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1.
Susan Jordan Marie Ellenor Gabe-Walters Alan Watkins Ioan Humphreys Louise Newson Sherrill Snelgrove Michael S Dennis 《PloS one》2015,10(10)
Background
People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines’ monitoring.Design
Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines’ monitoring versus usual care.Setting
Five UK private sector care homesParticipants
41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.Intervention
Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.Outcomes
Problems addressed and changes in medicines prescribed.Data Collection and Analysis
Information was collected from participants’ notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.Results
Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57–4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78–8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80–235.90] and 5.12 [1.45–18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15–17.22).Conclusion
The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines.Trial Registration
ISRCTN 48133332 相似文献2.
David Koslicki Saikat Chatterjee Damon Shahrivar Alan W. Walker Suzanna C. Francis Louise J. Fraser Mikko Vehkaper? Yueheng Lan Jukka Corander 《PloS one》2015,10(10)
Motivation
Estimation of bacterial community composition from high-throughput sequenced 16S rRNA gene amplicons is a key task in microbial ecology. Since the sequence data from each sample typically consist of a large number of reads and are adversely impacted by different levels of biological and technical noise, accurate analysis of such large datasets is challenging.Results
There has been a recent surge of interest in using compressed sensing inspired and convex-optimization based methods to solve the estimation problem for bacterial community composition. These methods typically rely on summarizing the sequence data by frequencies of low-order k-mers and matching this information statistically with a taxonomically structured database. Here we show that the accuracy of the resulting community composition estimates can be substantially improved by aggregating the reads from a sample with an unsupervised machine learning approach prior to the estimation phase. The aggregation of reads is a pre-processing approach where we use a standard K-means clustering algorithm that partitions a large set of reads into subsets with reasonable computational cost to provide several vectors of first order statistics instead of only single statistical summarization in terms of k-mer frequencies. The output of the clustering is then processed further to obtain the final estimate for each sample. The resulting method is called Aggregation of Reads by K-means (ARK), and it is based on a statistical argument via mixture density formulation. ARK is found to improve the fidelity and robustness of several recently introduced methods, with only a modest increase in computational complexity.Availability
An open source, platform-independent implementation of the method in the Julia programming language is freely available at https://github.com/dkoslicki/ARK. A Matlab implementation is available at http://www.ee.kth.se/ctsoftware. 相似文献3.
Carlo Cosimo Quattrocchi Maria Francesca de Pandis Claudia Piervincenzi Manuela Galli Jean Marc Melgari Gaetano Salomone Patrizio Sale Carlo Augusto Mallio Filippo Carducci Fabrizio Stocchi 《PloS one》2015,10(10)
Objective
The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease.Methods
Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition.Results
Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79).Conclusions
Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration.Classification of Evidence
This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest.Trial Registration
Clinical Trials.gov NCT01815281 相似文献4.
Jordi Adamuz Diego Viasus Antonella Simonetti Emilio Jiménez-Martínez Lorena Molero Maribel González-Samartino Elena Castillo María-Eulalia Juvé-Udina María-Jesús Alcocer Carme Hernández María-Pilar Buera Asunción Roel Emilia Abad Adelaida Zabalegui Pilar Ricart Anna Gonzalez Pilar Isla Jordi Dorca Carolina Garcia-Vidal Jordi Carratalà 《PloS one》2015,10(10)
Background
Additional healthcare visits and rehospitalizations after discharge are frequent among patients with community-acquired pneumonia (CAP) and have a major impact on healthcare costs. We aimed to determine whether the implementation of an individualized educational program for hospitalized patients with CAP would decrease subsequent healthcare visits and readmissions within 30 days of hospital discharge.Methods
A multicenter, randomized trial was conducted from January 1, 2011 to October 31, 2014 at three hospitals in Spain. We randomly allocated immunocompetent adults patients hospitalized for CAP to receive either an individualized educational program or conventional information before discharge. The educational program included recommendations regarding fluid intake, adherence to drug therapy and preventive vaccines, knowledge and management of the disease, progressive adaptive physical activity, and counseling for alcohol and smoking cessation. The primary trial endpoint was a composite of the frequency of additional healthcare visits and rehospitalizations within 30 days of hospital discharge. Intention-to-treat analysis was performed.Results
We assigned 102 patients to receive the individualized educational program and 105 to receive conventional information. The frequency of the composite primary end point was 23.5% following the individualized program and 42.9% following the conventional information (difference, -19.4%; 95% confidence interval, -6.5% to -31.2%; P = 0.003).Conclusions
The implementation of an individualized educational program for hospitalized patients with CAP was effective in reducing subsequent healthcare visits and rehospitalizations within 30 days of discharge. Such a strategy may help optimize available healthcare resources and identify post-acute care needs in patients with CAP.Trial Registration
Controlled-Trials.com ISRCTN39531840 相似文献5.
