Comparison of randomized branch sampling with and without replacement at the first stage

Abstract

Is It Possible to Predict the Manual Web Accessibility Result Using the Automatic Result?

The most adequate approach for benchmarking web accessibility is manual expert evaluation supplemented by automatic analysis tools. But manual evaluation has a high cost and is impractical to be applied on large websites. In reality, there is no choice but to rely on automated tools when reviewing large web sites for accessibility. The question is: to what extent the results from automatic evaluation of a web site and individual web pages can be used as an approximation for manual results? This paper presents the initial results of an investigation aimed at answering this question. He have performed both manual and automatic evaluations of the accessibility of web pages of two sites and we have compared the results. In our data set automatically retrieved results could most definitely be used as an approximation manual evaluation results.

The role of PLK-1 in asynchronous cell division of two-cell stage "C. elegans" embryos

Summary Acquisition of lineage-specific cell cycle duration is an important feature of metazoan development. In Caenorhabditis a/egans, differences in cell cycle duration are already apparent in two-cell stage embryos, when the larger anterior blastomere AB divides before the smaller posterior blastomere P1. This time difference is under the control of anterior-posterior (A-P) polarity cues set by the PAR proteins. The mechanism by which these cues regulate the cell cycle machinery differentially in AB and P1 are incompletely understood. Previous work established that retardation of P1 cell division is due in part to preferential activation of an ATL1/CHK-1 dependent checkpoint in P1 but how the remaining time difference is controlled was not known at the onset of my work. The principal line of work in this thesis established that differential timing relies also on a mechanism that promotes mitosis onset preferentially in AB. The polo-like kinase PLK-1, a positive regulator of mitotic entry, is distributed in an asymmetric manner in two-cell stage embryos, with more protein present in AB than in P1. We find that PLK-1 asymmetry is regulated by anterior-posterior (A-P) polarity cues through preferential protein retention in the embryo anterior. Importantly, mild inactivation of plk-1 by RNAi delays entry into mitosis in P1 but not in AB, in a manner that is independent of ATL-1/CHK-1. Together, these findings favor a model in which differential timing of mitotic entry in C. elegans embryos relies on two complementary mechanisms: ATL-1/CHK-1 dependent preferential retardation in P1 and PLK-1 dependent preferential promotion in AB, which together couple polarity cues and cell cycle progression during early development. Besides analyzing PLK-1 asymmetry and its role in differential timing of two-cells stage embryos, we also characterized t2190, a mutant that exhibits reduced differential timing between AB and P1. We found this mutant to be a new allele of par-1. Additionally, we analyzed the role of NMY-2 in regulating the asynchrony of two-cell stage embryos, which may be uncoupled from its role in A-P polarity establishment and carried out a preliminary analysis of the mechanism underlying CDC-25 asymmetry between AB and P,. Overall, our works bring new insights into the mechanism controlling cell cycle progression in early C. elegans embryos. As most of the players important in C. elegans are conserved in other organisms, analogous mechanisms may be utilized in polarized cells of other species. Résumé Au cours du développement, les processus de division cellulaire sont régulés dans l'espace et le temps afin d'aboutir à la formation d'un organisme fonctionnel. Chez les Métazoaires, l'un des mécanismes de contrôle s'effectue au niveau de la durée du cycle cellulaire, celle-ci étant specifiée selon la lignée cellulaire. L'embryon du nématode Caenorhabditis elegans apparaît comme un excellent modèle d'étude de la régulation temporelle du cycle cellulaire. En effet, suite à la première division du zygote, l'embryon est alors composé de deux cellules de taille et d'identité différentes, appelées blastomères AB et P1. Ces deux cellules vont ensuite se diviser de manière asynchrone, le grand blastomère antérieur AB se divisant plus rapidement que le petit blastomère postérieur P1. Cette asynchronie de division est sous le contrôle des protéines PAR qui sont impliquées dans l'établissement de l'axe antéro-postérieur de l'embryon. A ce jour, les mécanismes moléculaires gouvernant ce processus d'asynchronie ne sont que partiellement compris. Des études menées précédemment ont établit que le retard de division observé dans le petit blastomère postérieur P1 était dû, en partie, à l'activation préférentielle dans cette cellule de ATL-1/CHK-1, protéines contrôlant la réponse à des erreurs dans le processus de réplication de l'ADN. L'analyse des autres mécanismes responsables de la différence temporelle d'entrée en mitose des deux cellules a été entreprise au cours de cette thèse. Nous avons considéré la possibilité que l'asynchronie de division était du à l'entrée préférentielle en mitose du grand blastomère AB. Nous avons établi que la protéine kinase PLK-1 (polo-like kinase 1), impliquée dans la régulation positive de la mitose, était distribuée de manière asymétrique dans l'embryon deux cellules. PLK-1 est en effet enrichi dans le blastomère AB. Cette localisation asymétrique de PLK-1 est sous le contrôle des protéines PAR et semble établie via une rétention de PLK-1 dans la cellule AB. Par ailleurs, nous avons démontré que l'inactivation partielle de plk-7 par interférence à ARN (RNAi) conduit à un délai de l'entrée en mitose de la cellule P1 spécifiquement, indépendamment des protéines régulatrices ATL-1/CHK-1. En conclusion, nous proposons un modèle de régulation temporelle de l'entrée en mitose dans l'embryon deux cellules de C. elegans basé sur deux mécanismes complémentaires. Le premier implique l'activation préférentielle des protéines ATL-1/CHK-1, et conduit à un retard d'entrée en mitose spécifiquement dans la cellule P1. Le second est basé sur la localisation asymétrique de la protéine kinase PLK-1 dans la cellule AB et induit une entrée précoce en mitose de cette cellule. Par ailleurs, nous avons étudié un mutant appelé t2190 qui réduit la différence temporelle d'entrée en mitose entre les cellules AB et P1. Nous avons démontré que ce mutant correspondait à un nouvel allèle du Bene par-1. De plus, nous avons analysé le rôle de NMY-2, une protéine myosine qui agit comme moteur moléculaire sur les filaments d'active; dans la régulation de l'asynchronie de division des blastomères AB et P1, indépendamment de sa fonction dans l'établissement de l'axe antéro-postérieur. Par ailleurs, nous avons commencé l'étude du mécanisme moléculaire régulant la localisation asymétrique entre les cellules AB et P1 de la protéine phosphatase CDC25, qui est également un important régulateur de l'entrée en mitose. En conclusion, ce travail de thèse a permis une meilleure compréhension des mécanismes gouvernant la progression du cycle cellulaire dans l'embryon précoce de C. elegans. Etant donné que la plupart des protéines impliquées dans ces processus sont conservées chez d'autres organismes multicellulaires, il apparaît probable que les mécanismes moléculaires révélés dans cette étude soit aussi utilisés chez ceux-ci.

