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Showing papers by "University of Göttingen published in 2013"


Journal ArticleDOI
TL;DR: The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy.

2,831 citations


Journal ArticleDOI
S. Hong Lee1, Stephan Ripke2, Stephan Ripke3, Benjamin M. Neale2  +402 moreInstitutions (124)
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

2,058 citations


Journal ArticleDOI
29 Mar 2013-Science
TL;DR: Overall, wild insects pollinated crops more effectively; an increase in wild insect visitation enhanced fruit set by twice as much as an equivalent increase in honey bee visitation.
Abstract: The diversity and abundance of wild insect pollinators have declined in many agricultural landscapes. Whether such declines reduce crop yields, or are mitigated by managed pollinators such as honey bees, is unclear. We found universally positive associations of fruit set with flower visitation by wild insects in 41 crop systems worldwide. In contrast, fruit set increased significantly with flower visitation by honey bees in only 14% of the systems surveyed. Overall, wild insects pollinated crops more effectively; an increase in wild insect visitation enhanced fruit set by twice as much as an equivalent increase in honey bee visitation. Visitation by wild insects and honey bees promoted fruit set independently, so pollination by managed honey bees supplemented, rather than substituted for, pollination by wild insects. Our results suggest that new practices for integrated management of both honey bees and diverse wild insect assemblages will enhance global crop yields.

1,881 citations


Journal ArticleDOI
TL;DR: In this paper, a library of high-resolution synthetic spectra based on the stellar atmosphere code PHOENIX is presented, which can be used for a wide range of applications of spectral analysis and stellar parameter synthesis.
Abstract: Aims. We present a new library of high-resolution synthetic spectra based on the stellar atmosphere code PHOENIX that can be used for a wide range of applications of spectral analysis and stellar parameter synthesis. Methods. The spherical mode of PHOENIX was used to create model atmospheres and to derive detailed synthetic stellar spectra from them. We present a new self-consistent way of describing micro-turbulence for our model atmospheres. Results. The synthetic spectra cover the wavelength range from 500 A to 5.5 μm with resolutions of R = 500 000 in the optical and near IR, R = 100 000 in the IR and Δλ = 0.1 A in the UV. The parameter space covers 2300 K ≤ Teff ≤ 12 000 K, 0.0 ≤ log g ≤ +6.0, −4.0 ≤ [Fe/H] ≤ +1.0, and −0.2 ≤ [α/Fe] ≤ +1.2. The library is a work in progress and we expect to extend it up to Teff = 25 000 K.

1,398 citations


Journal ArticleDOI
TL;DR: This synthesis reveals that pollinator persistence will depend on both the maintenance of high-quality habitats around farms and on local management practices that may offset impacts of intensive monoculture agriculture.
Abstract: Bees provide essential pollination services that are potentially affected both by local farm management and the surrounding landscape. To better understand these different factors, we modelled the relative effects of landscape composition (nesting and floral resources within foraging distances), landscape configuration (patch shape, interpatch connectivity and habitat aggregation) and farm management (organic vs. conventional and local-scale field diversity), and their interactions, on wild bee abundance and richness for 39 crop systems globally. Bee abundance and richness were higher in diversified and organic fields and in landscapes comprising more high-quality habitats; bee richness on conventional fields with low diversity benefited most from high-quality surrounding land cover. Landscape configuration effects were weak. Bee responses varied slightly by biome. Our synthesis reveals that pollinator persistence will depend on both the maintenance of high-quality habitats around farms and on local management practices that may offset impacts of intensive monoculture agriculture.

