Bandit Models of Human Behavior: Reward Processing in Mental Disorders

Drawing an inspiration from behavioral studies of human decision making, we propose here a general parametric framework for multi-armed bandit problem, which extends the standard Thompson Sampling approach to incorporate reward processing biases associated with several neurological and psychiatric conditions, including Parkinson's and Alzheimer's diseases, attention-deficit/hyperactivity disorder (ADHD), addiction, and chronic pain. We demonstrate empirically that the proposed parametric approach can often outperform the baseline Thompson Sampling on a variety of datasets. Moreover, from the behavioral modeling perspective, our parametric framework can be viewed as a first step towards a unifying computational model capturing reward processing abnormalities across multiple mental conditions.Comment: Conference on Artificial General Intelligence, AGI-1

Haptics for the development of fundamental rhythm skills, including multi-limb coordination

This chapter considers the use of haptics for learning fundamental rhythm skills, including skills that depend on multi-limb coordination. Different sensory modalities have different strengths and weaknesses for the development of skills related to rhythm. For example, vision has low temporal resolution and performs poorly for tracking rhythms in real-time, whereas hearing is highly accurate. However, in the case of multi-limbed rhythms, neither hearing nor sight are particularly well suited to communicating exactly which limb does what and when, or how the limbs coordinate. By contrast, haptics can work especially well in this area, by applying haptic signals independently to each limb. We review relevant theories, including embodied interaction and biological entrainment. We present a range of applications of the Haptic Bracelets, which are computer-controlled wireless vibrotactile devices, one attached to each wrist and ankle. Haptic pulses are used to guide users in playing rhythmic patterns that require multi-limb coordination. One immediate aim of the system is to support the development of practical rhythm skills and multi-limb coordination. A longer-term goal is to aid the development of a wider range of fundamental rhythm skills including recognising, identifying, memorising, retaining, analysing, reproducing, coordinating, modifying and creating rhythms – particularly multi-stream (i.e. polyphonic) rhythmic sequences. Empirical results are presented. We reflect on related work, and discuss design issues for using haptics to support rhythm skills. Skills of this kind are essential not just to drummers and percussionists but also to keyboards players, and more generally to all musicians who need a firm grasp of rhythm

Exercise-based cardiac rehabilitation for coronary heart disease (Review)

