Properties of Cosmic Deuterons Measured by the Alpha Magnetic Spectrometer.

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of the deuteron (D) flux are presented. The measurements are based on 21×10^{6} D nuclei in the rigidity range from 1.9 to 21 GV collected from May 2011 to April 2021. We observe that over the entire rigidity range the D flux exhibits nearly identical time variations with the p, ^{3}He, and ^{4}He fluxes. Above 4.5 GV, the D/^{4}He flux ratio is time independent and its rigidity dependence is well described by a single power law ∝R^{Δ} with Δ_{D/^{4}He}=-0.108±0.005. This is in contrast with the ^{3}He/^{4}He flux ratio for which we find Δ_{^{3}He/^{4}He}=-0.289±0.003. Above ∼13 GV we find a nearly identical rigidity dependence of the D and p fluxes with a D/p flux ratio of 0.027±0.001. These unexpected observations indicate that cosmic deuterons have a sizable primarylike component. With a method independent of cosmic ray propagation, we obtain the primary component of the D flux equal to 9.4±0.5% of the ^{4}He flux and the secondary component of the D flux equal to 58±5% of the ^{3}He flux.

Meiofauna at a tropical sandy beach in the SW Atlantic: the influence of seasonality on diversity.

Background: Sandy beaches are dynamic environments housing a large diversity of organisms and providing important environmental services. Meiofaunal metazoan are small organisms that play a key role in the sediment. Their diversity, distribution and composition are driven by sedimentary and oceanographic parameters. Understanding the diversity patterns of marine meiofauna is critical in a changing world. Methods: In this study, we investigate if there is seasonal difference in meiofaunal assemblage composition and diversity along 1 year and if the marine seascapes dynamics (water masses with particular biogeochemical features, characterized by temperature, salinity, absolute dynamic topography, chromophoric dissolved organic material, chlorophyll-a, and normalized fluorescent line height), rainfall, and sediment parameters (total organic matter, carbonate, carbohydrate, protein, lipids, protein-to-carbohydrate, carbohydrate-to-lipids, and biopolymeric carbon) affect significatively meiofaunal diversity at a tropical sandy beach. We tested two hypotheses here: (i) meiofaunal diversity is higher during warmer months and its composition changes significatively among seasons along a year at a tropical sandy beach, and (ii) meiofaunal diversity metrics are significantly explained by marine seascapes characteristics and sediment parameters. We used metabarcoding (V9 hypervariable region from 18S gene) from sediment samples to assess the meiofaunal assemblage composition and diversity (phylogenetic diversity and Shannon's diversity) over a period of 1 year. Results: Meiofauna was dominated by Crustacea (46% of sequence reads), Annelida (28% of sequence reads) and Nematoda (12% of sequence reads) in periods of the year with high temperatures (>25 °C), high salinity (>31.5 ppt), and calm waters. Our data support our initial hypotheses revealing a higher meiofaunal diversity (phylogenetic and Shannon's Diversity) and different composition during warmer periods of the year. Meiofaunal diversity was driven by a set of multiple variables, including biological variables (biopolymeric carbon) and organic matter quality (protein content, lipid content, and carbohydrate-to-lipid ratio).

Lomustine with or without reirradiation for first progression of glioblastoma, LEGATO, EORTC-2227-BTG: study protocol for a randomized phase III study.

