Showing papers by "Cornell University published in 2005"

Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.

Abstract: Members of the Chamber Quantification Writing Group are: Roberto M. Lang, MD, FASE, Michelle Bierig, MPH, RDCS, FASE, Richard B. Devereux, MD, Frank A. Flachskampf, MD, Elyse Foster, MD, Patricia A. Pellikka, MD, Michael H. Picard, MD, Mary J. Roman, MD, James Seward, MD, Jack S. Shanewise, MD, FASE, Scott D. Solomon, MD, Kirk T. Spencer, MD, FASE, Martin St John Sutton, MD, FASE, and William J. Stewart, MD

The map-based sequence of the rice genome

Abstract: Rice, one of the world's most important food plants, has important syntenic relationships with the other cereal species and is a model plant for the grasses. Here we present a map-based, finished quality sequence that covers 95% of the 389 Mb genome, including virtually all of the euchromatin and two complete centromeres. A total of 37,544 non-transposable-element-related protein-coding genes were identified, of which 71% had a putative homologue in Arabidopsis. In a reciprocal analysis, 90% of the Arabidopsis proteins had a putative homologue in the predicted rice proteome. Twenty-nine per cent of the 37,544 predicted genes appear in clustered gene families. The number and classes of transposable elements found in the rice genome are consistent with the expansion of syntenic regions in the maize and sorghum genomes. We find evidence for widespread and recurrent gene transfer from the organelles to the nuclear chromosomes. The map-based sequence has proven useful for the identification of genes underlying agronomic traits. The additional single-nucleotide polymorphisms and simple sequence repeats identified in our study should accelerate improvements in rice production.

Intensive lipid lowering with atorvastatin in patients with stable coronary disease.

Abstract: background Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD). methods A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non–procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. results The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality. conclusions Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.

VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche

Abstract: The cellular and molecular mechanisms by which a tumour cell undergoes metastasis to a predetermined location are largely unknown. Here we demonstrate that bone marrow-derived haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1; also known as Flt1) home to tumour-specific pre-metastatic sites and form cellular clusters before the arrival of tumour cells. Preventing VEGFR1 function using antibodies or by the removal of VEGFR1(+) cells from the bone marrow of wild-type mice abrogates the formation of these pre-metastatic clusters and prevents tumour metastasis, whereas reconstitution with selected Id3 (inhibitor of differentiation 3)-competent VEGFR1+ cells establishes cluster formation and tumour metastasis in Id3 knockout mice. We also show that VEGFR1+ cells express VLA-4 (also known as integrin alpha4beta1), and that tumour-specific growth factors upregulate fibronectin--a VLA-4 ligand--in resident fibroblasts, providing a permissive niche for incoming tumour cells. Conditioned media obtained from distinct tumour types with unique patterns of metastatic spread redirected fibronectin expression and cluster formation, thereby transforming the metastatic profile. These findings demonstrate a requirement for VEGFR1+ haematopoietic progenitors in the regulation of metastasis, and suggest that expression patterns of fibronectin and VEGFR1+VLA-4+ clusters dictate organ-specific tumour spread.

Graphs over time: densification laws, shrinking diameters and possible explanations

Abstract: How do real graphs evolve over time? What are "normal" growth patterns in social, technological, and information networks? Many studies have discovered patterns in static graphs, identifying properties in a single snapshot of a large network, or in a very small number of snapshots; these include heavy tails for in- and out-degree distributions, communities, small-world phenomena, and others. However, given the lack of information about network evolution over long periods, it has been hard to convert these findings into statements about trends over time.Here we study a wide range of real graphs, and we observe some surprising phenomena. First, most of these graphs densify over time, with the number of edges growing super-linearly in the number of nodes. Second, the average distance between nodes often shrinks over time, in contrast to the conventional wisdom that such distance parameters should increase slowly as a function of the number of nodes (like O(log n) or O(log(log n)).Existing graph generation models do not exhibit these types of behavior, even at a qualitative level. We provide a new graph generator, based on a "forest fire" spreading process, that has a simple, intuitive justification, requires very few parameters (like the "flammability" of nodes), and produces graphs exhibiting the full range of properties observed both in prior work and in the present study.

