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Showing papers by "University of Buenos Aires published in 2015"


Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +5117 moreInstitutions (314)
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.

1,567 citations


Journal ArticleDOI
TL;DR: Benefiting from the power of multilinear algebra as their mathematical backbone, data analysis techniques using tensor decompositions are shown to have great flexibility in the choice of constraints which match data properties and extract more general latent components in the data than matrix-based methods.
Abstract: The widespread use of multisensor technology and the emergence of big data sets have highlighted the limitations of standard flat-view matrix models and the necessity to move toward more versatile data analysis tools. We show that higher-order tensors (i.e., multiway arrays) enable such a fundamental paradigm shift toward models that are essentially polynomial, the uniqueness of which, unlike the matrix methods, is guaranteed under very mild and natural conditions. Benefiting from the power of multilinear algebra as their mathematical backbone, data analysis techniques using tensor decompositions are shown to have great flexibility in the choice of constraints which match data properties and extract more general latent components in the data than matrix-based methods.

1,250 citations


Journal ArticleDOI
TL;DR: A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.
Abstract: The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation, and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The “Warburg effect” originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here, we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

907 citations


Journal ArticleDOI
Lorenzo Galluzzi1, J M Bravo-San Pedro2, Ilio Vitale, Stuart A. Aaronson3, John M. Abrams4, Dieter Adam5, Emad S. Alnemri6, Lucia Altucci7, David W. Andrews8, Margherita Annicchiarico-Petruzzelli, Eric H. Baehrecke9, Nicolas G. Bazan10, Mathieu J.M. Bertrand11, Mathieu J.M. Bertrand12, Katiuscia Bianchi13, Katiuscia Bianchi14, Mikhail V. Blagosklonny15, Klas Blomgren16, Christoph Borner17, Dale E. Bredesen18, Dale E. Bredesen19, Catherine Brenner20, Catherine Brenner21, Michelangelo Campanella22, Eleonora Candi23, Francesco Cecconi23, Francis Ka-Ming Chan9, Navdeep S. Chandel24, Emily H. Cheng25, Jerry E. Chipuk3, John A. Cidlowski26, Aaron Ciechanover27, Ted M. Dawson28, Valina L. Dawson28, V De Laurenzi29, R De Maria, Klaus-Michael Debatin30, N. Di Daniele23, Vishva M. Dixit31, Brian David Dynlacht32, Wafik S. El-Deiry33, Gian Maria Fimia34, Richard A. Flavell35, Simone Fulda36, Carmen Garrido37, Marie-Lise Gougeon38, Douglas R. Green, Hinrich Gronemeyer39, György Hajnóczky6, J M Hardwick28, Michael O. Hengartner40, Hidenori Ichijo41, Bertrand Joseph16, Philipp J. Jost42, Thomas Kaufmann43, Oliver Kepp2, Daniel J. Klionsky44, Richard A. Knight22, Richard A. Knight45, Sharad Kumar46, Sharad Kumar47, John J. Lemasters48, Beth Levine49, Beth Levine50, Andreas Linkermann5, Stuart A. Lipton, Richard A. Lockshin51, Carlos López-Otín52, Enrico Lugli, Frank Madeo53, Walter Malorni54, Jean-Christophe Marine55, Seamus J. Martin56, J-C Martinou57, Jan Paul Medema58, Pascal Meier, Sonia Melino23, Noboru Mizushima41, Ute M. Moll59, Cristina Muñoz-Pinedo, Gabriel Núñez44, Andrew Oberst60, Theocharis Panaretakis16, Josef M. Penninger, Marcus E. Peter24, Mauro Piacentini23, Paolo Pinton61, Jochen H. M. Prehn62, Hamsa Puthalakath63, Gabriel A. Rabinovich64, Kodi S. Ravichandran65, Rosario Rizzuto66, Cecília M. P. Rodrigues67, David C. Rubinsztein68, Thomas Rudel69, Yufang Shi70, Hans-Uwe Simon43, Brent R. Stockwell71, Brent R. Stockwell50, Gyorgy Szabadkai66, Gyorgy Szabadkai22, Stephen W.G. Tait72, H. L. Tang28, Nektarios Tavernarakis73, Nektarios Tavernarakis74, Yoshihide Tsujimoto, T Vanden Berghe12, T Vanden Berghe11, Peter Vandenabeele11, Peter Vandenabeele12, Andreas Villunger75, Erwin F. Wagner76, Henning Walczak22, Eileen White77, W. G. Wood78, Junying Yuan79, Zahra Zakeri80, Boris Zhivotovsky16, Boris Zhivotovsky81, Gerry Melino45, Gerry Melino23, Guido Kroemer1 