904 citations


Journal ArticleDOI
TL;DR: In this article, the authors evaluate competitive and mutualistic interactions between plants and microorganisms and analyse the ecological consequences of these interactions in the rhizosphere, and they find that despite strong competition between roots and micro-organisms for N, a temporal niche differentiation reflecting their generation times leads to mutualistic relationships in the root network.
Abstract: Demand of all living organisms on the same nutrients forms the basis for interspecific competition between plants and microorganisms in soils. This competition is especially strong in the rhizosphere. To evaluate competitive and mutualistic interactions between plants and microorganisms and to analyse ecological consequences of these interactions, we analysed 424 data pairs from 41 (15)N-labelling studies that investigated (15)N redistribution between roots and microorganisms. Calculated Michaelis-Menten kinetics based on K(m) (Michaelis constant) and V(max) (maximum uptake capacity) values from 77 studies on the uptake of nitrate, ammonia, and amino acids by roots and microorganisms clearly showed that, shortly after nitrogen (N) mobilization from soil organic matter and litter, microorganisms take up most N. Lower K(m) values of microorganisms suggest that they are especially efficient at low N concentrations, but can also acquire more N at higher N concentrations (V(max)) compared with roots. Because of the unidirectional flow of nutrients from soil to roots, plants are the winners for N acquisition in the long run. Therefore, despite strong competition between roots and microorganisms for N, a temporal niche differentiation reflecting their generation times leads to mutualistic relationships in the rhizosphere. This temporal niche differentiation is highly relevant ecologically because it: protects ecosystems from N losses by leaching during periods of slow or no root uptake; continuously provides roots with available N according to plant demand; and contributes to the evolutionary development of mutualistic interactions between roots and microorganisms.

858 citations


Journal ArticleDOI
TL;DR: Cardiorespiratory data showed a consistent and previously unrecognised pattern whereby rapid breathing developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiore Spiratory dysfunction, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal.
Abstract: Summary Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide Methods Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available Findings 147 (92%) of 160 units responded to the survey 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18–50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6–9·2) per 1000 patient-years, with a risk of 1·2 (0·6–2·1) per 10 000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal Interpretation SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest Improved supervision is warranted in epilepsy monitoring units, in particular during night time Funding Commission of European Affairs of the International League Against Epilepsy

814 citations


Journal ArticleDOI
TL;DR: I‐waves, input–output curves and cortical silent period are unaffected immediately after 2 mA stimulation and short intracortical inhibition and facilitation are shifted towards excitability enhancement after both anodal and cathodal stimulation.
Abstract: Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition. No significant changes were observed in the other protocols. Sham tDCS did not induce significant MEP alterations. These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation, but might also shift the direction of excitability alterations. This should be taken into account for applications of the stimulation technique using different intensities and durations in order to achieve stronger or longer lasting after-effects.

814 citations


Journal ArticleDOI
TL;DR: In the real-world, post-approval experience in Europe, patients undergoing the MitraClip therapy are high-risk, elderly patients, mainly affected by functional MR, and in this patient population, the MitRAClip procedure is effective with low rates of hospital mortality and adverse events.

741 citations


Journal ArticleDOI
TL;DR: A possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria is described.
Abstract: A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus.

727 citations


Journal ArticleDOI
TL;DR: The purpose of this paper is to present a method for taxonomy development that can be used in IS and demonstrates the efficacy of the method by developing a taxonomy in a domain in IS.
Abstract: A fundamental problem in many disciplines is the classification of objects in a domain of interest into a taxonomy. Developing a taxonomy, however, is a complex process that has not been adequately...