Paul C. Wang Albert Mwango Sarah Moberley Benjamin J. Brockman Alison L. Connor Penelope Kalesha-Masumbu Simon Mutembo Maximillian Bweupe Pascalina Chanda-Kapata Godfrey Biemba Davidson H. Hamer Benjamin Chibuye Elizabeth McCarthy 《PloS one》2015,10(10)
Background
We assessed the integration of early infant HIV diagnosis with the expanded programme for immunization in a rural Zambian setting with the aim of determining whether infant and postpartum maternal HIV testing rates would increase without harming immunization uptake.Methods
In an unblinded, location stratified, cluster randomised controlled trial, 60 facilities in Zambia’s Southern Province were equally allocated to a control group, Simple Intervention group that received a sensitization meeting and the resupply of HIV testing commodities in the event of a stock-out, and a Comprehensive Intervention group that received the Simple Intervention as well as on-site operational support to facilitate the integration of HIV testing services with EPI.Findings
The average change in number of first dose diphtheria, pertussis, and tetanus vaccine (DPT1) provided per month, per facility was approximately 0.86 doses higher [90% confidence interval (CI) -1.40, 3.12] in Comprehensive Intervention facilities compared to the combined average change in the Simple Intervention and control facilities. The interventions resulted in a 16.6% [90% CI: -7%, 46%, P-value = 0.26] and 10% [90% CI: -10%, 36%, P-value = 0.43] greater change in average monthly infant DBS testing compared to control for the Simple and Comprehensive facilities respectively. We also found 15.76 (90% CI: 7.12, 24.41, P-value < 0.01) and 10.93 (90% CI: 1.52, 20.33, P-value = 0.06) additional total maternal re-tests over baseline for the Simple and Comprehensive Facilities respectively.Conclusions
This study provides strong evidence to support Zambia’s policy of integration of HIV testing and EPI services. Actions in line with the interventions, including HIV testing material supply reinforcement, can increase HIV testing rates without harming immunization uptake. In response, Zambia’s Ministry of Health issued a memo to remind health facilities to provide HIV testing at under-five clinics and to include under-five HIV testing as part of district performance assessments.Trial Registration
ClinicalTrials.gov Registration Number: NCT02479659 相似文献6.
