Showing papers by "Federal University of Rio de Janeiro published in 2014"
University of Tasmania1, University of Portsmouth2, Stockholm Resilience Centre3, Charles Darwin Foundation4, Spanish National Research Council5, Wildlife Conservation Society6, Department of Water7, Pontifical Catholic University of Valparaíso8, National Park Service9, Federal University of Rio de Janeiro10, Scripps Institution of Oceanography11, University of Auckland12, University of Bologna13
TL;DR: The results show that global conservation targets based on area alone will not optimize protection of marine biodiversity, and more emphasis is needed on better MPA design, durable management and compliance to ensure that MPAs achieve their desired conservation value.
Abstract: In line with global targets agreed under the Convention on Biological Diversity, the number of marine protected areas (MPAs) is increasing rapidly, yet socio-economic benefits generated by MPAs remain difficult to predict and under debate1, 2. MPAs often fail to reach their full potential as a consequence of factors such as illegal harvesting, regulations that legally allow detrimental harvesting, or emigration of animals outside boundaries because of continuous habitat or inadequate size of reserve3, 4, 5. Here we show that the conservation benefits of 87 MPAs investigated worldwide increase exponentially with the accumulation of five key features: no take, well enforced, old (>10 years), large (>100 km2), and isolated by deep water or sand. Using effective MPAs with four or five key features as an unfished standard, comparisons of underwater survey data from effective MPAs with predictions based on survey data from fished coasts indicate that total fish biomass has declined about two-thirds from historical baselines as a result of fishing. Effective MPAs also had twice as many large (>250 mm total length) fish species per transect, five times more large fish biomass, and fourteen times more shark biomass than fished areas. Most (59%) of the MPAs studied had only one or two key features and were not ecologically distinguishable from fished sites. Our results show that global conservation targets based on area alone will not optimize protection of marine biodiversity. More emphasis is needed on better MPA design, durable management and compliance to ensure that MPAs achieve their desired conservation value.
1,355 citations
TL;DR: The value of the ratio of branching fractions for the dilepton invariant mass squared range 1 < q(2) < 6 GeV(2)/c(4) is measured to be 0.745(-0.074)(+0.090)(stat) ± 0.036(syst).
Abstract: A measurement of the ratio of the branching fractions of the B+→K+μ+μ− and B+→K+e+e− decays is presented using proton-proton collision data, corresponding to an integrated luminosity of 3.0 fb−1, recorded with the LHCb experiment at center-of-mass energies of 7 and 8 TeV. The value of the ratio of branching fractions for the dilepton invariant mass squared range 1
1,017 citations
TL;DR: The effect of PrEP is increased by greater uptake and adherence during periods of higher risk, and drug concentrations in dried blood spots are strongly correlated with protective benefit.
Abstract: Summary Background The effect of HIV pre-exposure prophylaxis (PrEP) depends on uptake, adherence, and sexual practices. We aimed to assess these factors in a cohort of HIV-negative people at risk of infection. Methods In our cohort study, men and transgender women who have sex with men previously enrolled in PrEP trials (ATN 082, iPrEx, and US Safety Study) were enrolled in a 72 week open-label extension. We measured drug concentrations in plasma and dried blood spots in seroconverters and a random sample of seronegative participants. We assessed PrEP uptake, adherence, sexual practices, and HIV incidence. Statistical methods included Poisson models, comparison of proportions, and generalised estimating equations. Findings We enrolled 1603 HIV-negative people, of whom 1225 (76%) received PrEP. Uptake was higher among those reporting condomless receptive anal intercourse (416/519 [81%] vs 809/1084 [75%], p=0·003) and having serological evidence of herpes (612/791 [77%] vs 613/812 [75%] p=0·03). Of those receiving PrEP, HIV incidence was 1·8 infections per 100 person-years, compared with 2·6 infections per 100 person-years in those who concurrently did not choose PrEP (HR 0·51, 95% CI 0·26–1·01, adjusted for sexual behaviours), and 3·9 infections per 100 person-years in the placebo group of the previous randomised phase (HR 0·49, 95% CI 0·31–0·77). Among those receiving PrEP, HIV incidence was 4·7 infections per 100 person-years if drug was not detected in dried blood spots, 2·3 infections per 100 person-years if drug concentrations suggested use of fewer than two tablets per week, 0·6 per 100 person-years for use of two to three tablets per week, and 0·0 per 100 person-years for use of four or more tablets per week (p Interpretation PrEP uptake was high when made available free of charge by experienced providers. The effect of PrEP is increased by greater uptake and adherence during periods of higher risk. Drug concentrations in dried blood spots are strongly correlated with protective benefit. Funding US National Institutes of Health.
996 citations
University of Pretoria1, Empresa Brasileira de Pesquisa Agropecuária2, Universidade Católica de Brasília3, Oak Ridge National Laboratory4, United States Department of Energy5, Joint Genome Institute6, Ghent University7, Institut national de la recherche agronomique8, University of Toulouse9, University of British Columbia10, University of Münster11, University of Düsseldorf12, Oregon State University13, Federal University of Rio de Janeiro14, University of São Paulo15, Australian National University16, Indian Institute of Chemical Technology17, University of Arizona18, Universidade Federal de Viçosa19, Universidade Federal do Rio Grande do Sul20, Department of Environment and Primary Industries21, University of Melbourne22, University of Tasmania23, University of the Sunshine Coast24, University of Brasília25
TL;DR: Of 36,376 predicted protein-coding genes, 34% occur in tandem duplications, the largest proportion thus far in plant genomes, which shows the highest diversity of genes for specialized metabolites such as terpenes that act as chemical defence and provide unique pharmaceutical oils.
Abstract: Eucalypts are the world's most widely planted hardwood trees. Their outstanding diversity, adaptability and growth have made them a global renewable resource of fibre and energy. We sequenced and assembled >94% of the 640-megabase genome of Eucalyptus grandis. Of 36,376 predicted protein-coding genes, 34% occur in tandem duplications, the largest proportion thus far in plant genomes. Eucalyptus also shows the highest diversity of genes for specialized metabolites such as terpenes that act as chemical defence and provide unique pharmaceutical oils. Genome sequencing of the E. grandis sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression. The E. grandis genome is the first reference for the eudicot order Myrtales and is placed here sister to the eurosids. This resource expands our understanding of the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology.
679 citations
TL;DR: The logistic regression procedure is explained using examples to make it as simple as possible and to avoid confounding effects by analyzing the association of all variables together.
Abstract: Logistic regression is used to obtain odds ratio in the presence of more than one explanatory variable. The procedure is quite similar to multiple linear regression, with the exception that the response variable is binomial. The result is the impact of each variable on the odds ratio of the observed event of interest. The main advantage is to avoid confounding effects by analyzing the association of all variables together. In this article, we explain the logistic regression procedure using examples to make it as simple as possible. After definition of the technique, the basic interpretation of the results is highlighted and then some special issues are discussed.
633 citations
26 May 2014
TL;DR: In this paper, a description of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices is provided.
Abstract: A description is provided of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices. Despite the very hostile environment at the LHC, the performance obtained with these algorithms is found to be excellent. For tt events under typical 2011 pileup conditions, the average track-reconstruction efficiency for promptly-produced charged particles with transverse momenta of p_T > 0.9GeV is 94% for pseudorapidities of |η| < 0.9 and 85% for 0.9 < |η| < 2.5. The inefficiency is caused mainly by hadrons that undergo nuclear interactions in the tracker material. For isolated muons, the corresponding efficiencies are essentially 100%. For isolated muons of p_T = 100GeV emitted at |η| < 1.4, the resolutions are approximately 2.8% in p_T, and respectively, 10μm and 30μm in the transverse and longitudinal impact parameters. The position resolution achieved for reconstructed primary vertices that correspond to interesting pp collisions is 10–12μm in each of the three spatial dimensions. The tracking and vertexing software is fast and flexible, and easily adaptable to other functions, such as fast tracking for the trigger, or dedicated tracking for electrons that takes into account bremsstrahlung.
