Wind-induced changes in the dynamics of fluorescent organic matter in the coastal NW Mediterranean

Original research paperMarine biogeochemistry dynamics in coastal marine areas is strongly influenced by episodic events such as rain, intense winds, river discharges and anthropogenic activities. We evaluated in this study the importance of these forcing events on modulating seasonal changes in the marine biogeochemistry of the northwestern coast of the Mediterranean Sea, based on data gathered from a fixed coastal sampling station in the area. A 4-year (2011–2014) monthly sampling at four depths (0.5 m, 20 m, 50 m and 80 m) was performed to examine the time variability of several oceanographic variables: seawater temperature, salinity, inorganic nutrient concentrations (NO3−, PO43 − and SiO2), chlorophyll a (Chl a), dissolved organic carbon (DOC) and fluorescent dissolved organic matter (FDOM). FDOM dynamics was predominantly influenced by upwelling events and mixing processes, driven by strong and characteristic wind episodes. SW wind episodes favored the upwelling of deeper and denser waters into the shallower shelf, providing a surplus of autochthonous humic-like material and inorganic nutrients, whereas northerlies favored the homogenization of the whole shelf water column by cooling and evaporation. These different wind-induced processes (deep water intrusion or mixing), reported along the four sampled years, determined a high interannual environmental variability in comparison with other Mediterranean sampling sites. Graphical abstract Image 1 Download : Download high-res image (344KB)Download : Download full-size imageECOSER (CTM2011-15937-E), DOREMI (CTM2012-342949), SUAVE (CTM2014/ 23456/1) and ANIMA (CTM2015-65720) from the Spanish Ministerio de Economía y Competitividad (MINECO) and the Grup de Recerca Consolidat 2014SGR1179 and 2014SGR1029 financed by the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) from the Generalitat de Catalunya; (JAEPre_2011_00923) from the Agencia Estatal Consejo Su perior de Investigaciones Científicas (CSIC) and the project FERMIO (MINECO, CTM2014-57334-JIN) co-financed with FEDER fundsVersión del editor3,25

First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors

Agonistic 4-1BB monoclonal antibodies were preclinically validated as promising cancer immunotherapies, both as monotherapy and as potentiators of the activity of PD-(L) 1–blocking agents. However, toxicity and a narrow therapeutic window have hampered their clinical development. DuoBodyPD-L1×4-1BB, a first-in-class, bispecific, next-generation checkpoint immunotherapy, was designed to overcome these limitations by activating T cells through conditional 4-1BB costimulation, while simultaneously blocking the PD-L1 axis. We present preliminary data from the ongoing, first-in-human, open-label, phase I/IIa trial of DuoBody-PD-L1×4-1BB in advanced solid tumors (NCT03917381)

Haloes gone MAD: The Halo-Finder Comparison Project

[abridged] We present a detailed comparison of fundamental dark matter halo properties retrieved by a substantial number of different halo finders. These codes span a wide range of techniques including friends-of-friends (FOF), spherical-overdensity (SO) and phase-space based algorithms. We further introduce a robust (and publicly available) suite of test scenarios that allows halo finder developers to compare the performance of their codes against those presented here. This set includes mock haloes containing various levels and distributions of substructure at a range of resolutions as well as a cosmological simulation of the large-scale structure of the universe. All the halo finding codes tested could successfully recover the spatial location of our mock haloes. They further returned lists of particles (potentially) belonging to the object that led to coinciding values for the maximum of the circular velocity profile and the radius where it is reached. All the finders based in configuration space struggled to recover substructure that was located close to the centre of the host halo and the radial dependence of the mass recovered varies from finder to finder. Those finders based in phase space could resolve central substructure although they found difficulties in accurately recovering its properties. Via a resolution study we found that most of the finders could not reliably recover substructure containing fewer than 30-40 particles. However, also here the phase space finders excelled by resolving substructure down to 10-20 particles. By comparing the halo finders using a high resolution cosmological volume we found that they agree remarkably well on fundamental properties of astrophysical significance (e.g. mass, position, velocity, and peak of the rotation curve).Comment: 27 interesting pages, 20 beautiful figures, and 4 informative tables accepted for publication in MNRAS. The high-resolution version of the paper as well as all the test cases and analysis can be found at the web site http://popia.ft.uam.es/HaloesGoingMA

