Development and Preliminary Validation of the Scale for Evaluation of Psychiatric Integrative and Continuous Care—Patient’s Version

This pilot study aimed to evaluate and examine an instrument that integrates relevant aspects of cross-sectoral (in- and outpatients) mental health care, is simply to use and shows satisfactory psychometric properties. The development of the scale comprised literature research, held 14 focus groups and 12 interviews with patients and health care providers, item-pool generation, content validation by a scientific expert panel, and face validation by 90 patients. The preliminary scale was tested on 385 patients across seven German hospitals with cross-sectoral mental health care (CSMHC) as part of their treatment program. Psychometric properties of the scale were evaluated using genuine and transformed data scoring. To check reliability and postdictive validity of the scale, Cronbach’s α coefficient and multivariable linear regression were used. This development process led to the development of an 18-item scale called the “Scale for Evaluation of Psychiatric Integrative and Continuous Care (SEPICC)” with a two-point and five-point response options. The scale consists of two sections. The first section assesses the presence or absence of patients’ experiences with various CSMHC’ relevant components such as home treatment, flexibility of treatments’ switching, case management, continuity of care, cross-sectoral therapeutic groups, and multidisciplinary teams. The second section evaluates the patients’ opinions about these relevant components. Using raw and transformed scoring resulted into comparable results. However, data distribution using transformed scoring showed a smaller deviation from normality. For the overall scale, the Cronbach’s α coefficient was 0.82. Self-reported experiences with relevant components of the CSMHC were positively associated with the patients approval of these components. In conclusion, the new scale provides a good starting point for further validation. It can be used as a tool to evaluate CSMHC. Methodologically, using transformed data scoring appeared to be preferable because of a smaller deviation from normality and a higher reliability measured by Cronbach’s α

Direct electrophysiological evidence for prefrontal control of hippocampal processing during voluntary forgetting

Forgetting does not necessarily reflect failure to encode information but can, to some extent, also be voluntarily controlled. Previous studies have suggested that voluntary forgetting relies on active inhibition of encoding processes in the hippocampus by the dorsolateral prefrontal cortex (DLPFC) [1, 2, 3, 4]. During attentional and sensorimotor processing, enhanced DLPFC theta power alongside increased alpha/beta oscillations are a neural signature of an inhibitory top-down mechanism, with theta oscillations reflecting prefrontal control and alpha/beta oscillations occurring in areas targeted by inhibition [5, 6, 7, 8, 9, 10, 11, 12]. Here, we used intracranial EEG recordings in presurgical epilepsy patients implanted in DLPFC (n = 13) and hippocampus (n = 15) during an item-method directed forgetting paradigm. We found that voluntary forgetting is associated with increased neural oscillations in the low theta band (3–5 Hz) in DLPFC and in a broad theta/alpha/beta (6–18 Hz) frequency range in hippocampus. Combining time-lagged correlation analysis, phase synchronization, and Granger causality in 6 patients with electrodes in both DLPFC and hippocampus, we obtained converging evidence for a top-down control of hippocampal activity by the DLPFC. Together, our results provide strong support for a model in which voluntary forgetting relies on enhanced inhibition of the hippocampus by the DLPFC

Investigations on Additively Manufactured Stainless Bearings

Additive manufacturing with multi-material design offers great possibilities for lightweight and function-integrated components. A process chain was developed in which hybrid steel–steel-components with high fatigue strength were produced. For this, a material combination of stainless powder material Rockit® (0.52 wt.% C, 0.9% Si, 14% Cr, 0.4% Mo, 1.8% Ni, 1.2% V, bal. Fe) cladded onto ASTM A572 mild steel by plasma arc powder deposition welding was investigated. Extensive material characterization has shown that defect-free claddings can be produced by carefully adjusting the welding process. With a tailored heat treatment strategy and machining of the semi-finished products, bearing washers for a thrust cylindrical roller bearing were produced. These washers showed a longer fatigue life than previously produced bearing washers with AISI 52100 bearing steel as cladding. It was also remarkable that the service life with the Rockit® cladding material was longer than that of conventional monolithic AISI 52100 washers. This was reached through a favourable microstructure with finely distributed vanadium and chromium carbides in a martensitic matrix as well as the presence of compressive residual stresses, which are largely retained even after testing. The potential for further enhancement of the cladding performance through Tailored Forming was investigated in compression and forging tests and was found to be limited due to low forming capacity of the material

Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal.

