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To ensure optimal resource allocation in technology demonstration projects, the evaluation of demonstrators of various maturity, scale, and nature has to be carried out. Most of the existing approaches focus on risk assessment or projected financial return; the need for a tool supporting multi-facet projects evaluation has been identified. This paper presents R2L framework based on three major criteria, defined in detail: Leap Potential, Learning, and Risk. The framework was applied to a real flight-test demonstrator project during workshops in a major aerospace company.

In 2021, smoking was considered to be the leading cause of avoidable death in the world, causing numerous pathologies. The rate of smoking in French department of Finistère is high, and the ARS (regional health authority) has funded a prevention campaign for a tobacco-free hospital and campus in Brest. Some health students' smoke (17.8%) and/or vape (5.6%). The aim of this article was to study the middle-term impact of the Smokefree campus prevention campaign.A descriptive cross-sectional study by self-administered questionnaire was carried out between 24/01/2022 and 21/02/2022, using Sphinx software.The participation rates were 29.9% (students) and 29.4% (professionals). Among students, 12.6% were smokers, as were 13.3% of professionals. Just over 75% of respondents were aware of Smokefree campus, and 75% knew that it concerned both vaping and smoking. Nearly 60% of respondents thought that the smoke-free campus program could improve coherence between (a) the care training function of the faculty and the IFPS and (b) its exemplarity on the issue of smoking. Among smokers, 44% thought that quitting smoking or vaping during working hours was possible, while and 44% thought that it was possible to quit, whatever the setting. For student smokers, this was contemplated by only 18.2%, and deemed possible by 24%.While the smoking rate has remained relatively high, the Smokefree campus campaign is widely known and understood. It is important to pursue this kind of prevention campaign insofar as it could have a positive impact on the health of future caregivers and their patients.

Resume Introduction Le tabagisme est l’une des principales causes evitables de mort dans le monde. Certaines etudes ont montre, chez les soignants et les etudiants en sante, des prevalences du tabagisme proches de celle de la population generale. L’objet de cet article etait d’etudier la prevalence aupres des etudiants en sante (medecine, odontologie, kinesitherapie, soins infirmiers) d’une universite et d’un CHRU en France. Materiel et methode Il s’agissait d’une etude transversale par auto-questionnaire. Cette etude se faisait dans le cadre d’une campagne soutenue par l’Agence Regionale de Sante Bretagne. Resultats Le taux de participation etait de 76,4 % soit 1349 repondants sur 1766 etudiants en sante interroges. La prevalence du tabagisme etait de 17,8 % et celle du vapotage de 5,6 %. Les etudiants en soins infirmiers fumaient et vapotaient plus que les etudiants des autres filieres : respectivement, pour le tabagisme, 21,8 % (73/335) vs 16,5 % (167/1014) (p Conclusion Le taux de tabagisme etait important, mais comparable aux donnees concernant les etudiants de sante. Les etudiants en soins infirmiers etaient significativement plus fumeurs, notamment en derniere annee. Le taux de vapotage etait plus eleve que dans les autres etudes.

The recommended treatment for Eating Disorders (EDs) is multidisciplinary and multimodal. Nonetheless, the complex linkage of the different disciplines involved is not necessarily simple. We analyzed the experience of healthcare professionals faced with psychiatric and psychological symptoms in adolescents with EDs in two "multidisciplinary" inpatient units embedded predominantly in different paradigms - one pediatric and one psychiatric.Qualitative analysis of 20 healthcare staff members' interviews from different professional backgrounds working in inpatient units for EDs in Montreal (Canada) and Paris (France).The "Complex patients" theme discusses the need for a global approach to the multiplicity of symptoms presented by these patients. "Management and its limits" describes the daily management of psychiatric symptoms in both units. "Psychiatry and Adolescent medicine: from opposition to collaboration" describes the different levels at which these disciplines work together and how this cooperation may be evolving.The complex entanglement intrinsic in EDs of the patients' somatic, psychosocial, psychiatric, and adolescent problems requires collaboration between disciplines, but the modalities of this collaboration are multiple and evolve non-linearly in specialized treatment units. A multilevel approach must be offered, with the degree of collaboration (multidisciplinary, interdisciplinary and transdisciplinary) appropriate to the complexity of each adolescent's issues.

