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Abstract Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by a microangiopathy and fibrosis of the skin and internal organs. No treatment has been proved to be efficient in case of early or advanced SSc to prevent or reduce fibrosis. There are strong arguments for a key role of topo-I in the pathogenesis of diffuse SSc. Irinotecan, a semisynthetic derivative of Camptothecin, specifically target topo-I. This study was undertaken to evaluate the effects of noncytotoxic doses of irinotecan or its active metabolite SN38 on collagen production in SSc fibroblasts. Dermal fibroblasts from 4 patients with SSc and 2 healthy donors were cultured in the presence or absence of irinotecan or SN38. Procollagen I release was determined by ELISA and expression of a panel of genes involved in fibrosis was evaluated by qRT-PCR. Subcytotoxic doses of irinotecan and SN38 caused a significant and dose-dependent decrease of the procollagen I production in dermal fibroblasts from SSc patients, respectively − 48 ± 3%, p

Objectives: To cross-sectionally describe brain alterations in PLHIV aged above 50 years old, receiving antiretroviral treatment (ART) and living in Senegal compared to HIV-negative subjects. Methods: Twenty PLHIV and 26 HIV-negative subjects with comparable socio-demographic and clinical characteristics underwent an MRI exam (3D-T1 and FLAIR sequences). Global atrophy and White Matter Hyperintensities (WMH) were evaluated. After assessing the feasibility and acceptability of MRI scans in this population, we described atrophy and WHM prevalence and associated factors using logistic regressions. Results: Overall, 43.5% of the study sample were aged ≥60 years, 58.7% were women, and 28.3% had hypertension. The overall prevalence of atrophy and WMH was 19.6% [95% CI: 8.1–31.1] and 30.4% [95% CI: 17.1–43.7]. HIV status had no significant effect on atrophy or WMH. Unemployment and hypertension were significantly associated with atrophy, whereas women were less likely to present atrophy. Aged ≥60 years was the only factor associated with WMH. Conclusions: A high prevalence of atrophy and WMH was observed in West African adults aged over 50 years without a clear HIV impact. As brain MRI studies are critical to better understand cognitive and emotional outcomes, we encourage those studies in older PLHIV in West Africa.

Abstract Background The objective of the study was to describe the evolution of chronic non-AIDS related diseases and their risk factors, in patients living with HIV (PLHIV) in the French ANRS CO3 Aquitaine prospective cohort, observed both in 2004 and in 2014 in order to improve long-term healthcare management. Methods The ANRS CO3 Aquitaine cohort prospectively collects epidemiological, clinical, biological and therapeutic data on PLHIV in the French Aquitaine region. Two cross sectional analyses were performed in 2004 and 2014, to investigate the patient characteristics, HIV RNA, CD4 counts and prevalence of some common comorbidities and treatment. Results 2138 PLHIV (71% male, median age 52.2 years in 2014) were identified for inclusion in the study, including participants who were registered in the cohort with at least one hospital visit recorded in both 2004 and 2014. Significant increases in the prevalence of diagnosed chronic kidney disease (CKD), bone fractures, cardiovascular events (CVE), hypertension, diabetes and dyslipidaemia, as well as an increase in treatment or prevention for these conditions (statins, clopidogrel, aspirin) were observed. It was also reflected in the increase in the proportion of patients in the “high” or “very high” risk groups of the disease risk scores for CKD, CVE and bone fracture score. Conclusions Between 2004 and 2014, the aging PLHIV population identified in the French ANRS CO3 Aquitaine prospective cohort experienced an overall higher prevalence of non-HIV related comorbidities, including CKD and CVD. Long-term healthcare management and long-term health outcomes could be improved for PLHIV by: careful HIV management according to current recommendations with optimal selection of antiretrovirals, and early management of comorbidities through recommended lifestyle improvements and preventative measures.

Abstract This paper presents an application to metal matrix composites (MMCs) of an enhanced elasto-viscoplastic Fast Fourier Transform (EVP-FFT) formulation coupled with a phenomenological continuum Mesoscale Field Dislocation Mechanics (MFDM) theory. Contrary to conventional crystal plasticity, which only accounts for plastic flow and hardening induced by statistically stored dislocations (SSDs), MFDM-EVP-FFT also describes the evolution of polarized geometrically necessary dislocation (GND) density and its effect on both plastic flow and hardening. Numerical results for a Fe–TiB2 MMC made of a ferrite matrix (α-Fe) and elastic ceramic particles (TiB2) are presented. Full-field simulations are performed using synthetic periodic unit cells representative of the MMC, with single-crystalline and polycrystalline matrix, for different particle interspacing distances. A strong dependence of the predicted equivalent stress, cumulated plastic strain and GND density fields with particle interspacing distance is observed, in contrast with conventional crystal plasticity. Correlations between these mechanical fields and microstructural features, and their influence on local and global mechanical behavior are examined for the different MMC microstructures.

