863 resultados para Linear Mixed Integer Multicriteria Optimization


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A lot sizing and scheduling problem prevalent in small market-driven foundries is studied. There are two related decision levels: (I the furnace scheduling of metal alloy production, and (2) moulding machine planning which specifies the type and size of production lots. A mixed integer programming (MIP) formulation of the problem is proposed, but is impractical to solve in reasonable computing time for non-small instances. As a result, a faster relax-and-fix (RF) approach is developed that can also be used on a rolling horizon basis where only immediate-term schedules are implemented. As well as a MIP method to solve the basic RF approach, three variants of a local search method are also developed and tested using instances based on the literature. Finally, foundry-based tests with a real-order book resulted in a very substantial reduction of delivery delays and finished inventory, better use of capacity, and much faster schedule definition compared to the foundry`s own practice. (c) 2006 Elsevier Ltd. All rights reserved.

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The purpose of this article is to present a new method to predict the response variable of an observation in a new cluster for a multilevel logistic regression. The central idea is based on the empirical best estimator for the random effect. Two estimation methods for multilevel model are compared: penalized quasi-likelihood and Gauss-Hermite quadrature. The performance measures for the prediction of the probability for a new cluster observation of the multilevel logistic model in comparison with the usual logistic model are examined through simulations and an application.

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Objective To investigate if a home environment test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression. Background Seventy-seven patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study at 10 clinics in Sweden and Norway; 40 of them were treated with levodopa-carbidopa intestinal gel (LCIG) and 37 patients were candidates for switching from oral PD treatment to LCIG. They utilized a mobile device test battery, consisting of self-assessments of symptoms and objective measures of motor function through a set of fine motor tests (tapping and spiral drawings), in their homes. Both the LCIG-naïve and LCIG-non-naïve patients used the test battery four times per day during week-long test periods. Methods Assessments The LCIG-naïve patients used the test battery at baseline (before LCIG), month 0 (first visit; at least 3 months after intraduodenal LCIG), and thereafter quarterly for the first year and biannually for the second and third years. The LCIG-non-naïve patients used the test battery from the first visit, i.e. month 0. Out of the 77 patients, only 65 utilized the test battery; 35 were LCIG-non-naïve and 30 LCIG-naïve. In 20 of the LCIG-naïve patients, assessments with the test battery were available during oral treatment and at least one test period after having started infusion treatment. Three LCIG-naïve patients did not use the test battery at baseline but had at least one test period of assessments thereafter. Hence, n=23 in the LCIG-naïve group. In total, symptom assessments in the full sample (including both patient groups) were collected during 379 test periods and 10079 test occasions. For 369 of these test periods, clinical assessments including UPDRS and PDQ-39 were performed in afternoons at the start of the test periods. The repeated measurements of the test battery were processed and summarized into scores representing patients’ symptom severities over a test period, using statistical methods. Six conceptual dimensions were defined; four subjectively-reported: ‘walking’, ‘satisfied’, ‘dyskinesia’, and ‘off’ and two objectively-measured: ‘tapping’ and ‘spiral’. In addition, an ‘overall test score’ (OTS) was defined to represent the global health condition of the patient during a test period. Statistical methods Change in the test battery scores over time, that is at baseline and follow-up test periods, was assessed with linear mixed-effects models with patient ID as a random effect and test period as a fixed effect of interest. The within-patient variability of OTS was assessed using intra-class correlation coefficient (ICC), for the two patient groups. Correlations between clinical rating scores and test battery scores were assessed using Spearman’s rank correlations (rho). Results In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. However, there were no significant changes in mean OTS scores of LCIG-non-naïve patients, except for worse mean OTS at month 36 (p<0.01, n=16). The mean scores of all subjectively-reported dimensions improved significantly throughout the course of the study, except ‘walking’ at month 36 (p=0.41, n=4). However, there were no significant differences in mean scores of objectively-measured dimensions between baseline and other test periods, except improved ‘tapping’ at month 6 and month 36, and ‘spiral’ at month 3 (p<0.05). The LCIG-naïve patients had a higher within-subject variability in their OTS scores (ICC=0.67) compared to LCIG-non-naïve patients (ICC=0.71). The OTS correlated adequately with total UPDRS (rho=0.59) and total PDQ-39 (rho=0.59). Conclusions In this 3-year follow-up study of advanced PD patients treated with LCIG we found that it is possible to monitor PD progression over time using a home environment test battery. The significant improvements in the mean OTS scores indicate that the test battery is able to measure functional improvement with LCIG sustained over at least 24 months.

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This thesis develops and evaluates statistical methods for different types of genetic analyses, including quantitative trait loci (QTL) analysis, genome-wide association study (GWAS), and genomic evaluation. The main contribution of the thesis is to provide novel insights in modeling genetic variance, especially via random effects models. In variance component QTL analysis, a full likelihood model accounting for uncertainty in the identity-by-descent (IBD) matrix was developed. It was found to be able to correctly adjust the bias in genetic variance component estimation and gain power in QTL mapping in terms of precision.  Double hierarchical generalized linear models, and a non-iterative simplified version, were implemented and applied to fit data of an entire genome. These whole genome models were shown to have good performance in both QTL mapping and genomic prediction. A re-analysis of a publicly available GWAS data set identified significant loci in Arabidopsis that control phenotypic variance instead of mean, which validated the idea of variance-controlling genes.  The works in the thesis are accompanied by R packages available online, including a general statistical tool for fitting random effects models (hglm), an efficient generalized ridge regression for high-dimensional data (bigRR), a double-layer mixed model for genomic data analysis (iQTL), a stochastic IBD matrix calculator (MCIBD), a computational interface for QTL mapping (qtl.outbred), and a GWAS analysis tool for mapping variance-controlling loci (vGWAS).

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OBJECTIVES: To develop a method for objective assessment of fine motor timing variability in Parkinson’s disease (PD) patients, using digital spiral data gathered by a touch screen device. BACKGROUND: A retrospective analysis was conducted on data from 105 subjects including65 patients with advanced PD (group A), 15 intermediate patients experiencing motor fluctuations (group I), 15 early stage patients (group S), and 10 healthy elderly subjects (HE) were examined. The subjects were asked to perform repeated upper limb motor tasks by tracing a pre-drawn Archimedes spiral as shown on the screen of the device. The spiral tracing test was performed using an ergonomic pen stylus, using dominant hand. The test was repeated three times per test occasion and the subjects were instructed to complete it within 10 seconds. Digital spiral data including stylus position (x-ycoordinates) and timestamps (milliseconds) were collected and used in subsequent analysis. The total number of observations with the test battery were as follows: Swedish group (n=10079), Italian I group (n=822), Italian S group (n = 811), and HE (n=299). METHODS: The raw spiral data were processed with three data processing methods. To quantify motor timing variability during spiral drawing tasks Approximate Entropy (APEN) method was applied on digitized spiral data. APEN is designed to capture the amount of irregularity or complexity in time series. APEN requires determination of two parameters, namely, the window size and similarity measure. In our work and after experimentation, window size was set to 4 and similarity measure to 0.2 (20% of the standard deviation of the time series). The final score obtained by APEN was normalized by total drawing completion time and used in subsequent analysis. The score generated by this method is hence on denoted APEN. In addition, two more methods were applied on digital spiral data and their scores were used in subsequent analysis. The first method was based on Digital Wavelet Transform and Principal Component Analysis and generated a score representing spiral drawing impairment. The score generated by this method is hence on denoted WAV. The second method was based on standard deviation of frequency filtered drawing velocity. The score generated by this method is hence on denoted SDDV. Linear mixed-effects (LME) models were used to evaluate mean differences of the spiral scores of the three methods across the four subject groups. Test-retest reliability of the three scores was assessed after taking mean of the three possible correlations (Spearman’s rank coefficients) between the three test trials. Internal consistency of the methods was assessed by calculating correlations between their scores. RESULTS: When comparing mean spiral scores between the four subject groups, the APEN scores were different between HE subjects and three patient groups (P=0.626 for S group with 9.9% mean value difference, P=0.089 for I group with 30.2%, and P=0.0019 for A group with 44.1%). However, there were no significant differences in mean scores of the other two methods, except for the WAV between the HE and A groups (P<0.001). WAV and SDDV were highly and significantly correlated to each other with a coefficient of 0.69. However, APEN was not correlated to neither WAV nor SDDV with coefficients of 0.11 and 0.12, respectively. Test-retest reliability coefficients of the three scores were as follows: APEN (0.9), WAV(0.83) and SD-DV (0.55). CONCLUSIONS: The results show that the digital spiral analysis-based objective APEN measure is able to significantly differentiate the healthy subjects from patients at advanced level. In contrast to the other two methods (WAV and SDDV) that are designed to quantify dyskinesias (over-medications), this method can be useful for characterizing Off symptoms in PD. The APEN was not correlated to none of the other two methods indicating that it measures a different construct of upper limb motor function in PD patients than WAV and SDDV. The APEN also had a better test-retest reliability indicating that it is more stable and consistent over time than WAV and SDDV.