Paris Descartes University1, Institut Gustave Roussy2, Mount Sinai Hospital3, University of Texas Southwestern Medical Center4, University of Kiel5, Thomas Jefferson University6, Seconda Università degli Studi di Napoli7, University of Toronto8, University of Massachusetts Medical School9, Louisiana State University10, Flanders Institute for Biotechnology11, Ghent University12, Cancer Research UK13, Queen Mary University of London14, Roswell Park Cancer Institute15, Karolinska Institutet16, University of Freiburg17, University of California, San Francisco18, Buck Institute for Research on Aging19, Université Paris-Saclay20, French Institute of Health and Medical Research21, University College London22, University of Rome Tor Vergata23, Northwestern University24, Memorial Sloan Kettering Cancer Center25, National Institutes of Health26, Technion – Israel Institute of Technology27, Johns Hopkins University28, University of Chieti-Pescara29, University of Ulm30, Genentech31, New York University32, Pennsylvania State University33, University of Salento34, Yale University35, Goethe University Frankfurt36, University of Burgundy37, Pasteur Institute38, University of Strasbourg39, University of Zurich40, University of Tokyo41, Technische Universität München42, University of Bern43, University of Michigan44, Medical Research Council45, University of Adelaide46, University of South Australia47, Medical University of South Carolina48, University of Texas at Dallas49, Howard Hughes Medical Institute50, St. John's University51, University of Oviedo52, University of Graz53, Istituto Superiore di Sanità54, Katholieke Universiteit Leuven55, Trinity College, Dublin56, University of Geneva57, University of Amsterdam58, Stony Brook University59, University of Washington60, University of Ferrara61, Royal College of Surgeons in Ireland62, La Trobe University63, University of Buenos Aires64, University of Virginia65, University of Padua66, University of Lisbon67, University of Cambridge68, University of Würzburg69, Soochow University (Suzhou)70, Columbia University71, University of Glasgow72, Foundation for Research & Technology – Hellas73, University of Crete74, Innsbruck Medical University75, Carlos III Health Institute76, Rutgers University77, University of Minnesota78, Harvard University79, City University of New York80, Moscow State University81
TL;DR: The Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
Abstract: Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.

809 citations


Journal ArticleDOI
A. Aab1, P. Abreu2, Marco Aglietta3, Marco Aglietta4  +640 moreInstitutions (64)
TL;DR: The Pierre Auger Observatory as mentioned in this paper, the world's largest cosmic ray observatory, has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000 km$^2$ sr yr.
Abstract: The Pierre Auger Observatory, located on a vast, high plain in western Argentina, is the world's largest cosmic ray observatory. The objectives of the Observatory are to probe the origin and characteristics of cosmic rays above $10^{17}$ eV and to study the interactions of these, the most energetic particles observed in nature. The Auger design features an array of 1660 water-Cherenkov particle detector stations spread over 3000 km$^2$ overlooked by 24 air fluorescence telescopes. In addition, three high elevation fluorescence telescopes overlook a 23.5 km$^2$, 61 detector infill array. The Observatory has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000 km$^2$ sr yr. This paper describes the design and performance of the detectors, related subsystems and infrastructure that make up the Auger Observatory.

615 citations


Journal ArticleDOI
TL;DR: Recommendations are provided that trials should be designed to evaluate effectiveness when possible, should include clinical outcome measures, and should obtain health resource use and health state utilities directly from study subjects, and articles should adhere to established standards for reporting results of cost-effectiveness analyses.

530 citations


Journal ArticleDOI
TL;DR: The aim of this review is to disclose the emerging roles of exosomes in normal and pathological conditions and to discuss their potential therapeutic applications.
Abstract: From the time when they were first described in the 1970s by the group of Johnstone and Stahl, exosomes are a target of constant research. Exosomes belong to the family of nano-vesicles which are of great interest for their many functions and potential for diagnosis and therapy in multiples diseases. Exosomes originate from the intraluminal vesicles of late endosomal compartments named multivesicular bodies and the fusion of these late endosomes with the cell membrane result in the release of the vesicles into the extracellular compartment. Moreover, their generation can be induced by many factors including extracellular stimuli, such as microbial attack and other stress conditions. The primary role attributed to exosomes was the removal of unnecessary proteins from the cells. Now, several studies have demonstrated that exosomes are involved in cell-cell communication, even though their biological function is not completely clear. The participation of exosomes in cancer is the field of microvesicle research that has expanded more over the last years. Evidence proving that exosomes derived from tumor-pulsed dendritic cells, neoplastic cells and malignant effusions, are able to present antigens to T‐cells, has led to numerous studies using them as cell free cancer vaccines. Since exosomes derive from all cell types, they contain proteins, lipids and miRNA capable of regulating a variety of target genes. Much research is being conducted, which focuses on the employment of these vesicles as biomarkers in the diagnosis of cancer in addition to innovative biomarkers for diagnosis, prognosis and management of cardiovascular diseases. Interesting findings indicating the role of exosomes in the pathogenesis of several diseases have encouraged researchers to consider their therapeutic potential not only in oncology but also in the treatment of autoimmune syndromes and neurodegenerative disorders such as Alzheimer´s and Parkinson´s disease; in addition to infectious disease

504 citations


Journal ArticleDOI
TL;DR: It is shown that dimer-like silicon-based single nanoantennas produce both high surface enhanced fluorescence and surface enhanced Raman scattering, while at the same time generating a negligible temperature increase in their hot spots and surrounding environments.
Abstract: Nanoplasmonics has recently revolutionized our ability to control light on the nanoscale. Using metallic nanostructures with tailored shapes, it is possible to efficiently focus light into nanoscale field ‘hot spots'. High field enhancement factors have been achieved in such optical nanoantennas, enabling transformative science in the areas of single molecule interactions, highly enhanced nonlinearities and nanoscale waveguiding. Unfortunately, these large enhancements come at the price of high optical losses due to absorption in the metal, severely limiting real-world applications. Via the realization of a novel nanophotonic platform based on dielectric nanostructures to form efficient nanoantennas with ultra-low light-into-heat conversion, here we demonstrate an approach that overcomes these limitations. We show that dimer-like silicon-based single nanoantennas produce both high surface enhanced fluorescence and surface enhanced Raman scattering, while at the same time generating a negligible temperature increase in their hot spots and surrounding environments.

459 citations


Journal ArticleDOI
26 Aug 2015
TL;DR: Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis, as well as outperforming classification from clinical interviews.
Abstract: BACKGROUND/OBJECTIVES: Psychiatry lacks the objective clinical tests routinely used in other specializations Novel computerized methods to characterize complex behaviors such as speech could be used to identify and predict psychiatric illness in individuals AIMS: In this proof-of-principle study, our aim was to test automated speech analyses combined with Machine Learning to predict later psychosis onset in youths at clinical high-risk (CHR) for psychosis METHODS: Thirty-four CHR youths (11 females) had baseline interviews and were assessed quarterly for up to 25 years; five transitioned to psychosis Using automated analysis, transcripts of interviews were evaluated for semantic and syntactic features predicting later psychosis onset Speech features were fed into a convex hull classification algorithm with leave-one-subject-out cross-validation to assess their predictive value for psychosis outcome The canonical correlation between the speech features and prodromal symptom ratings was computed RESULTS: Derived speech features included a Latent Semantic Analysis measure of semantic coherence and two syntactic markers of speech complexity: maximum phrase length and use of determiners (eg, which) These speech features predicted later psychosis development with 100% accuracy, outperforming classification from clinical interviews Speech features were significantly correlated with prodromal symptoms CONCLUSIONS: Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis Recent developments in computer science, including natural language processing, could provide the foundation for future development of objective clinical tests for psychiatry

