Observation of Pulsed γ-Rays Above 25 GeV from the Crab Pulsar with MAGIC

One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric γ-ray Imaging Cherenkov (MAGIC) telescope to 25 giga-electron volts. In this configuration, we detected pulsed γ-rays from the Crab pulsar that were greater than 25 giga-electron volts, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.

Les déterminants de la prolongation des séjours en SSRG et les indicateurs du devenir des patients après leur sortie : Étude rétrospective au CHRU de Strasbourg [Determinants of prolonged stays in geriatric rehabilitation department and indicators of patient outcome after discharge: A retrospective study in Strasbourg university hospital]

Objectif. Analyser les déterminants de la prolongation des séjours hospitaliers en service de soins de suite et réadaptation gériatrique (SSRG) et identifier les indicateurs du devenir des patients après leur sortie. Méthode. Étude rétrospective au CHRU de Strasbourg de l'ensemble des séjours de durée supérieure à 90 jours entre le 1 janvier 2012 et le 30 septembre 2013. L'ensemble des données sociodémographiques, descriptives des séjours et de l'état de santé des patients ont été analysées. Les patients ont été suivis 9 mois après leur sortie. Les réhospitalisations, l'admission en institution et le décès ont été informés par un contact téléphonique auprès du médecin traitant ou de la famille. Résultats. Quarante-six séjours ont été analysés. Les patients étaient à 68,0 % des femmes. La moyenne d'âge était de 82,9 ± 5,8 ans. Quatre-vingt-dix-huit pour cent d'entre eux vivaient à domicile avant l'admission en milieu hospitalier. Les raisons justifiant la prolongation étaient d'ordre médical (60,8 %), psychique (45,6 %), social (65,2 %) et liées à la difficulté de trouver une solution d'aval (58,7 %). À la fin de leur séjour, 9 patients ont pu regagner leur domicile et 37 ont été admis directement en institution. Durant la période de suivi, 17 patients ont été réhospitalisés au moins une fois et 3 jusqu'à trois fois. Au 9e mois, 9 patients étaient décédés dans un délai moyen de 75 jours après la sortie du SSRG. Les résultats des analyses unifactorielles et multivariées ont permis d'identifier des indicateurs d'évolution défavorable (décès et/ou réhospitalisation). Aucune des variables sociodémographiques ou de syndrome gériatrique n'a été identifiée. Par contre un « motif d'hospitalisation pour une maladie infectieuse », ou pour « un trouble de la marche ou une chute », une « prolongation du séjour en SSRG pour raison médicale » et un « séjour prolongé en court séjour » étaient les facteurs identifiés. Conclusion. Dans la tendance actuelle à améliorer la rentabilité de l'utilisation des ressources de santé, ces résultats rappellent qu'il est important de maintenir un juste équilibre entre utilisation raisonnée des ressources et les besoins spécifiques des patients âgés.

A prospective cohort study of healthcare visits and rehospitalizations after hospital discharge in community-acquired pneumonia

Background and objective: We aimed to identify the frequency of, reasons for and risk factors associated with additional healthcare visits and rehospitalizations (healthcare interactions) by patients with community-acquired pneumonia (CAP) within 30 days of hospital discharge. Methods: Observational analysis of a prospective cohort of adults hospitalized with CAP at a tertiary hospital (2007-2009). Additional healthcare interactions were defined as the visits to a primary care centre or emergency department and hospital readmissions within 30 days of discharge. Results: Of the 934 hospitalized patients with CAP, 282 (34.1%) had additional healthcare interactions within 30 days of hospital discharge: 149 (52.8%) needed an additional visit to their primary care centre and 177 (62.8%) attended the emergency department. Seventy-two (25.5%) patients were readmitted to hospital. The main reasons for additional healthcare interactions were worsening of signs or symptoms of CAP and new or worsening comorbid conditions independent of pneumonia, mainly cardiovascular and pulmonary diseases. The only independent factor associated with visits to primary care centre or emergency department was alcohol abuse (odds ratio [OR] = 1.65; 95% confidence interval [CI]: 1.03-2.64). Prior hospitalization (≤ 90 days) (OR = 2.47; 95% CI: 1.11-5.52) and comorbidities (OR = 3.99; 95% CI: 1.12-14.23) were independently associated with rehospitalization. Conclusions: Additional healthcare visits and rehospitalizations within 30 days of hospital discharge are common in patients with CAP. This is mainly due to a worsening of signs or symptoms of CAP and/or comorbid conditions. These findings may have implications for discharge planning and follow-up of patients with CAP.

A prospective cohort study of healthcare visits and rehospitalizations after hospital discharge in community-acquired pneumonia

Background and objective: We aimed to identify the frequency of, reasons for and risk factors associated with additional healthcare visits and rehospitalizations (healthcare interactions) by patients with community-acquired pneumonia (CAP) within 30 days of hospital discharge. Methods: Observational analysis of a prospective cohort of adults hospitalized with CAP at a tertiary hospital (2007-2009). Additional healthcare interactions were defined as the visits to a primary care centre or emergency department and hospital readmissions within 30 days of discharge. Results: Of the 934 hospitalized patients with CAP, 282 (34.1%) had additional healthcare interactions within 30 days of hospital discharge: 149 (52.8%) needed an additional visit to their primary care centre and 177 (62.8%) attended the emergency department. Seventy-two (25.5%) patients were readmitted to hospital. The main reasons for additional healthcare interactions were worsening of signs or symptoms of CAP and new or worsening comorbid conditions independent of pneumonia, mainly cardiovascular and pulmonary diseases. The only independent factor associated with visits to primary care centre or emergency department was alcohol abuse (odds ratio [OR] = 1.65; 95% confidence interval [CI]: 1.03-2.64). Prior hospitalization (≤ 90 days) (OR = 2.47; 95% CI: 1.11-5.52) and comorbidities (OR = 3.99; 95% CI: 1.12-14.23) were independently associated with rehospitalization. Conclusions: Additional healthcare visits and rehospitalizations within 30 days of hospital discharge are common in patients with CAP. This is mainly due to a worsening of signs or symptoms of CAP and/or comorbid conditions. These findings may have implications for discharge planning and follow-up of patients with CAP.

A prospective cohort study of healthcare visits and rehospitalizations after hospital discharge in community-acquired pneumonia

Background and objective: We aimed to identify the frequency of, reasons for and risk factors associated with additional healthcare visits and rehospitalizations (healthcare interactions) by patients with community-acquired pneumonia (CAP) within 30 days of hospital discharge. Methods: Observational analysis of a prospective cohort of adults hospitalized with CAP at a tertiary hospital (2007-2009). Additional healthcare interactions were defined as the visits to a primary care centre or emergency department and hospital readmissions within 30 days of discharge. Results: Of the 934 hospitalized patients with CAP, 282 (34.1%) had additional healthcare interactions within 30 days of hospital discharge: 149 (52.8%) needed an additional visit to their primary care centre and 177 (62.8%) attended the emergency department. Seventy-two (25.5%) patients were readmitted to hospital. The main reasons for additional healthcare interactions were worsening of signs or symptoms of CAP and new or worsening comorbid conditions independent of pneumonia, mainly cardiovascular and pulmonary diseases. The only independent factor associated with visits to primary care centre or emergency department was alcohol abuse (odds ratio [OR] = 1.65; 95% confidence interval [CI]: 1.03-2.64). Prior hospitalization (≤ 90 days) (OR = 2.47; 95% CI: 1.11-5.52) and comorbidities (OR = 3.99; 95% CI: 1.12-14.23) were independently associated with rehospitalization. Conclusions: Additional healthcare visits and rehospitalizations within 30 days of hospital discharge are common in patients with CAP. This is mainly due to a worsening of signs or symptoms of CAP and/or comorbid conditions. These findings may have implications for discharge planning and follow-up of patients with CAP.

Nursing discharge planning for older medical inpatients in Switzerland: A cross-sectional study.

Nursing discharge planning for elderly medical inpatients is an essential element of care to ensure optimal transition to home and to reduce post-discharge adverse events. The objectives of this cross-sectional study were to investigate the association between nursing discharge planning components in older medical inpatients, patients' readiness for hospital discharge and unplanned health care utilization during the following 30 days. Results indicated that no patients benefited from comprehensive discharge planning but most benefited from less than half of the discharge planning components. The most frequent intervention recorded was coordination, and the least common was patients' participation in decisions regarding discharge. Patients who received more nursing discharge components felt significantly less ready to go home and had significantly more readmissions during the 30-day follow-up period. This study highlights large gaps in the nursing discharge planning process in older medical inpatients and identifies specific areas where improvements are most needed.

Cyclosporine A kinetics in brain cell cultures and its potential of crossing the blood-brain barrier.

There is an increasing need to develop improved systems for predicting the safety of xenobiotics. However, to move beyond hazard identification the available concentration of the test compounds needs to be incorporated. In this study cyclosporine A (CsA) was used as a model compound to assess the kinetic profiles in two rodent brain cell cultures after single and repeated exposures. CsA induced-cyclophilin B (Cyp-B) secretion was also determined as CsA-specific pharmacodynamic endpoint. Since CsA is a potent p-glycoprotein substrate, the ability of this compound to cross the blood-brain barrier (BBB) was also investigated using an in vitro bovine model with repeated exposures up to 14days. Finally, CsA uptake mechanisms were studied using a parallel artificial membrane assay (PAMPA) in combination with a Caco-2 model. Kinetic results indicate a low intracellular CsA uptake, with no marked bioaccumulation or biotransformation. In addition, only low CsA amounts crossed the BBB. PAMPA and Caco-2 experiments revealed that CsA is mostly trapped to lipophilic compartments and exits the cell apically via active transport. Thus, although CsA is unlikely to enter the brain at cytotoxic concentrations, it may cause alterations in electrical activity and is likely to increase the CNS concentration of other compounds by occupying the BBBs extrusion capacity. Such an integrated testing system, incorporating BBB, brain culture models and kinetics could be applied for assessing neurotoxicity potential of compounds.

