Showing papers by "Ohio State University published in 2009"

Beyond Baron and Kenny: Statistical Mediation Analysis in the New Millennium

Abstract: Understanding communication processes is the goal of most communication researchers. Rarely are we satisfied merely ascertaining whether messages have an effect on some outcome of focus in a specif...

Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer

Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. Methods: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, a...

The Seventh Data Release of the Sloan Digital Sky Survey

Abstract: This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11,663 deg^2 of imaging data, with most of the ~2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry on a 120° long, 2°.5 wide stripe along the celestial equator in the Southern Galactic Cap, with some regions covered by as many as 90 individual imaging runs. We include a co-addition of the best of these data, going roughly 2 mag fainter than the main survey over 250 deg^2. The survey has completed spectroscopy over 9380 deg^2; the spectroscopy is now complete over a large contiguous area of the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog, reducing the rms statistical errors at the bright end to 45 milliarcseconds per coordinate. We further quantify a systematic error in bright galaxy photometry due to poor sky determination; this problem is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities.

The Large Area Telescope on the Fermi Gamma-ray Space Telescope Mission

Abstract: (Abridged) The Large Area Telescope (Fermi/LAT, hereafter LAT), the primary instrument on the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from below 20 MeV to more than 300 GeV. This paper describes the LAT, its pre-flight expected performance, and summarizes the key science objectives that will be addressed. On-orbit performance will be presented in detail in a subsequent paper. The LAT is a pair-conversion telescope with a precision tracker and calorimeter, each consisting of a 4x4 array of 16 modules, a segmented anticoincidence detector that covers the tracker array, and a programmable trigger and data acquisition system. Each tracker module has a vertical stack of 18 x,y tracking planes, including two layers (x and y) of single-sided silicon strip detectors and high-Z converter material (tungsten) per tray. Every calorimeter module has 96 CsI(Tl) crystals, arranged in an 8 layer hodoscopic configuration with a total depth of 8.6 radiation lengths. The aspect ratio of the tracker (height/width) is 0.4 allowing a large field-of-view (2.4 sr). Data obtained with the LAT are intended to (i) permit rapid notification of high-energy gamma-ray bursts (GRBs) and transients and facilitate monitoring of variable sources, (ii) yield an extensive catalog of several thousand high-energy sources obtained from an all-sky survey, (iii) measure spectra from 20 MeV to more than 50 GeV for several hundred sources, (iv) localize point sources to 0.3 - 2 arc minutes, (v) map and obtain spectra of extended sources such as SNRs, molecular clouds, and nearby galaxies, (vi) measure the diffuse isotropic gamma-ray background up to TeV energies, and (vii) explore the discovery space for dark matter.

Causes and consequences of microRNA dysregulation in cancer

Abstract: Over the past several years it has become clear that alterations in the expression of microRNA (miRNA) genes contribute to the pathogenesis of most — if not all — human malignancies. These alterations can be caused by various mechanisms, including deletions, amplifications or mutations involving miRNA loci, epigenetic silencing or the dysregulation of transcription factors that target specific miRNAs. Because malignant cells show dependence on the dysregulated expression of miRNA genes, which in turn control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumour suppressor genes, these small RNAs provide important opportunities for the development of future miRNA-based therapies.

Advanced Heart Failure Treated with Continuous-Flow Left Ventricular Assist Device

Abstract: Background Patients with advanced heart failure have improved survival rates and quality of life when treated with implanted pulsatile-flow left ventricular assist devices as compared with medical therapy. New continuous-flow devices are smaller and may be more durable than the pulsatile-flow devices. Methods In this randomized trial, we enrolled patients with advanced heart failure who were ineligible for transplantation, in a 2:1 ratio, to undergo implantation of a continuousflow device (134 patients) or the currently approved pulsatile-flow device (66 patients). The primary composite end point was, at 2 years, survival free from disabling stroke and reoperation to repair or replace the device. Secondary end points included survival, frequency of adverse events, the quality of life, and functional capacity. Results Preoperative characteristics were similar in the two treatment groups, with a median age of 64 years (range, 26 to 81), a mean left ventricular ejection fraction of 17%, and nearly 80% of patients receiving intravenous inotropic agents. The primary composite end point was achieved in more patients with continuous-flow devices than with pulsatile-flow devices (62 of 134 [46%] vs. 7 of 66 [11%]; P<0.001; hazard ratio, 0.38; 95% confidence interval, 0.27 to 0.54; P<0.001), and patients with continuous-flow devices had superior actuarial survival rates at 2 years (58% vs. 24%, P = 0.008). Adverse events and device replacements were less frequent in patients with the continuous-flow device. The quality of life and functional capacity improved significantly in both groups. Conclusions Treatment with a continuous-flow left ventricular assist device in patients with advanced heart failure significantly improved the probability of survival free from stroke and device failure at 2 years as compared with a pulsatile device. Both devices significantly improved the quality of life and functional capacity. (ClinicalTrials.gov number, NCT00121485.)

