Genetic algorithms for the scheduling of multiproduct batch plants within uncertain environment

This study addresses the problem of batch plant scheduling. In addition uncertainty on product demands is considered through probabilistic-based methods. In the resulting two-stage stochastic programming problem, the objective is to maximize an Expected Profit Value (EPV) while respecting a constraint forcing the makespan to be lower than a time horizon. A Genetic Algorithm (GA) is proposed for the solution of a multiproduct example. The variable encoding requires special attention. Computational tests are first carried out with a deterministic model to validate the GA efficiency. Then, different runs with different scenario sets highlight the existence of various solution classes, characterized by specific numbers of batches manufactured for each product. Further analysis finally enables to discuss if each schedule is really the best-fitted to the scenario set for which it has been determined

Tecnología y poder. : Un análisis foucaultiano de los discursos acerca de la monitorización electrónica

Nuestro trabajo pretende mostrar, por un lado, la importancia de la influencia FOUCAULTiana en los estudios sobre ciencia y tecnología y, por otro, mostrar de qué manera puede utilizarse el pensamiento de FOUCAULT para un estudio de las relaciones entre ciencia, tecnología y sociedad que tenga en cuenta los efectos de poder Para ilustrar la relevancia de estas herramientas analizamos la emergencia de una innovación concreta: la monitorización electrónica en el ámbito penitenciario. Pretendemos cartografiar las discontinuidades, las dispersiones del discurso, que sostienen las prácticas que hacen irrumpir y desarrollarse las diferentes materializaciones del dispositivo electrónico de control penitenciario. Al situar el análisis en el marco de la pregunta por las tecnologías de poder, más que analizar simplemente las ideologías y saberes que legitiman la monitorización electrónica, o sus capacidades técnicas, queremos reseguir el conjunto de discursos, retóricas, vocabularios, técnicas y procedimientos por los cuales el saber se entrelaza, da forma y se inscribe en el ejercicio del poder. Así mostraremos cómo la tecnología disciplinaria, una de las tecnologías de poder que FOUCAULT mejor describió para explicar nuestras sociedades, se articula, alimenta o se contradice con otras lógicas emergentes dibujando nuevas formas de regulación y control socialThe article aims to show the importance of FOUCAULT within social studies of science and technology. It also illustrates how a Foucauldian analysis can be useful for studies of science, technology and society focused on power effects. To accomplish these objectives we analyze the emergence of a specific techno-scientific innovation: the electronic monitoring of offenders. We map the discontinuities and discourse dispersions linked to those practices that constitute different materializations of this electronic device. Because we start from questions concerning power technologies, rather than simply analyzing the ideologies and knowledges that legitimate electronic monitoring and its technical reliability, we attend to the assemblage of discourses, rhetorics, vocabularies, techniques and procedures by which knowledge is intertwined and joins with the exercise of power. In this way, we show how one of FOUCAULT's technologies of power-disciplinary technology-is articulated, nourished and contradicted by other emergent logics drawing on new forms of regulation and social contro

Brentuximab-Induced Peripheral Neurotoxicity: A Multidisciplinary Approach to Manage an Emerging Challenge in Hodgkin Lymphoma Therapy

Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate approved to treat classical Hodgkin lymphoma (HL). BV-induced peripheral neurotoxicity (BVIN) is one of the greatest concerns for haematologists treating HL for several reasons. First, BVIN is highly frequent. Most patients receiving BV will experience some degree of BVIN, resulting in the primary reason for dose modification or discontinuation of HL therapy. Second, BV produces sensory, motor, and/or autonomic peripheral nerve dysfunction, which can present as severe, disabling forms of BVIN-predominantly motor-in some patients. Third, although largely reversible, BVIN may persist months or years after treatment and thereby become a major issue in HL survivorship. BVIN may, therefore, negatively affect the quality of life and work-life of often young patients with HL, in whom long-term survival is expected. Currently, the only strategy for BVIN includes dose adjustments and treatment discontinuation; however, this could interfere with LH therapy efficacy. In this setting, early recognition and adequate management of BVIN are critical in improving clinical outcomes. Careful neurologic monitoring may allow accurate diagnoses and gradation of ongoing forms of BVIN presentation. This review analysed current, available data on epidemiology, pathophysiology, patient- and treatment-related risk factors, clinical and neurophysiologic phenotypes, and management in patients with HL. Furthermore, this review specifically addresses limitations posed by BVIN assessments in clinical practice and provides skills and tools to improve neurologic assessments in these patients. Integrating this neurotoxic drug in clinical practice requires a multidisciplinary approach to avoid or minimise neurotoxicity burden in survivors of HL

