Effect of strain and magnetic field on the critical current and electric resistance of the joints between HTS coated conductors

Engineering of devices and systems such as magnets, fault current limiters or cables, based on High Temperature Superconducting wires requires a deep characterization of the possible degradation of their properties by handling at room temperature as well as during the service life thus establishing the limits for building up functional devices and systems. In the present work we report our study regarding the mechanical behavior of spliced joints between commercial HTS coated conductors based on YBCO at room temperature and service temperature, 77 K. Tensile tests under axial stress and the evolution of the critical current and the electric resistance of the joints have been measured. The complete strain contour for the tape and the joint has been obtained by using Digital Image Correlation. Also, tensile tests under external magnetic field have been performed and the effect of the applied field on the critical current and the electric resistance of the joints has been studied. Finally, a preliminary numerical study by means of Finite Element Method (FEM) of the mechanical behavior of the joints between commercial HTS is presented

Predictive model to identify multiple failure to biological therapy in patients with rheumatoid arthritis

Despite advances in the treatment of rheumatoid arthritis (RA) and the wide range of therapies available, there is a percentage of patients whose treatment presents a challenge for clinicians due to lack of response to multiple biologic and target-specific disease-modifying antirheumatic drugs (b/tsDMARDs).To develop and validate an algorithm to predict multiple failure to biological therapy in patients with RA.Observational retrospective study involving subjects from a cohort of patients with RA receiving b/tsDMARDs.Based on the number of prior failures to b/tsDMARDs, patients were classified as either multi-refractory (MR) or non-refractory (NR). Patient characteristics were considered in the statistical analysis to design the predictive model, selecting those variables with a predictive capability. A decision algorithm known as 'classification and regression tree' (CART) was developed to create a prediction model of multi-drug resistance. Performance of the prediction algorithm was evaluated in an external independent cohort using area under the curve (AUC).A total of 136 patients were included: 51 MR and 85 NR. The CART model was able to predict multiple failures to b/tsDMARDs using disease activity score-28 (DAS-28) values at 6 months after the start time of the initial b/tsDMARD, as well as DAS-28 improvement in the first 6 months and baseline DAS-28. The CART model showed a capability to correctly classify 94.1% NR and 87.5% MR patients with a sensitivity = 0.88, a specificity = 0.94, and an AUC = 0.89 (95% CI: 0.74-1.00). In the external validation cohort, 35 MR and 47 NR patients were included. The AUC value for the CART model in this cohort was 0.82 (95% CI: 0.73-0.9).Our model correctly classified NR and MR patients based on simple measurements available in routine clinical practice, which provides the possibility to characterize and individualize patient treatments during early stages.© The Author(s), 2022

HIV-associated neurocognitive disorders.

Currently, neuropsychological impairment among HIV+ patients on antiretroviral therapy leads to a reduction in the quality of life and it is an important challenge due to the high prevalence of HIV-associated neurocognitive disorders and its concomitant consequences in relation to morbidity and mortality- including those HIV+ patients with adequate immunological and virological status. The fact that the virus is established in CNS in the early stages and its persistence within the CNS can help us to understand HIV-related brain injury even when highly active antiretroviral therapy is effective. The rising interest in HIV associated neurocognitive disorders has let to development new diagnostic tools, improvement of the neuropsychological tests, and the use of new biomarkers and new neuroimaging techniques that can help the diagnosis. Standardization and homogenization of neurocognitive tests as well as normalizing and simplification of easily accessible tools that can identify patients with increased risk of cognitive impairment represent an urgent requirement. Future efforts should also focus on diagnostic keys and searching for useful strategies in order to decrease HIV neurotoxicity within the CNS

Is the New Mayo Clinic Quadratic Equation Useful for the Estimation of Glomerular Filtration Rate in Type 2 Diabetic Patients?

OBJECTIVE—To test the Mayo Clinic Quadratic (MCQ) equation against isotopic glomerular filtration rate, compared with the Modification of Diet in Renal Disease (MDRD) and the Cockcroft-Gault formulas, in type 2 diabetes

Longitudinal analysis of blood DNA methylation identifies mechanisms of response to tumor necrosis factor inhibitor therapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, immune-mediated inflammatory disease of the joints that has been associated with variation in the peripheral blood methylome. In this study, we aim to identify epigenetic variation that is associated with the response to tumor necrosis factor inhibitor (TNFi) therapy.Peripheral blood genome-wide DNA methylation profiles were analyzed in a discovery cohort of 62 RA patients at baseline and at week 12 of TNFi therapy. DNA methylation of individual CpG sites and enrichment of biological pathways were evaluated for their association with drug response. Using a novel cell deconvolution approach, altered DNA methylation associated with TNFi response was also tested in the six main immune cell types in blood. Validation of the results was performed in an independent longitudinal cohort of 60 RA patients.Treatment with TNFi was associated with significant longitudinal peripheral blood methylation changes in biological pathways related to RA (FDR<0.05). 139 biological functions were modified by therapy, with methylation levels changing systematically towards a signature similar to that of healthy controls. Differences in the methylation profile of T cell activation and differentiation, GTPase-mediated signaling, and actin filament organization pathways were associated with the clinical response to therapy. Cell type deconvolution analysis identified CpG sites in CD4+T, NK, neutrophils and monocytes that were significantly associated with the response to TNFi.Our results show that treatment with TNFi restores homeostatic blood methylation in RA. The clinical response to TNFi is associated to methylation variation in specific biological pathways, and it involves cells from both the innate and adaptive immune systems.The Instituto de Salud Carlos III.Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved

Leflunomide in the treatment of patients with early rheumatoid arthritis—results of a prospective non-interventional study

Leflunomide is effective and well tolerated in the treatment of rheumatoid arthritis (RA), however, data on its use in early RA are scarce. This study seeks to evaluate effectiveness and safety of leflunomide in the treatment of early RA in daily practice. This prospective, open-label, non-interventional, multi-center study was carried out over 24 weeks including adults with early RA (≤1 year since diagnosis). Leflunomide treatment was according to label instructions. Three hundred thirty-four patients were included. Disease activity score in 28 joints (DAS28) response (reduction in DAS28 of >1.2 or reduction of >0.6 and a DAS28 of ≤5.1) was 71.9% at week 12 and 84.6% at week 24. 25.0% of patients achieved clinical remission (DAS28 ≤ 2.6). Most frequently reported adverse drug reactions (ADR) were diarrhea (3.0%), nausea (2.4%), hypertension (1.8%), and headache (1.5%). Serious ADR were reported in four patients (1.2%). Leflunomide showed the effectiveness which was to be expected from controlled studies without revealing any new or hitherto unknown side effects. Onset of action was quick and significant improvement of disease was seen after 12 weeks of therapy and at even higher rates after 24 weeks irrespective of the use of a loading dose. Interestingly, the DAS28-remission rate achieved was similar to the rate seen with methotrexate or biologic therapy in other studies

Jasmonate-dependent modifications of the pectin matrix during potato development function as a defense mechanism targeted by Dickeya dadantii virulence factors

The plant cell wall constitutes an essential protection barrier against pathogen attack. In addition, cell-wall disruption leads to accumulation of jasmonates (JAs), which are key signaling molecules for activation of plant inducible defense responses. However, whether JAs in return modulate the cell-wall composition to reinforce this defensive barrier remains unknown. The enzyme 13-allene oxide synthase (13-AOS) catalyzes the first committed step towards biosynthesis of JAs. In potato (Solanum tuberosum), there are two putative St13-AOS genes, which we show here to be differentially induced upon wounding. We also determine that both genes complement an Arabidopsis aos null mutant, indicating that they encode functional 13-AOS enzymes. Indeed, transgenic potato plants lacking both St13-AOS genes (CoAOS1/2 lines) exhibited a significant reduction of JAs, a concomitant decrease in wound-responsive gene activation, and an increased severity of soft rot disease symptoms caused by Dickeya dadantii. Intriguingly, a hypovirulent D. dadantii pel strain lacking the five major pectate lyases, which causes limited tissue maceration on wild-type plants, regained infectivity in CoAOS1/2 plants. In line with this, we found differences in pectin methyl esterase activity and cell-wall pectin composition between wild-type and CoAOS1/2 plants. Importantly, wild-type plants had pectins with a lower degree of methyl esterification, which are the substrates of the pectate lyases mutated in the pel strain. These results suggest that, during development of potato plants, JAs mediate modification of the pectin matrix to form a defensive barrier that is counteracted by pectinolytic virulence factors from D. dadantii

Overview of IFMIF-DONES diagnostics: Requirements and techniques

The IFMIF-DONES Facility is a unique first-class scientific infrastructure whose construction is foreseen in Granada, Spain, in the coming years. Strong integration efforts are being made at the current project phase aiming at harmonizing the ongoing design of the different and complex Systems of the facility. The consolidation of the Diagnostics and Instrumentation, transversal across many of them, is a key element of this purpose. A top-down strategy is proposed for a systematic Diagnostics Review and Requirement definition, putting emphasis in the one-of-a-kind instruments necessary by the operational particularities of some of the Systems, as well as to the harsh environment that they shall survive. In addition, other transversal aspects such as the ones related to Safety and Machine Protection and their respective requirements shall be also considered. The goal is therefore to advance further and solidly in the respective designs, identify problems in advance, and steer the Diagnostics development and validation campaigns that will be required. The present work provides an overview of this integration strategy as well as a description of some of the most challenging Diagnostics and Instruments within the facility, including several proposed techniques currently under study