Objective
To investigate changes of muscle recruitment and coordination following constraint-induced movement therapy, constraint-induced movement therapy plus electrical stimulation, and traditional occupational therapy in treating hand dysfunction.Methods
In a randomized, single-blind, controlled trial, children with hemiplegic cerebral palsy were randomly assigned to receive constraint-induced movement therapy (n = 22), constraint-induced movement therapy plus electrical stimulation (n = 23), or traditional occupational therapy (n = 23). Three groups received a 2-week hospital-based intervention and a 6-month home-based exercise program following hospital-based intervention. Constraint-induced movement therapy involved intensive functional training of the involved hand during which the uninvolved hand was constrained. Electrical stimulation was applied on wrist extensors of the involved hand. Traditional occupational therapy involved functional unimanual and bimanual training. All children underwent clinical assessments and surface electromyography (EMG) at baseline, 2 weeks, 3 and 6 months after treatment. Surface myoelectric signals were integrated EMG, root mean square and cocontraction ratio. Clinical measures were grip strength and upper extremity functional test.Results
Constraint-induced movement therapy plus electrical stimulation group showed both a greater rate of improvement in integrated EMG of the involved wrist extensors and cocontraction ratio compared to the other two groups at 3 and 6 months, as well as improving in root mean square of the involved wrist extensors than traditional occupational therapy group (p<0.05). Positive correlations were found between both upper extremity functional test scores and integrated EMG of the involved wrist as well as grip strength and integrated EMG of the involved wrist extensors (p<0.05).Conclusions
Constraint-induced movement therapy plus electrical stimulation is likely to produce the best outcome in improving muscle recruitment and coordination in children with hemiplegic cerebral palsy compared to constraint-induced movement therapy alone or traditional occupational therapy.Trial registration
chictr.org ChiCTR-TRC-13004041 相似文献7.
Objective
To evaluate the efficacy of the program Keep Moving toward Healthy Heart and Healthy Brain (KM2H2) in encouraging physical activities for the prevention of heart attack and stroke among hypertensive patients enrolled in the Community-Based Hypertension Control Program (CBHCP).Design
Cluster randomized controlled trial with three waves of longitudinal assessments at baseline, 3 and 6 months post intervention.Setting
Community-based and patient-centered self-care for behavioral intervention in urban settings of China.Participants
A total of 450 participants diagnosed with hypertension from 12 community health centers in Wuhan, China were recruited, and were randomly assigned by center to receive either KM2H2 plus standard CBHCP care (6 centers and 232 patients) or the standard care only (6 centers and 218 patients).Intervention
KM2H2 is a behavioral intervention guided by the Transtheoretical Model, the Model of Personalized Medicine and Social Capital Theory. It consists of six intervention sessions and two booster sessions engineered in a progressive manner. The purpose is to motivate and maintain physical activities for the prevention of heart attack and stroke.Outcome Measures
Heart attack and stroke (clinically diagnosed, primary outcome), blood pressure (measured, secondary outcome), and physical activity (self-report, tertiary outcome) were assessed at the individual level during the baseline, 3- and 6-month post-intervention.Results
Relative to the standard care, receiving KM2H2 was associated with significant reductions in the incidence of heart attack (3.60% vs. 7.03%, p < .05) and stroke (5.11% vs. 9.90%, p<0.05), and moderate reduction in blood pressure (-3.72mmHg in DBP and -2.92 mmHg in DBP) at 6-month post-intervention; and significant increases in physical activity at 3- (d = 0.53, 95% CI: 0.21, 0.85) and 6-month (d = 0.45, 95% CI: 0.04, 0.85) post-intervention, respectively.Conclusion
The program KM2H2 is efficacious to reduce the risk of heart attack and stroke among senior patients who are on anti-hypertensive medication. Findings of this study provide solid data supporting a formal phase-III trial to establish the effectiveness of KM2H2 for use in community settings for prevention.Trial Registration
ISRCTN Register ISRCTN12608966 相似文献8.
Catherine Henderson Martin Knapp Ksenija Yeeles Stephen Bremner Sandra Eldridge Anthony S. David Nicola O’Connell Tom Burns Stefan Priebe 《PloS one》2015,10(10)
Background
Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined.Methods
Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of ‘good’ adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period).Findings
Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention); the adjusted costs difference was £598 (95% CI -£4 533, £5 730). The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8 020, £14 000). The extra cost per patient of achieving ''good'' adherence was £2 950 (CI -£19 400, £27 800). Probability of cost-effectiveness exceeded 97.5% at willingness-to-pay values of £14 000 for a 20% increase in adherence and £27 800 for good adherence.Interpretation
Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive) are unlikely to be increased by this intervention.Trial Registration
ISRCTN.com 77769281 相似文献9.
