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Showing papers by "University of Erlangen-Nuremberg published in 2011"


Proceedings Article
01 Jan 2011
TL;DR: The design of Kaldi is described, a free, open-source toolkit for speech recognition research that provides a speech recognition system based on finite-state automata together with detailed documentation and a comprehensive set of scripts for building complete recognition systems.
Abstract: We describe the design of Kaldi, a free, open-source toolkit for speech recognition research. Kaldi provides a speech recognition system based on finite-state automata (using the freely available OpenFst), together with detailed documentation and a comprehensive set of scripts for building complete recognition systems. Kaldi is written is C++, and the core library supports modeling of arbitrary phonetic-context sizes, acoustic modeling with subspace Gaussian mixture models (SGMM) as well as standard Gaussian mixture models, together with all commonly used linear and affine transforms. Kaldi is released under the Apache License v2.0, which is highly nonrestrictive, making it suitable for a wide community of users.

5,857 citations


Journal ArticleDOI
TL;DR: This review attempts to cover all aspects, including underlying principles and key functional features of TiO(2), in a comprehensive way and also indicates potential future directions of the field.
Abstract: TiO(2) is one of the most studied compounds in materials science. Owing to some outstanding properties it is used for instance in photocatalysis, dye-sensitized solar cells, and biomedical devices. In 1999, first reports showed the feasibility to grow highly ordered arrays of TiO(2) nanotubes by a simple but optimized electrochemical anodization of a titanium metal sheet. This finding stimulated intense research activities that focused on growth, modification, properties, and applications of these one-dimensional nanostructures. This review attempts to cover all these aspects, including underlying principles and key functional features of TiO(2), in a comprehensive way and also indicates potential future directions of the field.

2,735 citations


Journal ArticleDOI
TL;DR: Sarcopenia should be considered in all older patients who present with observed declines in physical function, strength, or overall health, and patients who meet these criteria should further undergo body composition assessment using dual energy x-ray absorptiometry with sarcopenia being defined using currently validated definitions.

2,378 citations


Journal ArticleDOI
TL;DR: This review comprehensively covers literature reports which have investigated specifically the effect of dissolution products of silicate bioactive glasses and glass-ceramics in relation to osteogenesis and angiogenesis and focuses on the ion release kinetics of the materials and the specific effect of the released ionic dissolution products on human cell behaviour.

2,056 citations


Journal ArticleDOI
TL;DR: KDIGO has convened a workgroup to develop a global clinical practice guideline for the definition, classification, and prognosis of chronic kidney disease.

1,912 citations


Journal ArticleDOI
Paul Hollingworth1, Denise Harold1, Rebecca Sims1, Amy Gerrish1  +174 moreInstitutions (59)
TL;DR: Meta-analyses of all data provided compelling evidence that ABCA7 and the MS4A gene cluster are new Alzheimer's disease susceptibility loci and independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance.
Abstract: We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10).

1,771 citations


Journal ArticleDOI
TL;DR: The authors examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects.
Abstract: We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).

1,671 citations


Journal ArticleDOI
TL;DR: Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults.
Abstract: Purpose Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults. A broad spectrum of histopathology has been included in the diagnosis of FCD. An ILAE task force proposes an international consensus classification system to better characterize specific clinicopathological FCD entities. Methods Thirty-two Task Force members have reevaluated available data on electroclinical presentation, imaging, neuropathological examination of surgical specimens as well as postsurgical outcome. Key findings The ILAE Task Force proposes a three-tiered classification system. FCD Type I refers to isolated lesions, which present either as radial (FCD Type Ia) or tangential (FCD Type Ib) dyslamination of the neocortex, microscopically identified in one or multiple lobes. FCD Type II is an isolated lesion characterized by cortical dyslamination and dysmorphic neurons without (Type IIa) or with balloon cells (Type IIb). Hence, the major change since a prior classification represents the introduction of FCD Type III, which occurs in combination with hippocampal sclerosis (FCD Type IIIa), or with epilepsy-associated tumors (FCD Type IIIb). FCD Type IIIc is found adjacent to vascular malformations, whereas FCD Type IIId can be diagnosed in association with epileptogenic lesions acquired in early life (i.e., traumatic injury, ischemic injury or encephalitis). Significance This three-tiered classification system will be an important basis to evaluate imaging, electroclinical features, and postsurgical seizure control as well as to explore underlying molecular pathomechanisms in FCD.

1,395 citations


Journal ArticleDOI
TL;DR: The hybrid simulation framework Veins (Vehicles in Network Simulation), composed of the network simulator OMNeT++ and the road traffic simulator SUMO, is developed and can advance the state-of-the-art in performance evaluation of IVC and provide means to evaluate developed protocols more accurately.
Abstract: Recently, many efforts have been made to develop more efficient Inter-Vehicle Communication (IVC) protocols for on-demand route planning according to observed traffic congestion or incidents, as well as for safety applications. Because practical experiments are often not feasible, simulation of network protocol behavior in Vehicular Ad Hoc Network (VANET) scenarios is strongly demanded for evaluating the applicability of developed network protocols. In this work, we discuss the need for bidirectional coupling of network simulation and road traffic microsimulation for evaluating IVC protocols. As the selection of a mobility model influences the outcome of simulations to a great extent, the use of a representative model is necessary for producing meaningful evaluation results. Based on these observations, we developed the hybrid simulation framework Veins (Vehicles in Network Simulation), composed of the network simulator OMNeT++ and the road traffic simulator SUMO. In a proof-of-concept study, we demonstrate its advantages and the need for bidirectionally coupled simulation based on the evaluation of two protocols for incident warning over VANETs. With our developed methodology, we can advance the state-of-the-art in performance evaluation of IVC and provide means to evaluate developed protocols more accurately.

1,356 citations


Journal ArticleDOI
Marcos Daniel Actis1, G. Agnetta2, Felix Aharonian3, A. G. Akhperjanian  +682 moreInstitutions (109)
TL;DR: The ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes as mentioned in this paper, which is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100GeV and above 100 TeV.
Abstract: Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.

1,006 citations


Journal ArticleDOI
TL;DR: It is concluded that "Sarcopenia, ie, reduced muscle mass, with limited mobility" should be considered an important clinical entity and that most older persons should be screened for this condition.

Journal ArticleDOI
13 Jan 2011-Nature
TL;DR: A covalent agonist-bound β2AR–T4L fusion protein is designed that can be covalently tethered to a specific site on the receptor through a disulphide bond, and is capable of activating a heterotrimeric G protein.
Abstract: G-protein-coupled receptors (GPCRs) are eukaryotic integral membrane proteins that modulate biological function by initiating cellular signalling in response to chemically diverse agonists. Despite recent progress in the structural biology of GPCRs, the molecular basis for agonist binding and allosteric modulation of these proteins is poorly understood. Structural knowledge of agonist-bound states is essential for deciphering the mechanism of receptor activation, and for structure-guided design and optimization of ligands. However, the crystallization of agonist-bound GPCRs has been hampered by modest affinities and rapid off-rates of available agonists. Using the inactive structure of the human β(2) adrenergic receptor (β(2)AR) as a guide, we designed a β(2)AR agonist that can be covalently tethered to a specific site on the receptor through a disulphide bond. The covalent β(2)AR-agonist complex forms efficiently, and is capable of activating a heterotrimeric G protein. We crystallized a covalent agonist-bound β(2)AR-T4L fusion protein in lipid bilayers through the use of the lipidic mesophase method, and determined its structure at 3.5 A resolution. A comparison to the inactive structure and an antibody-stabilized active structure (companion paper) shows how binding events at both the extracellular and intracellular surfaces are required to stabilize an active conformation of the receptor. The structures are in agreement with long-timescale (up to 30 μs) molecular dynamics simulations showing that an agonist-bound active conformation spontaneously relaxes to an inactive-like conformation in the absence of a G protein or stabilizing antibody.

Journal ArticleDOI
TL;DR: This study identifies two types of oxidative metal-oxide interaction on well-defined models of technologically important Pt-ceria catalysts and details the formation mechanism of the catalytically indispensable Pt-O species on ceria to elucidate the extraordinary structure-activity dependence of ceria-based catalysts in general.
Abstract: Interactions of metal particles with oxide supports can radically enhance the performance of supported catalysts. At the microscopic level, the details of such metal-oxide interactions usually remain obscure. This study identifies two types of oxidative metal-oxide interaction on well-defined models of technologically important Pt-ceria catalysts: (1) electron transfer from the Pt nanoparticle to the support, and (2) oxygen transfer from ceria to Pt. The electron transfer is favourable on ceria supports, irrespective of their morphology. Remarkably, the oxygen transfer is shown to require the presence of nanostructured ceria in close contact with Pt and, thus, is inherently a nanoscale effect. Our findings enable us to detail the formation mechanism of the catalytically indispensable Pt-O species on ceria and to elucidate the extraordinary structure-activity dependence of ceria-based catalysts in general.

