Predictive value of nonspecific bronchial responsiveness in occupational asthma

BACKGROUND: The diagnosis of occupational asthma (OA) can be challenging and needs a stepwise approach. However, the predictive value of the methacholine challenge has never been addressed specifically in this context. OBJECTIVE: We sought to evaluate the sensitivity, specificity, and positive and negative predictive values of the methacholine challenge in OA. METHODS: A Canadian database was used to review 1012 cases of workers referred for a suspicion of OA between 1983 and 2011 and having had a specific inhalation challenge. We calculated the sensitivity, specificity, and positive and negative predictive values of methacholine challenges at baseline of the specific inhalation challenge, at the workplace, and outside work. RESULTS: At baseline, the methacholine challenge showed an overall sensitivity of 80.2% and a specificity of 47.1%, with positive and negative predictive values of 36.5% and 86.3%, respectively. Among the 430 subjects who were still working, the baseline measures displayed a sensitivity of 95.4%, a specificity of 40.1%, and positive and negative predictive values of 41.1% and 95.2%, respectively. Among the 582 subjects tested outside work, the baseline measures demonstrated a sensitivity and specificity of 66.7% and 52%, respectively, and positive and negative predictive values of 31.9% and 82.2%, respectively. When considering all subjects tested by a methacholine challenge at least once while at work (479), the sensitivity, specificity, and positive and negative predictive values were 98.1%, 39.1%, and 44.0% and 97.7%, respectively. CONCLUSION: A negative methacholine challenge in a patient still exposed to the causative agent at work makes the diagnosis of OA very unlikely

The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington’s disease

Objective Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on huntingtin aggregation and levels. Results We found that CYP46A1 reduces the quantity and size of mutant huntingtin aggregates in cells, as well as the levels of mutant huntingtin protein. Additionally, our results suggest that the observed beneficial effects of CYP46A1 in HD cells are linked to the activation of autophagy. Taken together, our results further demonstrate that CYP46A1 is a pertinent target to counteract HD progression.This work was supported by Brainvectis and E.rare: E-Rare Joint Transnational Call for Proposals 2017 “Transnational Research Projects for Innovative Therapeutic Approaches for Rare Diseases”. CN laboratory is supported by the French Muscular Dystrophy Association (AFM-Téléthon), the Ataxia UK, and the Fundação para a Ciência e Tecnologia (project ALG-01-0145-FEDER-29480 “SeGrPolyQ”). AM is supported by a Ph.D. fellowship from FCT (SFRH/BD/133192/2017)info:eu-repo/semantics/publishedVersio

Evaluation of Doppler Shifts to Improve the Accuracy of Primary Atomic Fountain Clocks

We demonstrate agreement between measurements and ab initio calculations of the frequency shifts caused by distributed cavity phase variations in the microwave cavity of a primary atomic fountain clock. Experimental verification of the finite element models of the cavities gives the first quantitative evaluation of this leading uncertainty and allows it to be reduced to delta nu / nu = 8.4\times10^-17. Applying these experimental techniques to clocks with improved microwave cavities will yield negligible distributed cavity phase uncertainties, less than \pm1\times10^-17.Comment: To appear in PR

Improving adhesion strength analysis by the combination of ultrasonic and mechanical tests on single lap joints.

International audienceThe aim of this paper is to improve knowledge about adhesion strength in single-lap joints by comparison of data from both Non Destructive Testing (NDT) and standard mechanical tests. study presents a high-frequency ultrasonic imaging of aluminum-epoxy-aluminum joints that carefully chemically prepared using two different surface treatments of the aluminum substrate: silanization and chromic-sulfuric etching. The surface energy of the treated substrate is complete set of ultrasonic data are obtained using high-frequency focused transducers. After inspection, single-lap shear tests were performed, and the mechanical strength of each joint is determined. The good cor relations among the surface measurements, the mechanical tests and ultrasonic results are presented and discussed. The demonstration of a close correlation between ultrasonic images obtained at high frequency and the fracture surface is promising

Développement de la pratique infirmière avancée dans le système de santé du Bénin : une exploration contextuelle inspirée de l’Ethnonursing de Leininger et guidée par le modèle PEPPA

