Showing papers by "University of Siena published in 2014"
Paris 12 Val de Marne University1, French Institute of Health and Medical Research2, University of Göttingen3, Ghent University4, University Hospital of Lausanne5, University of Lisbon6, university of lille7, Università Campus Bio-Medico8, University of Belgrade9, University of Hamburg10, Turku University Hospital11, Aristotle University of Thessaloniki12, University of Regensburg13, University of Bern14, Ludwig Maximilian University of Munich15, University of Siena16, The Catholic University of America17, University College London18, University of Ulm19, Copenhagen University Hospital20, University of Oxford21, University of Barcelona22, University of Tübingen23
TL;DR: There is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rT MS of the left dorsolateral prefrontal cortex (DLPFC).
1,554 citations
University of Pennsylvania1, The Royal Marsden NHS Foundation Trust2, University of Pisa3, Odense University Hospital4, University of Siena5, Leipzig University6, Asan Medical Center7, University of Texas MD Anderson Cancer Center8, Radboud University Nijmegen9, Bayer HealthCare Pharmaceuticals10, Institut Gustave Roussy11
TL;DR: It is suggested that sorafenib is a new treatment option for patients with progressive radioactive iodine-refractory differentiated thyroid cancer and progression-free survival significantly improved in all prespecified clinical and genetic biomarker subgroups, irrespective of mutation status.
1,171 citations
University of Oxford1, Australian National University2, Queen's University Belfast3, University of Maryland, College Park4, University of the Basque Country5, Autonomous University of Madrid6, University of Siena7, Centre national de la recherche scientifique8, University of Tübingen9, University of La Laguna10, University of Cantabria11, University of Trento12, Royal Belgian Institute of Natural Sciences13, University of Massachusetts Amherst14, University of Arizona15, National University of Distance Education16, Weizmann Institute of Science17, Trent University18, University of Genoa19, University of Ferrara20, University of Oviedo21, Université de Montréal22, University College Dublin23, Natural History Museum24
TL;DR: Improved accelerator mass spectrometry 14C techniques are applied to construct robust chronologies from 40 key Mousterian and Neanderthal archaeological sites, showing that there was ample time for the transmission of cultural and symbolic behaviours, as well as possible genetic exchanges, between the two groups.
Abstract: The timing of Neanderthal disappearance and the extent to which they overlapped with the earliest incoming anatomically modern humans (AMHs) in Eurasia are key questions in palaeoanthropology. Determining the spatiotemporal relationship between the two populations is crucial if we are to understand the processes, timing and reasons leading to the disappearance of Neanderthals and the likelihood of cultural and genetic exchange. Serious technical challenges, however, have hindered reliable dating of the period, as the radiocarbon method reaches its limit at ∼50,000 years ago. Here we apply improved accelerator mass spectrometry (14)C techniques to construct robust chronologies from 40 key Mousterian and Neanderthal archaeological sites, ranging from Russia to Spain. Bayesian age modelling was used to generate probability distribution functions to determine the latest appearance date. We show that the Mousterian ended by 41,030-39,260 calibrated years bp (at 95.4% probability) across Europe. We also demonstrate that succeeding 'transitional' archaeological industries, one of which has been linked with Neanderthals (Châtelperronian), end at a similar time. Our data indicate that the disappearance of Neanderthals occurred at different times in different regions. Comparing the data with results obtained from the earliest dated AMH sites in Europe, associated with the Uluzzian technocomplex, allows us to quantify the temporal overlap between the two human groups. The results reveal a significant overlap of 2,600-5,400 years (at 95.4% probability). This has important implications for models seeking to explain the cultural, technological and biological elements involved in the replacement of Neanderthals by AMHs. A mosaic of populations in Europe during the Middle to Upper Palaeolithic transition suggests that there was ample time for the transmission of cultural and symbolic behaviours, as well as possible genetic exchanges, between the two groups.
605 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: Strains with resistance to multiple antibiotic classes have emerged among major Gram-positive and Gram-negative species including Staphylococcus aureus, Enterococcus spp.
502 citations
TL;DR: In line with the results obtained with the same PS NPs in several human cell lines, also in sea urchin embryos, differences in surface charges and aggregation in seawater strongly affect their embryotoxicity.
Abstract: Nanoplastic debris, resulted from runoff and weathering breakdown of macro- and microplastics, represents an emerging concern for marine ecosystems. The aim of the present study was to investigate disposition and toxicity of polystyrene nanoparticles (NPs) in early development of sea urchin embryos (Paracentrotus lividus). NPs with two different surface charges where chosen, carboxylated (PS-COOH) and amine (PS-NH2) polystyrene, the latter being a less common variant, known to induce cell death in several in vitro cell systems. NPs stability in natural seawater (NSW) was measured while disposition and embryotoxicity were monitored within 48 h of postfertilization (hpf). Modulation of genes involved in cellular stress response (cas8, 14-3-3e, p-38 MAPK, Abcb1, Abcc5) was investigated. PS-COOH forms microaggregates (PDI > 0.4) in NSW, whereas PS-NH2 results are better dispersed (89 ± 2 nm) initially, though they also aggregated partially with time. Their respectively anionic and cationic nature was confirmed by ζ-potential measurements. No embryotoxicity was observed for PS-COOH up to 50 μg mL(-1) whereas PS-NH2 caused severe developmental defects (EC50 3.85 μg mL(-1) 24 hpf and EC50 2.61 μg mL(-1) 48 hpf). PS-COOH accumulated inside embryo's digestive tract while PS-NH2 were more dispersed. Abcb1 gene resulted up-regulated at 48 hpf by PS-COOH whereas PS-NH2 induced cas8 gene at 24 hpf, suggesting an apoptotic pathway. In line with the results obtained with the same PS NPs in several human cell lines, also in sea urchin embryos, differences in surface charges and aggregation in seawater strongly affect their embryotoxicity.
477 citations
TL;DR: This work employed structure-based design with a focused chemical library to discover specific MRE11 endo- or exonuclease inhibitors and define distinct nuclease roles in DSB repair, and support a mechanism whereby M RE11 endonucleasing initiates resection, thereby licensing HR followed by MRE 11 exonuclelease and EXO1/BLM bidirectional resection toward and away from the DNA end, which commits to HR.
466 citations
TL;DR: A new measure based on topological concepts is introduced, aimed at evaluating the complexity of the function implemented by a neural network, used for classification purposes, and results seem to support the idea that deep networks actually implements functions of higher complexity, so that they are able, with the same number of resources, to address more difficult problems.
Abstract: Recently, researchers in the artificial neural network field have focused their attention on connectionist models composed by several hidden layers. In fact, experimental results and heuristic considerations suggest that deep architectures are more suitable than shallow ones for modern applications, facing very complex problems, e.g., vision and human language understanding. However, the actual theoretical results supporting such a claim are still few and incomplete. In this paper, we propose a new approach to study how the depth of feedforward neural networks impacts on their ability in implementing high complexity functions. First, a new measure based on topological concepts is introduced, aimed at evaluating the complexity of the function implemented by a neural network, used for classification purposes. Then, deep and shallow neural architectures with common sigmoidal activation functions are compared, by deriving upper and lower bounds on their complexity, and studying how the complexity depends on the number of hidden units and the used activation function. The obtained results seem to support the idea that deep networks actually implements functions of higher complexity, so that they are able, with the same number of resources, to address more difficult problems.
455 citations
TL;DR: An overview of the involvement of neuronal apoptosis and oxidative stress in the most important neurodegenerative diseases is presented, mainly focusing the attention on several genetic disorders, discussing the interaction between primary genetic abnormalities and the apoptotic pathways.
Abstract: Neurodegenerative disorders affect almost 30 million individuals leading to disability and death. These disorders are characterized by pathological changes in disease-specific areas of the brain and degeneration of distinct neuron subsets. Despite the differences in clinical manifestations and neuronal vulnerability, the pathological processes appear similar, suggesting common neurodegenerative pathways. Apoptosis seems to play a key role in the progression of several neurologic disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis as demonstrated by studies on animal models and cell lines. On the other hand, research on human brains reported contradictory results. However, many dying neurons have been detected in brains of patients with neurodegenerative diseases, and these conditions are often associated with significant cell loss accompanied by typical morphological features of apoptosis such as chromatin condensation, DNA fragmentation, and activation of cysteine-proteases, caspases. Cell death and neurodegenerative conditions have been linked to oxidative stress and imbalance between generation of free radicals and antioxidant defenses. Multiple sclerosis, stroke, and neurodegenerative diseases have been associated with reactive oxygen species and nitric oxide. Here we present an overview of the involvement of neuronal apoptosis and oxidative stress in the most important neurodegenerative diseases, mainly focusing the attention on several genetic disorders, discussing the interaction between primary genetic abnormalities and the apoptotic pathways.
