235 research outputs found

    Defining the criteria for the evaluation of self-study multimedia language learning materials: do they facilitate or inhibit learner autonomy?

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    Durant els darrers anys, s’han publicat un gran nombre de materials multimèdia destinats a l’aprenentatge de llengües, la major part dels quals son CD-ROM dissenyats com a cursos per l’autoaprenentatge. Amb aquests materials, els alumnes poden treballar independentment sense l’assessorament d’un professor, i per aquest motiu s’ha afirmat que promouen i faciliten l’aprenentatge autònom. Aquesta relació, però, no es certa, com Phil Benson i Peter Voller 1997:10) han manifestat encertadament:(…) Such claims are often dubious, however, because of the limited range of options and roles offered to the learner. Nevertheless, technologies of education in the broadest sense can be considered to be either more or less supportive of autonomy. The question is what kind of criteria do we apply in evaluating them? En aquest article presentem una investigació conjunta on es defineixen els criteris que poden ser utilitzats per avaluar materials multimèdia en relació a la seva facilitat per permetre l’aprenentatge autònom. Aquests criteris son la base d’un qüestionari que s’ha emprat per avaluar una selecció de CD-ROM destinats a l’autoaprenentatge de llengües. La estructura d’aquest article és la següent: - Una introducció de l’estudi - Els criteris que s’han utilitzar per la creació del qüestionari - Els resultats generals de l’avaluació - Les conclusions que s’han extret i la seva importància pel disseny instructiu multimèdiaOver recent years, a wide range of language learning multimedia materials have been published, most of which have taken the form of CD-ROM packages designed as complete language courses for self-study. Due to the fact that learners can work with these materials independently without teacher supervision, claims have been made as to the attributes of such packages in regard to promoting and facilitating autonomous learning. This relationship, whilst claimed, is not certain as Phil Benson and Peter Voller (1997:10) have succinctly pointed out:(...) Such claims are often dubious, however, because of the limited range of options and roles offered to the learner. Nevertheless, technologies of education in the broadest sense can be considered to be either more or less supportive of autonomy. The question is what kind of criteria do we apply in evaluating them? (our italics) In this paper we aim to present a joint investigation which defines the criteria which can be used to evaluate multimedia language learning application in terms of their propensity to allow users to exercise autonomy in their learning endeavours. These criteria formed the basis of a questionnaire which has been used to evaluate a selection of language learning CD-ROMs which claim to be suitable for a self-study context. The structure of the paper will be as follows: -An introduction to the study-The criteria which have been used for the creation of the questionnaire. -The general results of the evaluation. -The conclusions which have been drawn and their importance for multimedia instructional design.Durante los últimos años, se han publicado un gran número de materiales multimedia destinados al aprendizaje de idiomas, la mayor parte de los cuales son CD-ROM diseñados como cursos para el autoaprendizaje. Con estos materiales, los alumnos pueden trabajar independientemente sin el asesoramiento de un profesor, y por este motivo se ha afirmado que promueven y facilitan el aprendizaje autónomo. Pero esta relación no es cierta, como Phil Benson y Peter Voller (1997:10) han manifestado acertadamente: (...) Such claims are often dubious, however, because of the limited range of options and roles offered to the learner. Nevertheless, technologies of education in the broadest sense can be considered to be either more or less supportive of autonomy. The question is what kind of criteria do we apply in evaluating them? En este artículo presentamos una investigación conjunta donde se definen los criterios que pueden ser utilizados para evaluar materiales multimedia con relación a su facilidad de permitir el aprendizaje autónomo. Estos criterios son la base de un cuestionario que se ha usado para evaluar una selección de CD-ROM destinados al autoaprendizaje de idiomas. La estructura de este artículo es la siguiente: -Una introducción al estudio -Los criterios que se han utilizado para la creación del cuestionario -Los resultados generales de la evaluación -Las conclusiones que se han extraído y su importancia para el diseño instructivo multimedi

