consistently increased until present with high sensitivity to centennial-scale climatic events. Sedimentary organic matter (OM) inputs were dominated by terrigenous OM from the catchment soils until 2.4 kyr BP, as attested by carbon to nitrogen (C/N) and bromine to organic carbon (Br/TOC) ratios. From 2.4 kyr BP to present, lake primary production and soils equally contributed to sedimentary OM. Uranium fluxes to the sediments were well correlated to terrigenous OM fluxes from 7 kyr BP to present, showing that U supply to the lake was controlled by U scavenging in the soils of the watershed followed by transport of U bound to detrital organic particles. Higher U/OM ratios before 7 kyr BP likely reflect the development of the upstream wetland. The fluctuations of U sedimentary inputs appear to be independent of bottom water oxygenation, as estimated from constant Fe/Mn ratios and δ238U isotopic signatures, and rather controlled by the production, erosion and sedimentation of terrigenous OM. This finding confirms that the use of U (and potentially other metals with high affinity to OM) concentrations alone should be used with caution for paleo-redox reconstructions

Impact of the European Union directive on driving licences on a Multidisciplinary Sleep Clinic: a Cohort Study

Introduction: The threat of Obstructive Sleep Apnea (OSA) for motor vehicle accident has led to a revision of annex III of the European Union directive on driving licences that was implemented in all member states from December 31, 2015. In Belgium, it was followed by a shift in funding for OSA from January 1, 2017. Funding was allowed for moderate to severe OSA and the rules shifted for treatments delivery and monitoring by authorised medical opinion. Multidisciplinary Sleep Clinics have long existed, bringing together sleep specialists, dentists, orthodontists and surgeons. We aimed to assess whether a shift in treatment funding was associated with a change in the multidisciplinary sleep practice. Material and Methods: Sample consisted of all patients discussed in the sleep multidisciplinary team meetings of the University Hospital of Liege from January 2016 to December 2018. Interrupted times series, Mann-Whitney U tests and descriptive statistics were produced. Results: There were no differences in patients age, male sex preponderance, body mass index, clinical presentation and level of obstruction. Baseline OSA severity was significantly lower (mean apnea-hypopnea index and mean oxygen desaturation index lowered respectively with p = 0.0189 and p = 0.0466) after the funding rules changed. Oral appliance and ENT surgery were more often offered after the shift in funding. Conclusion: Sleep multidisciplinary team meeting changed patient selection and management after the implementation of the new funding rules for OSA. The shift in funding often resulted in treatment options change, reaching more people and offering more options

Controls of climate and organic matter on uranium fluxes to lake sediments over the Holocene

International audienceOne of the main factors controlling the behavior of uranium (U) in water bodies is bottom water oxygenation, which enables the use of U isotopic ratios and concentration in oceanic sedimentary records as paleo-redox proxies [1]. Here, we investigated the mechanisms governing U accumulation in the sediments of Lake Nègre (Mediterranean Alps, South-East France) over the past 9200 years. These sediments display exceptional natural U concentrations (300–1500 µg.g-1), allowing the use of high-resolution X-Ray Fluorescence core-scanning for the measurement of U. Chemical proxies (Ti content, Zr/K and K/Ti ratios) indicate that erosional sedimentary inputs were controlled by Holocene climatic variations. After a period of low erosion during the Holocene Climatic Optimum, a major regime shift was recorded at 4.2 kyr BP when terrigenous fluxes increased until present with high sensitivity to centennial-scale climatic events. The temporal evolution of carbon to nitrogen (C/N) and bromine to organic carbon (Br/TOC) ratios of sedimentary organic matter (OM) indicate that it was mostly of terrigenous origin from the catchment soils until 2.4 kyr BP. From 2.4 kyr BP to present, lake primary production and soils equally contributed to sedimentary OM. The Fe/Mn core profile points out that the lake bottom water oxygenation remained constant over the past 9200 years. Uranium depositional conditions were also constant over this period as attested by the 238U/235U ratio (expressed as δ238U) core profile. However, U fluxes to the sediments varied substantially and were correlated to terrigenous OM fluxes from 7 kyr BP to present. This correlation highlights that U supply to the lake was controlled by U scavenging in the soils of the watershed followed by transport of U bound to detrital organic particles. The fluctuations of U sedimentary inputs thus appear to be independent of bottom water oxygenation and rather controlled by climate-driven variations in terrigenous OM production and erosion. This finding confirms that the use of U (and potentially other metals with high affinity to OM) concentrations alone should be used with caution for paleo-redox reconstructions

Controls of climate and organic matter on uranium fluxes to lake sediments over the Holocene

