Éditeur(s) : HAL CCSD
Résumé : International audience
This study compared the hemorheological profile at rest and in response to a short supramaximal exercise test between sickle cell trait (SCT) carriers and a control group. Eight SCT carriers and eight control subjects performed a ramp exercise test on a cycle ergometer conducted to maximal oxygen uptake ðV_ O2maxÞ: One week later, they performed a supramaximal exercise test consisting of pedaling for 1 min at 110% V_ O2max: Blood viscosity (gb), plasma viscosity (gp), hematocrit (Hct) and red blood cell (RBC) rigidity were assessed at rest, at the end of exercise and at the 15th, 30th and 60th min of recovery. Exercise increased gb, gp and Hct above resting values in both groups and these parameters remained higher until the 15th or 30th min of recovery as compared to resting values. RBC rigidity was unchanged from baseline values in both groups during exercise and recovery. No difference was observed between the two groups for gp and Hct but gb and RBC rigidity were higher in the SCT carriers at every time point compared with the control group. The higher RBC rigidity and gb found in SCT carriers at rest and in response to a brief supramaximal exercise might constitute a risk factor for microcirculatory complications. Indeed, a short supramaximal exercise test may not be completely inoffensive for SCT carriers.
EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY

hal-00706158
https://hal.univ-antilles.fr/hal-00706158
DOI : 10.1007/s00421-006-0155-3

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported. In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders. The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients. Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs. ClinicalTrials.gov: No: NCT01225601 .
ISSN: 1750-1172

hal-01146047
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146047
PUBMED : 25887097
DOI : 10.1186/s13023-015-0249-2

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
OBJECTIVES:Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown.MATERIALS AND METHODS:Blood viscosity, red blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients.RESULTS:Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age.CONCLUSION:The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01669747
https://hal.univ-antilles.fr/hal-01669747
DOI : 10.1371/journal.pone.0158182
PUBMED : 27355589
PUBMEDCENTRAL : PMC4927160

Éditeur(s) : HAL CCSD
Résumé : International audience
Multiple chemicals are emitted in residential accommodation. Aggregate Daily Doses (ADD) (ng/kg-bw/d) were estimated for 32 semivolatile organic compounds (SVOCs) of different chemical families that are frequently detected in French dwellings in both air and settled dust. Daily doses were determined using steady-state models for the population, categorized into 11 age groups covering birth to age 30. Three routes of exposure were taken into account: dust ingestion, inhalation (gaseous and particulate phases) and dermal contact with the gaseous phase of air. Contamination levels were preferentially retrieved from large, nationwide representative datasets. A two-dimensional probabilistic approach was used to assess parametric uncertainty and identify the most influential factors. For children aged 2 to 3 years, ADD estimates spanned orders of magnitude, with median values ranging from 8.7 pg/kg-bw/d for 2,2′,3,4,4′-pentabromodiphenylether (BDE 85) to 1.3 μg/kg-bw/d for di-isobutyl phthalate (DiBP). Inhalation, ingestion and dermal pathway contributed at varying levels, and depending on compound, air was the dominant medium for 28 of the 32 compounds (either by inhalation or dermal contact). Indoor exposure estimate variance was mainly driven by indoor contamination variability, and secondarily by uncertainty in physical and chemical parameters. These findings lend support to the call for cumulative risk assessment of indoor SVOCs. © 2017 Elsevier Ltd
ISSN: 01604120

hal-01616433
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616433
DOI : 10.1016/j.envint.2017.08.024
PUBMED : 28950160

Éditeur(s) : HAL CCSD Oxford Journals
Résumé : International audience
Background - Several studies have investigated the implication of biological and environmental factors on geographic variations of end-stage renal disease (ESRD) incidence at large area scales, but none of them assessed the implication of neighbourhood characteristics (healthcare supply, socio-economic level and urbanization degree) on spatial repartition of ESRD. We evaluated the spatial implications of adjustment for neighbourhood characteristics on the spatial distribution of ESRD incidence at the smallest geographic unit in France.Methods - All adult patients living in Bretagne and beginning renal replacement therapy during the 2004–09 period were included. Their residential address was geocoded at the census block level. Each census block was characterized by socio-economic deprivation index, healthcare supply and rural/urban typology. Using a spatial scan statistic, we examined whether there were significant clusters of high risk of ESRD incidence.Results - The ESRD incidence was non-randomly spatially distributed, with a cluster of high risk in the western Bretagne region (relative risk, RR = 1.28, P-value = 0.0003). Adjustment for sex, age and neighbourhood characteristics induced cluster shifts. After these adjustments, a significant cluster (P = 0.013) persisted.Conclusions - Our spatial analysis of ESRD incidence at a fine scale, across a mixed rural/urban area, indicated that, beyond age and sex, neighbourhood characteristics explained a great part of spatial distribution of ESRD incidence. However, to better understand spatial variation of ESRD incidence, it would be necessary to research and adjust for other determinants of ESRD.
Clinical Kidney Journal

hal-01118626
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118626
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118626/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118626/file/Spatial%20distribution%20of%20end-stage%20renal%20disease.pdf
DOI : 10.1093/ckj/sfu131

Éditeur(s) : HAL CCSD American Medical Association (AMA)
Résumé : International audience
IMPORTANCE Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome. OBJECTIVE To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28. DESIGN, SETTING, AND PARTICIPANTS Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs. INTERVENTIONS Empirical treatment with micafungin (100mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). MAIN OUTCOMES AND MEASURES The primary end pointwas survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-beta-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia. RESULTS Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-beta-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-beta-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (> 8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P =.008). CONCLUSIONS AND RELEVANCE Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.
ISSN: 0098-7484

hal-01405822
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01405822
DOI : 10.1001/jama.2016.14655
PUBMED : 27706483

Éditeur(s) : HAL CCSD
Résumé : International audience
BACKGROUND: Semi Volatile Organic Compounds (SVOCs) are contaminants commonly found in dwellings as a result of their use as plasticizers, flame retardants, or pesticides in building materials and consumer products. Many SVOCs are suspected of being neurotoxic, based on mammal experimentation (impairment of locomotor activity, spatial learning/memory or behavioral changes), raising the question of cumulative risk assessment. The aim of this work is to estimate the relative toxicity of such SVOCs, based on neuronal death. METHOD: SVOCs fulfilling the following conditions were included: detection frequency >10% in dwellings, availability of data on effects or mechanism of action for neurotoxicity, and availability of dose-response relationships based on cell viability assays as a proxy of neuronal death. Benchmark concentration values (BMC) were estimated using a Hill model, and compared to assess relative toxicity. RESULTS: Of the 58 SVOCs selected, 28 were suspected of being neurotoxic in mammals, and 21 have been documented as inducing a decrease in cell viability in vitro. 13 have at least one dose-response relationship that can be used to derive a BMC based on a 10% fall in neuronal viability. Based on this in vitro endpoint, PCB-153 appeared to be the most toxic compound, having the lowest BMC10 (0.072μM) and diazinon the least toxic compound, having the highest BMC10 (94.35μM). We showed that experimental designs (in particular choice of cell lines) had a significant influence on BMC calculation. CONCLUSION: For the first time, the relative in vitro toxicity of 13 indoor contaminants belonging to different chemical families has been assessed on the basis of neuronal cell viability. Lack of comparable toxicity datasets limits the number of SVOCs that can be included. More standardized protocols in terms of cell lines, species and exposure duration should be developed with a view to cumulative risk assessment.
Toxicology Letters

hal-01579605
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579605
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579605/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01579605/file/Fournier%20et%20al.%20-%20Relative%20toxicity%20for%20indoor%20semi%20volatile%20organic.pdf
DOI : 10.1016/j.toxlet.2017.07.875

Éditeur(s) : HAL CCSD American Geophysical Union
Résumé : Giant earthquakes (Mw≥8.5) usually occur on the boundary between subducting and overriding plates of converging margins, but it is not yet clear which (if any) subduction zones are more prone to produce such a kind of events. Here we show that subduction zones may have different capabilities to produce giant earthquakes. We analyze the frequency-magnitude distribution of the interplate earthquakes at subduction zones that occurred during 1976–2007 and calculate the propensity (defined as the average annual rate) of giant events for about half of the subduction zones. We find that the b value of interplate earthquakes is significantly different among the subduction zones, and out-of-sample giant earthquakes (before 1976 and after 2007) have occurred preferentially in high-propensity areas. Besides the importance for seismic hazard assessment and risk mitigation, our results seem to indicate that a higher seismicity rate does not necessarily imply a higher likelihood to generate giant earthquakes, and the way in which the stress is released at a subduction interface does not change significantly after the occurrence of such events.
ISSN: 0148-0227

hal-01467738
https://hal.archives-ouvertes.fr/hal-01467738
DOI : 10.1002/2016JB013054

Éditeur(s) : HAL CCSD IEEE
Résumé : International audience
The main challenge in prostate cancer radiotherapy is to deliver the prescribed dose to the clinical target while minimizing the dose to the neighboring organs at risk and thus avoiding subsequent toxicity-related events. With the aim of improving toxicity prediction following prostate cancer radiotherapy, the goal of our work is to propose a new predictive variable computed with independent component analysis to predict late rectal toxicity, and to compare its performance to other models (logistic regression, normal tissue complication probability model and recent principal component analysis approach). Clinical data and dose-volume histograms were collected from 216 patients having received 3D conformal radiation for prostate cancer with at least two years of follow-up. Independent component analysis was trained to predict the risk of 3-year rectal bleeding Grade extgreater= 2. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve. Clinical parameters combined with the new variable were found to be predictors of rectal bleeding. The mean area under the receiving operating curve for our proposed approach was 0:75. The AUC values for the logistic regression, the Lyman-Kutcher-Burman model and the recent principal component analysis approach were 0:62, 0:53 and 0:62, respectively. Our proposed new variable may be an useful new tool in predicting late rectal toxicity. It appears as a strong predictive variable to improve classical models
2015 37th annual international conference of the IEEE Engineering in Medicine and Biology Society
Milan, Italy

hal-01304750
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01304750

Éditeur(s) : HAL CCSD ACSM
Résumé : International audience
A 26-yr-old man with sickle cell trait (SCT) suddenly lost visual acuity in the left eye after a cycling race in hot tropical environment. The cause was massive central retinal vein occlusion (CRVO) with hemorrhaging that rapidly worsened to neovascular glaucoma. Although medically treated, the eye is now marked by total retinal detachment. Cardiovascular function assessment shows no electrocardiographic abnormalities, no anomaly in the supra-aortic tree, and no evidence of structural heart disease. Although normal coagulation markers values (i.e., activated partial thromboplastin time, prothrombin time, fibrinogen concentration, antithrombin III, factor V, proteins C and S) were observed 2.5 months after the clinical event, a transesophageal echocardiogram performed few hours after the incident revealed the presence of four thrombi in the left atrium suggesting a postexercise hypercoagulable state at that time. Hemorheological measurements at distance of the events demonstrated high red blood cell rigidity at baseline. Therefore, marked blood rheological impairment and activation of the coagulation pathway in response to the heavy and prolonged cycling race could have promoted CRVO in this cyclist carrying SCT. These data suggest that SCT could be considered as a risk factor for significant ocular complications when severe exercise is performed and support the idea that SCT is a contributing factor in blood rheology and vascular dysfunctions.
Medicine & Science in Sports & exercise

Droits : info:eu-repo/semantics/OpenAccess
hal-00698572
https://hal.univ-antilles.fr/hal-00698572
https://hal.univ-antilles.fr/hal-00698572/document
https://hal.univ-antilles.fr/hal-00698572/file/Hedreville_et_al_revised_MSSE-D-08-00064R2.pdf
DOI : 10.1249/MSS.0b013e31818313d0

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Multiple chemicals are emitted in residential accommodation. Aggregate Daily Doses (ADD) (ng/kg-bw/d) were estimated for 32 semivolatile organic compounds (SVOCs) of different chemical families that are frequently detected in French dwellings in both air and settled dust. Daily doses were determined using steady-state models for the population, categorized into 11 age groups covering birth to age 30. Three routes of exposure were taken into account: dust ingestion, inhalation (gaseous and particulate phases) and dermal contact with the gaseous phase of air. Contamination levels were preferentially retrieved from large, nationwide representative datasets. A two-dimensional probabilistic approach was used to assess parametric uncertainty and identify the most influential factors. For children aged 2 to 3 years, ADD estimates spanned orders of magnitude, with median values ranging from 8.7 pg/kg-bw/d for 2,2′,3,4,4′-pentabromodiphenylether (BDE 85) to 1.3 μg/kg-bw/d for di-isobutyl phthalate (DiBP). Inhalation, ingestion and dermal pathway contributed at varying levels, and depending on compound, air was the dominant medium for 28 of the 32 compounds (either by inhalation or dermal contact). Indoor exposure estimate variance was mainly driven by indoor contamination variability, and secondarily by uncertainty in physical and chemical parameters. These findings lend support to the call for cumulative risk assessment of indoor SVOCs.
ISSN: 0160-4120

hal-01635777
https://hal.archives-ouvertes.fr/hal-01635777
https://hal.archives-ouvertes.fr/hal-01635777/document
https://hal.archives-ouvertes.fr/hal-01635777/file/Article_Expo_Pelletier_Manuscript%20Env%20Int%20rev2.pdf
DOI : 10.1016/j.envint.2017.08.024