Barrier-protective effects of activated protein C in human alveolar epithelial cells

Acute lung injury (ALI) is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI. We aimed to study the effects of activated protein C (APC) on mechanical tension and barrier integrity in human alveolar epithelial cells (A549) exposed to thrombin. Cells were pretreated for 3 h with APC (50 mg/ml) or vehicle (control). Subsequently, thrombin (50 nM) or medium was added to the cell culture. APC significantly reduced thrombin-induced cell monolayer permeability, cell stiffening, and cell contraction, measured by electrical impedance, optical magnetic twisting cytometry, and traction microscopy, respectively, suggesting a barrier-protective response. The dynamics of the barrier integrity was also assessed by western blotting and immunofluorescence analysis of the tight junction ZO-1. Thrombin resulted in more elongated ZO-1 aggregates at cell-cell interface areas and induced an increase in ZO-1 membrane protein content. APC attenuated the length of these ZO-1 aggregates and reduced the ZO-1 membrane protein levels induced by thrombin. In conclusion, pretreatment with APC reduced the disruption of barrier integrity induced by thrombin, thus contributing to alveolar epithelial barrier protection.

Au sortir de l'hôpital, comment renforcer la continuité de la prise en charge médicale [Discharge from hospital: how to improve continuity of medical care?].

Early readmission is the major success indicator of the transition between hospital and home. Patients admitted with heart failure reach a 20% rate. Potentially avoidable readmissions, defined as unpredictable and related to a known condition during index hospitalization, represent the improvement margin. For these latter, implementation of specific interventions can be effective. Complex interventions on transition, including several modalities and seeking to encourage patient autonomy seem more effective than others. We describe two models: a pragmatic one developed in a regional hospital, and a more complex one developed in a university hospital during the LEAR-HF study. In both cases, it is imperative to work on "medical liability": should it extend beyond discharge up to the threshold of the private practice?

Loss of intestinal epithelial barrier function in Salmonella Enteritidis infection

Intestinal infection with Salmonella enterica serotype Enteritidis, a food-borne infection spread to humans especially through contaminated eggs and egg-products as well as undercooked contaminated fresh meat, is the most common cause of intestinal inflammation in the European Union. Enteritis caused by Salmonella Enteritidis is characterized by fever, diarrhoea and abdominal pain. The disruption of the intestinal epithelial barrier function contributes to diarrhoea and is responsible for the perpetuation of the inflammatory process. In this sense, oxidative stress and the proinflammatory cytokines TNF-α, IFN-γ and IL-1β are described to induce the disorganization of the tight junctions (TJ), the most apical epithelial intercellular junctions and responsible for the paracellular permeability. The interest of this chapter relies not only in the investigation dealing with the mechanisms of TJ regulation but also in the contribution to the development of new tools for the prevention of epithelial barrier disruption in enteritis caused by Salmonella Enteritidis.

Effects of the epitaxial layer thickness on the noise properties of Schottky barrier diodes

An analytical theory to describe the combined effects of the epitaxial layer thickness and the ohmic contact on the noise properties of Schottky barrier diodes is presented. The theory, which provides information on both the local and the global noise properties, takes into account the finite size of the epitaxial layer and the effects of the back ohmic contact, and applies to the whole range of applied bias. It is shown that by scaling down the epitaxial layer thickness, the current regime in which the noise temperature displays a shot-noise-like behavior increases at the cost of reducing the current range in which the thermal-noise-like behavior dominates. This improvement in noise temperature is limited by the effects of the ohmic contact, which appear for large currents. The theory is formulated on general trends, allowing its application to the noise analysis of other semiconductor devices operating under strongly inhomogeneous distributions of the electric field and charge concentrations.

Effects of the epitaxial layer thickness on the noise properties of Schottky barrier diodes

An analytical theory to describe the combined effects of the epitaxial layer thickness and the ohmic contact on the noise properties of Schottky barrier diodes is presented. The theory, which provides information on both the local and the global noise properties, takes into account the finite size of the epitaxial layer and the effects of the back ohmic contact, and applies to the whole range of applied bias. It is shown that by scaling down the epitaxial layer thickness, the current regime in which the noise temperature displays a shot-noise-like behavior increases at the cost of reducing the current range in which the thermal-noise-like behavior dominates. This improvement in noise temperature is limited by the effects of the ohmic contact, which appear for large currents. The theory is formulated on general trends, allowing its application to the noise analysis of other semiconductor devices operating under strongly inhomogeneous distributions of the electric field and charge concentrations.