Evidence of Compton cooling during an X-ray flare supports a neutron star nature of the compact object in 4U1700-37

Based on new Chandra X-ray telescope data, we present empirical evidence of plasma Compton cooling during a flare in the non pulsating massive X-ray binary 4U1700-37. This behaviour might be explained by quasispherical accretion onto a slowly rotating magnetised neutron star. In quiescence, the neutron star in 4U1700-37 is surrounded by a hot radiatively cooling shell. Its presence is supported by the detection of mHz quasi periodic oscillations likely produced by its convection cells. The high plasma temperature and the relatively low X-ray luminosity observed during the quiescence, point to a small emitting area about 1 km, compatible with a hot spot on a NS surface. The sudden transition from a radiative to a significantly more efficient Compton cooling regime triggers an episode of enhanced accretion resulting in a flare. During the flare, the plasma temperature drops quickly. The predicted luminosity for such transitions, Lx = 3 x 10^35 erg s-1, is very close to the luminosity of 4U1700-37 during quiescence. The transition may be caused by the accretion of a clump in the stellar wind of the donor star. Thus, a magnetised NS nature of the compact object is strongly favoured.Comment: Accepted for publication in MNRA

High-resolution X-ray spectroscopy of the stellar wind in Vela X-1 during a flare

Context. We present a ~130 ks observation of the prototypical wind-accreting, high-mass X-ray binary Vela X-1 collected with XMM-Newton at orbital phases between 0.12 and 0.28. A strong flare took place during the observation that allows us to investigate the reaction of the clumpy stellar wind to the increased X-ray irradiation. Aims. To examine the wind’s reaction to the flare, we performed both time-averaged and time-resolved analyses of the RGS spectrum and examined potential spectral changes. Methods. We focused on the high-resolution XMM-Newton RGS spectra and divided the observation into pre-flare, flare, and post-flare phases. We modeled the time-averaged and time-resolved spectra with phenomenological components and with the self-consistent photoionization models calculated via CLOUDY and XSTAR in the pre-flare phase, where strong emission lines due to resonant transitions of highly ionized ions are seen. Results. In the spectra, we find emission lines corresponding to K-shell transitions in highly charged ions of oxygen, neon, magnesium, and silicon as well as radiative recombination continua (RRC) of oxygen. Additionally, we observe potential absorption lines of magnesium at a lower ionization stage and features identified as iron L lines. The CLOUDY and XSTAR photoionization models provide contradictory results, either pointing towards uncertainties in theory or possibly a more complex multi-phase plasma, or both. Conclusions. We are able to demonstrate the existence of a plethora of variable narrow features, including the firm detection of oxygen lines and RRC that RGS enables to observe in this source for the first time. We show that Vela X-1 is an ideal source for future high-resolution missions, such as XRISM and Athena.V.G. is supported through the Margarete von Wrangell fellowship by the ESF and the Ministry of Science, Research and the Arts Baden-Württemberg. We acknowledge support from the ESTEC Faculty Visiting Scientist Programme to V.G. S.B. acknowledges financial support from the Italian Space Agency under grant ASI-INAF 2017-14-H.O. Work at LLNL was performed under the auspieces of the U.S. Department of Energy under contract No. DE-AC52-07NA27344. S.M.N. acknowledges funding by the Spanish Ministry MCIU under project RTI2018-096686-B-C21 (MCIU/AEI/FEDER, UE), co-funded by FEDER funds and by the Unidad de Excelencia María de Maeztu, ref. MDM-2017-0765

Utility of circulating serum miRNA profiles to evaluate the potential risk and severity of immune-mediated inflammatory disorders

Immune-mediated inflammatory disorders (IMID) are a group of diseases that present inflammation as a major pathogenic mechanism. They affect 15% of the population and pose a heavy socio-economic burden. Despite the growing knowledge on the etiopathogenesis of these diseases and the marked improvement in their management, there is a lack of predictive markers of IMID development or severity suitable for early diagnosis and adjustment of treatment intensity. The possibility that certain circulating miRNA profiles could be used as biomarkers of risk of development and/or severity of several autoimmune diseases has fuelled the interest in using them to improve the selection of successful treatments. The multi-pronged approach proposed here sought to reveal circulating miRNAs and miRNA signatures that could act as new predictive biomarkers of IMID development and severity. Our results showed that the circulating levels of miR-19b and miR-26b were significantly decreased (p < 0.001) in IMID patients compared to controls. Furthermore, receiver operating characteristic (ROC) curve analysis showed that these miRNAs were suitable discriminators capable to identify an IMID, with areas under the curve (AUC) of 0.85 and 0.83, respectively. In addition, we established that miR-19a and miR-143 were significantly increased in IMID patients with severe disease (p < 0.05). In summary, our findings identify two different miRNA signatures. One of them is associated with the presence of IMIDs and could lead to the development of tools for their early detection. The second signature is able to discriminate between mild and severe forms of these disorders and could be a putative tool to select patient candidates for a more intense treatment.This work was supported by the following grants: Proyectos de Investigación en Salud (FIS) PIE13-0041, PI16-02091 and PI19-00584 (funded by Ministerio de Economía y Competitividad (MINECO), Instituto de Salud Carlos III (ISCIII)), TIRONET2-CM, B2017/BMD-3724 (funded by Comunidad de Madrid), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12) to MM; also by grants RD16/0011/0012 and PI18/0371 from MINECO, ISCIII to IGA; PI17/01972 (MINECO, ISCIIII) to E. D; and Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Fundación BBVA a equipos de Investigación Científica 2018 and from “la Caixa Banking Foundation” under the project code HR17-00016 to F·S.M and cofinanced by FEDER fund

External validation of multidimensional prognostic indices (ADO, BODEx and DOSE) in a primary care international cohort (PROEPOC/COPD cohort)

Background: Due to the heterogeneous and systemic nature of the chronic obstructive pulmonary disease (COPD), the new guidelines are oriented toward individualized attention. Multidimensional scales could facilitate its proper clinical and prognostic assessment, but not all of them were validated in an international primary care cohort, different from the original ones used for model development. Therefore, our main aim is to assess the prognostic capacity of the ADO, BODEx and DOSE indices in primary care for predicting mortality in COPD patients and to validate the models obtained in subgroups of patients, classified by revised Global Initiative for Chronic Obstructive Lung Disease (2011) and updated Spanish Guideline (2014). Besides, we want to confirm that the prognostic capacity of all indices increases if the number of exacerbations is substituted by the interval between them and to assess the impact on health of the patient''s lifestyle, social network and adherence to treatment. Methods: Design: External validation of scales, open and prospective cohort study in primary care. Setting: 36 health centres in 6 European high, medium and low income countries. Subjects: 477 patients diagnosed with COPD, captured in clinical visit by their General Practitioner/Nurse. Predictors: Detailed patient history, exacerbations, lung function test and questionnaires at baseline. Outcomes: Exacerbations, all-cause mortality and specific mortality, within 5 years of recruitment. Analysis: Multivariate logistic regression and Cox regression will be used. Possible non-linear effect of the indices will be studied by using Structured Additive Regression models with penalised splines. Subsequently, we will assess different aspects of the regression models: discrimination, calibration and diagnostic precision. Clinical variables modulated in primary care and the interval between exacerbations will be considered and incorporated into the analysis. Discussion: The Research Agenda for General Practice/Family Medicine highlights that the evidence on predictive values of prognostic indices in primary care is scarce. A prospective cohort like that of PROEPOC/COPD provides good opportunities for research into COPD and make communication easier between family practitioners, nursing staff, pneumologists and other professionals, supporting a multi-disciplinary approach to the treatment of these patients. Trial registration:ISRCTN52402811. Date: 15/01/2015. Prospectively registered

Utility of circulating serum miRNA profiles to evaluate the potential risk and severity of immune-mediated inflammatory disorders

This work was supported by the following grants: Proyectos de Investigación en Salud (FIS) PIE13-0041, PI16-02091 and PI19-00584 (funded by Ministerio de Economía y Competitividad (MINECO), Instituto de Salud Carlos III (ISCIII)), TIRONET2-CM, B2017/BMD-3724 (funded by Comunidad de Madrid), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12) to MM; also by grants RD16/0011/0012 and PI18/0371 from MINECO, ISCIII to IGA; PI17/01972 (MINECO, ISCIIII) to E. D; and Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Fundación BBVA a equipos de Investigación Científica 2018 and from “la Caixa Banking Foundation” under the project code HR17-00016 to F·S.M and cofinanced by FEDER funds.Immune-mediated inflammatory disorders (IMID) are a group of diseases that present inflammation as a major pathogenic mechanism. They affect 15% of the population and pose a heavy socio-economic burden. Despite the growing knowledge on the etiopathogenesis of these diseases and the marked improvement in their management, there is a lack of predictive markers of IMID development or severity suitable for early diagnosis and adjustment of treatment intensity. The possibility that certain circulating miRNA profiles could be used as biomarkers of risk of development and/or severity of several autoimmune diseases has fuelled the interest in using them to improve the selection of successful treatments. The multi-pronged approach proposed here sought to reveal circulating miRNAs and miRNA signatures that could act as new predictive biomarkers of IMID development and severity. Our results showed that the circulating levels of miR-19b and miR-26b were significantly decreased (p < 0.001) in IMID patients compared to controls. Furthermore, receiver operating characteristic (ROC) curve analysis showed that these miRNAs were suitable discriminators capable to identify an IMID, with areas under the curve (AUC) of 0.85 and 0.83, respectively. In addition, we established that miR19a and miR-143 were significantly increased in IMID patients with severe disease (p < 0.05). In summary, our findings identify two different miRNA signatures. One of them is associated with the presence of IMIDs and could lead to the development of tools for their early detection. The second signature is able to discriminate between mild and severe forms of these disorders and could be a putative tool to select patient candidates for a more intense treatment.Depto. de Biología CelularFac. de Ciencias BiológicasTRUEpu