Debris flows as a factor of hillslope evolution controlled by a continuous or a pulse process?

Flood effectiveness observations imply that two families of processes describe the formation of debris flow volume. One is related to the rainfall?erosion relationship, and can be seen as a gradual process, and one is related to additional geological/geotechnical events, those named hereafter extraordinary events. In order to discuss the hypothesis of coexistence of two modes of volume formation, some methodologies are applied. Firstly, classical approaches consisting in relating volume to catchments characteristics are considered. These approaches raise questions about the quality of the data rather than providing answers concerning the controlling processes. Secondly, we consider statistical approaches (cumulative number of events distribution and cluster analysis) and these suggest the possibility of having two distinct families of processes. However the quantitative evaluation of the threshold differs from the one that could be obtained from the first approach, but they all agree in the sense of the coexistence of two families of events. Thirdly, a conceptual model is built exploring how and why debris flow volume in alpine catchments changes with time. Depending on the initial condition (sediment production), the model shows that large debris flows (i.e. with important volume) are observed in the beginning period, before a steady-state is reached. During this second period debris flow volume such as is observed in the beginning period is not observed again. Integrating the results of the three approaches, two case studies are presented showing: (1) the possibility to observe in a catchment large volumes that will never happen again due to a drastic decrease in the sediment availability, supporting its difference from gradual erosion processes; (2) that following a rejuvenation of the sediment storage (by a rock avalanche) the magnitude?frequency relationship of a torrent can be differentiated into two phases, the beginning one with large and frequent debris flow and a later one with debris flow less intense and frequent, supporting the results of the conceptual model. Although the results obtained cannot identify a clear threshold between the two families of processes, they show that some debris flows can be seen as pulse of sediment differing from that expected from gradual erosion.

Die Krankheit Depression kann jeden treffen [In Process Citation].

The survey "Datenerhebung zur Depression in der Allgemeinbevölkerung" was conducted from fall 2010 to spring 2011 on several online platforms. The results show that there is a considerable timespan between the appearance of initial symptoms of depression and the first diagnosis of a patient. Intervention at early stages of the disease can reduce a potentially long time of suffering and can lead to the successful treatment of depression. General practitioners play an important role as the link between patient and psychiatrist.

Hémorragie intra-alvéolaire [Alveolar hemorrhage].

Diffuse alveolar hemorrhage (DAH) is defined by the presence of red blood cells originating from the lung capillaries or venules within the alveoli. The diagnosis is established on clinical features, radiological pattern, and especially bronchoalveolar lavage. Diffuse alveolar hemorrhage may have many immune or non-immune causes. Immune causes of DAH include vasculitides, connective tissue diseases, especially systemic lupus erythematosus, and antiglomerular basement membrane antibody disease (Goodpasture's syndrome). Treatment is both supportive and causal, often based on high dose corticosteroids and immunosuppressive therapy (especially intravenous cyclophosphamide). Plasma exchanges are performed in antiglomerular basement membrane antibody disease and systemic lupus erythematosus, and are considered in systemic vasculitis. Non-immune causes of DAH mainly include heart diseases, coagulation disorders, infections, drug toxicities and idiopathic DAH. Treatment of non-immune DAH is that of its cause. Whatever the cause, DAH is an emergency requiring prompt assessment and early treatment.

Linking supply to demand: the neuronal monocarboxylate transporter MCT2 and the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid receptor GluR2/3 subunit are associated in a common trafficking process.

MCT2 is the major neuronal monocarboxylate transporter (MCT) that allows the supply of alternative energy substrates such as lactate to neurons. Recent evidence obtained by electron microscopy has demonstrated that MCT2, like alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, is localized in dendritic spines of glutamatergic synapses. Using immunofluorescence, we show in this study that MCT2 colocalizes extensively with GluR2/3 subunits of AMPA receptors in neurons from various mouse brain regions as well as in cultured neurons. It also colocalizes with GluR2/3-interacting proteins, such as C-kinase-interacting protein 1, glutamate receptor-interacting protein 1 and clathrin adaptor protein. Coimmunoprecipitation of MCT2 with GluR2/3 and C-kinase-interacting protein 1 suggests their close interaction within spines. Parallel changes in the localization of both MCT2 and GluR2/3 subunits at and beneath the plasma membrane upon various stimulation paradigms were unraveled using an original immunocytochemical and transfection approach combined with three-dimensional image reconstruction. Cell culture incubation with AMPA or insulin triggered a marked intracellular accumulation of both MCT2 and GluR2/3, whereas both tumor necrosis factor alpha and glycine (with glutamate) increased their cell surface immunolabeling. Similar results were obtained using Western blots performed on membrane or cytoplasm-enriched cell fractions. Finally, an enhanced lactate flux into neurons was demonstrated after MCT2 translocation on the cell surface. These observations provide unequivocal evidence that MCT2 is linked to AMPA receptor GluR2/3 subunits and undergoes a similar translocation process in neurons upon activation. MCT2 emerges as a novel component of the synaptic machinery putatively linking neuroenergetics to synaptic transmission.