559 citations
TL;DR: Evidence indicating that inflammation, insulin resistance, and mitochondrial dysfunction are common features in AD and T2D are reviewed and the hypothesis that dementia and its underlying neuronal dysfunction are exacerbated or driven by peripheral inflammation is proposed.
Abstract: A growing body of evidence supports an intriguing clinical/epidemiological connection between Alzheimer disease (AD) and type 2 diabetes (T2D). T2D patients have significantly increased risk of developing AD and vice versa. Recent studies have begun to reveal common pathogenic mechanisms shared by AD and metabolic disorders, notably obesity and T2D. In T2D and obesity, low-grade chronic inflammation is a key mechanism leading to peripheral insulin resistance, which progressively causes tissue deterioration and overall health decline. In the brain, proinflammatory signaling was recently found to mediate impaired neuronal insulin signaling, synapse deterioration, and memory loss. Here, we review evidence indicating that inflammation, insulin resistance, and mitochondrial dysfunction are common features in AD and T2D. We further propose the hypothesis that dementia and its underlying neuronal dysfunction are exacerbated or driven by peripheral inflammation. Identification of central and peripheral inflammation as potential mediators of brain dysfunction in AD may lead to the development of effective treatments for this devastating disease.
461 citations
TL;DR: Variations in the glia/neuron ratio are proposed to be related not to the supposed larger metabolic cost of larger neurons (given that this cost is not found to vary with neuronal density), but simply to the large variation in neuronal sizes across brain structures and species in the face of less overall variation in glial cell sizes.
Abstract: It is a widespread notion that the proportion of glial to neuronal cells in the brain increases with brain size, to the point that glial cells represent "about 90% of all cells in the human brain." This notion, however, is wrong on both counts: neither does the glia/neuron ratio increase uniformly with brain size, nor do glial cells represent the majority of cells in the human brain. This review examines the origin of interest in the glia/neuron ratio; the original evidence that led to the notion that it increases with brain size; the extent to which this concept can be applied to white matter and whole brains and the recent supporting evidence that the glia/neuron ratio does not increase with brain size, but rather, and in surprisingly uniform fashion, with decreasing neuronal density due to increasing average neuronal cell size, across brain structures and species. Variations in the glia/neuron ratio are proposed to be related not to the supposed larger metabolic cost of larger neurons (given that this cost is not found to vary with neuronal density), but simply to the large variation in neuronal sizes across brain structures and species in the face of less overall variation in glial cell sizes, with interesting implications for brain physiology. The emerging evidence that the glia/neuron ratio varies uniformly across the different brain structures of mammalian species that diverged as early as 90 million years ago in evolution highlights how fundamental for brain function must be the interaction between glial cells and neurons.
440 citations
Proceedings Article•
30 Jul 2014
409 citations
TL;DR: The aim of this paper is to present some of the more important univariate and bivariate parametric and non-parametric statistical techniques and to highlight their uses based on practical examples in Food Science and Technology.
409 citations
TL;DR: In this article, a study of the distributions of the depth of maximum, X-max, of extensive air-shower profiles with energies above 10(17.8) eV was performed with the fluorescence telescopes of the Pierre Auger Observatory.
Abstract: We report a study of the distributions of the depth of maximum, X-max, of extensive air-shower profiles with energies above 10(17.8) eV as observed with the fluorescence telescopes of the Pierre Auger Observatory. The analysis method for selecting a data sample with minimal sampling bias is described in detail as well as the experimental cross-checks and systematic uncertainties. Furthermore, we discuss the detector acceptance and the resolution of the X-max measurement and provide parametrizations thereof as a function of energy. The energy dependence of the mean and standard deviation of the X-max distributions are compared to air-shower simulations for different nuclear primaries and interpreted in terms of the mean and variance of the logarithmic mass distribution at the top of the atmosphere.
TL;DR: Recent advances that provide insights into interactions between the microglia and the vascular system in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative disorders are reviewed.
Abstract: The blood-brain barrier (BBB), constituted by an extensive network of endothelial cells together with neurons and glial cells, including microglia, forms the neurovascular unit. The crosstalk between these cells guarantees a proper environment for brain function. In this context, changes in the endothelium-microglia interactions are associated with a variety of inflammation-related diseases in brain, where BBB permeability is compromised. Increasing evidences indicate that activated microglia modulate expression of tight junctions, which are essential for BBB integrity and function. On the other hand, the endothelium can regulate the state of microglial activation. Here, we review recent advances that provide insights into interactions between the microglia and the vascular system in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative disorders.
Universidade Federal de Mato Grosso1, National Institute of Amazonian Research2, University of Queensland3, Max Planck Society4, National University of General San Martín5, Federal University of Ceará6, Federal University of Rio de Janeiro7, Universidade do Vale do Rio dos Sinos8, University of São Paulo9, Universidade Estadual de Maringá10
TL;DR: In this article, a synthesis of the current body of knowledge on the distribution, hydrology, and vegetation cover of Brazilian wetlands is provided in order to establish a scientific basis for discussions on a national wetland policy that mandates the sustainable management of Brazil's extremely diverse and complex wetlands.
Abstract: Although 20% of Brazilian territory is covered by wetlands, wetland inventories are still incomplete. In 1993, Brazil signed the Ramsar Convention but a coherent national policy for the sustainable management and protection of wetlands has yet to be established. Major gaps in the definition of a specific wetland policy are twofold: (1) the lack of standardized criteria by which wetlands are defined and delineated that reflects the specific ecological conditions of the country and (2) the lack of a national classification of wetlands that takes into account specific hydrological conditions and respective plant communities. In recent years, efforts have been made at a regional level to improve public awareness of the ecology of Brazilian wetlands, their benefits to society, and the major threats endangering them. Studies have shown that wetlands play a crucial role in the regional hydrological cycle and provide multiple benefits for local populations. Furthermore, Brazilian wetlands contribute significantly to South American biodiversity. Therefore, wetland conservation and sustainable management should be given high legislative priority. This article provides a synthesis of the current body of knowledge on the distribution, hydrology, and vegetation cover of Brazilian wetlands. Their definition, delineation, and classification at the national level are proposed in order to establish a scientific basis for discussions on a national wetland policy that mandates the sustainable management of Brazil's extremely diverse and complex wetlands. This goal is particularly urgent in the face of the continuing and dramatic deterioration of wetlands resulting from large-scale agro-industrial expansion, and hydroelectric projects as well as the projected impact of global climate change on hydrological cycles.
TL;DR: This study reviews the classic infections that are controlled by ROS and the cases in which ROS appear as promoters of infection, challenging the paradigm, and discusses the possible mechanisms by which ROS could promote particular infections.
Abstract: Reactive oxygen species (ROS) are deadly weapons used by phagocytes and other cell types, such as lung epithelial cells, against pathogens. ROS can kill pathogens directly by causing oxidative damage to biocompounds or indirectly by stimulating pathogen elimination by various nonoxidative mechanisms, including pattern recognition receptors signaling, autophagy, neutrophil extracellular trap formation, and T-lymphocyte responses. Thus, one should expect that the inhibition of ROS production promote infection. Increasing evidences support that in certain particular infections, antioxidants decrease and prooxidants increase pathogen burden. In this study, we review the classic infections that are controlled by ROS and the cases in which ROS appear as promoters of infection, challenging the paradigm. We discuss the possible mechanisms by which ROS could promote particular infections. These mechanisms are still not completely clear but include the metabolic effects of ROS on pathogen physiology, ROS-i...
TL;DR: In this article, the authors measured the isospin asymmetries of the B (0) -> K ( 0) mu (+) mu (-), B (1) → K (1)-m (+) m mu (-) and B (2)→ K (2)-m (-) m (-), respectively.
Abstract: The isospin asymmetries of B -> K mu (+) mu (-) and B -> K (*) mu (+) mu (-) decays and the partial branching fractions of the B (0) -> K (0) mu (+) mu (-), B (+) -> K (+) mu (+) mu (-) and B (+) -> K (*+) mu (+) mu (-) decays are measured as functions of the dimuon mass squared, q (2). The data used correspond to an integrated luminosity of 3 fb(-1) from proton-proton collisions collected with the LHCb detector at centre-of-mass energies of 7 TeV and 8 TeV in 2011 and 2012, respectively. The isospin asymmetries are both consistent with the Standard Model expectations. The three measured branching fractions favour lower values than their respective theoretical predictions, however they are all individually consistent with the Standard Model.