455 citations


Journal ArticleDOI
01 May 2015-Gut
TL;DR: In vitro exploration showed that overexpression of miR-122 enhances alanine aminotransferase activity, and NAFLD has a distinguishing circulating miRNA profile associated with a global dysmetabolic disease state and cardiovascular risk.
Abstract: Objectives We used a screening strategy of global serum microRNA (miRNA) profiling, followed by a second stage of independent replication and exploration of liver expression of selected miRNAs to study: (1) the circulating miRNA signature associated with non-alcoholic fatty liver disease (NAFLD) progression and predictive power, (2) the role of miRNAs in disease biology and (3) the association between circulating miRNAs and features of the metabolic syndrome. Methods The study used a case-control design and included patients with NAFLD proven through biopsy and healthy controls. Results Among 84 circulating miRNAs analysed, miR-122, miR-192, miR-19a and miR-19b, miR-125b, and miR-375 were upregulated >2-fold (p Conclusions miR-122 plays a role of physiological significance in the biology of NAFLD; circulating miRNAs mirror the histological and molecular events occurring in the liver. NAFLD has a distinguishing circulating miRNA profile associated with a global dysmetabolic disease state and cardiovascular risk.

437 citations


Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek4  +2815 moreInstitutions (169)
TL;DR: In this article, a search for new phenomena in final states with an energetic jet and large missing transverse momentum was performed using 20.3 fb(-1) of root s = 8 TeV data collected in 2012.
Abstract: Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb(-1) of root s = 8 TeV data collected in 2012 ...

Proceedings ArticleDOI
13 Jun 2015
TL;DR: A detailed microarchitectural analysis of live datacenter jobs, measured on more than 20,000 Google machines over a three year period, and comprising thousands of different applications finds that WSC workloads are extremely diverse, breeding the need for architectures that can tolerate application variability without performance loss.
Abstract: With the increasing prevalence of warehouse-scale (WSC) and cloud computing, understanding the interactions of server applications with the underlying microarchitecture becomes ever more important in order to extract maximum performance out of server hardware. To aid such understanding, this paper presents a detailed microarchitectural analysis of live datacenter jobs, measured on more than 20,000 Google machines over a three year period, and comprising thousands of different applications. We first find that WSC workloads are extremely diverse, breeding the need for architectures that can tolerate application variability without performance loss. However, some patterns emerge, offering opportunities for co-optimization of hardware and software. For example, we identify common building blocks in the lower levels of the software stack. This "datacenter tax" can comprise nearly 30% of cycles across jobs running in the fleet, which makes its constituents prime candidates for hardware specialization in future server systems-on-chips. We also uncover opportunities for classic microarchitectural optimizations for server processors, especially in the cache hierarchy. Typical workloads place significant stress on instruction caches and prefer memory latency over bandwidth. They also stall cores often, but compute heavily in bursts. These observations motivate several interesting directions for future warehouse-scale computers.

Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, J. Abdallah4  +2914 moreInstitutions (169)
TL;DR: In this article, the jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector using proton-proton collision data with a centre-of-mass energy of [Formula: see text]TeV corresponding to an integrated luminosity of [formula] see text][formula:see text].
Abstract: The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector using proton-proton collision data with a centre-of-mass energy of [Formula: see text] TeV corresponding to an integrated luminosity of [Formula: see text][Formula: see text]. Jets are reconstructed from energy deposits forming topological clusters of calorimeter cells using the anti-[Formula: see text] algorithm with distance parameters [Formula: see text] or [Formula: see text], and are calibrated using MC simulations. A residual JES correction is applied to account for differences between data and MC simulations. This correction and its systematic uncertainty are estimated using a combination of in situ techniques exploiting the transverse momentum balance between a jet and a reference object such as a photon or a [Formula: see text] boson, for [Formula: see text] and pseudorapidities [Formula: see text]. The effect of multiple proton-proton interactions is corrected for, and an uncertainty is evaluated using in situ techniques. The smallest JES uncertainty of less than 1 % is found in the central calorimeter region ([Formula: see text]) for jets with [Formula: see text]. For central jets at lower [Formula: see text], the uncertainty is about 3 %. A consistent JES estimate is found using measurements of the calorimeter response of single hadrons in proton-proton collisions and test-beam data, which also provide the estimate for [Formula: see text] TeV. The calibration of forward jets is derived from dijet [Formula: see text] balance measurements. The resulting uncertainty reaches its largest value of 6 % for low-[Formula: see text] jets at [Formula: see text]. Additional JES uncertainties due to specific event topologies, such as close-by jets or selections of event samples with an enhanced content of jets originating from light quarks or gluons, are also discussed. The magnitude of these uncertainties depends on the event sample used in a given physics analysis, but typically amounts to 0.5-3 %.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +2827 moreInstitutions (148)
TL;DR: The Standard Model (SM) Higgs boson hypothesis is tested against several alternative spin scenarios, including non-SM spin-0 and spin-2 models with universal and non-universal couplings to fermions and vector bosons, and the observed distributions of variables sensitive to the non- SM tensor couplings are compatible with the SM predictions.
Abstract: Studies of the spin, parity and tensor couplings of the Higgs boson in the [Formula: see text], [Formula: see text] and [Formula: see text] decay processes at the LHC are presented. The investigations are based on [Formula: see text] of pp collision data collected by the ATLAS experiment at [Formula: see text] TeV and [Formula: see text] TeV. The Standard Model (SM) Higgs boson hypothesis, corresponding to the quantum numbers [Formula: see text], is tested against several alternative spin scenarios, including non-SM spin-0 and spin-2 models with universal and non-universal couplings to fermions and vector bosons. All tested alternative models are excluded in favour of the SM Higgs boson hypothesis at more than 99.9 % confidence level. Using the [Formula: see text] and [Formula: see text] decays, the tensor structure of the interaction between the spin-0 boson and the SM vector bosons is also investigated. The observed distributions of variables sensitive to the non-SM tensor couplings are compatible with the SM predictions and constraints on the non-SM couplings are derived.

Journal ArticleDOI
TL;DR: This study explores the delay in diagnosis for patients with HS on an international level and quantifies thedelay in diagnosis of HS compared with psoriasis with/without a family history.
Abstract: DEAR EDITOR, Hidradenitis suppurativa (HS) is clinically defined with recognized diagnostic criteria and recognizable physical characteristics. Untreated, the disease causes significant morbidity. The prevalence varies between 0 0003% and 4% depending on the study population. Estimates from insurance databases suggest a prevalence of < 0 1%. This variation strongly suggests a significant selection bias or misclassification, and it may be speculated that not all patients present for care. This is reinforced by clinical experience and published evidence indicating a significant delay in diagnosis. This study explores the delay in diagnosis for patients with HS on an international level. The study (survey) was conducted in 2013. Observational data were collected during routine visits or extracted from case records. Because of the simple and obvious symptomatology of recurrent painful lesions present in restricted welldefined areas of the body, patients’ self-reported history was considered valid regarding onset of symptoms. Consecutive patients with HS and psoriasis were included from each participating centre during a period of 4 months or less. The data were anonymized by removing any names, addresses and social security numbers, and included age, sex, age at disease onset, age at diagnosis, delay in diagnosis, time from onset of symptoms to first physician contact, age at first medical contact, number of physicians seen prior to the diagnosis, family history and disease severity. If the diagnosis was made by a primary care physician or by a specialist other than a dermatologist prior to seeing a dermatologist, this was recorded as the date of the diagnosis. Individual centres were responsible for and obtained any locally required permissions and signed informed consent forms, for example ethics committee approval, in accordance with national registry and data protection rules. Patients diagnosed with HS or psoriasis (and confirmed by the investigator) were included. The primary outcome was quantification of the delay in diagnosis. Additionally, documentation was made of both the delay in visiting a physician (and so gaining access to specialist treatment) and the relative delay in diagnosis of HS compared with psoriasis with/without a family history. The severity of HS was determined by Hurley’s staging criteria: stage I, mild; stage II, moderate and stage III, severe. In patients with psoriasis, severity was evaluated by the Psoriasis Area and Severity Index: score < 7, mild; 7–12, moderate and > 12, severe. The t-test, Wilcoxon rank sum test and v-test were used where appropriate. Univariate and multivariate logistic regression analyses were used to identify factors predictive of significant diagnostic delay. Diagnostic delay > 2 years was defined as significant. Diagnosis, sex, age of onset, family history and disease severity were selected as potentially important

Journal ArticleDOI
TL;DR: A provisional consensus definition of agitation can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment and may have regulatory applications in drug development programs.
Abstract: Background: Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs. Methods: The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process. Results: Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as strongly agree or somewhat agree (68-88 across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications. Conclusions: A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment. Copyright © International Psychogeriatric Association 2014.

Journal ArticleDOI
TL;DR: This article identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL).
Abstract: Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia(1,2). We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition.


Journal ArticleDOI
A. Aab1, P. Abreu1, Marco Aglietta1, E. J. Ahn1  +487 moreInstitutions (64)
TL;DR: In this article, the authors presented the first hybrid measurement of the average muon number in air showers at ultrahigh energies, initiated by cosmic rays with zenith angles between 62° and 80°.
Abstract: We present the first hybrid measurement of the average muon number in air showers at ultrahigh energies, initiated by cosmic rays with zenith angles between 62° and 80°. The measurement is based on 174 hybrid events recorded simultaneously with the surface detector array and the fluorescence detector of the Pierre Auger Observatory. The muon number for each shower is derived by scaling a simulated reference profile of the lateral muon density distribution at the ground until it fits the data. A 1019eV shower with a zenith angle of 67°, which arrives at the surface detector array at an altitude of 1450 m above sea level, contains on average (2.68±0.04±0.48(sys))×107 muons with energies larger than 0.3 GeV. The logarithmic gain dlnNμ/dlnE of muons with increasing energy between 4×1018eV and 5×1019eV is measured to be (1.029±0.024±0.030(sys)).

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +2841 moreInstitutions (148)
TL;DR: Since no evidence of third-generation squarks is found, exclusion limits are derived by combining several analyses and are presented in both a simplified model framework, assuming simple decay chains, as well as within the context of more elaborate phenomenological supersymmetric models.
Abstract: This paper reviews and extends searches for the direct pair production of the scalar supersymmetric partners of the top and bottom quarks in proton-proton collisions collected by the ATLAS collaboration during the LHC Run 1. Most of the analyses use 20 [Formula: see text] of collisions at a centre-of-mass energy of [Formula: see text] TeV, although in some case an additional [Formula: see text] of collision data at [Formula: see text] TeV are used. New analyses are introduced to improve the sensitivity to specific regions of the model parameter space. Since no evidence of third-generation squarks is found, exclusion limits are derived by combining several analyses and are presented in both a simplified model framework, assuming simple decay chains, as well as within the context of more elaborate phenomenological supersymmetric models.

Journal ArticleDOI
TL;DR: This article critically assess the recent neuroimaging studies in individuals with tinnitus that suggest that the disorder is accompanied by functional and structural brain abnormalities in distributed auditory and non-auditory brain regions.
Abstract: Tinnitus is the perception of phantom sound in the absence of a corresponding external source. It is a highly prevalent disorder, and most cases are caused by cochlear injury that leads to peripheral deafferentation, which results in adaptive changes in the CNS. In this article we critically assess the recent neuroimaging studies in individuals with tinnitus that suggest that the disorder is accompanied by functional and structural brain abnormalities in distributed auditory and non-auditory brain regions. Moreover, we consider how the identification of the neuronal mechanisms underlying the different forms of tinnitus would benefit from larger studies, replication and comprehensive clinical assessment of patients.

Journal ArticleDOI
TL;DR: The aim was to ascertain if administration of Emricasan, a pan‐caspase inhibitor, ameliorates liver injury and fibrosis in a murine model of NASH.
Abstract: Fil: Barreyro, Fernando Javier. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Quimicas y Naturales. Departamento de Microbiologia; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clinicas General San Martin. Laboratorio de Metabolismo del Oxigeno; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +2882 moreInstitutions (212)
TL;DR: In this article, a search for narrow resonances decaying into WW, WZ, or ZZ boson pairs using 20.3 fb(-1) of proton-proton collision data at a center-of-mass energy of root s = TeV recorded with the AT...
Abstract: A search is performed for narrow resonances decaying into WW, WZ, or ZZ boson pairs using 20.3 fb(-1) of proton-proton collision data at a centre-of-mass energy of root s = TeV recorded with the AT ...

Journal ArticleDOI
TL;DR: Barros, Vicente Ricardo, et al. as discussed by the authors presented a study on the role of the Atmosfera in the development of the Barros-Ricardo project.
Abstract: Fil: Barros, Vicente Ricardo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmosfera; Argentina

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek4  +2877 moreInstitutions (190)
TL;DR: In this article, the final ATLAS Run 1 measurements of Higgs boson production and couplings in the decay channel H -> ZZ* -> l(+)l(-)l(+) l'(-), where l, l' = e or mu, are presented.
Abstract: The final ATLAS Run 1 measurements of Higgs boson production and couplings in the decay channel H -> ZZ* -> l(+)l(-)l(+)l'(-), where l, l' = e or mu, are presented. These measurements were performed using pp collision data corresponding to integrated luminosities of 4.5 and 20.3 fb(-1) at center-of-mass energies of 7 and 8 TeV, respectively, recorded with the ATLAS detector at the LHC. The H -> ZZ* -> 4l signal is observed with a significance of 8.1 standard deviations, with an expectation of 6.2 standard deviations, at m(H) = 125.36 GeV, the combined ATLAS measurement of the Higgs boson mass from the H -> gamma gamma and H -> ZZ* -> 4l channels. The production rate relative to the Standard Model expectation, the signal strength, is measured in four different production categories in the H -> ZZ* -> 4l channel. The measured signal strength, at this mass, and with all categories combined, is 1.44(-0.33)(+0.40). The signal strength for Higgs boson production in gluon fusion or in association with (tt) over bar or (bb) over bar pairs is found to be 1.7(-0.4)(+0.5), while the signal strength for vector-boson fusion combined with WH/ZH associated production is found to be 0.3(-0.9)(+1.6).

Journal ArticleDOI
A. Aab1, P. Abreu2, Marco Aglietta3, Eun-Joo Ahn4  +490 moreInstitutions (65)
TL;DR: Al Almela, Daniel Alejandro as discussed by the authors, Federación Nacional de Investigaciones Cientificas y Tecnicas (FNCIT) and CONGESTO NACIONAL de Investigación Científicas (CICIT) of Argentina.
Abstract: Fil: Almela, Daniel Alejandro. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Parque Centenario. Instituto de Tecnologias en Deteccion y Astroparticulas; Argentina

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TL;DR: This review focuses on the current knowledge of the role of nitric oxide in adaptive plant responses to some specific abiotic stress conditions, particularly low mineral nutrient supply, drought, salinity and high UV-B radiation.
Abstract: Nitric oxide in plants may originate endogenously or come from surrounding atmosphere and soil. Interestingly, this gaseous free radical is far from having a constant level and varies greatly among tissues depending on a given plant´s ontogeny and environmental fluctuations. Proper plant growth, vegetative development, and reproduction require the integration of plant hormonal activity with the antioxidant network, as well as the maintenance of concentration of reactive oxygen and nitrogen species within a narrow range. Plants are frequently faced with abiotic stress conditions such as low nutrient availability, salinity, drought, high ultraviolet (UV) radiation and extreme temperatures, which can influence developmental processes and lead to growth restriction making adaptive responses the plant´s priority. The ability of plants to respond and survive under environmental-stress conditions involves sensing and signalling events where nitric oxide becomes a critical component mediating hormonal actions, interacting with reactive oxygen species, and modulating gene expression and protein activity. This review focuses on the current knowledge of the role of nitric oxide in adaptive plant responses to some specific abiotic stress conditions, particularly low mineral nutrient supply, drought, salinity and high UV-B radiation.

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Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +2841 moreInstitutions (194)
TL;DR: In this article, the results of a search for events containing at least one long-lived particle that decays at a significant distance from its production point into two leptons or into five or more charged particles are presented.
Abstract: Many extensions of the Standard Model posit the existence of heavy particles with long lifetimes. This article presents the results of a search for events containing at least one long-lived particle that decays at a significant distance from its production point into two leptons or into five or more charged particles. This analysis uses a data sample of proton-proton collisions at root s = 8 TeV corresponding to an integrated luminosity of 20.3 fb(-1) collected in 2012 by the ATLAS detector operating at the Large Hadron Collider. No events are observed in any of the signal regions, and limits are set on model parameters within supersymmetric scenarios involving R-parity violation, split supersymmetry, and gauge mediation. In some of the search channels, the trigger and search strategy are based only on the decay products of individual long-lived particles, irrespective of the rest of the event. In these cases, the provided limits can easily be reinterpreted in different scenarios.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek4  +2868 moreInstitutions (175)
TL;DR: Inclusive jet production is found to be suppressed by approximately a factor of 2 in central collisions compared to pp collisions, and the nuclear modification factor R(AA) shows a slight increase with p(T) and no significant variation with rapidity.
Abstract: Measurements of inclusive jet production are performed in pp and Pb+Pb collisions at √sNN = 2.76 TeV with the ATLAS detector at the LHC, corresponding to integrated luminosities of 4.0 pb−1 and 0.14 nb−1, respectively. The jets are identified with the anti-kt algorithm with R = 0.4, and the spectra are measured over the kinematic range of jet transverse momentum 32 < pT < 500 GeV, and absolute rapidity |y| < 2.1 and as a function of collision centrality. The nuclear modification factor, RAA, is evaluated and jets are found to be suppressed by approximately a factor of two in central collisions compared to pp collisions. The RAA shows a slight increase with pT and no significant variation with rapidity.

Journal ArticleDOI
Georges Aad1, Alexander Kupco2, Peter Davison3, Samuel Webb4  +2879 moreInstitutions (213)
TL;DR: In this paper, a search for heavy Majorana neutrinos in events containing a pair of high-p(T) leptons of the same charge and high p(t) jets is presented, which is consistent with the background-only hypothesis based on the Standard Model expectation.
Abstract: A search for heavy Majorana neutrinos in events containing a pair of high-p(T) leptons of the same charge and high-p(T) jets is presented. The search uses 20.3 fb(-1) of pp collision data collected with the ATLAS detector at the CERN Large Hadron Collider with a centre-of-mass energy of root s = 8TeV. The data are found to be consistent with the background-only hypothesis based on the Standard Model expectation. In the context of a Type-I seesaw mechanism, limits are set on the production cross-section times branching ratio for production of heavy Majorana neutrinos in the mass range between 100 and 500 GeV. The limits are subsequently interpreted as limits on the mixing between the heavy Majorana neutrinos and the Standard Model neutrinos. In the context of a left-right symmetric model, limits on the production cross-section times branching ratio are set with respect to the masses of heavy Majorana neutrinos and heavy gauge bosons W-R and Z'.