Influence of the LILRA3 Deletion on Multiple Sclerosis Risk: Original Data and Meta-Analysis.

BACKGROUND Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Additional risk loci with immunologically relevant genes were found significantly overrepresented. Nonetheless, it is accepted that most of the genetic architecture underlying susceptibility to the disease remains to be defined. Candidate association studies of the leukocyte immunoglobulin-like receptor LILRA3 gene in MS have been repeatedly reported with inconsistent results. OBJECTIVES In an attempt to shed some light on these controversial findings, a combined analysis was performed including the previously published datasets and three newly genotyped cohorts. Both wild-type and deleted LILRA3 alleles were discriminated in a single-tube PCR amplification and the resulting products were visualized by their different electrophoretic mobilities. RESULTS AND CONCLUSION Overall, this meta-analysis involved 3200 MS patients and 3069 matched healthy controls and it did not evidence significant association of the LILRA3 deletion [carriers of LILRA3 deletion: p = 0.25, OR (95% CI) = 1.07 (0.95-1.19)], even after stratification by gender and the HLA-DRB1*15:01 risk allele.

Biblioteca de l'heurística constructiva Clarke and Wright combinada amb simulació Monte Carlo per resoldre el problema d'adreçament de vehicles

En aquesta recerca es presenta una biblioteca de programari lliure basada en l'heurística constructiva de Clarke & Wright combinada amb simulació Monte Carlo que permet, de manera simple, generar solucions al problema d'adreçament de vehicles. Aquesta metodologia construeix solucions competents en poc temps i sense necessitat d'ajustar o configurar paràmetres previs. La biblioteca pot integrar-se fàcilment en projectes que resolguin variants del VRP amb canvis mínims sobre el codi. Aquest es troba ben documentat i accessible de manera lliure a través de la xarxa. Els resultats computacionals indiquen que es resolen instàncies VRP en temps i costos significativament inferiors a altres propostes de la mateixa família.

Software para la representación gráfica a la solución de ruteo y carga de vehículos en algoritmo de tipo 2L-CVRP

El siguiente artículo presenta el trabajo realizado en la creación de una aplicación de software libre que representa gráficamente las rutas generadas y la distribución de los elementos transportados en el interior de un vehículo de carga.

Paralelización del algoritmo Rho de Pollard utilizando el protocolo de paso por mensajes MPI

El agoritmo Rho de Pollard es uno de los mejores conocidos para resolver el problema del logaritmo discreto. Se trata de una implementación de una paralelización utilizando MPI sobre un clúster. El lector encontrará en este proyecto el algoritmo de paralelización utilizado, así como, un conjunto de pruebas y resultados de la ejecución debidamente analizados.

Anàlisis de la interacció i avaluació heurística d'un joc multijugador per a telèfons mòbils

This project is focused on an analysis and an heuristic evaluation of a multi-player game designed for mobile phone and based on an adaptation of Nielsen's and Molich's heuristics which was carried out by a group of researchers of the Lancaster University.

Assessing heterogeneity of effects on blood pressure in a meta-analysis of pharmacist interventions trials

Background: Recent reviews of randomized control trials have shown that pharmacist interventions improve cardiovascular diseases (CVD) risk factors in outpatients. Various interventions were evaluated in different settings, and a substantial heterogeneity was observed in the effect estimates. To better express uncertainties in the effect estimates, prediction intervals (PI) have been proposed but are, however, rarely reported. Objective: Pooling data from two systematic reviews, we estimated the effect of pharmacist interventions on systolic blood pressure (BP), computed PI, and evaluated potential causes of heterogeneity. Methods: Data were pooled from systematic reviews assessing the effect of pharmacist interventions on CVD risk factors in patients with or without diabetes, respectively. Effects were estimated using random effect models. Results: Systolic BP was the outcome in 31 trials including 12 373 patients. Pharmacist interventions included patient educational interventions, patient-reminder systems, measurement of BP, medication management and feedback to physician, or educational intervention to health care professionals. Pharmacist interventions were associated with a large reduction in systolic BP (-7.5 mmHg; 95% CI: -9.0 to -5.9). There was a substantial heterogeneity (I2: 66%). The 95% PI ranged from -13.9 to -1.0 mmHg. The effect tended to be larger if the intervention was conducted in a community pharmacy and if the pharmacist intervened at least monthly. Conclusion: On average, the effect of pharmacist interventions on BP was substantial. However, the wide PI suggests that the effect differed between interventions, with some having modest effects and others very large effects on BP. Part of the heterogeneity could be due to differences in the setting and in the frequency of the interventions.

Improving blood pressure control through pharmacist interventions: a meta-analysis of randomized controlled trials.

