The effect of magnetic activity saturation in chromospheric flux-flux relationships

We present a homogeneous study of chromospheric and coronal flux-flux relationships using a sample of 298 late-type dwarf active stars with spectral types F to M. The chromospheric lines were observed simultaneously in each star to avoid spread due to long term variability. Unlike other works, we subtract the basal chromospheric contribution in all the spectral lines studied. For the first time, we quantify the departure of dMe stars from the general relations. We show that dK and dKe stars also deviate from the general trend. Studying the flux-colour diagrams we demonstrate that the stars deviating from the general relations are those with saturated X-ray emission and that those stars also present saturation in the H$\alpha$ line. Using several age spectral indicators, we show that they are younger stars than those following the general relationships. The non-universality of flux-flux relationships found in this work should be taken into account when converting between fluxes in different chromospheric activity indicators.Comment: Accepted for publication in the Monthly Notices of the Royal Astronomical Societ

Analysis and modeling of high temporal resolution spectroscopic observations of flares on AD Leo

We report the results of a high temporal resolution spectroscopic monitoring of the flare star AD Leo. During 4 nights, more than 600 spectra were taken in the optical range using the Isaac Newton Telescope (INT) and the Intermediate Dispersion Spectrograph (IDS). We have observed a large number of short and weak flares occurring very frequently (flare activity > 0.71 hours-1). This is in favour of the very important role that flares can play in stellar coronal heating. The detected flares are non white-light flares and, though most of solar flares belong to this kind, very few such events had been previously observed on stars. The behaviour of different chromospheric lines (Balmer series from H_alpha to H_11, Ca II H & K, Na I D_1 & D_2, He I 4026 AA and He I D_3) has been studied in detail for a total of 14 flares. We have also estimated the physical parameters of the flaring plasma by using a procedure which assumes a simplified slab model of flares. All the obtained physical parameters are consistent with previously derived values for stellar flares, and the areas - less than 2.3% of the stellar surface - are comparable with the size inferred for other solar and stellar flares. Finally, we have studied the relationships between the physical parameters and the area, duration, maximum flux and energy released during the detected flares.Comment: Latex file with 17 pages, 11 figures. Available at http://www.ucm.es/info/Astrof/invest/actividad/actividad_pub.html Accepted for publication in: Astronomy & Astrophysics (A&A

The nearest young moving groups

The latest results in the research of forming planetary systems have led several authors to compile a sample of candidates for searching for planets in the vicinity of the sun. Young stellar associations are indeed excellent laboratories for this study, but some of them are not close enough to allow the detection of planets through adaptive optics techniques. However, the existence of very close young moving groups can solve this problem. Here we have compiled the members of the nearest young moving groups, as well as a list of new candidates from our catalogue of late-type stars possible members of young stellar kinematic groups, studying their membership through spectroscopic and photometric criteria.Comment: Latex file with 16 pages, 4 figures. Available at http://www.ucm.es/info/Astrof/invest/actividad/skg/skg_sag.html Accepted for publication in: The Astrophysical Journal (ApJ

Class-B CpG-ODN Formulated With a Nanostructure Induces Type I Interferons-Dependent and CD4+ T Cell-Independent CD8+ T-Cell Response Against Unconjugated Protein Antigen

There is a need for new vaccine adjuvant strategies that offer both vigorous antibody and T-cell mediated protection to combat difficult intracellular pathogens and cancer. To this aim, we formulated class-B synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) with a nanostructure (Coa-ASC16 or coagel) formed by self-assembly of 6-0-ascorbyl palmitate ester. Our previous results demonstrated that mice immunized with ovalbumin (OVA) and CpG-ODN formulated with Coa-ASC16 (OVA/CpG-ODN/Coa-ASC16) elicited strong antibodies (IgG1 and IgG2a) and Th1/Th17 cellular responses without toxic systemic effects. These responses were superior to those induced by a solution of OVA with CpG-ODN or OVA/CpG-ODN formulated with aluminum salts. In this study, we investigated the capacity of this adjuvant strategy (CpG-ODN/Coa-ASC16) to elicit CD8+ T-cell response and some of the underlying cellular and molecular mechanisms involved in adaptive response. We also analyzed whether this adjuvant strategy allows a switch from an immunization scheme of three-doses to one of single-dose. Our results demonstrated that vaccination with OVA/CpG-ODN/Coa-ASC16 elicited an antigen-specific long-lasting humoral response and importantly-high quality CD8+ T-cell immunity with a single-dose immunization. Moreover, Coa-ASC16 promoted co-uptake of OVA and CpG-ODN by dendritic cells. The CD8+ T-cell response induced by OVA/CpG-ODN/Coa-ASC16 was dependent of type I interferons and independent of CD4+ T-cells, and showed polyfunctionality and efficiency against an intracellular pathogen. Furthermore, the cellular and humoral responses elicited by the nanostructured formulation were IL-6-independent. This system provides a simple and inexpensive adjuvant strategy with great potential for future rationally designed vaccines

Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers

A significant proportion of the personal and economic burden of schizophrenia can be attributed to the late diagnosis or misdiagnosis of the disorder. A novel, objective diagnostic approaches could facilitate the early detection and treatment of schizophrenia and improve patient outcomes. In the present study, we aimed to identify robust schizophrenia-specific blood biomarkers, with the goal of developing an accurate diagnostic model. The levels of selected serum and peripheral blood mononuclear cell (PBMC) markers relevant to metabolic and immune function were measured in healthy controls (n?=?26) and recent-onset schizophrenia patients (n?=?36) using multiplexed immunoassays and flow cytometry. Analysis of covariance revealed significant upregulation of insulin receptor (IR) and fatty acid translocase (CD36) levels in T helper cells (F?=?10.75, P?=?0.002, Q?=?0.024 and F?=?21.58, P?=?2.8?×?10?5, Q?=?0.0004, respectively), as well as downregulation of glucose transporter 1 (GLUT1) expression in monocytes (F?=?21.46, P?=?2.9?×?10?5, Q?=?0.0004). The most robust predictors, monocyte GLUT1 and T helper cell CD36, were used to develop a diagnostic model, which showed a leave-one-out cross-validated area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI: 0.66?0.92). The diagnostic model was validated in two independent datasets. The model was able to distinguish first-onset, drug-naïve schizophrenia patients (n?=?34) from healthy controls (n?=?39) with an AUC of 0.75 (95% CI: 0.64?0.86), and also differentiated schizophrenia patients (n?=?22) from patients with other neuropsychiatric conditions, including bipolar disorder, major depressive disorder and autism spectrum disorder (n?=?68), with an AUC of 0.83 (95% CI: 0.75?0.92). These findings indicate that PBMC-derived biomarkers have the potential to support an accurate and objective differential diagnosis of schizophrenia.ACKNOWLEDGEMENTS: We are grateful to the participants and their families for their cooperation in this study. We would like to thank blood donors and the clinical centres, for the provision of biological samples, in addition, to supporting staff at the affiliated institutions. We also thank IDIVAL biobank (Inés Santiuste and Jana Arozamena) and UMCU Biobank for clinical sample and data preparation, as well as the PAFIP members for the data collection. This work was supported by the Stanley Medical Research Institute (grant number: 12T-008) and the Dutch Research Council (NWO; grant number: 40–00812–98–12154) received by IES; by grants to SB from the Stanley Medical Research Institute (SMRI) and the Engineering and Physical Sciences Research Council UK (EPSRC); and by grants to BC-F: SAF2016–76046-R and SAF2013–46292-R (MINECO) and PI16/00156 (ISCIII and FEDER)

Beneficial Effect of Ursodeoxycholic Acid in Patients with ACOX2 Deficiency-Associated Hypertransaminasemia