Journal ArticleDOI
TL;DR: It is shown that narcissistic admiration and rivalry are positively correlated dimensions, yet they have markedly different nomological networks and distinct intra- and interpersonal consequences, underscore the utility of a 2-dimensional conceptualization and measurement of narcissism.
Abstract: We present a process model that distinguishes 2 dimensions of narcissism: admiration and rivalry. We propose that narcissists' overarching goal of maintaining a grandiose self is pursued by 2 separate pathways, characterized by distinct cognitive, affective-motivational, and behavioral processes. In a set of 7 studies, we validated this 2-dimensional model using the newly developed Narcissistic Admiration and Rivalry Questionnaire (NARQ). We showed that narcissistic admiration and rivalry are positively correlated dimensions, yet they have markedly different nomological networks and distinct intra- and interpersonal consequences. The NARQ showed the hypothesized 2-dimensional multifaceted structure as well as very good internal consistencies (Study 1, N = 953), stabilities (Study 2, N = 93), and self-other agreements (Study 3, N = 96). Narcissistic admiration and rivalry showed unique relations to the Narcissistic Personality Inventory (NPI), the Big Five, self-esteem, pathological narcissism, and other narcissism-related traits like Machiavellianism, psychopathy, self-enhancement, and impulsivity (Study 4, Ns = 510-1,814). Despite the positive relation between admiration and rivalry, the 2 differentially predicted general interpersonal orientations and reactions to transgressions in friendships and romantic relationships (Study 5, N = 1,085), interpersonal perceptions during group interactions (Study 6, N = 202), and observed behaviors in experimental observations (Study 7, N = 96). For all studies, the NARQ outperformed the standard measure of narcissism, the NPI, in predicting outcome measures. Results underscore the utility of a 2-dimensional conceptualization and measurement of narcissism.

Journal ArticleDOI
TL;DR: It is shown that the equilibrium quantum phase transition and the dynamical phase transition in the transverse-field Ising model are intimately related.
Abstract: A phase transition indicates a sudden change in the properties of a large system. For temperature-driven phase transitions this is related to nonanalytic behavior of the free energy density at the critical temperature: The knowledge of the free energy density in one phase is insufficient to predict the properties of the other phase. In this Letter we show that a close analogue of this behavior can occur in the real time evolution of quantum systems, namely nonanalytic behavior at a critical time. We denote such behavior a dynamical phase transition and explore its properties in the transverse-field Ising model. Specifically, we show that the equilibrium quantum phase transition and the dynamical phase transition in this model are intimately related.

Journal ArticleDOI
TL;DR: The results are consistent with the idea that variation in response to rTMS plasticity probing protocols is strongly influenced by which interneuron networks are recruited by the TMS pulse.
Abstract: The after-effects of repetitive transcranial magnetic stimulation (rTMS) are highly variable between individuals. Because different populations of cortical neurons are stimulated more easily or are more excitable in different people at different times, the variability may not be due to differences between individuals in the plasticity of cortical synapses, but may instead be due to individual differences in the recruitment of cortical neurons. In this study, we examined the effects of rTMS in 56 healthy volunteers. The responses to excitatory and inhibitory theta burst stimulation (TBS) protocols were highly variable between individuals. Surprisingly, the TBS effect was highly correlated with the latency of motorevoked potentials (MEPs) evoked by TMS pulses that induced an anterior–posterior (AP) directed current across the central sulcus. Finally, we devised a new plasticity protocol using closely timed pairs of oppositely directed TMS current pulses across the central sulcus. Again, the after-effects were related to the latency of MEPs evoked by AP current. Our results are consistent with the idea that variation in response to rTMS plasticity probing protocols is strongly influenced by which interneuron networks are recruited by the TMS pulse.

Journal ArticleDOI
TL;DR: Red, single-wavelength GECIs, “RCaMPs,” engineered from circular permutation of the thermostable red fluorescent protein mRuby are described and 2-color calcium imaging is demonstrated both within the same cell (registering mitochondrial and somatic [Ca2+]) and between two populations of cells: neurons and astrocytes.
Abstract: Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Here we describe red, single-wavelength GECIs, "RCaMPs," engineered from circular permutation of the thermostable red fluorescent protein mRuby. High-resolution crystal structures of mRuby, the red sensor RCaMP, and the recently published red GECI R-GECO1 give insight into the chromophore environments of the Ca(2+)-bound state of the sensors and the engineered protein domain interfaces of the different indicators. We characterized the biophysical properties and performance of RCaMP sensors in vitro and in vivo in Caenorhabditis elegans, Drosophila larvae, and larval zebrafish. Further, we demonstrate 2-color calcium imaging both within the same cell (registering mitochondrial and somatic [Ca(2+)]) and between two populations of cells: neurons and astrocytes. Finally, we perform integrated optogenetics experiments, wherein neural activation via channelrhodopsin-2 (ChR2) or a red-shifted variant, and activity imaging via RCaMP or GCaMP, are conducted simultaneously, with the ChR2/RCaMP pair providing independently addressable spectral channels. Using this paradigm, we measure calcium responses of naturalistic and ChR2-evoked muscle contractions in vivo in crawling C. elegans. We systematically compare the RCaMP sensors to R-GECO1, in terms of action potential-evoked fluorescence increases in neurons, photobleaching, and photoswitching. R-GECO1 displays higher Ca(2+) affinity and larger dynamic range than RCaMP, but exhibits significant photoactivation with blue and green light, suggesting that integrated channelrhodopsin-based optogenetics using R-GECO1 may be subject to artifact. Finally, we create and test blue, cyan, and yellow variants engineered from GCaMP by rational design. This engineered set of chromatic variants facilitates new experiments in functional imaging and optogenetics.

Journal ArticleDOI
TL;DR: Repeated tDCS within a specific time window is able to induce l-LTP-like plasticity in the human motor cortex.

Journal ArticleDOI
TL;DR: The aim of this review is to give a comprehensive overview of the current knowledge on plant metabolites of mycotoxins, also called masked mycot oxins, which are secondary fungal metabolites, toxic to human and animals, and their impact on stakeholders.
Abstract: The aim of this review is to give a comprehensive overview of the current knowledge on plant metabolites of mycotoxins, also called masked mycotoxins. Mycotoxins are secondary fungal metabolites, toxic to human and animals. Toxigenic fungi often grow on edible plants, thus contaminating food and feed. Plants, as living organisms, can alter the chemical structure of mycotoxins as part of their defence against xenobiotics. The extractable conjugated or non-extractable bound mycotoxins formed remain present in the plant tissue but are currently neither routinely screened for in food nor regulated by legislation, thus they may be considered masked. Fusarium mycotoxins (deoxynivalenol, zearalenone, fumonisins, nivalenol, fusarenon-X, T-2 toxin, HT-2 toxin, fusaric acid) are prone to metabolisation or binding by plants, but transformation of other mycotoxins by plants (ochratoxin A, patulin, destruxins) has also been described. Toxicological data are scarce, but several studies highlight the potential threat to consumer safety from these substances. In particular, the possible hydrolysis of masked mycotoxins back to their toxic parents during mammalian digestion raises concerns. Dedicated chapters of this article address plant metabolism as well as the occurrence of masked mycotoxins in food, analytical aspects for their determination, toxicology and their impact on stakeholders.

Journal ArticleDOI
TL;DR: Because active microorganisms are the solely microbial drivers of main biogeochemical processes, analyses of the active and potentially active fractions are necessary in studies focused on soil functions.
Abstract: Microbial functioning refers to microbial activity because only the active microorganisms drive biogeochemical processes. Despite the importance of active microorganisms, most methods focus on estimating total microbial biomass and fail to evaluate its active fraction. At first, we have described the differences among the active , potentially active , and dormant microbial states in soil and suggested threshold values of parameters for their identification. Secondly, we critically reviewed the ability of a broad range of approaches to estimate and characterize the active and the potentially active microorganisms in soil. Following approaches were evaluated: plate count and microbial cultures; direct microscopy combined with cell staining; ATP, PLFA, DNA and RNA content; microarray analyses; PCR-based approaches; stable isotope probing; soil proteomics, enzymes activity; and various approaches based on respiration and substrate utilization. The “static” approaches, mainly based on the single-stage determination of cell components (ATP, DNA, RNA, and molecular biomarkers), detect well the presence of microorganisms and total biomass, but they fail to evaluate the active part and consequently the functions. In contrast, the dynamic approaches, estimating the changes of these parameters during microbial growth and based on process rates: substrate utilization and product formation, e.g., respiration, help to evaluate active microbial biomass and relate it to specific process rates. Based on a comparison of all approaches for their universality (possibility to analyze active, potentially active and dormant microorganisms), we concluded that 1) direct microscopy with complementary stains, 2) a combination of RNA-based FISH with staining of total microbial biomass, and 3) approaches based on microbial growth were the most advantageous and allowed simultaneous quantitative estimation of active , potentially active, and dormant microorganisms in soil. The active microorganisms compose only about 0.1–2% of the total microbial biomass and very seldom exceed 5% in soils without input of easily available substrates. Nonetheless, the fraction of potentially active microorganisms (ready to start utilization of available substrates within few hours) is much higher, contributing between 10 and 40% (up to 60%) of the total microbial biomass. Therefore, we emphasize the role of potentially active microorganisms with quick response to fluctuating substrate input in soil microhabitats and hotspots. The transition from the potentially active to the active state occurs in minutes to hours, but the shift from dormant to active state takes anywhere from hours to days. Despite very fast activation, the reverse process – fading to the potentially active and dormant stage – requires a much longer period and is very different for individual criteria: ATP, DNA, RNA, enzyme production, respiration rates. This leads to further difficulties in the estimation of the active part of microbial community by methods based on these parameters. Consequently, the standardization, further elaboration, and broad application of approaches focused on the portion of active microorganisms in soil and their functions are urgently needed. We conclude that because active microorganisms are the solely microbial drivers of main biogeochemical processes, analyses of the active and potentially active fractions are necessary in studies focused on soil functions.

Journal ArticleDOI
Z. Q. Liu, C. P. Shen1, C. Z. Yuan, I. Adachi  +188 moreInstitutions (56)
TL;DR: In a study of Y(4260) → π+ π- J/φ decays, a structure is observed in the M(π(±)J/ψ) mass spectrum with 5.2σ significance that can be interpreted as a new charged charmoniumlike state.
Abstract: The cross section for ee+ e- → π+ π- J/ψ between 3.8 and 5.5 GeV is measured with a 967 fb(-1) data sample collected by the Belle detector at or near the Υ(nS) (n = 1,2,…,5) resonances. The Y(4260) state is observed, and its resonance parameters are determined. In addition, an excess of π+ π- J/ψ production around 4 GeV is observed. This feature can be described by a Breit-Wigner parametrization with properties that are consistent with the Y(4008) state that was previously reported by Belle. In a study of Y(4260) → π+ π- J/ψ decays, a structure is observed in the M(π(±)J/ψ) mass spectrum with 5.2σ significance, with mass M = (3894.5 ± 6.6 ± 4.5) MeV/c2 and width Γ = (63 ± 24 ± 26) MeV/c2, where the errors are statistical and systematic, respectively. This structure can be interpreted as a new charged charmoniumlike state.