Dextrin/starch-graft-poly(butyl acrylate-co-styrene) copolymers have been synthesized by radical graft copolymerization and their structure and mechanical properties are reported. High molecular weight grafted chains formation is favored, leading to a low degree of substitution of starch hydroxyl groups. Wide-Angle-X-ray Scattering (WAXS) analysis indicates that all materials are amorphous and Transmission Electron Microscopy (TEM) investigations reveal a two-phase morphology. This is further confirmed by the presence of two glass transitions, one related to the starch/dextrin macromolecules and sensitive to water content, and one assigned to the grafted polymers that is composition dependent. Water uptake is controlled by dextrin/starch content but diffusivity increases with the butyl acrylate ratio. The mechanical behavior is dependent on monomer ratio, and water content. Increasing butyl acrylate ratio improves the ductility of the sample while materials become brittle as soon as styrene ratio is predominant in the grafted chains. While no effect of molecular weight of starch substrate on structure and thermal behavior is evidenced, dextrin-based materials are slightly more ductile than starchbased ones. The interest of using dextrin instead of starch is further highlighted by a lower viscosity of the reactive medium, together with an improved processability, as structural materials can be obtained over a wider range of composition than with native starch.

Abstract Background Autism spectrum disorder (ASD) is characterized by atypical behaviors in social environments and in reaction to changing events. While this dyad of symptoms is at the core of the pathology along with atypical sensory behaviors, most studies have investigated only one dimension. A focus on the sameness dimension has shown that intolerance to change is related to an atypical pre-attentional detection of irregularity. In the present study, we addressed the same process in response to emotional change in order to evaluate the interplay between alterations of change detection and socio-emotional processing in children and adults with autism. Methods Brain responses to neutral and emotional prosodic deviancies (mismatch negativity (MMN) and P3a, reflecting change detection and orientation of attention toward change, respectively) were recorded in children and adults with autism and in controls. Comparison of neutral and emotional conditions allowed distinguishing between general deviancy and emotional deviancy effects. Moreover, brain responses to the same neutral and emotional stimuli were recorded when they were not deviants to evaluate the sensory processing of these vocal stimuli. Results In controls, change detection was modulated by prosody: in children, this was characterized by a lateralization of emotional MMN to the right hemisphere, and in adults, by an earlier MMN for emotional deviancy than for neutral deviancy. In ASD, an overall atypical change detection was observed with an earlier MMN and a larger P3a compared to controls suggesting an unusual pre-attentional orientation toward any changes in the auditory environment. Moreover, in children with autism, deviancy detection depicted reduced MMN amplitude. In addition in children with autism, contrary to adults with autism, no modulation of the MMN by prosody was present and sensory processing of both neutral and emotional vocal stimuli appeared atypical. Conclusions Overall, change detection remains altered in people with autism. However, differences between children and adults with ASD evidence a trend toward normalization of vocal processing and of the automatic detection of emotion deviancy with age.

Objective: To evaluate the feasibility of the implementation of a commercial rapid molecular diagnostic test (Xpert MTB/RIF) for the routine diagnosis of smear-negative or extrapulmonary tuberculosis (TB) and its diagnostic accuracy, and to assess HIV prevalence in a real-life setting in Madagascar. This study was set in a tertiary care hospital in Madagascar. Methods: A prospective cohort study was conducted of all consecutive cases with suspected smear-negative and/or extrapulmonary TB over a 2-year period. Cases were classified as proven, probable, or possible TB cases, or as having an alternative diagnosis. Results: Of the 363 patients included, 183 (50.4%) had suspected smear-negative pulmonary TB and 180 (49.6%) had suspected extrapulmonary TB. For proven cases, the sensitivity, specificity, positive and negative predictive values of Xpert MTB/RIF were 82.4%, 98.8%, 98.3%, and 86.6%, respectively; for proven and probable cases grouped together, these values were 65%, 98.8%, 98.5%, and 64%, respectively. The diagnostic accuracy was slightly lower for extrapulmonary TB compared to smear-negative pulmonary TB. The prevalence of HIV infection was 12.1%, but almost half of these cases did not have TB (alternative diagnosis group). Conclusions: The implementation of a rapid diagnosis programme for TB in a resource-poor setting is feasible. The performance of the Xpert-MTB/RIF was remarkable in this difficult-to-diagnose population. HIV prevalence in this study was much higher than the prevalence reported in the general population in Madagascar, in patients with TB and patients with conditions other than TB. Keywords: Extrapulmonary tuberculosis, Smear-negative pulmonary tuberculosis, HIV, Molecular diagnostic test, Low resource countries, Xpert MTB/RIF