Journal ArticleDOI
TL;DR: The current state of knowledge and the implications for patient care in important topic areas, including coronary artery disease and myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease, and sudden cardiac death are defined.

Journal ArticleDOI
TL;DR: The basic phenomenon reflecting the last fifteen years is addressed, commenting on databases, modelling and annotation, the unit of analysis and prototypicality and automatic processing including discussions on features, classification, robustness, evaluation, and implementation and system integration.

Journal ArticleDOI
TL;DR: This review discusses a detailed layout of drinking water quality in Pakistan with special emphasis on major pollutants, sources of pollution and the consequent health problems.


Journal ArticleDOI
TL;DR: It is shown that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.
Abstract: BACKGROUND: Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. METHODS: We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. RESULTS: In case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors. CONCLUSIONS: This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.

Journal ArticleDOI
TL;DR: This Article reports on the first wet chemical bulk functionalization route beginning with pristine graphite that does not require initial oxidative damage of the graphene basal planes, and covalent functionalization of the charged graphene is achieved by organic diazonium salts.
Abstract: Efforts to make graphene more useful for applications include altering its bandgap and increasing its processability. Both of these can be solved by chemically modifying the material, and now a wet chemical method has been developed that functionalizes graphene in bulk starting from pristine graphite.

Journal ArticleDOI
TL;DR: In this paper, a survey of the use of X-ray computed tomography (CT) for dimensional quality control purposes is presented, focusing on issues such as accuracy, traceability to the unit of length (the meter), and measurement uncertainty.
Abstract: The paper gives a survey of the upcoming use of X-ray computed tomography (CT) for dimensional quality control purposes: i.e. for traceable measurement of dimensions of technical (mechanical) components and for tolerance verification of such components. It describes the basic principles of CT metrology, putting emphasis on issues as accuracy, traceability to the unit of length (the meter) and measurement uncertainty. It provides a state of the art (anno 2011) and application examples, showing the aptitude of CT metrology to: (i) check internal dimensions that cannot be measured using traditional coordinate measuring machines and (ii) combine dimensional quality control with material quality control in one single quality inspection run.

Journal ArticleDOI
TL;DR: The evidence points to CRPS being a multifactorial disorder that is associated with an aberrant host response to tissue injury, and variation in susceptibility to perturbed regulation of any of the underlying biological pathways probably accounts for the clinical heterogeneity of CRPS.
Abstract: A complex regional pain syndrome (CRPS)—multiple system dysfunction, severe and often chronic pain, and disability—can be triggered by a minor injury, a fact that has fascinated scientists and perplexed clinicians for decades. However, substantial advances across several medical disciplines have recently improved our understanding of CRPS. Compelling evidence implicates biological pathways that underlie aberrant infl ammation, vasomotor dysfunction, and maladaptive neuroplasticity in the clinical features of CRPS. Collectively, the evidence points to CRPS being a multifactorial disorder that is associated with an aberrant host response to tissue injury. Variation in susceptibility to perturbed regulation of any of the underlying biological pathways probably accounts for the clinical heterogeneity of CRPS.

Journal ArticleDOI
M. Ageron1, Juanan Aguilar2, I. Al Samarai1, Arnauld Albert  +284 moreInstitutions (21)
TL;DR: The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational neutrino telescope in the Mediterranean Sea as mentioned in this paper, where the main purpose of the detector is to perform neutrinos astronomy and the apparatus also offers facilities for marine and Earth sciences.
Abstract: The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given.

Journal ArticleDOI
TL;DR: One atomic layer of graphene exhibits Faraday rotations that would only be measurable in other materials many hundreds of micrometres thick as mentioned in this paper, which is known as the Faraday effect.
Abstract: The rotation of polarized light in certain materials when subject to a magnetic field is known as the Faraday effect. Remarkably, just one atomic layer of graphene exhibits Faraday rotations that would only be measurable in other materials many hundreds of micrometres thick.

