Posterior cortical atrophy : impact on daily living activities and exploration of a cognitive rehabilitation approach

Posterior cortical atrophy (PCA) is a neurodegenerative disease affecting the posterior region of the brain. Little is known about both the impact of PCA on functioning and how to support patients on a daily basis. The purpose of this study was to describe the functional profile of DD, a woman diagnosed with PCA, as well as to explore a pilot cognitive rehabilitation program designed to optimize functioning in daily living. The ADL Profile was used to assess the daily tasks that DD chose to undertake. Four operations, i.e. formulate a goal, plan, carry out and verify goal attainment, were scored for each task. Difficulties were observed during the execution of all tasks, as she struggled to find items or showed unsafe behaviors. Impairments were also seen in formulating a goal and planning, especially for less routine tasks. DD identified two tasks to be addressed in rehabilitation: setting the table and dealing cards. Learning was optimized using errorless learning and compensatory aids when setting the table, while dealing cards received no intervention. Only setting the table improved significantly with time. Further studies should be conducted to portray a wider functional profile of people living with PCA and develop effective rehabilitation programs

Analysis of the dust evolution in the circumstellar disks of TTauri stars

We present a compositional analysis of 8-13um spectra of 32 young stellar objects (YSOs). Our sample consists of 5 intermediate-mass stars and 27 low-mass stars. While the spectra and first scientific results have already been published by Przygodda et al. (2003) and Kessler-Silacci et al. (2004) we perform a more detailed analysis of the 10um silicate feature. In our analysis we assume that this emission feature can be represented by a linear superposition of the wavelength-dependent opacity $\kappa_{\rm abs}(\lambda)$ describing the optical properties of silicate grains with different chemical composition, structure, and grain size. The determination of an adequate fitting equation is another goal of this study. Using a restricted number of fitting parameters we investigate which silicate species are necessary for the compositional fitting. Particles with radii of 0.1um- and 1.5um consisting of amorphous olivine and pyroxene, forsterite, enstatite, and quartz have been considered. Only compact, homogeneous dust grains have been used in the presented fitting procedures. In this context we show that acceptable fitting results can also be achieved if emission properties of porous silicate grains are considered instead. Although some previous studies give reasons for the similarity between the dust in circumstellar disks of TTauri stars and Herbig Ae/Be stars, a quantitative comparison has been missing, so far. Therefore, we conclude with a discussion of the results of a 10um spectroscopic survey of van Boekel et al. (2005) who focus on Herbig Ae/Be stars, the higher mass counterparts of T Tauri stars and draw comparisons to this and other studies. We find that the results of our study of T Tauri systems partly agree with previous studies of Herbig Ae/Be stars.Comment: 17 pages, 6 figure

Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.

International audienceSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice

Mutations in the Mitochondrial Methionyl-tRNA Synthetase Cause a Neurodegenerative Phenotype in Flies and a Recessive Ataxia (ARSAL) in Humans

The study of Drosophila neurodegenerative mutants combined with genetic and biochemical analyses lead to the identification of multiple complex mutations in 60 patients with a novel form of ataxia/leukoencephalopathy

Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes

Maintaining the integrity of sperm DNA is vital to reproduction and male fertility. Sperm contain a number of molecules and pathways for the repair of base excision, base mismatches and DNA strand breaks. The presence of Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, and its homologues has recently been shown in male germ cells, specifically during stage VII of spermatogenesis. High PARP expression has been reported in mature spermatozoa and in proven fertile men. Whenever there are strand breaks in sperm DNA due to oxidative stress, chromatin remodeling or cell death, PARP is activated. However, the cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Therefore, cleaved PARP (cPARP) may be considered a marker of apoptosis. The presence of higher levels of cPARP in sperm of infertile men adds a new proof for the correlation between apoptosis and male infertility. This review describes the possible biological significance of PARP in mammalian cells with the focus on male reproduction. The review elaborates on the role played by PARP during spermatogenesis, sperm maturation in ejaculated spermatozoa and the potential role of PARP as new marker of sperm damage. PARP could provide new strategies to preserve fertility in cancer patients subjected to genotoxic stresses and may be a key to better male reproductive health

Caught in the Middle: How and When Psychological Contract Breach by Subordinates Relates to Weekly Emotional Exhaustion of Supervisors

