Behavioral Implications of Knockout for the Dyslexia-Risk Gene Dcdc2 in Mice

Several genetic linkage and epidemiological studies have provided strong evidence that DCDC2 is a candidate gene for developmental dyslexia, a disorder that impairs a person’s reading ability despite adequate intelligence, education, and socio-economic status. Studies investigating embryonic intra-ventricular RNA interference (RNAi) of Dcdc2, a rat homolog of the DCDC2 gene in humans, indicate disruptions in neuronal migration in the rat cortex during development. Interestingly, these anatomical anomalies are consistent with post mortem histological analysis of human dyslexic patients. Other rodent models of cortical developmental disruption have shown impairment in rapid auditory processing and learning maze tasks in affected subjects. The current study investigates the rapid auditory processing abilities of mice heterozygous for Dcdc2 (one functioning Dcdc2 allele) and mice with a homozygous knockout of Dcdc2 (no functioning Dcdc2 allele). It is important to note that this genetic model for behavioral assessment is still in the pilot stage. However, preliminary results suggest that mice with a genetic mutation of Dcdc2 have impaired rapid auditory processing, as well as non-spatial maze learning and memory ability, as compared to wildtypes. By genetically knocking out Dcdc2 in mice, behavioral features associated with Dcdc2 can be characterized, along with other neurological abnormalities that may arise due to the loss of the functioning gene.

Empirical Analysis of Credit Risk Regime Switching and Temporal Conditional Default Correlation in Credit Default Swap Valuation: The Market liquidity effect

In this paper, we extend the debate concerning Credit Default Swap valuation to include time varying correlation and co-variances. Traditional multi-variate techniques treat the correlations between covariates as constant over time; however, this view is not supported by the data. Secondly, since financial data does not follow a normal distribution because of its heavy tails, modeling the data using a Generalized Linear model (GLM) incorporating copulas emerge as a more robust technique over traditional approaches. This paper also includes an empirical analysis of the regime switching dynamics of credit risk in the presence of liquidity by following the general practice of assuming that credit and market risk follow a Markov process. The study was based on Credit Default Swap data obtained from Bloomberg that spanned the period January 1st 2004 to August 08th 2006. The empirical examination of the regime switching tendencies provided quantitative support to the anecdotal view that liquidity decreases as credit quality deteriorates. The analysis also examined the joint probability distribution of the credit risk determinants across credit quality through the use of a copula function which disaggregates the behavior embedded in the marginal gamma distributions, so as to isolate the level of dependence which is captured in the copula function. The results suggest that the time varying joint correlation matrix performed far superior as compared to the constant correlation matrix; the centerpiece of linear regression models.

Does Exchange Rate Risk Affect Exports Asymmetrically? Asian Evidence

The effects of exchange rate risk have interested researchers, since the collapse of fixed exchange rates. Little consensus exists, however, regarding its effect on exports. Previous studies implicitly assume symmetry. This paper tests the hypothesis of asymmetric effects of exchange rate risk with a dynamic conditional correlation bivariate GARCH(1,1)-M model. The asymmetry means that exchange rate risk (volatility) affects exports differently during appreciations and depreciations of the exchange rate. The data include bilateral exports from eight Asian countries to the US. The empirical results show that real exchange rate risk significantly affects exports for all countries, negative or positive, in periods of depreciation or appreciation. For five of the eight countries, the effects of exchange risk are asymmetric. Thus, policy makers can consider the stability of the exchange rate in addition to its depreciation as a method of stimulating export growth.

The Effects of Credit Risk on Dynamic Portfolio Management: A New Computational Approach

The study investigates the role of credit risk in a continuous time stochastic asset allocation model, since the traditional dynamic framework does not provide credit risk flexibility. The general model of the study extends the traditional dynamic efficiency framework by explicitly deriving the optimal value function for the infinite horizon stochastic control problem via a weighted volatility measure of market and credit risk. The model's optimal strategy was then compared to that obtained from a benchmark Markowitz-type dynamic optimization framework to determine which specification adequately reflects the optimal terminal investment returns and strategy under credit and market risks. The paper shows that an investor's optimal terminal return is lower than typically indicated under the traditional mean-variance framework during periods of elevated credit risk. Hence I conclude that, while the traditional dynamic mean-variance approach may indicate the ideal, in the presence of credit-risk it does not accurately reflect the observed optimal returns, terminal wealth and portfolio selection strategies.