COVID-19 (Coronavirus Disease 2019), the disease caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) is an ongoing global public health emergency. As understanding of the health effects of COVID-19 has improved, companies and agencies worldwide have worked together to identify therapeutic approaches, fast-track clinical trials and pathways for emergency use, and approve therapies for patients. This work has resulted in therapies that not only improve survival, reduce time of hospitalization, and time to recovery, but also include preventative measures, such as vaccines. This manuscript discusses development programs for 3 products that are approved or authorized for emergency use at the time of writing: VEKLURY (remdesivir, direct-acting antiviral from Gilead Sciences, Inc.), REGEN-COV (casirivimab and imdevimab antibody cocktail from Regeneron Pharmaceuticals Inc.), and Comirnaty (Pfizer-BioNTech COVID-19 Vaccine [Pfizer, Inc.-BioNTech]), and perspectives from the U.S. Food and Drug Administration.

Historically, identifying carcinogens has relied primarily on tumor studies in rodents, which require enormous resources in both money and time. In silico models have been developed for predicting rodent carcinogens but have not yet found general regulatory acceptance, in part due to the lack of a generally accepted protocol for performing such an assessment as well as limitations in predictive performance and scope. There remains a need for additional, improved in silico carcinogenicity models, especially ones that are more human-relevant, for use in research and regulatory decision-making. As part of an international effort to develop in silico toxicological protocols, a consortium of toxicologists, computational scientists, and regulatory scientists across several industries and governmental agencies evaluated the extent to which in silico models exist for each of the recently defined 10 key characteristics (KCs) of carcinogens. This position paper summarizes the current status of in silico tools for the assessment of each KC and identifies the data gaps that need to be addressed before a comprehensive in silico carcinogenicity protocol can be developed for regulatory use.

In the framework of a "tobacco-free hospital and campus" campaign, we conducted a study on the prevalence of smoking and vaping among a university hospital (CHRU) staff. The study took place in late 2020 (from 1 September to 15 December), and involved self-assessment of the impact of the covid-19 pandemic on smoking.A cross-sectional study was carried out using an online questionnaire, which was distributed by email and QR code posting and included socio-professional details as well as data on participants' smoking and vaping.There were 782 responses, representing a participation rate of 13.5%. The sample included 73.3% women and 22.7% men; 28.9% nurses, 24.9% medical staff, 3.6% nursing assistants and 42.6% other professional categories. The overall smoking rate was 13%. Sixty-two (7.9%) participants vaped; 37 (5%) vaped exclusively, 25 (3.2%) combined smoking and vaping. Men smoked more than women: 23.7% vs. 9.4% (P 0.01). Medical staff smoked and vaped less than other categories; 6.2% vs 14.8% (P 0.01) and 4.1% vs 9.1% respectively (P=0.02). Doctors were more often non-smokers: OR=2.71 (95% CI: 1.14-6.46). Among smokers, 25% said they had increased their cigarette consumption during the covid-19 pandemic, frequently as a means of combating stress or fatigue.This study showed a lower smoking rate than in the literature, possibly due to the high participation of physicians. Ours were the initial estimates of vaping among hospital staff.

Background: Hemodialysis patients had to face numerous challenges during the COVID-19 pandemic. They are at increased risk of severe complications of COVID-19 and continued to visit hospitals thrice weekly, increasing their risk of being infected. The objective of this study was to document the impact of the COVID-19 on patient's experience in hemodialysis in Quebec. Methods: Between November 2020 and May 2021, we conducted semi-structured interviews with 20 patients who were undergoing dialysis treatments in six hemodialysis units in Montreal. Interviews were transcribed and analyzed using thematic content analysis. Results: Patients were satisfied by the measures implemented within their units in order to prevent COVID-19 outbreaks, such as making masks mandatory, restricting access to the dialysis ward, and even limiting the number of accompanying persons allowed. Participants reported that following the public health guidelines (social distancing, wearing a mask and washing hands) was easy and important in order to ensure their own and their family members' safety. Because of this, participants were more likely to refuse to see their family resulting in feeling of isolation. This was particularly relevant for Indigenous patients who were having their hemodialysis treatment away from their home and family. This sub-group experienced particular issues due to the prolonged remoteness from their loved ones, change in their hemodialysis center and with the measures put in place by the hotel they were residing at. Even though their usual routine outside of dialysis might have changed due to the pandemic, hemodialysis treatments allowed patients to keep a certain normality in their lives. Positive consequences were mentioned such as frequent contact through telemedicine and the existing solidarity between patients during the pandemics. Conclusions: Patients undergoing hemodialysis faced particular challenges due to the COVID-19 pandemic. Nonetheless, they showed great resilience in their capacity to adapt to the new reality of their hemodialysis treatments.

