Molecular and brain volume changes following aerobic exercise, cognitive and combined training in physically inactive healthy Late-Middle-Aged Adults: The Projecte Moviment Randomized Controlled Trial

Behavioral interventions have shown promising neuroprotective effects, but the cascade of molecular, brain and behavioral changes involved in these benefits remains poorly understood. Projecte Moviment is a 12-week (5 days per week—45 min per day) multi-domain, single-blind, proof-of-concept randomized controlled trial examining the cognitive effect and underlying mechanisms of an aerobic exercise (AE), computerized cognitive training (CCT) and a combined (COMB) groups compared to a waitlist control group. Adherence was > 80% for 82/109 participants recruited (62% female; age = 58.38 ± 5.47). In this study we report intervention-related changes in plasma biomarkers (BDNF, TNF-α, HGF, ICAM-1, SDF1-α) and structural-MRI (brain volume) and how they related to changes in physical activity and individual variables (age and sex) and their potential role as mediators in the cognitive changes. Our results show that although there were no significant changes in molecular biomarker concentrations in any intervention group, changes in ICAM-1 and SDF1-α were negatively associated with changes in physical activity outcomes in AE and COMB groups. Brain volume changes were found in the CCT showing a significant increase in precuneus volume. Sex moderated the brain volume change in the AE and COMB groups, suggesting that men may benefit more than women. Changes in molecular biomarkers and brain volumes did not significantly mediate the cognitive-related benefits found previously for any group. This study shows crucial initial molecular and brain volume changes related to lifestyle interventions at early stages and highlights the value of examining activity parameters, individual difference characteristics and using a multi-level analysis approach to address these questions

Effects and Mechanisms of Cognitive, Aerobic Exercise, and Combined Training on Cognition, Health, and Brain Outcomes in Physically Inactive Older Adults : The Projecte Moviment Protocol

Altres ajuts: It has also been rewarded with three pre-doctoral fellowships ( FPU014/01460, FI-2016, and FI-2018).Introduction: Age-related health, brain, and cognitive impairment is a great challenge in current society. Cognitive training, aerobic exercise and their combination have been shown to benefit health, brain, cognition and psychological status in healthy older adults. Inconsistent results across studies may be related to several variables. We need to better identify cognitive changes, individual variables that may predict the effect of these interventions, and changes in structural and functional brain outcomes as well as physiological molecular correlates that may be mediating these effects. Projecte Moviment is a multi-domain randomized trial examining the effect of these interventions applied 5 days per week for 3 months compared to a passive control group. The aim of this paper is to describe the sample, procedures and planned analyses. Methods: One hundred and forty healthy physically inactive older adults will be randomly assigned to computerized cognitive training (CCT), aerobic exercise (AE), combined training (COMB), or a control group. The intervention consists of a 3 month home-based program 5 days per week in sessions of 45 min. Data from cognitive, physical, and psychological tests, cardiovascular risk factors, structural and functional brain scans, and blood samples will be obtained before and after the intervention. Results: Effects of the interventions on cognitive outcomes will be described in intention-to-treat and per protocol analyses. We will also analyze potential genetic, demographic, brain, and physiological molecular correlates that may predict the effects of intervention, as well as the association between cognitive effects and changes in these variables using the per protocol sample. Discussion: Projecte Moviment is a multi-domain intervention trial based on prior evidence that aims to understand the effects of CCT, AE, and COMB on cognitive and psychological outcomes compared to a passive control group, and to determine related biological correlates and predictors of the intervention effects. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03123900