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions

Haloes gone MAD: The Halo-Finder Comparison Project

We present a detailed comparison of fundamental dark matter halo properties retrieved by a substantial number of different halo finders. These codes span a wide range of techniques including friends-of-friends, spherical-overdensity and phase-space-based algorithms. We further introduce a robust (and publicly available) suite of test scenarios that allow halo finder developers to compare the performance of their codes against those presented here. This set includes mock haloes containing various levels and distributions of substructure at a range of resolutions as well as a cosmological simulation of the large-scale structure of the universe. All the halo-finding codes tested could successfully recover the spatial location of our mock haloes. They further returned lists of particles (potentially) belonging to the object that led to coinciding values for the maximum of the circular velocity profile and the radius where it is reached. All the finders based in configuration space struggled to recover substructure that was located close to the centre of the host halo, and the radial dependence of the mass recovered varies from finder to finder. Those finders based in phase space could resolve central substructure although they found difficulties in accurately recovering its properties. Through a resolution study we found that most of the finders could not reliably recover substructure containing fewer than 30-40 particles. However, also here the phase-space finders excelled by resolving substructure down to 10-20 particles. By comparing the halo finders using a high-resolution cosmological volume, we found that they agree remarkably well on fundamental properties of astrophysical significance (e.g. mass, position, velocity and peak of the rotation curve). We further suggest to utilize the peak of the rotation curve, vmax, as a proxy for mass, given the arbitrariness in defining a proper halo edg

Structural Conformers of (1,3-Dithiol-2-ylidene)ethanethioamides: The Balance Between Thioamide Rotation and Preservation of Classical Sulfur-Sulfur Hypervalent Bonds

The reaction of N-(2-phthalimidoethyl)-N-alkylisopropylamines and S2Cl2 gave 4-N-(2-phthalimidoethyl)-N-alkylamino-5-chloro-1,2-dithiol-3-thiones that quantitatively cycloadded to dimethyl or diethyl acetylenedicarboxylate to give stable thioacid chlorides, which in turn reacted with one equivalent of aniline or a thiole to give thioanilides or a dithioester. Several compounds of this series showed atropisomers that were studied by a combination of dynamic NMR, simulation of the signals, conformational analysis by DFT methods, and single crystal X-ray diffraction, showing a good correlation between the theoretical calculations, the experimental values of energies, and the preferred conformations in the solid state. The steric hindering of the crowded substitution at the central amine group was found to be the reason for the presence of permanent atropisomers in this series of compounds and the cause of a unique disposition of the thioxo group at close-to-right angles with respect to the plane defined by the 1,3-dithiole ring in the dithiafulvene derivatives, thus breaking the sulfur–sulfur hypervalent bond that is always found in this kind of compounds.Ministerio de Economıá y Competitividad, Spain (Project CTQ2012- 31611), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Project BU246A12-1), and the European Commission, Seventh Framework Programme (Project SNIFFER FP7-SEC-2012-312411

Comparative evaluation of 11 commercialized rapid diagnostic tests for detecting Trypanosoma cruzi antibodies in serum banks in areas of endemicity and nonendemicity

Chagas disease is one of the main public health issues in Latin America. Increasingly during the past few decades, Trypanosoma cruzi infection has been detected in North America, Europe, and the Western Pacific, mainly as a result of population movement. The limited availability of rapid serological diagnostic tests hinders rapid diagnosis and early treatment in areas of endemicity and nonendemicity. In collaboration with 11 national reference laboratories (NRLs) from different geographical areas, we evaluated the performances of commercialized serological rapid diagnostic tests (RDT) for T. cruzi infection. Eleven commercialized T. cruzi infection RDTs were evaluated on a total of 474 samples extensively tested with at least three different techniques for Chagas disease, maintained at controlled low temperatures, and stored in the serum banks of the 11 NRLs. We measured the sensitivity, specificity, and concordance of each RDT and provided an additional questionnaire to evaluate its ease of use. The selected RDTs in this study were performed under controlled laboratory conditions. Out of the 11 RDTs, we found 8 of them to be useful, with the cassette format favored over the strip. We did not observe significant differences in RDT performances in the different regions. Overall, the performance results were lower than those disclosed by the manufacturers. The results of this evaluation validate the possibility of using RDTs to diagnose Chagas disease, thereby decreasing the time to treatment at a primary health care facility for patients who are willing to be treated. Further studies should be conducted in the laboratory and in the field to confirm these data, expressly to evaluate reproducibility in resource-limited settings, or using whole blood in clinical settings in areas of endemicity and nonendemicity

Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis

Objective: structural brain imaging studies in obsessive compulsive disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in illness profile and developmental stage. To address these limitations, the authors conducted meta and mega-analyses of data from OCD sites worldwide. Method: T-1 images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients. Results: the meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen's d=-0.13; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=-0.29, % difference=-4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results. Conclusions: the results indicate different patterns of sub cortical abnormalities in pediatric and adult OCD patients. The patlidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful