FIRI - a Far-Infrared Interferometer

Half of the energy ever emitted by stars and accreting objects comes to us in the FIR waveband and has yet to be properly explored. We propose a powerful Far-InfraRed Interferometer mission, FIRI, to carry out high-resolution imaging spectroscopy in the FIR. This key observational capability is essential to reveal how gas and dust evolve into stars and planets, how the first luminous objects in the Universe ignited, how galaxies formed, and when super-massive black holes grew. FIRI will disentangle the cosmic histories of star formation and accretion onto black holes and will trace the assembly and evolution of quiescent galaxies like our Milky Way. Perhaps most importantly, FIRI will observe all stages of planetary system formation and recognise Earth-like planets that may harbour life, via its ability to image the dust structures in planetary systems. It will thus address directly questions fundamental to our understanding of how the Universe has developed and evolved - the very questions posed by ESA's Cosmic Vision.Comment: Proposal developed by a large team of astronomers from Europe, USA and Canada and submitted to the European Space Agency as part of "Cosmic Vision 2015-2025

Electrochemical synthesis of peroxomonophosphate using boron-doped diamond anodes

A new method for the synthesis of peroxomonophosphate, based on the use of boron-doped diamond electrodes, is described. The amount of oxidant electrogenerated depends on the characteristics of the supporting media (pH and solute concentration) and on the operating conditions (temperature and current density). Results show that the pH, between values of 1 and 5, does not influence either the electrosynthesis of peroxomonophosphate or the chemical stability of the oxidant generated. Conversely, low temperatures are required during the electrosynthesis process to minimize the thermal decomposition of peroxomonophosphate and to guarantee significant oxidant concentration. In addition, a marked influence of both the current density and the initial substrate is observed. This observation can be explained in terms of the contribution of hydroxyl radicals in the oxidation mechanisms that occur on diamond surfaces. In the assays carried out below the water oxidation potential, the generation of hydroxyl radicals did not take place. In these cases, peroxomonophosphate generation occurs through a direct electron transfer and, therefore, at these low current densities lower concentrations are obtained. On the other hand, at higher potentials both direct and hydroxyl radical-mediated mechanisms contribute to the oxidant generation and the process is more efficient. In the same way, the contribution of hydroxyl radicals may also help to explain the significant influence of the substrate concentration. Thus, the coexistence of both phosphate and hydroxyl radicals is required to ensure the generation of significant amounts of peroxomonophosphoric acid

First signs and symptoms of spondyloarthritis—data from an inception cohort with a disease course of two years or less (REGISPONSER-Early)

Objective. To determine the first signs and symptoms, and the clinical, biological and radiological characteristics of patients with early SpA

Prenatal Influence of an Androgen Agonist and Antagonist on the Differentiation of the Ovine Sexually Dimorphic Nucleus in Male and Female Lamb Fetuses

The ovine sexually dimorphic nucleus (oSDN) is 2 times larger in rams than in ewes. Sexual differentiation of the oSDN is produced by testosterone exposure during the critical period occurring between gestational day (GD)60 and GD90 (term, 147 d). We tested the hypothesis that testosterone acts through the androgen receptor to control development of the male-typical oSDN. In experiment 1, pregnant ewes received injections of vehicle, androgen receptor antagonist flutamide, or nonaromatizable androgen dihydrotestosterone (DHT) propionate during the critical period. Fetuses were delivered at GD135. Both antagonist and agonist treatments significantly reduced mean oSDN volume in males but had no effects in females. Experiment 2, we analyzed the effect of treatments on the fetal hypothalamic-pituitary-gonadal axis to determine whether compensatory changes in hormone secretion occurred that could explain the effect of DHT. Pregnant ewes were injected with vehicle, flutamide, or DHT propionate from GD60 to GD84, and fetuses were delivered on GD85. Flutamide significantly increased LH and testosterone in males, whereas DHT significantly decreased both hormones. In females, LH was unaffected by flutamide but significantly reduced by DHT exposure. DHT significantly decreased pituitary gonadotropin and hypothalamic kisspeptin mRNA expression in males and females. These results suggest that androgen receptor mediates the effect of testosterone on oSDN masculinization, because this process was blocked by the androgen receptor antagonist flutamide in eugonadal males. In contrast, the reduction of oSDN volume observed after DHT exposure appears to be mediated by a negative feedback mechanism exerted on the hypothalamus to reduce LH and testosterone secretion. The reduced androgen exposure most likely accounted for the decreased oSDN volume. We conclude that, during the critical period, the male reproductive axis in long gestation species, such as sheep, is sufficiently developed to react to perturbations in serum androgens and mitigate disruptions in brain masculinization

Diabetes y enfermedad cardiovascular, aspectos actuales de su manejo: la visión del cardiólogo

La diabetes es una enfermedad prevalente, con casos en aumento en todo el mundo, y se relaciona de forma directa con otras condiciones entre ellas la obesidad. Así, la diabetes supone un riesgo cardiovascular mayor en aquellos pacientes que la padecen y una vez se manifiesta es la causa más importante de morbimortalidad. A lo largo de los últimos años, hemos tenido un cambio en el paradigma del manejo de esta condición, razón por la cual se ha soslayado el enfoque glucocéntrico para hacer una aproximación integral al riesgo global y los demás factores asociados. Los estudios recientes han aportado una valiosa información de seguridad cardiovascular, pero lo más interesante es que han demostrado que algunos grupos farmacológicos generan un beneficio adicional en la población con condición cardiovascular. Es tan fuerte el impacto de estos medicamentos que se están posesionando como la estrategia de manejo inicial para la diabetes

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER)

Objectives: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. Methods: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. Results: Mean age (years) ± S.D. at diagnosis was 14.2 ± 2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ± S.D. was 1.27 ± 1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). Conclusions: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement

Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry

OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

Objective: To assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. Methods: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet =4 ACR-97 SLE criteria and disease onset <18 years old (jSLE), were retrospectively investigated for SI (defined as either the need for hospitalization with antibacterial therapy for a potentially fatal infection or death caused by the infection). Standardized SI rate was calculated per 100 patient years. Patients with and without SI were compared. Bivariate and multivariate logistic and Cox regression models were built to calculate associated factors to SI and relative risks. Results: A total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and =6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2–4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. Conclusions: The risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy

Preparation of polycaprolactone nanoparticles via supercritical carbon dioxide extraction of emulsions

Polycaprolactone (PCL) nanoparticles were produced via supercritical fluid extraction of emulsions (SFEE) using supercritical carbon dioxide (scCO2). The efficiency of the scCO2 extraction was investigated and compared to that of solvent extraction at atmospheric pressure. The effects of process parameters including polymer concentration (0.6–10% w/w in acetone), surfactant concentration (0.07 and 0.14% w/w) and polymer-to-surfactant weight ratio (1:1–16:1 w/w) on the particle size and surface morphology were also investigated. Spherical PCL nanoparticles with mean particle sizes between 190 and 350 nm were obtained depending on the polymer concentration, which was the most important factor where increase in the particle size was directly related to total polymer content in the formulation. Nanoparticles produced were analysed using dynamic light scattering and scanning electron microscopy. The results indicated that SFEE can be applied for the preparation of PCL nanoparticles without agglomeration and in a comparatively short duration of only 1 h

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators

BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention. METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [P=0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [P=0.17]). CONCLUSIONS: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks