208 research outputs found

    Needs-oriented discharge planning and monitoring for high utilisers of psychiatric services (NODPAM): Design and methods

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    <p>Abstract</p> <p>Background</p> <p>Attempts to reduce high utilisation of psychiatric inpatient care by targeting the critical time of hospital discharge have been rare.</p> <p>Methods</p> <p>This paper presents design and methods of the study "Effectiveness and Cost-Effectiveness of Needs-Oriented Discharge Planning and Monitoring for High Utilisers of Psychiatric Services" (NODPAM), a multicentre RCT conducted in five psychiatric hospitals in Germany. Inclusion criteria are receipt of inpatient psychiatric care, adult age, diagnosis of schizophrenia or affective disorder, defined high utilisation of psychiatric care during two years prior to the current admission, and given informed consent. Consecutive recruitment started in April 2006. Since then, during a period of 18 months, comprehensive outcome data of 490 participants is being collected at baseline and during three follow-up measurement points.</p> <p>The manualised intervention applies principles of needs-led care and focuses on the inpatient-outpatient transition. A trained intervention worker provides two intervention sessions: (a) Discharge planning: Just before discharge with the patient and responsible clinician at the inpatient service; (b) Monitoring: Three months after discharge with the patient and outpatient clinician. A written treatment plan is signed by all participants after each session.</p> <p>Primary endpoints are whether participants in the intervention group will show fewer hospital days and readmissions to hospital. Secondary endpoints are better compliance with aftercare, better clinical outcome and quality of life, as well as cost-effectiveness and cost-utility.</p> <p>Discussion</p> <p>If a needs-oriented discharge planning and monitoring proves to be successful in this RCT, a tool will be at hand to improve patient outcome and reduce costs via harmonising fragmented mental health service provision.</p> <p>Trial Registration</p> <p>ISRCTN59603527</p

    Sleep quality, the neglected outcome variable in clinical studies focusing on locomotor system; a construct validation study

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    Background: In addition to general health and pain, sleep is highly relevant to judging the well-being of an individual. Of these three important outcome variables, however, sleep is neglected in most outcome studies. Sleep is a very important resource for recovery from daily stresses and strains, and any alteration of sleep will likely affect mental and physical health, especially during disease. Sleep assessment therefore should be standard in all population-based or clinical studies focusing on the locomotor system. Yet current sleep assessment tools are either too long or too specific for general use. Methods: Based on a literature review and subsequent patient-based rating of items, an expert panel designed a four-item questionnaire about sleep. Construct validation of the questionnaire in a random sample of the German-speaking Swiss population was performed in 2003. Reliability, correlation, and tests for internal consistency and validity were analyzed. Results: Overall, 16,634 (70%) out of 23,763 eligible individuals participated in the study. Test-retest reliability coefficients ranged from 0.72 to 0.87, and a Cronbach’s alpha of 0.83 indicates good internal consistency. Results show a moderate to good correlation between sleep disturbances and health perception, and between sleep disturbances and overall pain. Conclusions: The Sleep Standard Evaluation Questionnaire (SEQ-Sleep) is a reliable and short tool with confirmed construct validity for sleep assessment in population-based observational studies. It is easy to administer and therefore suitable for postal surveys of the general population. Criterion validity remains to be determined

    Performance of the CMS Cathode Strip Chambers with Cosmic Rays

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    The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

    It's all about the children: a participant-driven photo-elicitation study of Mexican-origin mothers' food choices

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    Abstract Background There is a desperate need to address diet-related chronic diseases in Mexican-origin women, particularly for those in border region colonias (Mexican settlements) and other new destination communities in rural and non-rural areas of the U.S. Understanding the food choices of mothers, who lead food and health activities in their families, provides one way to improve health outcomes in Mexican-origin women and their children. This study used a visual method, participant-driven photo-elicitation, and grounded theory in a contextual study of food choices from the perspectives of Mexican-origin mothers. Methods Teams of trained promotoras (female community health workers from the area) collected all data in Spanish. Ten Mexican-origin mothers living in colonias in Hidalgo County, TX completed a creative photography assignment and an in-depth interview using their photographs as visual prompts and examples. English transcripts were coded inductively by hand, and initial observations emphasized the salience of mothers' food practices in their routine care-giving. This was explored further by coding transcripts in the qualitative data analysis software Atlas.ti. Results An inductive conceptual framework was created to provide context for understanding mothers' daily practices and their food practices in particular. Three themes emerged from the data: 1) a mother's primary orientation was toward her children; 2) leveraging resources to provide the best for her children; and 3) a mother's daily food practices kept her children happy, healthy, and well-fed. Results offer insight into the intricate meanings embedded in Mexican-origin mothers' routine food choices. Conclusions This paper provides a new perspective for understanding food choice through the eyes of mothers living in the colonias of South Texas -- one that emphasizes the importance of children in their routine food practices and the resilience of the mothers themselves. Additional research is needed to better understand mothers' perspectives and food practices with larger samples of women and among other socioeconomic groups

    Molecular Genetic Analysis of 103 Sporadic Colorectal Tumours in Czech Patients

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    The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in Europe. To evaluate whether sporadic CRCs in Czech patients have specific mutational profiles we analysed somatic genetic changes in known CRC genes (APC, KRAS, TP53, CTNNB1, MUTYH and BRAF, loss of heterozygosity (LOH) at the APC locus, microsatellite instability (MSI), and methylation of the MLH1 promoter) in 103 tumours from 102 individuals. The most frequently mutated gene was APC (68.9% of tumours), followed by KRAS (31.1%), TP53 (27.2%), BRAF (8.7%) and CTNNB1 (1.9%). Heterozygous germline MUTYH mutations in 2 patients were unlikely to contribute to the development of their CRCs. LOH at the APC locus was found in 34.3% of tumours, MSI in 24.3% and MLH1 methylation in 12.7%. Seven tumours (6.9%) were without any changes in the genes tested. The analysis yielded several findings possibly specific for the Czech cohort. Somatic APC mutations did not cluster in the mutation cluster region (MCR). Tumours with MSI but no MLH1 methylation showed earlier onset and more severe mutational profiles compared to MSI tumours with MLH1 methylation. TP53 mutations were predominantly located outside the hot spots, and transitions were underrepresented. Our analysis supports the observation that germline MUTYH mutations are rare in Czech individuals with sporadic CRCs. Our findings suggest the influence of specific ethnic genetic factors and/or lifestyle and dietary habits typical for the Czech population on the development of these cancers

    Development of an In Vitro Model for the Multi-Parametric Quantification of the Cellular Interactions between Candida Yeasts and Phagocytes

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    We developed a new in vitro model for a multi-parameter characterization of the time course interaction of Candida fungal cells with J774 murine macrophages and human neutrophils, based on the use of combined microscopy, fluorometry, flow cytometry and viability assays. Using fluorochromes specific to phagocytes and yeasts, we could accurately quantify various parameters simultaneously in a single infection experiment: at the individual cell level, we measured the association of phagocytes to fungal cells and phagocyte survival, and monitored in parallel the overall phagocytosis process by measuring the part of ingested fungal cells among the total fungal biomass that changed over time. Candida albicans, C. glabrata, and C. lusitaniae were used as a proof of concept: they exhibited species-specific differences in their association rate with phagocytes. The fungal biomass uptaken by the phagocytes differed significantly according to the Candida species. The measure of the survival of fungal and immune cells during the interaction showed that C. albicans was the more aggressive yeast in vitro, destroying the vast majority of the phagocytes within five hours. All three species of Candida were able to survive and to escape macrophage phagocytosis either by the intraphagocytic yeast-to-hyphae transition (C. albicans) and the fungal cell multiplication until phagocytes burst (C. glabrata, C. lusitaniae), or by the avoidance of phagocytosis (C. lusitaniae). We demonstrated that our model was sensitive enough to quantify small variations of the parameters of the interaction. The method has been conceived to be amenable to the high-throughput screening of mutants in order to unravel the molecular mechanisms involved in the interaction between yeasts and host phagocytes