Smoking is one of the leading causes of preventable death worldwide. Data from the literature show that caregivers and health students have a high prevalence. The purpose of this article was to study the prevalence among health students (medicine, dentistry, physiotherapy, nursing) at a University and a Teaching Hospital in France.This was a cross-sectional study using a self-administered questionnaire completed at the start of university meetings. This study was carried out as part of a campaign to combat smoking supported by the Brittany Regional Health Agency.The participation rate was 76.4%: 1349 respondents out of 1766 health students surveyed. The prevalence of smoking 17.8% and that of vaping 5.6%. Nursing students smoked and vaped more than students in other streams: respectively, for smoking, 21.8% (73/335) vs. 16.5% (167/1014) (P0.001), for vaping, 10.4% (35/335) vs. 4.0% (39/980) (P0.001). Students in 3rd year nursing smoked and vaped significantly more than those in the first 2 years (P=0.02 and P0.001).The smoking rate was high, but comparable to the data for health students. Nursing students were significantly greater smokers, especially in the last year. Their vaping rate was higher than in other studies.

Occupational toxicology is quite possibly one of the most challenging area in the field. Why? Because exposures are often much larger than in other setting, occur via different routes, and compounds can be extremely potent and sometimes have very limited data. In this chapter we will review some basic principles as they apply to occupational toxicology and go through five case studies to illustrate the complexity and challenges associated with being an occupational toxicologist. The case studies will include 8-methoxypsoralen, lead, crystalline silica, diacetyl, and soot. Finally we will review some of the key approaches used in the field to assess and mitigate the risk associated with occupational exposures.

The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information.

The field of toxicoepigenetics is rapidly emerging to provide new insights into the relationship between environmental factors, the epigenome, and public health. Toxicoepigenetic data have the potential to revolutionize our understanding of environmental exposure effects and susceptibility. Studies in recent years have demonstrated that exposure to air pollution alters epigenetic modification states; however, continued advancement of the field is limited by the intrinsic complexity of the epigenome and inherent limitations of different types of studies (epidemiological, clinical, and in vitro) that are used in toxicoepigenetics. Overcoming these challenges will require a concerted and collaborative effort between molecular and cellular biologists, toxicologists, epidemiologists, and risk assessors to develop a thorough and practical understanding of the relationship between air pollution exposure, the epigenome, and health effects. Here we review the current state of air pollution epigenetics and discuss perspectives on the necessary steps to move the field forward to determine the role that the epigenome plays in air pollution exposure effects and susceptibility.

In the United States, the 1970s and 1980s were characterized by growing interest in conservation tillage systems, both from their adoption and adaptation by farmers and their development and evaluation by the agricultural research community. Of particular interest has been the no-tillage (NT) system. Under periodic tillage, the question arises as to the fate of short-term changes in soil properties when a NT soil is periodically plowed. East Lansing is situated in the south-central part of the lower peninsula of Michigan, approximately equidistant from three of the Great Lakes — Michigan, Huron, and Erie. Soil test K levels were in the medium range for Michigan soils. In 1987, soil test K in NT was highly stratified in the surface 200 mm. Plowing a soil in NT management redistributed soil nutrients within the plow layer. The surface stratification of NT was not entirely lost when plowed and was increased over time, relative to conventional tillage.

Background: The APS ACTION International Clinical Database and Repository includes a secure web-based data capture system storing patient information including demographics, antiphospholipid antibodies (aPL)-related medical history, and aPL tests. Despite efforts at harmonization, inter-assay variability remains a problem in aPL testing. As a clinical repository open to researchers, ensuring comparability between assays and consistency in results between APS ACTION laboratories is essential to the validity of studies emerging from this network. Objective: To assess the level of agreement between an aPL-registry inclusion and core laboratory (core lab) anticardiolipin antibody (aCL) and anti-β 2 -glycoprotein-I antibody (aβ 2 GPI) ELISA testing results. Methods: Patients are recruited from 25 international centers based on positive aPL tests at inclusion. All samples are retested at the corresponding national APS ACTION core lab to confirm aPL positivity based on standard validated protocols. We analysed the categorical agreement, degree of linear association, and correlation between inclusion (local laboratory) and core lab aPL tests. Samples were included in this study only if results of aPL testing with ELISA at baseline were available. Results: 497 registry samples underwent confirmatory aPL tests. Categorical agreement between the inclusion and core lab values, as expressed by Cohen's kappa coefficients, ranged between 0.61 and 0.80 (as substantial agreement). The correlation between quantitative results in the aCL and aβ 2 GPI was better for IgM and IgA compared to IgG (Spearman rho 0.789 and 0.666 vs. 0.600 for aCL and rho 0.892 and 0.744 vs. 0.432 for aβ 2 GPI). Conclusions: The results of inclusion for aCL and aβ 2 GPI tests used for recruitment into the registry were in agreement to the results obtained by the APS ACTION core laboratories; aCL and aβ 2 GPI results showed very good categorical agreement. This agreement increased when considering high titer (>40 units) samples. APS ACTION is a reliable and useful research resource for APS. © 2019 Elsevier Ltd