Journal ArticleDOI
TL;DR: This tutorial review examines the influence of polymer molecular weight and blend composition upon device performance, and discusses how a variety of processing techniques can be used to control the blend microstructure, leading to improvements in solar cell efficiencies.
Abstract: The performance of organic photovoltaic devices based upon bulk heterojunction blends of donor and acceptor materials has been shown to be highly dependent on the thin film microstructure. In this tutorial review, we discuss the factors responsible for influencing blend microstructure and how these affect device performance. In particular we discuss how various molecular design approaches can affect the thin film morphology of both the donor and acceptor components, as well as their blend microstructure. We further examine the influence of polymer molecular weight and blend composition upon device performance, and discuss how a variety of processing techniques can be used to control the blend microstructure, leading to improvements in solar cell efficiencies.

Journal ArticleDOI
01 May 2011-Stroke
TL;DR: The cumulative risk of recurrence varies greatly up to 10 years, and methodological differences are likely to play an important role and consensus on definitions would improve future comparability of estimates and characterization of groups of stroke survivors at increased risk ofRecurrence.
Abstract: Background and Purpose—Estimates of risk of stroke recurrence are widely variable and focused on the short- term. A systematic review and meta-analysis was conducted to estimate the pooled cumulative risk of stroke recurrence. Methods—Studies reporting cumulative risk of recurrence after first-ever stroke were identified using electronic databases and by manually searching relevant journals and conference abstracts. Overall cumulative risks of stroke recurrence at 30 days and 1, 5, and 10 years after first stroke were calculated, and analyses for heterogeneity were conducted. A Weibull model was fitted to the risk of stroke recurrence of the individual studies and pooled estimates were calculated with 95% CI. Results—Sixteen studies were identified, of which 13 studies reported cumulative risk of stroke recurrence in 9115 survivors. The pooled cumulative risk was 3.1% (95% CI, 1.7–4.4) at 30 days, 11.1% (95% CI, 9.0–13.3) at 1 year, 26.4% (95% CI, 20.1–32.8) at 5 years, and 39.2% (95% CI, 27.2–51.2) at 10...

Journal ArticleDOI
TL;DR: Recent findings suggest that blockade of IL-6 signaling is effective in treating experimental models of autoimmune and chronic inflammatory diseases such as inflammatory bowel diseases, diabetes, multiple sclerosis, asthma and rheumatoid arthritis as well as models of inflammation-associated cancer.

Journal ArticleDOI
TL;DR: This Research News article reviews recent progress in the development of rear-earth (RE) ion doped up-conversion materials for solar cell applications and new trends for RE-ion-doped phosphors are briefly discussed.
Abstract: With the aim of utilizing the infrared region of solar radiation to improve solar cell performance, significant progress, including theoretical analysis and experimental achievement, has been made in the field of up-conversion for photovoltaic applications. This Research News article reviews recent progress in the development of rear-earth (RE) ion doped up-conversion materials for solar cell applications. In addition, new trends for RE-ion-doped phosphors are briefly discussed, among them trivalent RE-ion-doped up-conversion materials for organic solar cell applications.