Anne Pauly Carolin Wolf Andreas Mayr Bernd Lenz Johannes Kornhuber Kristina Friedland 《PloS one》2015,10(10)
Background
In psychiatry, hospital stays and transitions to the ambulatory sector are susceptible to major changes in drug therapy that lead to complex medication regimens and common non-adherence among psychiatric patients. A multi-dimensional and inter-sectoral intervention is hypothesized to improve the adherence of psychiatric patients to their pharmacotherapy.Methods
269 patients from a German university hospital were included in a prospective, open, clinical trial with consecutive control and intervention groups. Control patients (09/2012-03/2013) received usual care, whereas intervention patients (05/2013-12/2013) underwent a program to enhance adherence during their stay and up to three months after discharge. The program consisted of therapy simplification and individualized patient education (multi-dimensional component) during the stay and at discharge, as well as subsequent phone calls after discharge (inter-sectoral component). Adherence was measured by the “Medication Adherence Report Scale” (MARS) and the “Drug Attitude Inventory” (DAI).Results
The improvement in the MARS score between admission and three months after discharge was 1.33 points (95% CI: 0.73–1.93) higher in the intervention group compared to controls. In addition, the DAI score improved 1.93 points (95% CI: 1.15–2.72) more for intervention patients.Conclusion
These two findings indicate significantly higher medication adherence following the investigated multi-dimensional and inter-sectoral program.Trial Registration
German Clinical Trials Register DRKS00006358 相似文献10.
Lijuan Zhan Frederick A. Masoudi Xi Li Shuang Hu Arjun K. Venkatesh John A. Spertus Zhenqiu Lin Nihar R. Desai Jing Li Harlan M. Krumholz Lixin Jiang China PEACE Collaborative Group 《PloS one》2015,10(4)
Objectives
To describe trends in the availability of biomarker testing in Chinese hospitals and how practice complies with established standards for the diagnosis of acute myocardial infarction (AMI).Background
Cardiac biomarker testing is standard in high-income countries, but little is known about the availability and use of cardiac biomarker testing in low- and middle-income countries (LMICs) such as China.Methods
Based on a nationally representative sample of Chinese hospitals in 2001, 2006 and 2011, we describe the temporal trends and regional differences in the hospital capability and rates of use of cardiac biomarker testing, as well as the variation in use across hospitals with testing capability, for patients labeled with the diagnosis of AMI.Results
We sampled 175 hospitals (162 participated in the study) and 18,631 AMI admissions. 14,370 patients were included in analysis of biomarker use. The proportion of hospitals with biomarker testing capability was 57.4% in 2001 (25.0% troponin and 32.4% creatine kinase MB fraction (CK-MB) only) and 96.3% (81.4% troponin and 14.9% CK-MB only) in 2011. The proportion of hospitals with troponin testing capability in 2011 was significantly higher in urban compared with rural hospitals (96.8% vs. 71.4%, p< 0.001). In 2011, only 55.9% of hospitals with troponin testing capability (71 out of 127 hospitals) used the assay for more than 80% of their patients with AMI. Among hospitals with either biomarker testing capability, there was marked variation in use in both rural (from 7.1% to 100.0% of patients) and urban hospitals (from 57.9% to 100.0% of patients). In 2011, 36.1% of the patients with AMI did not have troponin tested and 4.9% did not have either biomarker measured.Conclusions
The recommended biomarker tests for AMI diagnosis are not universally available and the testing is not consistently applied when it is available in China.Trial Registration
ClinicalTrials.gov NCT01624883 相似文献11.