La desinstitucionalització i la crisi de les institucions

Parlar d'institucions s'ha convertit en parlar de la seva crisi. Amb l'assentament de la societat postindustrial sembla que s'han accentuat les dificultats de legitimació d'unes institucions creades per mantenir un tipus de formació social que esta en procés de desaparició. De fet, es pot dir que la crisi de les institucions no és més que un aspecte d'una altra de global que podríem anomenar crisi del projecte modern.Hablar de instituciones se ha convertido en hablar de crisis de las instituciones. En este sentido, la noción de desinstitucionalización ocupa un lugar relevante en la reflexión institucional. Por este motivo, en este artículo se lleva a cabo una revisión del concepto de institución v de las principales críticas que ha recibido como paso previo al análisis más detallado del fenómeno desinstitucionalizador en la práctica psiquiátrica. Tal análisis lleva a la elaboración de una propuesta alternativa que cuestiona la pertinencia de seguir hablando de instituciones, así como de procesos desinstitucionalizadores. Concretamente, se plantea que las especiales características de algunas prácticas psiquiátricas contemporáneas se ajustan mejor a la noción de ex-titución tomada de la obra de SerresSpeaking of the institutions implies nowadays speaking of the crisis of institutions. In that sense, the concept of disinstitutionalization fills a relevant role in the institutional reflection. For this reason, this article carries out a review of the concept of institution and the main criticisms that it has received as a previous step to a more detailed examination of the disinstitutionalizing phenomenon, in the framework of psychiatric experience. Such an examination leads to the making of an alternative proposal which questions the pertinence of keeping speaking of both institutions and disinstutionalizing processes. It is specifically argued that the special features of some contemporary psychiatric methods comply better with the concept of ex-titution, extracted from the Serres' work

A conserved function of Human DLC3 and Drosophila Cv-c in testis development

The identification of genes affecting gonad development is essential to understand the mechanisms causing Variations/Differences in Sex Development (DSD). Recently, a DLC3 mutation was associated with male gonadal dysgenesis in 46,XY DSD patients. We have studied the requirement of Cv-c, the Drosophila ortholog of DLC3, in Drosophila gonad development, as well as the functional capacity of DLC3 human variants to rescue cv-c gonad defects. We show that Cv-c is required to maintain testis integrity during fly development. We find that Cv-c and human DLC3 can perform the same function in fly embryos, as flies carrying wild type but not patient DLC3 variations can rescue gonadal dysgenesis, suggesting functional conservation. We also demonstrate that the StART domain mediates Cv-c's function in the male gonad independently from the GAP domain's activity. This work demonstrates a role for DLC3/Cv-c in male gonadogenesis and highlights a novel StART domain mediated function required to organize the gonadal mesoderm and maintain its interaction with the germ cells during testis development.This work was supported by María de Maeztu Unit excellence grants MDM-2016-0687 and CEX2020-001088 M and a Ministerio de Ciencia e Innovación grant PID2019-104656GB-I00 cofunded by the European Regional Development Fund (FEDER) to JC-GH. SV acknowledges support from the Swiss National Science Foundation (PP00P3_194807). This work was also supported by grants from the Swiss National Supercomputing Centre under project ID s1132 and has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 803952). AL-B acknowledges support from the Swiss National Science Foundation’s Grant 320030-184807. LL acknowledges support from the Swiss National Science Foundation (grant number SCOPES IZ73Z0_152347/1) and National Academy of Sciences of Ukraine, project 'Molecular-Genetic Mechanisms of Human Disorders of Sexual Development' [0121U110054]: With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (referencia del instituto). Por ejemplo: With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2020-001088)

Pyrosequencing versus methylation-specific PCR for assessment of MGMT methylation in tumor and blood samples of glioblastoma patients

Circulating biomarkers in blood may provide an interesting alternative to risky tissue biopsies in the diagnosis and follow-up of glioblastoma patients. We have assessed MGMT methylation status in blood and tissue samples from unresected glioblastoma patients who had been included in the randomized GENOM-009 trial. Paired blood and tissue samples were assessed by methylation-specific PCR (MSP) and pyrosequencing (PYR). After establishing the minimum PYR cut-off that could yield a significant difference in overall survival, we assessed the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the analyses. Methylation could be detected in cfDNA by both MSP and PYR but with low concordance with results in tissue. Sensitivity was low for both methods (31% and 38%, respectively), while specificity was higher for MSP in blood than for PYR in plasma (96% vs 76%) and NPV was similar (56 vs 57%). Concordance of results in tissue by MSP and PYR was 84.3% (P < 0.001) and correlated with outcome. We conclude that detection of cfDNA in the blood of glioblastoma patients can be an alternative when tumor tissue is not available but methods for the detection of cfDNA in blood must improve before it can replace analysis in tumor tissue

Sex differences in endocannabinoids during 3 years of Mediterranean diet intervention: association with insulin resistance and weight loss in a population with metabolic syndrome