Concurrent or Sequential Adjuvant Letrozole and Radiotherapy after Conservative Surgery for Early-stage Breast Cancer: Long-term Results of the Cohort Phase 2 Randomized Trial

Purpose/Objective(s): Letrozole radiosensitizes breast cancer cells in vitro. In clinical settings, no data exist for the combination of letrozole and radiotherapy. We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting.Materials/Methods: The present study is registered with ClinicalTrials.gov, number NCT00208273. This Phase 2 randomized trial was undertaken in two centers in France and one in Switzerland between January 12, 2005, and February 21, 2007. One hundred fifty postmenopausal women with early-stage breast cancer were randomly assigned after conserving surgery to either concurrent radiotherapy and letrozole (n = 75) or sequential radiotherapy and letrozole (n = 75). Randomization was open label with a minimization technique, stratified by investigational centers, chemotherapy (yes vs. no), radiation boost (yes vs. no), and value of radiation-induced lymphocyte apoptosis (#16% vs. .16%). The whole breast was irradiated to a total dose of 50 Gy in 25 fractions over 5 weeks. In the case of supraclavicular and internal mammary node irradiation, the dose was 44 - 50 Gy. Letrozole was administered orally once daily at a dose of 2 - 5 mg for 5 years (beginning 3 weeks pre-radiotherapy in the concomitant group, and 3 weeks postradiotherapy in the sequential group). The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced Grade 2 or worse toxic effects of the skin and lung (functional pulmonary test and lung CT-scan). Analyses were by intention-to-treat. The long-term follow-up after 2 years was only performed in Montpellier (n = 121) and evaluated skin toxicity (clinical examination every 6 months), lung fibrosis (one CT-scan yearly), cosmetic outcome.Results: All patients were analyzed apart from 1 in the concurrent group who withdrew consent before any treatment.Within the first 2 years (n = 149), no lung toxicity was identified by CT scan and no modification from baseline was noted by the lung diffusion capacity test. Two patients in each group had Grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis [RISF]). After 2 years (n = 121), and with a median follow-up of 50 months (38-62), 2 patients (1 in each arm) presented a Grade 3 RISF. No lung toxicity was identified by CT scan. Cosmetic results (photographies) and quality of life was good to excellent. All patients who had Grade 3 subcutaneous fibrosis had an RILA value of 16% or less, irrespective of the sequence with letrozole.Conclusions:With long-term follow-up, letrozole can be safely delivered shortly after surgery and concomitantly with radiotherapy.

Multispectral remote sensing for site-specific nitrogen fertilizer management

The objective of this work was to evaluate the use of multispectral remote sensing for site-specific nitrogen fertilizer management. Satellite imagery from the advanced spaceborne thermal emission and reflection radiometer (Aster) was acquired in a 23 ha corn-planted area in Iran. For the collection of field samples, a total of 53 pixels were selected by systematic randomized sampling. The total nitrogen content in corn leaf tissues in these pixels was evaluated. To predict corn canopy nitrogen content, different vegetation indices, such as normalized difference vegetation index (NDVI), soil-adjusted vegetation index (Savi), optimized soil-adjusted vegetation index (Osavi), modified chlorophyll absorption ratio index 2 (MCARI2), and modified triangle vegetation index 2 (MTVI2), were investigated. The supervised classification technique using the spectral angle mapper classifier (SAM) was performed to generate a nitrogen fertilization map. The MTVI2 presented the highest correlation (R²=0.87) and is a good predictor of corn canopy nitrogen content in the V13 stage, at 60 days after cultivating. Aster imagery can be used to predict nitrogen status in corn canopy. Classification results indicate three levels of required nitrogen per pixel: low (0-2.5 kg), medium (2.5-3 kg), and high (3-3.3 kg).

Treatment of brain metastases from non-small cell lung cancer with whole-brain radiotherapy (wbrt) in combination with gefitinib (gft) or temozolomide (tmz): a randomized multicenter phase ii trial of the swiss group of clinical cancer research (sakk #70/03)

BACKGROUND: Patients with BM rarely survive .6 months and are commonly excluded from clinical trials. We aimed at improving outcome by exploring 2 combined modality regimens with at the time novel agents for which single-agent activity had been shown. METHODS: NSCLC patients with multiple BM were randomized to WBRT (10 × 3 Gy) and either GFT 250 mg p.o. daily or TMZ 75 mg/m2 p.o. daily ×21/28 days, starting on Day 1 of RT and to be continued until PD. Primary endpoint was overall survival, a Simon's optimal 2-stage design was based on assumptions for the 3-month survival rate. Cognitive functioning and quality of life were also evaluated. RESULTS: Fifty-nine patients (36 M, 23 F; 9 after prior chemo) were included. Median age was 61 years (range 46-82), WHO PS was 0 in 18 patients, 1 in 31 patients, and 2 in 10 patients. All but 1 patients had extracranial disease; 33 of 43 (TMZ) and 15 of 16 (GFT) had adenocarcinoma histology. GFT arm was closed early after stage 1 analysis when the prespecified 3-mo survival rate threshold (66%) was not reached, causes of death were not GFT related. Main causes of death were PD in the CNS 24%, systemic 41%, both 8%, and toxicity 10% [intestinal perforation (2 patients), pneumonia (2), pulmonary emboli (1), pneumonitis NOS (1), seizure (1)]. We summarize here other patients' characteristics for the 2 trial arms: TMZ (n ¼ 43)/GFT (n ¼ 16); median treatment duration: 1.6 /1.8 mo; Grade 3-4 toxicity: lymphopenia 5 patients (12%)/0; fatigue 8 patients (19%)/2 patients (13%). Survival data for TMZ/GFT arms: 3-month survival rate: 58.1% (95% CI 42.1-73)/62.5% (95% CI 35- 85); median OS: 4.9 months (95% CI 2.5-5.6)/6.3 months (95% CI 2.2- 14.6); median PFS: 1.8 months (95% CI 1.5-1.8)/1.8 (95% CI 1.1-3.9); median time to neurol. progr.: 8.0 months (95% CI 2.2-X)/4.8 (95% CI 3.9-10.5). In a model to predict survival time including the variables' age, PS, number of BM, global QL, total MMSE score, and subjective cognitive function, none of the variables accounted for a significant improvement in survival time. CONCLUSIONS: The combinations of WBRT with GFT or TMZ were feasible. However, in this unselected patient population, survival remains poor and a high rate of complication was observed. Four patients died as a result of high-dose corticosteroids. Preliminary evaluation of cognitive function andQL failed to show significant improvement. Indications and patient selection for palliative treatment should be revisited and careful monitoring and supportive care is required. Research and progress for this frequent clinical situation is urgently needed. Trial partly supported by AstraZeneca (Switzerland), Essex Chemie (Switzerland) and Swiss Federal Government.

General electromagnetic simulation tool to predict the microwave nonlinear response of planar, arbitrarily-shaped HTS structures

This work describes a simulation tool being developed at UPC to predict the microwave nonlinear behavior of planar superconducting structures with very few restrictions on the geometry of the planar layout. The software is intended to be applicable to most structures used in planar HTS circuits, including line, patch, and quasi-lumped microstrip resonators. The tool combines Method of Moments (MoM) algorithms for general electromagnetic simulation with Harmonic Balance algorithms to take into account the nonlinearities in the HTS material. The Method of Moments code is based on discretization of the Electric Field Integral Equation in Rao, Wilton and Glisson Basis Functions. The multilayer dyadic Green's function is used with Sommerfeld integral formulation. The Harmonic Balance algorithm has been adapted to this application where the nonlinearity is distributed and where compatibility with the MoM algorithm is required. Tests of the algorithm in TM010 disk resonators agree with closed-form equations for both the fundamental and third-order intermodulation currents. Simulations of hairpin resonators show good qualitative agreement with previously published results, but it is found that a finer meshing would be necessary to get correct quantitative results. Possible improvements are suggested.

Nouvelles armes thérapeutiques contre le mélanome de stade IV [New therapeutic weapons in stage IV melanoma].

The treatment of stage IV melanoma has been revolutionized over the last years with the development of immunotherapies that, for the first time, have shown a significant benefit in overall survival, as well as with extremely effective targeted therapies, that also led to improved survival. These results are the fruits of an important translational research effort that allowed a rational approach with a very fast clinical development. The treatment of metastatic melanoma is, therefore, an illustration of the new paradigms of modern molecular research in oncology. In this review, we will present the various agents that have made the proof of their clinical benefit, as well as the scientific discoveries that allowed their development. Some of the remaining questions will be touched upon with the ongoing clinical trials. Inclusion of patients in these studies remains the top priority to improve on the clinical care.