Recent advances in single-cell technologies have permitted the investigation of heterogeneous cell populations at previously unattainable resolution. Here we apply such approaches to resolve the molecular mechanisms driving disease in mouse hematopoietic stem cells (HSCs), using JAK2V617F mutant myeloproliferative neoplasms (MPNs) as a model. Single-cell gene expression and functional assays identified a subset of JAK2V617F mutant HSCs that display defective self-renewal. This defect is rescued at the single HSC level by crossing JAK2V617F mice with mice lacking TET2, the most commonly comutated gene in patients with MPN. Single-cell gene expression profiling of JAK2V617F-mutant HSCs revealed a loss of specific regulator genes, some of which were restored to normal levels in single TET2/JAK2 mutant HSCs. Of these, Bmi1 and, to a lesser extent, Pbx1 and Meis1 overexpression in JAK2-mutant HSCs could drive a disease phenotype and retain durable stem cell self-renewal in functional assays. Together, these single-cell approaches refine the molecules involved in clonal expansion of MPNs and have broad implications for deconstructing the molecular network of normal and malignant stem cells.MS is the recipient of a BBSRC Industrial CASE PhD Studentship, and CAO and JF are recipients of Wellcome Trust PhD Studentships. Work in the Kent lab is supported by a Bloodwise Bennett Fellowship (15008), a European Hematology Association Non-Clinical Advanced Research Fellowship, and an ERC Starting Grant (ERC-2016-STG–715371). Work in the Green Lab is supported by the Wellcome Trust, Bloodwise, Cancer Research UK, the Kay Kendall Leukaemia Fund, and the Leukemia and Lymphoma Society of America. Dr. Kent, Professor Göttgens, and Professor Green are all supported by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute the National Institute for Health Research Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre

Disentangling dyskinesia from parkinsonism in motor structures of patients with schizophrenia

Patients with schizophrenia frequently suffer from motor abnormalities, but underlying alterations in neuroarchitecture remain unclear. Here, we aimed to disentangle dyskinesia from parkinsonism in motor structures of patients with schizophrenia and to assess associated molecular architecture. We measured grey matter of motor regions and correlated volumetric estimates with dyskinesia and parkinsonism severity. Associations with molecular architecture were identified by cross-modal spatial correlations between ensuing maps of abnormality-related volume alterations and neurotransmitter maps from healthy populations. Both phenomena were linked to (specific) striatal and basal forebrain reductions as well as to D1 receptor density. Dyskinesia also manifested in cerebellar decrease, while parkinsonism was associated with less motor cortex volume. The parkinsonism-related brain pattern was additionally associated with 5-HT1A/2A and µ-opioid receptors distribution. Findings suggest the need to develop psychopharmacological compounds that display not only selectivity for receptor subtypes but also anatomical selectivity for alleviating dyskinesia without worsening parkinsonism and vice versa

Identification of Potential Sites for Tryptophan Oxidation in Recombinant Antibodies Using tert-Butylhydroperoxide and Quantitative LC-MS