New Capabilities of the FLUKA Multi-Purpose Code

FLUKA is a general purpose Monte Carlo code able to describe the transport and interaction of any particle and nucleus type in complex geometries over an energy range extending from thermal neutrons to ultrarelativistic hadron collisions. It has many different applications in accelerator design, detector studies, dosimetry, radiation protection, medical physics, and space research. In 2019, CERN and INFN, as FLUKA copyright holders, together decided to end their formal collaboration framework, allowing them henceforth to pursue different pathways aimed at meeting the evolving requirements of the FLUKA user community, and at ensuring the long term sustainability of the code. To this end, CERN set up the FLUKA.CERN Collaboration1. This paper illustrates the physics processes that have been newly released or are currently implemented in the code distributed by the FLUKA.CERN Collaboration2 under new licensing conditions that are meant to further facilitate access to the code, as well as intercomparisons. The description of coherent effects experienced by high energy hadron beams in crystal devices, relevant to promising beam manipulation techniques, and the charged particle tracking in vacuum regions subject to an electric field, overcoming a former lack, have already been made available to the users. Other features, namely the different kinds of low energy deuteron interactions as well as the synchrotron radiation emission in the course of charged particle transport in vacuum regions subject to magnetic fields, are currently undergoing systematic testing and benchmarking prior to release. FLUKA is widely used to evaluate radiobiological effects, with the powerful support of the Flair graphical interface, whose new generation (Available at http://flair.cern) offers now additional capabilities, e.g., advanced 3D visualization with photorealistic rendering and support for industry-standard volume visualization of medical phantoms. FLUKA has also been playing an extensive role in the characterization of radiation environments in which electronics operate. In parallel, it has been used to evaluate the response of electronics to a variety of conditions not included in radiation testing guidelines and standards for space and accelerators, and not accessible through conventional ground level testing. Instructive results have been obtained from Single Event Effects (SEE) simulations and benchmarks, when possible, for various radiation types and energies. The code has reached a high level of maturity, from which the FLUKA.CERN Collaboration is planning a substantial evolution of its present architecture. Moving towards a modern programming language allows to overcome fundamental constraints that limited development options. Our long term goal, in addition to improving and extending its physics performances with even more rigorous scientific oversight, is to modernize its structure to integrate independent contributions more easily and to formalize quality assurance through state-of-the-art software deployment techniques. This includes a continuous integration pipeline to automatically validate the codebase as well as automatic processing and analysis of a tailored physics-case test suite. With regard to the aforementioned objectives, several paths are currently envisaged, like finding synergies with Geant4, both at the core structure and interface level, this way offering the user the possibility to run with the same input different Monte Carlo codes and crosscheck the results

Large-scale assessment of regeneration and diversity in Mediterranean planted pine forests along ecological gradients

15 pages, 4 figures, 4 tables, 87 references.There is increasing concern regarding sustainable management and restoration of planted forests, particularly in the Mediterranean Basin where pine species have been widely used. The aim of this study was to analyse the environmental and structural characteristics of Mediterranean planted pine forests in relation to natural pine forests. Specifically, we assessed recruitment and woody species richness along climatic, structural and perturbation gradients to aid in developing restoration guidelines.Location Continental Spain. We conducted a multivariate comparison of ecological characteristics in planted and natural stands of main Iberian native pine species (Pinus halepensis, Pinus pinea, Pinus pinaster, Pinus nigra and Pinus sylvestris). We fitted species-specific statistical models of recruitment and woody species richness and analysed the response of natural and planted stands along ecological gradients. Planted pine forests occurred on average on poorer soils and experienced higher anthropic disturbance rates (fire frequency and anthropic mortality) than natural pine forests. Planted pine forests had lower regeneration and diversity levels than natural pine forests, and these differences were more pronounced in mountain pine stands. The largest differences in recruitment – chiefly oak seedling abundance – and species richness between planted and natural stands occurred at low-medium values of annual precipitation, stand tree density, distance to Quercus forests and fire frequency, whereas differences usually disappeared in the upper part of the gradients.Main conclusions Structural characteristics and patterns of recruitment and species richness differ in pine planted forests compared to natural pine ecosystems in the Mediterranean, especially for mountain pines. However, management options exist that would reduce differences between these forest types, where restoration towards more natural conditions is feasible. To increase recruitment and diversity, vertical and horizontal heterogeneity could be promoted by thinning in high-density and homogeneous stands, while enrichment planting would be desirable in mesic and medium-density planted forests.This research was supported by INTERBOS3-CGL2008-04503- C03-03 (MCI) and SUM2008-00004-C03-01 (INIA) projects. P.R.B. was supported by a FPU fellowship from the Spanish MEC (AP2008-01325). We thank the MARM (Ministerio de Medio Ambiente, Medio Rural y Marino, Dirección General de Medio Natural y Política Forestal) for granting the access to the Spanish Forest Inventory Data.Peer reviewe

HE-LHC: The High-Energy Large Hadron Collider – Future Circular Collider Conceptual Design Report Volume 4

In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Genetic variation of growth rhythm traits in the limits of a latitudinal cline in Scots pine

Scots pine (Pinus sylvestris L.) has the widest distribution of pine species and the populations are locally adapted to very different environmental conditions. Adaptive traits such as those related to growth are optimal for understanding adaptation of populations to local conditions in widely distributed forest species. A study of the timing of growth during the first growing period of families in four populations from the latitudinal limits of the distribution range was conducted. Individual growth curves were fitted, and a set of variables related to growth rhythm and timing of budset was obtained for genetic analyses. Pooled heritabilities across populations were very high for most of the traits (0.43-1.09), and population differentiation for growth variables showed high values as well (QST = 0.19-0.71). Phenotypic correlations were higher than genetic ones, and most of them were positives. Even no general patterns of additive variances were found, the high additive genetic variance obtained (14% ± 8%, mean ± SE) suggests that additive genetic variance is not the limiting factor for adaptation to a new optimum within much of the range for these traits. Changes in means, additive genetic variances, and additive genetic coefficient of variation by population are also discussed. © 2007 NRC