Physical therapy and deep brain stimulation in Parkinson’s Disease: Protocol for a pilot randomized controlled trial

Abstract Background Subthalamic nucleus deep brain stimulation (STN-DBS) reduces tremor, muscle stiffness, and bradykinesia in people with Parkinson’s Disease (PD). Walking speed, known to be reduced in PD, typically improves after surgery; however, other important aspects of gait may not improve. Furthermore, balance may worsen and falls may increase after STN-DBS. Thus, interventions to improve balance and gait could reduce morbidity and improve quality of life following STN-DBS. Physical therapy (PT) effectively improves balance and gait in people with PD, but studies on the effects of PT have not been extended to those treated with STN-DBS. As such, the efficacy, safety, and feasibility of PT in this population remain to be determined. The purpose of this pilot study is to address these unmet needs. We hypothesize that PT designed to target balance and gait impairment will be effective, safe, and feasible in this population. Methods/design Participants with PD treated with STN-DBS will be randomly assigned to either a PT or control group. Participants assigned to PT will complete an 8-week, twice-weekly PT program consisting of exercises designed to improve balance and gait. Control group participants will receive the current standard of care following STN-DBS, which does not include prescription of PT. The primary aim is to assess preliminary efficacy of PT on balance (Balance Evaluation Systems Test). A secondary aim is to assess efficacy of PT on gait (GAITRite instrumented walkway). Participants will be assessed OFF medication/OFF stimulation and ON medication/ON stimulation at baseline and at 8 and 12 weeks after baseline. Adverse events will be measured over the duration of the study, and adherence to PT will be measured to determine feasibility. Discussion To our knowledge, this will be the first study to explore the preliminary efficacy, safety, and feasibility of PT for individuals with PD with STN-DBS. If the study suggests potential efficacy, then this would justify larger trials to test effectiveness and safety of PT for those with PD with STN-DBS. Trial registration NCT03181282 (clinicaltrials.gov). Registered on 7 June 2017

The simulation of a propulsive jet and force measurement using a magnetically suspended wind tunnel model

Models featuring the simulation of exhaust jets were developed for magnetic levitation in a wind tunnel. The exhaust gas was stored internally producing a discharge of sufficient duration to allow nominal steady state to be reached. The gas was stored in the form of compressed gas or a solid rocket propellant. Testing was performed with the levitated models although deficiencies prevented the detection of jet-induced aerodynamic effects. Difficulties with data reduction led to the development of a new force calibration technique, used in conjunction with an exhaust simulator and also in separate high incidence aerodynamic tests

Epidemiology of injuries in adventure racing athletes

OBJECTIVES: To assess the demographics and training characteristics of adventure racing athletes in the United Kingdom, the prevalence and anatomical distribution of hazardous encounter, and overuse injury in this population, and the effects these injuries have on training. METHODS: A retrospective training and injury questionnaire for the previous 18 months was distributed to 300 adventure racing athletes at two national race meetings. The definition of an injury was "any musculoskeletal problem causing a stop in training for at least one day, reduction in training mileage, taking of medicine, or seeking of medical aid." RESULTS: The data were derived from the responses of 223 athletes. Advanced level athletes did 11 (4) sessions and 17 (8) hours of training a week (mean (SD)). An injury was reported in the previous 18 months by 73% of the respondents. The most common site of acute injury was the ankle (23%) and of chronic/overuse injury, the knee (30%), followed by the lower back, shin, and Achilles tendon (12% each). There were significant correlations (p<0.01) between the hours spent cycling per week and number of acute injuries, and between the number of days off per week and number of chronic/overuse injuries. Injuries resulted in an average of 23 days training cessation or reduction. CONCLUSIONS: Acute injuries were sustained mainly as a result of the nature of the terrain over which athletes train and compete. In overuse injuries lack of adequate rest days was a significant contributing factor. Only a small proportion of training time was spent developing flexibility and core stability

Association of the Sweet-Liking Phenotype and Craving for Alcohol With the Response to Naltrexone Treatment in Alcohol Dependence: A Randomized Clinical Trial

Identification of moderators of the response to naltrexone hydrochloride treatment for alcohol dependence could improve clinical care for patients with alcohol use disorders. To investigate the preliminary finding that the sweet-liking (SL) phenotype interacts with a high level of craving for alcohol and is associated with an improved response to naltrexone in alcohol dependence. This 12-week double-blind, randomized, placebo-controlled clinical trial was conducted from February 1, 2010, to April 30, 2012, in an academic outpatient medical center. Eighty actively drinking patients were randomized by the SL (n = 22) or the sweet-disliking (SDL) (n = 58) phenotype and by pretreatment high (n = 40) or low (n = 40) craving for alcohol, with high craving defined as greater than the median. Patients and staff were blinded to categorization. Patients were excluded for unstable medical or psychiatric illness, including dependence on drugs other than nicotine. Four patients (2 in the placebo arm and 2 in the naltrexone arm) stopped medication therapy because of adverse effects. Data were analyzed from January 15, 2013, to May 15, 2016, based on intention to treat. Oral naltrexone hydrochloride, 50 mg/d, or daily placebo with weekly to biweekly brief counseling. The a priori hypothesis tested SL/SDL phenotype, pretreatment craving, and their interaction as moderators of frequency of abstinent and heavy drinking days during treatment, assessed with the timeline follow-back method. Eighty patients were randomized (57 men [71%]; 23 women [29%]; mean [SD] age, 47.0 [8.6] years). A nonsignificant effect of naltrexone on heavy drinking was noted (4.8 fewer heavy drinking days; Cohen d = 0.45; 95% CI, -0.01 to 0.90; F1,67 = 3.52; P = .07). The SL phenotype moderated the effect of naltrexone on heavy drinking (6.1 fewer heavy drinking days; Cohen d = 0.58; 95% CI, 0.12-1.03; F1,67 = 5.65; P = .02) and abstinence (10.0 more abstinent days; Cohen d = 0.57; 95% CI, 0.11-1.02; F1,67 = 5.36; P = .02), and high craving moderated heavy drinking (7.1 fewer heavy drinking days; Cohen d = 0.66; 95% CI, 0.20-1.11; F1,67 = 7.37; P = .008). The combination of the SL phenotype and high craving was associated with a strong response to naltrexone, with 17.1 fewer heavy drinking days (Cohen d = 1.07; 95% CI, 0.58-1.54; F1,67 = 19.33; P < .001) and 28.8 more abstinent days (Cohen d = 0.72; 95% CI, 0.25-1.17; F1,67 = 8.73; P = .004) compared with placebo. The SL phenotype and a high craving for alcohol independently and particularly in combination are associated with a positive response to naltrexone. The SL/SDL phenotype and a high craving for alcohol merit further investigation as factors to identify patients with alcohol dependence who are responsive to naltrexone. clinicaltrials.gov Identifier: NCT01296646

Impacts of climate change on coastal habitats, relevant to the coastal and marine environment around the UK

Coastal habitats are at risk from both direct (temperature, rainfall), and indirect (sea-level rise, coastal erosion) impacts due to a changing climate. Beyond the environmental impacts and ensuing habitat loss, the changing climate will have a significant societal impact to coastal communities ranging from health to livelihoods, as well as the loss of important ecosystem services such as coastal defence – particularly relevant with predicted increase in storminess. Vegetated coastal ecosystems sequester carbon – another ‘ecosystem service’ that could be disrupted due to climate change. There has been considerable recent attention to the potential role these habitats could play in climate mitigation, and also in transferring carbon across the land–sea interface. To understand the relative importance of these habitats within the global carbon cycle, coastal habitats need to be accounted for in national greenhouse gas inventories, and a true multidisciplinary catchment-to-coast approach to research is required. Management options exist that can reduce the immediate impacts of climate change, such as managed realignment and sediment recharge. Fixed landward coastal defences are becoming unsustainable and creating ‘coastal squeeze’, highlighting the need to work with natural processes to recreate more-natural shorelines where possible

Disease spread in age structure populations with maternal age effects

Fundamental ecological processes, such as extrinsic mortality, determine population age structure. This influences disease spread when individuals of different ages differ in susceptibility or when maternal age determines offspring susceptibility. We show that Daphnia magna offspring born to young mothers are more susceptible than those born to older mothers, and consider this alongside previous observations that susceptibility declines with age in this system. We used a susceptible- infected compartmental model to investigate how age-specific susceptibility and maternal age effects on offspring susceptibility interact with demographic factors affecting disease spread. Our results show a scenario where an increase in extrinsic mortality drives an increase in transmission potential. Thus, we identify a realistic context in which age effects and maternal effects produce conditions favouring disease transmission

Persistence of double-stranded RNA in insect hemolymph as a potential determiner of RNA interference success: Evidence from Manduca sexta and Blattella germanica

a b s t r a c t RNA interference (RNAi) is a specific gene silencing mechanism mediated by double-stranded RNA (dsRNA), which has been harnessed as a useful reverse genetics tool in insects. Unfortunately, however, this technology has been limited by the variable sensitivity of insect species to RNAi. We propose that rapid degradation of dsRNA in insect hemolymph could impede gene silencing by RNAi and experimentally investigate the dynamics of dsRNA persistence in two insects, the tobacco hornworm, Manduca sexta, a species in which experimental difficulty has been experienced with RNAi protocols and the German cockroach, Blattella germanica, which is known to be highly susceptible to experimental RNAi. An ex vivo assay revealed that dsRNA was rapidly degraded by an enzyme in M. sexta hemolymph plasma, whilst dsRNA persisted much longer in B. germanica plasma. A quantitative reverse transcription PCR-based assay revealed that dsRNA, accordingly, disappeared rapidly from M. sexta hemolymph in vivo. The M. sexta dsRNAse is inactivated by exposure to high temperature and is inhibited by EDTA. These findings lead us to propose that the rate of persistence of dsRNA in insect hemolymph (mediated by the action of one or more nucleases) could be an important factor in determining the susceptibility of insect species to RNAi

Different conformations and packing motifs in the crystal structures of four thiophene--carbohydrazide--pyridine derivatives

Peer reviewedPublisher PD

Excitations in the Halo Nucleus He-6 Following The Li-7(gamma,p)He-6 Reaction

A broad excited state was observed in 6-He with energy E_x = 5 +/- 1 MeV and width Gamma = 3 +/- 1 MeV, following the reaction Li-7(gamma,p)He-6. The state is consistent with a number of broad resonances predicted by recent cluster model calculations. The well-established reaction mechanism, combined with a simple and transparent analysis procedure confers considerable validity to this observation.Comment: 3 pages of LaTeX, 3 figures in PostScript, approved for publication in Phys. Rev. C, August, 200