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An uncertainty cascade model applied to stream flow forecasting seeks to evaluate the different sources of uncertainty of the complex rainfall-runoff process. The current trend focuses on the combination of Meteorological Ensemble Prediction Systems (MEPS) and hydrological model(s). However, the number of members of such a HEPS may rapidly increase to a level that may not be operationally sustainable. This paper evaluates the generalization ability of a simplification scheme of a 800-member HEPS formed by the combination of 16 lumped rainfall-runoff models with the 50 perturbed members from the European Centre for Medium-range Weather Forecasts (ECMWF) EPS. Tests are made at two levels. At the local level, the transferability of the 9th day hydrological member selection for the other 8 forecast horizons exhibits an 82% success rate. The other evaluation is made at the regional or cluster level, the transferability from one catchment to another from within a cluster of watersheds also leads to a good performance (85% success rate), especially for forecast time horizons above 3 days and when the basins that formed the cluster presented themselves a good performance on an individual basis. Diversity, defined as hydrological model complementarity addressing different aspects of a forecast, was identified as the critical factor for proper selection applications. [ABSTRACT FROM AUTHOR]

Hydrological Ensemble Prediction Systems (HEPS), obtained by forcing rainfall-runoff models with Meteorological Ensemble Prediction Systems (MEPS), have been recognized as useful approaches to quantify uncertainties of hydrological forecasting systems. This task is complex both in terms of the coupling of information and computational time, which may create an operational barrier. The main objective of the current work is to assess the degree of simplification (reduction of the number of hydrological members) that can be achieved with a HEPS configured using 16 lumped hydrological models driven by the 50 weather ensemble forecasts from the European Centre for Medium-range Weather Forecasts (ECMWF). Here, Backward Greedy Selection (BGS) is proposed to assess the weight that each model must represent within a subset that offers similar or better performance than a reference set of 800 hydrological members. These hydrological models' weights represent the participation of each hydrological model within a simplified HEPS which would issue realtime forecasts in a relatively short computational time. The methodology uses a variation of the k-fold cross-validation, allowing an optimal use of the information, and employs a multi-criterion framework that represents the combination of resolution, reliability, consistency, and diversity. Results show that the degree of reduction of members can be established in terms of maximum number of members required (complexity of the HEPS) or the maximization of the relationship between the different scores (performance). [ABSTRACT FROM AUTHOR]

Objective: Several randomized controlled trials indicate that a low density lipoprotein cholesterol (LDL-C) target <2.0 mmol/L is appropriate for individuals at high risk of coronary artery disease (CAD). Recently released Canadian lipid management guidelines (2006) have incorporated this evidence into their recommendations. A cross-sectional study of patients treated with statins for at least 8 weeks (CALIPSO) was used as a basis to project the ability of statin monotherapy in getting high CAD-risk patients to an LDL-C level <2.0 mmol/L.Research Design and Methods: The analysis was restricted to CALIPSO patients on statin monotherapy who were at high CAD-risk (including patients with established CAD). Assuming all patients could have their statin titrated up to the maximum dose, the proportion of patients that would reach an LDL-C level of <2.0 mmol/L was projected. To do this, the additional LDL-C reduction patients would achieve with maximal titration of their statin was estimated based on a meta-analysis of clinical trials evaluating LDL-C responses to various statin regimens, and applied to patients' current LDL-C level.Results: A total of 1795 high CAD-risk patients treated with statin monotherapy were included in the analysis, of whom 69.8% had an LDL-C > or =2.0 mmol/L. Depending on the statin that was used, it was projected that between 28.2% and 62.7% of high CAD-risk patients would not attain an LDL-C of <2.0 mmol/L following statin titration to maximum dose.Conclusions: Although the accuracy of our projections may be limited by the application of clinical trials data to an external sample of patients, our results suggest that for 38% of patients at high CAD-risk, titration of statin monotherapy will not be sufficient to achieve an LDL-C target of <2.0 mmol/L. For these patients, additional treatment approaches may be needed to further reduce the risk of coronary events. [ABSTRACT FROM AUTHOR]

