Showing papers by "Saint Louis University published in 2013"

A Randomized Trial of Adenotonsillectomy for Childhood Sleep Apnea

Abstract: Background Adenotonsillectomy is commonly performed in children with the obstructive sleep apnea syndrome, yet its usefulness in reducing symptoms and improving cognition, behavior, quality of life, and polysomnographic findings has not been rigorously evaluated. We hypothesized that, in children with the obstructive sleep apnea syndrome without prolonged oxyhemoglobin desaturation, early adenotonsillectomy, as compared with watchful waiting with supportive care, would result in improved outcomes. Methods We randomly assigned 464 children, 5 to 9 years of age, with the obstructive sleep apnea syndrome to early adenotonsillectomy or a strategy of watchful waiting. Polysomnographic, cognitive, behavioral, and health outcomes were assessed at baseline and at 7 months. Results The average baseline value for the primary outcome, the attention and executive-function score on the Developmental Neuropsychological Assessment (with scores ranging from 50 to 150 and higher scores indicating better functioning), was ...

Computer Programs in Seismology: An Evolving Tool for Instruction and Research

Abstract: Earthquake seismology, like most areas of geophysics, is a fascinating mix of theory, computation, and observation The past 50–60 years of earthquake seismology can be described as a synergistic interaction between the expanding quantity and improving quality of seismic data and important advances in practical wave‐propagation physics and computation An important impetus for many of these developments was the need to monitor and characterize nuclear explosions in the atmosphere, oceans, and underground, which stimulated a major investment in seismology during the 1960s that, combined with the plate tectonics revolution, initiated large growth in the field Substantial effort was invested to produce standard analysis packages and software tools for the processing and analysis of seismic observations As a result, high‐quality seismic data are readily accessible and sufficient computational power to routinely analyze these observations is available to almost everyone Turn‐key seismic networks are available from manufacturers who provide sensors, data acquisition and transmission, event location, and archival functions in a manner that requires training, but not a detailed understanding of the of the hardware or software packages As we advance toward more sophisticated analysis of ever‐larger data sets, including the effects of 3D structure, the practical and theoretical challenges facing students are substantial Students must adapt to research‐quality software and use it to develop the deep insight into seismic‐wave excitation and propagation before they can confidently apply the concepts to more sophisticated earth and earthquake models Although beginning students have the skills to use some tools such as word processors and have some scripting experience, many are less comfortable extending old or developing new analysis tools or even using existing codes to tackle realistic 1D problems The challenge facing educators is to enable students to quickly become proficient in basic seismic data processing so that they can move on to research …

Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs

Abstract: Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are believed to be the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not been developed. We report that Cre under control of the promoter of Pdgfrb (Pdgfrb-Cre) inactivates loxP-flanked genes in mouse HSCs with high efficiency. We used this system to delete the gene encoding α(v) integrin subunit because various α(v)-containing integrins have been suggested as central mediators of fibrosis in multiple organs. Such depletion protected mice from carbon tetrachloride-induced hepatic fibrosis, whereas global loss of β₃, β₅ or β₆ integrins or conditional loss of β₈ integrins in HSCs did not. We also found that Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of the α(v) integrin subunit using this system was protective in other models of organ fibrosis, including pulmonary and renal fibrosis. Pharmacological blockade of α(v)-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all α(v) integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.

Forecasting the Equity Risk Premium: The Role of Technical Indicators

Abstract: Academic research relies extensively on macroeconomic variables to forecast the U.S. equity risk premium, with relatively little attention paid to the technical indicators widely employed by practitioners. Our paper fills this gap by comparing the forecasting ability of technical indicators with that of macroeconomic variables. Technical indicators display statistically and economically significant in-sample and out-of-sample forecasting power, matching or exceeding that of macroeconomic variables. Furthermore, technical indicators and macroeconomic variables provide complementary information over the business cycle: technical indicators better detect the typical decline in the equity risk premium near business-cycle peaks, while macroeconomic variables more readily pick up the typical rise in the equity risk premium near cyclical troughs. Consistent with this behavior, we show that combining information from both technical indicators and macroeconomic variables significantly improves equity risk premium forecasts versus using either type of information alone. Overall, the substantial countercyclical fluctuations in the equity risk premium appear well captured by the combined information in technical indicators and macroeconomic variables.

Forecasting Stock Returns

Abstract: We survey the literature on stock return forecasting, highlighting the challenges faced by forecasters as well as strategies for improving return forecasts. We focus on U.S. equity premium forecastability and illustrate key issues via an empirical application based on updated data. Some studies argue that, despite extensive in-sample evidence of equity premium predictability, popular predictors from the literature fail to outperform the simple historical average benchmark forecast in out-of-sample tests. Recent studies, however, provide improved forecasting strategies that deliver statistically and economically significant out-of-sample gains relative to the historical average benchmark. These strategies – including economically motivated model restrictions, forecast combination, diffusion indices, and regime shifts – improve forecasting performance by addressing the substantial model uncertainty and parameter instability surrounding the data-generating process for stock returns. In addition to the U.S. equity premium, we succinctly survey out-of-sample evidence supporting U.S. cross-sectional and international stock return forecastability. The significant evidence of stock return forecastability worldwide has important implications for the development of both asset pricing models and investment management strategies.

Managerial Overconfidence and Accounting Conservatism: managerial overconfidence

Abstract: Overconfident managers overestimate IXWXUHUHWXUQVIURPWKHLUILUPV∂�LQYHVWPHQWV��7KXV��ZH� predict that overconfident managers will tend to accelerate good news recognition, delay loss recognition, and generally use less conservative accounting. Furthermore, we test whether external monitoring helps to mitigate this effect. Using measures of both conditional and unconditional conservatism, we find robust evidence of a negative relation between CEO overconfidence and accounting conservatism. We further find that external monitoring does not appear to mitigate this effect. Our findings add to the growing literature on overconfidence and complements findings in Schrand and Zechman (2011) that overconfidence affects financial reporting behavior.

Functions of autophagy in normal and diseased liver

Abstract: Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases.

Public health program capacity for sustainability: a new framework

Abstract: Public health programs can only deliver benefits if they are able to sustain activities over time. There is a broad literature on program sustainability in public health, but it is fragmented and there is a lack of consensus on core constructs. The purpose of this paper is to present a new conceptual framework for program sustainability in public health. This developmental study uses a comprehensive literature review, input from an expert panel, and the results of concept-mapping to identify the core domains of a conceptual framework for public health program capacity for sustainability. The concept-mapping process included three types of participants (scientists, funders, and practitioners) from several public health areas (e.g., tobacco control, heart disease and stroke, physical activity and nutrition, and injury prevention). The literature review identified 85 relevant studies focusing on program sustainability in public health. Most of the papers described empirical studies of prevention-oriented programs aimed at the community level. The concept-mapping process identified nine core domains that affect a program’s capacity for sustainability: Political Support, Funding Stability, Partnerships, Organizational Capacity, Program Evaluation, Program Adaptation, Communications, Public Health Impacts, and Strategic Planning. Concept-mapping participants further identified 93 items across these domains that have strong face validity—89% of the individual items composing the framework had specific support in the sustainability literature. The sustainability framework presented here suggests that a number of selected factors may be related to a program’s ability to sustain its activities and benefits over time. These factors have been discussed in the literature, but this framework synthesizes and combines the factors and suggests how they may be interrelated with one another. The framework presents domains for public health decision makers to consider when developing and implementing prevention and intervention programs. The sustainability framework will be useful for public health decision makers, program managers, program evaluators, and dissemination and implementation researchers.

Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition

Abstract: Topoisomerase I (TOP1) inhibitors are an important class of anticancer drugs. The cytotoxicity of TOP1 inhibitors can be modulated by replication fork reversal through a process that requires poly(ADP-ribose) polymerase (PARP) activity. Whether regressed forks can efficiently restart and what factors are required to restart fork progression after fork reversal are still unknown. We have combined biochemical and EM approaches with single-molecule DNA fiber analysis to identify a key role for human RECQ1 helicase in replication fork restart after TOP1 inhibition that is not shared by other human RecQ proteins. We show that the poly(ADP-ribosyl)ation activity of PARP1 stabilizes forks in the regressed state by limiting their restart by RECQ1. These studies provide new mechanistic insights into the roles of RECQ1 and PARP in DNA replication and offer molecular perspectives to potentiate chemotherapeutic regimens based on TOP1 inhibition.

Is the Optimal Level of Protein Intake for Older Adults Greater Than the Recommended Dietary Allowance

Abstract: Background. Protein is a macronutrient essential for growth, muscle function, immunity and overall tissue homeostasis. Suboptimal protein intake can significantly impact physical function and overall health in older adults.

Blaming the organization for abusive supervision: The roles of perceived organizational support and supervisor's organizational embodiment

Abstract: Why do employees who experience abusive supervision retaliate against the organization? We apply organizational support theory to propose that employees hold the organization partly responsible for abusive supervision. Depending on the extent to which employees identify the supervisor with the organization (i.e., supervisor's organizational embodiment), we expected abusive supervision to be associated with low perceived organizational support (POS) and consequently with retribution against the organization. Across 3 samples, we found that abusive supervision was associated with decreased POS as moderated by supervisor's organizational embodiment. In turn, reduced POS was related to heightened counterproductive work behavior directed against the organization and lowered in-role and extra-role performance. These findings suggest that employees partly attribute abusive supervision to negative valuation by the organization and, consequently, behave negatively toward and withhold positive contributions to it.

The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage

Abstract: Background: We describe the genome of the western painted turtle, Chrysemys picta bellii, one of the most widespread, abundant, and well-studied turtles. We place the genome into a comparative evolutionary context, and focus on genomic features associated with tooth loss, immune function, longevity, sex differentiation and determination, and the species’ physiological capacities to withstand extreme anoxia and tissue freezing. Results: Our phylogenetic analyses confirm that turtles are the sister group to living archosaurs, and demonstrate an extraordinarily slow rate of sequence evolution in the painted turtle. The ability of the painted turtle to withstand complete anoxia and partial freezing appears to be associated with common vertebrate gene networks, and we identify candidate genes for future functional analyses. Tooth loss shares a common pattern of pseudogenization and degradation of tooth-specific genes with birds, although the rate of accumulation of mutations is much slower in the painted turtle. Genes associated with sex differentiation generally reflect phylogeny rather than convergence in sex determination functionality. Among gene families that demonstrate exceptional expansions or show signatures of strong natural selection, immune function and musculoskeletal patterning genes are consistently over-represented. Conclusions: Our comparative genomic analyses indicate that common vertebrate regulatory networks, some of which have analogs in human diseases, are often involved in the western painted turtle’s extraordinary physiological capacities. As these regulatory pathways are analyzed at the functional level, the painted turtle may offer important insights into the management of a number of human health disorders.

Epidemiology, clinical presentation and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women

Abstract: Background. Herpes simplex virus infections type 1 (HSV-1) and type 2 (HSV-2) are common, but the epidemiology of HSV disease is changing. Methods. HSV-seronegative women, aged 18–30 years, who were in the control arm of the HERPEVAC Trial for Women were followed for 20 months for primary HSV infections. Results. Of the 3438 evaluable participants, 183 became infected with HSV: 127 (3.7%) with HSV-1 and 56 (1.6%) with HSV-2. The rate of infection for HSV-1 (2.5 per 100 person-years) was more than twice that for HSV-2 (1.1 per 100 person-years). Most infections (74% of HSV-1 and 63% of HSV-2) occurred without recognized signs or symptoms of herpes disease. The HSV-2 infection rate was 2.6 times higher in non-Hispanic black participants than in Hispanics and 5.5 times higher than in non-Hispanic whites (P < .001), while the HSV-1 infection rate was 1.7 times higher in non-Hispanic whites than non-Hispanic blacks. Younger participants (18–22 years) were more likely to acquire HSV-1 infections and less likely to develop recognized disease than older participants. Overall, 84% of recognized disease cases were genital. No differences were noted in the clinical manifestations of genital HSV-1 vs genital HSV-2 disease. The clinicians’ assessment that cases were caused by HSV was good when they assessed cases as clinically confirmed or unlikely (validated in 83% and 100% of cases, respectively). Conclusions. HSV-1 is now more common than HSV-2 as a cause of oral and genital mucosal infections in young women, but there are important age and race differences.

North American Climate in CMIP5 experiments. Part I: Evaluation of historical simulations of continental and regional climatology

Abstract: This is the first part of a three-part paper on North American climate in phase 5 of the Coupled Model Intercomparison Project (CMIP5) that evaluates the historical simulations of continental and regional climatology with a focus on a core set of 17 models. The authors evaluate the models for a set of basic surface climate and hydrological variables and their extremes for the continent. This is supplemented by evaluations for selected regional climate processes relevant to North American climate, including cool season western Atlantic cyclones, the North American monsoon, the U.S. Great Plains low-level jet, and Arctic sea ice. In general, the multimodel ensemble mean represents the observed spatial patterns of basic climate and hydrological variables but with large variability across models and regions in the magnitude and sign of errors. No single model stands out as being particularly better or worse across all analyses, although some models consistently outperform the others for certain variab...

Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: The TODAY clinical trial

Abstract: OBJECTIVE-Among adolescents with type 2 diabetes, there is limited information regarding incidence and progression of hypertension and microalbuminuria. Hypertension and microalbuminuria assessments made during the TODAY clinical trial were analyzed for effect of treatment, glycemic control, sex, and race/ethnicity. RESEARCH DESIGN ANP METHODS-A cohort of 699 adolescents, 10-17 years of age, 70 mL/min, were randomized to metformin, metformin plus rosiglitazone, or metformin plus intensive lifestyle intervention. Primary study outcome was loss of glycemic control for 6 months or sustained metabolic decompensation requiring insulin. Hypertension and microalbuminuria were managed aggressively with standardized therapy to maintain BP < 130/80 or <95th percentile for age, sex, and height and microalbuminuria <30 µg/mg. RESULTS-In this cohort, 319 (45.6%) reached primary study outcome, and 11.6% were hypertensive at baseline and 33.8% by end of study (average follow-up 3.9 years). Male sex and higher BMI significantly increased the risk for hypertension. Microalbuminuria was found in 6.3% at baseline and rose to 16.6% by end of study. Diagnosis of microalbuminuria was not significantly different between treatment arms, sex, or race/ethnicity, but higher levels of HbA^sub 1c^ were significantly related to risk of developing microalbuminuria. CONCLUSIONS-Prevalence of hypertension and microalbuminuria increased over time among adolescents with type 2 diabetes regardless of diabetes treatment. The greatest risk for hypertension was male sex and higher BM1. The risk for microalbuminuria was more closely related to glycemic control.