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BACKGROUND: Misoprostol is established for the treatment of incomplete abortion but has not been systematically assessed when provided by midwives at district level in a low-resource setting. We investigated the effectiveness and safety of midwives diagnosing and treating incomplete abortion with misoprostol, compared with physicians. METHODS: We did a multicentre randomised controlled equivalence trial at district level at six facilities in Uganda. Eligibility criteria were women with signs of incomplete abortion. We randomly allocated women with first-trimester incomplete abortion to clinical assessment and treatment with misoprostol either by a physician or a midwife. The randomisation (1:1) was done in blocks of 12 and was stratified for study site. Primary outcome was complete abortion not needing surgical intervention within 14-28 days after initial treatment. The study was not masked. Analysis of the primary outcome was done on the per-protocol population with a generalised linear-mixed effects model. The predefined equivalence range was -4% to 4%. The trial was registered at ClinicalTrials.gov, number NCT01844024. FINDINGS: From April 30, 2013, to July 21, 2014, 1108 women were assessed for eligibility. 1010 women were randomly assigned to each group (506 to midwife group and 504 to physician group). 955 women (472 in the midwife group and 483 in the physician group) were included in the per-protocol analysis. 452 (95·8%) of women in the midwife group had complete abortion and 467 (96·7%) in the physician group. The model-based risk difference for midwife versus physician group was -0·8% (95% CI -2·9 to 1·4), falling within the predefined equivalence range (-4% to 4%). The overall proportion of women with incomplete abortion was 3·8% (36/955), similarly distributed between the two groups (4·2% [20/472] in the midwife group, 3·3% [16/483] in the physician group). No serious adverse events were recorded. INTERPRETATION: Diagnosis and treatment of incomplete abortion with misoprostol by midwives is equally safe and effective as when provided by physicians, in a low-resource setting. Scaling up midwives' involvement in treatment of incomplete abortion with misoprostol at district level would increase access to safe post-abortion care. FUNDING: The Swedish Research Council, Karolinska Institutet, and Dalarna University.

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OBJECTIVE: This study aimed to assess women´s acceptability of diagnosis and treatment of incomplete abortion with misoprostol by midwives, compared with physicians. METHODS: This was an analysis of secondary outcomes from a multi-centre randomized controlled equivalence trial at district level in Uganda. Women with first trimester incomplete abortion were randomly allocated to clinical assessment and treatment with misoprostol by a physician or a midwife. The randomisation (1:1) was done in blocks of 12 and stratified for health care facility. Acceptability was measured in expectations and satisfaction at a follow up visit 14-28 days following treatment. Analysis of women's overall acceptability was done using a generalized linear mixed-effects model with an equivalence range of -4% to 4%. The study was not masked. The trial is registered at ClinicalTrials.org, NCT 01844024. RESULTS: From April 2013 to June 2014, 1108 women were assessed for eligibility of which 1010 were randomized (506 to midwife and 504 to physician). 953 women were successfully followed up and included in the acceptability analysis. 95% (904) of the participants found the treatment satisfactory and overall acceptability was found to be equivalent between the two study groups. Treatment failure, not feeling calm and safe following treatment, experiencing severe abdominal pain or heavy bleeding following treatment, were significantly associated with non-satisfaction. No serious adverse events were recorded. CONCLUSIONS: Treatment of incomplete abortion with misoprostol by midwives and physician was highly, and equally, acceptable to women. TRIAL REGISTRATION: ClinicalTrials.gov NCT01844024.