BACKGROUND: Control of blood pressure (BP) remains a major challenge in primary care. Innovative interventions to improve BP control are therefore needed. By updating and combining data from 2 previous systematic reviews, we assess the effect of pharmacist interventions on BP and identify potential determinants of heterogeneity. METHODS AND RESULTS: Randomized controlled trials (RCTs) assessing the effect of pharmacist interventions on BP among outpatients with or without diabetes were identified from MEDLINE, EMBASE, CINAHL, and CENTRAL databases. Weighted mean differences in BP were estimated using random effect models. Prediction intervals (PI) were computed to better express uncertainties in the effect estimates. Thirty-nine RCTs were included with 14 224 patients. Pharmacist interventions mainly included patient education, feedback to physician, and medication management. Compared with usual care, pharmacist interventions showed greater reduction in systolic BP (-7.6 mm Hg, 95% CI: -9.0 to -6.3; I(2)=67%) and diastolic BP (-3.9 mm Hg, 95% CI: -5.1 to -2.8; I(2)=83%). The 95% PI ranged from -13.9 to -1.4 mm Hg for systolic BP and from -9.9 to +2.0 mm Hg for diastolic BP. The effect tended to be larger if the intervention was led by the pharmacist and was done at least monthly. CONCLUSIONS: Pharmacist interventions - alone or in collaboration with other healthcare professionals - improved BP management. Nevertheless, pharmacist interventions had differential effects on BP, from very large to modest or no effect; and determinants of heterogeneity could not be identified. Determining the most efficient, cost-effective, and least time-consuming intervention should be addressed with further research.

La teoría de Morales-Ramis y el algoritmo de Kovacic

La teor\'\ı a de Morales–Ramis es la teor\'\ı a de Galois en el contextode los sistemas din\'amicos y relaciona dos tipos diferentes de integrabilidad:integrabilidad en el sentido de Liouville de un sistema hamiltonianoe integrabilidad en el sentido de la teor\'\ı a de Galois diferencial deuna ecuaci\'on diferencial. En este art\'\i culo se presentan algunas aplicacionesde la teor\'\i a de Morales–Ramis en problemas de no integrabilidadde sistemas hamiltonianos cuya ecuaci\'on variacional normal a lo largode una curva integral particular es una ecuaci\'on diferencial lineal desegundo orden con coeficientes funciones racionales. La integrabilidadde la ecuaci\'on variacional normal es analizada mediante el algoritmode Kovacic.

Diagnostic Accuracy of (18)F-FDG-PET and PET/CT in the Differential Diagnosis between Malignant and Benign Pleural Lesions: A Systematic Review and Meta-Analysis.

RATIONALE AND OBJECTIVES: To systematically review and meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the differential diagnosis between malignant and benign pleural lesions. METHODS AND MATERIALS: A comprehensive literature search of studies published through June 2013 regarding the diagnostic performance of (18)F-FDG-PET and PET/CT in the differential diagnosis of pleural lesions was carried out. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) of (18)F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions on a per-patient-based analysis were calculated. The area under the summary receiver operating characteristic curve (AUC) was calculated to measure the accuracy of these methods. Subanalyses considering device used (PET or PET/CT) were performed. RESULTS: Sixteen studies including 745 patients were included in the systematic review. The meta-analysis of 11 selected studies provided the following results: sensitivity 95% (95% confidence interval [95%CI]: 92-97%), specificity 82% (95%CI: 76-88%), LR+ 5.3 (95%CI: 2.4-11.8), LR- 0.09 (95%CI: 0.05-0.14), DOR 74 (95%CI: 34-161). The AUC was 0.95. No significant improvement of the diagnostic accuracy considering PET/CT studies only was found. CONCLUSIONS: (18)F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods in the differential diagnosis between malignant and benign pleural lesions; nevertheless, possible sources of false-negative and false-positive results should be kept in mind.

Impact of pharmacist care in the management of cardiovascular disease risk factors: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Pharmacists may improve the clinical management of major risk factors for cardiovascular disease (CVD) prevention. A systematic review was conducted to determine the impact of pharmacist care on the management of CVD risk factors among outpatients. METHODS: The MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials that involved pharmacist care interventions among outpatients with CVD risk factors. Two reviewers independently abstracted data and classified pharmacists' interventions. Mean changes in blood pressure, total cholesterol, low-density lipoprotein cholesterol, and proportion of smokers were estimated using random effects models. RESULTS: Thirty randomized controlled trials (11 765 patients) were identified. Pharmacist interventions exclusively conducted by a pharmacist or implemented in collaboration with physicians or nurses included patient educational interventions, patient-reminder systems, measurement of CVD risk factors, medication management and feedback to physician, or educational intervention to health care professionals. Pharmacist care was associated with significant reductions in systolic/diastolic blood pressure (19 studies [10 479 patients]; -8.1 mm Hg [95% confidence interval {CI}, -10.2 to -5.9]/-3.8 mm Hg [95% CI,-5.3 to -2.3]); total cholesterol (9 studies [1121 patients]; -17.4 mg/L [95% CI,-25.5 to -9.2]), low-density lipoprotein cholesterol (7 studies [924 patients]; -13.4 mg/L [95% CI,-23.0 to -3.8]), and a reduction in the risk of smoking (2 studies [196 patients]; relative risk, 0.77 [95% CI, 0.67 to 0.89]). While most studies tended to favor pharmacist care compared with usual care, a substantial heterogeneity was observed. CONCLUSION: Pharmacist-directed care or in collaboration with physicians or nurses improve the management of major CVD risk factors in outpatients.

