426 research outputs found

    Analysis of Eligibility Criteria Complexity in Clinical Trials

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    Formal, computer-interpretable representations of eligibility criteria would allow computers to better support key clinical research and care use cases such as eligibility determination. To inform the development of such formal representations for eligibility criteria, we conducted this study to characterize and quantify the complexity present in 1000 eligibility criteria randomly selected from studies in ClinicalTrials.gov. We classified the criteria by their complexity, semantic patterns, clinical content, and data sources. Our analyses revealed significant semantic and clinical content variability. We found that 93% of criteria were comprehensible, with 85% of these criteria having significant semantic complexity, including 40% relying on temporal data. We also identified several domains of clinical content. Using the findings of the study as requirements for computer-interpretable representations of eligibility, we discuss the challenges for creating such representations for use in clinical research and practice

    Interacting Frobenius Algebras are Hopf

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    Theories featuring the interaction between a Frobenius algebra and a Hopf algebra have recently appeared in several areas in computer science: concurrent programming, control theory, and quantum computing, among others. Bonchi, Sobocinski, and Zanasi (2014) have shown that, given a suitable distributive law, a pair of Hopf algebras forms two Frobenius algebras. Here we take the opposite approach, and show that interacting Frobenius algebras form Hopf algebras. We generalise (BSZ 2014) by including non-trivial dynamics of the underlying object---the so-called phase group---and investigate the effects of finite dimensionality of the underlying model. We recover the system of Bonchi et al as a subtheory in the prime power dimensional case, but the more general theory does not arise from a distributive law.Comment: 32 pages; submitte

    Categories of Quantum and Classical Channels (extended abstract)

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    We introduce the CP*-construction on a dagger compact closed category as a generalisation of Selinger's CPM-construction. While the latter takes a dagger compact closed category and forms its category of "abstract matrix algebras" and completely positive maps, the CP*-construction forms its category of "abstract C*-algebras" and completely positive maps. This analogy is justified by the case of finite-dimensional Hilbert spaces, where the CP*-construction yields the category of finite-dimensional C*-algebras and completely positive maps. The CP*-construction fully embeds Selinger's CPM-construction in such a way that the objects in the image of the embedding can be thought of as "purely quantum" state spaces. It also embeds the category of classical stochastic maps, whose image consists of "purely classical" state spaces. By allowing classical and quantum data to coexist, this provides elegant abstract notions of preparation, measurement, and more general quantum channels.Comment: In Proceedings QPL 2012, arXiv:1407.842

    The test–retest reliability of four functional mobility tests in apparently healthy adults

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    Background: Simple field tests are often used to assess functional mobility in clinical settings. Despite having many benefits, these tests are susceptible to measurement error and individual variation. Objectives: To examine the test-retest and absolute reliability of timed up and go test (TUG), five times sit-to-stand (FTSTS), stair climb test (SCT) and 6 minute walk (6MWT). Methods: Over two sessions, thirty-five subjects (30-74 years), repeated the five tests approximately four weeks apart. Test-retest reliability (intraclass correlations [ICC]) and absolute reliability (95% limit of agreements [95% LOA]; standard error of measurement [SEM] and minimum detectable change [MDC]) were calculated. Results: All five tests had high test-retest reliability (ICC > 0.95) although significant between session changes were present for the TUG and FTSTS (p < 0.05). FTSTS displayed the greatest measurement error whilst 95% LOA was the most conservative measure of absolute reliability. Conclusions: The results of this study indicate that the TUG, FTSTS, SCT and 6MWT are reliable when performed four weeks apart. Furthermore, the inclusion of SEM, MDC and 95% LOA provides reference values to aid in identifying changes over time above those of measurement error and individual variation

    Design and feasibility testing of a novel group intervention for young women who binge drink in groups

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    BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

    Amiloride, fluoxetine or riluzole to reduce brain volume loss in secondary progressive multiple sclerosis: the MS-SMART four-arm RCT

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    Background: Neuroprotective drugs are needed to slow or prevent neurodegeneration and disability accrual in secondary progressive multiple sclerosis. Amiloride, fluoxetine and riluzole are repurposed drugs with potential neuroprotective effects. Objectives: To assess whether or not amiloride, fluoxetine and riluzole can reduce the rate of brain volume loss in people with secondary progressive multiple sclerosis over 96 weeks. The secondary objectives that were assessed were feasibility of a multiarm trial design approach, evaluation of anti-inflammatory effects, clinician- and patient-reported efficacy and three mechanistic substudies. Design: A multicentre, multiarm, randomised, double-blind, placebo-controlled, parallel-group Phase IIb trial with follow-up at 4, 8, 12, 24, 36, 48, 72 and 96 weeks. Patients, investigators (including magnetic resonance imaging analysts), and treating and independent assessing neurologists were blinded to the treatment allocation. The target sample size was 440 patients. Setting: Thirteen UK clinical neuroscience centres. Participants: Participants were aged 25–65 years, had secondary progressive multiple sclerosis with evidence of disease progression independent of relapses in the previous 2 years, and had an Expanded Disability Status Scale score of 4.0–6.5. Patients were ineligible if they could not have a magnetic resonance imaging scan; had a relapse or steroids in the previous 3 months; or had epilepsy, depression, bipolar disorder, glaucoma, bleeding disorders or significant organ comorbidities. Exclusion criteria were concurrent disease-modified treatments, immunosuppressants or selective serotonin reuptake inhibitors. Interventions: Participants received amiloride (5 mg), fluoxetine (20 mg), riluzole (50 mg) or placebo (randomised 1 : 1 : 1 : 1) twice daily. Main outcome measures: The primary end point was magnetic resonance imaging-derived percentage brain volume change at 96 weeks. Secondary end points were new/enlarging T2 lesions, pseudoatrophy, and clinician- and patient-reported measures (including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, Symbol Digit Modalities Test, low-contrast letter visual acuity, Multiple Sclerosis Impact Scale 29 items, version 2, Multiple Sclerosis Walking Scale, version 2, and questionnaires addressing pain and fatigue). The exploratory end points included measures of persistent new T1 hypointensities and grey matter volume changes. The substudies were advanced magnetic resonance imaging, optical coherence tomography and cerebrospinal fluid analyses. Results: Between December 2014 and June 2016, 445 patients were randomised (analysed) to amiloride [n = 111 (99)], fluoxetine [n = 111 (96)], riluzole [n = 111 (99)] or placebo [n = 112 (99)]. A total of 206 randomised patients consented to the advanced magnetic resonance imaging substudy, 260 consented to the optical coherence tomography substudy and 70 consented to the cerebrospinal fluid substudy. No significant difference was seen between the active drugs and placebo in percentage brain volume change at week 96 as follows (where negative values mean more atrophy than placebo): amiloride minus placebo 0.0% (Dunnett-adjusted 95% confidence interval –0.4% to 0.5%), fluoxetine minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.5% to 0.3%); riluzole minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.6% to 0.3%). There was good adherence to study drugs. The proportion of patients experiencing adverse events was similar in the treatment and placebo groups. There were no emergent safety issues. Limitations: There was a lower than expected uptake in the cerebrospinal fluid substudy. Conclusions: A multiarm Phase II paradigm is efficient in determining which neuroprotective agents to take through to Phase III trials. Amiloride, fluoxetine and riluzole were not effective in reducing the brain atrophy rate in people with secondary progressive multiple sclerosis. Mechanistic pathobiological insight was gained. Future work: To use the information gained from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) to inform future trial design as new candidate agents are identified. Trial registration: Current Controlled Trials ISRCTN28440672, NCT01910259 and EudraCT 2012-005394-31. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 3. See the NIHR Journals Library website for further project information. This trial also received funding from the UK MS Society and the US National Multiple Sclerosis Society

    Music and the brain: disorders of musical listening

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    The study of the brain bases for normal musical listening has advanced greatly in the last 30 years. The evidence from basic and clinical neuroscience suggests that listening to music involves many cognitive components with distinct brain substrates. Using patient cases reported in the literature, we develop an approach for understanding disordered musical listening that is based on the systematic assessment of the perceptual and cognitive analysis of music and its emotional effect. This approach can be applied both to acquired and congenital deficits of musical listening, and to aberrant listening in patients with musical hallucinations. Both the bases for normal musical listening and the clinical assessment of disorders now have a solid grounding in systems neuroscience
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