US Corporate Default Swap Valuation: The Market Liquidity Hypothesis and Autonomous Credit Risk

This paper develops a reduced form three-factor model which includes a liquidity proxy of market conditions which is then used to provide implicit prices. The model prices are then compared with observed market prices of credit default swaps to determine if swap rates adequately reflect market risks. The findings of the analysis illustrate the importance of liquidity in the valuation process. Moreover, market liquidity, a measure of investors. willingness to commit resources in the credit default swap (CDS) market, was also found to improve the valuation of investors. autonomous credit risk. Thus a failure to include a liquidity proxy could underestimate the implied autonomous credit risk. Autonomous credit risk is defined as the fractional credit risk which does not vary with changes in market risk and liquidity conditions.

A Simple Model of Credit Rationing with Information Externalities

Credit-rationing model similar to Stiglitz and Weiss [1981] is combined with the information externality model of Lang and Nakamura [1993] to examine the properties of mortgage markets characterized by both adverse selection and information externalities. In a credit-rationing model, additional information increases lenders ability to distinguish risks, which leads to increased supply of credit. According to Lang and Nakamura, larger supply of credit leads to additional market activities and therefore, greater information. The combination of these two propositions leads to a general equilibrium model. This paper describes properties of this general equilibrium model. The paper provides another sufficient condition in which credit rationing falls with information. In that, external information improves the accuracy of equity-risk assessments of properties, which reduces credit rationing. Contrary to intuition, this increased accuracy raises the mortgage interest rate. This allows clarifying the trade offs associated with reduced credit rationing and the quality of applicant pool.

Depressive symptoms and sexual risk behaviors in adolescents

The purpose of this study was to determine whether depression is a factor in explaining the difference in sex behaviors among adolescents with different ethnic backgrounds, family and school contexts. We hypothesize that adolescents with a higher number of depressive symptoms are more likely to engage in sexual risk behaviors than adolescents with fewer depressive symptoms. Further, adolescent depression and sexual behaviors are mediated or moderated by individual characteristics, family and school contexts. ^ Background. large ethnic disparities exist in adolescent engagement in risky sexual behaviors, yet, there is little in the literature that explains these disparities. Studies of sexual behavior of youths abound; yet, there is little literature on the prevalence and correlates of depression or the association between depression and sexual behaviors among different ethnic groups. Objectives. (1) To determine ethnic differences in the prevalence of depressive symptoms using data collected through the National Longitudinal Study of Adolescent Health (Add Health). (2) To determine predictors of sex risk behaviors among adolescents, including the role of depression. (3) To identify predictors of depression among these adolescents. Methods. Add Health data from wave 1 and wave 2 interviews of 7th–12th graders were analyzed using multivariate models constructed with both depression and sexual behavior as outcome variables. Logistic regression models determined whether and to what extent the independent variables, including depression, sex behaviors, demographic factors, individual and family characteristics, and school context were related to the probability of engaging in risky sexual behaviors. Results. Ethnic differences in depressive symptoms did not persist after demographic and contextual variables were included in the model. Sex behaviors all shared the hypothesized relationship with depressive symptoms. The odds of risky sex behaviors increased as number of depressive symptoms increased. Depression was predicted by marijuana use and having a serious argument with father for males at Wave 1 and by age and future orientation for females. Wave 2 depression was predicted by Wave 1 depression. ^

Risk factors for Clostridium difficile nosocomial diarrhea in patients at the Michael E. Debakey Veterans Affairs Medical Center, Houston, Texas

Background. Clostridium difficile is the leading cause of hospital associated infectious diarrhea and colitis. About 3 million cases of Clostridium difficile diarrhea occur each year with an annual cost of $1 billion. ^ About 20% of patients acquire C. difficile during hospitalization. Infection with Clostridium difficile can result in serious complications, posing a threat to the patient's life. ^ Purpose. The aim of this research was to demonstrate the uniqueness in the characteristics of C. difficile positive nosocomial diarrhea cases compared with C. difficile negative nosocomial diarrhea controls admitted to a local hospital. ^ Methods. One hundred and ninety patients with a positive test and one hundred and ninety with a negative test for Clostridium difficile nosocomial diarrhea, selected from patients tested between January 1, 2002 and December 31, 2003, comprised the study population. Demographic and clinical data were collected from medical records. Logistic regression analyses were conducted to determine the associated odds between selected variables and the outcome of Clostridium difficile nosocomial diarrhea. ^ Results. For the antibiotic classes, cephalosporins (OR, 1.87; CI 95, 1.23 to 2.85), penicillins (OR, 1.57; CI 95, 1.04 to 2.37), fluoroquinolones (OR, 1.65; CI 95, 1.09 to 2.48) and antifungals (OR, 2.17; CI 95, 1.20 to 3.94), were significantly associated with Clostridium difficile nosocomial diarrhea Ceftazidime (OR, 1.95; CI 95, 1.25 to 3.03, p=0.003), gatifloxacin (OR, 1.97; CI 95, 1.31 to 2.97, p=0.001), clindamycin (OR, 3.13; CI 95, 1.99 to 4.93, p<0.001) and vancomycin (OR, 1.77; CI 95, 1.18 to 2.66, p=0.006, were also significantly associated with the disease. Vancomycin was not statistically significant when analyzed in a multivariable model. Other significantly associated drugs were, antacids, laxatives, narcotics and ranitidine. Prolong use of antibiotics and an increased number of comorbid conditions were also associated with C. difficile nosocomial diarrhea. ^ Conclusion. The etiology for C. difficile diarrhea is multifactorial. Exposure to antibiotics and other drugs, prolonged antibiotic usage, the presence and severity of comorbid conditions and prolonged hospital stay were shown to contribute to the development of the disease. It is imperative that any attempt to prevent the disease, or contain its spread, be done on several fronts. ^

Assessing residents' readiness to screen for domestic violence: Utilizing the transtheoretical model - stages of change, decisional balance and self-efficacy

Domestic violence is a major public health problem, yet most physicians do not effectively identify patients at risk. Medical students and residents are not routinely educated on this topic and little is known about the factors that influence their decisions to include screening for domestic violence in their subsequent practice. In order to assess the readiness of primary care residents to screen all patients for domestic violence, this study utilized a survey incorporating constructs from the Transtheoretical Model, including Stages of Change, Decisional Balance (Pros and Cons) and Self-Efficacy. The survey was distributed to residents at the University of Texas Health Science Center Medical School in Houston in: Internal Medicine, Medicine/Pediatrics, Pediatrics, Family Medicine, and Obstetrics and Gynecology. Data from the survey was analyzed to test the hypothesis that residents in the earlier Stages of Change report more costs and fewer benefits with regards to screening for domestic violence, and that those in the later stages exhibit higher Self-Efficacy scores. The findings from this study were consistent with the model in that benefits to screening (Pros) and Self-Efficacy were correlated with later Stages of Change, however reporting fewer costs (Cons) was not. Very few residents were ready to screen all of their patients.^

Obesity and risk of multiple myeloma: A case-control study

Introduction. Several studies have reported a positive association of body mass index (BMI) with multiple myeloma; however, the period of adulthood where BMI is most important remains unclear. In addition, it is well known that body fat is associated with both sex-steroid hormone storage and with increasing insulin levels; therefore, it was hypothesized that the association between obesity and multiple myeloma may be attributed to increased aromatization of androgen in adipose tissue. Objective. The overall objective of this case-control study was to determine whether multiple myeloma cases had higher BMI and greater adult weight gain relative to healthy controls. In addition, we tested the hypothesis that hormone replacement therapy use among women will further increase the association between BMI and risk of multiple myeloma. This study used data from a pilot case-control study at M.D. Anderson Cancer Center (MDACC), entitled Etiology of multiple myeloma, directed by Dr. Sara Strom and Dr. Sergio Giralt. Methods. The pilot study recruited a total of 122 cases of histopathologically confirmed multiple myeloma from MDACC. Controls (n=183) were selected from a database of random digit dialing controls accrued in the Department of Epidemiology at MDACC and were frequency matched to the cases on age (±5 years), gender, and race/ethnicity. Demographic and risk factor information were obtained from all participants who completed a self-administered questionnaire. Items included in the questionnaire include demographic information, height and weight at age 25, 40 and current/diagnosis, medical history, family history of cancer, smoking and alcohol use. Statistical analysis. Initial descriptive analysis included Student's t-test and Pearson's chi-squared tests. Odds ratios and 95% confidence intervals were calculated to quantify the association between the variables of interest and multiple myeloma. A multivariable model will be developed using unconditional logistic regression. Results. MM cases were 1.79 times (95% CI=0.99-3.32) more likely to have been overweight or obese (BMI > 25 kg/m2) at age 25 relative to healthy controls after controlling for age, gender, race/ethnicty, education and family history of cancer. Being overweight or obese at age 40 was not significantly associated with mutliple myeloma risk (OR=1.42, 95% CI=0.86-2.34) nor was being overweight or obses at diagnosis (OR=1.43, 95% CI=0.78, 2.63). We observed a statistically significant 2-fold increased odds of multiple myeloma in individuals who gained more than 4.7 kg during between 25 and 40 years (OR=1.97, 95% CI=1.15-3.39). When assessing HRT as a modifier of the BMI and multiple myeloma association among women (N=123), no association between obesity and MM status was observed among women who have never used HRT (OR=0.60, 95% CI=0.23-1.61; n=73). Yet among women who have ever used HRT (n=50), being overweight or obese was associated with an increase in MM risk (OR=2. 93, 95% CI=0.81-10.6) after adjusting for age; however, the association was not statistically significant. Significance. This study provides further evidence that increased BMI increases the risk of multiple myeloma. Furthermore, among women, HRT use may modify risk of disease. ^

A case-control study of tea/coffee consumption and lung cancer risk

Background. Despite the increasing attention to the effects of dietary factors on lung cancer risk, epidemiological research on the role of black/green tea and coffee intake and lung cancer risk is scarce. The purpose of this study was to explore the following three hypotheses: (1) the preventive (protective) effect from lung cancer is higher in green tea than in black tea and coffee consumption. (2) brewed tea (either black or green) daily drinkers have lower odds of lung cancer than non-drinkers of brewed tea (3) regular black and green tea have more preventive effect against lung cancer than decaffeinated teas due to the synergistic effect of caffeine and other tea components. ^ Methods. Data on 1,088 lung cancer cases and 1,127 controls from an ongoing epidemiological study of lung cancer by the Department of Epidemiology of the University of Texas M.D. Anderson Cancer were analyzed. Multiple logistic regressions were performed for testing associations between frequency of specific types of tea/coffee consumption and the risk of lung cancer. ^ Results. We observed that more than a cup a week of green tea and decaffeinated black tea were significantly associated with reduced odds of lung cancer by 64% for green tea (adjusted OR = 0.44; 95% CI = 0.31–0.64), 36% for decaffeinated black tea (OR = 0.64; 95% CI = 0.45–0.90), when compared with non-drinkers and those who drank less than a cup a week. On the other hand, increasing intake of regular coffee (more than 3 cups a day) was associated with a 30% higher odds ratio of lung cancer (OR = 1.30; 95% CI = 1.01–1.09). No association was found between regular black tea, decaffeinated coffee consumption and the odds ratio of lung cancer. However, when drinkers of other tea/coffee beverages were excluded from each model in order to explore the independent effect of each type of tea/coffee, green tea and decaffeinated black tea-lung cancer associations remained but no association was observed for drinkers of regular coffee. ^ Conclusion. We report the chemopreventive effects of more than a cup a week of green tea and decaffeinated black tea on lung cancer. ^

Diabetes genes and risk of prostate cancer in the Atherosclerosis Risk in Communities study