Validation of a model to predict adverse outcomes in patients with pulmonary embolism.

AIMS: To validate a model for quantifying the prognosis of patients with pulmonary embolism (PE). The model was previously derived from 10 534 US patients. METHODS AND RESULTS: We validated the model in 367 patients prospectively diagnosed with PE at 117 European emergency departments. We used baseline data for the model's 11 prognostic variables to stratify patients into five risk classes (I-V). We compared 90-day mortality within each risk class and the area under the receiver operating characteristic curve between the validation and the original derivation samples. We also assessed the rate of recurrent venous thrombo-embolism and major bleeding within each risk class. Mortality was 0% in Risk Class I, 1.0% in Class II, 3.1% in Class III, 10.4% in Class IV, and 24.4% in Class V and did not differ between the validation and the original derivation samples. The area under the curve was larger in the validation sample (0.87 vs. 0.78, P=0.01). No patients in Classes I and II developed recurrent thrombo-embolism or major bleeding. CONCLUSION: The model accurately stratifies patients with PE into categories of increasing risk of mortality and other relevant complications. Patients in Risk Classes I and II are at low risk of adverse outcomes and are potential candidates for outpatient treatment.

Serum hyperglycosylated human chorionic gonadotropin to predict the gestational outcome in in vitro fertilization/intracytoplasmic sperm injection pregnancies.

Hyperglycosylated human chorionic gonadotropin (H-hCG) is secreted by the placenta in early pregnancy. Decreased H-hCG levels have been associated with abortion in spontaneous pregnancy. We retrospectively measured H-hCG and dimeric hCG in the sera of 87 in vitro fertilization patients obtained in the 3 weeks following embryo transfer and set the results in relation to pregnancy outcome. H-hCG and dimeric hCG were correlated (r(2) = 0.89), and were significantly decreased in biochemical pregnancy (2 microg/l and 18 IU/l, respectively) compared to early pregnancy loss (22 microg/l and 331 IU/l) and ongoing pregnancy (32 microg/l and 353 IU/l). Only H-hCG tended to discriminate between these last two groups.

Identification of the pathological alterations underlying respiratory failure in myotonic dystrophy transgenic mice