Animal health planning activities are not always providing a satisfactory positive impact on herd health and welfare. Moreover, evaluating the impact of advisory programmes is complex due to multiple interacting elements that influence its outcome. Therefore, measuring solely health outcomes is not sufficient: the whole process of the implementation and use of such programmes should be evaluated. In order to evaluate the impact of an intervention with a Herd Health and Production Management (HHPM) programme a process evaluation framework was designed and used. The intervention involved 20 organic dairy cattle farmers and their advisors, in both France and Sweden. In both countries 20 organic dairy farms were selected as control herds. The evaluation of the HHPM programme was based on: (a) the compliance to the programme; (b) the programme’s functions influencing herd health management practices and stimulating dialogue between farmers and advisors; (c) its effectiveness in terms of improving herd health compared with control farms. Complete compliance to the programme was fulfilled by 21 out of 40 farmers–advisors. Results from a questionnaire showed that the programme functioned as intended (e.g. by allowing early identification of herd health problems), stimulated change in farmers’ herd health management practices and farmer–advisor dialogue. Even though the majority of the users perceived that the programme contributed to herd health improvements, no significant differences in health outcomes were found when compared with control farms 12 months after the start of the intervention. The programme allowed creating an environment promoting the exchange of information between farmers and advisors, necessary to define pertinent advice in a farm-specific situation. Future research should aim at improving methods for the evaluation of the effect of advisory programmes, by identifying early indicators for effective advice and developing methods to evaluate the quality of advisory situations without interfering with them.

Abstract Background Post-transplant diabetes is a frequent and serious complication of kidney transplantation. There is currently no treatment to prevent or delay the disease. Nevertheless, identification of risk factors make it possible to target a population at risk of developing de novo diabetes. We hypothesized that a short-term treatment with vildagliptin may prevent new onset diabetes after transplantation (NODAT) in high-risk patients. Methods/design This is a multicenter, double-blind, placebo-controlled randomized clinical trial. Patients undergoing first kidney transplantation will be included from ten French transplant centers. Included patients will be randomized (1:1) to receive either vildagliptin 100 or 50 mg/day (depending on glomerular filtration rate) during 2 months (the first dose being administered before entering the operating theatres) or placebo. Additional antidiabetic therapy could be administered according to glycemic control. The primary outcome is the proportion of diabetic patients 1 year after transplantation, defined as patients receiving a diabetic treatment, or having a fasting glucose above 7 mmol/l, and/or with an abnormal oral glucose tolerance test. Secondary outcomes include glycated hemoglobin, the occurrence of acute rejection, infection, graft loss and patient death at 3 months, 6 months, and 12 months after transplantation. Outcomes will be correlated to clinical and general characteristics of the patient, cardiovascular history, nephropathy, dialysis history, transplantation data, biological data, health-related quality of life, and the cost-effectiveness of prevention of diabetes with vildagliptin. Discussion We have scarce data on the pharmacological prevention of post-transplant diabetes. If our hypothesis is verified, our results will have a direct application in clinical practice and could limit diabetes-associated morbidity, reduce cardiovascular complications, increase quality of life of renal transplant patients, and consequently promote graft and patient survival. Our results may possibly serve for non-transplant patients carrying a high-risk of diabetes associated with other co-morbidities. Trial registration ClinicalTrials.gov, NCT02849899. Registered on 8 February 2016.

Purpose: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT). Patients and methods: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry. Results: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (± standard deviation) for RIS (53.7 ± 16.0 Gy) and control patients (57.1 ± 15.1 Gy) (p = .053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5–55.7] and 22.3% [3.8–52.2] (p = .0008). Thus, patients with a RILA >21.3% are less likely to develop RIS (p

Abstract Determining herbage intake is pivotal for studies on grazing ecology. Direct observation of animals allows describing the interactions of animals with the pastoral environment along the complex grazing process. The objectives of the study were to evaluate the reliability of the continuous bite monitoring (CBM) method in determining herbage intake in grazing sheep compared to the standard double‐weighing technique method during 45‐min feeding bouts; evaluate the degree of agreement between the two techniques; and to test the effect of different potential sources of variation on the reliability of the CBM. The CBM method has been used to describe the intake behavior of grazing herbivores. In this study, we evaluated a new approach to this method, that is, whether it is a good proxy for determining the intake of grazing animals. Three experiments with grazing sheep were carried out in which we tested for different sources of variations, such as the number of observers, level of detail of bite coding grid, forage species, forage allowance, sward surface height heterogeneity, experiment site, and animal weight, to determine the short‐term intake rate (45 min). Observer (Pexp1 = 0.018, Pexp2 = 0.078, and Pexp3 = 0.006), sward surface height (Pexp2