Amino acid oxidation is known to affect the structure, activity, and rate of degradation of proteins. Methionine oxidation is one of the several chemical degradation pathways for recombinant antibodies. In this study, we have identified for the first time a solvent accessible tryptophan residue (Trp-32) in the complementary-determining region (CDR) of a recombinant IgG1 antibody susceptible to oxidation under real-time storage and elevated temperature conditions. The degree of light chain Trp-32 oxidation was found to be higher than the oxidation level of the conserved heavy chain Met-429 and the heavy chain Met-107 of the recombinant IgG1 antibody HER2, which have already been identified as being solvent accessible and sensitive to chemical oxidation. In order to reduce the time for simultaneous identification and functional evaluation of potential methionine and tryptophan oxidation sites, a test system employing tert-butylhydroperoxide (TBHP) and quantitative LC-MS was developed. The optimized oxidizing conditions allowed us to specifically oxidize the solvent accessible methionine and tryptophan residues that displayed significant oxidation in the real-time stability and elevated temperature study. The achieved degree of tryptophan oxidation was adequate to identify the functional consequence of the tryptophan oxidation by binding studies. In summary, the here presented approach of employing TBHP as oxidizing reagent combined with quantitative LC-MS and binding studies greatly facilitates the efficient identification and functional evaluation of methionine and tryptophan oxidation sites in the CDR of recombinant antibodies

Covid-19 triage in the emergency department 2.0: how analytics and AI transform a human-made algorithm for the prediction of clinical pathways

The Covid-19 pandemic has pushed many hospitals to their capacity limits. Therefore, a triage of patients has been discussed controversially primarily through an ethical perspective. The term triage contains many aspects such as urgency of treatment, severity of the disease and pre-existing conditions, access to critical care, or the classification of patients regarding subsequent clinical pathways starting from the emergency department. The determination of the pathways is important not only for patient care, but also for capacity planning in hospitals. We examine the performance of a human-made triage algorithm for clinical pathways which is considered a guideline for emergency departments in Germany based on a large multicenter dataset with over 4,000 European Covid-19 patients from the LEOSS registry. We find an accuracy of 28 percent and approximately 15 percent sensitivity for the ward class. The results serve as a benchmark for our extensions including an additional category of palliative care as a new label, analytics, AI, XAI, and interactive techniques. We find significant potential of analytics and AI in Covid-19 triage regarding accuracy, sensitivity, and other performance metrics whilst our interactive human-AI algorithm shows superior performance with approximately 73 percent accuracy and up to 76 percent sensitivity. The results are independent of the data preparation process regarding the imputation of missing values or grouping of comorbidities. In addition, we find that the consideration of an additional label palliative care does not improve the results

All-In-One: Advanced preparation of Human Parenchymal and Non-Parenchymal Liver Cells

BACKGROUND & AIMS: Liver cells are key players in innate immunity. Thus, studying primary isolated liver cells is necessary for determining their role in liver physiology and pathophysiology. In particular, the quantity and quality of isolated cells are crucial to their function. Our aim was to isolate a large quantity of high-quality human parenchymal and non-parenchymal cells from a single liver specimen. METHODS: Hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and stellate cells were isolated from liver tissues by collagenase perfusion in combination with low-speed centrifugation, density gradient centrifugation, and magnetic-activated cell sorting. The purity and functionality of cultured cell populations were controlled by determining their morphology, discriminative cell marker expression, and functional activity. RESULTS: Cell preparation yielded the following cell counts per gram of liver tissue: 2.0+/-0.4x107 hepatocytes, 1.8+/-0.5x106 Kupffer cells, 4.3+/-1.9x105 liver sinusoidal endothelial cells, and 3.2+/-0.5x105 stellate cells. Hepatocytes were identified by albumin (95.5+/-1.7%) and exhibited time-dependent activity of cytochrome P450 enzymes. Kupffer cells expressed CD68 (94.5+/-1.2%) and exhibited phagocytic activity, as determined with 1mum latex beads. Endothelial cells were CD146+ (97.8+/-1.1%) and exhibited efficient uptake of acetylated low-density lipoprotein. Hepatic stellate cells were identified by the expression of alpha-smooth muscle actin (97.1+/-1.5%). These cells further exhibited retinol (vitamin A)-mediated autofluorescence. CONCLUSIONS: Our isolation procedure for primary parenchymal and non-parenchymal liver cells resulted in cell populations of high purity and quality, with retained physiological functionality in vitro. Thus, this system may provide a valuable tool for determining liver function and disease

VR China: Gesetz ueber Vertrags-Joint-Ventures, 1988 und Gesetz ueber volkseigene Industrieunternehmen (Unternehmensgesetz), 1988

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