Success of referral for alcohol dependent patients from a general hospital : predictive value of patient and process characteristics

RESUME: Introduction L'objectif de cette étude prospective de cohorte était d'estimer l'efficacité d'un processus de prise en charge standardisé de patients dépendants de l'alcool dans le contexte d'un hôpital universitaire de soins généraux. Ce modèle de prise en charge comprenait une évaluation multidisciplinaire puis des propositions de traitements individualisées et spécifiques (« projet thérapeutique »). Patients et méthode 165 patients alcoolo-dépendants furent recrutés dans différents services de l'hôpital universitaire, y compris la policlinique de médecine. Ils furent dans un premier temps évalués par une équipe multidisciplinaire (médecin interniste, psychiatre, assistant social), puis un projet thérapeutique spécialisé et individualisé leur fut proposé lors d'une rencontre réunissant le patient et l'équipe. Tous les patients éligibles acceptant de participer à l'étude (n=68) furent interrogés au moment de l'inclusion puis 2 et 6 mois plus tard par une psychologue. Des informations standardisées furent recueillies sur les caractéristiques des patients, le processus de prise en charge et l'évolution à 6 mois. Les critères de succès utilisés à 6 mois furent: l'adhérence au traitement proposé et l'abstinence d'alcool. Résultats Lors de l'évaluation à 6 mois, 43% des patients étaient toujours en traitement et 28% étaient abstinents. Les variables prédictrices de succès parmi les caractéristiques des patients étaient un âge de plus de 45 ans, ne pas vivre seul, avoir un travail et être motivé pour un traitement (RAATE-A <18). Pour les variables dépendantes du processus de prise en charge, un sevrage complet de l'alcool lors de la rencontre multidisciplinaire ainsi que la présence de tous les membres de l'équipe à cette réunion étaient des facteurs associés au succès. Conclusion L'efficacité de ce modèle d'intervention pour patients dépendants de l'alcool en hôpital de soins généraux s'est montrée satisfaisante, en particulier pour le critère de succès adhérence au traitement. Des variables associées au succès ou à l'échec à 6 mois ont pu être mises en évidence, permettant d'identifier des populations de patients évoluant différemment. Des stratégies de prise en charge tenant compte de ces éléments pourraient donc être développées, permettant de proposer des traitements plus adaptés ainsi qu'une meilleure rétention des patients alcooliques dans les programmes thérapeutiques. ABSTRACT. To assess the effectiveness of a multidisciplinary evaluation and referral process in a prospective cohort of general hospital patients with alcohol dependence, alcohol-dependent patients were identified in the wards of the general hospital and its primary care center. They were evaluated and then referred to treatment by a multidisciplinary team; those patients who accepted to participate in this cohort study were consecutively included and followed for 6 months. Not included patients were lost for follow-up, whereas all included patients were assessed at time of inclusion, 2 and 6 months later by a research psychologist in order to collect standardized baseline patients' characteristics, process salient features and patients outcomes (defined as treatment adherence and abstinence). Multidisciplinary evaluation and therapeutic referral was feasible and effective, with a success rate of 43% for treatment adherence and 28% for abstinence at 6 months. Among patients' characteristics, predictors of success were an age over 45, not living alone, being employed and being motivated to treatment (RAATE-A score < 18), whereas successful process characteristics included detoxification of the patient at time of referral and a full multidisciplinary referral meeting. This multidisciplinary model of evaluation and referral of alcohol dependent patients of a general hospital had a satisfactory level of effectiveness. Predictors of success and failure allow the identification of subsets of patients for whom new strategies of motivation and treatment referral should be designed.

Minimal information about T cell assays: the process of reaching the community of T cell immunologists in cancer and beyond.

Many assays to evaluate the nature, breadth, and quality of antigen-specific T cell responses are currently applied in human medicine. In most cases, assay-related protocols are developed on an individual laboratory basis, resulting in a large number of different protocols being applied worldwide. Together with the inherent complexity of cellular assays, this leads to unnecessary limitations in the ability to compare results generated across institutions. Over the past few years a number of critical assay parameters have been identified which influence test performance irrespective of protocol, material, and reagents used. Describing these critical factors as an integral part of any published report will both facilitate the comparison of data generated across institutions and lead to improvements in the assays themselves. To this end, the Minimal Information About T Cell Assays (MIATA) project was initiated. The objective of MIATA is to achieve a broad consensus on which T cell assay parameters should be reported in scientific publications and to propose a mechanism for reporting these in a systematic manner. To add maximum value for the scientific community, a step-wise, open, and field-spanning approach has been taken to achieve technical precision, user-friendliness, adequate incorporation of concerns, and high acceptance among peers. Here, we describe the past, present, and future perspectives of the MIATA project. We suggest that the approach taken can be generically applied to projects in which a broad consensus has to be reached among scientists working in fragmented fields, such as immunology. An additional objective of this undertaking is to engage the broader scientific community to comment on MIATA and to become an active participant in the project.