Background: Excess circulating endocannabinoids (eCBs) and imbalanced N-acylethanolamines (NAEs) related eCBs abundance could influence dietary weight loss success. We aimed to examine sex differences in the impact of a 3-years Mediterranean diet (MedDiet) intervention on circulating eCBs, NAEs and their precursor fatty acids, and to analyze the interplay between changes in eCBs or NAEs ratios, insulin resistance and the achievement of clinically meaningful weight reductions. Methods: Prospective cohort study in a subsample of N = 105 participants (54.3% women; 65.6 ± 4.6 years) with overweight or obesity and metabolic syndrome that underwent a 3-years MedDiet intervention (PREDIMED-Plus study). Plasma eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), fatty acids, diet, glycemic homeostasis (including the assessment of insulin resistance-HOMA-IR), and cardiovascular risk markers were monitored (at 0-6-12-36 months). Results: Mediterranean diet adherence increased in both sexes and remained high during the 3 years of follow-up. Reductions in body weight, glycemic and cardiovascular parameters were larger in men than in women. Women presented higher concentrations of NAEs than men throughout the study. In both sexes, AEA and other NAEs (including OEA, and PEA) decreased after 6 months (for AEA: -4.9%), whereas the ratio OEA/AEA increased after 1 year (+5.8%). Changes in 2-AG (-3.9%) and the ratio OEA/PEA (+8.2%) persisted over the 3 years of follow-up. In women, 6-months changes in AEA (OR = 0.65) and the ratio OEA/AEA (OR = 3.28) were associated with the achievement of 8% weight reductions and correlated with HOMA-IR changes (r = 0.29 and r = -0.34). In men, OEA/PEA changes were associated with 8% weight reductions (OR = 2.62) and correlated with HOMA-IR changes (r = -0.32). Conclusion: A 3-years MedDiet intervention modulated plasma concentrations of eCBs and NAEs. Changes in AEA and in the relative abundance of NAEs were associated with clinically meaningful weight reductions. However, marked sex differences were identified in eCBs and NAEs, as well as in the efficacy of the intervention in terms of glycemic and cardiovascular parameters, which could be related to post-menopause alterations in glucose metabolism. These findings support a sex-balanced research strategy for a better understanding of the mechanisms underlying the regulation of body weight loss

Current Incidence and risk factors of fecal incontinence after acute stroke affecting functionally independent people

Background: Previously published retrospective series show a high prevalence of fecal incontinence (FI) in stroke patients. We aimed to analyze in a prospective series the current incidence of FI in acute stroke in functionally independent patients and its evolution over time and the patient characteristics associated with the appearance of FI in acute stroke. Methods: We included consecutive patients with acute stroke admitted in our stroke unit who fulfilled the following inclusion criteria: a first episode of stroke, aged >18 years, with no previous functional dependency [modified Rankin Scale (mRS) = 2] and without previous known FI. FI was assessed by a multidisciplinary trained team using dedicated questionnaires at 72 ± 24 h (acute phase) and at 90 ± 15 days (chronic phase). Demographic, medical history, clinical and stroke features, mortality, and mRS at 7 days were collected. Results: Three hundred fifty-nine (48.3%) of 749 patients (mean age 65.9 ± 10, 64% male, 84.1% ischemic) fulfilled the inclusion criteria and were prospectively included during a 20-month period. FI was identified in 23 patients (6.4%) at 72 ± 24 h and in 7 (1.9%) at 90 days ± 15 days after stroke onset. FI was more frequent in hemorrhagic strokes (18 vs. 5%, p 0.007) and in more severe strokes [median National Institute of Health Stroke Scale (NIHSS) 18 (14–22) vs. 5 (3–13), p < 0.0001]. No differences were found regarding age, sex, vascular risk factors, or other comorbidities, or affected hemisphere. Patients with NIHSS =12 (AUC 0.81, 95% CI 0.71 to 0.89) had a 17-fold increase for the risk of FI (OR 16.9, IC 95% 4.7–60.1) adjusted for covariates.Peer ReviewedPostprint (published version

SMART-QUAL: a dashboard for quality measurement in higher education institutions

Purpose – The paper aims to define a dashboard of indicators to assess the quality performance of higher education institutions (HEI). The instrument is termed SMART-QUAL. Design/methodology/approach –Two sources were used in order to explore potential indicators. In the first step, information disclosed in official websites or institutional documentation of 36 selected HEIs was analyzed. This first step also included in depth structured high managers’ interviews. A total of 223 indicators emerged. In a second step, recent specialized literature was revised searching for indicators, capturing additional 302 indicators. Findings – Each one of the 525 total indicators was classified according to some attributes and distributed into 94 intermediate groups. These groups feed a debugging, prioritization and selection process, which ended up in the SMART-QUAL instrument: a set of 56 key performance indicators, which are grouped in 15 standards, and, in turn, classified into the 3 HEI missions. A basic model and an extended model are also proposed. Originality/value – The paper provides a useful measure of quality performance of HEIs, showing a holistic view to monitor HEI quality from three fundamental missions. This instrument might assist HEI managers for both assessing and benchmarking purposes. The paper ends with recommendations for university managers and public administration authorities

Bicyclic enol cyclocarbamates inhibit penicillin-binding proteins

Natural products form attractive leads for the development of chemical probes and drugs. The antibacterial lipopeptide Brabantamide A contains an unusual enol cyclocarbamate and we used this scaffold as inspiration for the synthesis of a panel of enol cyclocarbamate containing compounds. By equipping the scaffold with different groups, we identified structural features that are essential for antibacterial activity. Some of the derivatives block incorporation of hydroxycoumarin carboxylic acid-amino d-alanine into the newly synthesized peptidoglycan. Activity-based protein-profiling experiments revealed that the enol carbamates inhibit a specific subset of penicillin-binding proteins in B. subtilis and S. pneumoniae