2,435 research outputs found

    Fast track children's hearing pilot: final report of the evaluation of the pilot

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    This report presents key findings of the evaluation of the Fast Track children’s hearings pilot in Scotland1. The research was undertaken by staff at the Universities of Glasgow, Stirling and Strathclyde between February 2003 and January 2005

    Progressive impairment of CaV1.1 function in the skeletal muscle of mice expressing a mutant type 1 Cu/Zn superoxide dismutase (G93A) linked to amyotrophic lateral sclerosis

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    Background: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder that is typically fatal within 3–5 years of diagnosis. While motoneuron death is the defining characteristic of ALS, the events that underlie its pathology are not restricted to the nervous system. In this regard, ALS muscle atrophies and weakens significantly before presentation of neurological symptoms. Since the skeletal muscle L-type Ca2+ channel (CaV1.1) is a key regulator of both mass and force, we investigated whether CaV1.1 function is impaired in the muscle of two distinct mouse models carrying an ALS-linked mutation. Methods: We recorded L-type currents, charge movements, and myoplasmic Ca2+ transients from dissociated flexor digitorum brevis (FDB) fibers to assess CaV1.1 function in two mouse models expressing a type 1 Cu/Zn superoxide dismutase mutant (SOD1G93A). Results: In FDB fibers obtained from “symptomatic” global SOD1G93A mice, we observed a substantial reduction of SR Ca2+ release in response to depolarization relative to fibers harvested from age-matched control mice. L-type current and charge movement were both reduced by ~40 % in symptomatic SOD1G93A fibers when compared to control fibers. Ca2+ transients were not significantly reduced in similar experiments performed with FDB fibers obtained from “early-symptomatic” SOD1G93A mice, but L-type current and charge movement were decreased (~30 and ~20 %, respectively). Reductions in SR Ca2+ release (~35 %), L-type current (~20 %), and charge movement (~15 %) were also observed in fibers obtained from another model where SOD1G93A expression was restricted to skeletal muscle. Conclusions: We report reductions in EC coupling, L-type current density, and charge movement in FDB fibers obtained from symptomatic global SOD1G93A mice. Experiments performed with FDB fibers obtained from early-symptomatic SOD1G93A and skeletal muscle autonomous MLC/SOD1G93A mice support the idea that events occurring locally in the skeletal muscle contribute to the impairment of CaV1.1 function in ALS muscle independently of innervation status

    Community Organization for Litter Control

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    23 leaves. Advisor: Margaret E. Lloyd.The problem. Many procedures have been used by federal, state and local agencies to control the littering problem. However, few of these procedures have been adequately evaluated. The present study is an evaluation of one community's attempt to control its litter problem. Procedures. A litter clean-up drive was planned by a local neighborhood association in which residents were encouraged to clean up the litter on their blocks. Block leaders were identified who were responsible for organizing teams of residents from each of ten experimental blocks to clean up the litter on the blocks. Ten control blocks which were similar in size and traffic flow did not have block leaders. All residents who attended a regular meeting of the association were informed of the clean-up drive and it was promoted by the news media. Findings. Sixty percent of the litter which was on the ground in the experimental blocks was removed while only 8% of the litter in the control blocks was removed. Conclusions. The block leader procedure is an effective way to get neighborhood residents to pick up the litter on their blocks as part of a litter clean-up drive. Recommendations. The organization should use block leaders for all blocks in future clean-up drives. Further research should examine ways to make the procedure more than 60% effective

    Dynamical Drivers of the Local Wind Regime in a Himalayan Valley

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    Understanding the local valley wind regimes in the Hindu-Kush Karakoram Himalaya is vital for future predictions of the glacio-hydro-meteorological system. Here the Weather Research and Forecasting model is employed at a resolution of 1 km to investigate the forces driving the local valleywind regime in a river basin in the Nepalese Himalaya, during July 2013 and January 2014. Comparing withobservations shows that the model represents the diurnal cycle of the winds well, with strong daytime up-valley winds and weak nighttime winds in both months. A momentum budget analysis of the model output shows that in the summer run the physical drivers of the near-surface valley wind also have a clear diurnal cycle, and are dominated by the pressure gradient, advection, and turbulent vertical mixing,as well as a nonphysical numerical diffusion term. By contrast, the drivers in the winter run have a less consistent diurnal cycle. In both months, the pressure gradient, advection, numerical diffusion, and Coriolis terms dominate up to 5,000 m above the ground. The drivers are extremely variable over the valley, and also influenced by the presence of glaciers. When glaciers are removed from the model in the summer run, the wind continues further up the valley, indicating how the local valley winds might respond to future glacier shrinkage. The spatial variability of the drivers over both months is consistent with the complex topography in the basin, which must therefore be well represented in weather and regional climate models to generate accurate output

    The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli

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    Skeletal metastases are frequently accompanied by chronic pain that is mechanoceptive in nature. Mechanistically, cancer-induced bone pain (CIBP) is mediated by peripheral sensory neurons innervating the cancerous site, the cell bodies of which are housed in the dorsal root ganglia (DRG). How these somatosensory neurons encode sensory information in CIBP remains only partly explained. Using a validated rat model, we first confirmed cortical bone destruction in CIBP but not sham-operated rats (day 14 after surgery, designated “late”-stage bone cancer). This occurred with behavioural mechanical hypersensitivity (Kruskal–Wallis H for independent samples; CIBP vs sham-operated, day 14; P < 0.0001). Next, hypothesising that the proportion and phenotype of primary afferents would be altered in the disease state, dorsal root ganglia in vivo imaging of genetically encoded calcium indicators and Markov Cluster Analysis were used to analyse 1748 late-stage CIBP (n = 10) and 757 sham-operated (n = 9), neurons. Distinct clusters of responses to peripheral stimuli were revealed. In CIBP rats, upon knee compression of the leg ipsilateral to the tumour, (1) 3 times as many sensory afferents responded (repeated-measures analysis of variance: P < 0.0001 [vs sham]); (2) there were significantly more small neurons responding (Kruskal–Wallis for independent samples (vs sham): P < 0.0001); and (3) approximately 13% of traced tibial cavity afferents responded (no difference observed between CIBP and sham-operated animals). We conclude that an increased sensory afferent response is present in CIBP rats, and this is likely to reflect afferent recruitment from outside of the bone rather than increased intraosseous afferent activity
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