An array of monolithic wide-tunable lasers is integrated using selective area growth to shift the bandgap of their gain section. A gap-free tuning is demonstrated from the combination of the tuning ranges of the lasers, and single-mode operation is verified.

Selective area growth is used for the first time in the TU/e generic integration platform to modify independently the bandgap of active sections. A chip combining 4 tunable lasers with shifted wavelength ranges has been fabricated. A 96 nm wide tuning range is demonstrated.

BACKGROUND: There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission. METHODS: In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264. FINDINGS: Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0-3·5). At baseline, 6816 patients (56·8%) had diabetes, 3991 (33·3%) prediabetes, and 1193 (9·9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg (95% CI 2·3-2·9) for those with diabetes, 2·8 kg (2·5-3·2) for those with prediabetes, and 3·3 kg (2·6-4·0) for those with normoglycaemia (p

Data Availability: Data, associated metadata, and calculation tools are available from the corresponding author (dries.knapen@uantwerpen.be). Supplemental Data: The Supplemental Data are available on the Wiley Online Library at DOI: https://doi.org/10.1002/etc.4125. Copyright © 2018 The Authors. Based on the results of a SETAC-sponsored Horizon Scanning exercise focused on advancing the adverse outcome pathway (AOP) framework, the development of guidance related to AOP network development was identified as a critical need. This not only included questions focusing directly on AOP networks, but also on related topics such as mixture toxicity assessment and the implementation of feedback loops within the AOP framework. A set of two papers has been developed to begin exploring these concepts. In the present paper (part I), derivation of AOP networks is considered in the context of how it differs from development of individual AOPs. We then propose the use of filters and layers to tailor AOP networks to suit the needs of a given research question or application. We briefly introduce a number of analytical approaches that may be used to characterize the structure of AOP networks. These analytical concepts are further described in a dedicated, complementary paper (part II). Finally, we present a number of case studies that illustrate concepts underlying development, analysis and application of AOP networks. The concepts described in this paper, and in its companion paper focused on AOP network analytics, are intended to serve as a starting point for further development of the AOP network concept, but also to catalyze AOP network development and application by the different stakeholder communities. This article is protected by copyright. All rights reserved.

Background. CD8 T-cell counts remain elevated in human immunodeficiency virus (HIV) infection even after long-term antiretroviral therapy (ART), which is associated with an increased risk of non–AIDS-related events. We assessed the impact of ART initiation in early versus chronic HIV infection on trajectories of CD8 cell counts over time. Methods. Of 280 individuals enrolled during primary HIV infection (PHI), 251 were followed up for 24 months; 84 started ART before 6 months of infection (eART), 49 started between 6 and 24 months, and 118 remained untreated. Plasma HIV viral load (VL), CD4 and CD8 cell counts were assessed at each study visit. CD8 counts were also examined in 182 age-matched HIV-infected individuals who started ART during chronic infection and maintained undetectable plasma VL for ≥5 years. Results. At PHI baseline, higher CD8 cell counts were associated with more recent infection (P = .02), higher CD4 cell counts (P < .001), and higher VL (P < .001). The CD8 count in the eART group decreased from 797 to 588 cells/µL over 24 months (P < .001), to a level lower than that in untreated PHI (834 cells/µL; P = .004) or in long-term–treated patients with chronic HIV infection (743 cells/µL; P = .047). More prominent CD4 T-cell recovery was observed in the eART group than in the delayed ART group. Conclusions. ART initiated in early HIV infection is associated with improved resolution of CD8 T-cell elevation compared with long-term ART initiated in chronic infection. Early ART may help reduce the risk of non–AIDS-related events by alleviating this elevation.

