155 research outputs found

    Reflecting on the reasons pros and cons coercive measures for patients in psychiatric and somatic care: The role of clinical ethics consultation. A pilot study

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    Background and aim: Coercive measures in patient care have come under criticism leading to implement guidelines dedicated to the reduction of coercion. This development of bringing to light clinical ethics support is hoped to serve as a means of building up awareness and potentially reducing the use of coercion. This study explores the specific features of ethics consultation (EC) while dealing with coercion. Material and method: Basel EC documentation presents insight to all persons involved with a case. The EC database of two Basel university hospitals was developed on the grounds of systematic screening and categorization by two reviewers. One hundred fully documented EC cases databased from 2013 to 2016 were screened for the discussion of coercive measures (somatic hospital and psychiatry: 50% cases). Results: Twenty-four out of 100 EC cases addressed coercion in relation to a clinically relevant question, such as compulsory treatment (70.8%), involuntary committal (50%), or restricting liberty (16.6%). Only 58.3% of EC requests mentioned coercion as an ethical issue prior to the meeting. In no case was patient decisional capacity given, capacity was impaired (43.5%), not given (33.3%), or unclear (21.7%; one not available). Discussion: As clinical staff appears sensitive to perceiving ethical uncertainty or conflict, but less prepared to articulate ethical concern, EC meetings serve to "diagnose" and "solve" the ethical focus of the problem(s) presented in EC. Patient decisional incapacity proved to be an important part of reasoning, when discussing the principle of harm prevention. While professional judgment of capacity remains unsystematic, rationality or even ethicality of decision making will be hampered. The documented EC cases show a variety of decisions about whether or not coercion was actually applied. Ethical reasoning on the competing options seemed to be instrumental for an unprejudiced decision complying with the normative framework and for building a robust consensus. Conclusions: The recommendation is whether EC should be used as a standard practice whenever coercion is an issue-ideally before coercion is applied, or otherwise. Moreover, more efforts should be made toward early and professional assessment of patient capacity and advance care counseling including the offer of advance directives

    Differentiation of In Vitro–Modified Human Peripheral Blood Monocytes Into Hepatocyte–like and Pancreatic Islet-like Cells

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    BACKGROUND & AIMS: Adult stem cells provide a promising alternative for the treatment of diabetes mellitus and end-stage liver diseases. We evaluated the differentiation potential of human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells. METHODS: Monocytes were treated with macrophage colony-stimulating factor and interleukin 3 for 6 days, followed by incubation with hepatocyte and pancreatic islet-specific differentiation media. Cells were characterized by flow cytometry, gene-expression analysis, metabolic assays, and transplantation for their state of differentiation and tissue-specific functions. RESULTS: In response to macrophage colony-stimulating factor and interleukin 3, monocytes resumed cell division in a CD115-dependent fashion, which was associated with a down-regulation of the PRDM1 and ICSBP genes. These programmable cells of monocytic origin were capable of differentiating into neohepatocytes, which closely resemble primary human hepatocytes with respect to morphology, expression of hepatocyte markers, and specific metabolic functions. After transplantation into the liver of severe combined immunodeficiency disease/nonobese diabetic mice, neohepatocytes integrated well into the liver tissue and showed a morphology and albumin expression similar to that of primary human hepatocytes transplanted under identical conditions. Programmable cells of monocytic origin-derived pancreatic neoislets expressed beta cell-specific transcription factors, secreted insulin and C peptide in a glucose-dependent manner, and normalized blood glucose levels when xenotransplanted into immunocompetent, streptozotocin-treated diabetic mice. Programmable cells of monocytic origin retained monocytic characteristics, notably CD14 expression, a monocyte-specific methylation pattern of the CD115 gene, and expression of the transcription factor PU.1. CONCLUSIONS: The ability to reprogram, expand, and differentiate peripheral blood monocytes in large quantities opens the real possibility of the clinical application of programmable cells of monocytic origin in tissue repair and organ regeneration

    Competing electric and magnetic excitations in backward electron scattering from heavy deformed nuclei

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    Important E2E2 contributions to the (e,eâ€Č)(e,e^{\prime}) cross sections of low-lying orbital M1M1 excitations are found in heavy deformed nuclei, arising from the small energy separation between the two excitations with IπK=2+1I^{\pi}K = 2^+1 and 1+1^+1, respectively. They are studied microscopically in QRPA using DWBA. The accompanying E2E2 response is negligible at small momentum transfer qq but contributes substantially to the cross sections measured at Ξ=165∘\theta = 165 ^{\circ} for 0.6<qeff<0.90.6 < q_{\rm eff} < 0.9 fm−1^{-1} (40≀Ei≀7040 \le E_i \le 70 MeV) and leads to a very good agreement with experiment. The electric response is of longitudinal C2C2 type for Ξ≀175∘\theta \le 175 ^{\circ} but becomes almost purely transverse E2E2 for larger backward angles. The transverse E2E2 response remains comparable with the M1M1 response for qeff>1.2q_{\rm eff} > 1.2 fm−1^{-1} (Ei>100E_i > 100 MeV) and even dominant for Ei>200E_i > 200 MeV. This happens even at large backward angles Ξ>175∘\theta > 175 ^{\circ}, where the M1M1 dominance is limited to the lower qq region.Comment: RevTeX, 19 pages, 8 figures included Accepted for publication in Phys Rev

    A four-dimensional probabilistic atlas of the human brain

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    The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype-phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders

    A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

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    © The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

    Comparison of scores for bimodality of gene expression distributions and genome-wide evaluation of the prognostic relevance of high-scoring genes

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    <p>Abstract</p> <p>Background</p> <p>A major goal of the analysis of high-dimensional RNA expression data from tumor tissue is to identify prognostic signatures for discriminating patient subgroups. For this purpose genome-wide identification of bimodally expressed genes from gene array data is relevant because distinguishability of high and low expression groups is easier compared to genes with unimodal expression distributions.</p> <p>Recently, several methods for the identification of genes with bimodal distributions have been introduced. A straightforward approach is to cluster the expression values and score the distance between the two distributions. Other scores directly measure properties of the distribution. The kurtosis, e.g., measures divergence from a normal distribution. An alternative is the outlier-sum statistic that identifies genes with extremely high or low expression values in a subset of the samples.</p> <p>Results</p> <p>We compare and discuss scores for bimodality for expression data. For the genome-wide identification of bimodal genes we apply all scores to expression data from 194 patients with node-negative breast cancer. Further, we present the first comprehensive genome-wide evaluation of the prognostic relevance of bimodal genes. We first rank genes according to bimodality scores and define two patient subgroups based on expression values. Then we assess the prognostic significance of the top ranking bimodal genes by comparing the survival functions of the two patient subgroups. We also evaluate the global association between the bimodal shape of expression distributions and survival times with an enrichment type analysis.</p> <p>Various cluster-based methods lead to a significant overrepresentation of prognostic genes. A striking result is obtained with the outlier-sum statistic (<it>p </it>< 10<sup>-12</sup>). Many genes with heavy tails generate subgroups of patients with different prognosis.</p> <p>Conclusions</p> <p>Genes with high bimodality scores are promising candidates for defining prognostic patient subgroups from expression data. We discuss advantages and disadvantages of the different scores for prognostic purposes. The outlier-sum statistic may be particularly valuable for the identification of genes to be included in prognostic signatures. Among the genes identified as bimodal in the breast cancer data set several have not yet previously been recognized to be prognostic and bimodally expressed in breast cancer.</p

    A four-dimensional probabilistic atlas of the human brain

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    The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype– phenotype–behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders

    Anatomical Global Spatial Normalization

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    Anatomical global spatial normalization (aGSN) is presented as a method to scale high-resolution brain images to control for variability in brain size without altering the mean size of other brain structures. Two types of mean preserving scaling methods were investigated, “shape preserving” and “shape standardizing”. aGSN was tested by examining 56 brain structures from an adult brain atlas of 40 individuals (LPBA40) before and after normalization, with detailed analyses of cerebral hemispheres, all gyri collectively, cerebellum, brainstem, and left and right caudate, putamen, and hippocampus. Mean sizes of brain structures as measured by volume, distance, and area were preserved and variance reduced for both types of scale factors. An interesting finding was that scale factors derived from each of the ten brain structures were also mean preserving. However, variance was best reduced using whole brain hemispheres as the reference structure, and this reduction was related to its high average correlation with other brain structures. The fractional reduction in variance of structure volumes was directly related to ρ2, the square of the reference-to-structure correlation coefficient. The average reduction in variance in volumes by aGSN with whole brain hemispheres as the reference structure was approximately 32%. An analytical method was provided to directly convert between conventional and aGSN scale factors to support adaptation of aGSN to popular spatial normalization software packages
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