721 research outputs found

    Neuropsychological characterization of aggressive behavior in children and adolescents with cd/odd and effects of single doses of medications: The protocol of the matrics_wp6-1 study

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    Aggressive behaviors and disruptive/conduct disorders are some of the commonest reasons for referral to youth mental health services; nevertheless, the efficacy of therapeutic interventions in real-world clinical practice remains unclear. In order to define more appropriate targets for innovative pharmacological therapies for disruptive/conduct disorders, the European Commission within the Seventh Framework Programme (FP7) funded the MATRICS project (Multidisciplinary Approaches to Translational Research in Conduct Syndromes) to identify neural, genetic, and molecular factors underpinning the pathogenesis of aggression/antisocial behavior in preclinical models and clinical samples. Within the program, a multicentre case-control study, followed by a single-blind, placebo-controlled, cross-over, randomized acute single-dose medication challenge, was conducted at two Italian sites. Aggressive children and adolescents with conduct disorder (CD) or oppositional defiant disorder (ODD) were compared to the same age (10–17 y) typically developing controls (TDC) on a neuropsychological tasks battery that included both “cold” (e.g., inhibitory control, decision making) and “hot” executive functions (e.g., moral judgment, emotion processing, risk assessment). Selected autonomic measures (heart rate variability, skin conductance, salivary cortisol) were recorded before/during/after neuropsychological testing sessions. The acute response to different drugs (methylphenidate/atomoxetine, risperidone/aripiprazole, or placebo) was also examined in the ODD/CD cohort in order to identify potential neuropsychological/physiological mechanisms underlying aggression. The paper describes the protocol of the clinical MATRICS WP6-1 study, its rationale, the specific outcome measures, and their implications for a precision medicine approach

    Evaluation of Passing Process on Two-Lane Rural Highways in Spain with New Methodology Based on Video Data

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    Drivers need sufficient passing sight distance (PSD) to pass slower vehicles with safety. This distance can help to improve traffic operation on two-way, two-lane highways. Existing models propose different values of PSD because of different assumptions. In only some cases were these models based on field data of passing maneuvers. This research proposed the design of a methodology to observe passing maneuvers on existing highways with the help of six video cameras installed at a fixed point next to passing sections. The use of more cameras allows complete registration of trajectories along the entire passing zone, with uniform image resolution. The methodology was applied to register a sample of 234 maneuvers on four passing zones. Trajectories of 58 maneuvers were completely described and analyzed with specific restitution software. Results were compared with those from existing PSD models. The distances traveled proposed by the AASHTO model on the left lane were (a) similar to average observed distances when the passed vehicle was one truck and (b) between 50 and 100 m higher when one passenger car was passed. Higher differences, greater than 100 m, were found between measured data and the PSD model (published previously), especially at high design speeds. The observed average speed difference between passing and impeding vehicles was significantly higher than that in any model. Variables with the strongest influence on the time and distance traveled on the opposing lane were the type and speed of the passed vehicle and the length of the passing zone. Left-lane time and distance increase with this length.Llorca Garcia, C.; GarcĂ­a GarcĂ­a, A. (2011). Evaluation of Passing Process on Two-Lane Rural Highways in Spain with New Methodology Based on Video Data. Transportation Research Record. 2262:42-51. doi:10.3141/2262-05S42512262Farah, H., Bekhor, S., & Polus, A. (2009). Risk evaluation by modeling of passing behavior on two-lane rural highways. Accident Analysis & Prevention, 41(4), 887-894. doi:10.1016/j.aap.2009.05.006Rilett, L. R., Hutchinson, B. G., & Whitney, M. (1990). Mechanics of the passing maneuver and the impact of large trucks. Transportation Research Part A: General, 24(2), 121-128. doi:10.1016/0191-2607(90)90019-3Wang, Y., & Cartmell, M. P. (1998). New Model for Passing Sight Distance on Two-Lane Highways. Journal of Transportation Engineering, 124(6), 536-545. doi:10.1061/(asce)0733-947x(1998)124:6(536)Polus, A., Livneh, M., & Frischer, B. (2000). Evaluation of the Passing Process on Two-Lane Rural Highways. Transportation Research Record: Journal of the Transportation Research Board, 1701(1), 53-60. doi:10.3141/1701-07Carlson, P., Miles, J., & Johnson, P. (2006). Daytime High-Speed Passing Maneuvers Observed on Rural Two-Lane, Two-Way Highway: Findings and Implications. Transportation Research Record: Journal of the Transportation Research Board, 1961, 9-15. doi:10.3141/1961-02Harwood, D. W., Gilmore, D. K., & Richard, K. R. (2010). Criteria for Passing Sight Distance for Roadway Design and Marking. Transportation Research Record: Journal of the Transportation Research Board, 2195(1), 36-46. doi:10.3141/2195-0

    Relating constructs of attention and working memory to social withdrawal in Alzheimer's disease and schizophrenia: issues regarding paradigm selection

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    Central nervous system diseases are not currently diagnosed based on knowledge of biological mechanisms underlying their symptoms. Greater understanding may be offered through an agnostic approach to traditional disease categories, where learning more about shared biological mechanisms across conditions could potentially reclassify sub-groups of patients to allow realisation of more effective treatments. This review represents the output of the collaborative group “PRISM”, tasked with considering assay choices for assessment of attention and working memory in a transdiagnostic cohort of Alzheimer''s disease and schizophrenia patients exhibiting symptomatic spectra of social withdrawal. A multidimensional analysis of this nature has not been previously attempted. Nominated assays (continuous performance test III, attention network test, digit symbol substitution, N-back, complex span, spatial navigation in a virtual environment) reflected a necessary compromise between the need for broad assessment of the neuropsychological constructs in question with several pragmatic criteria: patient burden, compatibility with neurophysiologic measures and availability of preclinical homologues

    Relating constructs of attention and working memory to social withdrawal in Alzheimer's disease and schizophrenia: issues regarding paradigm selection

    Get PDF
    Central nervous system diseases are not currently diagnosed based on knowledge of biological mechanisms underlying their symptoms. Greater understanding may be offered through an agnostic approach to traditional disease categories, where learning more about shared biological mechanisms across conditions could potentially reclassify sub-groups of patients to allow realisation of more effective treatments. This review represents the output of the collaborative group "PRISM", tasked with considering assay choices for assessment of attention and working memory in a transdiagnostic cohort of Alzheimer's disease and schizophrenia patients exhibiting symptomatic spectra of social withdrawal. A multidimensional analysis of this nature has not been previously attempted. Nominated assays (continuous performance test III, attention network test, digit symbol substitution, N-back, complex span, spatial navigation in a virtual environment) reflected a necessary compromise between the need for broad assessment of the neuropsychological constructs in question with several pragmatic criteria: patient burden, compatibility with neurophysiologic measures and availability of preclinical homologues

    Fit for purpose? A cross-sectional study to evaluate the acceptability and usability of HeadUp, a novel neck support collar for neurological neck weakness

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    The HeadUp collar (previously known as the Sheffield Support Snood) provides support for neck weakness caused by amyotrophic lateral sclerosis (ALS) and has shown to be superior to alternative options in a small cohort of patients from one single center. Here we report the assessment of the HeadUp collar in a larger cohort of patients, exploring the use in other neurological conditions and expanding to other centers across the UK and Ireland. An interventional cross-sectional study design was implemented to investigate the usability and acceptability of the HeadUp collar. A total of 139 patients were recruited for the study, 117 patients had a diagnosis of ALS and 22 patients presented with neck weakness due to other neurological conditions. Participants were assessed at baseline, fitted a HeadUp collar and followed-up one month later. The performance of the HeadUp collar was rated favorably compared to previously worn collars in terms of the ability to eat, drink and swallow. Findings suggest that the collar also permitted a more acceptable range of head movements whilst maintaining a good level of support. We conclude that the HeadUp collar is a suitable option for patients with neck weakness due to ALS and other neurological conditions

    Rapid Diagnostic Algorithms as a Screening Tool for Tuberculosis: An Assessor Blinded Cross-Sectional Study

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    Background: A major obstacle to effectively treat and control tuberculosis is the absence of an accurate, rapid, and low-cost diagnostic tool. A new approach for the screening of patients for tuberculosis is the use of rapid diagnostic classification algorithms. Methods: We tested a previously published diagnostic algorithm based on four biomarkers as a screening tool for tuberculosis in a Central European patient population using an assessor-blinded cross-sectional study design. In addition, we developed an improved diagnostic classification algorithm based on a study population at a tertiary hospital in Vienna, Austria, by supervised computational statistics. Results: The diagnostic accuracy of the previously published diagnostic algorithm for our patient population consisting of 206 patients was 54% (CI: 47%–61%). An improved model was constructed using inflammation parameters and clinical information. A diagnostic accuracy of 86% (CI: 80%–90%) was demonstrated by 10-fold cross validation. An alternative model relying solely on clinical parameters exhibited a diagnostic accuracy of 85% (CI: 79%–89%). Conclusion: Here we show that a rapid diagnostic algorithm based on clinical parameters is only slightly improved by inclusion of inflammation markers in our cohort. Our results also emphasize the need for validation of new diagnostic algorithms in different settings and patient populations

    The correlation of RNase A enzymatic activity with the changes in the distance between Nepsilon2-His12 and N delta1-His119 upon addition of stabilizing and destabilizing salts.

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    The effect of stabilizing and destabilizing salts on the catalytic behavior of ribonuclease A (RNase A) was investigated at pH 7.5 and 25 degrees C, using spectrophotometric, viscometric and molecular dynamic methods. The changes in the distance between N(epsilon2) of His(12) and N(delta1) of His(119) at the catalytic center of RNase A upon the addition of sodium sulfate, sodium hydrogen sulfate and sodium thiocyanate were evaluated by molecular dynamic methods. The compactness and expansion in terms of Stokes radius of RNase A upon the addition of sulfate ions as kosmotropic salts, and thiocyanate ion as a chaotropic salt, were estimated by viscometric measurements. Enzyme activity was measured using cytidine 2', 3'-cyclic monophosphate as a substrate. The results from the measurements of distances between N(epsilon2) of His(12) and N(delta1) of His(119) and Stokes radius suggest (i) that the presence of sulfate ions decreases the distance between the catalytic His residues and increases the globular compactness, and (ii) that there is an expansion of the enzyme surface as well as elongation of the catalytic center in the presence of thiocyanate ion. These findings are in agreement with activity measurements
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