In silico toxicology (IST) approaches to rapidly assess chemical hazard, and usage of such methods is increasing in all applications but especially for regulatory submissions, such as for assessing chemicals under REACH as well as the ICH M7 guideline for drug impurities. There are a number of obstacles to performing an IST assessment, including uncertainty in how such an assessment and associated expert review should be performed or what is fit for purpose, as well as a lack of confidence that the results will be accepted by colleagues, collaborators and regulatory authorities. To address this, a project to develop a series of IST protocols for different hazard endpoints has been initiated and this paper describes the genetic toxicity in silico (GIST) protocol. The protocol outlines a hazard assessment framework including key effects/mechanisms and their relationships to endpoints such as gene mutation and clastogenicity. IST models and data are reviewed that support the assessment of these effects/mechanisms along with defined approaches for combining the information and evaluating the confidence in the assessment. This protocol has been developed through a consortium of toxicologists, computational scientists, and regulatory scientists across several industries to support the implementation and acceptance of in silico approaches.

Scanning tunneling microscopy (STM) observations resolve the structure and dynamics of metallic glass Cu$_{100-x}$Hf$_{x}$ films and demonstrate STM control of aging at a metallic glass surface. Surface clusters exhibit heterogeneous hopping dynamics. Low Hf concentration films feature an aged surface of larger, slower clusters. Argon ion-sputtering destroys the aged configuration, yielding a surface in constant fluctuation. STM can locally restore the relaxed state, allowing for nanoscale lithographic definition of aged sections., Comment: 10 pages, 3 figures, 9 pages supplement 6 supplemental figures, 3 supplemental movies

Studies on therapeutic drug disposition in humans have shown significant alterations as the result of pregnancy. However, it is not known whether pesticide metabolic capacity changes throughout pregnancy, which could affect exposure of the developing brain. We sought to determine the effect of pregnancy on the expression of hepatic enzymes involved in the metabolism of pesticides. Livers were collected from virgin and pregnant C57BL/6 mice at gestational days (GD)7, GD11, GD14, GD17, and postpartum days (PD)1, PD15, and PD30. Relative mRNA expression of several enzymes involved in the metabolism of pesticides, including hepatic cytochromes (Cyp) P450s, carboxylesterases (Ces), and paraoxonase 1 (Pon1), were assessed in mice during gestation and the postpartum period. Compared with virgin mice, alterations in the expression occurred at multiple time points, with the largest changes observed on GD14. At this time point, the expression of most of the Cyps involved in pesticide metabolism in the liver (Cyp1a2, Cyp2d22, Cyp2c37, Cyp2c50, Cyp2c54, and Cyp3a11) were downregulated by 30% or more. Expression of various Ces isoforms and Pon1 were also decreased along with Pon1 activity. These data demonstrate significant alterations in the expression of key enzymes that detoxify pesticides during pregnancy, which could alter exposure of developing animals to these chemicals.

Background: Lead (Pb) exposure has been associated with a host of pathological conditions in humans. In rodents Pb exposure has been shown to alter the hypothalamic–pituitary–adrenal (HPA) axis function. Objective: We investigated the effects of lead on responses of the HPA axis to a psychosocial laboratory stressor administered to Pb-exposed workers. Methods: Seventy male participants completed the Trier Social Stress Test (TSST). Serum cortisol (CORT) and plasma adrenocorticotropic hormone (ACTH) were assessed in response to and during recovery from the stressor. We measured Pb in blood, a biomarker of recent exposure, and in tibia bone by X-ray fluorescence (XRF), a biomarker of chronic exposure. Results: The TSST induced statistically significant increases in ACTH and CORT in the participants. At baseline, ACTH was not significantly higher (p = 0.052) in participants with higher blood Pb concentration, but CORT was significantly lower in these participants (p = 0.016). Adjusted linear regression models indicated a positive association between blood and bone Pb and the increase in ACTH in response to stress. However, Pb was not strongly associated with changes in CORT in response to stress. Pb was also associated with the ACTH:CORT ratio at baseline and throughout the course of the protocol, suggesting an adrenal hyporesponsiveness in participants with higher Pb concentrations. Conclusion: The altered HPA-axis stress response observed in participants exposed to higher levels of Pb further supports the idea that lead may contribute to a host of biological dysfunctions beyond the classical neurotoxic effects.

Resume Nous avons precedemment developpe l’autoquestionnaire FAQ, un outil adapte a partir de l’autoquestionnaire AQ de S. Baron-Cohen, destine a mettre en evidence des endophenotypes appartenant au spectre autistique chez les apparentes de sujets autistes. Nous avons montre que les reponses des parents d’enfants autistes differaient de celles des parents temoins, notamment dans le domaine de la socialisation. L’objectif de ce travail est de valider l’autoquestionnaire FAQ en population normale et de confirmer nos resultats concernant le groupe des parents d’enfants autistes sur des effectifs plus importants. Parmi les parents,127 parents temoins et 66 parents d’enfants autistes ont rempli l’autoquestionnaire FAQ, pour la validation statistique de l’outil et la comparaison des resultats obtenus par les deux groupes. Nous montrons que FAQ presente deux facteurs principaux, le premier correspondant aux dimensions « socialisation et communication », le second aux dimensions « rigidite et imagination », avec une bonne fidelite test-retest. Nous confirmons par ailleurs les resultats obtenus lors de notre premiere etude concernant la comparaison entre parents d’enfants autistes et parents du groupe temoin sur de plus grands effectifs, en identifiant une difference tres significative entre les deux groupes pour le facteur « communication et socialisation ». Nous montrons enfin que les scores obtenus par les parents d’enfants autistes n’evoluent pas significativement entre l’enfance et l’âge adulte, contrairement aux scores des parents temoins. FAQ est le premier autoquestionnaire valide en francais permettant de detecter des endophenotypes associes au spectre autistique chez les parents d’enfants autistes. Cet outil peut etre utile a la caracterisation du phenotype des apparentes dans le cadre d’etudes genetiques.

We report the case of a patient with rheumatoid arthritis (RA) on etanercept who presented with panniculitis and focal myositis as manifestations of disseminated histoplasmosis. Systematic search of the literature showed 11 additional case reports of disseminated histoplasmosis with tumour necrosis factor-alpha (TNFalpha) blockade therapy (infliximab, n = 8; etanercept, n = 3). Although disseminated histoplasmosis may manifest with classical symptoms of fever and respiratory complaints, it may also present atypically, such as with panniculitis and focal myositis. This review illustrates and emphasizes the importance of being highly suspicious for infection, including by opportunistic organisms, and to exclude such process in patients treated with a TNFalpha inhibitor when faced with unusual complications, even when an alternative aetiology appears plausible.

Resume L’autisme est une pathologie du developpement psychoaffectif d’origine polyfactorielle, associant une composante genetique et environnementale. Les facteurs de vulnerabilite genetique impliques dans l’autisme pourraient egalement contribuer aux troubles du langage ou de la socialisation, dont la frequence est accrue chez les apparentes de sujets autistes. Dans cette etude, nous avons construit et teste aupres d’un groupe de 20 parents d’enfants autistes et d’un groupe de 21 parents controles, la pertinence d’un autoquestionnaire visant la caracterisation d’un endophenotype parental, defini par la presence significative de « traits apparentes » aux troubles autistiques, dans les domaines de la socialisation, de la communication, de l’imagination et des interets restreints et stereotypes. Cet autoquestionnaire est apparu comme un outil facile et rapide d’utilisation, permettant de mettre en evidence de facon fine des « particularites endophenotypiques » chez des adultes ne presentant pas de psychopathologie averee, notamment dans le domaine de la socialisation. L’utilisation de cet autoquestionnaire pourrait permettre de prendre en compte la presence d’endophenotypes parentaux dans l’analyse des etudes de liaison genetique.

The bioavailability and toxicity of dissolved metals are closely linked to the metals' chemical speciation in solution. Normally the complexation of a metal by a ligand would be expected to decrease its bioavailability. The aqueous speciation of uranium undergoes tremendous changes within a pH range of 4 to 8 and in the presence of ligands commonly found in natural waters (carbonate, phosphate, hydroxide and natural organic matter). In the present project, we intend to establish links between speciation, medium composition and bioavailability of uranium. To study these links, we have chosen a unicellular green alga. Short-term metal uptake rates are determined in simple inorganic media with particular emphasis on the differentiation between adsorbed and intracellular metal. The Free-Ion Model (FIM) is tested to determine if U uptake is governed by the free uranyl species (UO2 2+ ) or if other species can be assimilated (i.e. passive diffusion of neutral, presumably lipophilic, species such as UO2 (OH)2 ; facilitated diffusion of metal bound to an assimilable ligand such as uranium-phosphate complexes). Results of our preliminary experiments indicate that complexation by phosphate decreases uranium bioavailability, as predicted by the FIM. However, uptake was stimulated when pH was increased from 5 to 7 in spite of the substantial decrease (55 → 0.02 %) in free uranyl ion concentration in solution.

