Trans-amidate platinum complexes anchoring water and N-donor molecules. The importance of hydrogen bonding

The square planar bisnitrile platinum(II) derivatives PtCl2(NCR)2 (R=Ph (1 a); Et (1 b); p-C6H4F (1 c); p-C6H4tBu (1 d); m-C6H3Me2 (1 e); o, p-C6H2Me3 (1 f)) react with tetrabutylammonium hydroxide to render the monoaquo NBu4]trans-PtCl(HNCOR)2(OH2)] (2 a–2 f). The water molecule is s-coordinated to platinum and the binding is reinforced by two strong hydrogen bonds to the neighboring amidate ligands (OH···OC). Substitution of water in 2 a by N-donor ligands can be efficiently achieved only in the presence of a dehydrating agent as magnesium sulphate or 4 Å molecular sieves. By following this strategy, compounds NBu4]trans-PtCl(HNCOPh)2(NH2R’)] (R’=H (3), NH2 (4), tBu (5 a), p-C6H4Me (5 b) have been isolated. The incoming ligands are s-coordinated to platinum and also establish strong hydrogen bonds to the amidates (NH···OC). Treatment of 2 a with halogens causes oxidation at the metal center, rendering the platinum(IV) derivatives NBu4]PtClX2(HNCOPh)2(OH2)] (X=Cl (6 a), Br (6 b), I (6 c))

The Late Medieval archaeological site of Plaça dels Maristes (Pontós, Alt Empordà)

Aquesta excavació preventiva va permetre documentar un modest establiment rural, molt afectat pel fet de trobar-se immediatament a sota del nivell del sòl, que caldria datar entre la segona meitat potser avançada del segle vii i els inicis del ix. No es tracta d’un fet aïllat sinó d’un tipus d’hàbitat que va ocupar el territori després de la fallida de les vil·les.A rescue excavation brought to light a modest rural settlement in a poor state of conservation due to its position directly beneath the surface. The site is dated between the end of the second half of the 7th century and the beginning of 9th century. It is not isolated as this type of settlement was spread accross the territory after the collapse of the villae

Global-scale changes to extreme ocean wave events due to anthropogenic warming

Extreme surface ocean waves are often primary drivers of coastal flooding and erosion over various time scales. Hence, understanding future changes in extreme wave events owing to global warming is of socio-economic and environmental significance. However, our current knowledge of potential changes in high-frequency (defined here as having return periods of less than 1 year) extreme wave events are largely unknown, despite being strongly linked to coastal hazards across time scales relevant to coastal management. Here, we present global climate-modeling evidence, based on the most comprehensive multi-method, multi-model wave ensemble, of projected changes in a core set of extreme wave indices describing high-frequency, extra-tropical storm-driven waves. We find changes in high-frequency extreme wave events of up to ∼50%-100% under RCP8.5 high-emission scenario; which is nearly double the expected changes for RCP4.5 scenario, when globally integrated. The projected changes exhibit strong inter-hemispheric asymmetry, with strong increases in extreme wave activity across the tropics and high latitudes of the Southern Hemisphere region, and a widespread decrease across most of the Northern Hemisphere. We find that the patterns of projected increase across these extreme wave events over the Southern Hemisphere region resemble their historical response to the positive anomaly of the Southern Annular Mode. Our findings highlight that many countries with low-adaptive capacity are likely to face increasing exposure to much more frequent extreme wave events in the future

The Tordera Delta, a hotspot to storm impacts in the coast northwards ofBarcelona (NW Mediterranean)

The Catalan coast, as most of the developed Mediterranean coastal zone, can be characterized as a high-risk area to the impact of storms due to the large concentrationof values together with the dominance of eroding shorelines. In consequence, any long-term coastal management scheme must include a risk analysis to permitdecision makers to better allocate resources. This can be done in a nested approach in which hotspots are first identified along the coast at a regional scale andsecondly, they are further analysed to produce dedicated risk reduction strategies. In this work, we apply the methodology developed within the RISC-KIT project foridentifying and analysing coastal hotspots in the Catalan coast as a test for applying it to Mediterranean conditions. Obtained results show that this methodology isvery efficient in identifying hotspots of storm-induced flooding and erosion at a regional scale. The adoption of the response approach resulted in the direct assessmentof the hazards' probability distributions, which allowed for the selection of the severity of the hotspots to be identified. When a given coastal stretch behaves as ahotspot for both hazards, it is identified as a very highly-sensitive area to storm impacts. In the study area, the Tordera Delta possesses this condition of very high“hotspotness.” This has been demonstrated by the large and frequent damages suffered by the site during the past decades. The paper analyses different aspects related to the risk management of this area, including stakeholder actions

Prognostic ability of EndoPredict compared to research-based versions of the PAM50 risk of recurrence (ROR) scores in node-positive, estrogen receptor-positive, and HER2-negative breast cancer. A GEICAM/9906 sub-study

There are several prognostic multigene-based tests for managing breast cancer (BC), but limited data comparing them in the same cohort. We compared the prognostic performance of the EndoPredict (EP) test (standardized for pathology laboratory) with the research-based PAM50 non-standardized qRT-PCR assay in node-positive estrogen receptor-positive (ER+) and HER2-negative (HER2−) BC patients receiving adjuvant chemotherapy followed by endocrine therapy (ET) in the GEICAM/9906 trial. EP and PAM50 risk of recurrence (ROR) scores [based on subtype (ROR-S) and on subtype and proliferation (ROR-P)] were compared in 536 ER+/HER2− patients. Scores combined with clinical information were evaluated: ROR-T (ROR-S, tumor size), ROR-PT (ROR-P, tumor size), and EPclin (EP, tumor size, nodal status). Patients were assigned to risk-categories according to prespecified cutoffs. Distant metastasis-free survival (MFS) was analyzed by Kaplan–Meier. ROR-S, ROR-P, and EP scores identified a low-risk group with a relative better outcome (10-year MFS: ROR-S 87%; ROR-P 89%; EP 93%). There was no significant difference between tests. Predictors including clinical information showed superior prognostic performance compared to molecular scores alone (10-year MFS, low-risk group: ROR-T 88%; ROR-PT 92%; EPclin 100%). The EPclin-based risk stratification achieved a significantly improved prediction of MFS compared to ROR-T, but not ROR-PT. All signatures added prognostic information to common clinical parameters. EPclin provided independent prognostic information beyond ROR-T and ROR-PT. ROR and EP can reliably predict risk of distant metastasis in node-positive ER+/HER2− BC patients treated with chemotherapy and ET. Addition of clinical parameters into risk scores improves their prognostic ability.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-3725-z) contains supplementary material, which is available to authorized users

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo -expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates

PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical–pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-013-2416-2) contains supplementary material, which is available to authorized users

<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data