Sentinel Injuries in Infants Evaluated for Child Physical Abuse

Abstract: OBJECTIVE: Relatively minor abusive injuries can precede severe physical abuse in infants. Our objective was to determine how often abused infants have a previous history of “sentinel” injuries, compared with infants who were not abused. METHODS: Case-control, retrospective study of 401, <12-month-old infants evaluated for abuse in a hospital-based setting and found to have definite, intermediate concern for, or no abuse after evaluation by the hospital-based Child Protection Team. A sentinel injury was defined as a previous injury reported in the medical history that was suspicious for abuse because the infant could not cruise, or the explanation was implausible. RESULTS: Of the 200 definitely abused infants, 27.5% had a previous sentinel injury compared with 8% of the 100 infants with intermediate concern for abuse (odds ratio: 4.4, 95% confidence interval: 2.0–9.6; P < .001). None of the 101 nonabused infants (controls) had a previous sentinel injury ( P < .001). The type of sentinel injury in the definitely abused cohort was bruising (80%), intraoral injury (11%), and other injury (7%). Sentinel injuries occurred in early infancy: 66% at <3 months of age and 95% at or before the age of 7 months. Medical providers were reportedly aware of the sentinel injury in 41.9% of cases. CONCLUSIONS: Previous sentinel injuries are common in infants with severe physical abuse and rare in infants evaluated for abuse and found to not be abused. Detection of sentinel injuries with appropriate interventions could prevent many cases of abuse. * Abbreviations: AHT — : abusive head trauma CHW — : Children’s Hospital of Wisconsin CPT — : Child Protection Team

Ideology and Prejudice The Role of Value Conflicts

Abstract: In three studies, we tested whether prejudice derives from perceived similarities and dissimilarities in political ideologies (the value-conflict hypothesis). Across three diverse samples in Study 1, conservatives had less favorable impressions than liberals of groups that were identified as liberal (e.g., African Americans, homosexuals), but more favorable impressions than liberals of groups identified as conservative (e.g., Christian fundamentalists, businesspeople). In Studies 2 and 3, we independently manipulated a target’s race (European American or African American) and political attitudes (liberal or conservative). Both studies found symmetrical preferences, with liberals and conservatives each liking attitudinally similar targets more than dissimilar targets. The amount of prejudice was comparable for liberals and conservatives, and the race of the target had no effect. In all three studies, the same patterns were obtained even after controlling for individual differences on prejudice-related dime...

Adrenocortical carcinoma: Clinical outcomes and prognosis of 330 patients at a tertiary care center

Abstract: Objective: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Herein, we describe the clinical features and outcomes for a large series of ACC patients. Design and methods: Retrospective review of ACC patients seen at The University of Texas MD Anderson Cancer Center from 1998 through 2011. Results: A total of 330 patients with median age at diagnosis of 48.5 years; 12 (3.6%) patients were under 18 years. Hormonally functioning tumors represented 41.8% (nZ138) of all cases. Surgical resection for the primary tumor was done in 275 (83.3%) patients (45 at MD Anderson (16.4%)). For those who had surgical resection, the median local-recurrence-free time was 1.04 years. Factors associated with local recurrence included positive surgical margins (PZ0.007) and advanced disease stage (PZ0.026). Median overall survival time for all patients was 3.21 years. Median survival times were 24.1, 6.08, 3.47, and 0.89 years for stages I, II, III, and IV respectively. In multivariable analysis, older age, functioning tumors, and higher disease stage remained significant prognostic factors associated with poor survival. Conclusion: ACC prognosis remains poor with the use of currently available treatments. Older age, functioning tumors, and incomplete resections are clinical factors associated with poor survival. Surgical expertise is important to achieve complete resections and to improve outcome.

A 3D printed fluidic device that enables integrated features.

Abstract: Fluidic devices fabricated using conventional soft lithography are well suited as prototyping methods. Three-dimensional (3D) printing, commonly used for producing design prototypes in industry, allows for one step production of devices. 3D printers build a device layer by layer based on 3D computer models. Here, a reusable, high throughput, 3D printed fluidic device was created that enables flow and incorporates a membrane above a channel in order to study drug transport and affect cells. The device contains 8 parallel channels, 3 mm wide by 1.5 mm deep, connected to a syringe pump through standard, threaded fittings. The device was also printed to allow integration with commercially available membrane inserts whose bottoms are constructed of a porous polycarbonate membrane; this insert enables molecular transport to occur from the channel to above the well. When concentrations of various antibiotics (levofloxacin and linezolid) are pumped through the channels, approximately 18–21% of the drug migrates t...