Journal ArticleDOI
27 Feb 2013-JAMA
TL;DR: In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction.
Abstract: Importance Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression. Objective To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction. The primary objective was to determine whether spironolactone is superior to placebo in improving diastolic function and maximal exercise capacity in patients with heart failure with preserved ejection fraction. Design and Setting The Aldo-DHF trial, a multicenter, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2012 at 10 sites in Germany and Austria that included 422 ambulatory patients (mean age, 67 [SD, 8] years; 52% female) with chronic New York Heart Association class II or III heart failure, preserved left ventricular ejection fraction of 50% or greater, and evidence of diastolic dysfunction. Intervention Patients were randomly assigned to receive 25 mg of spironolactone once daily (n=213) or matching placebo (n=209) with 12 months of follow-up. Main Outcome Measures The equally ranked co–primary end points were changes in diastolic function (E/e′) on echocardiography and maximal exercise capacity (peak VO 2 ) on cardiopulmonary exercise testing, both measured at 12 months. Results Diastolic function (E/e′) decreased from 12.7 (SD, 3.6) to 12.1 (SD, 3.7) with spironolactone and increased from 12.8 (SD, 4.4) to 13.6 (SD, 4.3) with placebo (adjusted mean difference, −1.5; 95% CI, −2.0 to −0.9; P 2 did not significantly change with spironolactone vs placebo (from 16.3 [SD, 3.6] mL/min/kg to 16.8 [SD, 4.6] mL/min/kg and from 16.4 [SD, 3.5] mL/min/kg to 16.9 [SD, 4.4] mL/min/kg, respectively; adjusted mean difference, +0.1 mL/min/kg; 95% CI, −0.6 to +0.8 mL/min/kg; P = .81). Spironolactone induced reverse remodeling (left ventricular mass index declined; difference, −6 g/m 2 ; 95% CI, −10 to−1 g/m 2 ; P = .009) and improved neuroendocrine activation (N-terminal pro–brain-type natriuretic peptide geometric mean ratio, 0.86; 95% CI, 0.75-0.99; P = .03) but did not improve heart failure symptoms or quality of life and slightly reduced 6-minute walking distance (–15 m; 95% CI, –27 to –2 m; P = .03). Spironolactone also modestly increased serum potassium levels (+0.2 mmol/L; 95% CI, +0.1 to +0.3; P 2 ; 95% CI, −8 to −3 mL/min/1.73 m 2 ; P Conclusions and Relevance In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations. Trial Registration clinicaltrials.gov Identifier: ISRCTN94726526; Eudra-CT No: 2006-002605-31

Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah  +2942 moreInstitutions (201)
TL;DR: In this paper, the spin and parity quantum numbers of the Higgs boson were studied based on the collision data collected by the ATLAS experiment at the LHC, and the results showed that the standard model spin-parity J(...

Journal ArticleDOI
TL;DR: Significant progress has been accomplished in direct olefinations through twofold C-H bond functionalization of arenes and heteroarenes employing readily accessible, selective and relatively inexpensive ruthenium catalysts as discussed by the authors.
Abstract: Significant progress has been accomplished in direct olefinations through twofold C–H bond functionalization of arenes and heteroarenes employing readily accessible, selective and relatively inexpensive ruthenium catalysts. Particularly, ruthenium(II) complexes have allowed challenging direct double C–H/C–H bond alkenylations of arenes with ample scope. These catalysts set the stage for step-economical C–H/C–H bond functionalization with electron-rich as well as electron-deficient arenes and heteroarenes, and, thereby, provide versatile access to diversely decorated styrenes.

Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah4  +2942 moreInstitutions (200)
TL;DR: In this article, the production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs were measured using the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of 7 TeV and 8 TeV, corresponding to an integrated luminosity of about 25/fb.

Journal ArticleDOI
TL;DR: The results show that this new electrode arrangement for tDCS is efficient for the induction of neuroplasticity in the primary motor cortex and might be compatible with the concept of GABA-mediated surround inhibition.

Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, J. Abdallah4  +2897 moreInstitutions (184)
TL;DR: In this article, the luminosity calibration for the ATLAS detector at the LHC during pp collisions at root s = 7 TeV in 2010 and 2011 is presented, and a luminosity uncertainty of delta L/L = +/- 3.5 % is obtained.
Abstract: The luminosity calibration for the ATLAS detector at the LHC during pp collisions at root s = 7 TeV in 2010 and 2011 is presented. Evaluation of the luminosity scale is performed using several luminosity-sensitive detectors, and comparisons are made of the long-term stability and accuracy of this calibration applied to the pp collisions at root s = 7 TeV. A luminosity uncertainty of delta L/L = +/- 3.5 % is obtained for the 47 pb(-1) of data delivered to ATLAS in 2010, and an uncertainty of delta L/L = +/- 1.8 % is obtained for the 5.5 fb(-1) delivered in 2011.

Journal ArticleDOI
TL;DR: It is shown that microclimatic effects brought about by forest canopy closure can buffer biotic responses to macroclimate warming, thus explaining an apparent climatic lag.
Abstract: Recent global warming is acting across marine, freshwater, and terrestrial ecosystems to favor species adapted to warmer conditions and/or reduce the abundance of cold-adapted organisms (i.e., “thermophilization” of communities). Lack of community responses to increased temperature, however, has also been reported for several taxa and regions, suggesting that “climatic lags” may be frequent. Here we show that microclimatic effects brought about by forest canopy closure can buffer biotic responses to macroclimate warming, thus explaining an apparent climatic lag. Using data from 1,409 vegetation plots in European and North American temperate forests, each surveyed at least twice over an interval of 12–67 y, we document significant thermophilization of ground-layer plant communities. These changes reflect concurrent declines in species adapted to cooler conditions and increases in species adapted to warmer conditions. However, thermophilization, particularly the increase of warm-adapted species, is attenuated in forests whose canopies have become denser, probably reflecting cooler growing-season ground temperatures via increased shading. As standing stocks of trees have increased in many temperate forests in recent decades, local microclimatic effects may commonly be moderating the impacts of macroclimate warming on forest understories. Conversely, increases in harvesting woody biomass—e.g., for bioenergy—may open forest canopies and accelerate thermophilization of temperate forest biodiversity.

Journal ArticleDOI
TL;DR: It is demonstrated, by experiment and theory, that the temporal shape of femtosecond spin current bursts can be manipulated by using specifically designed magnetic heterostructures, which opens the door to engineering high-speed spintronic devices and, potentially, broadband terahertz emitters.
Abstract: In spin-based electronics, information is encoded by the spin state of electron bunches Processing this information requires the controlled transport of spin angular momentum through a solid, preferably at frequencies reaching the so far unexplored terahertz regime Here, we demonstrate, by experiment and theory, that the temporal shape of femtosecond spin current bursts can be manipulated by using specifically designed magnetic heterostructures A laser pulse is used to drive spins from a ferromagnetic iron thin film into a non-magnetic cap layer that has either low (ruthenium) or high (gold) electron mobility The resulting transient spin current is detected by means of an ultrafast, contactless amperemeter based on the inverse spin Hall effect, which converts the spin flow into a terahertz electromagnetic pulse We find that the ruthenium cap layer yields a considerably longer spin current pulse because electrons are injected into ruthenium d states, which have a much lower mobility than gold sp states Thus, spin current pulses and the resulting terahertz transients can be shaped by tailoring magnetic heterostructures, which opens the door to engineering high-speed spintronic devices and, potentially, broadband terahertz emitters

Proceedings ArticleDOI
23 Jun 2013
TL;DR: A novel over-segmentation algorithm which uses voxel relationships to produce over-Segmentations which are fully consistent with the spatial geometry of the scene in three dimensional, rather than projective, space is proposed.
Abstract: Unsupervised over-segmentation of an image into regions of perceptually similar pixels, known as super pixels, is a widely used preprocessing step in segmentation algorithms Super pixel methods reduce the number of regions that must be considered later by more computationally expensive algorithms, with a minimal loss of information Nevertheless, as some information is inevitably lost, it is vital that super pixels not cross object boundaries, as such errors will propagate through later steps Existing methods make use of projected color or depth information, but do not consider three dimensional geometric relationships between observed data points which can be used to prevent super pixels from crossing regions of empty space We propose a novel over-segmentation algorithm which uses voxel relationships to produce over-segmentations which are fully consistent with the spatial geometry of the scene in three dimensional, rather than projective, space Enforcing the constraint that segmented regions must have spatial connectivity prevents label flow across semantic object boundaries which might otherwise be violated Additionally, as the algorithm works directly in 3D space, observations from several calibrated RGB+D cameras can be segmented jointly Experiments on a large data set of human annotated RGB+D images demonstrate a significant reduction in occurrence of clusters crossing object boundaries, while maintaining speeds comparable to state-of-the-art 2D methods

Journal ArticleDOI
21 Mar 2013-Blood
TL;DR: A combined immunohistochemistry or FISH/immunohistochemical score predicts outcome in DLBCL patients independent of the IPI and identifies a subset of 15% of patients with dismal prognosis in the high-risk IPI group following treatment with R-CHOP.

Journal ArticleDOI
Danila Seidel1, Thomas Zander1, Lukas C. Heukamp2, Martin Peifer1, Marc Bos2, Lynnette Fernandez-Cuesta2, Frauke Leenders2, Xin Lu2, Sascha Ansén2, Masyar Gardizi2, Chau Nguyen3, Chau Nguyen2, Johannes Berg2, Prudence A. Russell, Zoe Wainer4, Hans-Ulrich Schildhaus2, Hans-Ulrich Schildhaus5, Toni-Maree Rogers, Benjamin Solomon, William Pao6, Scott L. Carter7, Gad Getz7, D. Neil Hayes8, Matthew D. Wilkerson8, Erik Thunnissen9, William D. Travis10, Sven Perner11, Gavin M. Wright4, Elisabeth Brambilla, Reinhard Buettner2, Juergen Wolf2, Roman K. Thomas1, Franziska Gabler1, Ines Wilkening1, Christian Mueller2, Ilona Dahmen2, Roopika Menon11, Katharina Koenig2, Kerstin Albus2, Sabine Merkelbach-Bruse2, Jana Fassunke2, Katja Schmitz2, Helen Kuenstlinger2, Michaela Angelika Kleine2, Elke Binot2, Silvia Querings1, Janine Altmueller2, Ingelore Boessmann2, Peter Nuemberg2, Peter M. Schneider2, Magdalena Bogus2, Alex Soltermann12, Holger Moch12, Odd Terje Brustugun13, Steinar Solberg13, Marius Lund-Iversen13, Åslaug Helland13, Thomas Muley14, Hans Hoffmann14, Philipp A. Schnabel14, Yuan Chen15, Harry J.M. Groen16, Wim Timens, Hannie Sietsma, Joachim H. Clement15, Walter Weder12, Joerg Saenger, Erich Stoelben, Corinna Ludwig, Walburga Engel-Riedel, Egbert F. Smit, Danille A. M. Heideman9, Peter J.F. Snijders9, Lucia Nogova2, Martin L. Sos1, Christian Mattonet2, Karin Toepelt2, Matthias Scheffler2, Eray Goekkurt17, Eray Goekkurt2, Rainer Kappes2, Stefan Krueger2, Kato Kambartel2, Dirk Behringer2, Wolfgang Schulte2, Wolfgang Galetke2, Winfried Randerath2, Matthias Heldwein2, Andreas Schlesinger2, Monika Serke2, Khosro Hekmat2, Konrad Frank2, Roland Schnell2, Marcel Reiser2, Ali-Nuri Huenerlituerkoglu2, Stephan Schmitz2, Lisa Meffert2, Yon-Dschun Ko2, Markus Litt-Lampe2, Ulrich Gerigk2, Rainer Fricke, Benjamin Besse, Christian Brambilla18, Sylvie Lantuejoul18, Philippe Lorimier, Denis Moro-Sibilot18, Federico Cappuzzo, C. Ligorio19, Stefania Damiani19, John K. Field20, Russell Hyde20, Pierre Validire, Philippe Girard, Lucia Anna Muscarella, Vito Michele Fazio, Michael Hallek2, Jean-Charles Soria21, Viktor Achter2, Ulrich Lang2 
TL;DR: Support is provided for broad implementation of genome-based diagnosis of lung cancer by demonstrating the correlation between lung tumor subtype and its predominant mutations, and the benefit of genetic testing and targeted therapy in these patients.
Abstract: We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.