222 research outputs found

    Fast Transport of Neurofilament Protein along Microtubules in Squid Axoplasm

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    Using squid axoplasm as a model system, we have visualized the fast transport of non-filamentous neurofilament protein particles along axonal microtubules. This transport occurs at speeds of 0.5-1.0 microm/second and the majority of neurofilament particles stain with kinesin antibody. These observations demonstrate, for the first time, that fast (0.5-1.0 microm/second) transport of neurofilament proteins occurs along microtubules. In addition, our studies suggest that neurofilament protein can be transported as non-membrane bound, nonfilamentous subunits along axons, and that the transport is kinesin-dependent. Microtubule-based fast transport might therefore provide a mechanism for the distribution and turnover of neurofilament, and perhaps other cytoskeletal proteins, throughout neurons

    Fast Transport of Neurofilament Protein along Microtubules in Squid Axoplasm

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    Using squid axoplasm as a model system, we have visualized the fast transport of non-filamentous neurofilament protein particles along axonal microtubules. This transport occurs at speeds of 0.5-1.0 microm/second and the majority of neurofilament particles stain with kinesin antibody. These observations demonstrate, for the first time, that fast (0.5-1.0 microm/second) transport of neurofilament proteins occurs along microtubules. In addition, our studies suggest that neurofilament protein can be transported as non-membrane bound, nonfilamentous subunits along axons, and that the transport is kinesin-dependent. Microtubule-based fast transport might therefore provide a mechanism for the distribution and turnover of neurofilament, and perhaps other cytoskeletal proteins, throughout neurons

    Japanese lesson study: a numeracy coach\u27s view

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    This paper reports findings based on interview data from a professional teacher educator who was a Numeracy Coach for a group of schools that participated in a research project, Implementing structured problem-solving mathematics lessons through Lesson Study. The Numeracy Coach was a highly-skilled professional teacher educator, whose position was such that she was both a support person to the teachers and a participant in the project. Her insights into the processes and effects of Japanese Lesson Study, on teachers, as well as herself, are extremely enlightening, and form the data for this paper. While the evidence is from a single source, the evidence is consistent with other projects into the effectiveness of the Japanese model of Lesson Study. Aspects of the project with implications for teacher professional development are detailed

    Systematic review of the clinical effectiveness and cost-effectiveness of oesophageal Doppler monitoring in critically ill and high-risk surgical patients

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    Objectives: To assess the effectiveness and costeffectiveness of oesophageal Doppler monitoring (ODM) compared with conventional clinical assessment and other methods of monitoring cardiovascular function. Data sources: Electronic databases and relevant websites from 1990 to May 2007 were searched. Review methods: This review was based on a systematic review conducted by the US Agency for Healthcare Research and Quality (AHRQ), supplemented by evidence from any additional studies identified. Comparator interventions for effectiveness were standard care, pulmonary artery catheters (PACs), pulse contour analysis monitoring and lithium or thermodilution cardiac monitoring. Data were extracted on mortality, length of stay overall and in critical care, complications and quality of life. The economic assessment evaluated strategies involving ODM compared with standard care, PACs, pulse contour analysis monitoring and lithium or thermodilution cardiac monitoring. Results: The AHRQ report contained eight RCTs and was judged to be of high quality overall. Four comparisons were reported: ODM plus central venous pressure (CVP) monitoring plus conventional assessment vs CVP monitoring plus conventional assessment during surgery; ODM plus conventional assessment vs CVP monitoring plus conventional assessment during surgery; ODM plus conventional assessment vs conventional assessment during surgery; and ODM plus CVP monitoring plus conventional assessment vs CVP monitoring plus conventional assessment postoperatively. Five studies compared ODM plus CVP monitoring plus conventional assessment with CVP monitoring plus conventional assessment during surgery. There were fewer deaths [Peto odds ratio (OR) 0.13, 95% CI 0.02–0.96], fewer major complications (Peto OR 0.12, 95% CI 0.04–0.31), fewer total complications (fixed-effects OR 0.43, 95% CI 0.26–0.71) and shorter length of stay (pooled estimate not presented, 95% CI –2.21 to –0.57) in the ODM group. The results of the meta analysis of mortality should be treated with caution owing to the low number of events and low overall number of patients in the combined totals. Three studies compared ODM plus conventional assessment with conventional assessment during surgery. There was no evidence of a difference in mortality (fixed-effects OR 0.81, 95% CI 0.23–2.77). Length of hospital stay was shorter in all three studies in the ODM group. Two studies compared ODM plus CVP monitoring plus conventional assessment vs CVP monitoring plus conventional assessment in critically ill patients. The patient groups were quite different (cardiac surgery and major trauma) and neither study, nor a meta-analysis, showed a statistically significant difference in mortality (fixed-effects OR 0.84, 95% CI 0.41–1.70). Fewer patients in the ODM group experienced complications (OR 0.49, 95% CI 0.30–0.81) and both studies reported a statistically significant shorter median length of hospital stay in that group. No economic evaluations that met the inclusion criteria were identified from the existing literature so a series of balance sheets was constructed. The results show that ODM strategies are likely to be cost-effective. Conclusions: More formal economic evaluation would allow better use of the available data. All identified studies were conducted in unconscious patients. However, further research is needed to evaluate new ODM probes that may be tolerated by awake patients. Given the paucity of the existing economic evidence base, any further primary research should include an economic evaluation or should provide data suitable for use in an economic model.The Health Services Research Unit and the Health Economics Research Unit are both core funded by the Chief Scientist Office of the Scottish Government Health Directorate.Peer reviewedPublisher PD

    OS-WALK-EU: An open-source tool to assess health-promoting residential walkability of European city structures

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    Introduction This paper introduces OS-WALK-EU, a new open-source walkability assessment tool developed specifically for urban neighbourhoods and using open-source spatial data. A free and open-source tool, OS-WALK-EU is accessible to the general public. It uses open data available worldwide and free online services to compute accessibility, while at the same time allowing users to integrate local datasets if available. Based on a review of existing measurement concepts, the paper adopts dimensions of walkability that were tested in European city environments and explains their conceptualization for software development. We invite the research community to collaboratively test, adopt and use the tool as part of the increasing need to monitor walkability as part of health-promoting urban development. Methods Tool development is based on spatial analysis methods to compute indicators for five dimensions of walkability: residential density, weighted proximities to amenities, pedestrian radius of activity, share of green and blue infrastructure, and slope. Sample uses in the cities of Dublin, Düsseldorf and Lisbon test the validity of input data and results, including scenarios for target groups like older people. Results Overall, application of the tool in Dublin, Düsseldorf and Lisbon shows conclusive results that conform to local knowledge. Shortcomings can be attributed to deficiencies in open source input data. Local administrative data, if available, is suitable to improve results. Conclusions OS-WALK-EU is the first software tool that allows free and open walkability assessments with pedestrian routing capacities for ‘proximity to facilities’ calculations. Large scale implementation for 33 German city regions in an online application shows the value of comparative assessments of walkable neighbourhoods between urban and suburban neighbourhoods. Such assessments are important to monitor progress in a mobility transition towards improved walkability and public health

    Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy:A systematic review and economic assessment

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    Background: Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are more severe and the most severe form of NVP – hyperemesis gravidarum (HG) – affects 0.3–1.0% of pregnant women. There is no widely accepted point at which NVP becomes HG. Objectives: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of treatments for NVP and HG. Data sources: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, PsycINFO, Commonwealth Agricultural Bureaux (CAB) Abstracts, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, British Nursing Index, Science Citation Index, Social Sciences Citation Index, Scopus, Conference Proceedings Index, NHS Economic Evaluation Database, Health Economic Evaluations Database, China National Knowledge Infrastructure, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from inception to September 2014. References from studies and literature reviews identified were also examined. Obstetric Medicine was hand-searched, as were websites of relevant organisations. Costs came from NHS sources. Review methods: A systematic review of randomised and non-randomised controlled trials (RCTs) for effectiveness, and population-based case series for adverse events and fetal outcomes. Treatments: vitamins B6 and B12, ginger, acupressure/acupuncture, hypnotherapy, antiemetics, dopamine antagonists, 5-hydroxytryptamine receptor antagonists, intravenous (i.v.) fluids, corticosteroids, enteral and parenteral feeding or other novel treatment. Two reviewers extracted data and quality assessed studies. Results were narratively synthesised; planned meta-analysis was not possible due to heterogeneity and incomplete reporting. A simple economic evaluation considered the implied values of treatments. Results: Seventy-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder (n = 20) it was unclear. The non-randomised studies (n = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo (n = 12); steroid versus usual treatment (n = 7); ginger versus placebo (n = 6); ginger versus vitamin B6 (n = 6); and vitamin B6 versus placebo (n = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin® [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices. Limitations: The main limitations were the quantity and quality of the data available. Conclusion: There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and larger trials of the main therapies considered within the UK NHS are needed. Study registration: This study is registered as PROSPERO CRD42013006642. Funding: The National Institute for Health Research Health Technology Assessment programme

    Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy

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    Importance Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse physical and psychological sequelae.Objective To summarize current evidence on effective treatments for nausea and vomiting in pregnancy and hyperemesis gravidarum.Evidence Review Databases were searched to June 8, 2016. Relevant websites and bibliographies were also searched. Titles and abstracts were assessed independently by 2 reviewers. Results were narratively synthesized; planned meta-analysis was not possible because of heterogeneity and incomplete reporting of findings.Findings Seventy-eight studies (n  = 8930 participants) were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies. Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6, antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and ondansetron (for moderate symptoms) were associated with improved symptoms compared with placebo. One RCT (n = 86) reported greater improvements in moderate symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms} to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]). For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine combination taken preemptively reduced risk of recurrence of moderate-severe symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]). One RCT (n = 83) found that ondansetron was associated with lower nausea scores on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9] for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there was no difference in trend in nausea scores over the 14-day study period, trend in vomiting scores was better in the ondansetron group (P = .042). One RCT (n = 159) found no difference between metoclopramide and promethazine after 24 hours (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1-4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or promethazine or metoclopramide in women with severe symptoms. Improvements were seen in all corticosteroid groups, but only a significant difference between corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5% at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]). For other interventions, evidence was limited.Conclusions and Relevance For mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. Overall the quality of evidence was low
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