678 research outputs found

    Das enttÀuschte Versprechen der Integration: Migrantennachkommen in Frankreich und Deutschland

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    Dieser Beitrag beschĂ€ftigt sich mit den sozialstrukturellen Voraussetzungen, die der Dynamik bzw. dem Ausbleiben von Protestverhalten zu Grunde liegen. Ausgehend von drei theoretischen ErklĂ€rungsansĂ€tzen wird empirisch anhand von reprĂ€sentativen Mikrodaten gezeigt, dass die Konzeption der Integration der Migrantennachkommen durch die StaatsbĂŒrgerschaft und die Schule in Frankreich als ein Versprechen der Integration verstanden werden kann, das im Übergang auf den Arbeitsmarkt strukturell enttĂ€uscht wird. DemgegenĂŒber setzt die Ausgrenzung von Migrantennachkommen in Deutschland schon im Bildungssystem ein, so dass grĂ¶ĂŸere Erwartungshaltungen gar nicht erst entstehen. Die Revolten der jungen MigrantInnen in Frankreich können damit u.a. als Ergebnis von strukturell enttĂ€uschten Erwartungen interpretiert werden.Integration, Zweite Generation, Migration, Deutschland, Frankreich

    Apoptosis and p53 expression in rat adjuvant arthritis

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    INTRODUCTION: RA is a chronic inflammatory disorder that is characterized by inflammation and proliferation of synovial tissue. The amount of DNA fragmentation is significantly increased in rheumatoid synovium. Only low numbers of apoptotic cells are present in rheumatoid synovial tissue, however. The proportion of cells with DNA strand breaks is so great that this disparity suggests impaired apoptosis. Therefore, the development of novel therapeutic strategies that are aimed at inducing apoptosis in rheumatoid synovial tissue is an attractive goal. Although animal models for arthritis only approximate RA, they provide a useful test system for the evaluation of apoptosis-inducing therapies. AA in rats is among the most commonly used animal models for RA. For the interpretation of such studies, it is essential to characterize the extent to which apoptosis occurs during the natural course of the disease. Therefore, we evaluated the number of apoptotic cells and the expression of p53 in various phases of AA. MATERIALS AND METHODS: In order to generate the AA rat model, Lewis rats were immunized with Mycobacterium tuberculosis in mineral oil on day 0. Paw swelling usually started around day 10. For the temporal analysis rats were sacrificed on days 0, 5 (prearthritis), 11 (onset of arthritis), 17 (accelerating arthritis), or 23 (chronic arthritis). For the detection of apoptotic cells, the hind paws were harvested on days 0(n=6),5 (n=6), 11 (n=6), 17 (n=6), or 23 (n=4). The right ankle joints were fixed in formalin, decalcified in ethylenediaminetetra-acetic acid, embedded in paraffin, and sectioned. The TUNEL method was applied. The percentage of TUNEL-positive cells of the total inflammatory cell infiltrate was noted. For Western blot analysis, hind paws were harvested on days 0 (n=2), 5 (n=3), 11 (n=4), 17 (n=4), or 23 (n=4). In addition, hind paws of normal rats (n=2) were studied. The right ankle joints were snap frozen and pulverized. Synovial tissue was also obtained by arthroscopy of three patients with longstanding (>5 years) RA. After protein extraction in lysis buffer, equal amounts of protein samples from lysates were pooled and examined by Western bolt analysis using anti-p53 monoclonal antibody D07, which recognizes wild-type and mutant p53 from rodents and humans. For immunohistochemical analysis, six rats were sacrificed on day 23 after immunization and synovial tissue of the right ankle joints was snap frozen and evaluated by immunohistochemistry using anti-p53-pan. The sections were evaluated semi-quantitatively using a 0-4 scale. The kruskal-Wallis test for several group means was used to compare the percentage of TUNEL-positive cells at different time points. RESULTS: The percentages of TUNEL-positive cells were strongly dependent on the stage of the disease. Very few TUNEL-positive cells were detected in normal rats or in the early phases of AA; the number of TUNEL-positive cells was 1% or less of the total cell infiltrate, including neutrophils, from days 0-17 (Table 1). On day 23, however, the percentage of TUNEL-positive cells was significantly increased [15.8±5.1% (mean ± standard error of the mean); P=0.01]. TUNEL-positive cells were observed in the intimal lining layer and synovial sublining of the invasive front, as well as in the articular cartilage (Fig. 1). Subsequently, we examined expression of the tumor suppressor gene p53, because this is a key regulator of apoptosis. Expression of p53 in pooled rat AA joint extracts gradually increased from day 0 (6 arbitrary units) to day 23 (173 arbitrary units), which was markedly higher than p53 levels in RA synovium (32 arbitrary units; Table 1). Overexpression of p53 protein on day 23 was confirmed by immunohistochemistry in a separate experiment in six rats with AA. Overexpression of p53 was observed in the intimal lining layer and synovial sublining in all rats on day 23. In all cases a semiquantitative score of 4 was assigned, indicating that 51% or more of the cells were positive, whereas control sections were negative. DISCUSSION: The results presented here reveal that the number of TUNEL-positive cells remained very low until chronic arthritis developed. This indicates that, although there was sufficient DNA damage to cause an increment in p53 expression in the early phases, DNA strand breaks that can be detected by TUNEL assays only occurred in chronic AA. The observation that TUNEL-positive cells were nearly absent in early AA clearly indicates that only very few cells were undergoing programmed cell death. This is an important observation, which makes it possible to study the effects of apoptosis-inducing therapies in situ in early and accelerating AA. An effective therapy would obviously increase the number of TUNEL-positive cells. There is already some overexpression of p53 in the preclinical phase and during the onset of the arthritis, with an additional increment in p53 expression during accelerating and chronic arthritis. Presumably, this is wild-type p53, because the disease duration is likely too short to allow for the development of p53 mutations. Transcription of p53 is probably increased in response to the toxic environment of the inflamed joint. The increased expression of p53 in the joints of rats with chronic AA was even greater than that observed in synovial tissue of RA patients with long-standing disease. Overexpression of p53 and increased numbers of apoptotic cells did not occur simultaneously in this model; rather p53 overexpression preceded increased apoptosis. Activation of p53 leads to induction of cell growth arrest, allowing time for DNA repair. It appears that DNA damage is only extensive enough to induce apoptosis in the latter stages of AA. Factors other than p53 may also play an important role in the actual induction of apoptosis Taken together, significant apoptosis only occurs late in AA and it follows marked p53 overexpression, making it a useful model for testing proapoptotic therapies. AA is not the best model for p53 gene therapy, however, because dramatic p53 overexpression occurs in the latter stages of the disease