The car sequencing problem is the ordering of the production of a list of vehicles which are of the same type, but which may have options or variations that require higher work content and longer operation times for at least one assembly workstation. A feasible production sequence is one that does not schedule vehicles with options in such a way that one or more workstations are overloaded. In variations of the problem, other constraints may apply. We describe and compare three approaches to the modeling and solution of this problem. The first uses integer programming to model and solve the problem. The second approaches the question as a constraint satisfaction problem (CSP). The third method proposes an adaptation of the Ant Colony Optimization for the car sequencing problem. Test-problems are drawn from CSPLib, a publicly available set of problems available through the Internet. We quote results drawn both from our own work and from other research. The literature review is not intended to be exhaustive but we have sought to include representative examples and the more recent work. Our conclusions bear on likely research avenues for the solution of problems of practical size and complexity. A new set of larger benchmark problems was generated and solved. These problems are available to other researchers who may wish to solve them using their own methods. [ABSTRACT FROM AUTHOR]

Ezetimibe is a lipid-lowering drug that inhibits the intestinal absorption of dietary and biliary cholesterol by blocking passage across the intestinal wall. The efficacy and safety of adding ezetimibe to ongoing statin therapy in patients with primary hypercholesterolemia was evaluated in a randomized, double-blind, placebo-controlled study. The study group included 769 adults (aged > or =18 years) with primary hypercholesterolemia who had not achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel II goals with dietary alteration and statin monotherapy. Patients receiving a stable dose of a statin for > or =6 weeks were randomized to receive concurrent treatment with placebo (n = 390) or ezetimibe (n = 379), 10 mg/day, in addition to continuing their open-label statin for 8 weeks. The primary efficacy variable was the percent change in low-density lipoprotein (LDL) cholesterol from baseline with statin monotherapy to end point after intervention (secondary variables: high-density lipoprotein [HDL] cholesterol and triglycerides). Ongoing statin therapy plus ezetimibe led to changes of -25.1% for LDL cholesterol (HDL cholesterol +2.7%; triglycerides -14.0%) compared with LDL cholesterol -3.7% (p <0.001), HDL cholesterol +1.0% (p <0.05), and triglycerides -2.9% (p <0.001) for placebo added to ongoing statin therapy. Among patients not at LDL cholesterol goal at on-statin baseline, 71.5% receiving statin plus ezetimibe versus 18.9% receiving statin plus placebo reached goal at end point (odds ratio 23.7; p <0.001). The co-administration of statin and ezetimibe was generally well tolerated. Adding ezetimibe to ongoing statin therapy led to substantial additional reduction in LDL cholesterol levels, facilitating attainment of NCEP goals. Ezetimibe offers a new therapeutic option for patients receiving statins who require further reduction in LDL cholesterol. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolaemia is characterised by a decreased removal of low density lipoproteins and premature coronary artery disease. Tendinous xanthomata are a hallmark of the disease. The affected joints may also be the sites of inflammation and pain. Arthropathy has been associated mainly with the homozygous form of familial hypercholesterolaemia, but it is also known to occur in the heterozygous form. We report on the articular manifestations in 73 patients with heterozygous familial hypercholesterolaemia. About 40% of these patients had at least one episode of articular symptoms. The observed articular manifestations may be classified into four types: Achilles pain (18%), Achilles tendinitis (11%), oligoarticular arthritis (7%), polyarticular or rheumatic fever-like arthritis (4%). It is concluded that in heterozygous familial hypercholesterolaemia articular manifestations are frequent, diverse, and may be the first symptom of this metabolic disorder. [ABSTRACT FROM PUBLISHER]

Abstract Background HMG-CoA reductase inhibitors (statins) are commonly used in medicine to control blood lipid disorder. Large clinical trials have demonstrated that statins greatly reduces cardiovascular-related morbidity and mortality in patients with and without coronary artery disease. Also, the use of HMG-CoA reductase inhibitors has been reported to have immunosuppressive effects. Case presentation We describe an unusual case of regression of vitiligo in a patient treated with high dose simvastatin. The relation between simvastatin and regression of vitiligo in this case report may be related to the autoimmune pathophysiology of the disease. Conclusion This unexpected beneficial impact provides another scientific credence to the hypothesis that immune mechanisms play a role in the development of vitiligo and that the use of statins as immuno-modulator could be of use not only for treatment relative to organ transplant but in other pathologies such as vitiligo.