    Lasers for Satellite Uplinks and Downlinks

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    The article of record as published may be found at http://dx.doi.org/10.3390/sci2030071The use of Light Amplification by Stimulated Emission of Radiation (i.e., LASERs or lasers) by the U.S. Department of Defense is not new and includes laser weapons guidance, laser-aided measurements, even lasers as weapons (e.g., Airborne Laser). Lasers in support of telecommunications is also not new. The use of laser light in fiber optics shattered thoughts on communications bandwidth and throughput. Even the use of lasers in space is no longer new. Lasers are being used for satellite-to-satellite crosslinking. Laser communication can transmit orders-of-magnitude more data using orders-of-magnitude less power and can do so with minimal risk of exposure to the sending and receiving terminals. What is new is using lasers as the uplink and downlink between the terrestrial segment and the space segment of satellite systems. More so, the use of lasers to transmit and receive data between moving terrestrial segments (e.g., ships at sea, airplanes in flight) and geosynchronous satellites is burgeoning. This manuscript examines the technological maturation of employing lasers as the signal carrier for satellite communications linking terrestrial and space systems. The purpose of the manuscript is to develop key performance parameters (KPPs) to inform U.S. Department of Defense initial capabilities documents (ICDs) for near-future satellite acquisition and development. By appreciating the history and technological challenges of employing lasers rather than traditional radio frequency sources for satellite uplink and downlink signal carrier, this manuscript recommends ways for the U.S. Department of Defense to employ lasers to transmit and receive high bandwidth, large-throughput data from moving platforms that need to retain low probabilities of detection, intercept, and exploitation (e.g., carrier battle group transiting to a hostile area of operations, unmanned aerial vehicle collecting over adversary areas). The manuscript also intends to identify commercial sector early-adopter fields and those fields likely to adapt to laser employment for transmission and receipt.U.S. Air Forc

    Importance of Alternative Reactor Vessel Flow Paths During Loss-of-Coolant Accident Scenarios with Debris-Induced Core Blockage

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    During the initial stage of a Loss of Coolant Accident (LOCA), known as the blowdown phase, the high-temperature and pressure break flow can impinge on thermal insulation and generate a substantial amount of debris in containment. This debris can accumulate in the sump compartment and become a major safety concern by potentially impacting the capabilities of the Emergency Core Cooling System (ECCS). Debris can accumulate in the sump and could cause ECCS pump head loss and/or pass through the filtering systems (debris bed and sump strainer) into the reactor primary system during the long term cooling phase. This scenario and its possible downstream effects are of primary concern under the US Nuclear Regulatory Commission (NRC) Generic Safety Issue 191 (GSI-191). If the debris was to bypass the filtering and accumulate at the core inlet, core flow could theoretically decrease, affecting the core coolability (decay heat removal). If the debris accumulation at the lower core plate was high enough, it could potentially block the flow through the base of the core, the primary coolant flow path. In an even more severe scenario, debris could block all flow from the bottom of the core by blocking both the core inlet and core baffle/barrel bypass. Under such conditions, core coolability is dependent on coolant reaching the core through alternative flow paths. One of these key flow paths is the core bypass (baffle/barrel). Additionally, the effectiveness of bypass flow in reaching and cooling the core is heavily impacted by certain plant specific features. One such plant specific feature, which the presence or lack of can have a major impact on core coolability, are the pressure relief (LOCA) holes. When the core inlet and bypass are unavailable, coolant must reach the core from the top by passing through the upper head region or steam generators. The primary response during each phase of a double-end guillotine (DEG) Loss-of-Coolant Accident (LOCA) was analyzed for the model of a typical 4-loop Pressurized Water Reactor (PWR) using RELAP5-3D. The effectiveness of core cooling under the hypothesized cold leg break with full core inlet blockage was analyzed for models with and without pressure relief holes. Core cooling was also evaluated under a hypothesized hot leg DEG break with full core inlet and core bypass blockages, with particular emphasis on comparing simplified upper head geometry to a more realistic and more conservative model. The results of the cold leg break with inlet blockage simulation showed that the presence of alternative flow paths from the bypass into the core may significantly increase core coolability and prevent cladding temperatures from reaching safety limits, while the lack of LOCA holes may lead to a conservative over-prediction of the cladding temperature. The simulation results also showed the impact of LOCA holes on total liquid level maintained in the core and driving flow through the bypass. The hot leg full inlet/bypass blockage showed that the upper head path was able to provide sufficient coolant, even under conservative models. These simulation results help inform safety impacts of some severe accidents under GSI-191 and serve as a reminder of the importance of modeling plant-specific features when performing best-estimate safety calculations