A systematic review and meta-analysis of perineural dexamethasone for peripheral nerve blocks.

We systematically reviewed the safety and efficacy of perineural dexamethasone as an adjunct for peripheral nerve blockade in 29 controlled trials of 1695 participants. We grouped trials by the duration of local anaesthetic action (short- or medium- vs long-term). Dexamethasone increased the mean (95% CI) duration of analgesia by 233 (172-295) min when injected with short- or medium-term action local anaesthetics and by 488 (419-557) min when injected with long-term action local anaesthetics, p < 0.00001 for both. However, these results should be interpreted with caution due to the extreme heterogeneity of results, with I2 exceeding 90% for both analyses. Meta-regression did not show an interaction between dose of perineural dexamethasone (4-10 mg) and duration of analgesia (r2 = 0.02, p = 0.54). There were no differences between 4 and 8 mg dexamethasone on subgroup analysis.

Diagnostic Performance of Magnetic Resonance Imaging and Computed Tomography for Advanced Retinoblastoma: A Systematic Review and Meta-analysis.

PURPOSE: To determine and compare the diagnostic performance of magnetic resonance imaging (MRI) and computed tomography (CT) for the diagnosis of tumor extent in advanced retinoblastoma, using histopathologic analysis as the reference standard. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Patients with advanced retinoblastoma who underwent MRI, CT, or both for the detection of tumor extent from published diagnostic accuracy studies. METHODS: Medline and Embase were searched for literature published through April 2013 assessing the diagnostic performance of MRI, CT, or both in detecting intraorbital and extraorbital tumor extension of retinoblastoma. Diagnostic accuracy data were extracted from included studies. Summary estimates were based on a random effects model. Intrastudy and interstudy heterogeneity were analyzed. MAIN OUTCOME MEASURES: Sensitivity and specificity of MRI and CT in detecting tumor extent. RESULTS: Data of the following tumor-extent parameters were extracted: anterior eye segment involvement and ciliary body, optic nerve, choroidal, and (extra)scleral invasion. Articles on MRI reported results of 591 eyes from 14 studies, and articles on CT yielded 257 eyes from 4 studies. The summary estimates with their 95% confidence intervals (CIs) of the diagnostic accuracy of conventional MRI at detecting postlaminar optic nerve, choroidal, and scleral invasion showed sensitivities of 59% (95% CI, 37%-78%), 74% (95% CI, 52%-88%), and 88% (95% CI, 20%-100%), respectively, and specificities of 94% (95% CI, 84%-98%), 72% (95% CI, 31%-94%), and 99% (95% CI, 86%-100%), respectively. Magnetic resonance imaging with a high (versus a low) image quality showed higher diagnostic accuracies for detection of prelaminar optic nerve and choroidal invasion, but these differences were not statistically significant. Studies reporting the diagnostic accuracy of CT did not provide enough data to perform any meta-analyses. CONCLUSIONS: Magnetic resonance imaging is an important diagnostic tool for the detection of local tumor extent in advanced retinoblastoma, although its diagnostic accuracy shows room for improvement, especially with regard to sensitivity. With only a few-mostly old-studies, there is very little evidence on the diagnostic accuracy of CT, and generally these studies show low diagnostic accuracy. Future studies assessing the role of MRI in clinical decision making in terms of prognostic value for advanced retinoblastoma are needed.

Intravenous insulin treatment in acute stroke: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Poststroke hyperglycemia has been associated with unfavorable outcome. Several trials investigated the use of intravenous insulin to control hyperglycemia in acute stroke. This meta-analysis summarizes all available evidence from randomized controlled trials in order to assess its efficacy and safety. METHODS: We searched PubMed until 15/02/2013 for randomized clinical trials using the following search items: 'intravenous insulin' or 'hyperglycemia', and 'stroke'. Eligible studies had to be randomized controlled trials of intravenous insulin in hyperglycemic patients with acute stroke. Analysis was performed on intention-to-treat basis using the Peto fixed-effects method. The efficacy outcomes were mortality and favorable functional outcome. The safety outcomes were mortality, any hypoglycemia (symptomatic or asymptomatic), and symptomatic hypoglycemia. RESULTS: Among 462 potentially eligible articles, nine studies with 1491 patients were included in the meta-analysis. There was no statistically significant difference in mortality between patients who were treated with intravenous insulin and controls (odds ratio: 1.16, 95% confidence interval: 0.89-1.49). Similarly, the rate of favorable functional outcome was not statistically different (odds ratio: 1.01, 95% confidence interval: 0.81-1.26). The rates of any hypoglycemia (odds ratio: 8.19, 95% confidence interval: 5.60-11.98) and of symptomatic hypoglycemia (odds ratio: 6.15, 95% confidence interval: 1.88-20.15) were higher in patients treated with intravenous insulin. There was no heterogeneity across the included trials in any of the outcomes studied. CONCLUSIONS: This meta-analysis of randomized controlled trials does not support the use of intravenous insulin in hyperglycemic stroke patients to improve mortality or functional outcome. The risk of hypoglycemia is increased, however.