Exact Scalable Sensitivity Analysis for the Next Release Problem

The nature of the requirements analysis problem, based as it is on uncertain and often inaccurate estimates of costs and effort, makes sensitivity analysis important. Sensitivity analysis allows the decision maker to identify those requirements and budgets that are particularly sensitive to misestimation. However, finding scalable sensitivity analysis techniques is not easy because the underlying optimization problem is NP-hard. This article introduces an approach to sensitivity analysis based on exact optimization. We implemented this approach as a tool, OATSAC, which allowed us to experimentally evaluate the scalability and applicability of Requirements Sensitivity Analysis (RSA). Our results show that OATSAC scales sufficiently well for practical applications in Requirements Sensitivity Analysis. We also show how the sensitivity analysis can yield insights into difficult and otherwise obscure interactions between budgets, requirements costs, and estimate inaccuracies using a real-world case study

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever

Background Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT. Methods Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT. Results The incidence of NF among the groups was reduced (64%, 44%, and 24%; P2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05). Conclusions G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial

Do not do in COPD: consensus statement on overuse

Felipe Villar-Álvarez,1 Raúl Moreno-Zabaleta,2 Jose Joaquin Mira-Solves,3 Eduardo Calvo-Corbella,4 Salvador Díaz-Lobato,5 Fernando González-Torralba,6 Ascensión Hernando-Sanz,7 Sara Núñez-Palomo,8 Sergio Salgado-Aranda,9 Beatriz Simón-Rodríguez,10 Paz Vaquero-Lozano,11 Isabel María Navarro-Soler12On behalf of “Do not do in COPD” Working Group of the Madrid Society of Pulmonology and Thoracic Surgery (Neumomadrid)1Department of Pulmonology, IIS–Fundación Jiménez Díaz, CIBERES, UAM, 2Pulmonology, Inpatient and Noninvasive Mechanical Ventilation, Hospital Universitario Infanta Sofía, Madrid, 3Alicante-Sant Joan Health District, Alicante/Universidad Miguel Hernández Elche/REDISEC, 4Family and Community Medicine, CSU Pozuelo Estación, School of Medicine, UAM, 5Department of Pulmonology, Hospital Ramón y Cajal, Madrid, 6Pulmonology Section, Hospital Universitario del Tajo, Aranjuez, 7Department of Pulmonology, Hospital Universitario 12 de Octubre, 8C.S. Torrelaguna, 9Pulmonology Section, Hospital del Sureste, 10FisioRespiración-Respiratory Physiotherapy Unit, Escuela Universitaria Gimbernat Cantabria, 11S. Pulmonology, CEP Hnos. Sangro HGU Gregorio Marañón, Madrid, 12Calitè Research Group, Universidad Miguel Hernández de Elche, Elche, SpainBackground: To identify practices that do not add value, cause harm, or subject patients with chronic obstructive pulmonary disease (COPD) to a level of risk that outweighs possible benefits (overuse).Methods: A qualitative approach was applied. First, a multidisciplinary group of healthcare professionals used the Metaplan technique to draft and rank a list of overused procedures as well as self-care practices in patients with stable and exacerbated COPD. Second, in successive consensus-building rounds, description files were created for each “do not do” (DND) recommendation, consisting of a definition, description, quality of supporting evidence for the recommendation, and the indicator used to measure the degree of overuse. The consensus group comprised 6 pulmonologists, 2 general practitioners, 1 nurse, and 1 physiotherapist.Results: In total, 16 DND recommendations were made for patients with COPD: 6 for stable COPD, 6 for exacerbated COPD, and 4 concerning self-care.Conclusion: Overuse poses a risk for patients and jeopardizes care quality. These 16 DND recommendations for COPD will lower care risks and improve disease management, facilitate communication between physicians and patients, and bolster patient ability to provide self-care.Keywords: COPD, consensus, patient safety, quality assuranc