Modelling the evolution of the Guadalquivir foreland basin (South Spain).

Previous quantitative studies dealing with the origin of foreland basins have focused primarily either on the rheological basis of the lithosphere mechanical response or on the relationship between orogenic loading and sediment geometry. To link the evolution of the Guadalquivir foreland basin (South Iberia) with the thermomechanical stratification of the Iberian lithosphere, we combine quantitative approaches to deep and shallow processes: thrust loading, lithospheric flexure, thickness changes of the crust and the lithospheric mantle, and surface mass transport. A planform flexural analysis of the present-day load distribution shows that basement subsidence is related not only to upper crustal thrusting but also to a deep-seated additional load. On the basis of the observed gravity and geoid fields, we propose this additional load to be related to a lithospheric mantle thickening larger than the coeval crustal thickening. Further modeling of the evolution of a basin cross section reveals that the architecture of the sedimentary basin is additionally related to the lithosphere rheological response. The quantitative study of the evolution of basement faulting and the forebulge uplift of Sierra Morena leads us to conclude that viscous stress relaxation and/or plastic yielding within the lithosphere are key processes to explain the flexural evolution of the basin

A Review of the current knowledge of the crustal and lithospheric structure of the Valencia Trough Basin

In this paper, we review the current geophysical knowledge of the Valencia Trough Basin, and the surrounding areas. For this purpose, we summarize the most significant regional geophysical datasets acquired since the seventies to investigate the trough (seismic, gravity, geoid and heat flow data). We then focus on the discussion regarding the geometry and physical properties of the present day crustal and lithospheric structure derived from seismic images, as well as combined potential field modelling and their relationships with the Alpine geodynamic evolution of the Valencia Trough. Finally, we discuss the differences in the results regarding the geometry of the lithosphere-asthenosphere boundary obtained by different modelling approaches and the features that, in our view, require further investigation to unravel the true nature of the Valencia Trough, including what could have caused the differences between the crustal structure observed in the SW region compared to the NE region, the asymmetric style of thinning across the trough; the origin of the changes in the lower crustal reflectivity across the basin; the fabric of the uppermost mantle, characterized by anomalously low P-wave velocities; and the physical properties of the lithosphere mantle (density, Pwaves velocity, thermal conductivity, temperature distribution, mineralogical composition, etc.)

What Matters Most to Patients and Rheumatologists? A Discrete Choice Experiment in Rheumatoid Arthritis

Introduction: To determine patient and rheumatologist preferences for rheumatoid arthritis (RA) treatment attributes in Spain and to evaluate their attitude towards shared decision-making (SDM). Methods: Observational, descriptive, exploratory and cross-sectional study based on a discrete choice experiment (DCE). To identify the attributes and their levels, a literature review and two focus groups (patients [P] = 5; rheumatologists [R] = 4) were undertaken. Seven attributes with 2–4 levels were presented in eight scenarios. Attribute utility and relative importance (RI) were assessed using a conditional logit model. Patient preferences for SDM were assessed using an ad hoc questionnaire. Results: Ninety rheumatologists [52.2% women; mean years of experience 18.1 (SD: 9.0); seeing an average of 24.4 RA patients/week (SD: 15.3)] and 137 RA patients [mean age: 47.5 years (SD: 10.7); 84.0% women; mean time since diagnosis of RA: 14.2 years (SD: 11.8) and time in treatment: 13.2 years (SD: 11.2), mean HAQ score 1.2 (SD: 0.7)] participated in the study. In terms of RI, rheumatologists and RA patients viewed: time with optimal QoL: R: 23.41%/P: 35.05%; substantial symptom improvement: R: 13.15%/P: 3.62%; time to onset of treatment action: R: 16.24%/P: 13.56%; severe adverse events: R: 10.89%/P: 11.20%; mild adverse events: R: 4.16%/P: 0.91%; mode of administration: R: 25.23%/P: 25.00%; and added cost: R: 6.93%/P: 10.66%. Nearly 73% of RA patients were involved in treatment decision-making to a greater or lesser extent; however, 27.4% did not participate at all. Conclusion: Both for rheumatologists and patients, the top three decision-making drivers are time with optimal quality, treatment mode of administration and time to onset of action, although in different ranking order. Patients were willing to be more involved in the treatment decision-making process

Long-term observations of the pulsars in 47 Tucanae. I. A study of four elusive binary systems

For the past couple of decades, the Parkes radio telescope has been regularly observing the millisecond pulsars in 47 Tucanae (47 Tuc). This long-term timing program was designed to address a wide range of scientific issues related to these pulsars and the globular cluster where they are located. In this paper, the first of a series, we address one of these objectives: the characterization of four previously known binary pulsars for which no precise orbital parameters were known, namely 47 Tuc P, V, W and X (pulsars 47 Tuc R and Y are discussed elsewhere). We determined the previously unknown orbital parameters of 47 Tuc V and X and greatly improved those of 47 Tuc P and W. For pulsars W and X we obtained, for the first time, full coherent timing solutions across the whole data span, which allowed a much more detailed characterization of these systems. 47 Tuc W, a well-known tight eclipsing binary pulsar, exhibits a large orbital period variability, as expected for a system of its class. 47 Tuc X turns out to be in a wide, extremely circular, 10.9-day long binary orbit and its position is ~3.8 arcmin away from the cluster center, more than three times the distance of any other pulsar in 47 Tuc. These characteristics make 47 Tuc X a very different object with respect to the other pulsars of the cluster.Comment: Accepted for publication by MNRAS, 18 pages, 11 figure

A Cosmic Census of Radio Pulsars with the SKA

The Square Kilometre Array (SKA) will make ground breaking discoveries in pulsar science. In this chapter we outline the SKA surveys for new pulsars, as well as how we will perform the necessary follow-up timing observations. The SKA's wide field-of-view, high sensitivity, multi-beaming and sub-arraying capabilities, coupled with advanced pulsar search backends, will result in the discovery of a large population of pulsars. These will enable the SKA's pulsar science goals (tests of General Relativity with pulsar binary systems, investigating black hole theorems with pulsar-black hole binaries, and direct detection of gravitational waves in a pulsar timing array). Using SKA1-MID and SKA1-LOW we will survey the Milky Way to unprecedented depth, increasing the number of known pulsars by more than an order of magnitude. SKA2 will potentially find all the Galactic radio-emitting pulsars in the SKA sky which are beamed in our direction. This will give a clear picture of the birth properties of pulsars and of the gravitational potential, magnetic field structure and interstellar matter content of the Galaxy. Targeted searches will enable detection of exotic systems, such as the ~1000 pulsars we infer to be closely orbiting Sgr A*, the supermassive black hole in the Galactic Centre. In addition, the SKA's sensitivity will be sufficient to detect pulsars in local group galaxies. To derive the spin characteristics of the discoveries we will perform live searches, and use sub-arraying and dynamic scheduling to time pulsars as soon as they are discovered, while simultaneously continuing survey observations. The large projected number of discoveries suggests that we will uncover currently unknown rare systems that can be exploited to push the boundaries of our understanding of astrophysics and provide tools for testing physics, as has been done by the pulsar community in the past.Comment: 20 pages, 7 figures, to be published in: "Advancing Astrophysics with the Square Kilometre Array", Proceedings of Science, PoS(AASKA14)04

Long-term observations of the pulsars in 47 Tucanae - II. Proper motions, accelerations and jerks

This paper is the second in a series where we report the results of the long-term timing of the millisecond pulsars (MSPs) in 47 Tucanae with the Parkes 64-m radio telescope. We obtain improved timing parameters that provide additional information for studies of the cluster dynamics: a) the pulsar proper motions yield an estimate of the proper motion of the cluster as a whole ($\mu_{\alpha}\, = \, 5.00\, \pm \, 0.14\, \rm mas \, yr^{-1}$, $\mu_{\delta}\, = \, -2.84\, \pm \, 0.12\, \rm mas \, yr^{-1}$) and the motion of the pulsars relative to each other. b) We measure the second spin-period derivatives caused by the change of the pulsar line-of-sight accelerations; 47 Tuc H, U and possibly J are being affected by nearby objects. c) For ten binary systems we now measure changes in the orbital period caused by their acceleration in the gravitational field of the cluster. From all these measurements, we derive a cluster distance no smaller than $\sim\,$4.69 kpc and show that the characteristics of these MSPs are very similar to their counterparts in the Galactic disk. We find no evidence in favour of an intermediate mass black hole at the centre of the cluster. Finally, we describe the orbital behaviour of the four "black widow" systems. Two of them, 47 Tuc J and O, exhibit orbital variability similar to that observed in other such systems, while for 47 Tuc I and R the orbits seem to be remarkably stable. It appears, therefore, that not all "black widows" have unpredictable orbital behaviour.Comment: 21 pages in journal format, 9 figures, 4 tables, accepted for publication in MNRAS, several clarifications made and typos fixe

Increase of Circulating Monocyte–Platelet Conjugates in Rheumatoid Arthritis Responders to IL-6 Blockage

Monocytes; Rheumatoid arthritis; TocilizumabMonocitos; Artritis reumatoide; TocilizumabMonòcits; Artritis reumatoide; TocilizumabPlatelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte–PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte–PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6.This study is supported by Instituto de Salud Carlos III and Fondos FEDER (PI17/00072 and PI20/00184)

Altered CD39 and CD73 Expression in Rheumatoid Arthritis: Implications for Disease Activity and Treatment Response

Rheumatoid arthritis; TocilizumabArtritis reumatoide; TocilizumabArtritis reumatoide; TocilizumabIn rheumatoid arthritis (RA) synovium, ATP, and ADP are released, sparking inflammation. Ectoenzymes CD39 and CD73 metabolize these purine nucleotides, generating anti-inflammatory adenosine. Therefore, dysregulated CD39 and CD73 expression may impact RA development. We assessed CD39 and CD73 expression in peripheral blood from 15 healthy controls (Cs) and 35 RA patients at baseline and after 3 and 6 months of tocilizumab treatment using flow cytometry. Additionally, ectoenzyme expression was examined on cultured T cells to understand activation and IL-6 effects. At baseline, RA patients exhibited a lower CD8+CD39−CD73+ cell percentage, which inversely correlated with DAS28. Additionally, they had lower percentages of Treg CD39+CD73+ and CD39−CD73− cells. Good responders tended to have lower B CD39+CD73+ cell percentages at baseline and 3 months. Additionally, Treg, CD8+ T and B cells inversely correlated with DAS28. T-cell activation increased CD39 and decreased CD73 expression, regardless of IL-6. IL-6 reduced IFNγ-secreting CD4+ T-cell percentage in Cs, but increased the percentage of IFNγ-secreting CD4+ and CD8+ T cells in RA patients. These findings indicate differing CD39 and CD73 expression in RA and Cs, influenced by T-cell activation and IL-6. Correlations between these molecules and RA activity suggest their role in dysregulated inflammation in RA.The research reported in this publication was supported by Roche Farma S.A., IIBSP-TOC-2016-09 (Institut Recerca Hospital de la Santa Creu i Sant Pau); ML30151 (Roche)

Explosive forming of 2219 aluminum final report

Variables affecting metal springback of aluminum during explosive deformation and influence of high energy forming on metallurgical behavio