Fei Xu Robert S. Ware Eva Leslie Lap Ah Tse Zhiyong Wang Jiequan Li Youfa Wang 《PloS one》2015,10(10)
Background
Childhood obesity has been increasing rapidly worldwide. There is limited evidence for effective lifestyle interventions to prevent childhood obesity worldwide, especially in developing countries like China. The objective of this study was to assess the effectiveness of a school-based multi-component lifestyle childhood obesity prevention program (the CLICK-Obesity study) in Mainland China.Methods
A cluster randomized controlled trial was developed among grade 4 students from 8 urban primary schools (638 students in intervention, 544 as control) in Nanjing City, China. Students were randomly allocated to the control or intervention group at school-level. A one-year multi-component intervention program (classroom curriculum, school environment support, family involvement and fun programs/events) together with routine health education was provided to the intervention group, while the control group received routine health education only. The main outcome variables assessed were changes in body mass index, obesity occurrence, obesity-related lifestyle behaviors and knowledge.Results
Overall, 1108 (93.7%) of the 1182 enrolled students completed the intervention study. The intervention group had a larger marginal reduction than did the control group in overall mean BMI value (-0.32±1.36 vs. -0.29±1.40, p = 0.09), although this was not significant. Compared with the control group, the intervention group was more likely to decrease their BMI (OR = 1.44, 95%CI = 1.10, 1.87) by 0.5 kg/m2 or above, increase the frequency of jogging/running (OR = 1.55, 95%CI = 1.18, 2.02), decrease the frequency of TV/computer use (OR = 1.41, 95%CI = 1.09, 1.84) and of red meat consumption (OR = 1.50, 95%CI = 1.15, 1.95), change commuting mode to/from school from sedentary to active mode (OR = 2.24, 95%CI = 1.47, 3.40), and be aware of the harm of selected obesity risk factors.Conclusions
The school-based lifestyle intervention program was practical and effective in improving health behaviors and obesity-related knowledge for children in China. This study provides important policy implications on school-based intervention programs for modifications of obesity-related lifestyles.Trial Registration
Chinese Clinical Trial Registry ChiCTR-ERC-11001819 相似文献12.
Franck Maunoury Anastasiia Motrunich Maria Palka-Santini Stéphanie F. Bernatchez Stéphane Ruckly Jean-Fran?ois Timsit 《PloS one》2015,10(6)
Objective
To model the cost-effectiveness impact of routine use of an antimicrobial chlorhexidine gluconate-containing securement dressing compared to non-antimicrobial transparent dressings for the protection of central vascular lines in intensive care unit patients.Design
This study uses a novel health economic model to estimate the cost-effectiveness of using the chlorhexidine gluconate dressing versus transparent dressings in a French intensive care unit scenario. The 30-day time non-homogeneous markovian model comprises eight health states. The probabilities of events derive from a multicentre (12 French intensive care units) randomized controlled trial. 1,000 Monte Carlo simulations of 1,000 patients per dressing strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The outcome is the number of catheter-related bloodstream infections avoided. Costs of intensive care unit stay are based on a recent French multicentre study and the cost-effectiveness criterion is the cost per catheter-related bloodstream infections avoided. The incremental net monetary benefit per patient is also estimated.Patients
1000 patients per group simulated based on the source randomized controlled trial involving 1,879 adults expected to require intravascular catheterization for 48 hours.Intervention
Chlorhexidine Gluconate-containing securement dressing compared to non-antimicrobial transparent dressings.Results
The chlorhexidine gluconate dressing prevents 11.8 infections /1,000 patients (95% confidence interval: [3.85; 19.64]) with a number needed to treat of 85 patients. The mean cost difference per patient of €141 is not statistically significant (95% confidence interval: [€-975; €1,258]). The incremental cost-effectiveness ratio is of €12,046 per catheter-related bloodstream infection prevented, and the incremental net monetary benefit per patient is of €344.88.Conclusions
According to the base case scenario, the chlorhexidine gluconate dressing is more cost-effective than the reference dressing.Trial Registration
This model is based on the data from the RCT registered with www.clinicaltrials.gov (NCT01189682). 相似文献13.
Bianca L. Share Geraldine A. Naughton Philippe Obert Jennifer K. Peat Elizabeth A. Aumand Justin G. Kemp 《PloS one》2015,10(6)
Background
Young women are under-represented in cardiovascular disease research, with obesity and cardiometabolic risk factor interventions generally targeting older adults. Furthermore, appropriate study designs for young women remain uncertain. This study aimed to assess the impact of a 12 week multi-disciplinary lifestyle intervention on cardiometabolic risk factors in premenopausal women with abdominal obesity.Methods
Women aged 18–30 y with abdominal obesity [waist circumference (WC) ≥ 80 cm] were randomised to a 12 week lifestyle intervention (n = 26) of physical activity, nutrition education and cognitive behavioural therapy, or a wait-list control group (n = 17). Both groups completed anthropometric, biochemical, nutrition and fitness testing, at pre (0 weeks) and post (12 weeks), with intervention participants completed follow-up testing at 24 weeks.Results
Results from a linear mixed model showed no between-group differences, other than increased physical activity in the intervention group, at post. In the intervention group alone, positive within-group changes were observed in WC, waist-hip-ratio (WHR), waist-height-ratio (WHtR), resting heart rate, blood pressure, predicted VO2max, and total energy intake. Most changes were maintained at 24 weeks post-intervention. Similar within-group improvements were observed in control participants in WC, WHR, WHtR, and systolic blood pressure but no changes were detected in physical activity and nutrition.Conclusions
Cardiometabolic risk factors were decreased as a result of a lifestyle intervention in young women with abdominal obesity. It is difficult to describe observations in the control group without greater understanding of the behaviour of wait-list participants.Trial Registration
Australian New Zealand Clinical Trials Registry ACTRN12612001017819 相似文献14.
Enis Afgan Clare Sloggett Nuwan Goonasekera Igor Makunin Derek Benson Mark Crowe Simon Gladman Yousef Kowsar Michael Pheasant Ron Horst Andrew Lonie 《PloS one》2015,10(10)
Background
Analyzing high throughput genomics data is a complex and compute intensive task, generally requiring numerous software tools and large reference data sets, tied together in successive stages of data transformation and visualisation. A computational platform enabling best practice genomics analysis ideally meets a number of requirements, including: a wide range of analysis and visualisation tools, closely linked to large user and reference data sets; workflow platform(s) enabling accessible, reproducible, portable analyses, through a flexible set of interfaces; highly available, scalable computational resources; and flexibility and versatility in the use of these resources to meet demands and expertise of a variety of users. Access to an appropriate computational platform can be a significant barrier to researchers, as establishing such a platform requires a large upfront investment in hardware, experience, and expertise.Results
We designed and implemented the Genomics Virtual Laboratory (GVL) as a middleware layer of machine images, cloud management tools, and online services that enable researchers to build arbitrarily sized compute clusters on demand, pre-populated with fully configured bioinformatics tools, reference datasets and workflow and visualisation options. The platform is flexible in that users can conduct analyses through web-based (Galaxy, RStudio, IPython Notebook) or command-line interfaces, and add/remove compute nodes and data resources as required. Best-practice tutorials and protocols provide a path from introductory training to practice. The GVL is available on the OpenStack-based Australian Research Cloud (http://nectar.org.au) and the Amazon Web Services cloud. The principles, implementation and build process are designed to be cloud-agnostic.Conclusions
This paper provides a blueprint for the design and implementation of a cloud-based Genomics Virtual Laboratory. We discuss scope, design considerations and technical and logistical constraints, and explore the value added to the research community through the suite of services and resources provided by our implementation. 相似文献15.