Background Coronary heart disease (CHD) is the most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people living with CHD may need support to manage their symptoms and prognosis. Exercise‐based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane Review previously published in 2016. Objectives To assess the clinical effectiveness and cost‐effectiveness of exercise‐based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with 'no exercise' control, on mortality, morbidity and health‐related quality of life (HRQoL) in people with CHD. Search methods We updated searches from the previous Cochrane Review, by searching CENTRAL, MEDLINE, Embase, and two other databases in September 2020. We also searched two clinical trials registers in June 2021. Selection criteria We included randomised controlled trials (RCTs) of exercise‐based interventions with at least six months’ follow‐up, compared with 'no exercise' control. The study population comprised adult men and women who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or have angina pectoris, or coronary artery disease. Data collection and analysis We screened all identified references, extracted data and assessed risk of bias according to Cochrane methods. We stratified meta‐analysis by duration of follow‐up: short‐term (6 to 12 months); medium‐term (> 12 to 36 months); and long‐term ( > 3 years), and used meta‐regression to explore potential treatment effect modifiers. We used GRADE for primary outcomes at 6 to 12 months (the most common follow‐up time point). Main results This review included 85 trials which randomised 23,430 people with CHD. This latest update identified 22 new trials (7795 participants). The population included predominantly post‐MI and post‐revascularisation patients, with a mean age ranging from 47 to 77 years. In the last decade, the median percentage of women with CHD has increased from 11% to 17%, but females still account for a similarly small percentage of participants recruited overall ( < 15%). Twenty‐one of the included trials were performed in low‐ and middle‐income countries (LMICs). Overall trial reporting was poor, although there was evidence of an improvement in quality over the last decade. The median longest follow‐up time was 12 months (range 6 months to 19 years). At short‐term follow‐up (6 to 12 months), exercise‐based CR likely results in a slight reduction in all‐cause mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.73 to 1.04; 25 trials; moderate certainty evidence), a large reduction in MI (RR 0.72, 95% CI 0.55 to 0.93; 22 trials; number needed to treat for an additional beneficial outcome (NNTB) 75, 95% CI 47 to 298; high certainty evidence), and a large reduction in all‐cause hospitalisation (RR 0.58, 95% CI 0.43 to 0.77; 14 trials; NNTB 12, 95% CI 9 to 21; moderate certainty evidence). Exercise‐based CR likely results in little to no difference in risk of cardiovascular mortality (RR 0.88, 95% CI 0.68 to 1.14; 15 trials; moderate certainty evidence), CABG (RR 0.99, 95% CI 0.78 to 1.27; 20 trials; high certainty evidence), and PCI (RR 0.86, 95% CI 0.63 to 1.19; 13 trials; moderate certainty evidence) up to 12 months' follow‐up. We are uncertain about the effects of exercise‐based CR on cardiovascular hospitalisation, with a wide confidence interval including considerable benefit as well as harm (RR 0.80, 95% CI 0.41 to 1.59; low certainty evidence). There was evidence of substantial heterogeneity across trials for cardiovascular hospitalisations (I2 = 53%), and of small study bias for all‐cause hospitalisation, but not for all other outcomes. At medium‐term follow‐up, although there may be little to no difference in all‐cause mortality (RR 0.90, 95% CI 0.80 to 1.02; 15 trials), MI (RR 1.07, 95% CI 0.91 to 1.27; 12 trials), PCI (RR 0.96, 95% CI 0.69 to 1.35; 6 trials), CABG (RR 0.97, 95% CI 0.77 to 1.23; 9 trials), and all‐cause hospitalisation (RR 0.92, 95% CI 0.82 to 1.03; 9 trials), a large reduction in cardiovascular mortality was found (RR 0.77, 95% CI 0.63 to 0.93; 5 trials). Evidence is uncertain for difference in risk of cardiovascular hospitalisation (RR 0.92, 95% CI 0.76 to 1.12; 3 trials). At long‐term follow‐up, although there may be little to no difference in all‐cause mortality (RR 0.91, 95% CI 0.75 to 1.10), exercise‐based CR may result in a large reduction in cardiovascular mortality (RR 0.58, 95% CI 0.43 to 0.78; 8 trials) and MI (RR 0.67, 95% CI 0.50 to 0.90; 10 trials). Evidence is uncertain for CABG (RR 0.66, 95% CI 0.34 to 1.27; 4 trials), and PCI (RR 0.76, 95% CI 0.48 to 1.20; 3 trials). Meta‐regression showed benefits in outcomes were independent of CHD case mix, type of CR, exercise dose, follow‐up length, publication year, CR setting, study location, sample size or risk of bias. There was evidence that exercise‐based CR may slightly increase HRQoL across several subscales (SF‐36 mental component, physical functioning, physical performance, general health, vitality, social functioning and mental health scores) up to 12 months' follow‐up; however, these may not be clinically important differences. The eight trial‐based economic evaluation studies showed exercise‐based CR to be a potentially cost‐effective use of resources in terms of gain in quality‐adjusted life years (QALYs). Authors' conclusions This updated Cochrane Review supports the conclusions of the previous version, that exercise‐based CR provides important benefits to people with CHD, including reduced risk of MI, a likely small reduction in all‐cause mortality, and a large reduction in all‐cause hospitalisation, along with associated healthcare costs, and improved HRQoL up to 12 months' follow‐up. Over longer‐term follow‐up, benefits may include reductions in cardiovascular mortality and MI. In the last decade, trials were more likely to include females, and be undertaken in LMICs, increasing the generalisability of findings. Well‐designed, adequately‐reported RCTs of CR in people with CHD more representative of usual clinical practice are still needed. Trials should explicitly report clinical outcomes, including mortality and hospital admissions, and include validated HRQoL outcome measures, especially over longer‐term follow‐up, and assess costs and cost‐effectiveness

Exercise-based cardiac rehabilitation for coronary heart disease

PublishedReviewThis review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2016, Issue 1. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.Background Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and prognosis. Exercise-based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane systematic review previously published in 2011. Objectives To assess the effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with usual care on mortality, morbidity and HRQL in patients with CHD. To explore the potential study level predictors of the effectiveness of exercise-based CR in patients with CHD. Search methods We updated searches from the previous Cochrane review, by searching Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 6, 2014) from December 2009 to July 2014. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and Science Citation Index Expanded (December 2009 to July 2014). Selection criteria We included randomised controlled trials (RCTs) of exercise-based interventions with at least six months’ follow-up, compared with a no exercise control. The study population comprised men and women of all ages who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or who have angina pectoris, or coronary artery disease. We included RCTs that reported at least one of the following outcomes: mortality, MI, revascularisations, hospitalisations, health-related quality of life (HRQL), or costs. Data collection and analysis Two review authors independently screened all identified references for inclusion based on the above inclusion and exclusion criteria. One author extracted data from the included trials and assessed their risk of bias; a second review author checked data. We stratified meta-analysis by the duration of follow up of trials, i.e. short-term: 6 to 12 months, medium-term: 13 to 36 months, and long-term: > 3 years. Main results This review included 63 trials which randomised 14,486 people with CHD. This latest update identified 16 new trials (3872 participants). The population included predominantly post-MI and post-revascularisation patients and the mean age of patients within the trials ranged from 47.5 to 71.0 years.Women accounted for fewer than 15% of the patients recruited. Overall trial reporting was poor, although there was evidence of an improvement in quality of reporting in more recent trials. As we found no significant difference in the impact of exercise-based CR on clinical outcomes across follow-up, we focused on reporting findings pooled across all trials at their longest follow-up (median 12 months). Exercise-based CR reduced cardiovascular mortality compared with no exercise control (27 trials; risk ratio (RR) 0.74, 95% CI 0.64 to 0.86). There was no reduction in total mortality with CR (47 trials, RR 0.96, 95% CI 0.88 to 1.04). The overall risk of hospital admissions was reduced with CR (15 trials; RR 0.82, 95% CI 0.70 to 0.96) but there was no significant impact on the risk of MI (36 trials; RR 0.90, 95% CI 0.79 to 1.04), CABG (29 trials; RR 0.96, 95% CI 0.80 to 1.16) or PCI (18 trials; RR 0.85, 95% CI 0.70 to 1.04). There was little evidence of statistical heterogeneity across trials for all event outcomes, and there was evidence of small study bias for MI and hospitalisation, but no other outcome. Predictors of clinical outcomes were examined across the longest follow-up of studies using univariate meta-regression. Results show that benefits in outcomes were independent of participants’ CHD case mix (proportion of patients with MI), type of CR (exercise only vs comprehensive rehabilitation) dose of exercise, length of follow-up, trial publication date, setting (centre vs home-based), study location (continent), sample size or risk of bias. Given the heterogeneity in outcome measures and reporting methods, meta-analysis was not undertaken for HRQL. In five out of 20 trials reporting HRQL using validated measures, there was evidence of significant improvement in most or all of the sub-scales with exercise-based CR compared to control at follow-up. Four trial-based economic evaluation studies indicated exercise-based CR to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years. The quality of the evidence for outcomes reported in the review was rated using the GRADE method. The quality of the evidence varied widely by outcome and ranged from low to moderate. Authors’ conclusions This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based CR reduces the risk of cardiovascular mortality but not total mortality. We saw a significant reduction in the risk of hospitalisation with CR but not in the risk of MI or revascularisation. We identified further evidence supporting improved HRQL with exercise-based CR. More recent trials were more likely to be well reported and include older and female patients. However, the population studied in this review still consists predominantly of lower risk individuals following MI or revascularisation. Further well conducted RCTs are needed to assess the impact of exercise-based CR in higher risk CHD groups and also those presenting with stable angina. These trials should include validated HRQL outcome measures, explicitly report clinical event outcomes including mortality and hospital admissions, and assess costs and cost-effectiveness

Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity

Predicting illness progression for children with lower respiratory infections (LRTI) presenting to primary care