442 citations
TL;DR: The prevalence, determinants, regional variation, and prognostic implications of co‐morbidities in patients with chronic HF in Europe in Europe are assessed.
Abstract: A total of 3226 European outpatients with chronic HF were included in this analysis of the European Society of Cardiology (ESC) Heart Failure Pilot Survey. The following co-morbidities were considered: diabetes, hyper- and hypothyroidism, stroke, COPD, sleep apnoea, chronic kidney disease (CKD), and anaemia. Prognostic implications of co-morbidities were evaluated using population attributable risks (PARs), and patients were divided into geographic regions. Clinical endpoints were all-cause mortality and HF hospitalization. The majority of patients (74%) had a least one co-morbidity, the most prevalent being CKD (41%), anaemia (29%), and diabetes (29%). Co-morbidities were independently associated with higher age (P < 0.001), higher NYHA functional class (P < 0.001), ischaemic aetiology of HF (P < 0.001), higher heart rate (P = 0.011), history of hypertension (P < 0.001), and AF (P < 0.001). Only diabetes, CKD, and anaemia were independently associated with a higher risk of mortality and/or HF hospitalization. There were marked regional differences in prevalence and prognostic implications of co-morbidities. Prognostic implications of co-morbidities (PARs) were: CKD = 41%, anaemia = 37%, diabetes = 14%, COPD = 10%, and <10% for all other
360 citations
S. Chatrchyan1, Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1 +2280 more•Institutions (177)
TL;DR: In this paper, a search for a standard model Higgs boson decaying into a pair of tau leptons is performed using events recorded by the CMS experiment at the LHC in 2011 and 2012.
Abstract: A search for a standard model Higgs boson decaying into a pair of tau leptons is performed using events recorded by the CMS experiment at the LHC in 2011 and 2012. The dataset corresponds to an integrated luminosity of 4.9 inverse femtobarns at a centre-of-mass energy of 7 TeV and 19.7 inverse femtobarns at 8 TeV. Each tau lepton decays hadronically or leptonically to an electron or a muon, leading to six different final states for the tau-lepton pair, all considered in this analysis. An excess of events is observed over the expected background contributions, with a local significance larger than 3 standard deviations for m[H] values between 115 and 130 GeV. The best fit of the observed H to tau tau signal cross section for m[H] = 125 GeV is 0.78 +- 0.27 times the standard model expectation. These observations constitute evidence for the 125 GeV Higgs boson decaying to a pair of tau leptons.
University of Naples Federico II1, University of L'Aquila2, University of Turin3, University of Bari4, University of Bologna5, University of Catania6, University of Genoa7, University of Foggia8, Sapienza University of Rome9, University of Pisa10, University of Chieti-Pescara11, University of Siena12, University of Parma13, University of Salerno14, University of Milan15, University of Cagliari16, University of Brescia17, University of Padua18, University of Rome Tor Vergata19, University of Eastern Piedmont20
TL;DR: The observed complex associations among investigated predictors, mediators and real‐life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.
TL;DR: The results show higher concentration of MEHP in the muscle of basking shark in comparison to fin whale blubber, and these species can be proposed as indicators of microplastics in the pelagic environment in the implementation of Descriptor 8 and 10 of the EU Marine Strategy Framework Directive (MSFD).
TL;DR: This contribution provides an overview of the mechanism of action of nutraceuticals and functional food ingredients on lipids and their role in the management of lipid disorders.
TL;DR: In this paper, a search for new physics in multijet events with large missing transverse momentum produced in proton-proton collisions at 8 TeV using a data sample corresponding to an integrated luminosity of 19.5 inverse femtobarns collected with the CMS detector at the LHC.
Abstract: A search for new physics is performed in multijet events with large missing transverse momentum produced in proton-proton collisions at sqrt(s)=8 TeV using a data sample corresponding to an integrated luminosity of 19.5 inverse femtobarns collected with the CMS detector at the LHC. The data sample is divided into three jet multiplicity categories (3-5, 6-7, and 8 or more jets), and studied further in bins of two variables: the scalar sum of jet transverse momenta and the missing transverse momentum. The observed numbers of events in various categories are consistent with backgrounds expected from standard model processes. Exclusion limits are presented for several simplified supersymmetric models of squark or gluino pair production.
17 Jan 2014
TL;DR: In this article, a search for the standard model Higgs boson decaying to a W-boson pair at the LHC is reported, and an excess of events above background is observed.
Abstract: A search for the standard model Higgs boson decaying to a W-boson pair at the LHC is reported. The event sample corresponds to an integrated luminosity of 4.9 fb−1 and 19.4 fb−1 collected with the CMS detector in pp collisions at s√ = 7 and 8 TeV, respectively. The Higgs boson candidates are selected in events with two or three charged leptons. An excess of events above background is observed, consistent with the expectation from the standard model Higgs boson with a mass of around 125 GeV. The probability to observe an excess equal or larger than the one seen, under the background-only hypothesis, corresponds to a significance of 4.3 standard deviations for m H = 125.6 GeV. The observed signal cross section times the branching fraction to WW for m H = 125.6 GeV is 0.72+0.20−0.18 times the standard model expectation. The spin-parity J P = 0+ hypothesis is favored against a narrow resonance with J P = 2+ or J P = 0− that decays to a W-boson pair. This result provides strong evidence for a Higgs-like boson decaying to a W-boson pair.
University of Malaya1, Natural Environment Research Council2, Monash University3, Swedish University of Agricultural Sciences4, National Institute of Water and Atmospheric Research5, Lamont–Doherty Earth Observatory6, University of Siena7, University of Waikato8, Antarctica New Zealand9, University of Bristol10, Ohio State University11, University of Tasmania12, Autonomous University of Madrid13, University of Wollongong14, University of Genoa15, Colorado State University16
TL;DR: In this paper, the authors synthesized current knowledge on environmental variability across terrestrial, freshwater, and marine Antarctic biomes and related this to the observed biotic patterns, showing that the most important physical driver of Antarctic terrestrial communities is the availability of liquid water, itself driven by solar irradiance intensity.
Abstract: Patterns of environmental spatial structure lie at the heart of the most fundamental and familiar patterns of diversity on Earth. Antarctica contains some of the strongest environmental gradients on the planet and therefore provides an ideal study ground to test hypotheses on the relevance of environmental variability for biodiversity. To answer the pivotal question, “How does spatial variation in physical and biological environmental properties across the Antarctic drive biodiversity?” we have synthesized current knowledge on environmental variability across terrestrial, freshwater, and marine Antarctic biomes and related this to the observed biotic patterns. The most important physical driver of Antarctic terrestrial communities is the availability of liquid water, itself driven by solar irradiance intensity. Patterns of biota distribution are further strongly influenced by the historical development of any given location or region, and by geographical barriers. In freshwater ecosystems, free water is also crucial, with further important influences from salinity, nutrient availability, oxygenation, and characteristics of ice cover and extent. In the marine biome there does not appear to be one major driving force, with the exception of the oceanographic boundary of the Polar Front. At smaller spatial scales, ice cover, ice scour, and salinity gradients are clearly important determinants of diversity at habitat and community level. Stochastic and extreme events remain an important driving force in all environments, particularly in the context of local extinction and colonization or recolonization, as well as that of temporal environmental variability. Our synthesis demonstrates that the Antarctic continent and surrounding oceans provide an ideal study ground to develop new biogeographical models, including life history and physiological traits, and to address questions regarding biological responses to environmental variability and change.
TL;DR: In this article, an overview of some of the large, shallow, semi-enclosed coastal systems (SECS) in Europe is given, which are important both from the ecological and the economic perspective (socio-ecological systems) and provide many valuable ecosystem goods and services.
Abstract: The paper gives an overview of some of the large, shallow, semi-enclosed coastal systems (SECS) in Europe, These SECS are important both from the ecological and the economic perspective (socio-ecological systems) and provide many valuable ecosystem goods and services. Although some of the systems are transitional waters under the Water Framework Directive, this is not the case for all of the systems. The paper adopts a Driver-Pressure-State-Impact-Response approach to analyse the ecological status, vulnerability and future perspectives of these systems in the context of global change.
TL;DR: For example, in the field of sedimentology and palaeontology, Tufas and travertines have been used as proxy indicators of climate change as mentioned in this paper, showing that carbonate precipitation is a shared product of physico-chemical and microbiological biomediation processes.
Abstract: Traditionally, fresh water carbonate research has focused on the sedimentology and palaeontology of ancient lacustrine deposits. Lithofacies in such low-energy deposits are typically fine-grained, developed uniformly in a generally concentric distribution (‘bulls-eye’ pattern) and are predictable even when preserved imperfectly. In contrast, because of their local lithofacies and palaeontological complexities, fluvial carbonates were either delegated to a status of ‘minor geomorphological features’ or barely considered prior to the 1970s. This viewpoint was based on the depositional record of fluvial and spring-fed fresh water carbonates, which were considered to be restricted generally to localized karstic areas. Such deposits are often preserved as scattered patches of ambient temperature tufa. Occasionally, however, in active tectonic areas, localized travertine deposits are also developed from deeply circulating hydrothermal waters. With a few exceptions (for example, basins with high subsidence rates or in arid climate zones), these fresh water carbonates are prone to erosion from continuing river incision and thus may not be preserved in the geological record. A partial record of fluvial and spring-deposited carbonates is often preserved in Quaternary deposits, but the record in older deposits is typically fragmentary and often diagenetically modified. Yet once their unique facies architecture (and specialized nomenclature) is understood, these carbonates provide an important record of past sedimentological cycles of great value in palaeoenvironmental landscape modelling. The emphasis of modern research is to acquire information that explains how active systems function. In this respect, tufas reveal much of how carbonate precipitation is a shared product of physico-chemical and microbiological biomediation processes. Likewise, travertines not only show an intimate interrelation with active tectonism but also hold great potential as monitors of past volcanic carbon dioxide emissions. In addition, both tufas and travertines contain palynological records that can be used as proxy indicators of climate change. Perhaps no other field of sedimentology has witnessed more developments and applications over such a brief period of study.
TL;DR: It is suggested that mgrB alteration can be a common mechanism of colistin resistance among KPC-KP in the clinical setting and implementation experiments restored colistIn susceptibility and basal expression levels of phoQ and pmrK genes in strains carrying different types of mgr B alterations.
Abstract: Klebsiella pneumoniae strains producing KPC-type carbapenemases (KPC-KP) are challenging multidrug-resistant pathogens due to their extensively drug-resistant phenotypes and potential for epidemic dissemination in health care settings. Colistin is a key component of the combination antimicrobial regimens used for treatment of severe KPC-KP infections. We previously reported that insertional inactivation of the mgrB gene, encoding a negative-feedback regulator of the PhoQ-PhoP signaling system, can be responsible for colistin resistance in KPC-KP, due to the resulting upregulation of the Pmr lipopolysaccharide modification system. In this work we investigated the status of the mgrB gene in a collection of 66 colistin-resistant nonreplicate clinical strains of KPC-KP isolated from different hospitals in Italy and Greece. Overall, 35 strains (53%) exhibited alterations of the mgrB gene, including insertions of different types of mobile elements (IS5-like, IS1F-like, or ISKpn14), nonsilent point mutations, and small intragenic deletions. Four additional strains had a larger deletion of the mgrB locus, while the remaining 27 strains (41%) did not show mgrB alterations. Transcriptional upregulation of the phoQ and pmrK genes (part of the phoPQ and pmrHFIJKLM operon, respectively) was observed in all strains with mgrB alterations. Complementation experiments with a wild-type mgrB gene restored colistin susceptibility and basal expression levels of phoQ and pmrK genes in strains carrying different types of mgrB alterations. The present results suggest that mgrB alteration can be a common mechanism of colistin resistance among KPC-KP in the clinical setting.
TL;DR: CAF procedures alone or with CTG, EMD are supported by large evidence in modern periodontal plastic surgery and achieved the best clinical outcomes in single gingival recessions with or without iCAL.
Abstract: Background
The aim of this Systematic Review (SR) was to assess the clinical efficacy of periodontal plastic surgery procedures in the treatment of localized gingival recessions (Rec) with or without inter-dental clinical attachment loss (iCAL).
Material and Methods
Electronic and hand searches were performed to identify randomized clinical trials (RCTs) on treatment of single gingival recessions with at least 6 months of follow-up. Primary outcome variable was complete root coverage (CRC). Secondary outcome variables were recession reduction (RecRed) and keratinized tissue (KT) gain. To evaluate treatment effect, Odds Ratios were combined for dichotomous data and mean differences in continuous data using a random-effect model.
Results
Fifty-one RCTs (53 articles) with a total of 1574 treated patients (1744 recessions) were included in this SR. Finally, 30 groups of comparisons were identified and a total of 80 meta-analyses were performed. Coronally Advanced Flap (CAF) was associated with higher probability of CRC and higher amount of RecRed than Semilunar Coronal Positioned Flap (SCPF). The combination CAF plus Connective Tissue Graft (CAF+CTG) or CAF plus Enamel Matrix Derivative (CAF+EMD) was more effective than CAF alone in terms of CRC and RecRed. The combination CAF plus Collagen Matrix (CAF+CM) achieved higher RecRed than CAF alone. In addition, CAF+CTG achieved CRC more frequently than CAF+EMD, SCPF, Free Gingival Graft (FGG) and Laterally Positioned Flap (LPS). CAF+CTG was also associated with higher RecRed than Barrier Membranes (CAF+GTR), CAF+EMD and CAF+CM. GTR was not able to improve the clinical efficacy of CAF. Studies adding Acellular Dermal Matrix (ADM) under CAF showed a large heterogeneity and not significant benefits compared with CAF alone. Multiple combinations, using more than a single graft/biomaterial under the flap, usually provide similar or less benefits than simpler, control procedures in term of root coverage outcomes.
Conclusions
CAF procedures alone or with CTG, EMD are supported by large evidence in modern periodontal plastic surgery. CAF+CTG achieved the best clinical outcomes in single gingival recessions with or without iCAL.
TL;DR: A carefully conducted trial shows benefi cial eff ects of 11-βHSD1 inhibition on body and liver fat in overweight, insulin-resistant patients with liver steatosis, but data suggestive of effi cacy in patients with non-alcoholic steatohepatitis cannot be inferred and need to be obtained from future, liver-oriented trials with relevant histological endpoints.
TL;DR: Data provide supportive evidence that a meaningful number of RIS subjects evolve to a first clinical symptom, and an age <37 y, male sex, and spinal cord involvement appear to be the most important independent predictors of symptom onset.
Abstract: Objective
To report the 5-year risk and to identify risk factors for the development of a seminal acute or progressive clinical event in a multi-national cohort of asymptomatic subjects meeting 2009 RIS Criteria.
TL;DR: A large-scale survey of genomic nucleotide composition across monocots has enabled the first rigorous testing, to the authors' knowledge, of its biological significance in plants, and shows that genomic DNA base composition (GC content) is significantly associated with genome size and holocentric chromosomal structure.
Abstract: Genomic DNA base composition (GC content) is predicted to significantly affect genome functioning and species ecology. Although several hypotheses have been put forward to address the biological impact of GC content variation in microbial and vertebrate organisms, the biological significance of GC content diversity in plants remains unclear because of a lack of sufficiently robust genomic data. Using flow cytometry, we report genomic GC contents for 239 species representing 70 of 78 monocot families and compare them with genomic characters, a suite of life history traits and climatic niche data using phylogeny-based statistics. GC content of monocots varied between 33.6% and 48.9%, with several groups exceeding the GC content known for any other vascular plant group, highlighting their unusual genome architecture and organization. GC content showed a quadratic relationship with genome size, with the decreases in GC content in larger genomes possibly being a consequence of the higher biochemical costs of GC base synthesis. Dramatic decreases in GC content were observed in species with holocentric chromosomes, whereas increased GC content was documented in species able to grow in seasonally cold and/or dry climates, possibly indicating an advantage of GC-rich DNA during cell freezing and desiccation. We also show that genomic adaptations associated with changing GC content might have played a significant role in the evolution of the Earth’s contemporary biota, such as the rise of grass-dominated biomes during the mid-Tertiary. One of the major selective advantages of GC-rich DNA is hypothesized to be facilitating more complex gene regulation.
