34 research outputs found

    Appropriateness of acute admissions and last in-patient day for patients with long term neurological conditions

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    <p>Abstract</p> <p>Background</p> <p>To examine the appropriateness of admissions and in-patient stay for patients with long term neurological conditions (LTNCs). To identify variables predictive of appropriateness and explore management alternatives.</p> <p>Methods</p> <p>Adults admitted as acute patients to Derby Hospitals NHS Foundation Trust (England). Data were collected prospectively and examined by a multi-disciplinary expert panel to determine the appropriateness of admission and length of stay (LoS). Management alternatives were discussed.</p> <p>Results</p> <p>A total of 119 participants were recruited. 32 admissions were inappropriate and 83 were for an inappropriate duration. Whether a participant lived in their own home was predictive of an inappropriate admission. The number of LTNCs, number of presenting complaints and whether the participant lived alone in their own home were predictive of an inappropriate LoS. For admissions judged to be inappropriate, the panel suggested management alternatives.</p> <p>Conclusion</p> <p>Patients with LTNCs are being admitted to hospital when other services, e.g. ambulatory care, are available which could meet their needs. Inefficiencies in hospital procedures, such as discharge planning and patient transfers, continue to exist. Recognition of the need to plan for discharge at admission and to ensure in-patient services are provided in a timely manner may contribute towards improved efficiency.</p

    Key-music: an expert system environment for music composition

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    In this paper we briefly explain the main concepts underlying the Key-Music system, a prototype of Artificial Intelligence tool for music knowledge representation and music composition. Key-Music is based on the Petri nets theory in conjunction with Knowledge Representation for storing general definitions about musical timed process, under the form of semantic frame-based multiple inheritance networks; representations of actual, individual music process can be generated as instances of a general definition, and Petri nets are automati cally derived to describe and perform them. Presently, the output of the system can be both a midi and a cmusic file

    Meta-Analysis of the role of p53 status in isogenic systems tested for sensitivity to cytotoxic antoneoplastic drugs

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    The role of p53 in modifying sensitivity to cytotoxic drugs has been commonly studied by creating transfection pairs of wt p53 parental cells and altered p53 daughter cells, or vice versa. Authors inevitably tended to extrapolate and generalize their experimental observations, and conflicting reports have been more the rule than the exception. We have performed a meta-analysis of 356 independent studies. Average changes of drug sensitivity after a change of p53 status were observed. E6 transfection predominantly induces sensitization to cytotoxic drugs, whereas p53-/- knockout cells are more drug-resistant than their normal p53+/+ counterpart. Unexpectedly, transfection with a mutated p53 does not change much the drug sensitivity of most wt p53 cancer lines, with the notable exception of A2780, a predominant cell line in the studies analyzed (A2780 cells show increased resistance after transfection with a mutated p53). Rather interestingly, mitotic spindle poisons acted differently from other classes of cytotoxic drugs. A crucial indication of our findings is that the role of p53 alone in determining sensitivity/resistance to cytotoxic drugs is limited: the individual molecular pathology and differentiation of a given cancer line prevail over any average trend, and are causal to a broad spreading of the data. We also identify major "confounding factors", alias independent categorical variables, capable of affecting the average outcome

    Novel 5-arylamino pyrazoles able to interfere with angiogenesis and Ca2+ homeostasis

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    In the last years, several pyrazole derivatives have been reported as antiangiogenetic agents. In particular, 5-phenylamino pyrazole I proved to inhibit Akt phosphorylation in human foreskin fibroblasts (HFF) and human umbilical vein endothelial cells (HUVEC) and to interfere with HFF migration in wound healing assays, being more active than our reference compound GeGe-3. In functional proteomics investigations on HUVEC, GeGe-3 proved to affect intracellular Ca2+ levels in a dose dependent fashion through the interaction with calreticulin (CALR). Docking simulations helped to elucidate the molecular basis of pyrazole I/CALR interaction. To further extend the SARs of derivatives I, novel 5-arylamino pyrazoles II and III were designed and synthesized. The new molecules share with I and GeGe-3 the N1- hydroxyalkyl or hydroxy phenyl chains and the free amino group at position five of the ring. Differently from their parents’ compounds, the novel derivatives presented variously substituted aryl-amino moieties at position three. All the isolated compounds were preliminary screened by MTT assays to prove the absence of cytotoxicity against normal human cells. Additionally, the effects on angiogenesis and calcium mobilization were evaluate in vitro on HUVEC. Selected derivatives showed improved antiangiogenic activities compared to GeGe-3 and I

    The three-dimensional structure of NK cell receptor NKp44, a triggering partner in natural cytotoxicity

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    none9noneBORDO D; CANTONI C; PONASSI M; BIASSONI R; CONTE R; A. SPALLAROSSA; MORETTA A; MORETTA L; BOLOGNESI M.Bordo, D; Cantoni, Claudia; Ponassi, M; Biassoni, R; Conte, R; Spallarossa, Andrea; Moretta, A; Moretta, L; Bolognesi, M

    p63 and p73, members of the p53 gene family, transactivate PKC delta

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    The p53 family comprises three genes that encode for p53, p63 and p73. These genes have a significant degree of sequence homology, especially in the central sequence-specific DNA-binding domain. The high homology among the three DNA-binding domains indicates that these transcription factors have identical residues interacting with DNA, and thus potentially can recognize the same transcriptional targets. In this study, we demonstrate that PKC delta is induced by p63 and p73 in Saos2 cells. The putative human PKC delta promoter harbours three p53-like binding sites (RE I, RE II, RE III). In order to confirm the transactivation of PKC delta by p53 family members, we performed transcription assays using the entire or selected regions of the promoter upstream of a luciferase reporter gene. The results obtained demonstrated that, at least in vitro, the p53 family members tested (TAp63 alpha, TAp73 alpha, Delta Np63 alpha, but not Delta Np73 alpha) were able to drive transcription from the PKC delta promoter. (c) 2006 Elsevier Inc. All rights reserved
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