Pictorial Structures for Object Recognition

Abstract: In this paper we present a computationally efficient framework for part-based modeling and recognition of objects. Our work is motivated by the pictorial structure models introduced by Fischler and Elschlager. The basic idea is to represent an object by a collection of parts arranged in a deformable configuration. The appearance of each part is modeled separately, and the deformable configuration is represented by spring-like connections between pairs of parts. These models allow for qualitative descriptions of visual appearance, and are suitable for generic recognition problems. We address the problem of using pictorial structure models to find instances of an object in an image as well as the problem of learning an object model from training examples, presenting efficient algorithms in both cases. We demonstrate the techniques by learning models that represent faces and human bodies and using the resulting models to locate the corresponding objects in novel images.

Micrometre-scale silicon electro-optic modulator

Abstract: Metal interconnections are expected to become the limiting factor for the performance of electronic systems as transistors continue to shrink in size. Replacing them by optical interconnections, at different levels ranging from rack-to-rack down to chip-to-chip and intra-chip interconnections, could provide the low power dissipation, low latencies and high bandwidths that are needed. The implementation of optical interconnections relies on the development of micro-optical devices that are integrated with the microelectronics on chips. Recent demonstrations of silicon low-loss waveguides, light emitters, amplifiers and lasers approach this goal, but a small silicon electro-optic modulator with a size small enough for chip-scale integration has not yet been demonstrated. Here we experimentally demonstrate a high-speed electro-optical modulator in compact silicon structures. The modulator is based on a resonant light-confining structure that enhances the sensitivity of light to small changes in refractive index of the silicon and also enables high-speed operation. The modulator is 12 micrometres in diameter, three orders of magnitude smaller than previously demonstrated. Electro-optic modulators are one of the most critical components in optoelectronic integration, and decreasing their size may enable novel chip architectures.

Low-level environmental lead exposure and children's intellectual function: an international pooled analysis.

Abstract: Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 µg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 µg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5‐10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 µg/dL and declined to 9.4 µg/dL by 5‐7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 µg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 µg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a loglinear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2‐9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 µg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 µg/dL, 10 to 20 µg/dL, and 20 to 30 µg/dL were 3.9 (95% CI, 2.4‐5.3), 1.9 (95% CI, 1.2‐2.6), and 1.1 (95% CI, 0.7‐1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 µg/dL was significantly greater than that observed for those with a maximal blood lead level ≥ 7.5 µg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 µg/dL is asso

The Subsystems Approach to Genome Annotation and its Use in the Project to Annotate 1000 Genomes

Abstract: The release of the 1000th complete microbial genome will occur in the next two to three years. In anticipation of this milestone, the Fellowship for Interpretation of Genomes (FIG) launched the Project to Annotate 1000 Genomes. The project is built around the principle that the key to improved accuracy in high-throughput annotation technology is to have experts annotate single subsystems over the complete collection of genomes, rather than having an annotation expert attempt to annotate all of the genes in a single genome. Using the subsystems approach, all of the genes implementing the subsystem are analyzed by an expert in that subsystem. An annotation environment was created where populated subsystems are curated and projected to new genomes. A portable notion of a populated subsystem was defined, and tools developed for exchanging and curating these objects. Tools were also developed to resolve conflicts between populated subsystems. The SEED is the first annotation environment that supports this model of annotation. Here, we describe the subsystem approach, and offer the first release of our growing library of populated subsystems. The initial release of data includes 180 177 distinct proteins with 2133 distinct functional roles. This data comes from 173 subsystems and 383 different organisms.

Annotating Expressions of Opinions and Emotions in Language

Abstract: This paper describes a corpus annotation project to study issues in the manual annotation of opinions, emotions, sentiments, speculations, evaluations and other private states in language. The resulting corpus annotation scheme is described, as well as examples of its use. In addition, the manual annotation process and the results of an inter-annotator agreement study on a 10,000-sentence corpus of articles drawn from the world press are presented.

Doubly robust estimation in missing data and causal inference models

Abstract: The goal of this article is to construct doubly robust (DR) estimators in ignorable missing data and causal inference models. In a missing data model, an estimator is DR if it remains consistent when either (but not necessarily both) a model for the missingness mechanism or a model for the distribution of the complete data is correctly specified. Because with observational data one can never be sure that either a missingness model or a complete data model is correct, perhaps the best that can be hoped for is to find a DR estimator. DR estimators, in contrast to standard likelihood-based or (nonaugmented) inverse probability-weighted estimators, give the analyst two chances, instead of only one, to make a valid inference. In a causal inference model, an estimator is DR if it remains consistent when either a model for the treatment assignment mechanism or a model for the distribution of the counterfactual data is correctly specified. Because with observational data one can never be sure that a model for the treatment assignment mechanism or a model for the counterfactual data is correct, inference based on DR estimators should improve upon previous approaches. Indeed, we present the results of simulation studies which demonstrate that the finite sample performance of DR estimators is as impressive as theory would predict. The proposed method is applied to a cardiovascular clinical trial.

Cancer/testis antigens, gametogenesis and cancer.

Abstract: Cancer/testis (CT) antigens, of which more than 40 have now been identified, are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumour types, including melanoma, and carcinomas of the bladder, lung and liver These immunogenic proteins are being vigorously pursued as targets for therapeutic cancer vaccines CT antigens are also being evaluated for their role in oncogenesis — recapitulation of portions of the germline gene-expression programme might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, hypomethylation and metastatic capacity

Accurately interpreting clickthrough data as implicit feedback

Abstract: This paper examines the reliability of implicit feedback generated from clickthrough data in WWW search. Analyzing the users' decision process using eyetracking and comparing implicit feedback against manual relevance judgments, we conclude that clicks are informative but biased. While this makes the interpretation of clicks as absolute relevance judgments difficult, we show that relative preferences derived from clicks are reasonably accurate on average.

Ethanol Production Using Corn, Switchgrass, and Wood; Biodiesel Production Using Soybean and Sunflower

Abstract: Energy outputs from ethanol produced using corn, switchgrass, and wood biomass were each less than the respective fossil energy inputs. The same was true for producing biodiesel using soybeans and sunflower, however, the energy cost for producing soybean biodiesel was only slightly negative compared with ethanol production. Findings in terms of energy outputs compared with the energy inputs were: • Ethanol production using corn grain required 29% more fossil energy than the ethanol fuel produced. • Ethanol production using switchgrass required 50% more fossil energy than the ethanol fuel produced. • Ethanol production using wood biomass required 57% more fossil energy than the ethanol fuel produced. • Biodiesel production using soybean required 27% more fossil energy than the biodiesel fuel produced (Note, the energy yield from soy oil per hectare is far lower than the ethanol yield from corn). • Biodiesel production using sunflower required 118% more fossil energy than the biodiesel fuel produced.

Regulation of NMDA receptor trafficking by amyloid-beta.

Abstract: Amyloid-beta peptide is elevated in the brains of patients with Alzheimer disease and is believed to be causative in the disease process. Amyloid-beta reduces glutamatergic transmission and inhibits synaptic plasticity, although the underlying mechanisms are unknown. We found that application of amyloid-beta promoted endocytosis of NMDA receptors in cortical neurons. In addition, neurons from a genetic mouse model of Alzheimer disease expressed reduced amounts of surface NMDA receptors. Reducing amyloid-beta by treating neurons with a gamma-secretase inhibitor restored surface expression of NMDA receptors. Consistent with these data, amyloid-beta application produced a rapid and persistent depression of NMDA-evoked currents in cortical neurons. Amyloid-beta-dependent endocytosis of NMDA receptors required the alpha-7 nicotinic receptor, protein phosphatase 2B (PP2B) and the tyrosine phosphatase STEP. Dephosphorylation of the NMDA receptor subunit NR2B at Tyr1472 correlated with receptor endocytosis. These data indicate a new mechanism by which amyloid-beta can cause synaptic dysfunction and contribute to Alzheimer disease pathology.

Guidelines for Management of Small Pulmonary Nodules Detected on CT Scans: A Statement from the Fleischner Society

Abstract: Lung nodules are detected very commonly on computed tomographic (CT) scans of the chest, and the ability to detect very small nodules improves with each new generation of CT scanner. In reported studies, up to 51% of smokers aged 50 years or older have pulmonary nodules on CT scans. However, the existing guidelines for follow-up and management of noncalcified nodules detected on nonscreening CT scans were developed before widespread use of multi–detector row CT and still indicate that every indeterminate nodule should be followed with serial CT for a minimum of 2 years. This policy, which requires large numbers of studies to be performed at considerable expense and with substantial radiation exposure for the affected population, has not proved to be beneficial or cost-effective. During the past 5 years, new information regarding prevalence, biologic characteristics, and growth rates of small lung cancers has become available; thus, the authors believe that the time-honored requirement to follow every smal...

The New Transnational Activism

Abstract: The New Transnational Activism, first published in 2005, shows how even the most prosaic activities can assume broader political meanings when they provide ordinary people with the experience of crossing transnational space. This means that we cannot be satisfied with defining transnational activists through the ways they think. The defining feature of transnationalism in this book is relational, and not cognitive. This emphasis on activism's relational structure means that even as they make transnational claims, transnational activists draw on the resources, the networks, and the opportunities in which they are embedded, and only then - if at all - on more distant transnational links. But we can no more sharply draw a line between domestic and international politics in studying transnational activism than we could ignore local politics in studying its national equivalent. Understanding the processes that link the local, the national and the international is the major undertaking of the book.

The Association between Outside Directors, Institutional Investors and the Properties of Management Earnings Forecasts

Abstract: We investigate the relation of the board of directors and institutional ownership with the properties of management earnings forecasts. We find that firms with more outside directors and greater institutional ownership are more likely to issue a forecast and are inclined to forecast more frequently. In addition, these forecasts tend to be more specific, accurate and less optimistically biased. These results are robust to changes specification, Granger causality tests, and simultaneous equation analyses. The results are similar in the pre– and post–Regulation Fair Disclosure (Reg FD) eras. Additional analysis suggests that concentrated institutional ownership is negatively associated with forecast properties. This association is less negative in the post–Reg FD environment, which is consistent with Reg FD reducing the ability of firms to privately communicate information to select audiences.

Predicting good probabilities with supervised learning

Abstract: We examine the relationship between the predictions made by different learning algorithms and true posterior probabilities. We show that maximum margin methods such as boosted trees and boosted stumps push probability mass away from 0 and 1 yielding a characteristic sigmoid shaped distortion in the predicted probabilities. Models such as Naive Bayes, which make unrealistic independence assumptions, push probabilities toward 0 and 1. Other models such as neural nets and bagged trees do not have these biases and predict well calibrated probabilities. We experiment with two ways of correcting the biased probabilities predicted by some learning methods: Platt Scaling and Isotonic Regression. We qualitatively examine what kinds of distortions these calibration methods are suitable for and quantitatively examine how much data they need to be effective. The empirical results show that after calibration boosted trees, random forests, and SVMs predict the best probabilities.

Mitochondrial metabolism of reactive oxygen species.