    Independent prescribing by advanced physiotherapists for patients with low back pain in primary care:a feasibility trial with an embedded qualitative component

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    BACKGROUND: Low back pain (LBP) is the most prevalent musculoskeletal condition. Guidelines advocate a multimodal approach, including prescription of medications. Advanced Physiotherapy Practitioners (APPs) are well placed to manage LBP. To date no trial has evaluated the efficacy of physiotherapist-prescribing for LBP. OBJECTIVES: To evaluate the feasibility, suitability and acceptability of assessing the effectiveness of physiotherapist-prescribing for LBP in primary care; informing the design of a future definitive stepped-wedged cluster trial (SWcRCT). METHODS: Mixed-methods, single-arm feasibility design with two components. 1) Trial component: participants with medium-risk LBP +/-leg pain were recruited across 3 sites. Outcome measures (primary outcome measures-Pain/RMDQ) were completed at baseline, 6 and 12 weeks Physical activity/sedentary behaviour were assessed over 7 days using accelerometery. A CONSORT diagram analysed recruitment/follow-up rates. Descriptive analysis evaluated procedure/floor-effects. 2) Embedded qualitative component: focus groups (n = 6) and semi-structured interviews (n = 3) evaluated the views/experiences of patients and APPs about feasibility/suitability/acceptability of the proposed trial. Thematic analysis synthesised the qualitative data. Findings were evaluated against a priori success criteria. RESULTS: n = 29 participants were recruited. 90% of success criteria were met. Loss to follow-up at 12 weeks (65.5%) did not satisfy success criteria. Primary and secondary outcome measures were suitable and acceptable with no floor effects. The addition of a sleep assessment tool was advised. Accelerometer use was acceptable with 100% adherence. APPs felt all patients presenting with non-specific LBP +/- leg pain and capture data representative of the full scope of physiotherapist independent prescribing should be included. Data collection methods were acceptable to APPs and patients. APPs advocated necessity for using research assistants owing to time limitations. CONCLUSIONS: Methods evaluated are feasible, suitable and acceptable for a definitive SWcRCT, with modification of eligibility criteria, and use of research assistants to overcome limited clinician capacity. A definitive SWcRCT is feasible with minor modifications

    Whole-genome sequencing shows that patient-to-patient transmission rarely accounts for acquisition of Staphylococcus aureus in an intensive care unit

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    BACKGROUND  Strategies to prevent Staphylococcus aureus infection in hospitals focus on patient-to-patient transmission. We used whole-genome sequencing to investigate the role of colonized patients as the source of new S. aureus acquisitions, and the reliability of identifying patient-to-patient transmission using the conventional approach of spa typing and overlapping patient stay. METHODS Over 14 months, all unselected patients admitted to an adult intensive care unit (ICU) were serially screened for S. aureus. All available isolates (n = 275) were spa typed and underwent whole-genome sequencing to investigate their relatedness at high resolution. RESULTS Staphylococcus aureus was carried by 185 of 1109 patients sampled within 24 hours of ICU admission (16.7%); 59 (5.3%) patients carried methicillin-resistant S. aureus (MRSA). Forty-four S. aureus (22 MRSA) acquisitions while on ICU were detected. Isolates were available for genetic analysis from 37 acquisitions. Whole-genome sequencing indicated that 7 of these 37 (18.9%) were transmissions from other colonized patients. Conventional methods (spa typing combined with overlapping patient stay) falsely identified 3 patient-to-patient transmissions (all MRSA) and failed to detect 2 acquisitions and 4 transmissions (2 MRSA). CONCLUSIONS Only a minority of S. aureus acquisitions can be explained by patient-to-patient transmission. Whole-genome sequencing provides the resolution to disprove transmission events indicated by conventional methods and also to reveal otherwise unsuspected transmission events. Whole-genome sequencing should replace conventional methods for detection of nosocomial S. aureus transmission

    Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis

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    Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership, U.S. Agency for International Development, U.K. Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin.Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. Results: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. Conclusions: The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.)Publisher PDFPeer reviewe

    DeepAMR for predicting co-occurrent resistance of Mycobacterium tuberculosis.

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    MOTIVATION: Resistance co-occurrence within first-line anti-tuberculosis (TB) drugs is a common phenomenon. Existing methods based on genetic data analysis of Mycobacterium tuberculosis (MTB) have been able to predict resistance of MTB to individual drugs, but have not considered the resistance co-occurrence and cannot capture latent structure of genomic data that corresponds to lineages. RESULTS: We used a large cohort of TB patients from 16 countries across six continents where whole-genome sequences for each isolate and associated phenotype to anti-TB drugs were obtained using drug susceptibility testing recommended by the World Health Organization. We then proposed an end-to-end multi-task model with deep denoising auto-encoder (DeepAMR) for multiple drug classification and developed DeepAMR_cluster, a clustering variant based on DeepAMR, for learning clusters in latent space of the data. The results showed that DeepAMR outperformed baseline model and four machine learning models with mean AUROC from 94.4% to 98.7% for predicting resistance to four first-line drugs [i.e. isoniazid (INH), ethambutol (EMB), rifampicin (RIF), pyrazinamide (PZA)], multi-drug resistant TB (MDR-TB) and pan-susceptible TB (PANS-TB: MTB that is susceptible to all four first-line anti-TB drugs). In the case of INH, EMB, PZA and MDR-TB, DeepAMR achieved its best mean sensitivity of 94.3%, 91.5%, 87.3% and 96.3%, respectively. While in the case of RIF and PANS-TB, it generated 94.2% and 92.2% sensitivity, which were lower than baseline model by 0.7% and 1.9%, respectively. t-SNE visualization shows that DeepAMR_cluster captures lineage-related clusters in the latent space. AVAILABILITY AND IMPLEMENTATION: The details of source code are provided at http://www.robots.ox.ac.uk/?davidc/code.php. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

    A comparison of liquid and solid culture for determining relapse and durable cure in phase III TB trials for new regimens

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    Supported by the Global Alliance for TB Drug Development with support from the Bill & Melinda Gates Foundation, the Medical Research Council (MC_UU_12023/27), the European and Developing Countries Clinical Trials Partnership (grant IP.2007.32011.011), the US Agency for International Development, the UK Department for International Development, the Directorate General for International Cooperation of the Netherlands, Irish Aid, the Australia Department of Foreign Affairs and Trade and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636 and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin. Additional grants were from Chief Scientist Office, Scottish Government, British Society of Antimicrobial Chemotherapy.Background:  Tuberculosis kills more people than any other infectious disease, and new regimens are essential. The primary endpoint for confirmatory phase III trials for new regimens is a composite outcome that includes bacteriological treatment failure and relapse. Culture methodology is critical to the primary trial outcome. Patients in clinical trials can have positive cultures after treatment ends that may not necessarily indicate relapse, which was ascribed previously to laboratory cross-contamination or breakdown of old lesions. Löwenstein-Jensen (LJ) medium was the previous standard in clinical trials, but almost all current and future trials will use the Mycobacteria Growth Indicator Tube (MGIT) system due to its simplicity and consistency of use, which will affect phase III trial results. LJ was used for the definition of the primary endpoint in the REMoxTB trial, but every culture was also inoculated in parallel into the MGIT system. The data from this trial, therefore, provide a unique opportunity to investigate and compare the incidence of false ‘isolated positives’ in liquid and solid media and their potential impact on the primary efficacy results. Methods:  All post-treatment positive cultures were reviewed in the REMoxTB clinical trial. Logistic regression models were used to model the incidence of isolated positive cultures on MGIT and LJ. Results:  A total of 12,209 sputum samples were available from 1652 patients; cultures were more often positive on MGIT than LJ. In 1322 patients with a favourable trial outcome, 126 (9.5%) had cultures that were positive in MGIT compared to 34 (2.6%) patients with positive cultures on LJ. Among patients with a favourable outcome, the incidence of isolated positives on MGIT differed by study laboratory (p < 0.0001) with 21.9% of these coming from one laboratory investigating only 4.9% of patients. No other baseline factors predicted isolated positives on MGIT after adjusting for laboratory. There was evidence of clustering of isolated positive cultures in some patients even after adjusting for laboratory, p < 0.0001. The incidence of isolated positives on MGIT did not differ by treatment arm (p = 0.845, unadjusted). Compared to negative MGIT cultures, positive MGIT cultures were more likely to be associated with higher grade TB symptoms reported within 7 days either side of sputum collection in patients with an unfavourable primary outcome (p < 0.0001) but not in patients with a favourable outcome (p = 0.481). Conclusions:  Laboratory cross-contamination was a likely cause of isolated positive MGIT cultures which were clustered in some laboratories. Certain patients had repeated positive MGIT cultures that did not meet the definition of a relapse. This pattern was too common to be explained by cross-contamination only, suggesting that host factors were also responsible. We conclude that MGIT can replace LJ in phase III TB trials, but there are implications for the definition of the primary outcome and patient management in trials in such settings. Most importantly, the methodologies differ in the incidence of isolated positives and in their capacity for capturing non-tuberculosis mycobacteria. It emphasises the importance of effective medical monitoring after treatment ends and consideration of clinical signs and symptoms for determining treatment failure and relapse.Publisher PDFPeer reviewe

    A crowd of BashTheBug volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates

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    Tuberculosis is a respiratory disease that is treatable with antibiotics. An increasing prevalence of resistance means that to ensure a good treatment outcome it is desirable to test the susceptibility of each infection to different antibiotics. Conventionally, this is done by culturing a clinical sample and then exposing aliquots to a panel of antibiotics, each being present at a pre-determined concentration, thereby determining if the sample isresistant or susceptible to each sample. The minimum inhibitory concentration (MIC) of a drug is the lowestconcentration that inhibits growth and is a more useful quantity but requires each sample to be tested at a range ofconcentrations for each drug. Using 96-well broth micro dilution plates with each well containing a lyophilised pre-determined amount of an antibiotic is a convenient and cost-effective way to measure the MICs of several drugs at once for a clinical sample. Although accurate, this is still an expensive and slow process that requires highly-skilled and experienced laboratory scientists. Here we show that, through the BashTheBug project hosted on the Zooniverse citizen science platform, a crowd of volunteers can reproducibly and accurately determine the MICs for 13 drugs and that simply taking the median or mode of 11–17 independent classifications is sufficient. There is therefore a potential role for crowds to support (but not supplant) the role of experts in antibiotic susceptibility testing

    Evaluation of Nanopore sequencing for Mycobacterium tuberculosis drug susceptibility testing and outbreak investigation: a genomic analysis

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    Mycobacterium tuberculosis whole-genome sequencing (WGS) has been widely used for genotypic drug susceptibility testing (DST) and outbreak investigation. For both applications, Illumina technology is used by most public health laboratories; however, Nanopore technology developed by Oxford Nanopore Technologies has not been thoroughly evaluated. The aim of this study was to determine whether Nanopore sequencing data can provide equivalent information to Illumina for transmission clustering and genotypic DST for M tuberculosis
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