An exact approach for the reliable fixed-charge location problem with capacity constraints

Introducing capacities in the reliable fixed charge location problem is a complex task since successive failures might yield in high facility overloads. Ideally, the goal consists in minimizing the total cost while keeping the expected facility overloads under a given threshold. Several heuristic approaches have been proposed in the literature for dealing with this goal. In this paper, we present the first exact approach for this problem, which is based on a cutting planes algorithm. Computational results illustrate its good performancePostprint (published version

Introducing capacitaties in the location of unreliable facilities

The goal of this paper is to introduce facility capacities into the Reliability Fixed-Charge Location Problem in a sensible way. To this end, we develop and compare different models, which represent a tradeoff between the extreme models currently available in the literature, where a priori assignments are either fixed, or can be fully modified after failures occur. In a series of computational experiments we analyze the obtained solutions and study the price of introducing capacity constraints according to the alternative models both, in terms of computational burden and of solution cost.Peer ReviewedPostprint (author's final draft

Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases : multicentre study of 80 patients

Objectives To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID). Methods Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year. Results We studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1), Conclusions CZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs

Problemas de localización de instalaciones no fiables

The aim of facility location problems consists on deciding where to optimally locate several plants or facilities (like industries, warehouses, schools, hospitals, distribution centers, datawarehouse, etc.) as well as how to optimally assign the clients to these facilities satisfying their demand. These decisions are usually determined considering the opening costs, and the costs of serving the clients. In the literature, it is frequently assumed that the open facilities are always availaible. Nevertheles, in practice some facilities can interrupt their service and become unavailaible. A lot of location problems of the most recent literature include the failing distribution of the plants in their models, and this type of problems are known like reliability facility location problems. The three contributions collected in the present dissertation are referred to reliability facility location problems. The objective of this dissertation is to analyze the properties of the so called Reliability Fixed-Charge Location Problem. Paper 1.- In this first paper, we discuss the previously known formulation of the Reliability Fixed-Charge Location Problem, in which the number of open facilities has to be decided and depends on the opening costs and it is assumed that some of the facilities, called failable, may fail with a given probability, which is identical for all of them. We reformulate the original mathematical programming model as a set packing problem and we study some polyhedral properties of this type of problems. Then, conditions for optimal solutions are introduced. We propose an improved compact formulation for the problem and we check the performance through an extensive computational study. Paper 2.- In this paper, we analyze which allocation variables in the Reliability Fixed-Charge Location Problem formulation can be linearized so that the optimal value match the optimal value of the binary problem.We prove that we can relax the integrality of all the allocation variables associated to non-failable facilities or all the allocation variables associated to failable facilities, but not both simultaneously. We also demonstrate that we can relax the integrality of all the allocation variables whenever a family of valid inequalities is added to the set of constraints or whenever the parameters of the problem satisfy certain conditions. Finally, on solving the instances in a data set, we discuss which integrality relaxation or which modification of the problem performs better in terms of resolution time, and we illustrate that to inappropriately relax the integrality of the allocation variables can incur in a high difference at the objective value. Paper 3.- In the last paper we propose and discuss different models to include capacity constraints into the Reliability Fixed-Charge Location Problem. In all cases, the proposed models represent a trade off between the extreme models that can be found in the literature, where a priori assignments are either fixed, or can be fully modified at each scenario. By several computational experiments, we analyze the obtained solutions of introducing capacity constraints according to the different proposed models, in terms of computational burden and in terms of solution cost.La finalidad de los problemas de localizaci´on de plantas consiste en decidir d´onde ubicar de forma ´optima plantas o instalaciones (industrias, almacenes, escuelas, hospitales, centros de distribuci´on, centros de datos, etc.) as´ı como la asignaci´on ´optima de los clientes a estas instalaciones de forma que se satisfaga su demanda. Estas decisiones se toman habitualmente considerando los costes relativos al establecimiento de las plantas o costes de apertura, as´ı como los costes relativos al servicio de la demanda o costes de transporte. En la literatura cl´asica frecuentemente se asume que las plantas abiertas siempre est´an disponibles, sin embargo, en la pr´actica, las plantas pueden fallar interrumpiendo su prestaci´on de servicio y no estar disponibles. Problemas de localizaci´on de la literatura m´as recientes consideran en sus modelos distribuciones de probabilidad para el fallo de las plantas, es decir, la fiabilidad de las plantas. Las tres contribuciones recogidas en la presente tesis se refieren a este tipo de modelos. El objetivo de esta tesis es analizar propiedades del problema de localizaci´on de instalaciones no fiables, en ingl´es Reliability Fixed-Charge Location Problem. Esta tesis se estructura en torno a tres art´ıculos: Art´ıculo 1.- En esta primera aportaci´on los autores reformulan el problema de localizaci´on de instalaciones no fiables desde el enfoque de un problema de empaquetamiento de conjuntos, estudiando determinadas propiedades poli´edricas referidas al pol´ıtopo que conforma la regi´on factible e identificando todas las facetas asociadas a cliques. Consecuentemente, se estudian ciertas condiciones para las soluciones ´optimas. Se propone adem´as una formulaci´on compacta, probando su eficacia mediante un amplio estudio computacional. Art´ıculo 2.- En este segundo trabajo se estudia bajo qu´e condiciones podr´ıan relajarse el car´acter entero de todas las variables de asignaci´on, probando que puede ser relajado el car´acter entero para todas las variables de asignaci´on relativas a las instalaciones completamente fiables; o para las variables de asignaci´on relativas a las plantas cuyo servicio puede presentar interrupciones; mas no para ambas simult´aneamente. Finalmente, se propone una familia de desigualdades v´alidas cuya introducci´on en el modelo permite la relajaci´on del car´acter entero de todas las variables de asignaci´on.Art´ıculo 3.- En el tercer trabajo los autores proponen y estudian diferentes modelos que incluyen restricciones de capacidad en el modelo de localizaci´on de instalaciones no fiables. Para ello a˜naden a la formulaci´on ya existente diversas restricciones de capacidad encaminadas a acotar la sobrecarga de demanda con la que se enfrentan algunas instalaciones en caso de producirse fallos en las plantas. Adem´as, mediante una serie de pruebas computacionales se analizan las soluciones obtenidas y la bondad de los diferentes m´etodos empleados

