Summary
Background
Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline ...phosphatase ALP and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long‐term effectiveness of second‐line treatments remains uncertain.
Aims
To evaluate the long‐term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation).
Methods
We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non‐responsive PBC patients (Paris‐II criteria) from Spain and Portugal who received OCA ± fibrates.
Results
Of 255 patients, median follow‐up was 35.1 months (IQR: 20.2–53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE‐PBC and 5‐year UK‐PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension.
Conclusion
Triple therapy was superior in achieving therapeutic goals in UDCA‐nonresponsive PBC. Decompensation was linked to pre‐existing portal hypertension.
Longitudinal, real‐world study on 255 UDCA‐nonresponsive PBC patients (Per Paris II criteria); median follow‐up of 35.1 months (IQR: 20–53). All patients received obeticholic acid (OCA), with 25% receiving later add‐on fibrate treatment (triple therapy). In multivariate analysis, triple therapy outperformed dual therapy across all surrogate biochemical endpoints of outcomes.
In this paper we measure the merger fraction and rate, both minor and major, of massive early-type galaxies (M_star >= 10^11 M_Sun) in the COSMOS field, and study their role in mass and size ...evolution. We use the 30-band photometric catalogue in COSMOS, complemented with the spectroscopy of the zCOSMOS survey, to define close pairs with a separation 10h^-1 kpc <= r_p <= 30h-1 kpc and a relative velocity Delta v <= 500 km s^-1. We measure both major (stellar mass ratio mu = M_star,2/M_star,1 >= 1/4) and minor (1/10 <= mu < 1/4) merger fractions of massive galaxies, and study their dependence on redshift and on morphology. The merger fraction and rate of massive galaxies evolves as a power-law (1+z)^n, with major mergers increasing with redshift, n_MM = 1.4, and minor mergers showing little evolution, n_mm ~ 0. When split by their morphology, the minor merger fraction for early types is higher by a factor of three than that for spirals, and both are nearly constant with redshift. Our results show that massive early-type galaxies have undergone 0.89 mergers (0.43 major and 0.46 minor) since z ~ 1, leading to a mass growth of ~30%. We find that mu >= 1/10 mergers can explain ~55% of the observed size evolution of these galaxies since z ~ 1. Another ~20% is due to the progenitor bias (younger galaxies are more extended) and we estimate that very minor mergers (mu < 1/10) could contribute with an extra ~20%. The remaining ~5% should come from other processes (e.g., adiabatic expansion or observational effects). This picture also reproduces the mass growth and velocity dispersion evolution of these galaxies. We conclude from these results that merging is the main contributor to the size evolution of massive ETGs at z <= 1, accounting for ~50-75% of that evolution in the last 8 Gyr. Nearly half of the evolution due to mergers is related to minor (mu < 1/4) events.
To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT).
We performed a multinational case-control study that retrospectively ...recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy.
We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07–179.46; p 0.009) was identified as an independent risk factor for late IPA.
More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.
Abstract
In Montero-Dorta et al., we show that luminous red galaxies (LRGs) from the SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS) at z ∼ 0.55 can be divided into two groups based on their ...star formation histories. So-called fast-growing LRGs assemble 80 per cent of their stellar mass at z ∼ 5, whereas slow-growing LRGs reach the same evolutionary state at z ∼ 1.5. We further demonstrate that these two subpopulations present significantly different clustering properties on scales of ∼1−30 Mpc. Here, we measure the mean halo mass of each subsample using the galaxy–galaxy lensing technique, in the ${\sim }190\deg ^2$ overlap of the LRG catalogue and the CS82 and CFHTLenS shear catalogues. We show that fast- and slow-growing LRGs have similar lensing profiles, which implies that they live in haloes of similar mass: $\log (M_{\rm halo}^{\rm fast}/h^{-1}\mathrm{M}_{{\odot }}) = 12.85^{+0.16}_{-0.26}$ and $\log (M_{\rm halo}^{\rm slow}/h^{-1}\mathrm{M}_{{\odot }}) =12.92^{+0.16}_{-0.22}$. This result, combined with the clustering difference, suggests the existence of galaxy assembly bias, although the effect is too subtle to be definitively proven, given the errors on our current weak-lensing measurement. We show that this can soon be achieved with upcoming surveys like DES.
Here, we investigated for the first time the frequency and number of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of newly diagnosed patients with localized and systemic plasma cell ...neoplasms (PCN) using next-generation flow cytometry (NGF) and correlated our findings with the distinct diagnostic and prognostic categories of the disease. Overall, 508 samples from 264 newly diagnosed PCN patients, were studied. CTPC were detected in PB of all active multiple myeloma (MM; 100%), and smoldering MM (SMM) patients (100%), and in more than half (59%) monoclonal gammopathy of undetermined significance (MGUS) cases (p <0.0001); in contrast, CTPC were present in a small fraction of solitary plasmacytoma patients (18%). Higher numbers of CTPC in PB were associated with higher levels of BM infiltration and more adverse prognostic features, together with shorter time to progression from MGUS to MM (p <0.0001) and a shorter survival in MM patients with active disease requiring treatment (p ≤ 0.03). In summary, the presence of CTPC in PB as assessed by NGF at diagnosis, emerges as a hallmark of disseminated PCN, higher numbers of PB CTPC being strongly associated with a malignant disease behavior and a poorer outcome of both MGUS and MM.
•The temperature inside asphalt binder specimen during cyclic testing was measured.•Cyclic testing caused an important increase in the inside temperature of the binder.•At least 88% of the modulus ...loss was explained by temperature change.•Mixture resistance to cyclic testing showed strong dependency on rest periods.•Heating has to be taken into account on fatigue life prediction.
This paper’s objective is to evaluate the reversible phenomena that take place when asphalt materials are subjected to cyclic loads, i.e., self-heating and thixotropy. A strain sweep test was adapted to capture the stiffness variation of binders with the change in strain amplitude. The evolution of the internal temperature of the binder during the test was measured. Results show that the temperature can increase very significantly during cyclic testing and can account for a great part of all stiffness reduction captured during the test at different strain amplitudes. These results led to the conclusion that internal heating should be very important in asphalt mixtures as well. For that reason two types of time sweep tests were performed on the same mixture, with the introduction of rest periods in one of them long enough to let the inside temperature of the material lower after cycling. The results showed that the specimen that was allowed to cool down did not experience any loss of stiffness, while the specimen submitted to the conventional time sweep test failed in a few cycles. These results show the importance of the sequencing of loading and discourage the application of the Miner’s law to estimate pavement life.
A key open issue for galaxy evolution and formation models is the understanding of the different mechanisms of galaxy assembly at various cosmic epochs. The aim of this study is to derive the global ...and spatially-resolved metal content in high-redshift galaxies. Using VLT/SINFONI IFU spectroscopy of a first sample of 50 galaxies at z~1.2 in the MASSIV survey, we are able to measure the Ha and NII6584 emission lines. Using the N2 ratio as a proxy for oxygen abundance in the interstellar medium, we measure the metallicity of the sample galaxies. We develop a tool to extract spectra in annular regions of these galaxies, leading to a spatially-resolved estimate of the oxygen abundance in each galaxy. We derive a metallicity gradient for 26 galaxies in our sample and discover a significant fraction of galaxies with a "positive" gradient. Using a simple chemical evolution model, we derive infall rates of pristine gas onto the disks. Seven galaxies display a positive gradient at a high confidence level. Four out of these are interacting and one is a chain galaxy. We suggest that interactions might be responsible for shallowing and even inverting the abundance gradient. We also identify two interesting correlations in our sample: a) galaxies with higher gas velocity dispersion have shallower/positive gradients; and b) metal-poor galaxies tend to show a positive gradient whereas metal-rich ones tend to show a negative one. This last observation can be explained by the infall of metal-poor gas into the center of the disks. We address the question of the origin of this infall under the influence of gas flows triggered by interactions and/or cold gas accretion.
Understanding how galaxies evolve and assemble their mass across cosmic time is still a fundamental unsolved issue. To get insight into the various processes of galaxy mass assembly, the Mass ...Assembly Survey with SINFONI in VVDS (MASSIV) aims at probing the kinematical and chemical properties of a significant and representative sample of high-redshift (0.9 < z < 1.8) star-forming galaxies. This paper presents the selection function, the observing strategy and the global properties of the MASSIV sample. This sample contains 84 star-forming galaxies, selected from the VIMOS VLT Deep Survey (VVDS) and observed with the SINFONI IFU at the VLT. We present the redshift distribution, and derive the stellar masses and SED-based star formation rates (SFR). Integrated metallicities and the presence of type-2 AGNs are investigated using composite 1D spectra built from VIMOS and SINFONI observations. The MASSIV selection function, based on star formation criteria (OII emission-line strength up to z~1.5 and colors/UV absorption lines at higher redshifts), provides a good representation of "normal" star-forming galaxies with SED-based SFRs between 5 and 400 Msun/yr in the stellar mass regime 10^9 - 10^11 Msun. Analysis of typical emission-line ratios performed on composite spectra reveals that the contamination by type-2 AGNs is very low and that the integrated metallicity of the galaxies follows the well-known mass-metallicity relation. The MASSIV sample has been built upon a simple selection function, fully representative of the star-forming galaxy population at 0.9 < z < 1.8 for SFR > 5 Msun/yr. Together with the size of the sample, the spatially-resolved SINFONI data therefore enables us to discuss global, volume averaged, galaxy kinematic and chemical properties all accross the mass and SFR range of the survey to derive robust conclusions on galaxy mass assembly over cosmological timescales.
Spectrophotometry constitutes a unique way to obtain the whole diagnostics
(density, temperature, ionic abundances) of ionized gas nebulae, thus providing
invaluable information about the objects ...where they reside. If such nebulae are
in the low excitation regime, the diagnostics have to relie on the observation
of the more intense emission lines. We have compiled data for a sample of HII
regions, GEHR and HII galaxies and compared them with results derived from
photoionizacion models whose parameters cover the physical conditions of the
nebulae. Our results confirm a lower uncertainty for the diagnostics when using
empirical methods based on the strong lines of SII and SIII replacing and
complementing those based on the OII and OIII lines.
A long-term multi-parameter skill assessment of a 5-MHz Coastal Ocean Dynamics Applications Radar (CODAR) SeaSonde High-Frequency radar (HFR) network deployed along the Galician Coast (NW Iberian ...Peninsula) was attempted for 2014-2016. To this aim, wave estimations from two HFR sites, obtained directly by the CODAR radar proprietary software, were independently validated against hourly in situ observations from two moored buoys for two different periods. The accuracy assessment of significant wave height (H
s
) revealed a consistent agreement with Pearson´s correlation coefficients (r) above 0.75 and normalized root mean squared errors below 0.4. An overall slight overestimation of H
s
radar estimations was evidenced, likely due to spurious contributions to the directional spectra. The seasonal analysis revealed that the performance of this low mono-frequency radar was more precise for high-sea states during wintertime, whereas the quality and availability of radar data decreased under summer less energetic conditions, in accordance with previous works. In the case of the centroid wave period, HFR performance was consistent through the different years, with r values emerging in the range of 0.61-0.74. The directional accuracy was moderately good, with NW and W-NW as predominant sectors. Despite r values above 0.74, a tendency for CODAR HFR-derived incoming mean wave direction to be aligned more perpendicular to the coast compared to offshore in situ data was also observed. Furthermore, the relationship between the North Atlantic Oscillation (NAO) and HFR wave estimations was explored. A subtle but statistically significant connection was found, with H
s
and centroid wave period being positively correlated with NAO daily index. Complementarily, the skill of the Galician HFR system was evaluated under positive and negative NAO conditions in order to elucidate whether the radar accuracy is or is not NAO-phase dependent. No substantial differences could be found for each of the three parameters analysed as HFR accuracy remained mostly unaffected by swings in the NAO index. Finally, it can be concluded that properly treated CODAR radar-derived wave estimations can be potentially employed for operational coastal monitoring across a wide range of sea states.
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