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BACKGROUND: Annually, 2.8 million neonatal deaths occur worldwide, despite the fact that three-quarters of them could be prevented if available evidence-based interventions were used. Facilitation of community groups has been recognized as a promising method to translate knowledge into practice. In northern Vietnam, the Neonatal Health - Knowledge Into Practice trial evaluated facilitation of community groups (2008-2011) and succeeded in reducing the neonatal mortality rate (adjusted odds ratio, 0.51; 95 % confidence interval 0.30-0.89). The aim of this paper is to report on the process (implementation and mechanism of impact) of this intervention. METHODS: Process data were excerpted from diary information from meetings with facilitators and intervention groups, and from supervisor records of monthly meetings with facilitators. Data were analyzed using descriptive statistics. An evaluation including attributes and skills of facilitators (e.g., group management, communication, and commitment) was performed at the end of the intervention using a six-item instrument. Odds ratios were analyzed, adjusted for cluster randomization using general linear mixed models. RESULTS: To ensure eight active facilitators over 3 years, 11 Women's Union representatives were recruited and trained. Of the 44 intervention groups, composed of health staff and commune stakeholders, 43 completed their activities until the end of the study. In total, 95 % (n = 1508) of the intended monthly meetings with an intervention group and a facilitator were conducted. The overall attendance of intervention group members was 86 %. The groups identified 32 unique problems and implemented 39 unique actions. The identified problems targeted health issues concerning both women and neonates. Actions implemented were mainly communication activities. Communes supported by a group with a facilitator who was rated high on attributes and skills (n = 27) had lower odds of neonatal mortality (odds ratio, 0.37; 95 % confidence interval, 0.19-0.73) than control communes (n = 46). CONCLUSIONS: This evaluation identified several factors that might have influenced the outcomes of the trial: continuity of intervention groups' work, adequate attributes and skills of facilitators, and targeting problems along a continuum of care. Such factors are important to consider in scaling-up efforts.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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This paper proposes a methodology to achieve integrated planning and projects for secondary distribution circuits. The planning model is formulated as a mixed integer nonlinear programming problem (MINLP). In order to resolve this problem, a tabu search (TS) algorithm is used, with a neighborhood structure developed to explore the physical characteristics of specific geographies included in the planning and expansion of secondary networks, thus obtaining effective solutions as well as low operating costs and investments. The project stage of secondary circuits consists of calculating the mechanical efforts to determine the support structures of the primary and secondary distribution systems and determining the types of structures that should be used in the system according to topological and electrical parameters of the network and, therefore, accurately assessing the costs involved in the construction and/or reform of secondary systems. A constructive heuristic based on information of the electrical and topological conditions between the medium voltage and low voltage systems is used to connect the primary systems and secondary circuits. The results obtained from planning and design simulations of a real secondary system of electric energy distribution are presented.

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O objetivo deste trabalho foi estimar os ganhos genéticos de um teste de progênies de seringueira para a produção de borracha seca e, com base no maior tamanho efetivo populacional e maior ganho genético, obter os melhores indivíduos. Foram utilizadas 30 progênies de meios-irmãos, provenientes de sementes de polinização mista - alogamia e autogamia - de testes clonais no Estado de São Paulo. Utilizou-se o delineamento experimental de blocos ao acaso, com 30 tratamentos (progênies), 3 repetições e parcelas lineares de 10 plantas, em um espaçamento de 3x3 m, o que totalizou 900 plantas úteis. Aos três anos, o perímetro, a 50 cm do solo (PA50), e a produção de borracha seca (PBS) foram avaliadas por meio do teste precoce de produção Hamaker Morris-Mann (HMM). As variáveis foram analisadas pelo método de modelo linear misto, via procedimento REML/BLUP, em progênies com sistema reprodutivo misto e taxa de autofecundação de 22%. A identificação dos 20 melhores indivíduos quanto à PBS e ao PA50 proporcionou ganho genético de 67,96 e 16,48%, respectivamente, e um coeficiente de endogamia de aproximadamente 2,82%. O teste de progênies proporciona produção de sementes com melhor valor genético, grande variabilidade e baixa endogamia

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The aim of the work was to study the effect of milking fraction on electrical conductivity of milk (EC) to improve its use in dairy goat mastitis detection using automatic EC measurements during milking. The experiment was carried out on a group of 84 Murciano-Granadina goats (28 primiparous and 56 multiparous). Goats were in the fourth month of lactation. A linear mixed model was used to analyse the relationship between EC or somatic cell count (SCC) of gland milk and parity, mammary gland health status, analysed fraction (first 100 mL=F-1; machine milk=F-2; and stripping milk=F-3) and their first order interactions. Additionally, the mastitis detection characteristics (sensitivity, specificity, positive predictive value and negative predictive value) of SCC and EC were studied at different thresholds.All factors considered were significant for EC and SCC. EC decreased significantly as milking progressed (from F-1 to F-3) in both healthy and infected glands. EC was not significantly different between healthy and infected glands in F-1 and F-2 fractions, but EC of healthy glands (5.01 mS/cm) was significantly lower than in infected glands (5.03 mS/cm) at F-3.Mastitis detection characteristics of EC did not differ amongst studied fractions. The small significant difference of EC between healthy and infected glands obtained in F-3 fraction did not yield better sensitivity results compared to F-1 and F-2. The best EC mastitis detection characteristics were obtained at 5.20 mS/cm threshold (sensitivity of 70% and specificity of 50%). The best SCC mastitis detection characteristics were obtained at 300,000 cells/mL threshold and F-3 fraction (sensitivity of 85% and specificity of 65%).It was concluded that mastitis detection characteristics of EC were similar in the three milking fractions analysed, being slightly better for SCC in F-3 fraction. As shown in previous studies, there are no factors other than the mammary gland health status that affect milk EC and should be considered in the algorithms for mastitis detection to improve the results. (C) 2012 Elsevier B.V. All rights reserved.

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Objetivou-se com esse trabalho comparar estimativas de componentes de variâncias obtidas por meio de modelos lineares mistos Gaussianos e Robustos, via Amostrador de Gibbs, em dados simulados. Foram simulados 50 arquivos de dados com 1.000 animais cada um, distribuídos em cinco gerações, em dois níveis de efeito fixo e três valores fenotípicos distintos para uma característica hipotética, com diferentes níveis de contaminação. Exceto para os dados sem contaminação, quando os modelos foram iguais, o modelo Robusto apresentou melhores estimativas da variância residual. As estimativas de herdabilidade foram semelhantes em todos os modelos, mas as análises de regressão mostraram que os valores genéticos preditos com uso do modelo Robusto foram mais próximos dos valores genéticos verdadeiros. Esses resultados sugerem que o modelo linear normal contaminado oferece uma alternativa flexível para estimação robusta em melhoramento genético animal.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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It is often necessary to run response surface designs in blocks. In this paper the analysis of data from such experiments, using polynomial regression models, is discussed. The definition and estimation of pure error in blocked designs are considered. It is recommended that pure error is estimated by assuming additive block and treatment effects, as this is more consistent with designs without blocking. The recovery of inter-block information using REML analysis is discussed, although it is shown that it has very little impact if thc design is nearly orthogonally blocked. Finally prediction from blocked designs is considered and it is shown that prediction of many quantities of interest is much simpler than prediction of the response itself.