International audienceOne of the main factors controlling the behavior of uranium (U) in water bodies is bottom water oxygenation, which enables the use of U isotopic ratios and concentration in oceanic sedimentary records as paleo-redox proxies [1]. Here, we investigated the mechanisms governing U accumulation in the sediments of Lake Nègre (Mediterranean Alps, South-East France) over the past 9200 years. These sediments display exceptional natural U concentrations (300–1500 µg.g-1), allowing the use of high-resolution X-Ray Fluorescence core-scanning for the measurement of U. Chemical proxies (Ti content, Zr/K and K/Ti ratios) indicate that erosional sedimentary inputs were controlled by Holocene climatic variations. After a period of low erosion during the Holocene Climatic Optimum, a major regime shift was recorded at 4.2 kyr BP when terrigenous fluxes increased until present with high sensitivity to centennial-scale climatic events. The temporal evolution of carbon to nitrogen (C/N) and bromine to organic carbon (Br/TOC) ratios of sedimentary organic matter (OM) indicate that it was mostly of terrigenous origin from the catchment soils until 2.4 kyr BP. From 2.4 kyr BP to present, lake primary production and soils equally contributed to sedimentary OM. The Fe/Mn core profile points out that the lake bottom water oxygenation remained constant over the past 9200 years. Uranium depositional conditions were also constant over this period as attested by the 238U/235U ratio (expressed as δ238U) core profile. However, U fluxes to the sediments varied substantially and were correlated to terrigenous OM fluxes from 7 kyr BP to present. This correlation highlights that U supply to the lake was controlled by U scavenging in the soils of the watershed followed by transport of U bound to detrital organic particles. The fluctuations of U sedimentary inputs thus appear to be independent of bottom water oxygenation and rather controlled by climate-driven variations in terrigenous OM production and erosion. This finding confirms that the use of U (and potentially other metals with high affinity to OM) concentrations alone should be used with caution for paleo-redox reconstructions

Impact of a Shift in Treatment Funding on a Multidisciplinary Sleep Clinic: a Cohort Study

peer reviewedIntroduction and Aim: A shift in Obstructive Sleep Apnea (OSA) funding was implemented in Belgium on January 1, 2017. Funding was allowed for moderate to severe OSA and the rules shifted for treatments delivery and monitoring by authorised medical opinion. Multidisciplinary Sleep Clinics have long existed, bringing together sleep specialists, dentists, orthodontists and surgeons. We aimed to assess whether a shift in treatment funding was associated with a change in the multidisciplinary sleep practice. Material and Methods: Sample consisted of all patients discussed in the sleep multidisciplinary team meetings of the University Hospital of Liege from January 2016 to December 2018. Interrupted times series, Mann-Whitney U tests and descriptive statistics were produced. Results: There were no differences in patients age, male sex preponderance, body mass index, clinical presentation and level of obstruction. Baseline OSA severity was significantly lower (mean apnea-hypopnea index and mean oxygen desaturation index lowered respectively with p = 0.0189 and p = 0.0466) after the funding rules changed. Oral appliance and ENT surgery were more often offered after the shift in funding. Conclusion: Sleep multidisciplinary team meeting changed patient selection and management after the implementation of the new funding rules for OSA. The shift in funding often resulted in treatment options change, reaching more people and offering more options

Controls of climate and organic matter on uranium fluxes to lake sediments over the Holocene

International audienceOne of the main factors controlling the behavior of uranium (U) in water bodies is bottom water oxygenation, which enables the use of U isotopic ratios and concentration in oceanic sedimentary records as paleo-redox proxies [1]. Here, we investigated the mechanisms governing U accumulation in the sediments of Lake Nègre (Mediterranean Alps, South-East France) over the past 9200 years. These sediments display exceptional natural U concentrations (300–1500 µg.g-1), allowing the use of high-resolution X-Ray Fluorescence core-scanning for the measurement of U. Chemical proxies (Ti content, Zr/K and K/Ti ratios) indicate that erosional sedimentary inputs were controlled by Holocene climatic variations. After a period of low erosion during the Holocene Climatic Optimum, a major regime shift was recorded at 4.2 kyr BP when terrigenous fluxes increased until present with high sensitivity to centennial-scale climatic events. The temporal evolution of carbon to nitrogen (C/N) and bromine to organic carbon (Br/TOC) ratios of sedimentary organic matter (OM) indicate that it was mostly of terrigenous origin from the catchment soils until 2.4 kyr BP. From 2.4 kyr BP to present, lake primary production and soils equally contributed to sedimentary OM. The Fe/Mn core profile points out that the lake bottom water oxygenation remained constant over the past 9200 years. Uranium depositional conditions were also constant over this period as attested by the 238U/235U ratio (expressed as δ238U) core profile. However, U fluxes to the sediments varied substantially and were correlated to terrigenous OM fluxes from 7 kyr BP to present. This correlation highlights that U supply to the lake was controlled by U scavenging in the soils of the watershed followed by transport of U bound to detrital organic particles. The fluctuations of U sedimentary inputs thus appear to be independent of bottom water oxygenation and rather controlled by climate-driven variations in terrigenous OM production and erosion. This finding confirms that the use of U (and potentially other metals with high affinity to OM) concentrations alone should be used with caution for paleo-redox reconstructions