Background Antibiotics are commonly prescribed for children with lower respiratory tract infections (LRTIs), fuelling antibiotic resistance, and there are few prognostic tools available to inform management. Aim To externally validate an existing prognostic model (STARWAVe) to identify children at low risk of illness progression, and if model performance was limited to develop a new internally validated prognostic model. Design and setting Prospective cohort study with a nested trial in a primary care setting. Method Children aged 6 months to 12 years presenting with uncomplicated LRTI were included in the cohort. Children were randomised to receive amoxicillin 50 mg/kg per day for 7 days or placebo, or if not randomised they participated in a parallel observational study to maximise generalisability. Baseline clinical data were used to predict adverse outcome (illness progression requiring hospital assessment). Results A total of 758 children participated (n= 432 trial, n= 326 observational). For predicting illness progression the STARWAVe prognostic model had moderate performance (area under the receiver operating characteristic [AUROC] 0.66, 95% confidence interval [CI] = 0.50 to 0.77), but a new, internally validated model (seven items: baseline severity; respiratory rate; duration of prior illness; oxygen saturation; sputum or a rattly chest; passing urine less often; and diarrhoea) had good discrimination (bootstrapped AUROC 0.83, 95% CI = 0.74 to 0.92) and calibration. A three-item model (respiratory rate; oxygen saturation; and sputum or a rattly chest) also performed well (AUROC 0.81, 95% CI = 0.70 to 0.91), as did a score (ranging from 19 to 102) derived from coefficients of the model (AUROC 0.78, 95% CI = 0.67 to 0.88): a score of &lt;70 classified 89% (n= 600/674) of children having a low risk (&lt;5%) of progression of illness. Conclusion A simple three-item prognostic score could be useful as a tool to identify children with LRTI who are at low risk of an adverse outcome and to guide clinical management.</p

Developments in CLARA accelerator design and simulations

We present recent developments in the accelerator design of CLARA (Compact Linear Accelerator for Research and Applications), the proposed UK FEL test facility at Daresbury Laboratory. Updates on the electron beam simulations and code comparisons including wakefields are described. Simulations of the effects of geometric wakefields in the small-aperture FEL undulator are shown, as well as further simulations on potential FEL experiments using chirped beams. We also present the results of simulations on post-FEL diagnostics

Impact of antibiotics for children presenting to general practice with cough on adverse outcomes: secondary analysis from a multicentre prospective cohort study

BACKGROUND: Clinicians commonly prescribe antibiotics to prevent major adverse outcomes in children presenting in primary care with cough and respiratory symptoms, despite limited meaningful evidence of impact on these outcomes. AIM: To estimate the effect of children's antibiotic prescribing on adverse outcomes within 30 days of initial consultation. DESIGN AND SETTING: Secondary analysis of 8320 children in a multicentre prospective cohort study, aged 3 months to <16 years, presenting in primary care across England with acute cough and other respiratory symptoms. METHOD: Baseline clinical characteristics and antibiotic prescribing data were collected, and generalised linear models were used to estimate the effect of antibiotic prescribing on adverse outcomes within 30 days (subsequent hospitalisations and reconsultation for deterioration), controlling for clustering and clinicians' propensity to prescribe antibiotics. RESULTS: Sixty-five (0.8%) children were hospitalised and 350 (4%) reconsulted for deterioration. Clinicians prescribed immediate and delayed antibiotics to 2313 (28%) and 771 (9%), respectively. Compared with no antibiotics, there was no clear evidence that antibiotics reduced hospitalisations (immediate antibiotic risk ratio [RR] 0.83, 95% confidence interval [CI] = 0.47 to 1.45; delayed RR 0.70, 95% CI = 0.26 to 1.90, overall P = 0.44). There was evidence that delayed (rather than immediate) antibiotics reduced reconsultations for deterioration (immediate RR 0.82, 95% CI = 0.65 to 1.07; delayed RR 0.55, 95% CI = 0.34 to 0.88, overall P = 0.024). CONCLUSION: Most children presenting with acute cough and respiratory symptoms in primary care are not at risk of hospitalisation, and antibiotics may not reduce the risk. If an antibiotic is considered, a delayed antibiotic prescription may be preferable as it is likely to reduce reconsultation for deterioration

The Demographic and Socioeconomic Factors Predictive for Populations at High-Risk for La Crosse Virus Infection in West Virginia

Although a large body of literature exists for the environmental risk factors for La Crosse virus (LACV) transmission, the demographic and socioeconomic risk factors for developing LACV infection have not been investigated. Therefore, this study investigated the demographic and socioeconomic risk factors for LACV infection in West Virginia from 2003 to 2007, using two forward stepwise discriminant analyses. The discriminant analyses were used to evaluate a number of demographic and socioeconomic factors for their ability to predict: 1) those census tracts with at least one reported case of LACV infection versus those census tracts with no reported cases of LACV infection and 2) to evaluate significantly high-risk clusters for LACV infection versus significantly low-risk clusters for LACV infection. In the first model, a high school education diploma or a general education diploma or less and a lower housing densit