Background
Programs based on hash tables and Burrows-Wheeler are very fast for mapping short reads to genomes but have low accuracy in the presence of mismatches and gaps. Such reads can be aligned accurately with the Smith-Waterman algorithm but it can take hours and days to map millions of reads even for bacteria genomes.Results
We introduce a GPU program called MaxSSmap with the aim of achieving comparable accuracy to Smith-Waterman but with faster runtimes. Similar to most programs MaxSSmap identifies a local region of the genome followed by exact alignment. Instead of using hash tables or Burrows-Wheeler in the first part, MaxSSmap calculates maximum scoring subsequence score between the read and disjoint fragments of the genome in parallel on a GPU and selects the highest scoring fragment for exact alignment. We evaluate MaxSSmap’s accuracy and runtime when mapping simulated Illumina E.coli and human chromosome one reads of different lengths and 10% to 30% mismatches with gaps to the E.coli genome and human chromosome one. We also demonstrate applications on real data by mapping ancient horse DNA reads to modern genomes and unmapped paired reads from NA12878 in 1000 genomes.Conclusions
We show that MaxSSmap attains comparable high accuracy and low error to fast Smith-Waterman programs yet has much lower runtimes. We show that MaxSSmap can map reads rejected by BWA and NextGenMap with high accuracy and low error much faster than if Smith-Waterman were used. On short read lengths of 36 and 51 both MaxSSmap and Smith-Waterman have lower accuracy compared to at higher lengths. On real data MaxSSmap produces many alignments with high score and mapping quality that are not given by NextGenMap and BWA. The MaxSSmap source code in CUDA and OpenCL is freely available from http://www.cs.njit.edu/usman/MaxSSmap.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-969) contains supplementary material, which is available to authorized users. 相似文献16.
Claudia Spies Alawi Luetz Gunnar Lachmann Markus Renius Clarissa von Haefen Klaus-Dieter Wernecke Marcus Bahra Alexander Schiemann Marco Paupers Christian Meisel 《PloS one》2015,10(12)
Purpose
Surgical patients are at high risk for developing infectious complications and postoperative delirium. Prolonged infections and delirium result in worse outcome. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and influenza vaccination are known to increase HLA-DR on monocytes and improve immune reactivity. This study aimed to investigate whether GM-CSF or vaccination reverses monocyte deactivation. Secondary aims were whether it decreases infection and delirium days after esophageal or pancreatic resection over time.Methods
In this prospective, randomized, placebo-controlled, double-blind, double dummy trial setting on an interdisciplinary ICU of a university hospital 61 patients with immunosuppression (monocytic HLA-DR [mHLA-DR] <10,000 monoclonal antibodies [mAb] per cell) on the first day after esophageal or pancreatic resection were treated with either GM-CSF (250 μg/m2/d), influenza vaccination (Mutagrip 0.5 ml/d) or placebo for a maximum of 3 consecutive days if mHLA-DR remained below 10,000 mAb per cell. HLA-DR on monocytes was measured daily until day 5 after surgery. Infections and delirium were followed up for 9 days after surgery. Primary outcome was HLA-DR on monocytes, and secondary outcomes were duration of infection and delirium.Results
mHLA-DR was significantly increased compared to placebo (p < 0.001) and influenza vaccination (p < 0.001) on the second postoperative day. Compared with placebo, GM-CSF-treated patients revealed shorter duration of infection (p < 0.001); the duration of delirium was increased after vaccination (p = 0.003).Conclusion
Treatment with GM-CSF in patients with postoperative immune suppression was safe and effective in restoring monocytic immune competence. Furthermore, therapy with GM-CSF reduced duration of infection in immune compromised patients. However, influenza vaccination increased duration of delirium after major surgery.Trial Registration
www.controlled-trials.com ISRCTN27114642 相似文献17.
Usha Ramakrishnan Amanda Stinger Ann M. DiGirolamo Reynaldo Martorell Lynnette M. Neufeld Juan A. Rivera Lourdes Schnaas Aryeh D. Stein Meng Wang 《PloS one》2015,10(8)
Objective
We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age.Design
Randomized placebo double-blind controlled trial.Settings
Cuernavaca, Mexico.Participants and Methods
We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment.Interventions or Main Exposures
400 mg/day of algal DHA.Outcome Measures
Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores.Results
Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation.Conclusions
Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments.Trial Registration
Clinicaltrials.gov NCT00646360 相似文献18.
Jessica McClelland Maria Kekic Natali Bozhilova Steffen Nestler Tracy Dew Frederique Van den Eynde Anthony S. David Katya Rubia Iain C. Campbell Ulrike Schmidt 《PloS one》2016,11(3)
Background
Anorexia nervosa (AN) is associated with morbid fear of fatness, extreme food restriction and altered self-regulation. Neuroimaging data implicate fronto-striatal circuitry, including the dorsolateral prefrontal cortex (DLPFC).Methods
In this double-blind parallel group study, we investigated the effects of one session of sham-controlled high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC (l-DLPFC) in 60 individuals with AN. A food exposure task was administered before and after the procedure to elicit AN-related symptoms.Outcomes
The primary outcome measure was ‘core AN symptoms’, a variable which combined several subjective AN-related experiences. The effects of rTMS on other measures of psychopathology (e.g. mood), temporal discounting (TD; intertemporal choice behaviour) and on salivary cortisol concentrations were also investigated. Safety, tolerability and acceptability were assessed.Results
Fourty-nine participants completed the study. Whilst there were no interaction effects of rTMS on core AN symptoms, there was a trend for group differences (p = 0.056): after controlling for pre-rTMS scores, individuals who received real rTMS had reduced symptoms post-rTMS and at 24-hour follow-up, relative to those who received sham stimulation. Other psychopathology was not altered differentially following real/sham rTMS. In relation to TD, there was an interaction trend (p = 0.060): real versus sham rTMS resulted in reduced rates of TD (more reflective choice behaviour). Salivary cortisol concentrations were unchanged by stimulation. rTMS was safe, well–tolerated and was considered an acceptable intervention.Conclusions
This study provides modest evidence that rTMS to the l-DLPFC transiently reduces core symptoms of AN and encourages prudent decision making. Importantly, individuals with AN considered rTMS to be a viable treatment option. These findings require replication in multiple-session studies to evaluate therapeutic efficacy.Trial Registration
www.Controlled-Trials.com ISRCTN22851337 相似文献19.
Petchara Sundarathiti Benno von Bormann Ronnarat Suvikapakornkul Panuwat Lertsithichai Vanlapa Arnuntasupakul 《PloS one》2015,10(6)
Introduction
Paravertebral block (PVB) is an alternative to general anaesthesia (GA) for breast surgery. However, for extensive surgery multiple punctures are needed increasing the immanent risk of the method. The purpose of this study was to evaluate PVB via catheter and injections at three different levels. Primary outcome was the quality of postoperative analgesia, in particular, the number of patients requiring additional morphine.Methods
In a randomised single blinded clinical study patients scheduled for breast surgery including axillary approach, were randomly allocated to different anaesthetic techniques, n = 35 each. Patients received either GA with sevoflurane or PVB with catheter at level Th 4. In PVB-patients a 1:2 mixture of bupivacaine 0.5% and lidocaine 2% with adrenaline was injected sequentially 10 ml each at three different levels.Results
Complication-free catheter insertion was possible in all 35 scheduled patients. The need for postoperative analgesics was higher after GA compared to PVB (22 vs.14 patients); p = 0.056. Postoperative morphine consumption was 1.55 (GA) and 0.26 mg (PVB) respectively (p < 0.001). Visual rating score (VRS) for pain at rest and at movement was higher in GA patients on post anaesthesia care unit (PACU) as well as on the ward at 1 - 6h and 6 - 12h. Readiness for discharge was earlier after PVB (4.96 and 6.52 hours respectively). After GA the incidence and severity of postoperative nausea and vomiting (PONV) was higher, though not significantly. Patients’ satisfaction was comparable in both groups.Conclusions
Three-level injection PVB via catheter for extensive mastectomy was efficient and well accepted. Using a catheter may enhance safety by avoiding multiple paravertebral punctures when extended spread of analgesia is required.Trial Registration
www.ClinicalTrial.gov NCT02065947 相似文献20.
Cheuk-Chun Szeto Bonnie C. H. Kwan Kai-Ming Chow Phyllis M. S. Cheng Vickie W. K. Kwong Agnes S. M. Choy Man-Ching Law Chi-Bon Leung Philip K. T. Li 《PloS one》2015,10(10)