    Thermodynamics-Based Models of Transcriptional Regulation by Enhancers: The Roles of Synergistic Activation, Cooperative Binding and Short-Range Repression

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    Quantitative models of cis-regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation. However, the few models available today have been based on simplistic assumptions about the sequences being modeled, or heuristic approximations of the underlying regulatory mechanisms. We have developed a thermodynamics-based model to predict gene expression driven by any DNA sequence, as a function of transcription factor concentrations and their DNA-binding specificities. It uses statistical thermodynamics theory to model not only protein-DNA interaction, but also the effect of DNA-bound activators and repressors on gene expression. In addition, the model incorporates mechanistic features such as synergistic effect of multiple activators, short range repression, and cooperativity in transcription factor-DNA binding, allowing us to systematically evaluate the significance of these features in the context of available expression data. Using this model on segmentation-related enhancers in Drosophila, we find that transcriptional synergy due to simultaneous action of multiple activators helps explain the data beyond what can be explained by cooperative DNA-binding alone. We find clear support for the phenomenon of short-range repression, where repressors do not directly interact with the basal transcriptional machinery. We also find that the binding sites contributing to an enhancer's function may not be conserved during evolution, and a noticeable fraction of these undergo lineage-specific changes. Our implementation of the model, called GEMSTAT, is the first publicly available program for simultaneously modeling the regulatory activities of a given set of sequences

    Immunoscreening of the extracellular proteome of colorectal cancer cells

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    <p>Abstract</p> <p>Background</p> <p>The release of proteins from tumors can trigger an immune response in cancer patients involving T lymphocytes and B lymphocytes, which results in the generation of antibodies to tumor-derived proteins. Many studies aim to use humoral immune responses, namely autoantibody profiles, directly, as clinical biomarkers. Alternatively, the antibody immune response as an amplification system for tumor associated alterations may be used to indicate putative protein biomarkers with high sensitivity. Aiming at the latter approach we here have implemented an autoantibody profiling strategy which particularly focuses on proteins released by tumor cells in vitro: the so-called secretome.</p> <p>Methods</p> <p>For immunoscreening, the extracellular proteome of five colorectal cancer cell lines was resolved on 2D gels, immobilized on PVDF membranes and used for serological screening with individual sera from 21 colorectal cancer patients and 24 healthy controls. All of the signals from each blot were assigned to a master map, and autoantigen candidates were defined based of the pattern of immunoreactivities. The corresponding proteins were isolated from preparative gels, identified by MALDI-MS and/or by nano-HPLC/ESI-MS/MS and exemplarily confirmed by duplex Western blotting combining the human serum samples with antibodies directed against the protein(s) of interest.</p> <p>Results</p> <p>From 281 secretome proteins stained with autoantibodies in total we first defined the "background patterns" of frequently immunoreactive extracellular proteins in healthy and diseased people. An assignment of these proteins, among them many nominally intracellular proteins, to the subset of exosomal proteins within the secretomes revealed a large overlap. On this basis we defined and consequently confirmed novel biomarker candidates such as the extreme C-terminus of the extracellular matrix protein agrin within the set of cancer-enriched immunorectivities.</p> <p>Conclusions</p> <p>Our findings suggest, first, that autoantibody responses may be due, in large part, to cross-presentation of antigens to the immune system via exosomes, membrane vesicles released by tumor cells and constituting a significant fraction of the secretome. In addition, this immunosecretomics approach has revealed novel biomarker candidates, some of them secretome-specific, and thus serves as a promising complementary tool to the frequently reported immunoproteomic studies for biomarker discovery.</p
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