TL;DR: The measurement of brain volume in clinical trials and practice, the effect of DMTs on brain volume change across trials and the clinical relevance of brainVolume loss in MS are reviewed.
Abstract: Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS and proceeding throughout the disease course, may be an accurate measure of neurodegeneration and tissue damage. There are a number of magnetic resonance imaging-based methods for determining global or regional brain volume, including cross-sectional (e.g. brain parenchymal fraction) and longitudinal techniques (e.g. SIENA [Structural Image Evaluation using Normalization of Atrophy]). Although these methods are sensitive and reproducible, caution must be exercised when interpreting brain volume data, as numerous factors (e.g. pseudoatrophy) may have a confounding effect on measurements, especially in a disease with complex pathological substrates such as MS. Brain volume loss has been correlated with disability progression and cognitive impairment in MS, with the loss of grey matter volume more closely correlated with clinical measures than loss of white matter volume. Preventing brain volume loss may therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy on reducing the rate of brain volume loss. This article reviews the measurement of brain volume in clinical trials and practice, the effect of DMTs on brain volume change across trials and the clinical relevance of brain volume loss in MS.
TL;DR: Results indicate that ERK and NR1, but not GluR1 and DARPP-32, are differentially phosphorylated as a consequence of acquisition and expression of aversive associative learning and suggest the involvement of ERK cascade in learning-associated synaptic plasticity.
Abstract: Conditioned taste aversion (CTA) can be applied to study associative learning and its relevant underpinning molecular mechanisms in discrete brain regions. The present study examined, by immunohistochemistry and immunocytochemistry, the effects of acquisition and expression of lithium-induced CTA on activated Extracellular signal Regulated Kinase (p-ERK) in the prefrontal cortex (PFCx) and nucleus accumbens (Acb) of male Sprague-Dawley rats. The study also examined, by immunoblotting, whether acquisition and expression of lithium-induced CTA resulted in modified levels of phosphorylation of glutamate receptor subunits (NR1 and GluR1) and Thr34- and Thr75-Dopamine-and-cAMP-Regulated PhosphoProtein (DARPP-32). CTA acquisition was associated with an increase of p-ERK-positive neurons and phosphorylated NR1 receptor subunit (p-NR1) in the PFCx, whereas p-GluR1, p-Thr34- and p-Thr75-DARPP-32 levels were not changed in this brain region. CTA expression increased the number of p-ERK-positive neurons in the shell (AcbSh) and core (AcbC) but left unmodified p-NR1, p-GluR1, p-Thr34- and p-Thr75-DARPP-32 levels. Furthermore, post-embedding immunogold quantitative analysis in AcbSh revealed that CTA expression significantly increased nuclear p-ERK immunostaining as well as p-ERK-labeled axo-spinous contacts. Overall, these results indicate that ERK and NR1, but not GluR1 and DARPP-32, are differentially phosphorylated as a consequence of acquisition and expression of aversive associative learning. Moreover, these results confirm that CTA represents an useful approach to study the molecular basis of associative learning in rats and suggest the involvement of ERK cascade in learning-associated synaptic plasticity.
TL;DR: In RRMS, the treatment effect on brain atrophy is correlated with the effect on disability progression over 2 years, independent of the effect of active MRI lesions on disability; the 2 MRI measures predict the treatment effects on disability more closely when used in combination.
Abstract: Objective
To evaluate the extent to which treatment effect on brain atrophy is able to mediate, at the trial level, the treatment effect on disability progression in relapsing–remitting multiple sclerosis (RRMS).
Methods
We collected all published randomized clinical trials in RRMS lasting at least 2 years and including as endpoints disability progression (defined as 6 or 3 months confirmed 1-point increase on the Expanded Disability Status Scale), active magnetic resonance imaging (MRI) lesions (defined as new/enlarging T2 lesions), and brain atrophy (defined as change in brain volume between month 24 and month 6–12). Treatment effects were expressed as relative reductions. A linear regression, weighted for trial size and duration, was used to assess the relationship between the treatment effects on MRI markers and on disability progression.