Journal ArticleDOI
TL;DR: In this article, the authors present various realizations of both photoconductive and p-i-n diode-based photomixers to overcome the limitations of operation at high frequencies, namely transit time or lifetime rolloff, antenna (R)-device (C) RC roll-off, current screening and blocking and heat dissipation.
Abstract: This review is focused on the latest developments in continuous-wave (CW) photomixing for Terahertz (THz) generation. The first part of the paper explains the limiting factors for operation at high frequencies ∼ 1 THz, namely transit time or lifetime roll-off, antenna (R)-device (C) RC roll-off, current screening and blocking, and heat dissipation. We will present various realizations of both photoconductive and p-i-n diode–based photomixers to overcome these limitations, including perspectives on novel materials for high-power photomixers operating at telecom wavelengths (1550 nm). In addition to the classical approach of feeding current originating from a small semiconductor photomixer device to an antenna (antenna-based emitter, AE), an antennaless approach in which the active area itself radiates (large area emitter, LAE) is discussed in detail. Although we focus on CW photomixing, we briefly discuss recent results for LAEs under pulsed conditions. Record power levels of 1.5 mW average power and conversion efficiencies as high as 2 × 10−3 have been reached, about 2 orders of magnitude higher than those obtained with CW antenna-based emitters. The second part of the paper is devoted to applications for CW photomixers. We begin with a discussion of the development of novel THz optics. Special attention is paid to experiments exploiting the long coherence length of CW photomixers for coherent emission and detection of THz arrays. The long coherence length comes with an unprecedented narrow linewidth. This is of particular interest for spectroscopic applications, the field in which THz research has perhaps the highest impact. We point out that CW spectroscopy systems may potentially be more compact, cheaper, and more accurate than conventional pulsed systems. These features are attributed to telecom-wavelength compatibility, to excellent frequency resolution, and to their huge spectral density. The paper concludes with prototype experiments of THz wireless LAN applications. For future telecommunication systems, the limited bandwidth of photodiodes is inadequate for further upshifting carrier frequencies. This, however, will soon be required for increased data throughput. The implementation of telecom-wavelength compatible photomixing diodes for down-conversion of an optical carrier signal to a (sub-)THz RF signal will be required.

Journal ArticleDOI
TL;DR: In this article, a mismatch in visibility of acute ischaemic lesion between diffusion-weighted MRI (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI was used to detect patients within the recommended time window for thrombolysis.
Abstract: Summary Background Many patients with stroke are precluded from thrombolysis treatment because the time from onset of their symptoms is unknown. We aimed to test whether a mismatch in visibility of an acute ischaemic lesion between diffusion-weighted MRI (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI (DWI-FLAIR mismatch) can be used to detect patients within the recommended time window for thrombolysis. Methods In this multicentre observational study, we analysed clinical and MRI data from patients presenting between Jan 1, 2001, and May 31, 2009, with acute stroke for whom DWI and FLAIR were done within 12 h of observed symptom onset. Two neurologists masked to clinical data judged the visibility of acute ischaemic lesions on DWI and FLAIR imaging, and DWI-FLAIR mismatch was diagnosed by consensus. We calculated predictive values of DWI-FLAIR mismatch for the identification of patients with symptom onset within 4·5 h and within 6 h and did multivariate regression analysis to identify potential confounding covariates. This study is registered with ClinicalTrials.gov, number NCT01021319. Findings The final analysis included 543 patients. Mean age was 66·0 years (95% CI 64·7–67·3) and median National Institutes of Health Stroke Scale score was 8 (IQR 4–15). Acute ischaemic lesions were identified on DWI in 516 patients (95%) and on FLAIR in 271 patients (50%). Interobserver agreement for acute ischaemic lesion visibility on FLAIR imaging was moderate (κ=0·569, 95% CI 0·504–0·634). DWI-FLAIR mismatch identified patients within 4·5 h of symptom onset with 62% (95% CI 57–67) sensitivity, 78% (72–84) specificity, 83% (79–88) positive predictive value, and 54% (48–60) negative predictive value. Multivariate regression analysis identified a longer time to MRI (p Interpretation Patients with an acute ischaemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomised trial of thrombolysis in patients with unknown time of symptom onset. Funding Else Kroner-Fresenius-Stiftung, National Institutes of Health.

Journal ArticleDOI
TL;DR: The easy-to-use nomograms can predict LR, DM, and OS over a 5-year period after surgery and may be used as decision support tools in future trials by using the three defined risk groups to select patients for postoperative chemotherapy and close follow-up.
Abstract: Purpose The purpose of this study was to develop accurate models and nomograms to predict local recurrence, distant metastases, and survival for patients with locally advanced rectal cancer treated with long-course chemoradiotherapy (CRT) followed by surgery and to allow for a selection of patients who may benefit most from postoperative adjuvant chemotherapy and close follow-up. Patients and Methods All data (N = 2,795) from five major European clinical trials for rectal cancer were pooled and used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from one trial was used as an external validation set. The variables used in the analysis were sex, age, clinical tumor stage stage, tumor location, radiotherapy dose, concurrent and adjuvant chemotherapy, surgery procedure, and pTNM stage. Model performance was evaluated by the concordance index (c-index). Risk group stratification was proposed for the nomograms. Results The nomograms are able to pred...