3,179 research outputs found

    The Effective Fragment Molecular Orbital Method for Fragments Connected by Covalent Bonds

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    We extend the effective fragment molecular orbital method (EFMO) into treating fragments connected by covalent bonds. The accuracy of EFMO is compared to FMO and conventional ab initio electronic structure methods for polypeptides including proteins. Errors in energy for RHF and MP2 are within 2 kcal/mol for neutral polypeptides and 6 kcal/mol for charged polypeptides similar to FMO but obtained two to five times faster. For proteins, the errors are also within a few kcal/mol of the FMO results. We developed both the RHF and MP2 gradient for EFMO. Compared to ab initio, the EFMO optimized structures had an RMSD of 0.40 and 0.44 {\AA} for RHF and MP2, respectively.Comment: Revised manuscrip

    Can you believe what you read in the papers?

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    The number of reports of clinical trials grows by hundreds every week. However, this does not mean that people making decisions about healthcare are finding it easier to obtain reliable knowledge for these decisions. Some of the information is unreliable. Systematic reviews are helping to resolve this by bringing together the research on a topic, appraising and summarising it. But the quality of these reviews depends greatly on the quality of the studies, and this usually means the quality of their reports. If there are fundamental flaws within a study, such as the use of inappropriate 'randomisation' techniques in the context of reviews of the effects of interventions, the reviewers will not be able to fix these. Worse still, if they are not aware of underlying flaws, they might make incorrect judgements about the quality of the research in their review. A study by Wu and colleagues of 'randomised trials' from China provides a reminder of the cautious approach needed by users of scientific articles. They contacted the authors of more than 2000 research articles, which purported to be reports of randomised trials; and concluded that ten of every 11 studies claiming to be a randomised trial probably did not use random allocation. Better education of researchers, peer reviewers and editors about what is, and is not, a properly randomised trial is needed; along with better reporting of the details for how participants were allocated to the different interventions. Systematic reviewers must be cautious in making assumptions about the conduct of trials based on simple phrases about the trial methodology, rather than a full description of the methods actually used. It's not that you can't believe anything that you read in the papers, just that you cannot believe everything

    Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: An economic evaluation alongside a randomised controlled trial

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    Objective: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS') and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. Methods: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov) model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY) estimated using both EQ-5D and SF-6D. Results: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100) and generated 0.002 more QALYs. Conclusion: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most costeffective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial. Copyright: © 2014 Sanghera et al

    Reporting of prognostic markers: current problems and development of guidelines for evidence-based practice in the future

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    Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome (e.g. recurrence of disease), and are important tools in the management of cancer and many other diseases. Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because (sometimes conflicting) evidence relating to markers is often published across a number of studies. To investigate the practicality of this approach, an empirical investigation of a systematic review of tumour markers for neuroblastoma was performed; 260 studies of prognostic markers were identified, which considered 130 different markers

    Simultaneous temporal trends in dementia incidence and prevalence, 2005–2013 : a population-based retrospective cohort study in Saskatchewan, Canada

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    Original studies published over the last decade regarding time trends in dementia report mixed results. The aims of the present study were to use linked administrative health data for the province of Saskatchewan for the period 2005/2006 to 2012/2013 to: (1) examine simultaneous temporal trends in annual age- and sex-specific dementia incidence and prevalence among individuals aged 45 and older, and (2) stratify the changes in incidence over time by database of identification. Using a population-based retrospective cohort study design, data were extracted from seven provincial administrative health databases linked by a unique anonymized identification number. Individuals 45 years and older at first identification of dementia between April 1, 2005 and March 31, 2013 were included, based on case definition criteria met within any one of four administrative health databases (hospital, physician, prescription drug, and long-term care). Between 2005/2006 and 2012/2013, the 12-month age-standardized incidence rate of dementia declined significantly by 11.07% and the 12-month age-standardized prevalence increased significantly by 30.54%. The number of incident cases decreased from 3,389 to 3,270 and the number of prevalent cases increased from 8,795 to 13,012. Incidence rate reductions were observed in every database of identification. We observed a simultaneous trend of decreasing incidence and increasing prevalence of dementia over a relatively short 8-year time period from 2005/2006 to 2012/2013. These trends indicate that the average survival time of dementia is lengthening. Continued observation of these time trends is warranted given the short study period

    Bilateral Assessment of Functional Tasks for Robot-assisted Therapy Applications

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    This article presents a novel evaluation system along with methods to evaluate bilateral coordination of arm function on activities of daily living tasks before and after robot-assisted therapy. An affordable bilateral assessment system (BiAS) consisting of two mini-passive measuring units modeled as three degree of freedom robots is described. The process for evaluating functional tasks using the BiAS is presented and we demonstrate its ability to measure wrist kinematic trajectories. Three metrics, phase difference, movement overlap, and task completion time, are used to evaluate the BiAS system on a bilateral symmetric (bi-drink) and a bilateral asymmetric (bi-pour) functional task. Wrist position and velocity trajectories are evaluated using these metrics to provide insight into temporal and spatial bilateral deficits after stroke. The BiAS system quantified movements of the wrists during functional tasks and detected differences in impaired and unimpaired arm movements. Case studies showed that stroke patients compared to healthy subjects move slower and are less likely to use their arm simultaneously even when the functional task requires simultaneous movement. After robot-assisted therapy, interlimb coordination spatial deficits moved toward normal coordination on functional tasks

    How are falls and fear of falling associated with objectively measured physical activity in a cohort of community-dwelling older men?

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    BACKGROUND: Falls affect approximately one third of community-dwelling older adults each year and have serious health and social consequences. Fear of falling (FOF) (lack of confidence in maintaining balance during normal activities) affects many older adults, irrespective of whether they have actually experienced falls. Both falls and fear of falls may result in restrictions of physical activity, which in turn have health consequences. To date the relation between (i) falls and (ii) fear of falling with physical activity have not been investigated using objectively measured activity data which permits examination of different intensities of activity and sedentary behaviour. METHODS: Cross-sectional study of 1680 men aged 71-92 years recruited from primary care practices who were part of an on-going population-based cohort. Men reported falls history in previous 12 months, FOF, health status and demographic characteristics. Men wore a GT3x accelerometer over the hip for 7 days. RESULTS: Among the 12% of men who had recurrent falls, daily activity levels were lower than among non-fallers; 942 (95% CI 503, 1381) fewer steps/day, 12(95% CI 2, 22) minutes less in light activity, 10(95% CI 5, 15) minutes less in moderate to vigorous PA [MVPA] and 22(95% CI 9, 35) minutes more in sedentary behaviour. 16% (n = 254) of men reported FOF, of whom 52% (n = 133) had fallen in the past year. Physical activity deficits were even greater in the men who reported that they were fearful of falling than in men who had fallen. Men who were fearful of falling took 1766(95% CI 1391, 2142) fewer steps/day than men who were not fearful, and spent 27(95% CI 18, 36) minutes less in light PA, 18(95% CI 13, 22) minutes less in MVPA, and 45(95% CI 34, 56) minutes more in sedentary behaviour. The significant differences in activity levels between (i) fallers and non-fallers and (ii) men who were fearful of falling or not fearful, were mediated by similar variables; lower exercise self-efficacy, fewer excursions from home and more mobility difficulties. CONCLUSIONS: Falls and in particular fear of falling are important barriers to older people gaining health benefits of walking and MVPA. Future studies should assess the longitudinal associations between falls and physical activity
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