There is a need to develop technology to allow the remediation of soil in polar regions that have been contaminated by hydrocarbon fuel spills. Bioremediation is potentially useful for this purpose, but has not been well demonstrated in polar regions. We investigated biopiles for on-site bioremediation of soil contaminated with Arctic diesel fuel in two independent small-scale field experiments at different sites on the Arctic tundra. The results were highly consistent with one another. In biopiles at both sites, extensive hydrocarbon removal occurred after one summer. After 1 year in treatments with optimal conditions, total petroleum hydrocarbons were reduced from 196 to below 10 mg per kg of soil at one site, and from 2,109 to 195 mg per kg of soil at the other site. Addition of ammonium chloride and sodium phosphate greatly stimulated hydrocarbon removal and indicates that biodegradation was the primary mechanism by which this was achieved. Inoculation with cold-adapted, mixed microbial cultures further stimulated hydrocarbon removal during the summer immediately following inoculation. At one site, soil temperature was monitored during the summer season, and a clear plastic cover increased biopile soil temperature, measured as degree-day accumulation, by 30-49%. Our results show that on-site bioremediation of fuel-contaminated soil at Arctic tundra sites is feasible.

Objective: To determine the incidence and clinical effects of antibodies that develop during treatment with natalizumab. Methods: In two randomized, double-blind, placebo-controlled studies (natalizumab safety and efficacy in relapsing remitting multiple sclerosis [MS, AFFIRM] and safety and efficacy of natalizumab in combination with interferon β-1a [INFβ1a] in patients with relapsing remitting MS [SENTINEL]) of patients with relapsing multiple sclerosis, blood samples were obtained at baseline and every 12 weeks to determine the presence of antibodies against natalizumab. Antibodies to natalizumab were measured using an ELISA. Patients were categorized as “transiently positive” if they had detectable antibodies (≥0.5 μg/mL) at a single time point or “persistently positive” if they had antibodies at two or more time points ≥6 weeks apart. Results: In the AFFIRM study, antibodies were detected in 57 of 625 (9%) of natalizumab-treated patients: Twenty (3%) were transiently positive and 37 (6%) were persistently positive. Persistently positive patients showed a loss of clinical efficacy as measured by disability progression ( p ≤ 0.05), relapse rate ( p = 0.009), and MRI ( p ≤ 0.05) compared with antibody-negative patients. In transiently positive patients, full efficacy was achieved after approximately 6 months of treatment, the time when patients were becoming antibody negative. The incidence of infusion-related adverse events was significantly higher in persistently positive patients. Results of SENTINEL were similar to AFFIRM, except with regard to sustained disability progression; differences between persistently positive and antibody-negative patients were not statistically significant. Conclusions: The incidence of persistent antibody positivity associated with natalizumab is 6%. Reduced clinical efficacy is apparent in persistently positive patients. Patients with a suboptimal clinical response or persistent infusion-related adverse events should be considered for antibody testing. GLOSSARY: BLQ = below the limit of quantification; EDSS = Expanded Disability Status Scale; Gd+ = gadolinium enhancing; IFNβ1a = interferon β-1a; MS = multiple sclerosis; MSFC = multiple sclerosis functional composite; OD = optical density.

In this paper, we present the study of the growth conditions of metamorphic GaAs on InP(0 0 1) substrate using gas source molecular beam epitaxy (GSMBE). We examined the influence of various growth parameters, such as growth temperature and Group V pressure, and determined optimized conditions to produce low roughness (11.6 A rms) GaAs. We also demonstrate the existence of a critical thickness limit under which dislocations are generated, or propagate, in the substrate. We experimented different types of post-growth cooling rates, annealing and observed their influence on the localization of the substrate dislocations. Altogether, these experiments indicate that the metamorphic growth of GaAs on InP is a valid approach for long wavelength vertical cavity surface emitting lasers.

