Performance of Gradient-Based Solutions versus Genetic Algorithms in the Correlation of Thermal Mathematical Models of Spacecrafts

The correlation of the thermal mathematical models (TMMs) of spacecrafts with the results of the thermal test is a demanding task in terms of time and effort. Theoretically, it can be automatized by means of optimization techniques, although this is a challenging task. Previous studies have shown the ability of genetic algorithms to perform this task in several cases, although some limitations have been detected. In addition, gradient-based methods, although also presenting some limitations, have provided good solutions in other technical fields. For this reason, the performance of genetic algorithms and gradient-based methods in the correlation of TMMs is discussed in this paper to compare the pros and cons of them. The case of study used in the comparison is a real space instrument flown on board the International Space Station

Radio interferometric observations of candidate water-maser-emitting planetary nebulae

We present Very Large Array (VLA) observations of H2O and OH masers, as well as radio continuum emission at 1.3 and 18 cm toward three sources previously cataloged as planetary nebulae (PNe) and in which single-dish detections of H2O masers have been reported: IRAS 17443-2949, IRAS 17580-3111, and IRAS 18061-2505. Our goal was to unambiguously confirm their nature as water-maser-emitting PNe, a class of objects of which only two bona-fide members were previously known. We detected and mapped H2O maser emission toward all three sources, while OH maser emission is detected in IRAS 17443-2949 and IRAS 17580-3111 as well as in other two objects within the observed fields: IRAS 17442-2942 (unknown nature) and IRAS 17579-3121 (also cataloged as a possible PN). We found radio continuum emission associated only with IRAS 18061-2505. Our results confirm IRAS 18061-2505 as the third known case of a PN associated with H2O maser emission. The three known water-maser-emitting PNe have clear bipolar morphologies, which suggests that water maser emission in these objects is related to non-spherical mass-loss episodes. We speculate that these bipolar PNe would have ``water-fountain'' Asymptotic Giant Branch (AGB) and post-AGB stars as their precursors. A note of caution is given for other objects that have been classified as OHPNe (objects with both OH maser and radio continuum emission, that could be extremely young PNe) based on single-dish observations, since interferometric data of both OH masers and continuum are necessary for a proper identification as members of this class.Comment: 33 pages, 10 figures. Accepted by The Astronomical Journa

Role of Human Organic Cation Transporter 1 (hOCT1) Polymorphisms in Lamivudine (3TC) Uptake and Drug-Drug Interactions

Lamivudine (3TC), a drug used in the treatment of HIV infection, needs to cross the plasma membrane to exert its therapeutic action. Human Organic cation transporter 1 (hOCT1), encoded by the SLC22A1 gene, is the transporter responsible for its uptake into target cells. As SLC22A1 is a highly polymorphic gene, the aim of this study was to determine how SNPs in the OCT1-encoding gene affected 3TC internalization and its interaction with other co-administered drugs. HEK293 cells stably transfected with either the wild type form or the polymorphic variants of hOCT1 were used to perform kinetic and drug-drug interaction studies. Protein co-immunoprecipitation was used to assess the impact of selected polymorphic cysteines on the oligomerization of the transporter. Results showed that 3TC transport efficiency was reduced in all polymorphic variants tested (R61C, C88R, S189L, M420del, and G465R). This was not caused by lack of oligomerization in case of variants located at the transporter extracellular loop (R61C and C88R). Drug-drug interaction measurements showed that co-administered drugs [abacavir (ABC), zidovudine (AZT), emtricitabine (FTC), tenofovir diproxil fumarate (TDF), efavirenz (EFV) and raltegravir (RAL)], differently inhibited 3TC uptake depending upon the polymorphic variant analyzed. These data highlight the need for accurate analysis of drug transporter polymorphic variants of clinical relevance, because polymorphisms can impact on substrate (3TC) translocation but even more importantly they can differentially affect drug-drug interactions at the transporter level

An expert patient program to improve the empowerment and quality of life of people with multiple sclerosis: protocol for a multicenter pre-post intervention study

Health education; Multiple sclerosis; Quality of lifeEducación para la salud; Esclerosis múltiple; Calidad de vidaEducació sanitaria; Esclerosi múltiple; Qualitat de vidaIntroduction: Multiple sclerosis (MS) causes a progressive disability, which substantially impacts the quality of life (QoL). Health interventions that meet the needs and demands of people with MS are essential to minimize QoL impairment. Expert patient programs (EPPs) facilitate health-related empowerment through peer learning. Based on a previous focus group study, we designed an EPP for MS coordinated by nursing professionals for implementation in the different MS reference units of Catalonia (Southwestern Europe). This study aims to evaluate the effects on quality of life, disease-related knowledge, and self-management related to the health process of the participants of the Expert Patient Program Catalonia™ for people with multiple sclerosis (EPPC-MS). Methods: Pre-post intervention multicenter clinical study involving 12 groups of 12 participants: six groups including relapsing and six groups including progressive MS patients, with 144 participants from 7 MS reference units from all over Catalonia, organized in six teams. The intervention will consist of nine telematic learning peer-led sessions (one weekly session). The expert patient (EP) leading the sessions will be an individual with MS with disease-related knowledge, who will be further trained by nurses to lead the sessions. Study variables will be measured before and immediately after the intervention and 6 and 12 months after the end of the sessions and will include: QoL, emotional impact, activation of the person, MS-related knowledge, fatigue, habits and lifestyles, health services use, and program-related experience. Baseline characteristics considered will be sociodemographic data, date of MS diagnosis and type, family history, and treatment characteristics. Variables related to disease follow-up will be new relapses and characteristics and changes in the ongoing treatment. The number of sessions attended will also be collected. Study variables will be analyzed using a pre-post comparison. Discussion: Peer-led learning programs led by EP help empower people with chronic conditions and offer them tools to improve their autonomy and QoL. This study’s intervention will be performed remotely, offering advantages both for people with chronic conditions and the healthcare system regarding the facilitation of family and work conciliation, saving time, simplifying attendance to meetings, lowering costs, and using fewer material resources.This study was promoted by the MS unit at Vall d’Hebron Hospital Campus and had no external sponsor. The PhD candidate/first author was supported through the Strategic Plan for Research and Innovation in Health 2016–2020 (PERIS) (ref. BDNS 542793) funded by the Health Department of Catalonia. This study had been partially funded by the Official College of Nurses of Barcelona (www.coib.cat) as part of the Nurse Research Projects Grants (PRN-475/2021). None of the funders were involved in the design of the study, manuscript writing or data collection, and will not be involved in data analysis or interpretation and manuscript writing in the future. The only funders’ requirement is that any publications associate with this study must be open access and deposited in an institutional repository

Prognostic utility of serum free light chain ratios and heavy-light chain ratios in multiple myeloma in three PETHEMA/GEM phase III clinical trials

We investigated the prognostic impact and clinical utility of serum free light chains (sFLC) and serum heavy-light chains (sHLC) in patients with multiple myeloma treated according to the GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65 PETHEMA/GEM phase III clinical trials. Serum samples collected at diagnosis were retrospectively analyzed for sFLC (n = 623) and sHLC (n = 183). After induction or autologous transplantation, 309 and 89 samples respectively were available for sFLC and sHLC assays. At diagnosis, a highly abnormal (HA) sFLC ratio (sFLCr) (32) was not associated with higher risk of progression. After therapy, persistence of involved-sFLC levels >100 mg/L implied worse survival (overall survival [OS], P = 0.03; progression-free survival [PFS], P = 0.007). Among patients that achieved a complete response, sFLCr normalization did not necessarily indicate a higher quality response. We conducted sHLC investigations for IgG and IgA MM. Absolute sHLC values were correlated with monoclonal protein levels measured with serum protein electrophoresis. At diagnosis, HA-sHLCrs (73) showed a higher risk of progression (P = 0.006). Additionally, involved-sHLC levels >5 g/L after treatment were associated with shorter survival (OS, P = 0.001; PFS, P = 0.018). The HA-sHLCr could have prognostic value at diagnosis; absolute values of involved-sFLC >100 mg/L and involved-sHLC >5 g/L could have prognostic value after treatment

Effective Phone Calls

“Effective Phone Calls” is a practical and accessible course specifically designed to develop students` essential communication and language skills. It is divided into six units, which contain face-to-face with teacher and self-study materials. The course aims to develop both competence and confi-dence in a variety of situations, so that by the end of the period of study students will have acquired the necessary skills to handle almost any kind of call in business setting

Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma

PURPOSE: Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG). PATIENTS AND METHODS: In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1, 100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10-6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial. RESULTS: Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%. CONCLUSION: The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM