Evaluating the use of the Model of Human Occupation Screening Tool in mental health services

Introduction: While the Model of Human Occupation Screening Tool has undergone psychometric development and testing and is widely used in mental health practice, only a few small-scale studies to date have examined its use in clinical practice. Method: A national survey was conducted with UK occupational therapists working in mental health settings to evaluate the use of the MOHOST. The survey included the modified version of the USE questionnaire and two open-ended questions. The latter were coded through inductive content analysis and all responses were analysed using Statistical Package for the Social Sciences. Results: n=105 questionnaires were analysed. The MOHOST was found to be a useful tool, with most therapists scoring it favourably on the usefulness (74.7%), ease of use (76.1%), ease of learning (81.2%) and satisfaction (80.6%) subscales. It was praised as a valuable outcome measure, guiding interventions and providing a comprehensive overview of assessed individuals. Time consumption, inaccessible terminology and lack of sensitivity to change were indicated as possible downfalls. Conclusion: Therapists valued the MOHOST as an assessment tool, but more importance should be placed on training to overcome some of the limitations identified here. Also, its suitability to the setting in which it is used should be considered before implementation in practice

Exotic Differentiable Structures and General Relativity

We review recent developments in differential topology with special concern for their possible significance to physical theories, especially general relativity. In particular we are concerned here with the discovery of the existence of non-standard (``fake'' or ``exotic'') differentiable structures on topologically simple manifolds such as $S^7$, \R and $S^3\times {\bf R^1}.$ Because of the technical difficulties involved in the smooth case, we begin with an easily understood toy example looking at the role which the choice of complex structures plays in the formulation of two-dimensional vacuum electrostatics. We then briefly review the mathematical formalisms involved with differentiable structures on topological manifolds, diffeomorphisms and their significance for physics. We summarize the important work of Milnor, Freedman, Donaldson, and others in developing exotic differentiable structures on well known topological manifolds. Finally, we discuss some of the geometric implications of these results and propose some conjectures on possible physical implications of these new manifolds which have never before been considered as physical models.Comment: 11 pages, LaTe

The Effects of Malignant Transformation on Susceptibility of Human Urothelial Cells to CD40-Mediated Apoptosis

Background: The tumor necrosis factor (TNF) superfamily of ligands and receptors mediates immune cell survival. Some members possess a death domain, a protein motif that functions to transmit apoptotic signals, whereas others, such as CD40, do not. CD40 is expressed by both normal and malignant epithelial cells. To investigate the functional significance of this expression, we studied the effects of ligation of CD40, Fas, and TNF receptors (TNFRs) on the proliferation and survival of normal and malignant human urothelial cells and urothelial cells with disabled p53 function. Methods: Normal and malignant human urothelial cells were cultured with soluble TNF family agonists (CD40 ligand [CD40L], TNF-α, anti-Fas antibody, or cocultured with mouse fibroblasts stably transfected with plasmids that caused the cells to constitutively express CD40L or CD32; cell proliferation was estimated by an [3H]thymidine incorporation assay, and apoptosis was determined by Annexin V staining and by a DNA fragmentation assay. Messenger RNA levels for CD40 and potential downstream effector molecules were quantified by polymerase chain reaction-based and ribonuclease protection assays, respectively, and nuclear factor (NF) κB nuclear translocation was detected by immunofluorescence. All statistical tests were two-sided. Results: Soluble trimeric CD40L inhibited the growth of normal and malignant urothelial cells but did not induce apoptosis. Cell surface-presented CD40L induced massive apoptosis in CD40-positive transitional cell carcinoma cells but not in normal urothelial cells. Normal cells underwent CD40L-mediated apoptosis only in the presence of other TNFR agonists. An agonistic anti-CD40 antibody presented on the surface of CD32-transfected fibroblasts also induced apoptosis in transitional cell carcinoma cells and in normal urothelial cells. Apoptotic responses of tumor (but not normal) cells to soluble agonists were enhanced by blocking protein synthesis. Karyotypically normal urothelial cells with disabled p53 function underwent apoptosis during coculture with CD40L-expressing fibroblasts alone but were not additionally sensitive to additional TNFR agonists. Conclusions: Susceptibility to CD40 ligation-induced apoptosis may be a novel mechanism for eliminating neoplastically transformed urothelial cells. Loss of CD40 expression may be an important adaptive mechanism for transitional cell carcinoma development and progressio

Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent Apoptosis, but are insensitive to direct activation with exogenous fas ligand

Introduction Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF) receptor family members; CD40 and Fas (CD95). Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma. Aims To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines. Results Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both. Conclusions 1) Both primary and malignant cholangiocytes are relatively resistant to Fas–mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2) The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes

The visual nonverbal memory trace is fragile when actively maintained, but endures passively for tens of seconds

Despite attempts at active maintenance in the focus of attention, the fragile nature of the visual nonverbal memory trace may be revealed when the retention interval between target memoranda and probed recall on a trial is extended. In contrast, a passively maintained or unattended visual memory trace may be revealed as persisting proactive interference extending across quite extended intervals between trials in a recent probes task. The present study, comprising five experiments, used this task to explore the persistence of such a passive visual memory trace over time. Participants viewed some target visual items (for example, abstract colored patterns) followed by a variable retention interval and a probe item. The task was to report whether the probe matched one of the targets or not. A decaying active memory trace was indicated by poorer performance as the memory retention interval was extended on a trial. However, when the probe was a member of the target set from the preceding trial, task performance was poorer than a comparison novel probe, demonstrating proactive interference. Manipulations of the intertrial interval revealed that the temporal persistence of the passive memory trace of an old target was impressive, and proactive interference was largely resilient to a simple ‘cued forgetting’ manipulation. These data support the proposed two-process memory conception (active–passive memory) contrasting fragile active memory traces decaying over a few seconds with robust passive traces extending to tens of seconds