BACKGROUND: Ezetimibe (EZE) is a cholesterol-lowering drug that inhibits absorption of dietary and biliary cholesterol across the intestinal wall without affecting absorption of bile acids, fatty acids, fat-soluble vitamins, or triglycerides. It has a complementary mechanism of action to the statins, which inhibit cholesterol synthesis in the liver. Coadministration of EZE and statins provides inhibition of 2 sources of cholesterol, leading to greater reductions in low-density lipoprotein cholesterol (LDL-C) than with either agent alone. OBJECTIVES: This study evaluated the long-term safety and tolerability profiles and lipid-modifying efficacy of treatment with EZE 10 mg/d plus simvastatin (SIMVA) 10, 20, 40, or 80 mg/d for 48 weeks in patients with primary hypercholesterolemia. METHODS: This was an extension of a multicenter, double-blind, placebo (PBO)-controlled base study in which hypercholesterolemic patients were randomized to receive EZE 10 mg/d or PBO in addition to their current statin for 8 weeks. Patients who successfully completed the base study could enter the extension study if they were willing to switch from their current statin to an approximately equipotent dose of SIMVA for the 54-week study period. After a 6-week open-label SIMVA run-in phase, patients were rerandomized to receive EZE 10 mg/d or PBO in a 4:1 ratio, respectively, for 48 weeks. At each clinic visit, beginning at week 12, the dose of SIMVA was titrated upward until patients reached their National Cholesterol Education Program Adult Treatment Panel II LDL-C goal or the maximum SIMVA dose of 80 mg/d. Safety/tolerability and lipid efficacy parameters were assessed at 12-week intervals. RESULTS: Of 433 patients entering the extension study, 355 were randomized to receive EZE and 78 were randomized to receive PBO. Baseline demographic characteristics and lipid levels were similar between treatment groups. Overall, coadministration of EZE + SIMVA was well tolerated. There were no clinically meaningful differences between the EZE and PBO groups with regard to the incidence of treatment-related adverse events (AEs) (19% vs 17%, respectively), discontinuations due to AEs (7% vs 10%), serious AEs (12% vs 17%), consecutive elevations in liver function tests > or =3 times the upper limit of normal (ULN) (0.3% vs 0%), or elevations in creatine kinase > or =10 times the ULN (both, 0%). As in the base study, LDL-C levels were significantly lower with the addition of EZE to SIMVA compared with the addition of PBO (-24% vs 3%; P < 0.001). CONCLUSION: In these patients with primary hypercholesterolemia, EZE 10 mg/d added to ongoing SIMVA treatment for 48 weeks had a favorable safety and tolerability profile and was more efficacious than SIMVA monotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite the progress made in smoking prevention among youth, few scientific reports have identified the determinants underlying the abstinence from cigarettes, and even fewer have made an assessment of their evolution over time. It has been proposed that this could be done by modeling after theoretical frameworks. METHODS: A self-reported questionnaire developed according to Ajzen's Theory of Planned Behavior was repeatedly administered to a cohort of 373 grade 5 students (191 girls and 182 boys) during their transition from elementary to secondary school. Four measures spanning a 26-month period were thus obtained and analyzed according to the GEE method. RESULTS: After 26 months, 76.14% of the students in the sample remained abstinent from cigarettes. The perceived smoking behaviors of friends and of a brother, intention over time, perceived self-efficacy, parental supervision, and socioeconomic status predicted the maintenance of abstinence from smoking. The final predictive model had a sensitivity of 79.8% and a specificity of 75.6%, with an average rate of accurate classification of 79.1%. CONCLUSIONS: The predictive model yielded by this study represents an important step toward developing tools to help 10-12 years olds maintaining their abstinent behavior. It emphasizes positive protective factors and guides health promoters in the choice of their interventions' contents and targets. © 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]