Analysis of the potential of museums in environmental mediation Although from a theoretical point of view environmental education is already a well-explored field, its establishment is trickier, especially in schools. The scientific partners of schools appear therefore as relays in environmental education that can complete existing efforts and compensate certain deficiencies. Museums can offer a variety of environmental mediation techniques. The aim of this research is therefore to clarify this offer by canying out a typology of the different types of mediation aimed at schools. The first mediation is based on the protection of biodiversity and proposes activities with collections (dead or alive). The second mediation is based on the responsibility of pupils faced with environmental problems and is carried out through projects. Finally, the last type of mediation is based on enhancing value and on national and regional development, and invites local classes to reflect on the notion of heritage., Si l’éducation à l’environnement est un domaine déjà bien exploré d’un point de vue théorique, sa mise en place réelle est plus délicate, surtout en milieu scolaire. Les partenaires scientifiques de l’école apparaissent alors comme des relais d’éducation à l’environnement, qui permettent de compléter les efforts et de pallier à certains déficits. Ainsiles institutions muséales sont-elles susceptibles d’offrir une palette variée en matière de médiation environnementale. Le but de cette recherche est donc de clarifier cette offre en réalisant une typologie de ces différentes formes de médiation. Les résultats montrent ainsi l’existence de trois types de médiation en direction des scolaires. La première médiation est ancrée sur la préservation de la biodiversité et propose essen¬ tiellement des activités autour des collections (mortes ou vivantes). La deuxième médiation repose sur la responsabilisation des élèves face à des problèmes environnementaux, et ce par le biais de projets. Enfin le dernier type de médiation participe à la valorisation et l’aménagement d’un territoire en invitant les classes locales à réfléchir sur la notion de patrimoine., Análisis de las ofertas de las instituciones de los museos de mediación medio-ambientales Si la educación al medio es un campo bien explorado de un punto de vista teórico, su puesta en marcha real es más delicada, sobre todo en medio escolar. Los asociados científicos de la escuela aparecen entonces como relevo de la educación al medio, que permiten de completar los esfuerzos y rellenar ciertos déficit. Así las instituciones de los museos son susceptibles de ofrecer una paleta variada en materia de mediación del medio ambiente. El objetivo de esta investigación es pues, clarificar esta oferta, realizando una tipología de esas diferentes formas de mediación. Los resultados muestran así, la existencia de tres tipos de mediación en dirección de los escolares. La primera mediación está basada sobre la preservación de la biodiversidad y propone esencialmente actividades alrededor de las colecciones (muertas o vivas). La segunda mediación descansa sobre la responsabilización de los alumnos frente a los problemas del medio ambiente y es basada por el aspecto de los proyectos. Al fin, el último tipo de mediación participa a la valorización y a la disposición de un territorio invitando las clases locales a reflexionar sobre la noción de patrimonio., Fortin-Debart Cécile. Analyse de l'offre des institutions muséales en médiation environnementale . In: Aster, recherches en didactique des sciences expérimentales, n°29, 1999. L'école et ses partenaires scientifiques. pp. 85-100.

We present and give details about the conception and realization of the first monolithic long wavelength vertical-cavity surface-emitting laser (VCSEL) operating continuous wave at room temperature. This approach relies on two originalities: a metamorphic GaAs-AlAs distributed Bragg reflector and an injection through a reverse-biased tunnel junction. Record output powers as high as 1 mW and a maximum operating temperature of 47/spl deg/C have thus been achieved. Furthermore, in this paper, we present the optimization work on the different constituting parts of the VCSEL.

Background Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an α 4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. Methods We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. Results Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Kaplan–Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P

Compressively strained GaInAsP quantum wells (QW's), with a square potential profile and grown on InP substrates, have demonstrated their high potential for the improvement of 1.55-/spl mu/m lasers. Recently, we have proposed another approach which consists of creating a linear variation of the bandgap inside the well, by means of a linear variation in the As concentration. Calculations show that, in such a V-shaped structure: (1) the effective density of states related to the heavy hole bands is reduced compared to that of a large abrupt-shaped QW and (2) the overlap between the electron and the hole wavefunctions is expected to be greater than in a narrow abrupt-shaped QW. The consequences of these effects are described.

This study investigated the short-term memory of dynamic changes in acute pain using psychophysical methods. Pain intensity or unpleasantness induced by painful contact-heat stimuli of 8, 9, or 10 s was rated continuously during the stimulus or after a 14-s delay using an electronic visual analog scale in 10 healthy volunteers. Because the continuous visual analog scale time courses contained large amounts of redundant information, a principal component analysis was applied to characterize the main features inherent to both the concurrent rating and retrospective evaluations. Three components explained about 90% of the total variance across all trials and subjects, with the first component reflecting the global perceptual profile, and the second and third components explaining finer perceptual aspects (eg, changes in slope at onset and offset and shifts in peak latency). We postulate that these 3 principal components may provide some information about the structure of the mental representations of what one perceives, stores, and remembers during the course of few seconds. Analysis performed on the components confirmed significant memory distortions and revealed that the discriminative information about pain dimensions in concurrent ratings was partly or completely lost in retrospective ratings. Importantly, our results highlight individual differences affecting these memory processes. These results provide further evidence of the important transformations underlying the processing of pain in explicit memory and raise fundamental questions about the conversion of dynamic nociceptive signals into a mental representation of pain in perception and memory.