Search for Fractional Charges Produced in Heavy-Ion Collisions at 1.9 GeV/nucleon

An experiment was performed to capture fractionally charged particles produced in heavy-ion collisions and to concentrate them in samples suitable for analysis by various techniques. Two of the samples so produced have been searched, with use of an automated version of Millikan\u27s oil-drop apparatus. The beam was 56Fe at 1.9 GeV/nucleon, incident on a lead target. Less than one fractional charge per 1.0× 104 Fe-Pb collisions was found to be produced, and, with further assumptions, less than one per 2.0× 106 collisions

Robot-assisted training compared with an enhanced upper limb therapy programme and with usual care for upper limb functional limitation after stroke: the RATULS three-group RCT

Background Loss of arm function is common after stroke. Robot-assisted training may improve arm outcomes. Objective The objectives were to determine the clinical effectiveness and cost-effectiveness of robot-assisted training, compared with an enhanced upper limb therapy programme and with usual care. Design This was a pragmatic, observer-blind, multicentre randomised controlled trial with embedded health economic and process evaluations. Setting The trial was set in four NHS trial centres. Participants Patients with moderate or severe upper limb functional limitation, between 1 week and 5 years following first stroke, were recruited. Interventions Robot-assisted training using the Massachusetts Institute of Technology-Manus robotic gym system (InMotion commercial version, Interactive Motion Technologies, Inc., Watertown, MA, USA), an enhanced upper limb therapy programme comprising repetitive functional task practice, and usual care. Main outcome measures The primary outcome was upper limb functional recovery ‘success’ (assessed using the Action Research Arm Test) at 3 months. Secondary outcomes at 3 and 6 months were the Action Research Arm Test results, upper limb impairment (measured using the Fugl-Meyer Assessment), activities of daily living (measured using the Barthel Activities of Daily Living Index), quality of life (measured using the Stroke Impact Scale), resource use costs and quality-adjusted life-years. Results A total of 770 participants were randomised (robot-assisted training, n = 257; enhanced upper limb therapy, n = 259; usual care, n = 254). Upper limb functional recovery ‘success’ was achieved in the robot-assisted training [103/232 (44%)], enhanced upper limb therapy [118/234 (50%)] and usual care groups [85/203 (42%)]. These differences were not statistically significant; the adjusted odds ratios were as follows: robot-assisted training versus usual care, 1.2 (98.33% confidence interval 0.7 to 2.0); enhanced upper limb therapy versus usual care, 1.5 (98.33% confidence interval 0.9 to 2.5); and robot-assisted training versus enhanced upper limb therapy, 0.8 (98.33% confidence interval 0.5 to 1.3). The robot-assisted training group had less upper limb impairment (as measured by the Fugl-Meyer Assessment motor subscale) than the usual care group at 3 and 6 months. The enhanced upper limb therapy group had less upper limb impairment (as measured by the Fugl-Meyer Assessment motor subscale), better mobility (as measured by the Stroke Impact Scale mobility domain) and better performance in activities of daily living (as measured by the Stroke Impact Scale activities of daily living domain) than the usual care group, at 3 months. The robot-assisted training group performed less well in activities of daily living (as measured by the Stroke Impact Scale activities of daily living domain) than the enhanced upper limb therapy group at 3 months. No other differences were clinically important and statistically significant. Participants found the robot-assisted training and the enhanced upper limb therapy group programmes acceptable. Neither intervention, as provided in this trial, was cost-effective at current National Institute for Health and Care Excellence willingness-to-pay thresholds for a quality-adjusted life-year. Conclusions Robot-assisted training did not improve upper limb function compared with usual care. Although robot-assisted training improved upper limb impairment, this did not translate into improvements in other outcomes. Enhanced upper limb therapy resulted in potentially important improvements on upper limb impairment, in performance of activities of daily living, and in mobility. Neither intervention was cost-effective. Future work Further research is needed to find ways to translate the improvements in upper limb impairment seen with robot-assisted training into improvements in upper limb function and activities of daily living. Innovations to make rehabilitation programmes more cost-effective are required. Limitations Pragmatic inclusion criteria led to the recruitment of some participants with little prospect of recovery. The attrition rate was higher in the usual care group than in the robot-assisted training or enhanced upper limb therapy groups, and differential attrition is a potential source of bias. Obtaining accurate information about the usual care that participants were receiving was a challenge. Trial registration Current Controlled Trials ISRCTN69371850. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 54. See the NIHR Journals Library website for further project information

Multicentre individual randomised controlled trial of screening and brief alcohol intervention to prevent risky drinking in young people aged 14-15 in a high school setting (SIPS JR-HIGH): study protocol.

