201 research outputs found

    Integrated Block Sharing: A Winā€“Win Strategy for Hospitals and Surgeons

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    We consider the problem of balancing two competing objectives in the pursuit of efļ¬cient management of operating rooms in a hospital: providing surgeons with predictable, reliable access to the operating room and maintaining high utilization of capacity. The common solution to the ļ¬rst problem (in practice) is to grant exclusive ā€œblock time,ā€ in which a portion of the week in an operating room is designated to a particular surgeon, barring other surgeons from using this room/time. As a major improvement over this existing approach, we model the possibility of ā€œsharedā€ block time, which need only satisfy capacity constraints in expectation. We reduce the computational difļ¬culty of the resulting NP-hard block-scheduling problem by implementing a column-generation approach and demonstrate the efļ¬cacy of this technique using simulation, calibrated to a real hospitalā€™s historical data and objectives. Our simulations illustrate substantial beneļ¬ts to hospitals under a variety of circumstances and demonstrate the advantages of our new approach relative to a benchmark method taken from the recent literature

    Prevalence and nature of multi-sensory and multi-modal hallucinations in people with first episode psychosis

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    Hallucinations can occur in single or multiple sensory modalities. This study explored how common these experiences were in people with first episode of psychosis (n = 82). Particular attention was paid to the number of modalities reported and whether the experiences were seen to be linked temporally and thematically. It was predicted that those people reporting a greater number of hallucinations would report more delusional ideation, greater levels of distress generally and lower functioning. All participants reported hallucinations in the auditory domain, given the nature of the recruitment. The participants also reported a range of other unusual sensory experiences, with visual and tactile hallucinations being reported by over half. Moreover, single sensory experiences or unimodal hallucinations were less common than two or more hallucination modalities which was reported by 78% of the participants. The number of hallucinations was significantly associated with greater delusional ideation and higher levels of general distress, but not with reduced functioning. It is clear there is a need to refine psychological treatments so that they are better matched to the actual experiences reported by people with psychosis. Theoretical implications are also considered

    Effects of a novel, brief psychological therapy (Managing Unusual Sensory Experiences) for hallucinations in first episode psychosis (MUSE FEP): findings from an exploratory randomised controlled trial.

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    Hallucinations are a common feature of psychosis, yet access to effective psychological treatment is limited. The Managing Unusual Sensory Experiences for First-Episode-Psychosis (MUSE-FEP) trial aimed to establish the feasibility and acceptability of a brief, hallucination-specific, digitally provided treatment, delivered by a non-specialist workforce for people with psychosis. MUSE uses psychoeducation about the causal mechanisms of hallucinations and tailored interventions to help a person understand and manage their experiences. We undertook a two-site, single-blind (rater) Randomised Controlled Trial and recruited 82 participants who were allocated 1:1 to MUSE and treatment as usual (TAU) (n=40) or TAU alone (n=42). Participants completed assessments before and after treatment (2 months), and at follow up (3-4 months). Information on recruitment rates, adherence, and completion of outcome assessments was collected. Analyses focussed on feasibility outcomes and initial estimates of intervention effects to inform a future trial. The trial is registered with the ISRCTN registry 16793301. Criteria for the feasibility of trial methodology and intervention delivery were met. The trial exceeded the recruitment target, had high retention rates (87.8%) at end of treatment, and at follow up (86.6%), with good acceptability of treatment. There were 3 serious adverse events in the therapy group, and 5 in the TAU group. Improvements were evident in both groups at the end of treatment and follow up, with a particular benefit in perceived recovery in the MUSE group. We showed it was feasible to increase access to psychological intervention but a definitive trial requires further changes to the trial design or treatment

    Chronic electroconvulsive shock treatment elicits up-regulation of CRF and AVP mRNA in select populations of neuroendocrine neurons

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    The effects of repeated electroconvulsive seizures (ECS) on expression of mRNAs coding for corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical (HPA) axis and hypothalamo-neurohypophysial system (HNS) were assessed via semi-quantitative in situ hybridization histochemical analysis. Measures of mRNA content were accompanied by measurement of peptide- and hormone-expression in the relevant neuroendocrine systems. Following 7 daily ECS treatments, CRF mRNA was significantly increased in the medial parvocellular paraventricular nucleus (PVN) of treated rats relative to controls. CRF peptide content of whole PVN homogenates was decreased to 50% of control levels. Changes in CRF message and peptide levels were accompanied by increases in pituitary ACTH content and by elevated plasma corticosterone, suggesting ECS elicits long-term up-regulation of the HPA axis. AVP mRNA in the medial parvocellular PVN, which is known to up-regulate in response to HPA challenge by adrenalectomy, was not increased by ECS. Chronic ECS causes a clear up-regulation of HNS neurons of the supraoptic nucleus, characterized by increased AVP mRNA content, decreased AVP peptide content, and depletion of neurohypophysial AVP. However, no changes were observed in magnocellular vasopressinergic neurons of the PVN, indicating that magnocellular SON and PVN neurons respond differentially to stimulation by ECS. The data indicate that ECS is a potent stimulus for activation of select components of both the HPA axis and the HNS. As such, ECS provides a useful tool for examining mechanism underlying neuroendocrine processes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27688/1/0000072.pd

    Modular architecture of nucleotide-binding pockets

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    Recently, modularity has emerged as a general attribute of complex biological systems. This is probably because modular systems lend themselves readily to optimization via random mutation followed by natural selection. Although they are not traditionally considered to evolve by this process, biological ligands are also modular, being composed of recurring chemical fragments, and moreover they exhibit similarities reminiscent of mutations (e.g. the few atoms differentiating adenine and guanine). Many ligands are also promiscuous in the sense that they bind to many different protein folds. Here, we investigated whether ligand chemical modularity is reflected in an underlying modularity of binding sites across unrelated proteins. We chose nucleotides as paradigmatic ligands, because they can be described as composed of well-defined fragments (nucleobase, ribose and phosphates) and are quite abundant both in nature and in protein structure databases. We found that nucleotide-binding sites do indeed show a modular organization and are composed of fragment-specific protein structural motifs, which parallel the modular structure of their ligands. Through an analysis of the distribution of these motifs in different proteins and in different folds, we discuss the evolutionary implications of these findings and argue that the structural features we observed can arise both as a result of divergence from a common ancestor or convergent evolution
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