    The intensive care infection score - a novel marker for the prediction of infection and its severity

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    Background: The prediction of infection and its severity remains difficult in the critically ill. A novel, simple biomarker derived from five blood-cell derived parameters that characterize the innate immune response in routine blood samples, the intensive care infection score (ICIS), could be helpful in this respect. We therefore compared the predictive value of the ICIS with that of the white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT) for infection and its severity in critically ill patients. Methods: We performed a multicenter, cluster-randomized, crossover study in critically ill patients between January 2013 and September 2014. Patients with a suspected infection for which blood cultures were taken by the attending intensivist were included. Blood was taken at the same time for WBC, ICIS, CRP and PCT measurements in the control study periods. Results of imaging and cultures were collected. Patients were divided into groups of increasing likelihood of infection and invasiveness: group 1 without infection or with possible infection irrespective of cultures, group 2 with probable or microbiologically proven local infection without blood stream infection (BSI) and group 3 with BSI irrespective of local infection. Septic shock was assessed. Results: In total, 301 patients were enrolled. CRP, PCT and ICIS were higher in groups 2 and 3 than group 1. The area under the receiver operating characteristic curve (AUROC) for the prediction of infection was 0.70 for CRP, 0.71 for PCT and 0.73 for ICIS (P < 0.001). For the prediction of septic shock the AUROC was 0.73 for CRP, 0.85 for PCT and 0.76 for ICIS. These AUROC did not differ fro

    Cerebellar Cathodal Transcranial Direct Stimulation and Performance on a Verb Generation Task: A Replication Study

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    The role of the cerebellum in cognitive processing is increasingly recognized but still poorly understood. A recent study in this field applied cerebellar Transcranial Direct Current Stimulation (c-tDCS) to the right cerebellum to investigate the role of prefrontal-cerebellar loops in language aspects of cognition. Results showed that the improvement in participants' verbal response times on a verb generation task was facilitated immediately after cathodal c-tDCS, compared to anodal or sham c-tDCS. The primary aim of the present study is to replicate these findings and additionally to investigate possible longer term effects. A crossover within-subject design was used, comparing cathodal and sham c-tDCS. The experiment consisted of two visits with an interval of one week. Our results show no direct contribution of cathodal c-tDCS over the cerebellum to language task performance. However, one week later, the group receiving cathodal c-tDCS in the first visit show less improvement and increased variability in their verbal response times during the second visit, compared to the group receiving sham c-tDCS in the first visit. These findings suggest a potential negative effect of c-tDCS and warrant further investigation into long term effects of c-tDCS before undertaking clinical studies with poststroke patients with aphasia

    Food security among dryland pastoralists and agropastoralists: The climate, land-use change, and population dynamics nexus

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    During the last decades, pastoralist, and agropastoralist populations of the world’s drylands have become exceedingly vulnerable to regional and global changes. Specifically, exacerbated stressors imposed on these populations have adversely affected their food security status, causing humanitarian emergencies and catastrophes. Of these stressors, climate variability and change, land-use and management practices, and dynamics of human demography are of a special importance. These factors affect all four pillars of food security, namely, food availability, access to food, food utilization, and food stability. The objective of this study was to critically review relevant literature to assess the complex web of interrelations and feedbacks that affect these factors. The increasing pressures on the world’s drylands necessitate a comprehensive analysis to advise policy makers regarding the complexity and linkages among factors, and to improve global action. The acquired insights may be the basis for alleviating food insecurity of vulnerable dryland populations.info:eu-repo/semantics/acceptedVersio
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