INTRODUCTION: Drinking has adverse impacts on health, well-being, education and social outcomes for adolescents. Adolescents in England are among the heaviest drinkers in Europe. Recently, the proportion of adolescents who drink alcohol has fallen, although consumption among those who do drink has actually increased. This trial seeks to investigate how effective and efficient an alcohol brief intervention is with 11-15 years olds to encourage lower alcohol consumption. METHODS AND ANALYSIS: This is an individually randomised two-armed trial incorporating a control arm of usual school-based practice and a leaflet on a healthy lifestyle (excl. alcohol), and an intervention arm that combines usual practice with a 30 min brief intervention delivered by school learning mentors and a leaflet on alcohol. At least 30 schools will be recruited from four regions in England (North East, North West, London, Kent and Medway) to follow-up 235 per arm. The primary outcome is total alcohol consumed in the last 28 days, using the 28 day Timeline Follow Back questionnaire measured at the 12-month follow-up. The analysis of the intervention will consider effectiveness and cost-effectiveness. A qualitative study will explore, via 1:1 in-depth interviews with (n=80) parents, young people and school staff, intervention experience, intervention fidelity and acceptability issues, using thematic narrative synthesis to report qualitative data. ETHICS AND DISSEMINATION: Ethical approval was granted by Teesside University. Dissemination plans include academic publications, conference presentations, disseminating to local and national education departments and the wider public health community, including via Fuse, and engaging with school staff and young people to comment on whether and how the project can be improved. TRIAL REGISTRATION TRIAL: ISRCTN45691494; Pre-results

Feasibility of trial procedures for a randomised controlled trial of a community based group exercise intervention for falls prevention for visually impaired older people: the VIOLET study

Background Visually impaired older people (VIOP) have a higher risk of falling than their sighted peers, and are likely to avoid physical activity. The aim was to adapt the existing Falls Management Exercise (FaME) programme for VIOP, delivered in the community, and to investigate the feasibility of conducting a definitive randomised controlled trial (RCT) of this adapted intervention. Methods Two-centre randomised mixed methods pilot trial and economic evaluation of the adapted group-based FaME programme for VIOP versus usual care. A one hour exercise programme ran weekly over 12 weeks at the study sites (Newcastle and Glasgow), delivered by third sector (voluntary and community) organisations. Participants were advised to exercise at home for an additional two hours over the week. Those randomised to the usual activities group received no intervention. Outcome measures were completed at baseline, 12 and 24 weeks. The potential primary outcome was the Short Form Falls Efficacy Scale – International (SFES-I). Participants’ adherence was assessed by reviewing attendance records and self-reported compliance to the home exercises. Adherence with the course content (fidelity) by instructors was assessed by a researcher. Adverse events were collected in a weekly phone call. Results Eighteen participants, drawn from community-living VIOP were screened; 68 met the inclusion criteria; 64 participants were randomised with 33 allocated to the intervention and 31 to the usual activities arm. 94% of participants provided data at the 12 week visit and 92% at 24 weeks. Adherence was high. The intervention was found to be safe with 76% attending nine or more classes. Median time for home exercise was 50 min per week. There was little or no evidence that fear of falling, balance and falls risk, physical activity, emotional, attitudinal or quality of life outcomes differed between trial arms at follow-up. Conclusions The intervention, FaME, was implemented successfully for VIOP and all progression criteria for a main trial were met. The lack of difference between groups on fear of falling was unsurprising given it was a pilot study but there may have been other contributory factors including suboptimal exercise dose and apparent low risk of falls in participants. These issues need addressing for a future trial

Robot assisted training for the upper limb after stroke (RATULS): a multicentre randomised controlled trial

Background Loss of arm function is a common problem after stroke. Robot-assisted training might improve arm function and activities of daily living. We compared the clinical effectiveness of robot-assisted training using the MIT-Manus robotic gym with an enhanced upper limb therapy (EULT) programme based on repetitive functional task practice and with usual care. Methods RATULS was a pragmatic, multicentre, randomised controlled trial done at four UK centres. Stroke patients aged at least 18 years with moderate or severe upper limb functional limitation, between 1 week and 5 years after their first stroke, were randomly assigned (1:1:1) to receive robot-assisted training, EULT, or usual care. Robot-assisted training and EULT were provided for 45 min, three times per week for 12 weeks. Randomisation was internet-based using permuted block sequences. Treatment allocation was masked from outcome assessors but not from participants or therapists. The primary outcome was upper limb function success (defined using the Action Research Arm Test [ARAT]) at 3 months. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN69371850. Findings Between April 14, 2014, and April 30, 2018, 770 participants were enrolled and randomly assigned to either robot-assisted training (n=257), EULT (n=259), or usual care (n=254). The primary outcome of ARAT success was achieved by 103 (44%) of 232 patients in the robot-assisted training group, 118 (50%) of 234 in the EULT group, and 85 (42%) of 203 in the usual care group. Compared with usual care, robot-assisted training (adjusted odds ratio [aOR] 1·17 [98·3% CI 0·70–1·96]) and EULT (aOR 1·51 [0·90–2·51]) did not improve upper limb function; the effects of robot-assisted training did not differ from EULT (aOR 0·78 [0·48–1·27]). More participants in the robot-assisted training group (39 [15%] of 257) and EULT group (33 [13%] of 259) had serious adverse events than in the usual care group (20 [8%] of 254), but none were attributable to the intervention. Interpretation Robot-assisted training and EULT did not improve upper limb function after stroke compared with usual care for patients with moderate or severe upper limb functional limitation. These results do not support the use of robot-assisted training as provided in this trial in routine clinical practice

Randomised controlled trial of welfare rights advice accessed via primary health care: pilot study [ISRCTN61522618]

BACKGROUND: Little research has directly evaluated the impact of increasing financial or material resources on health. One way of assessing this lies with assisting people to obtain full welfare benefit entitlements. In 2000–1, 2.3 million pensioners were living in poverty in the UK and estimates suggest that around one million do not claim the financial support to which they are entitled. The effectiveness of welfare rights advice services delivered via primary health care to promote health and reduce health inequalities is unknown. METHODS: The main objectives of this study were to assess the feasibility and acceptability of a randomised controlled trial of welfare rights advice in a community setting and identify appropriate health and social outcome measures in order to plan a definitive trial. This was a single blind, community-based, pilot randomised controlled trial. 126 men and women aged 60 years and over, recruited from 4 general practices in Newcastle upon Tyne, UK, participated. The intervention comprised a structured welfare rights assessment followed by active assistance with welfare benefit claims over the following 24 months. The control group received the intervention after a six month delay. A range of socio-economic, health, behavioural and psycho-social outcomes were measured. RESULTS: 126 out of 400 people invited agreed to participate and 109 were followed up at 24 months. Both the intervention and research procedures were feasible and acceptable to participants and professionals involved. 68 (58%) of all participants received a welfare benefit award (31 financial, 16 non-financial and 21 both). Median time to receipt of benefits from initial assessment was 14 (range 1 to 78) weeks and median financial award was £55 (€81, $98) per household per week. There was little evidence of health-related differences between groups or over time, which could be due to limitations of the study design. CONCLUSION: Modification of the study design, including selection of study participants, timing of interventions and length of follow up are recommended for a definitive trial. More appropriate health and psycho-social outcome measures relevant to the elderly population should be sought, particularly focussing on those issues highlighted in the accompanying qualitative study

Brief alcohol intervention for risky drinking in young people aged 14–15 years in secondary schools: the SIPS JR-HIGH RCT

Background: Adverse effects from young people’s alcohol consumption manifest in a range of physical and psychosocial factors, including neurological issues, cognitive impairment and risk-taking behaviours. The SIPS JR-HIGH pilot trial showed alcohol screening and brief intervention (ASBI) to be acceptable to young people and schools in the north-east of England. Objectives: To conduct a two-arm, individually randomised controlled trial to evaluate the effectiveness and cost-effectiveness of ASBI for risky drinking in young people aged 14–15 years in the school setting, to monitor the fidelity of ASBI and to explore the barriers to, and facilitators of, implementation with staff, young people and parents. Design: A baseline survey with a 12-month follow-up. Interviews with 30 school staff, 21 learning mentors and nine teachers, and 33 young people and two parents. Setting: Thirty state schools in four areas of England: north-east, north-west, Kent and London. Participants: Year 10 school pupils who consented to the study (aged 14–15 years, recruited between November 2015 and June 2016), school-based staff and parents of the young people who took part in the study Interventions: Young people who screened positively on a single alcohol screening question andconsented were randomised to the intervention or control arm (blinded). The intervention was a 30-minute one-to-one structured brief intervention with a trained learning mentor and an alcohol leaflet. The control group received a healthy lifestyle leaflet (no alcohol information). Main outcome measures: The primary outcome measure was total alcohol consumed in the last 28 days. Secondary outcomes related to risky drinking, general psychological health, sexual risk-taking, energy drink consumption, age of first smoking, quality of life, quality-adjusted life-years, service utilisation and demographic information. Results: A total of 4523 young people completed the baseline survey, with 1064 screening positively (24%) and 443 being eligible to take part in the trial. Of those 443, 233 (53%) were randomised to the control arm and 210 were randomised to the intervention arm. Of the 443, 374 (84%) were successfully followed up at 12 months (intervention, n = 178; control, n = 196). The results were that the intervention showed no evidence of benefit for any alcohol-related measure when compared with the control arm. At 12 months we found a reduction from 61.9% to 43.3% using the Alcohol Use Disorders Identification Test cut-off point of 8 and cut-off point of 4 (69.0% to 60.7%). These results were not significant. A cost-effectiveness analysis showed that the average net cost saving of the brief intervention was £2865 (95% confidence interval –£11,272 to £2707) per year compared with usual practice, with the intervention showing a 76% probability of being cost saving compared with usual practice. The interview findings showed that school was an acceptable setting to carry out ASBI among staff and young people. Limitations: Recruitment of parents to take part in interviews was poor. Only 18 ASBI sessions were recorded, making it difficult to assess internal validity. Conclusions: Although the intervention was ineffective in reducing risky drinking in young people aged 14–15 years, it was well received by the young people and school staff who participated. Future work: Uniform reporting of the outcomes used for ASBI would generate more robust conclusions on the effectiveness of ASBI in the future. Pilot feasibility studies should include more than one geographical area. Future work on involving parents is needed

Robot Assisted Training for the Upper Limb after Stroke (RATULS): study protocol for a randomised controlled trial.

BACKGROUND: Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke. METHODS/DESIGN: Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation. SETTING: NHS stroke services. PARTICIPANTS: adults with acute or chronic first-ever stroke (1 week to 5 years post stroke) causing moderate to severe upper limb functional limitation. Randomisation groups: 1. Robot-assisted training using the InMotion robotic gym system for 45 min, three times/week for 12 weeks 2. Enhanced upper limb therapy for 45 min, three times/week for 12 weeks 3. Usual NHS care in accordance with local clinical practice Randomisation: individual participant randomisation stratified by centre, time since stroke, and severity of upper limb impairment. PRIMARY OUTCOME: upper limb function measured by the Action Research Arm Test (ARAT) at 3 months post randomisation. SECONDARY OUTCOMES: upper limb impairment (Fugl-Meyer Test), activities of daily living (Barthel ADL Index), quality of life (Stroke Impact Scale, EQ-5D-5L), resource use, cost per quality-adjusted life year and adverse events, at 3 and 6 months. Blinding: outcomes are undertaken by blinded assessors. Economic analysis: micro-costing and economic evaluation of interventions compared to usual NHS care. A within-trial analysis, with an economic model will be used to extrapolate longer-term costs and outcomes. Process evaluation: semi-structured interviews with participants and professionals to seek their views and experiences of the rehabilitation that they have received or provided, and factors affecting the implementation of the trial. SAMPLE SIZE: allowing for 10% attrition, 720 participants provide 80% power to detect a 15% difference in successful outcome between each of the treatment pairs. Successful outcome definition: baseline ARAT 0-7 must improve by 3 or more points; baseline ARAT 8-13 improve by 4 or more points; baseline ARAT 14-19 improve by 5 or more points; baseline ARAT 20-39 improve by 6 or more points. DISCUSSION: The results from this trial will determine whether robot-assisted training improves upper limb function post stroke. TRIAL REGISTRATION: ISRCTN, identifier: ISRCTN69371850 . Registered 4 October 2013

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC

A systematic review of the health, social and financial impacts of welfare rights advice delivered in healthcare settings

BACKGROUND: Socio-economic variations in health, including variations in health according to wealth and income, have been widely reported. A potential method of improving the health of the most deprived groups is to increase their income. State funded welfare programmes of financial benefits and benefits in kind are common in developed countries. However, there is evidence of widespread under claiming of welfare benefits by those eligible for them. One method of exploring the health effects of income supplementation is, therefore, to measure the health effects of welfare benefit maximisation programmes. We conducted a systematic review of the health, social and financial impacts of welfare rights advice delivered in healthcare settings. METHODS: Published and unpublished literature was accessed through searches of electronic databases, websites and an internet search engine; hand searches of journals; suggestions from experts; and reference lists of relevant publications. Data on the intervention delivered, evaluation performed, and outcome data on health, social and economic measures were abstracted and assessed by pairs of independent reviewers. Results are reported in narrative form. RESULTS: 55 studies were included in the review. Only seven studies included a comparison or control group. There was evidence that welfare rights advice delivered in healthcare settings results in financial benefits. There was little evidence that the advice resulted in measurable health or social benefits. This is primarily due to lack of good quality evidence, rather than evidence of an absence of effect. CONCLUSION: There are good theoretical reasons why income supplementation should improve health, but currently little evidence of adequate robustness and quality to indicate that the impact goes beyond increasing income