Results
Thirteen trials including >13,500 RRMS patients were included in the meta-analysis. Treatment effects on disability progression were correlated with treatment effects both on brain atrophy (R2 = 0.48, p = 0.001) and on active MRI lesions (R2 = 0.61, p < 0.001). When the effects on both MRI endpoints were included in a multivariate model, the correlation was higher (R2 = 0.75, p < 0.001), and both variables were retained as independently related to the treatment effect on disability progression.
Interpretation
In RRMS, the treatment effect on brain atrophy is correlated with the effect on disability progression over 2 years. This effect is independent of the effect of active MRI lesions on disability; the 2 MRI measures predict the treatment effect on disability more closely when used in combination. ANN NEUROL 2014;75:43–49
TL;DR: The pathogenesis, diagnosis, and treatment of myocardial depression in sepsis is summarized and the cornerstone of management is control of the underlying infectious process and hemodynamic stabilization (fluids, vasopressor and inotropic agents).
Istituto Giannina Gaslini1, Charité2, French Institute of Health and Medical Research3, University of Siena4, Utrecht University5, University of Barcelona6, University of Paris-Sud7, University of Brescia8, Necker-Enfants Malades Hospital9, Hospital Universitario La Paz10, Boston Children's Hospital11, Ljubljana University Medical Centre12, Hacettepe University13, Ludwig Maximilian University of Munich14, University of Genoa15
TL;DR: The largest reported case series to date, the genetic heterogeneity of TRAPS is accompanied by a variable phenotype at presentation, with little evidence of a significant effect of age or genotype on disease features at presentation.
Abstract: Objective To evaluate the genetic findings, demographic features and clinical presentation of tumour necrosis factor receptor-associated autoinflammatory syndrome (TRAPS) in patients from the Eurofever/ EUROTRAPS international registry. Methods A web-based registry collected retrospective data on patients with TNFRSF1A sequence variants and inflammatory symptoms. Participating hospitals included paediatric rheumatology centres and adult centres with a specific interest in autoinflammatory diseases. Cases were independently validated by experts in the disease. Results Complete information on 158 validated patients was available. The most common TNFRSF1A variant was R92Q (34% of cases), followed by T50M (10%). Cysteine residues were disrupted in 27% of cases, accounting for 39% of sequence variants. A family history was present in 19% of patients with R92Q and 64% of those with other variants. The median age at which symptoms began was 4.3 years but 9.1% of patients presented after 30 years of age. Attacks were recurrent in 88% and the commonest features associated with the pathogenic variants were fever (88%), limb pain (85%), abdominal pain (74%), rash (63%) and eye manifestations (45%). Disease associated with R92Q presented slightly later at a median of 5.7 years with significantly less rash or eye signs and more headaches. Children were more likely than adults to present with lymphadenopathy, periorbital oedema and abdominal pains. AA amyloidosis has developed in 16 (10%) patients at a median age of 43 years. Conclusions In this, the largest reported case series to date, the genetic heterogeneity of TRAPS is accompanied by a variable phenotype at presentation. Patients had a median 70 symptomatic days a year, with fever, limb and abdominal pain and rash the commonest symptoms. Overall, there is little evidence of a significant effect of age or genotype on disease features at presentation.
Vardan Khachatryan, Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1 +2194 more•Institutions (180)
TL;DR: In this article, a search for the standard model Higgs boson produced in association with a top-quark pair (ttH) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb^(−1) and 19.7 fb+1, collected in pp collisions at center of mass energies of 7 TeV and 8 TeV respectively.
Abstract: A search for the standard model Higgs boson produced in association with a top-quark pair (ttH) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb^(−1) and 19.7 fb^(−1) collected in pp collisions at center-of-mass energies of 7 TeV and 8 TeV respectively. The search is based on the following signatures of the Higgs boson decay: H → hadrons, H → photons, and H → leptons. The results are characterized by an observed ttH signal strength relative to the standard model cross section, μ=σ/σ SM,under the assumption that the Higgs boson decays as expected in the standard model. The best fit value is μ = 2.8 ± 1.0 for a Higgs boson mass of 125.6 GeV.