Surfactant palmitoylmyristoylphosphatidylcholine is a marker for alveolar size during disease.

Two common lung-related complications in the neonate are respiratory distress syndrome, which is associated with a failure to generate low surface tension at the air-liquid interface because of pulmonary surfactant insufficiency, and bronchopulmonary dysplasia (BPD), a chronic lung injury with reduced alveolarization. Surfactant phosphatidylcholine (PC) molecular species composition during alveolarization has not been examined. Mass spectrometry analysis of bronchoalveolar lavage fluid of rodents and humans revealed significant changes in surfactant PC during alveolar development and BPD. In rats, total PC content rose during alveolarization, which was caused by an increase in palmitoylmyristoyl-PC (16:0/14:0PC) concentration. Furthermore, two animal models of BPD exhibited a specific reduction in 16:0/14:0PC content. In humans, 16:0/14:0PC content was specifically decreased in patients with BPD and emphysema compared with patients without alveolar pathology. Palmitoylmyristoyl-PC content increased with increasing intrinsic surfactant curvature, suggesting that it affects surfactant function in the septating lung. The changes in acyl composition of PC were attributed to type II cells producing an altered surfactant during alveolar development. These data are compatible with extracellular surfactant 16:0/14:0PC content being an indicator of alveolar architecture of the lung.

An allele-specific, stochastic gene expression process controls the expression of multiple Ly49 family genes and generates a diverse, MHC-specific NK cell receptor repertoire.

Mouse NK cells express MHC class I-specific inhibitory Ly49 receptors. Since these receptors display distinct ligand specificities and are clonally distributed, their expression generates a diverse NK cell receptor repertoire specific for MHC class I molecules. We have previously found that the Dd (or Dk)-specific Ly49A receptor is usually expressed from a single allele. However, a small fraction of short-term NK cell clones expressed both Ly49A alleles, suggesting that the two Ly49A alleles are independently and randomly expressed. Here we show that the genes for two additional Ly49 receptors (Ly49C and Ly49G2) are also expressed in a (predominantly) mono-allelic fashion. Since single NK cells can co-express multiple Ly49 receptors, we also investigated whether mono-allelic expression from within the tightly linked Ly49 gene cluster is coordinate or independent. Our clonal analysis suggests that the expression of alleles of distinct Ly49 genes is not coordinate. Thus Ly49 alleles are apparently independently and randomly chosen for stable expression, a process that directly restricts the number of Ly49 receptors expressed per single NK cell. We propose that the Ly49 receptor repertoire specific for MHC class I is generated by an allele-specific, stochastic gene expression process that acts on the entire Ly49 gene cluster.

Alveolar epithelial CNGA1 channels mediate cGMP-stimulated, amiloride-insensitive, lung liquid absorption.

Impairment of lung liquid absorption can lead to severe respiratory symptoms, such as those observed in pulmonary oedema. In the adult lung, liquid absorption is driven by cation transport through two pathways: a well-established amiloride-sensitive Na(+) channel (ENaC) and, more controversially, an amiloride-insensitive channel that may belong to the cyclic nucleotide-gated (CNG) channel family. Here, we show robust CNGA1 (but not CNGA2 or CNGA3) channel expression principally in rat alveolar type I cells; CNGA3 was expressed in ciliated airway epithelial cells. Using a rat in situ lung liquid clearance assay, CNG channel activation with 1 mM 8Br-cGMP resulted in an approximate 1.8-fold stimulation of lung liquid absorption. There was no stimulation by 8Br-cGMP when applied in the presence of either 100 μM L: -cis-diltiazem or 100 nM pseudechetoxin (PsTx), a specific inhibitor of CNGA1 channels. Channel specificity of PsTx and amiloride was confirmed by patch clamp experiments showing that CNGA1 channels in HEK 293 cells were not inhibited by 100 μM amiloride and that recombinant αβγ-ENaC were not inhibited by 100 nM PsTx. Importantly, 8Br-cGMP stimulated lung liquid absorption in situ, even in the presence of 50 μM amiloride. Furthermore, neither L: -cis-diltiazem nor PsTx affected the β(2)-adrenoceptor agonist-stimulated lung liquid absorption, but, as expected, amiloride completely ablated it. Thus, transport through alveolar CNGA1 channels, located in type I cells, underlies the amiloride-insensitive component of lung liquid reabsorption. Furthermore, our in situ data highlight the potential of CNGA1 as a novel therapeutic target for the treatment of diseases characterised by lung liquid overload.