In psychological contract research, the side of the supervisor is strongly underexposed. However, supervisors are responsible for maintaining relationships with both their subordinates and senior management and are likely to be influenced by events unfolding in these relationships. In this study, we state that supervisor well-being may be affected by subordinates who fail to meet their obligations. This study adds to psychological contract research by developing an understanding of how and when subordinate psychological contract break (PCB) is associated with supervisor emotional exhaustion. Through a weekly diary survey among 56 Dutch supervisors, we test hypotheses about the relationships between subordinate PCB and the emotional exhaustion of the supervisor, the mediating role of perceptions of performance pressure by the supervisor in this relationship, and the moderating role of i-deals between the supervisor and senior management. Multilevel analyses support the first two hypotheses, but contradictory to our expectations show that the positive association between subordinate PCB and the emotional exhaustion of the supervisor is strengthened when the supervisor has high levels of i-deals with senior management. We discuss the findings in relation to their contribution to psychological contract theory

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Caractérisation thermo-électro-mécanique des interfaces fonte-acier-carbone dans une cuve d'électrolyse

Depuis des milliers d'années, les métaux ont pourvu aux besoins matériels des gens. L'aluminium ne fait pas exception, et est certainement l'un des métaux les plus prisé en raison de sa légèreté. Ce n'est que dans les années 1800 que sa fabrication (son extraction en fait) est rendu possible avec le procédé de Hall-Héroult. Aujourd'hui encore, ce procédé est le seul utilisé à l'échelle industrielle, et requiert un appareillage complexe impliquant les domaines thermique et électrique. Étant donnée que certaines parties de la cuve de Hall-Héroult sont particulièrement importantes, elles font l'objet d'études particulières. C'est le cas notamment des anodes et des cathodes. Le but de ce présent ouvrage était de comprendre et de quantifier les phénomènes de résistance de contact thermique et électrique se produisant à la cathode ainsi qu'à l'anode d'une cuve d'électrolyse. Ces données ont été traduites sous formes de loi de comportement. La problématique du mauvais transfert électrique et de chaleur entre deux matériaux provient du fait que les aspérités et les cavités des surfaces en contact créent un espace interstitiel entre les solides; il peut même y avoir une couche de gaz emprisonnée dans les cavités. Si bien que les deux surfaces ne se touchent qu'avec moins de 3% de leur surface apparente, même si une énorme pression est appliquée sur les solides. Cela crée un étranglement des lignes de courant aux points de contact réels, engendrant la résistance de contact. Il existe plusieurs modèles théoriques de résistance de contact thermique et électrique. Ces modèles sont cependant basés sur des hypothèses assez restrictives ainsi que sur des propriétés des matériaux qui peuvent être très difficiles à obtenir pour des températures élevées. Une méthodologie expérimentale a donc été préférée à une approche théorique. Un montage expérimental a été conçu et fabriqué dans les laboratoires de l'Université. Des échantillons ont été fabriqués à l'usine Alcan Grande-Baie. Une attention particulière a été prise pour que la fabrication des échantillons soit la plus fidèle possible à la réalité des scellements d'anode et de cathode des usines Aîcan. Plusieurs essais ont été réalisés sur les échantillons de fonte/carbone et de fonte/acier anodiques et cathodiques. Tel que prévu, les résistances de contact thermiques et électriques diminuent avec la pression et la température. Cependant il semble que les valeurs des résultats expérimentaux soient plus élevées que celles prédites par les modèles théoriques. En effet, les résistances électriques sont de 3 à 5 fois supérieures aux modèles théoriques, tandis que les résistances thermiques sont 2 à 3 fois supérieures aux différents modèles théoriques. De plus, un comportement monotonique entre les valeurs des résistances de contact et la température était attendu. Or, une variation non-monotonique, vers 500°C, a été observée de façon récurrente. Ces phénomènes « non attendu » ne seraient peut-être pas étrangers à certaines observations faites en laboratoire. Effectivement, un durcissement de la fonte en surface, un recuit de relaxation de la fonte, une formation d'oxydes de surface, une décarburisation de la fonte, des zones de soudure entre la fonte et l'acier ont été observés tout au long des essais en laboratoire. Ces perturbations métalurgico-chimique qui surviennent sans doute également en usine, pourrait sans doute expliquer la variation des valeurs expérimentales par rapport aux modèles théoriques, de même que la non-monotonicité des résistances de contact selon la température. Ces perturbations sont en majorité des mécanismes se produisant principalement à hautes températures (mis à part le durcissement de la surface de la fonte). Une validation de ces mécanismes serait pertinente pour bien comprendre toutes les variables relatives aux résistances de contact