BACKGROUND: Chemotherapy with lomustine is widely considered as standard treatment option for progressive glioblastoma. The value of adding radiotherapy to second-line chemotherapy is not known. METHODS: EORTC-2227-BTG (LEGATO, NCT05904119) is an investigator-initiated, pragmatic (PRECIS-2 score: 34 out of 45), randomized, multicenter phase III trial in patients with first progression of glioblastoma. A total of 411 patients will be randomized in a 1:1 ratio to lomustine (110 mg/m2 every 6 weeks) or lomustine (110 mg/m2 every 6weeks) plus radiotherapy (35 Gy in 10 fractions). Main eligibility criteria include histologic confirmation of glioblastoma, isocitrate dehydrogenase gene (IDH) wild-type per WHO 2021 classification, first progression at least 6 months after the end of prior radiotherapy, radiologically measurable disease according to RANO criteria with a maximum tumor diameter of 5 cm, and WHO performance status of 0-2. The primary efficacy endpoint is overall survival (OS) and secondary endpoints include progression-free survival, response rate, neurocognitive function, health-related quality of life, and health economic parameters. LEGATO is funded by the European Union's Horizon Europe Research program, was activated in March 2024 and will enroll patients in 43 sites in 11 countries across Europe with study completion projected in 2028. DISCUSSION: EORTC-2227-BTG (LEGATO) is a publicly funded pragmatic phase III trial designed to clarify the efficacy of adding reirradiation to chemotherapy with lomustine for the treatment of patients with first progression of glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT05904119. Registered before start of inclusion, 23 May 2023.

Soil greenhouse gas emissions from dead and natural mangrove forests in Southeastern Brazil.

Mangroves forests may be important sinks of carbon in coastal areas but upon their death, these forests may become net sources of carbon dioxide (CO2) and methane (CH4) to the atmosphere. Here we assessed the spatial and temporal variability in soil CO2 and CH4 fluxes from dead mangrove forests and paired intact sites in SE-Brazil. Our findings demonstrated that during warmer and drier conditions, CO2 soil flux was 183 % higher in live mangrove forests when compared to the dead mangrove forests. Soil CH4 emissions in live forests were > 1.4-fold higher than the global mangrove average. During the wet season, soil GHG emissions dropped significantly at all sites. During warmer conditions, mangroves were net sources of GHG, with a potential warming effect (GWP100) of 32.9 ± 10.2 (±SE) Mg CO2e ha-1 y-1. Overall, we found that dead mangroves did not release great amounts of GHG after three years of forest loss.

[Synthetic indicator of compliance with standards for Quality Units of health centers and multicenter prospective pilot study]. / Indicador sintético de cumplimiento de estándares para Unidades de Calidad de centros sanitarios y estudio de pilotaje prospectivo multicéntrico.

BACKGROUND AND OBJECTIVE: In Spain, Quality Units play a key and unique role in advising healthcare centers on the methodology of healthcare quality. The objectives of the study were to develop computer algorithms to obtain a synthetic indicator of standard compliance for Quality Units and to pilot its functioning in these units. MATERIALS AND METHODS: The Excel program was used to establish evaluation algorithms, and quantitatively interrelate and weight various categories of standards, as a computer evaluation tool, to build a continuous improvement cycle system, and offer a global synthetic indicator of compliance. The tool was tested in a prospective multicenter pilot study, in which coordinators of Quality Units from different health centers and care settings participated, to evaluate the usefulness of the tool and compliance with the standards, in addition to analyzing the content validity of each standard. RESULTS: The formulas for the structured computer algorithms were developed, consecutively, in a «PLAN-DO-CHECK-ACT¼ improvement cycle for the 9 categories of standards, resulting in a single synthetic indicator of compliance. Twenty-one Quality Units participated in the piloting. The overall average compliance rate for the synthetic indicator was 55.63% with differences between centers (P=.002) and between categories (P<.0001), but not by autonomous communities (P=.86) or by areas (P=.97). Content validity was ensured through the variable of «understanding¼ of the standards (P<.001), and through their «justification¼ with documentary evidence (P<.001). CONCLUSIONS: The computer tool with the synthetic indicator have allowed for the evaluation of standard compliance in Quality Units of healthcare centers.

Milk quality of Italian Mediterranean Buffalo as affected by Temperature-Humidity Index during late spring and summer.

Eighteen Italian Mediterranean buffalo cows were subjected to fortnightly milk sampling from May to July 2022. Air temperature and relative humidity were monitored throughout the trial; temperature-humidity index (THI) was calculated and ranged from 69 to 79 so that 3 classes were set to study the effect of different THI on milk quality: THI less than 72 - THI < 72; THI ranging from 72 to 76 THI72-76, and THI over 76 - THI > 76. Individual milk samples from buffalo cows were analyzed for milk composition and coagulation traits, fatty acid and amino-acid composition, enzymatic and mineral profile. The THI > 76 class registered the highest lactose content and poorer milk clot characteristics in comparison with THI < 72. Exposure to THI over 76 resulted in increased contents of saturated and short- chain fatty acids in milk as well as in the highest values of atherogenic and thrombogenic indexes and the lowest essential amino-acid content. Moreover, the lowest value of Calcium, Copper and Selenium contents were found in the milk of buffalo cows exposed to THI over 72. Results confirm that Italian Mediterranean buffalo expresses a good level of thermo-tolerance, even though exposure to daily THI over 76 has a deleterious effect on some nutritional and technological properties of milk.

The inclusion of Amazon mangroves in Brazil's REDD+ program.

The Legal Amazon of Brazil holds vast mangrove forests, but a lack of awareness of their value has prevented their inclusion into results-based payments established by the United Nations Framework Convention on Climate Change. Based on an inventory from over 190 forest plots in Amazon mangroves, we estimate total ecosystem carbon stocks of 468 ± 67 Megagrams (Mg) ha-1; which are significantly higher than Brazilian upland biomes currently included into national carbon offset financing. Conversion of mangroves results in potential emissions of 1228 Mg CO2e ha-1, which are 3-fold higher than land use emissions from conversion of the Amazon rainforest. Our work provides the foundation for the inclusion of mangroves in Brazil's intended Nationally Determined Contribution, and here we show that halting mangrove deforestation in the Legal Amazon would generate avoided emissions of 0.9 ± 0.3 Teragrams (Tg) CO2e yr-1; which is equivalent to the annual carbon accumulation in 82,400 ha of secondary forests.

2-step lignin-first catalytic fractionation with bifunctional Pd/ß-zeolite catalyst in a flow-through reactor.

This work demonstrates an additive and hydrogen-free 2-step lignin-first fractionation in flow-through. First, solvolytic delignification renders lignin liquors with its native chemical structure largely intact; and second, ß-zeolite catalytic depolymerization of these liquors leads to similar monomer yields as the corresponding 1-step fractionation process. Higher delignification temperatures lead to slightly lower ß-O-4 content in the solvated lignin, but does not affect significantly the monomer yield, so a higher temperature was overall preferred as it promotes faster delignification. Deposition of Pd on ß-zeolite resulted in a bifunctional hydrogenation/dehydration catalyst, tested during the catalytic depolymerization of solvated lignin with and without hydrogen addition. Pd/ß-zeolite displays synergistic effects (compared to the Pd/γ-Al2O3 and ß-zeolite tested individually and as a mixed bed), resulting in higher monomer yield. This is likely caused by increased acidity and the proximity between the metallic and acid active sites. Furthermore, different ß-zeolite with varying SAR and textural properties were studied to shed light onto the effect of acidity and porosity in the stabilization of lignin monomers. While some of the catalysts showed stable performance, characterization of the spent catalyst reveals Al leaching (causing acidity loss and changes in textural properties), and some degree of coking and Pd sintering.

Polycyclic aromatic hydrocarbons in estuarine sediments as a consequence of the mine tailings remobilization and transport in the Rio Doce basin.

The Fundão dam failure in 2015 severely impaired the economy, the lives of riverine communities, and the aquatic ecosystems of the Rio Doce basin in southeast Brazil. Several contaminants, including polycyclic aromatic hydrocarbons (PAHs), were transported downstream, deposited in the estuary, and released into the Atlantic Ocean. The high concentration of PAHs in estuarine sediments may pose ecological risks and deleterious effects to benthic organisms, so here we aimed at determining the source and fate of these compounds before and after the tailings' arrival. The mean concentration of the analyzed Σ16PAHs increased from 34.05 µg kg-1 in the prefailure period to 751.77 µg kg-1 one year after the arrival of the tailing. The classification of the sediment quality changed from low to moderate contamination. Our results suggest that there was PAHs remobilization by mine tailings along the Rio Doce basin. The target analytes exhibited mostly a pyrolytic profile from fossil fuel and biomass burning. In addition to other contaminants deposited in the estuary after the arrival of the tailings, this study revealed that the profile change of PAHs in the estuary region is a consequence of the mud's erosive power. Integr Environ Assess Manag 2024;20:169-178. © 2023 SETAC.

[Development and validation of standards for quality units of health centers]. / Desarrollo y validación de estándares para unidades de calidad de centros sanitarios.

OBJECTIVE: In Spain, the Quality Units advise health centres, services and professionals on the methodology of continuous improvement of the quality of care. A system based on good practice standards could provide these units with a tool to improve their results and value their work. The objective was to develop, agree on and validate standards, to properly guide and orient the functions, results and continuous improvement of the Quality Units in health centers. MATERIAL AND METHODS: A qualitative-quantitative, prospective and cross-sectional study was carried out, applying the Metaplan method, the e-Delphi technique and a simulation study. The participants were coordinators of these units, belonging to 14 Spanish Autonomous Communities and distributed in four experts' panels. They agreed on the standards to be used and evaluated the different types of validity. RESULTS: The 204 standards proposed by the scientific committee were reduced to 157 with Metaplan, to 110 with e-Delphi, and to 96 with the committee's final review (87.3% consensus, content validity). The construct validity showed a Cronbach's alpha >0.7 (P<.001); the validity of content was reaffirmed in the simulation workshop (80% "understood" each other, P<.001; and there was "documentary evidence" in 84%, P<.001); face validity was accepted (75% "related to quality dimensions", P<.001); and the validity of the criteria was verified with a sensitivity of 84.2%, a specificity of 98.3%, and a kappa index of 0.84. CONCLUSIONS: Valid standards have been developed for Quality Units in health centers.

A large scale temporal and spatial environmental DNA biodiversity survey of marine vertebrates in Brazil following the Fundão tailings dam failure.

Seawater contains a wealth of genetic information, representing the biodiversity of numerous species residing within a particular marine habitat. Environmental DNA (eDNA) metabarcoding offers a cost effective, non-destructive method for large scale monitoring of environments, as diverse taxonomic groups are detected using metabarcoding assays. A large-scale eDNA monitoring program of marine vertebrates was conducted across three sampling seasons (Spring 2018, Autumn 2019; Spring 2019) in coastal waters of Brazil. The program was designed to investigate eDNA as a testing method for long term monitoring of marine vertebrates following the Fundão tailings dam failure in November 2015. While no baseline samples were available prior to the dam failure there is still value in profiling the taxa that use the impacted area and the trajectory of recovery. A total of 40 sites were sampled around the mouths of eight river systems, covering approximately 500 km of coastline. Metabarcoding assays targeting the mitochondrial genes 16S rRNA and COI were used to detect fish, marine mammals and elasmobranchs. We detected temporal differences between seasons and spatial differences between rivers/estuaries sampled. Overall, the largest eDNA survey in Brazil to date revealed 69 families from Class Actinopterygii (fish), 15 species from Class Chondrichthyes (sharks and rays), 4 species of marine and estuarine mammals and 23 species of conservation significance including 2 species of endangered dolphin. Our large-scale study reinforces the value eDNA metabarcoding can bring when monitoring the biodiversity of coastal environments and demonstrates the importance of collection of time-stamped environmental samples to better understand the impacts of anthropogenic activities.

Temporal Structures in Positron Spectra and Charge-Sign Effects in Galactic Cosmic Rays.

We present the precision measurements of 11 years of daily cosmic positron fluxes in the rigidity range from 1.00 to 41.9 GV based on 3.4×10^{6} positrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The positron fluxes show distinctly different time variations from the electron fluxes at short and long timescales. A hysteresis between the electron fluxes and the positron fluxes is observed with a significance greater than 5σ at rigidities below 8.5 GV. On the contrary, the positron fluxes and the proton fluxes show similar time variation. Remarkably, we found that positron fluxes are modulated more than proton fluxes with a significance greater than 5σ for rigidities below 7 GV. These continuous daily positron fluxes, together with AMS daily electron, proton, and helium fluxes over an 11-year solar cycle, provide unique input to the understanding of both the charge-sign and mass dependencies of cosmic rays in the heliosphere.

Long-term impacts on estuarine benthic assemblages (2015-2020) after a mine tailing spill in SE Brazil.

The Rio Doce estuary was critically impacted in 2015 by the world's largest mining tailing spill, with still unclear long-term effects on the aquatic biota. Here we present a long-term (2015 to 2020) assessment of estuarine benthic assemblages, where we demonstrate that despite a decline in the absolute concentrations of potentially toxic elements; sediment contamination is still above pre-impact conditions. The presence of these contaminants is likely responsible for a continued low habitat quality for the benthic fauna, characterized by a reduction of 96 % of the macroinvertebrate density and persistent change in the benthic assemblage composition. Our study supports previous work indicating the long-term nature of pollution impacts in estuaries, and demonstrate that although water quality levels were quickly adequate under regulatory terms, they largely lack significance to the overall ecosystem health assessment, as they are not related to the recovery of bottom- dwelling assemblages in estuarine ecosystems.

Universal evaluation of MLC models in treatment planning systems based on a common set of dynamic tests.

PURPOSE: To demonstrate the feasibility of characterising MLCs and MLC models implemented in TPSs using a common set of dynamic beams. MATERIALS AND METHODS: A set of tests containing synchronous (SG) and asynchronous sweeping gaps (aSG) was distributed among twenty-five participating centres. Doses were measured with a Farmer-type ion chamber and computed in TPSs, which provided a dosimetric characterisation of the leaf tip, tongue-and-groove, and MLC transmission of each MLC, as well as an assessment of the MLC model in each TPS. Five MLC types and four TPSs were evaluated, covering the most frequent combinations used in radiotherapy departments. RESULTS: Measured differences within each MLC type were minimal, while large differences were found between MLC models implemented in clinical TPSs. This resulted in some concerning discrepancies, especially for the HD120 and Agility MLCs, for which differences between measured and calculated doses for some MLC-TPS combinations exceeded 10%. These large differences were particularly evident for small gap sizes (5 and 10 mm), as well as for larger gaps in the presence of tongue-and-groove effects. A much better agreement was found for the Millennium120 and Halcyon MLCs, differences being within ± 5% and ± 2.5%, respectively. CONCLUSIONS: The feasibility of using a common set of tests to assess MLC models in TPSs was demonstrated. Measurements within MLC types were very similar, but TPS dose calculations showed large variations. Standardisation of the MLC configuration in TPSs is necessary. The proposed procedure can be readily applied in radiotherapy departments and can be a valuable tool in IMRT and credentialing audits.

Levelling-up rhodolith-bed science to address global-scale conservation challenges.

Global marine conservation remains fractured by an imbalance in research efforts and policy actions, limiting progression towards sustainability. Rhodolith beds represent a prime example, as they have ecological importance on a global scale, provide a wealth of ecosystem functions and services, including biodiversity provision and potential climate change mitigation, but remain disproportionately understudied, compared to other coastal ecosystems (tropical coral reefs, kelp forests, mangroves, seagrasses). Although rhodolith beds have gained some recognition, as important and sensitive habitats at national/regional levels during the last decade, there is still a notable lack of information and, consequently, specific conservation efforts. We argue that the lack of information about these habitats, and the significant ecosystem services they provide, is hindering the development of effective conservation measures and limiting wider marine conservation success. This is becoming a pressing issue, considering the multiple severe pressures and threats these habitats are exposed to (e.g., pollution, fishing activities, climate change), which may lead to an erosion of their ecological function and ecosystem services. By synthesizing the current knowledge, we provide arguments to highlight the importance and urgency of levelling-up research efforts focused on rhodolith beds, combating rhodolith bed degradation and avoiding the loss of associated biodiversity, thus ensuring the sustainability of future conservation programs.

Adaptive Staged-Dose Gamma Knife Radiosurgery for the Treatment of Large Brain Metastases: Report of 40 Consecutive Cases and Analysis of Literature.

Background: Brain metastases are the most common brain tumors, being one of the most frequent neurological complications of systemic cancer and an important cause of morbidity and mortality. Stereotactic radiosurgery is efficacious and safe in the treatment of brain metastases, with good local control rates and low adverse effects rate. Large brain metastases present some issues in balancing local control and treatment-related toxicity. Objective: Demonstrating adaptive staged-dose Gamma Knife radiosurgery (ASD-GKRS) being a safe and effective treatment for large brain metastases. Materials and Methods: We retrospectively analyzed our series of patients treated with two-stage Gamma Knife radiosurgery for large brain metastases in [BLINDED], between February 2018 and May 2020. Results: Forty patients with large brain metastases underwent adaptive staged-dose Gamma Knife radiosurgery, with median prescription dose of 12 Gy and a median interval between stages of 30 days. At three-month follow-up, the survival rate was 75.0% with a local control rate of 100%. At six-month follow-up, the survival rate was 75.0% with a local control rate of 96.7%. The mean volume reduction was 21.81 cm3 (16.76-26.86; 95% CI). The difference between baseline volume and six-month follow-up volume was statistically significant. Conclusions: Adaptive staged-dose Gamma Knife radiosurgery is a safe, non-invasive and effective treatment for brain metastases, with a low rate of side effects. Large prospective trials are needed to strengthen data obtained about the effectiveness and safety of this technique in managing large brain metastases.

Transition of an estuarine benthic meiofauna assemblage 1.7 and 2.8 years after a mining disaster.

Background: Estuaries are transitional coastal ecosystems that are threatened by multiple sources of human pollution. In 2015, mining tailings from an upstream dam failure caused massive metal contamination that impacted benthic assemblages on the Brazilian Rio Doce estuary. Methods: In this study, we investigate and compare meiofaunal assemblages with eDNA metabarcoding 1.7 years (2017) and 2.8 years (2018) after the initial contamination by mine tailings in order to evaluate the continued impact of sediment mine tailing contaminants on the structure of benthic assemblages after the disaster. Results: The community was dominated by Arthropoda and Nematoda 1.7 yr after the impacts (42 and 29% of meiofaunal sequence reads, respectively) but after 2.8 years Arthropoda (64.8% of meiofaunal sequence reads) and Rotifera (11.8%) were the most common taxa. This continued impact on meiofaunal assemblage revealed a lower phylogenetic diversity (7.8-fold) in 2018, despite overall decrease in metal concentration (Al, Ba, Cr, As, Fe, Zn, Mn, Pb, Cd, Co) in sediments. Our data suggests that differences in benthic assemblages and loss of diversity may be influenced by contaminants in sediments of this estuary, and indicate that broad eDNA assessments are greatly useful to understand the full range of biodiversity changes in dynamic estuarine ecosystems.

Benthic biogeographic patterns on the deep Brazilian margin.

The Brazilian continental margin (BCM) extends from the Tropical to the Subtropical Atlantic Ocean, with much of its seafloor within deep waters, supporting rich geomorphological features and under wide productivity gradients. Deep-sea biogeographic boundaries on the BCM have been limited to studies that used water mass and salinity properties of deep-water masses, partly as a result of historical under sampling and a lack of consolidation of available biological and ecological datasets. The aim of this study was to consolidate benthic assemblage datasets and test current oceanographic biogeographical deep-sea boundaries (200-5,000 m) using available faunal distributions. We retrieved over 4,000 benthic data records from open-access databases and used cluster analysis to examine assemblage distributions against the deep-sea biogeographical classification scheme from Watling et al. (2013). Starting from the assumption that vertical and horizontal distribution patterns can vary regionally, we test other schemes incorporating latitudinal and water masses stratification within the Brazilian margin. As expected, the classification scheme based on benthic biodiversity is in overall agreement with the general boundaries proposed by Watling et al. (2013). However, our analysis allowed much refinement in the former boundaries, and here we propose the use of two biogeographic realms, two provinces and seven bathyal ecoregions (200-3,500 m), and three abyssal provinces (>3,500 m) along the BCM. The main driver for these units seems to be latitudinal gradients as well as water mass characteristics such as temperature. Our study provides a significant improvement of benthic biogeographic ranges along the Brazilian continental margin allowing a more detailed recognition of its biodiversity and ecological value, and also supports the needed spatial management for industrial activities occurring in its deep waters.

Incidence and risk factors for anxiety disorders in young adults: A population-based prospective cohort study.

Anxiety disorders are among the most common psychiatric disorders in the general population. Our objective was to describe the cumulative incidence and risk factors of anxiety disorders, including obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD), in a follow-up of young adults over a five-year period. This is a prospective cohort conducted in two waves. The first took place from 2007 to 2009, in which 1,560 young adults aged between 18 and 24 years were evaluated using the Mini-International Neuropsychiatric Interview (MINI). Subjects were invited to participate in the second wave, which wave took place from 2012 to 2014, where 1,244 young adults were evaluated using the MINI-Plus. Our findings showed a cumulative incidence of 10.9% for any anxiety disorder, 6.5% for generalized anxiety disorder, 6.0% for agoraphobia, 2.0% for OCD, 1.6% for panic disorder, 1.1% for social anxiety and 0.7% for PTSD. Being female and having had a depressive episode were risk factors to develop any anxiety disorder. We observed a high cumulative incidence of anxiety disorders in a population-based sample of young adults. Our data highlights the importance of the early identification of these disorders as this could lead to early illness detection, early illness management and a reduced burden of disease.

Methotrexate improves endothelial function in early rheumatoid arthritis patients after 3 months of treatment.

BACKGROUND: Endothelial dysfunction contributes to increased cardiovascular (CV) disease in rheumatoid arthritis (RA). Angiogenic T cells (Tang) are a key regulator of vascular function via their interaction with endothelial progenitor cells (EPCs). Methotrexate (MTX) has been associated to reduced CV disease risk, but its effects on endothelial homeostasis have been poorly explored. We investigated MTX effects on endothelial homeostasis in early, treatment-naïve RA patients. METHODS: Fifteen untreated, early RA patients and matched healthy controls (HC) were enrolled. RA patients with long-standing disease in remission or low disease activity treated with MTX for at least 6 months were selected as controls. Circulating CD28+ and CD28null Tang cell, endothelial microparticle (EMP), EPC and soluble vascular cell adhesion molecule (sVCAM)-1 levels were measured. RESULTS: Tang percentage was higher in early RA than in HCs and significantly increased after 3-month MTX treatment. Tang cells in RA were characterized by higher percentage of CD28null and lower CD28-positive cells than HCs. MTX restored a Tang cell phenotype similar to HCs. Altered sVCAM-1, EMP and EPC were restored to levels similar to HCs after a 3-month MTX. Biomarker levels after 3 months of MTX were not different to those of patients with long-standing treatment. CONCLUSIONS: MTX has a positive effect on Tang, sVCAM-1, EPCs and EMPs in RA. Restoration of imbalance between CD28 + and CD28null Tang by MTX may be one of the mechanisms underlying its favourable effects on endothelial dysfunction. These effects seem to be long-lasting and independent from systemic inflammation reduction, suggesting a direct effect of MTX on the endothelium.