Fire in the Earth System

Abstract: Fire is a worldwide phenomenon that appears in the geological record soon after the appearance of terrestrial plants. Fire influences global ecosystem patterns and processes, including vegetation distribution and structure, the carbon cycle, and climate. Although humans and fire have always coexisted, our capacity to manage fire remains imperfect and may become more difficult in the future as climate change alters fire regimes. This risk is difficult to assess, however, because fires are still poorly represented in global models. Here, we discuss some of the most important issues involved in developing a better understanding of the role of fire in the Earth system.

Human skin wounds: a major and snowballing threat to public health and the economy.

Abstract: In the United States, chronic wounds affect 6.5 million patients. An estimated excess of US$25 billion is spent annually on treatment of chronic wounds and the burden is rapidly growing due to increasing health care costs, an aging population and a sharp rise in the incidence of diabetes and obesity worldwide. The annual wound care products market is projected to reach $15.3 billion by 2010. Chronic wounds are rarely seen in individuals who are otherwise healthy. In fact, chronic wound patients frequently suffer from "highly branded" diseases such as diabetes and obesity. This seems to have overshadowed the significance of wounds per se as a major health problem. For example, NIH's Research Portfolio Online Reporting Tool (RePORT; http://report.nih.gov/), directed at providing access to estimates of funding for various disease conditions does list several rare diseases but does not list wounds. Forty million inpatient surgical procedures were performed in the United States in 2000, followed closely by 31.5 million outpatient surgeries. The need for post-surgical wound care is sharply on the rise. Emergency wound care in an acute setting has major significance not only in a war setting but also in homeland preparedness against natural disasters as well as against terrorism attacks. An additional burden of wound healing is the problem of skin scarring, a $12 billion annual market. The immense economic and social impact of wounds in our society calls for allocation of a higher level of attention and resources to understand biological mechanisms underlying cutaneous wound complications.

Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study.

Abstract: Summary Background Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens. Methods In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m 2 per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French–American–British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799. Findings Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21·1 months (IQR 15·1–26·9), median overall survival was 24·5 months (9·9–not reached) for the azacitidine group versus 15·0 months (5·6–24·1) for the conventional care group (hazard ratio 0·58; 95% CI 0·43–0·77; stratified log-rank p=0·0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50·8% (95% CI 42·1–58·8) of patients in the azacitidine group were alive compared with 26·2% (18·7–34·3) in the conventional care group (p Interpretation Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care. Funding Celgene Corporation.

Computational procedures for probing interactions in OLS and logistic regression: SPSS and SAS implementations.

Abstract: Researchers often hypothesize moderated effects, in which the effect of an independent variable on an outcome variable depends on the value of a moderator variable. Such an effect reveals itself statistically as an interaction between the independent and moderator variables in a model of the outcome variable. When an interaction is found, it is important to probe the interaction, for theories and hypotheses often predict not just interaction but a specific pattern of effects of the focal independent variable as a function of the moderator. This article describes the familiar pick-a-point approach and the much less familiar Johnson-Neyman technique for probing interactions in linear models and introduces macros for SPSS and SAS to simplify the computations and facilitate the probing of interactions in ordinary least squares and logistic regression. A script version of the SPSS macro is also available for users who prefer a point-and-click user interface rather than command syntax.

Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord.

Abstract: Macrophages dominate sites of CNS injury in which they promote both injury and repair. These divergent effects may be caused by distinct macrophage subsets, i.e., "classically activated" proinflammatory (M1) or "alternatively activated" anti-inflammatory (M2) cells. Here, we show that an M1 macrophage response is rapidly induced and then maintained at sites of traumatic spinal cord injury and that this response overwhelms a comparatively smaller and transient M2 macrophage response. The high M1/M2 macrophage ratio has significant implications for CNS repair. Indeed, we present novel data showing that only M1 macrophages are neurotoxic and M2 macrophages promote a regenerative growth response in adult sensory axons, even in the context of inhibitory substrates that dominate sites of CNS injury (e.g., proteoglycans and myelin). Together, these data suggest that polarizing the differentiation of resident microglia and infiltrating blood monocytes toward an M2 or "alternatively" activated macrophage phenotype could promote CNS repair while limiting secondary inflammatory-mediated injury.

Histopathological Image Analysis: A Review

Abstract: Over the past decade, dramatic increases in computational power and improvement in image analysis algorithms have allowed the development of powerful computer-assisted analytical approaches to radiological data. With the recent advent of whole slide digital scanners, tissue histopathology slides can now be digitized and stored in digital image form. Consequently, digitized tissue histopathology has now become amenable to the application of computerized image analysis and machine learning techniques. Analogous to the role of computer-assisted diagnosis (CAD) algorithms in medical imaging to complement the opinion of a radiologist, CAD algorithms have begun to be developed for disease detection, diagnosis, and prognosis prediction to complement the opinion of the pathologist. In this paper, we review the recent state of the art CAD technology for digitized histopathology. This paper also briefly describes the development and application of novel image analysis technology for a few specific histopathology related problems being pursued in the United States and Europe.

MicroRNAs in Cancer.

Abstract: MicroRNAs (miRNAs) are small, noncoding RNAs with important functions in development, cell differentiation, and regulation of cell cycle and apoptosis. MiRNA expression is deregulated in cancer by a variety of mechanisms including amplification, deletion, mutation, and epigenetic silencing. Several studies have now shown that miRNAs are involved in the initiation and progression of cancer. In this review, we briefly describe miRNA biogenesis and discuss how miRNAs can act as oncogenes and tumor suppressors. We also address the role of miRNAs in the diagnosis, prognosis, and treatment of cancer.

A Multicenter, Randomized Trial of Treatment for Mild Gestational Diabetes

Abstract: Background It is uncertain whether treatment of mild gestational diabetes mellitus improves pregnancy outcomes. Methods Women who were in the 24th to 31st week of gestation and who met the criteria for mild gestational diabetes mellitus (i.e., an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per deciliter [5.3 mmol per liter]) were randomly assigned to usual prenatal care (control group) or dietary intervention, self-monitoring of blood glucose, and insulin therapy, if necessary (treatment group). The primary outcome was a composite of stillbirth or perinatal death and neonatal complications, including hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma. Results A total of 958 women were randomly assigned to a study group — 485 to the treatment group and 473 to the control group. We observed no significant difference between groups in the frequency of the composite outcome (32.4% and 37.0% in the treatment and control groups, respectively; P=0.1...

Complex Organic Interstellar Molecules

Abstract: Of the over 150 different molecular species detected in the interstellar and circumstellar media, approximately 50 contain 6 or more atoms. These molecules, labeled complex by astronomers if not by chemists, all contain the element carbon and so can be called organic. In the interstellar medium, complex molecules are detected in the denser sources only. Although, with one exception, complex molecules have only been detected in the gas phase, there is strong evidence that they can be formed in ice mantles on interstellar grains. The nature of the gaseous complex species depends dramatically on the source where they are found: in cold, dense regions they tend to be unsaturated (hydrogen-poor) and exotic, whereas in young stellar objects, they tend to be quite saturated (hydrogen-rich) and terrestrial in nature. Based on both their spectra and chemistry, complex molecules are excellent probes of the physical conditions and history of the sources where they reside. Because they are detected in young stellar objects, complex molecules are expected to be common ingredients for new planetary systems. In this review, we discuss both the observation and chemistry of complex molecules in assorted interstellar regions in the Milky Way.

Heart rate variability, prefrontal neural function, and cognitive performance: the neurovisceral integration perspective on self-regulation, adaptation, and health.

Abstract: In the present paper, we describe a model of neurovisceral integration in which a set of neural structures involved in cognitive, affective, and autonomic regulation are related to heart rate variability (HRV) and cognitive performance. We detail the pathways involved in the neural regulation of the cardiovascular system and provide pharmacological and neuroimaging data in support of the neural structures linking the central nervous system to HRV in humans. We review a number of studies from our group showing that individual differences in HRV are related to performance on tasks associated with executive function and prefrontal cortical activity. These studies include comparisons of executive- and nonexecutive-function tasks in healthy participants, in both threatening and nonthreatening conditions. In addition, we show that manipulating resting HRV levels is associated with changes in performance on executive-function tasks. We also examine the relationship between HRV and cognitive performance in ecologically valid situations using a police shooting simulation and a naval navigation simulation. Finally, we review our studies in anxiety patients, as well as studies examining psychopathy. These findings in total suggest an important relationship among cognitive performance, HRV, and prefrontal neural function that has important implications for both physical and mental health. Future studies are needed to determine exactly which executive functions are associated with individual differences in HRV in a wider range of situations and populations.