TL;DR: The observed evolution of the Z(4430)^{-} amplitude with the ψ^{ fb^{-1} mass establishes the resonant nature of this particle.
Abstract: Resonant structures in B-0 -> psi'pi K--(+) decays are analyzed by performing a four-dimensional fit of the decay amplitude, using pp collision data corresponding to 3 fb(-1) collected with the LHCb detector. The data cannot be described with K+pi(-) resonances alone, which is confirmed with a model-independent approach. A highly significant Z(4430)(-) -> psi'pi(-) component is required, thus confirming the existence of this state. The observed evolution of the Z(4430)(-) amplitude with the psi'pi(-) mass establishes the resonant nature of this particle. The mass and width measurements are substantially improved. The spin parity is determined unambiguously to be 1(+).
TL;DR: In this paper, the ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to dielectron or dimuon final states.
Abstract: The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to dielectron or dimuon final states. Results are presented from an analysis of proton-proton (pp) collisions at a center-of-mass energy of 8 TeV corresponding to an integrated luminosity of 20.3 fb(-1) in the dimuon channel. A narrow resonance with Standard Model Z couplings to fermions is excluded at 95% confidence level for masses less than 2.79 TeV in the dielectron channel, 2.53 TeV in the dimuon channel, and 2.90 TeV in the two channels combined. Limits on other model interpretations are also presented, including a grand-unification model based on the E-6 gauge group, Z* bosons, minimal Z' models, a spin-2 graviton excitation from Randall-Sundrum models, quantum black holes, and a minimal walking technicolor model with a composite Higgs boson.
TL;DR: In this article, the authors presented the electron and photon energy calibration achieved with the ATLAS detector using about 25 fb(-1) of LHC proton-proton collision data taken at center-of-mass energies of root s = 7 and 8 TeV.
Abstract: This paper presents the electron and photon energy calibration achieved with the ATLAS detector using about 25 fb(-1) of LHC proton-proton collision data taken at centre-of-mass energies of root s = 7 and 8 TeV. The reconstruction of electron and photon energies is optimised using multivariate algorithms. The response of the calorimeter layers is equalised in data and simulation, and the longitudinal profile of the electromagnetic showers is exploited to estimate the passive material in front of the calorimeter and reoptimise the detector simulation. After all corrections, the Z resonance is used to set the absolute energy scale. For electrons from Z decays, the achieved calibration is typically accurate to 0.05% in most of the detector acceptance, rising to 0.2% in regions with large amounts of passive material. The remaining inaccuracy is less than 0.2-1% for electrons with a transverse energy of 10 GeV, and is on average 0.3% for photons. The detector resolution is determined with a relative inaccuracy of less than 10% for electrons and photons up to 60 GeV transverse energy, rising to 40% for transverse energies above 500 GeV.
TL;DR: In this paper, a measurement of the Z/gamma* boson transverse momentum spectrum using ATLAS proton-proton collision data at a centre-of-mass energy of root s = 7TeV at the LHC is described.
Abstract: This paper describes a measurement of the Z/gamma* boson transverse momentum spectrum using ATLAS proton-proton collision data at a centre-of-mass energy of root s = 7TeV at the LHC. The measurement is performed in the Z/gamma* -> e(+)e(-) and Z/gamma* -> mu(+)mu(-) channels, using data corresponding to an integrated luminosity of 4.7 fb(-1). Normalized differential cross sections as a function of the Z/gamma* boson transverse momentum are measured for transverse momenta up to 800 GeV. The measurement is performed inclusively for Z/gamma* rapidities up to 2.4, as well as in three rapidity bins. The channel results are combined, compared to perturbative and resummed QCD calculations and used to constrain the parton shower parameters of Monte Carlo generators.
TL;DR: In this article, a search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented.
Abstract: A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector.
TL;DR: Analysis of metagenomic sequence data revealed an increase in abundance of genes involved in denitrification pathways in samples that exceeded the Environmental Protection Agency (EPA)’s benchmarks for polycyclic aromatic hydrocarbons (PAHs) compared with those that did not.
Abstract: The Deepwater Horizon (DWH) oil spill in the spring of 2010 resulted in an input of ∼4.1 million barrels of oil to the Gulf of Mexico; >22% of this oil is unaccounted for, with unknown environmental consequences. Here we investigated the impact of oil deposition on microbial communities in surface sediments collected at 64 sites by targeted sequencing of 16S rRNA genes, shotgun metagenomic sequencing of 14 of these samples and mineralization experiments using (14)C-labeled model substrates. The 16S rRNA gene data indicated that the most heavily oil-impacted sediments were enriched in an uncultured Gammaproteobacterium and a Colwellia species, both of which were highly similar to sequences in the DWH deep-sea hydrocarbon plume. The primary drivers in structuring the microbial community were nitrogen and hydrocarbons. Annotation of unassembled metagenomic data revealed the most abundant hydrocarbon degradation pathway encoded genes involved in degrading aliphatic and simple aromatics via butane monooxygenase. The activity of key hydrocarbon degradation pathways by sediment microbes was confirmed by determining the mineralization of (14)C-labeled model substrates in the following order: propylene glycol, dodecane, toluene and phenanthrene. Further, analysis of metagenomic sequence data revealed an increase in abundance of genes involved in denitrification pathways in samples that exceeded the Environmental Protection Agency (EPA)'s benchmarks for polycyclic aromatic hydrocarbons (PAHs) compared with those that did not. Importantly, these data demonstrate that the indigenous sediment microbiota contributed an important ecosystem service for remediation of oil in the Gulf. However, PAHs were more recalcitrant to degradation, and their persistence could have deleterious impacts on the sediment ecosystem.
University of São Paulo1, Columbia University2, Peking Union Medical College Hospital3, Hungkuang University4, National Defense Medical Center5, Federal University of Rio de Janeiro6, Oregon Health & Science University7, Erasmus University Medical Center8, University of Edinburgh9, Novartis10, University of Birmingham11
TL;DR: Pasireotide LAR demonstrated superior efficacy over octreotide LAR and is a viable new treatment option for acromegaly.
Abstract: Context: Biochemical control reduces morbidity and increases life expectancy in patients with acromegaly. With current medical therapies, including the gold standard octreotide long-acting-release (LAR), many patients do not achieve biochemical control. Objective: Our objective was to demonstrate the superiority of pasireotide LAR over octreotide LAR in medically naive patients with acromegaly. Design and Setting: We conducted a prospective, randomized, double-blind study at 84 sites in 27 countries. Patients: A total of 358 patients with medically naive acromegaly (GH >5 μg/L or GH nadir ≥1 μg/L after an oral glucose tolerance test (OGTT) and IGF-1 above the upper limit of normal) were enrolled. Patients either had previous pituitary surgery but no medical treatment or were de novo with a visible pituitary adenoma on magnetic resonance imaging. Interventions: Patients received pasireotide LAR 40 mg/28 days (n = 176) or octreotide LAR 20 mg/28 days (n = 182) for 12 months. At months 3 and 7, titration to ...
TL;DR: The concept that peripheral and central nervous system inflammation link the pathogenesis of AD and metabolic diseases is discussed and the contribution of brain inflammation to defective insulin signaling and neuronal dysfunction is explored.
Abstract: A link between Alzheimer's disease (AD) and metabolic disorders has been established, with patients with type 2 diabetes at increased risk of developing AD and vice versa. The incidence of metabolic disorders, including insulin resistance and type 2 diabetes is increasing at alarming rates worldwide, primarily as a result of poor lifestyle habits. In parallel, as the world population ages, the prevalence of AD, the most common form of dementia in the elderly, also increases. In addition to their epidemiologic and clinical association, mounting recent evidence indicates shared mechanisms of pathogenesis between metabolic disorders and AD. We discuss the concept that peripheral and central nervous system inflammation link the pathogenesis of AD and metabolic diseases. We also explore the contribution of brain inflammation to defective insulin signaling and neuronal dysfunction. Last, we review recent evidence indicating that targeting neuroinflammation may provide novel therapeutic avenues for AD.
Proceedings Article•
31 Jul 2014
TL;DR: Recent evidence is reviewed that sheds light on how brain insulin dysfunction is initiated at a molecular level and why abnormal insulin signaling culminates in synaptic failure and memory decline and provides pathophysiological background for identification of novel molecular targets and for development of alternative therapeutic approaches in AD.
Abstract: Compelling preclinical and clinical evidence supports a pathophysiological connection between Alzheimer's disease (AD) and diabetes. Altered metabolism, inflammation, and insulin resistance are key pathological features of both diseases. For many years, it was generally considered that the brain was insensitive to insulin, but it is now accepted that this hormone has central neuromodulatory functions, including roles in learning and memory, that are impaired in AD. However, until recently, the molecular mechanisms accounting for brain insulin resistance in AD have remained elusive. Here, we review recent evidence that sheds light on how brain insulin dysfunction is initiated at a molecular level and why abnormal insulin signaling culminates in synaptic failure and memory decline. We also discuss the cellular basis underlying the beneficial effects of stimulation of brain insulin signaling on cognition. Discoveries summarized here provide pathophysiological background for identification of novel molecular targets and for development of alternative therapeutic approaches in AD.
Leipzig University1, Odense University Hospital2, Université libre de Bruxelles3, Universidade Federal do Estado do Rio de Janeiro4, University Health Network5, Nottingham University Hospitals NHS Trust6, Ege University7, Ankara University8, Université de Montréal9, Universidade Federal do Rio Grande do Sul10, Federal University of Rio de Janeiro11, Hannover Medical School12, University of Plymouth13, University of New South Wales14, Cairo University15, Örebro University16, Ain Shams University17, Dokuz Eylül University18, Karolinska University Hospital19, Federal University of São Paulo20, Carlos III Health Institute21, University of Copenhagen22, State University of Campinas23, University of São Paulo24, Medical University of Vienna25, Masaryk University26, University of Manitoba27, Istanbul University28, University of British Columbia29, Aalborg University30, Katholieke Universiteit Leuven31, University of Western Ontario32, University of Düsseldorf33, University of Zurich34, University of Calgary35, Geneva College36, Dalhousie University37, Queen Elizabeth II Health Sciences Centre38, Monash University39, University College London40, Goethe University Frankfurt41, University of St. Gallen42, Université catholique de Louvain43, Medical University of Graz44, University of Melbourne45, Charles University in Prague46, Ghent University Hospital47, University of Hasselt48, Ghent University49, Copenhagen University Hospital50, University of Antwerp51, Karolinska Institutet52
TL;DR: In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use, and Diagnosis, treatment and transplant levels also differed considerably between countries.
Abstract: Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
Federal University of Rio de Janeiro1, University of São Paulo2, Centre national de la recherche scientifique3, Academy of Medical Sciences, United Kingdom4, Oregon Health & Science University5, I.M. Sechenov First Moscow State Medical University6, University of Lyon7, Rabin Medical Center8, Novartis9
TL;DR: Pasireotide provides superior efficacy compared with continued treatment with octreotide or lanreotide, and could become the new standard pituitary-directed treatment in patients with acromegaly who are inadequately controlled using first-generation somatostatin analogues.
TL;DR: In this paper, an improved measurement of the mass of the Higgs boson is derived from a combined fit to the reconstructed invariant mass spectra of the decay channels H -> gamma gamma and H -> ZZ* -> 4l.
Abstract: An improved measurement of the mass of the Higgs boson is derived from a combined fit to the reconstructed invariant mass spectra of the decay channels H -> gamma gamma and H -> ZZ* -> 4l. The analysis uses the pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at center-of-mass energies of 7 TeV and 8 TeV, corresponding to an integrated luminosity of 25 fb(-1). The measured value of the Higgs boson mass is m(H) = 125.36 +/- 0.37(stat) +/- 0.18 (syst) GeV. This result is based on improved energy-scale calibrations for photons, electrons, and muons as well as other analysis improvements, and supersedes the previous result from ATLAS. Upper limits on the total width of the Higgs boson are derived from fits to the invariant mass spectra of the H -> gamma gamma and H -> ZZ* -> 4l decay channels.
Braunschweig University of Technology1, Federal University of Rio Grande do Norte2, University of Los Andes3, Smithsonian Tropical Research Institute4, University of São Paulo5, University of Trier6, Centre national de la recherche scientifique7, Sao Paulo State University8, Spanish National Research Council9, Vrije Universiteit Brussel10, Národní muzeum11, Federal University of Rio de Janeiro12, La Salle University13, Hessisches Landesmuseum Darmstadt14, Venezuelan Institute for Scientific Research15, State University of Santa Cruz16, East Carolina University17
TL;DR: The results, at a spatial scale and resolution unprecedented for a Neotropical vertebrate, confirm that widespread amphibian species occur in lowland South America, yet at the same time a large proportion of cryptic diversity still remains to be discovered.
Abstract: Species distributed across vast continental areas and across major biomes provide unique model systems for studies of biotic diversification, yet also constitute daunting financial, logistic and political challenges for data collection across such regions. The tree frog Dendropsophus minutus (Anura: Hylidae) is a nominal species, continentally distributed in South America, that may represent a complex of multiple species, each with a more limited distribution. To understand the spatial pattern of molecular diversity throughout the range of this species complex, we obtained DNA sequence data from two mitochondrial genes, cytochrome oxidase I (COI) and the 16S rhibosomal gene (16S) for 407 samples of D. minutus and closely related species distributed across eleven countries, effectively comprising the entire range of the group. We performed phylogenetic and spatially explicit phylogeographic analyses to assess the genetic structure of lineages and infer ancestral areas. We found 43 statistically supported, deep mitochondrial lineages, several of which may represent currently unrecognized distinct species. One major clade, containing 25 divergent lineages, includes samples from the type locality of D. minutus. We defined that clade as the D. minutus complex. The remaining lineages together with the D. minutus complex constitute the D. minutus species group. Historical analyses support an Amazonian origin for the D. minutus species group with a subsequent dispersal to eastern Brazil where the D. minutus complex originated. According to our dataset, a total of eight mtDNA lineages have ranges >100,000 km2. One of them occupies an area of almost one million km2 encompassing multiple biomes. Our results, at a spatial scale and resolution unprecedented for a Neotropical vertebrate, confirm that widespread amphibian species occur in lowland South America, yet at the same time a large proportion of cryptic diversity still remains to be discovered.
TL;DR: In this paper, a measurement of the production processes of the recently discovered Higgs boson is performed in the two-photon final state using 4.5 fb(-1) of proton-proton collisions data at root s = 7 TeV and 20.4 GeV.
Abstract: A measurement of the production processes of the recently discovered Higgs boson is performed in the two-photon final state using 4.5 fb(-1) of proton-proton collisions data at root s = 7 TeV and 20.3 fb(-1) at root s = 8 TeV collected by the ATLAS detector at the Large Hadron Collider. The number of observed Higgs boson decays to diphotons divided by the corresponding Standard Model prediction, called the signal strength, is found to be mu = 1.17 +/- 0.27 at the value of the Higgs boson mass measured by ATLAS, m(H) = 125.4 GeV. The analysis is optimized to measure the signal strengths for individual Higgs boson production processes at this value of m(H). They are found to be mu(ggF) = 1.32 +/- 0.38, mu(VBF) = 0.8 +/- 0.7, mu(WH) = 1.0 +/- 1.6, mu(ZH) = 0.1(-0.1)(+3.7), and mu t (t) over barH = 1.6(-1.8)(+2.7), for Higgs boson production through gluon fusion, vector-boson fusion, and in association with a W or Z boson or a top-quark pair, respectively. Compared with the previously published ATLAS analysis, the results reported here also benefit from a new energy calibration procedure for photons and the subsequent reduction of the systematic uncertainty on the diphoton mass resolution. No significant deviations from the predictions of the Standard Model are found.