Introduction: The reform of the training system in Nursing and Midwifery Sciences (NMS) in Benin made it possible to train nurses at the academic master's level in the Advanced Practice Nurse (APN) profile. However, despite the recognition of this new training on an academic level, the role of the APN in the health system where these nurses will be called upon to practice in a multidisciplinary team at the heart of a very diversified medical and nursing culture and practices, is not yet clarified.   Objectives: 1- Identify the areas of intervention, scope of action, roles, mandates and possible activities of the APN, as well as the factors favorable and unfavorable to the development of Advanced Nursing Practice (ANP) in the Benin health system; 2- Determine the constituent elements of a formal and regulatory framework for the exercise of ANP in Benin. Methods: This qualitative research based on Leininger's theory of universality and diversity of care (1991) will also be based on the PEPPA model (Participatory, Evidence-Based, Patient-Focused Process for Advanced Practice Nursing) proposed by Bryant-Lukosius and Dicenso (2004) for sequencing the stages of development, implementation and evaluation of a new APN role. Semi-directed individual interviews and focused groups with nurses and midwives of Beninese nationality holding a master's degree in NMS will be conducted. Self-administered questionnaires and collection of texts will be used to collect data from health personnel and managers of clinical care structures and services. Discussion and Research Spin-offs: This study will identify the benchmarks that will support the implementation of the APN role in Benin's health system, clarifying its areas of intervention, scope of action, mandates and possible activities, as well as the context necessary for its implementation.Introduction : La réforme du système de formation en sciences infirmières et obstétricales (SIO) au Bénin a permis de former des infirmiers de niveau maitrise académique dans le profil infirmière en pratique avancée (IPA). Cependant, malgré la reconnaissance de cette nouvelle formation sur le plan académique, le rôle de l’IPA dans le système de santé où ces infirmiers sont appelés à exercer dans une équipe multidisciplinaire au cœur d’une culture et de pratiques médicales et infirmières très diversifiées n’est pas encore clarifié. Objectifs : 1- Identifier les domaines d’intervention, les périmètres d’action, les rôles, les mandats et les activités possibles de l’IPA, ainsi que les facteurs favorables et défavorables au développement de la pratique infirmière avancée (PIA) dans le système de santé du Bénin; 2- Déterminer les éléments constitutifs d’un cadre formel et réglementaire d’exercice de la PIA au Bénin. Méthodes : Cette recherche qualitative basée sur la théorie de l’universalité et de la diversité des soins de Leininger (1991) s’appuiera sur le modèle PEPPA (Participatory, Evidence-Based, Patient-Focused Process for Advanced Practice Nursing) proposé par Bryant-Lukosius et Dicenso (2004) pour la séquence des étapes de développement, d’implantation et d’évaluation d’un nouveau rôle d’IPA. Des entrevues individuelles semi-dirigées et groupes focalisés auprès des infirmiers et sages-femmes de nationalité béninoise titulaires d’une maitrise en SIO seront réalisés. Des questionnaires auto-administrés et un recueil de textes permettront de collecter des données auprès du personnel de santé et des responsables des structures et services de soins cliniques. Discussion et retombées anticipées : Cette étude permettra d’identifier les balises qui soutiendront l’implantation du rôle de l’IPA dans le système de santé du Bénin, clarifiant ses domaines d’intervention, ses périmètres d’action, ses mandats et activités possibles, ainsi que le contexte nécessaire pour son implantation

Insulin resistance and associated factors among HIV-infected patients in sub-Saharan Africa: a cross sectional study from Cameroon

BACKGROUND: Little is known on the magnitude and correlates of insulin resistance in HIV-infected people in Africa. We determined the prevalence of insulin resistance and investigated associated factors in HIV-infected adult Cameroonians. METHODS: We conducted a cross-sectional study at the Yaoundé Central Hospital, Cameroon; during which we enrolled HIV-infected people aged 30 to 74 years with no previous history of cardiovascular disease. An homeostatic model assessment of insulin resistance (HOMA-IR) like index served to assess insulin sensitivity with insulin resistance defined by values of 2.1 or higher. RESULTS: We included 452 patients (20% men). Their mean age was 44.4 ± 9.8 years and 88.5% of them were on antiretroviral therapy (93.3% on first line regimen including Zidovudine, lamivudine and Efavirenz/Nevirapine). Of all participants, 28.5% were overweight, 19.5% had obesity and 2.0% had diabetes. The prevalence of insulin resistance was 47.3% without any difference between patients on ART and those ART-naïve (48.5% vs. 38.5%; p = 0.480). Obesity was the only factor independently associated with insulin resistance (adjusted odds ratio: 2.28; 95% confidence interval: 1.10-4.72). CONCLUSION: Insulin resistance is present in nearly half of HIV-infected patients in Cameroon despite a low prevalence rate of diabetes, and is associated with obesity

Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review

Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients’ characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05–1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6–13/20 vs. 10–18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use