Background: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly trihydroxycholestanoic acid (THCA). Aims: To investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration. Methods & results: Among 33 patients with unexplained hypertransaminasemia from 11 hospitals, and 13 of their relatives, 7 individuals with abnormally high C27-BA levels (>50% of total BAs) were identified by HPLC-MS/MS. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in 2 patients and 3 family members. Two additional non-related patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In ADAH patients, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized transaminases levels. Incubation of HuH-7 liver cells with THCA, which was efficiently taken up, but not through BA transporters, increased ROS production (flow cytometry), ER stress biomarkers (GRP78, CHOP and XBP1-S/XBP1-U ratio), and BAX¿ expression (RT-qPCR and immunoblot), whereas cell viability was decreased (MTT). THCA-induced cell toxicity was higher than that of major C24-BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site-directed mutagenesis) and expressed in HuH-7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH. Conclusion: Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a non-invasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.This study was supported by the following grants: CIBERehd (EHD15PI05/2016); Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI19/00819 and PI20/00189), co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”; “Junta de Castilla y León” (SA074P20); Fundació Marato TV3 (201916–31); AECC Scientific Foundation (2017/2020), Spain; and “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from grants PID2019-111669RBI- 100, PID2020-115055RB- I00 from Plan Nacional de I+D funded by the “Agencia Estatal de Investigación” (AEI) and the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA/NIH, as well as support from AGAUR of the “Generalitat de Catalunya” SGR-2017- 1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network. Marta Alonso-Peña was the recipient of a predoctoral fellowship from “Ministerio de Educación, Cultura y Deporte” (BOE-A- 2015- 9456; FPU-14/ 00214) and a Mobility Grant for Short Stays from “Ministerio de Ciencia, Innovación y Universidades” (EST17/00186). Ricardo Espinosa-Escudero is the recipient of a predoctoral fellowship from “Junta de Castilla y León” and “Fondo Social Europeo” (EDU/574/2018). The funding sources were not involved in the research design or preparation of the articl

Exploring the neuropsychiatric spectrum using high-content functional analysis of single-cell signaling networks.

Neuropsychiatric disorders overlap in symptoms and share genetic risk factors, challenging their current classification into distinct diagnostic categories. Novel cross-disorder approaches are needed to improve our understanding of the heterogeneous nature of neuropsychiatric diseases and overcome existing bottlenecks in their diagnosis and treatment. Here we employ high-content multi-parameter phospho-specific flow cytometry, fluorescent cell barcoding and automated sample preparation to characterize ex vivo signaling network responses (n = 1764) measured at the single-cell level in B and T lymphocytes across patients diagnosed with four major neuropsychiatric disorders: autism spectrum condition (ASC), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ; n = 25 each), alongside matched healthy controls (n = 100). We identified 25 nodes (individual cell subtype-epitope-ligand combinations) significantly altered relative to the control group, with variable overlap between different neuropsychiatric diseases and heterogeneously expressed at the level of each individual patient. Reconstruction of the diagnostic categories from the altered nodes revealed an overlapping neuropsychiatric spectrum extending from MDD on one end, through BD and SCZ, to ASC on the other end. Network analysis showed that although the pathway structure of the epitopes was broadly preserved across the clinical groups, there were multiple discrete alterations in network connectivity, such as disconnections within the antigen/integrin receptor pathway and increased negative regulation within the Akt1 pathway in CD4+ T cells from ASC and SCZ patients, in addition to increased correlation of Stat1 (pY701) and Stat5 (pY694) responses in B cells from BD and MDD patients. Our results support the "dimensional" approach to neuropsychiatric disease classification and suggest potential novel drug targets along the neuropsychiatric spectrum

Riesgo quirúrgico tras resección pulmonar anatómica en cirugía torácica. Modelo predictivo a partir de una base de datos nacional multicéntrica

Introduction: the aim of this study was to develop a surgical risk prediction model in patients undergoing anatomic lung resections from the registry of the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). Methods: data were collected from 3,533 patients undergoing anatomic lung resection for any diagnosis between December 20, 2016 and March 20, 2018. We defined a combined outcome variable: death or Clavien Dindo grade IV complication at 90 days after surgery. Univariate and multivariate analyses were performed by logistic regression. Internal validation of the model was performed using resampling techniques. Results: the incidence of the outcome variable was 4.29% (95% CI 3.6-4.9). The variables remaining in the final logistic model were: age, sex, previous lung cancer resection, dyspnea (mMRC), right pneumonectomy, and ppo DLCO. The performance parameters of the model adjusted by resampling were: C-statistic 0.712 (95% CI 0.648-0.750), Brier score 0.042 and bootstrap shrinkage 0.854. Conclusions: the risk prediction model obtained from the GEVATS database is a simple, valid, and reliable model that is a useful tool for establishing the risk of a patient undergoing anatomic lung resection

Grupo español de cirugía torácica asistida por videoimagen: método, auditoría y resultados iniciales de una cohorte nacional prospectiva de pacientes tratados con resecciones anatómicas del pulmón

Introduction: our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). Methods: we conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for '90-day mortality' and 'Grade IIIb-V complications'. Results: the series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). Conclusions: more than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort