140 research outputs found

    Ethnic variations in falls and road traffic injuries resulting in hospitalisation or death in Scotland: the Scottish Health and Ethnicity Linkage Study (SHELS) Public Health

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    Objectives: To investigate ethnic differences in falls and road traffic injuries (RTIs) in Scotland. Study design: A retrospective cohort of 4.62 million people, linking the Scottish Census 2001, with self-reported ethnicity, to hospitalisation and death records for 2001–2013. Methods: We selected cases with International Classification of Diseases–10 diagnostic codes for falls and RTIs. Using Poisson regression, age-adjusted risk ratios (RRs, multiplied by 100 as percentages) and 95% confidence intervals (CIs) were calculated by sex for 10 ethnic groups with the White Scottish as reference. We further adjusted for country of birth and socio-economic status (SES). Results: During about 49 million person-years, there were 275,995 hospitalisations or deaths from fall-related injuries and 43,875 from RTIs. Compared with the White Scottish, RRs for falls were higher in most White and Mixed groups, e.g., White Irish males (RR: 131; 95% CI: 122–140) and Mixed females (126; 112–143), but lower in Pakistani males (72; 64–81) and females (72; 63–82) and African females (79; 63–99). For RTIs, RRs were higher in other White British males (161; 147–176) and females (156; 138–176) and other White males (119; 104–137) and females (143; 121–169) and lower in Pakistani females (74; 57–98). The ethnic variations differed by road user type, with few cases among non-White motorcyclists and non-White female cyclists. The RRs were minimally altered by adjustment for country of birth or SES. Conclusion: We found important ethnic variations in injuries owing to falls and RTIs, with generally lower risks in non-White groups. Culturally related differences in behaviour offer the most plausible explanation, including variations in alcohol use. The findings do not point to the need for new interventions in Scotland at present. However, as the ethnic mix of each country is unique, other countries could benefit from similar data linkage-based research

    Lidar System Model for Use With Path Obscurants and Experimental Validation

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    When lidar pulses travel through a short path that includes a relatively high concentration of aerosols, scattering phenomena can alter the power and temporal properties of the pulses significantly, causing undesirable effects in the received pulse. In many applications the design of the lidar transmitter and receiver must consider adverse environmental aerosol conditions to ensure the desired performance. We present an analytical model of lidar system operation when the optical path includes aerosols for use in support of instrument design, simulations, and system evaluation. The model considers an optical path terminated with a solid object, although it can also be applied, with minor modifications, to cases where the expected backscatter occurs from nonsolid objects. The optical path aerosols are characterized by their attenuation and backscatter coefficients derived by the Mie theory from the concentration and particle size distribution of the aerosol. Other inputs include the lidar system parameters and instrument response function, and the model output is the time-resolved received pulse. The model is demonstrated and experimentally validated with military fog oil smoke for short ranges (several meters). The results are obtained with a lidar system operating at a wavelength of 0.905 μm within and outside the aerosol. The model goodness of fit is evaluated using the statistical coefficient of determination whose value ranged from 0.88 to 0.99 in this study

    Life expectancy of different ethnic groups using death records linked to population census data for 4.62 million people in Scotland

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    Background: Few countries record the data needed to estimate life expectancy by ethnic group. Such information is helpful in assessing the extent of health inequality. Method: Life tables were created using 3 years of deaths (May 2001–April 2004) linked to Scottish 2001 Census data for 4.62 million individuals with self-reported ethnicity. We created 8 ethnic groups based on the census definitions, each with at least 5000 individuals and 40 deaths. Life expectancy at birth was calculated using the revised Chiang method. Results: The life expectancy of White Scottish males at birth was 74.7 years (95% CI 74.6 to 74.8), similar to Mixed Background (73.0; 70.2 to 75.8) and White Irish (75.0; 74.0 to 75.9), but shorter than Indian (80.9; 78.4 to 83.4), Pakistani (79.3; 76.9 to 81.6), Chinese (79.0; 76.5 to 81.5), Other White British (78.9; 78.6 to 79.2) and Other White (77.2; 76.4 to 78.1). The life expectancy of White Scottish females was 79.4 years (79.3 to 79.5), similar to mixed background (79.3; 76.6 to 82.0), but shorter than Pakistani (84.6; 82.0 to 87.3), Chinese (83.4; 81.1 to 85.7), Indian (83.3; 80.7 to 85.9), Other White British (82.6; 82.3 to 82.9), other White (82.0; 81.3 to 82.8) and White Irish (81; 80.2 to 81.8). Conclusions: Males and females in most of the larger ethnic minority groups in Scotland have longer life expectancies than the majority White Scottish population

    Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

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    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2–5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction

    Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

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    Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe) are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a Kiapp value of 3.8±0.8 µM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC50 value of 100 µM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 Å2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750–1,500 Å2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a Ki value of 760±170 nM using synthesis-based computer-aided molecular design (SBCAMD). This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight into structural modification of known small-molecule BoNTAe inhibitors. It also demonstrates that SBCAMD is capable of improving potency of an inhibitor lead by nearly one order of magnitude, even for BoNTAe as one of the most challenging protein targets. The results are insightful for developing effective small-molecule inhibitors of protein targets with large active sites
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