The Domatic Partition Problem in Separable Graphs

The domatic partition problem consists of partitioning a given graph into a maximum number of disjoint dominating sets. This problem is related with the domatic number problem, which consists of quantifying this maximum number of disjoint dominating sets. Both problems were proved to be NP-complete. In this paper, we present a decomposition algorithm for finding a domatic partition on separable graphs, that is, on graphs with blocks, and as a consequence, its domatic number, highly reducing the computational complexity. Computational results illustrate the benefits of the block decomposition algorithm

The Domatic Partition Problem in Separable Graphs

The domatic partition problem consists of partitioning a given graph into a maximum number of disjoint dominating sets. This problem is related with the domatic number problem, which consists of quantifying this maximum number of disjoint dominating sets. Both problems were proved to be NP-complete. In this paper, we present a decomposition algorithm for finding a domatic partition on separable graphs, that is, on graphs with blocks, and as a consequence, its domatic number, highly reducing the computational complexity. Computational results illustrate the benefits of the block decomposition algorithm

Introducing capacitaties in the location of unreliable facilities

The goal of this paper is to introduce facility capacities into the Reliability Fixed-Charge Location Problem in a sensible way. To this end, we develop and compare different models, which represent a tradeoff between the extreme models currently available in the literature, where a priori assignments are either fixed, or can be fully modified after failures occur. In a series of computational experiments we analyze the obtained solutions and study the price of introducing capacity constraints according to the alternative models both, in terms of computational burden and of solution cost.Peer Reviewe

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (&gt;59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P &lt;.001). Overall motor and cognitive performance (P &lt;.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P &lt;.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P &lt;.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P &lt;.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients