Hydration of an amphiphilic excipient, Gelucire 44/14

The hydration behavior of an amphiphilic excipient, Gelucire 44/14, has been investigated. Two types of hydration processes were studied: one with increasing humidity to investigate the conditions during storage, and one with increasing water contents to study the behavior during dissolution. In addition, the main components of the excipient were investigated separately. These were polyethylene glycol (PEG), PEG monolaurate and PEG dilaurate (PEG esters), trilaurin (glyceride) and glycerol. The water uptake of Gelucire 44/14 at humidity ratios less than 60%RH was very low (about 1 wt%), which was attributed to the dissolution of the most hydrophilic component, glycerol. The water uptake increased substantially above 70%RH as PEG started to dissolve, followed by the PEG esters. It was concluded that each component equilibrates separately with the aqueous solution, which itself is in equilibrium with the humid air. Hence, a liquid phase can form between the crystals with a chemical potential decided by the humidity ratio. The water uptake of Gelucire 44/14 could be described as a sum of the uptake of the individual components, weighted according to their relative amounts in the mixture. Phase maps of the Gelucire 44/14 and its components at different water contents were constructed. Dry Gelucire 44/14 contains lamellar crystals of mainly PEG and PEG esters which melt at 44 ºC. The crystals do not swell at increasing humidity, but dissolve above 75%RH at a water content of 5 wt% in the excipient. At increasing water contents Gelucire 44/14 forms white gels composed of hexagonal and lamellar mesophases dispersed in a continuous liquid phase. These liquid crystalline phases dissolve at 35 ºC, i.e. below physiological temperatures. A dramatic viscosity maximum was observed in the lamellar region at 50 wt% water, which may be attributed to the formation of networks of PEG esters. The pure PEG esters were found to form cubic mesophases at 50 wt% water. The instruments used in this study were Dynamic Vapor Sorption (DVS), Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Small- and Wide Angle X-ray Scattering (SWAXS) and Optical Microscopy

Gestão otimista do stresse: um estudo piloto de aplicação dum programa com enfermeiros portugueses

O presente estudo mostra os resultados de uma intervenção baseada na psicologia para a gestão do stresse em enfermeiros. Surge de uma amostra de três enfermeiras que responderam a instrumentos de avaliação quantitativa e qualitativa. A intervenção consistiu na aplicação do programa “Gestão Otimista do Stresse”, administrado em diferentes momentos de acordo com o desenho experimental de linha de base múltipla. Procurou-se dotar os enfermeiros de ferramentas para diminuir os níveis de stresse e consequentemente adquirirem competências. Especificamente pretendeu-se ensinar técnicas para lidar com stresse através de programas de treino e posteriormente verificar a sua eficácia. Os resultados obtidos sugerem que a intervenção permite uma diminuição dos níveis de stresse, porém as limitações centraram-se no tamanho da amostra, no horário pós-laboral e na falta de seguimento. As hipóteses foram comprovadas quase na sua totalidade, reforçando a ideia de que deveriam ser implementados programas de gestão do stresse no setor público; ABSTRACT: Optimistic stress management: a pilot study of the application of a program with portuguese nurses The current study shows the results of a psychology based intervention for the stress management in nurses. It arises from a sample of three nurses who answered to quantitative and qualitative evaluation instruments. The intervention consisted on the application of the program “Optimistic Stress Management”, applied at different times according to the multiple baseline experimental design. We sought to provide the nurses with tools to reduce stress levels and, consequently, to acquire skills. Specifically, it was intended to teach techniques to deal with stress through training programs, and later to verify their effectiveness. The results suggest that the intervention allows a reduction of the stress levels, however the limitations were centered on the sample size, on the post-work hours and lack of follow-up. The hypotheses have been proven almost in their totality, reinforcing the idea that stress management programs should be implemented in the public sector

A research program on stress management for health professionals

Occupational stress has been considered a serious public health problem. Nursing is a highly specialized work done under conditions of considerable pressure, therefore a stressing profession. Stress in nurses has considerable implications on their health and on the quality of their service, and it is associated with considerable economic costs. The current contribution is a report on the stress management line of research carried on presently in Portugal. The efficacy of a stress management intervention program in a nursing professionals sample is assessed through a quasi-experimental multiple baseline design in several groups of health professionals. Three studies with different groups of nurses in different hospitals have been conducted. Preliminary results show significant levels of stress reduction, as well as an improvement of the number and efficacy of the coping skills of the participants.FCT – Fundação para a Ciência e a Tecnologia, I.P.,no âmbito do projeto UID/CED/04312/201

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Establishment of a Policy Analysis Capability in Romania

The Romanian government, like other governments of former communist countries, emerged from the collapsed Soviet Union ill prepared to confront the complex challenges of governing under a democratic, free market system. At the core of governments that formulate sound public policies, successfully implement programs, and respond effectively to rapidly changing situations is the capacity to carry out independent, high quality research and analysis that results in improved decision making. During the 21st century, the need and acceptance of the incorporation of policy analysis courses in public administration curricula in Romania is expected to grow. In time, educational programs are expected to result in the following consequences: _ Formation of a body of strong independent policy researchers employed by the national and local governments as well as by universities and non-profit institutions _ Utilization of analytical outcomes as tools of political, social and economic improvement by the executive, legislative and judicial branches and by non-profit and private sectors _ Greater public understanding of and participation in public policy processes.</p

Sous le signe de Moïra (l'univers féminin dans l'œuvre romanesque de Julien Green)

Julien Green a avoué avoir recours à l art pour y enfermer tout ce que le monde lui offrait de déplaisant, voire d inquiétant. Son équilibre mental dépendait de cette démarche créative et cathartique. Une telle expérience a fait surgir un univers tourmenté, dominé par des forces maléfiques dont l influence voue les êtres au tragique. Dans une logique tout d abord conventionnelle, les figures féminines apparaissent comme l image la plus visible d influences néfastes. Leur drame provient de l obsession extrême d un corps porté à les trahir. Qu elles soient laides ou belles, l attachement à leur image mine l existence des héroïnes et les voue à la déchéance, car elles deviennent le champ de bataille où les forces du bien et du mal s opposent. Elles sont alors pour Green le support privilégié d une réflexion qui sonde la profondeur de l imprégnation tragique des récits de fiction.L encadrement social et religieux apparaît comme une forme de protection de la femme face au mal auquel elle semble promise. Mais la soumission aux normes bourgeoises s avère pernicieuse : elle enferme les êtres sur eux-mêmes et nourrit fatalement en eux les caractéristiques propices au développement d un mal dont l évolution se révèle incontrôlable. En dépit de la charge négative attribuée à nombreuses de ses héroïnes, Green dépasse la représentation misogyne première. La femme bénéfique, souvent imparfaite mais purifiée par les peines endurées, par son besoin de vivre dans la vérité, devient le signe discret d une ouverture face au tragique. Par sa présence Green parvient à introduire subtilement dans ses romans l espérance chrétienne, sans rendre son œuvre édifiante.Julien Green admitted turning to art to encompass everything in the world he found unpleasant or even worrying. His mental well-being depended on this creative and cathartic practice. It brought to the forefront a tormented universe dominated by malevolent forces, with tragic consequences for those involved.In accordance with conventional logic, female characters are portrayed as bearing the brunt of these harmful influences. Their drama springs from an obsession with their bodies which is destined to betray them. Be they ugly or beautiful, their attachment to their image undermines them as heroines and dooms them to failure, for they become the battlefield on which the forces of good and evil are opposed. For Green they are the preferred medium through which he fathoms the depths of the tragic in his works of fiction. The social and religious setting of the novels may appear to be a form of protection for women in the face of the evil which awaits them. But their compliance to the norms of the bourgeoisie proves to be harmful: it imprisons them within themselves and, fatally, engenders characteristics which lead to the development of an evil which proves to be out of control.In spite of the negative charges against numerous of his heroines, Green rises above simple misogyny. The altruistic woman, often far from perfect, but tempered by hardships endured, becomes, by her need to live the truth, a discreet sign of hope in the face of tragedy. It is through his female characters that Green succeeds in introducing subtly the notion of Christian hope in his novels, without making his work 'edifying'.PARIS4-Bib. électronique (751059905) / SudocSudocFranceF

Recherche précompétitive, une mise en synergie des ressources publiques et privées : pour quels objectifs, comment et dans quel cadre juridique ?

L’objectif de la Table Ronde était d’aborder la Recherche Pré-compétitive pour la première fois lors des Rencontres de Giens. Les participants venaient de l’industrie du médicament, des biotech, de l’industrie du dispositif, de l’académie, des services et sociétés de valorisation, des ministères, du monde de la recherche clinique et fondamentale. Ils ont fait le constat des changements profonds dans la connaissance des maladies et dans le développement des médicaments. À l’aide d’exemples dans le monde de la Santé et en dehors, ils ont identifié les principes, les enjeux, les facteurs de succès et de risque de la recherche précompétitive. Les particularités de la gestion de la propriété intellectuelle ont été plus particulièrement étudiées. La Table Ronde a conclu sur les principes de la recherche précompétitive en Santé, une révolution culturelle nécessaire. C’est développer une recherche en partenariat fondée sur des principes nouveaux : i) comprendre et partager; ii) intégrer la complexité du vivant; iii) agir dans l’interdisciplinarité