570 research outputs found

    A Comparison of the Accuracy and Reliability of the Wahoo KICKR and SRM Power Meter

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    The Wahoo KICKR cycling trainer is a new direct-drive electromagnetically braked bike-trainer that allows cyclists to use their own bicycles as ergometer. It is purported to provide ±3% accuracy in power, despite costing considerably less than other cycling ergometers. The purpose of this study was to assess the accuracy and reliability of several KICKR units against the more established SRM power meter using a first-principles based dynamic calibration rig (CALRIG).Five KICKRs and one SRM unit were assessed by a CALRIG-driven incremental test. Following a 15 min warm-up and ‘calibration’ as per manufacturer instructions, power was increased (starting at 50 W) by 50 W every 2 min up to 400 W. Each unit was tested twice non-consecutively, in random order. Data was recorded at 1 Hz, with the last 10 s of each stage being averaged for analysis. The mean error (%) and coefficient of determination (R2) versus CALRIG; as well as the change in mean error and Typical Error of Measurement (TEM) (expressed as a % coefficient of variation) between trials was calculated for each device.The mean error across all KICKR units was -1.5% (range: -3.1% to 0.0%) compared to -1.6% reported by the SRM. R2 >0.999 was found for all KICKR units and SRM compared to the CALRIG. The mean TEM for the KICKRs was 1.5% (range: 1.1% to 1.9%), whereas the SRM reported 0.7%. For test-retest reproducibility, two KICKRs had statistically significant changes in mean error, with an average 1.3% change across all KICKRs. Comparatively, the SRM reported a 0.4% change between trials. The Wahoo KICKR trainer measures power to a similar level of accuracy to the more reputable SRM power meter during an incremental exercise test. Although not as reproducible, the KICKR still demonstrates an acceptable level of reliability for assessing cycling performance

    Synergistic melanoma cell death mediated by inhibition of both MCL1 and BCL2 in high-risk tumors driven by NF1/PTEN loss

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    Melanomas driven by loss of the NF1 tumor suppressor have a high risk of treatment failure and effective therapies have not been developed. Here we show that loss-of-function mutations of nf1 and pten result in aggressive melanomas in zebrafish, representing the first animal model of NF1-mutant melanomas harboring PTEN loss. MEK or PI3K inhibitors show little activity when given alone due to cross-talk between the pathways, and high toxicity when given together. The mTOR inhibitors, sirolimus, everolimus, and temsirolimus, were the most active single agents tested, potently induced tumor-suppressive autophagy, but not apoptosis. Because addition of the BCL2 inhibitor venetoclax resulted in compensatory upregulation of MCL1, we established a three-drug combination composed of sirolimus, venetoclax, and the MCL1 inhibitor S63845. This well-tolerated drug combination potently and synergistically induces apoptosis in both zebrafish and human NF1/PTEN-deficient melanoma cells, providing preclinical evidence justifying an early-stage clinical trial in patients with NF1/PTEN-deficient melanoma

    Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

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    .Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

    An evaluation of Canada's Compassionate Care Benefit from a family caregiver's perspective at end of life

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    <p>Abstract</p> <p>Background</p> <p>The goal of Canada's Compassionate Care Benefit (CCB) is to enable family members and other loved ones who are employed to take a temporary <it>secured </it>leave to care for a terminally ill individual at end of life. Successful applicants of the CCB can receive up to 55% of their average insured earnings, up to a maximum of CDN$435 per week, over a six week period to provide care for a gravely ill family member at risk of death within a six month period, as evidenced by a medical certificate. The goal of this study is to evaluate the CCB from the perspective of family caregivers providing care to individuals at end of life. There are three specific research objectives. Meeting these objectives will address our study purpose which is to make policy-relevant recommendations informed by the needs of Canadian family caregivers and input from other key stakeholders who shape program uptake. Being the first study that will capture family caregivers' experiences and perceptions of the CCB and gather contextual data with front-line palliative care practitioners, employers, and human resources personnel, we will be in a unique position to provide policy solutions/recommendations that will address concerns raised by numerous individuals and organizations.</p> <p>Methods</p> <p>We will achieve the research goal and objectives through employing utilization-focused evaluation as our methodology, in-depth interviews and focus groups as our techniques of data collection, and constant comparative as our technique of data analysis. Three respondent groups will participate: (1) family caregivers who are providing or who have provided end of life care via phone interview; (2) front-line palliative care practitioners via phone interview; and (3) human resources personnel and employers via focus group. Each of these three groups has a stake in the successful administration of the CCB. A watching brief of policy documents, grey literature, media reports, and other relevant items will also be managed throughout data collection.</p> <p>Discussion</p> <p>We propose to conduct this study over a three year period beginning in October, 2006 and ending in October, 2009.</p

    Computer-assisted and patient-specific 3-D planning and evaluation of a single-cut rotational osteotomy for complex long-bone deformities

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    Malunion after long bone fracture results in an incorrect position of the distal bone segment. This misalignment may lead to reduced function of the limb, early osteoarthritis and chronic pain. An established treatment option is a corrective osteotomy. For complex malunions, a single-cut rotational osteotomy is sometimes preferred in cases of angular deformity in three dimensions. However, planning and performing this type of osteotomy is relatively complex. This report describes a computer-assisted method for 3-D planning and realizing a single-cut rotational osteotomy with a patient-specific cutting guide for orienting the osteotomy and an angled jig for adjusting the rotation angle. The accuracy and reproducibility of the method is evaluated experimentally using plastic bones. In addition, complex rotational deformities are simulated by a computer to investigate the relation between deformity and correction parameters. The computed relation between deformity and correction parameters enables the surgeon to judge the feasibility of a single-cut rotational osteotomy. This appears possible for deformities combining axial misalignment with sufficient axial rotation. The proposed 3-D method of preoperative planning and transfer with a patient-specific cutting guide and angled jig renders the osteotomy procedure easily applicable, accurate, reproducible, and is a good alternative for complex and expensive navigation systems

    How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

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    Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

    A Systems Approach to Improving Rural Care in Ethiopia

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    Background: Multiple interventions have been launched to improve the quality, access, and utilization of primary health care in rural, low-income settings; however, the success of these interventions varies substantially, even within single studies where the measured impact of interventions differs across sites, centers, and regions. Accordingly, we sought to examine the variation in impact of a health systems strengthening intervention and understand factors that might explain the variation in impact across primary health care units. Methodology/Principal Findings: We conducted a mixed methods positive deviance study of 20 Primary Health Care Units (PHCUs) in rural Ethiopia. Using longitudinal data from the Ethiopia Millennium Rural Initiative (EMRI), we identified PHCUs with consistently higher performance (n = 2), most improved performance (n = 3), or consistently lower performance (n = 2) in the provision of antenatal care, HIV testing in antenatal care, and skilled birth attendance rates. Using data from site visits and in-depth interviews (n = 51), we applied the constant comparative method of qualitative data analysis to identify key themes that distinguished PHCUs with different performance trajectories. Key themes that distinguished PHCUs were 1) managerial problem solving capacity, 2) relationship with the woreda (district) health office, and 3) community engagement. In higher performing PHCUs and those with the greatest improvement after the EMRI intervention, health center and health post staff were more able to solve day-to-day problems, staff had better relationships with the woreda health official, an
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