Medullary thyroid cancer: management guidelines of the American Thyroid Association.

Abstract: Background: Inherited and sporadic medullary thyroid cancer (MTC) is an uncommon and challenging malignancy. The American Thyroid association (ATA) chose to create specific MTC Clinical Guidelines that would bring together and update the diverse MTC literature and combine it with evidence-based medicine and the knowledge and experience of a panel of expert clinicians. Methods: Relevant articles were identified using a systematic PubMed search and supplemented with additional published materials. Evidence-based recommendations were created and then categorized using criteria adapted from the United States Preventive Services Task Force, Agency for Healthcare Research and Quality. Results: Clinical topics addressed in this scholarly dialog included: initial diagnosis and therapy of preclinical disease (including RET oncogene testing and the timing of prophylactic thyroidectomy), initial diagnosis and therapy of clinically apparent disease (including preoperative testing and imaging, extent of surgery, and h...

Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes

Abstract: Delivery of genes to the brain and spinal cord across the blood-brain barrier (BBB) has not yet been achieved. Here we show that adeno-associated virus (AAV) 9 injected intravenously bypasses the BBB and efficiently targets cells of the central nervous system (CNS). Injection of AAV9-GFP into neonatal mice through the facial vein results in extensive transduction of dorsal root ganglia and motor neurons throughout the spinal cord and widespread transduction of neurons throughout the brain, including the neocortex, hippocampus and cerebellum. In adult mice, tail vein injection of AAV9-GFP leads to robust transduction of astrocytes throughout the entire CNS, with limited neuronal transduction. This approach may enable the development of gene therapies for a range of neurodegenerative diseases, such as spinal muscular atrophy, through targeting of motor neurons, and amyotrophic lateral sclerosis, through targeting of astrocytes. It may also be useful for rapid postnatal genetic manipulations in basic neuroscience studies.

Reliability and Validity

Abstract: Reliability and its antonym unreliability are related to the consistency with which observations can be measured and recorded. Validity depends on reliable observations but addresses the user confidence in or credibility of a study. Both notions are evaluated with respect to a relative notion of ‘truth’ that requires a specification of against what reference we are evaluating observations or conclusions. Methods to evaluate reliability and validity depend on the research purpose, assumptions, and methodologies and may involve quantitative as well as qualitative assessments.

SEGUE: A SPECTROSCOPIC SURVEY OF 240,000 STARS WITH g = 14-20

Abstract: The Sloan Extension for Galactic Understanding and Exploration (SEGUE) Survey obtained {approx}240,000 moderate-resolution (R {approx} 1800) spectra from 3900 {angstrom} to 9000 {angstrom} of fainter Milky Way stars (14.0 10 per resolution element, stellar atmospheric parameters are estimated, including metallicity, surface gravity, and effective temperature. SEGUE obtained 3500 deg{sup 2} of additional ugriz imaging (primarily at low Galactic latitudes) providing precise multicolor photometry ({sigma}(g, r, i) {approx} 2%), ({sigma}(u, z) {approx} 3%) and astrometry ({approx}0.1) for spectroscopic target selection. The stellar spectra, imaging data, and derived parameter catalogs for this survey are publicly available as part of Sloan Digital Sky Survey Data Release 7.

Biomimetics: lessons from nature--an overview.

Abstract: Nature has developed materials, objects and processes that function from the macroscale to the nanoscale. These have gone through evolution over 3.8Gyr. The emerging field of biomimetics allows one...

The Information paradox: A Pedagogical introduction

Abstract: The black hole information paradox is a very poorly understood problem. It is often believed that Hawking's argument is not precisely formulated, and a more careful accounting of naturally occurring quantum corrections will allow the radiation process to become unitary. We show that such is not the case, by proving that small corrections to the leading order Hawking computation cannot remove the entanglement between the radiation and the hole. We formulate Hawking's argument as a 'theorem': assuming 'traditional' physics at the horizon and usual assumptions of locality we will be forced into mixed states or remnants. We also argue that one cannot explain away the problem by invoking AdS/CFT duality. We conclude with recent results on the quantum physics of black holes which show that the interior of black holes have a 'fuzzball' structure. This nontrivial structure of microstates resolves the information paradox and gives a qualitative picture of how classical intuition can break down in black hole physics.