Temporal-Difference Learning to Assist Human Decision Making during the Control of an Artificial Limb

In this work we explore the use of reinforcement learning (RL) to help with human decision making, combining state-of-the-art RL algorithms with an application to prosthetics. Managing human-machine interaction is a problem of considerable scope, and the simplification of human-robot interfaces is especially important in the domains of biomedical technology and rehabilitation medicine. For example, amputees who control artificial limbs are often required to quickly switch between a number of control actions or modes of operation in order to operate their devices. We suggest that by learning to anticipate (predict) a user's behaviour, artificial limbs could take on an active role in a human's control decisions so as to reduce the burden on their users. Recently, we showed that RL in the form of general value functions (GVFs) could be used to accurately detect a user's control intent prior to their explicit control choices. In the present work, we explore the use of temporal-difference learning and GVFs to predict when users will switch their control influence between the different motor functions of a robot arm. Experiments were performed using a multi-function robot arm that was controlled by muscle signals from a user's body (similar to conventional artificial limb control). Our approach was able to acquire and maintain forecasts about a user's switching decisions in real time. It also provides an intuitive and reward-free way for users to correct or reinforce the decisions made by the machine learning system. We expect that when a system is certain enough about its predictions, it can begin to take over switching decisions from the user to streamline control and potentially decrease the time and effort needed to complete tasks. This preliminary study therefore suggests a way to naturally integrate human- and machine-based decision making systems.Comment: 5 pages, 4 figures, This version to appear at The 1st Multidisciplinary Conference on Reinforcement Learning and Decision Making, Princeton, NJ, USA, Oct. 25-27, 201

Molecular confirmation of Sarcocystis fayeri in a donkey

Sarcocystis fayeri is a canine protozoan parasite with an equine intermediate host. Historically classified as an incidental pathogen, recent literature has described the toxic effects of Sarcocystis fayeri in human food poisoning, and highlighted potential involvement in equine neuromuscular disease. Until now, horses were believed to be the exclusive intermediate host. This study reports the first molecular confirmation of S. fayeri in a donkey, and gives rise to the consideration of donkeys being a potential reservoir for the parasite. This finding is of particular importance in understanding the epidemiology of this disease

Safety and efficacy of three trypanocides in confirmed field cases of trypanosomiasis in working equines in The Gambia: a prospective, randomised, non-inferiority trial

Background: Globally, working equines have a continued and growing socioeconomic role in supporting the livelihoods of between 300–600 million people in low income countries which is rarely recognised at a national or international level. Infectious diseases have significant impact on welfare and productivity in this population and equine trypanosomiasis is a priority disease due to its severity and prevalence. Strategies are required to improve the prevention, diagnosis, management and treatment of trypanosomiasis in equines and more data are required on the efficacy and safety of current trypanocidal drugs. Methods: A prospective randomised, open-label non-inferiority trial was performed in The Gambia on horses and donkeys that fulfilled 2/5 clinical inclusion criteria (anaemia, poor body condition, pyrexia, history of abortion, oedema). Following randomised trypanocidal treatment (diminazene diaceturate, melarsomine dihydrochloride or isometamidium chloride), animals were observed for immediate adverse drug reactions and follow-up assessment was performed at 1 and 2 weeks. Blood samples underwent PCR analysis with specific Trypanosoma sp. primers. Treatment efficacy was assessed by measuring changes in clinical parameters, clinicopathological results and PCR-status post-treatment after evaluating for bias. Using PCR status as the outcome variable, non-inferiority of isometamidium treatment was determined if the upper bound limit of a 2-sided 95% CI was less than 10%. Results: There was a significant beneficial effect upon the Trypanosoma sp. PCR positive population following trypanocidal treatment for all groups. The findings of clinical evaluation and PCR status supported a superior treatment effect for isometamidium. Melarsomine dihydrochloride efficacy was inferior to isometamidium. There were immediate, self-limiting side effects to isometamidium in donkeys (26%). Diminazene had the longest duration of action as judged by PCR status. Conclusions: The data support the continued use of isometamidium following careful dose titration in donkeys and diminazene for trypanosomiasis in equines using the doses and routes of administration reported

Leadership and Management of Wildlife Reintroduction Programs

Wildlife reintroduction programs are a type of conservation initiative meant to preserve biodiversity through the restoration of damaged areas and the reintroduction of extirpated species. Unfortunately, such reintroductions have a history of limited success, ad hoc procedures, and little focus on hypothetico-deductive design. This study sought to identify some of the trends in the leadership, management, and structure of wildlife reintroduction programs through the use of a case study and survey. The survey was distributed to reintroduction practitioners and biologists worldwide in an attempt to identify patterns of organizational behavior within the field. Some general trends indicated that most reintroductions had active and monitoring phases of 4 or more years (59% and 75% of respondents respectively), adhered closely to World Conservation Union (IUCN) Reintroduction Guidelines (43% of respondents), had a somewhat hierarchical structure (50% of respondents), held annual long-term goal-setting meetings (56%), observed annual employee evaluations (63%), and underwent project evaluations annually, using both internal (74%) and external (39%) evaluative instruments. Opinion questions regarding the ultimate performance of the project indicated that although 75% of researchers felt that their project had made good progress, only 63% said that a formal evaluation had confirmed this statement

Variation in disease phenotype is marked in equine trypanosomiasis

Background: Equine trypanosomiasis is a severe and prevalent disease that has the greatest impact globally upon working equids due to its distribution across lower income countries. Morbidity and mortality rates are high; disease management strategies in endemic regions are ineffective and cost prohibitive. Individual variation in disease phenotype in other species suggests host factors could reveal novel treatment and control targets but has not been investigated in equids. Methods: A prospective clinical evaluation of equines presenting for a free veterinary examination was performed in hyperendemic villages in The Gambia. Age, body condition score and body weight were estimated by validated methods, and haematocrit and total protein concentration measured. Animals fulfilling 2 out of 5 clinical inclusion criteria (anaemia, poor body condition, pyrexia, history of abortion, oedema) for a diagnosis of trypanosomiasis received trypanocidal treatment with follow-up at 1 and 2 weeks. Blood samples underwent PCR analysis with specific Trypanosoma spp. primers and results were compared to the subject’s clinical and clinicopathological features. A mixed effects generalised linear model was generated to evaluate the association of infection status with degree of pyrexia and anaemia. Results: Morbidity was high within examined (n = 641) and selected (n = 247) study populations. PCR status was not associated with a defined disease phenotype; there was intra- and inter-species variability. Donkeys were more frequently Trypanosoma spp.-positive (P < 0.001) and febrile (P < 0.001) than horses, but infected horses were more anaemic (P < 0.001), and in poorer body condition (P < 0.001) than donkeys. Sex was correlated to disease phenotype: males were more anaemic (P = 0.03) and febrile (P < 0.001). Haemoparasite co-infections were more common than a single infection. Conclusions: There was evidence of diversity in trypanosomiasis clinical signs plus variable disease phenotypes within equid subpopulations that warrant further investigation. The complex co-infection profile of field cases requires greater consideration to optimise disease management

Comparison of loop-mediated isothermal amplification (LAMP) and PCR for the diagnosis of infection with Trypanosoma brucei ssp. in equids in The Gambia

Introduction: Infection of equids with Trypanosoma brucei (T. brucei) ssp. is of socioeconomic importance across sub-Saharan Africa as the disease often progresses to cause fatal meningoencephalitis. Loop-mediated isothermal amplification (LAMP) has been developed as a cost-effective molecular diagnostic test and is potentially applicable for use in field-based laboratories. Part I: Threshold levels for T. brucei ssp. detection by LAMP were determined using whole equine blood specimens spiked with known concentrations of parasites. Results were compared to OIE antemortem gold standard of T. brucei-PCR (TBR-PCR). Results I: Threshold for detection of T. brucei ssp. on extracted DNA from whole blood was 1 parasite/ml blood for LAMP and TBR-PCR, and there was excellent agreement (14/15) between tests at high (1 x 103/ml) concentrations of parasites. Detection threshold was 100 parasites/ml using LAMP on whole blood (LWB). Threshold for LWB improved to 10 parasites/ml with detergent included. Performance was excellent for LAMP at high (1 x 103/ml) concentrations of parasites (15/15, 100%) but was variable at lower concentrations. Agreement between tests was weak to moderate, with the highest for TBR-PCR and LAMP on DNA extracted from whole blood (Cohen’s kappa 0.95, 95% CI 0.64–1.00). Part II: A prospective cross-sectional study of working equids meeting clinical criteria for trypanosomiasis was undertaken in The Gambia. LAMP was evaluated against subsequent TBR-PCR. Results II: Whole blood samples from 321 equids in The Gambia were processed under field conditions. There was weak agreement between LWB and TBR-PCR (Cohen’s kappa 0.34, 95% CI 0.19–0.49) but excellent agreement when testing CSF (100% agreement on 6 samples). Conclusions: Findings support that LAMP is comparable to PCR when used on CSF samples in the field, an important tool for clinical decision making. Results suggest repeatability is low in animals with low parasitaemia. Negative samples should be interpreted in the context of clinical presentation

Erratum to: Arrhythmogenic right ventricular cardiomyopathy secondary to adipose infiltration as a cause of episodic collapse in a horse

[This corrects the article DOI: 10.1186/s13620-015-0052-3.]

Exploring the reactions of small rings.

PhDSmall rings are frequently found in natural products as well as incorporated into drugs and agrochemicals in which they impart valuable properties on the biological activity of these compounds. Cyclopropanes are also extremely useful as reagents in organic synthesis, in particular as “umpolung” reagents, allowing access to products which would otherwise be more difficult to synthesise. This thesis will describe forays into the synthesis and further substitution of small rings as well as the iminium-catalysed ring-opening of cyclopropanes. The introduction will outline the uses and properties of cyclopropanes, and will also describe some of the more common ways for incorporating cyclopropanes into larger structures. This will include the Horner–Wadsworth–Emmons procedure which has previously been developed by the group. The second chapter describes efforts towards the iminium-catalysed nucleophilic ring-opening of cyclopropanes. This is followed by Chapter 3, in which the Horner–Wadsworth–Emmons methodology for the synthesis of the cyclopropanes used in Chapter 2 is investigated as a procedure for the synthesis of 4-membered heterocycles. Chapter 4 describes the development of a decarboxylative method for the protodecarboxylation of cyclopropanecarboxylic acids. This was developed as the first step towards decarboxylative cross-coupling of cyclopropanes. Decarboxylative cross-couplings have been extensively developed as environmentally friendly and facile alternatives to the current cross-coupling methods. In Chapter 5 the attempted development of a decarboxylative cross-coupling reaction of cyclopropanes is described. Conclusions and future work are outlined in Chapter 6, followed by the experimental details in Chapter 7.Queen Mary University of London

Randomised evaluation of pre-notification of trial participants before self-report outcome data collection to improve retention: SWAT86

Background Retention is considered the second highest trial methods priority in the UK after recruitment. There is limited evidence on whether notifying trial participants that a follow-up questionnaire will be sent soon (‘pre-notification’) affects retention. Methods This Study Within a Trial (SWAT) evaluated whether sending a pre-notification letter or email around 2 weeks before sending a self-report questionnaire increased retention, in terms of provision of the host trial primary outcome. The SWAT was a randomised, two-arm, parallel-design (1:1 allocation ratio) trial, controlled by ‘no pre-notification letter’. It was embedded within the WORKWELL host trial, which evaluated the impact of job retention vocational rehabilitation on work-related and health-related outcomes of employed people with inflammatory arthritis. The SWAT primary outcome was a valid response for the WORKWELL primary outcome. Results Two hundred forty-four trial participants took part in the SWAT. All were included in the analysis. Among those sent a pre-reminder, 100/121 (83%) provided a valid response for the WORKWELL primary outcome, compared to 97/123 (79%) of those not sent a pre-reminder. The estimated adjusted odds ratio was 1.28 (95% confidence interval 0.67–2.42), with a risk difference of 3.8% (95% CI -6.1 to 13.6%), favouring the prereminder. The estimated intervention cost per additional participant retained was £53.42, and the total cost per additional participant retained was £46.52. Conclusion Researchers may have a small improvement in trial retention by using pre-notification. The cost per additional participant retained is relatively low. However, further evaluations are merited

Reducing falls risk with Kinect based falls prevention EXERGAMES: a 12 week twocentre, cluster RCT of community-dwelling older adults living in sheltered housing

Introduction: Falls are the leading cause of fatal and non-fatal unintentional injuries in older people. Despite overwhelming evidence for strength/balance training, adherence to both group and home-exercise programmes is often poor1. A novel approach is the use of home-based, strength and balance video-games (EXERGAMES) but data from randomized controlled trials are limited2. The aim of this study was to test whether a 12 week EXERGAMES home-based intervention, co-developed with older adults and therapists, can improve the risk of falling [by Berg Balance Scale (BBS)] in older adults living in sheltered housing. Methods: We conducted a two-site (Manchester/Glasgow) cluster RCT. Twelve sheltered housing facilities were randomised (1:1) to either a 12wk standard care plus 3 times/ week EXERGAMES physiotherapist one-to-one intervention (n=56) or standard care (control group n=50). Standard care involved the provision of a home exercise booklet (standard approach for those unable/unwilling to attend group exercise programmes in the community). Results: A total of 106 older adults (83F, 23M) with a mean age of 77.8y (SD 10.2; range 55-101y), were recruited for the study. A total of 91 (86%) participants completed all study visits. Over 12 weeks the EXERGAMES intervention had a significant positive impact on BBS [p=0.003; mean (SD), 44.6 (10.7) (EXERGAMES) vs. 37.6 (14.9) (Control)]. The mean change of BBS from baseline was 2.9 (8.5) for the EXERGAMES and -2.8 (6.5) for the control group. The estimated increase in BBS score due to EXERGAMES was 6.2 (95% CI 2.4 to 9.9) which is greater than the minimal detectable change for the scale of 4.93. Conclusions: Balance, and thus risk of falling, can be improved through a 12wk physiotherapy led EXERGAMES programme. This type of home based intervention could be considered as an effective alternative to traditional falls prevention exercise regimes to support outcomes for patients