2,998 research outputs found

    A casemix analysis of hospital admissions in six specialties for Barking & Havering Health Authority.

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    To examine admission rates for Barking & Havering residents to six surgical specialties by first looking at elective, emergency and total workloads, then at the casemix of elective work using Healthcare Resource Groups. To compare findings to other London areas

    Combining social network analysis and the NATO Approach Space to define agility. Topic 2: networks and networking

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    This paper takes the NATO SAS-050 Approach Space, a widely accepted model of command and control, and gives each of its primary axes a quantitative measure using social network analysis. This means that the actual point in the approach space adopted by real-life command and control organizations can be plotted along with the way in which that point varies over time and function. Part 1 of the paper presents the rationale behind this innovation and how it was subject to verification using theoretical data. Part 2 shows how the enhanced approach space was put to use in the context of a large scale military command post exercise. Agility is represented by the number of distinct areas in the approach space that the organization was able to occupy and there was a marked disparity between where the organization thought it should be and where it actually was, furthermore, agility varied across function. The humans in this particular scenario bestowed upon the organization the levels of agility that were observed, thus the findings are properly considered from a socio-technical perspective

    Axonal Membranes and Their Domains: Assembly and Function of the Axon Initial Segment and Node of Ranvier

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    Neurons are highly specialized cells of the nervous system that receive, process and transmit electrical signals critical for normal brain function. Here, we review the intricate organization of axonal membrane domains that facilitate rapid action potential conduction underlying communication between complex neuronal circuits. Two critical excitable domains of vertebrate axons are the axon initial segment (AIS) and the nodes of Ranvier, which are characterized by the high concentrations of voltage-gated ion channels, cell adhesion molecules and specialized cytoskeletal networks. The AIS is located at the proximal region of the axon and serves as the site of action potential initiation, while nodes of Ranvier, gaps between adjacent myelin sheaths, allow rapid propagation of the action potential through saltatory conduction. The AIS and nodes of Ranvier are assembled by ankyrins, spectrins and their associated binding partners through the clustering of membrane proteins and connection to the underlying cytoskeleton network. Although the AIS and nodes of Ranvier share similar protein composition, their mechanisms of assembly are strikingly different. Here we will cover the mechanisms of formation and maintenance of these axonal excitable membrane domains, specifically highlighting the similarities and differences between them. We will also discuss recent advances in super resolution fluorescence imaging which have elucidated the arrangement of the submembranous axonal cytoskeleton revealing a surprising structural organization necessary to maintain axonal organization and function. Finally, human mutations in axonal domain components have been associated with a growing number of neurological disorders including severe cognitive dysfunction, epilepsy, autism, neurodegenerative diseases and psychiatric disorders. Overall, this review highlights the assembly, maintenance and function of axonal excitable domains, particularly the AIS and nodes of Ranvier, and how abnormalities in these processes may contribute to disease

    Ankyrin-B is lipid-modified by S-palmitoylation to promote dendritic membrane scaffolding of voltage-gated sodium channel NaV1.2 in neurons

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    Neuronal ankyrin-B is an intracellular scaffolding protein that plays multiple roles in the axon. By contrast, relatively little is known about the function of ankyrin-B in dendrites, where ankyrin-B is also localized in mature neurons. Recently, we showed that ankyrin-B acts as a scaffold for the voltage-gated sodium channel, NaV1.2, in dendrites of neocortical pyramidal neurons. How ankyrin-B is itself targeted to the dendritic membrane is not well understood. Here, we report that ankyrin-B is lipid-modified by S-palmitoylation to promote dendritic localization of NaV1.2. We identify the palmitoyl acyl transferase zDHHC17 as a key mediator of ankyrin-B palmitoylation in heterologous cells and in neurons. Additionally, we find that zDHHC17 regulates ankyrin-B protein levels independently of its S-acylation function through a conserved binding mechanism between the ANK repeat domain of zDHHC17 and the zDHHC ankyrin-repeat binding motif of ankyrin-B. We subsequently identify five cysteines in the N-terminal ankyrin repeat domain of ankyrin-B that are necessary for ankyrin-B palmitoylation. Mutation of these five cysteines to alanines not only abolishes ankyrin-B palmitoylation, but also prevents ankyrin-B from scaffolding NaV1.2 at dendritic membranes of neurons due to ankyrin-Bā€™s inability to localize properly at dendrites. Thus, we show palmitoylation is critical for localization and function of ankyrin-B at dendrites. Strikingly, loss of ankyrin-B palmitoylation does not affect ankyrin-B-mediated axonal cargo transport of synaptic vesicle synaptotagmin-1 in neurons. This is the first demonstration of S-palmitoylation of ankyrin-B as an underlying mechanism required for ankyrin-B localization and function in scaffolding NaV1.2 at dendrites

    Simple conditions for convergence of sequential Monte Carlo genealogies with applications

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    We present simple conditions under which the limiting genealogical process associated with a class of interacting particle systems with non-neutral selection mechanisms, as the number of particles grows, is a time-rescaled Kingman coalescent. Sequential Monte Carlo algorithms are popular methods for approximating integrals in problems such as non-linear filtering and smoothing which employ this type of particle system. Their performance depends strongly on the properties of the induced genealogical process. We verify the conditions of our main result for standard sequential Monte Carlo algorithms with a broad class of low-variance resampling schemes, as well as for conditional sequential Monte Carlo with multinomial resampling.Comment: 22 pages, 1 figur

    Debt income and mental disorder in the general population

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    Background The association between poor mental health and poverty is well known but its mechanism is not fully understood. This study tests the hypothesis that the association between low income and mental disorder is mediated by debt and its attendant financial hardship. Method The study is a cross-sectional nationally representative survey of private households in England, Scotland and Wales, which assessed 8580 participants aged 16ā€“74 years living in general households. Psychosis, neurosis, alcohol abuse and drug abuse were identified by the Clinical Interview Schedule ā€“ Revised, the Schedule for Assessment in Neuropsychiatry (SCAN), the Alcohol Use Disorder Identification Test (AUDIT) and other measures. Detailed questions were asked about income, debt and financial hardship. Results Those with low income were more likely to have mental disorder [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.68ā€“2.59] but this relationship was attenuated after adjustment for debt (OR 1.58, 95% CI 1.25ā€“1.97) and vanished when other sociodemographic variables were also controlled (OR 1.07, 95% CI 0.77ā€“1.48). Of those with mental disorder, 23% were in debt (compared with 8% of those without disorder), and 10% had had a utility disconnected (compared with 3%). The more debts people had, the more likely they were to have some form of mental disorder, even after adjustment for income and other sociodemographic variables. People with six or more separate debts had a six-fold increase in mental disorder after adjustment for income (OR 6.0, 95% CI 3.5ā€“10.3). Conclusions Both low income and debt are associated with mental illness, but the effect of income appears to be mediated largely by debt
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