Abstract: Oxidative stress is considered a major contributor to etiology of both "normal" senescence and severe pathologies with serious public health implications. Mitochondria generate reactive oxygen species (ROS) that are thought to augment intracellular oxidative stress. Mitochondria possess at least nine known sites that are capable of generating superoxide anion, a progenitor ROS. Mitochondria also possess numerous ROS defense systems that are much less studied. Studies of the last three decades shed light on many important mechanistic details of mitochondrial ROS production, but the bigger picture remains obscure. This review summarizes the current knowledge about major components involved in mitochondrial ROS metabolism and factors that regulate ROS generation and removal. An integrative, systemic approach is applied to analysis of mitochondrial ROS metabolism, which is now dissected into mitochondrial ROS production, mitochondrial ROS removal, and mitochondrial ROS emission. It is suggested that mitochondria augment intracellular oxidative stress due primarily to failure of their ROS removal systems, whereas the role of mitochondrial ROS emission is yet to be determined and a net increase in mitochondrial ROS production in situ remains to be demonstrated.

Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial.

Abstract: Background and Purpose—The only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given intravenously within 3 hours of symptom onset. An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy, especially for patients ineligible for intravenous tPA. Methods—We investigated the safety and efficacy of a novel embolectomy device (Merci Retriever) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospective, nonrandomized, multicenter trial. All patients were ineligible for intravenous tPA. Primary outcomes were recanalization and safety, and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients. Results—Recanalization was achieved in 46% (69/151) of patients on intention to treat analysis, and in 48% (68/141) of patients in whom the device was deployed. This rate is significantly higher than that expected using an historical control of 18% (P0.0001). Clinically significant procedural complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes (modified Rankin score 2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P0.0001), and mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89; P0.01). Conclusions—A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics. (Stroke. 2005;36:1432-1440.)

A pooled analysis of bone marrow micrometastasis in breast cancer

Abstract: BACKGROUND We assessed the prognostic significance of the presence of micrometastasis in the bone marrow at the time of diagnosis of breast cancer by means of a pooled analysis. METHODS We combined individual patient data from nine studies involving 4703 patients with stage I, II, or III breast cancer. We evaluated patient outcomes over a 10-year follow-up period (median, 5.2 years), using a multivariable piecewise Cox regression model. RESULTS Micrometastasis was detected in 30.6 percent of the patients. As compared with women without bone marrow micrometastasis, patients with bone marrow micrometastasis had larger tumors and tumors with a higher histologic grade and more often had lymph-node metastases and hormone receptor-negative tumors (P<0.001 for all variables). The presence of micrometastasis was a significant prognostic factor with respect to poor overall survival and breast-cancer-specific survival (univariate mortality ratios, 2.15 and 2.44, respectively; P<0.001 for both outcomes) and poor disease-free survival and distant-disease-free survival during the 10-year observation period (incidence-rate ratios, 2.13 and 2.33, respectively; P<0.001 for both outcomes). In the multivariable analysis, micrometastasis was an independent predictor of a poor outcome. In the univariate subgroup analysis, breast-cancer-specific survival among patients with micrometastasis was significantly shortened (P<0.001 for all comparisons) among those receiving adjuvant endocrine treatment (mortality ratio, 3.22) or cytotoxic therapy (mortality ratio, 2.32) and among patients who had tumors no larger than 2 cm in diameter without lymph-node metastasis and who did not receive systemic adjuvant therapy (mortality ratio, 3.65). CONCLUSIONS The presence of micrometastasis in the bone marrow at the time of diagnosis of breast cancer is associated with a poor prognosis.

Existing Knowledge, Knowledge Creation Capability, and the Rate of New Product Introduction in High-Technology Firms

Abstract: A field study of top management teams and knowledge workers from 72 technology firms demonstrated that the rate of new product and service introduction was a function of organization members’ ability to combine and exchange knowledge. We tested the following as bases of that ability: the existing knowledge of employees (their education levels and functional heterogeneity), knowledge from member ego networks (number of direct contacts and strength of ties), and organizational climates for risk taking and teamwork.