AbstractMyotonic dystrophy type 1 (DM1), also known as Steinert's disease, is an inherited autosomal dominant disease. DM1 is characterized by myotonia, muscular weakness and atrophy, but it has a multisystemic phenotype. The genetic basis of the disease is the abnormal expansion of CTG repeats in the 3' untranslated region of the DM protein kinase (DMPK) gene on chromosome 19. The size of the expansion correlates to the severity of the disease and the age of onset.Respiratory problems have long been recognized to be a major feature of the disease and are the main factor contributing to mortality ; however the mechanisms are only partly known. The aim of our study is to investigate whether respiratory failure results only from the involvement of the dystrophic process at the level of the respiratory muscles or comes also from abnormalities in the neuronal network that generates and controls the respiratory rhythm. The generation of valid transgenic mice displaying the human DM1 phenotype by the group of Dr. Gourdon provided us a useful tool to analyze the brain stem respiratory neurons, spinal phrenic motoneurons and phrenic nerves. We examined therefore these structures in transgenic mice carrying 350-500 CTGs and displaying a mild form of the disease (DM1 mice). The morphological and morphometric analysis of diaphragm muscle sections revealed a denervation of the end-plates (EPs), characterized by a decrease in size and shape complexity of EPs and a reduction in the density of acetylcholine receptors (AChRs). Also a strong and significant reduction in the number of phrenic unmyelinated fibers was detected, but not in the myelinated fibers. In addition, no pathological changes were detected in the cervical motoneurons and medullary respiratory centers (Panaite et al., 2008). These results suggest that the breathing rhythm is probably not affected in mice expressing a mild form of DM1, but rather the transmission of action potentials at the level of diaphragm NMJs is deficient.Because size of the mutation increases over generations, new transgenic mice were obtained from the mice with 350-500 CTGs, resulting from a large increase of CTG repeat in successive generations, these mice carry more than 1300 CTGs (DMSXL) and display a severe DM1 phenotype (Gomes-Pereira et al., 2007). Before we study the mechanism underlying the respiratory failure in DMSXL mice, we analyzed the peripheral nervous system (PNS) in these mice by electrophysiological, histological and morphometric methods. Our results provide strong evidence that DMSXL mice have motor neuropathy (Panaite et al., 2010, submitted). Therefore the DMSXL mice expressing severe DM1 features represent for us a good tool to investigate, in the future, the physiological, structural and molecular alterations underlying respiratory failure in DM1. Understanding the mechanism of respiratory deficiency will help to better target the therapy of these problems in DM1 patients. In addition our results may, in the future, orientate pharmaceutical and clinical research towards possible development of therapy against respiratory deficits associated with the DM1.RésuméLa dystrophic myotonique type 1 (DM1), aussi dénommée maladie de Steinert, est une maladie héréditaire autosomique dominante. Elle est caractérisée par une myotonie, une faiblesse musculaire avec atrophie et se manifeste aussi par un phénotype multisystémique. La base génétique de la maladie est une expansion anormale de répétitions CTG dans une région non traduite en 3' du gène de la DM protéine kinase (DMPK) sur le chromosome 19. La taille de l'expansion est corrélée avec la sévérité et l'âge d'apparition de DM1.Bien que les problèmes respiratoires soient reconnus depuis longtemps comme une complication de la maladie et soient le principal facteur contribuant à la mortalité, les mécanismes en sont partiellement connus. Le but de notre étude est d'examiner si l'insuffisance respiratoire de la DM1 est dû au processus dystrophique au niveau des muscles respiratoires ou si elle est entraînée aussi par des anomalies dans le réseau neuronal qui génère et contrôle le rythme respiratoire. La production par le groupe du Dr. Gourdon de souris transgéniques de DM1, manifestant le phénotype de DM1 humaine, nous a fourni un outil pour analyser les nerfs phréniques, les neurones des centres respiratoires du tronc cérébral et les motoneurones phréniques. Par conséquence, nous avons examiné ces structures chez des souris transgéniques portant 350-500 CTG et affichant une forme légère de la maladie (souris DM1). L'analyse morphologique et morphométrique des sections du diaphragme a révélé une dénervation des plaques motrices et une diminution de la taille et de la complexité de la membrane postsynaptîque, ainsi qu'une réduction de la densité des récepteurs à l'acétylcholine. Nous avons aussi détecté une réduction significative du nombre de fibres nerveuses non myélinisées mais pas des fibres myélinisées. Par ailleurs, aucun changement pathologique n'a été détecté pour les neurones moteurs médullaires cervicaux et centres respiratoires du tronc cérébral (Panaite et al., 2008). Ces résultats suggèrent que le iythme respiratoire n'est probablement pas affecté chez les souris manifestant une forme légère du DM1, mais plutôt que la transmission des potentiels d'action au niveau des plaques motrices du diaphragme est déficiente.Comme la taille du mutation augmente au fil des générations, de nouvelles souris transgéniques ont été générés par le groupe Gourdon; ces souris ont plus de 1300 CTG (DMSXL) et manifestent un phénotype sévère du DM1 (Gomes-Pereira et al., 2007). Avant d'étudier le mécanisme sous-jacent de l'insuffisance respiratoire chez les souris DMSXL, nous avons analysé le système nerveux périphérique chez ces souris par des méthodes électrophysiologiques, histologiques et morphométriques. Nos résultats fournissent des preuves solides que les souris DMSXL manifestent une neuropathie motrice (Panaite et al., 2010, soumis). Par conséquent, les souris DMSXL représentent pour nous un bon outil pour étudier, à l'avenir, les modifications physiologiques, morphologiques et moléculaires qui sous-tendent l'insuffisance respiratoire du DM1. La connaissance du mécanisme de déficience respiratoire en DM1 aidera à mieux cibler le traitement de ces problèmes aux patients. De plus, nos résultats pourront, à l'avenir, orienter la recherche pharmaceutique et clinique vers le développement de thérapie contre le déficit respiratoire associé à DM1.

Strategies and tools for preventing neurotoxicity: to test, to predict and how to do it

A change in paradigm is needed in the prevention of toxic effects on the nervous system, moving from its present reliance solely on data from animal testing to a prediction model mostly based on in vitro toxicity testing and in silico modeling. According to the report published by the National Research Council (NRC) of the US National Academies of Science, high-throughput in vitro tests will provide evidence for alterations in"toxicity pathways" as the best possible method of large scale toxicity prediction. The challenges to implement this proposal are enormous, and provide much room for debate. While many efforts address the technical aspects of implementing the vision, many questions around it need also to be addressed. Is the overall strategy the only one to be pursued? How can we move from current to future paradigms? Will we ever be able to reliably model for chronic and developmental neurotoxicity in vitro? This paper summarizes four presentations from a symposium held at the International Neurotoxicology Conference held in Xi"an, China, in June 2011. A. Li reviewed the current guidelines for neurotoxicity and developmental neurotoxicity testing, and discussed the major challenges existing to realize the NCR vision for toxicity testing. J. Llorens reviewed the biology of mammalian toxic avoidance in view of present knowledge on the physiology and molecular biology of the chemical senses, taste and smell. This background information supports the hypothesis that relating in vivo toxicity to chemical epitope descriptors that mimic the chemical encoding performed by the olfactory system may provide a way to the long term future of complete in silico toxicity prediction. S. Ceccatelli reviewed the implementation of rodent and human neural stem cells (NSCs) as models for in vitro toxicity testing that measures parameters such as cell proliferation, differentiation and migration. These appear to be sensitive endpoints that can identify substances with developmental neurotoxic potential. C. Sun ol reviewed the use of primary neuronal cultures in testing for neurotoxicity of environmental pollutants, including the study of the effects of persistent exposures and/or in differentiating cells, which allow recording of effects that can be extrapolated to human developmental neurotoxicity.

External validation of the ASTRAL score to predict 3- and 12-month functional outcome in the China National Stroke Registry.

BACKGROUND AND PURPOSE: The ASTRAL score was recently introduced as a prognostic tool for acute ischemic stroke. It predicts 3-month outcome reliably in both the derivation and the validation European cohorts. We aimed to validate the ASTRAL score in a Chinese stroke population and moreover to explore its prognostic value to predict 12-month outcome. METHODS: We applied the ASTRAL score to acute ischemic stroke patients admitted to 132 study sites of the China National Stroke Registry. Unfavorable outcome was assessed as a modified Rankin Scale score >2 at 3 and 12 months. Areas under the curve were calculated to quantify the prognostic value. Calibration was assessed by comparing predicted and observed probability of unfavorable outcome using Pearson correlation coefficient. RESULTS: Among 3755 patients, 1473 (39.7%) had 3-month unfavorable outcome. Areas under the curve for 3 and 12 months were 0.82 and 0.81, respectively. There was high correlation between observed and expected probability of unfavorable 3- and 12-month outcome (Pearson correlation coefficient: 0.964 and 0.963, respectively). CONCLUSIONS: ASTRAL score is a reliable tool to predict unfavorable outcome at 3 and 12 months after acute ischemic stroke in the Chinese population. It is a useful tool that can be readily applied in clinical practice to risk-stratify acute stroke patients.