Prostate cancer (PrCa) is a leading cause of morbidity and mortality, yet the etiology remains uncertain. Meta-analyses show that PrCa risk is reduced by 16% in men with type 2 diabetes (T2D), but the mechanism is unknown. Recent genome-wide association studies and meta-analyses have found single nucleotide polymorphisms (SNPs) that consistently predict T2D risk. We evaluated associations of incident PrCa with 14 T2D SNPs in the Atherosclerosis Risk in Communities (ARIC) study. From 1987-2000, there were 397 incident PrCa cases ascertained from state or local cancer registries among 6,642 men (1,560 blacks and 5,082 whites) aged 45-64 years at baseline. Genotypes were determined by TaqMan assay. Cox proportional hazards models were used to assess the association between PrCa and increasing number of T2D risk-raising alleles for individual SNPs and for genetic risk scores (GRS) comprised of the number of T2D risk-raising alleles across SNPs. Two-way gene-gene interactions were evaluated with likelihood ratio tests. Using additive genetic models, the T2D risk-raising allele was associated with significantly reduced risk of PrCa for IGF2BP2 rs4402960 (hazard ratio [HR]=0.79; P=0.07 among blacks only), SLC2A2 rs5400 (race-adjusted HR=0.85; P=0.05) and UCP2 rs660339 (race-adjusted HR=0.84; P=0.02), but significantly increased risk of PrCa for CAPN10 rs3792267 (race-adjusted HR=1.20; P=0.05). No other SNPs were associated with PrCa using an additive genetic model. However, at least one copy of the T2D risk-raising allele for TCF7L2 rs7903146 was associated with reduced PrCa risk using a dominant genetic model (race-adjusted HR=0.79; P=0.03). These results imply that the T2D-PrCa association may be partly due to shared genetic variation, but these results should be verified since multiple tests were performed. When the combined, additive effects of these SNPs were tested using a GRS, there was nearly a 10% reduction in risk of PrCa per T2D risk-raising allele (race-adjusted HR=0.92; P=0.02). SNPs in IGF2BP2, KCNJ11 and SLC2A2 were also involved in multiple synergistic gene-gene interactions on a multiplicative scale. In conclusion, it appears that the T2D-PrCa association may be due, in part, to common genetic variation. Further knowledge of T2D gene-PrCa mechanisms may improve understanding of PrCa etiology and may inform PrCa prevention and treatment.^

Gender associated risk factors of aortic aneurysms and dissections

Objectives. Predict who will develop a dissection. To create male and female prediction models using the risk factors: age, ethnicity, hypertension, high cholesterol, smoking, alcohol use, diabetes, heart attack, congestive heart failure, congenital and non-congenital heart disease, Marfan syndrome, and bicuspid aortic valve. ^ Methods. Using 572 patients diagnosed with aortic aneurysms, a model was developed for each of males and females using 80% of the data and then verified using the remaining 20% of the data. ^ Results. The male model predicted the probability of a male in having a dissection (p=0.076) and the female model predicted the probability of a female in having a dissection (p=0.054). The validation models did not support the choice of the developmental models. ^ Conclusions. The best models obtained suggested that those who are at a greater risk of having a dissection are males with non-congenital heart disease and who drink alcohol, and females with non-congenital heart disease and bicuspid aortic valve.^

Prevalence and risk factors for human immunodefiency virus and hepatitis C virus co-infection among drug users in innercity neighborhoods in Houston, Texas

Background. There are 200,000 HIV/HCV co-infected people in the US and IDUs are at highest risk of exposure. Between 52-92% of HIV infected IDUs are chronically infected with HCV. African Americans and Hispanics bear the largest burden of co-infections. Furthermore HIV/HCV co-infection is associated with high morbidity and mortality if not treated. The present study investigates the demographic, sexual and drug related risk factors for HIV/HCV co-infection among predominantly African American injecting and non-injecting drug users living in two innercity neighborhoods in Houston, Texas. ^ Methods. This secondary analysis used data collected between February 2004 and June 2005 from 1,889 drug users. Three case-comparison analyses were conducted to investigate the risk factors for HIV/HCV co-infection. HIV mono-infection, HCV mono-infection and non-infection were compared to HIV/HCV co-infection to build multivariate logistic regression models. Race/ethnicity and age were forced into each model regardless of significance in the univariate analysis. ^ Results. The overall prevalence of HIV/HCV co-infection was 3.9% while 39.8% of HIV infected drug users were co-infected with HCV and 10.7% of HCV infected drug users were co-infected with HIV. Among HIV infected IDUs the prevalence of HCV was 71.7% and among HIV infected NIDUs the prevalence of HCV was 24%. In the multivariate analysis, HIV/HCV co-infection was associated with injecting drug use when compared to HIV mono-infection, with MSM when compared to HCV mono-infection and with injecting drug use as well as MSM when compared to non-infection. ^ Conclusion. HIV/HCV co-infection was associated with a combination of sexual and risky injecting practices. More data on the prevalence and risk factors for co-infection among minority populations is urgently needed to support the development of targeted interventions and treatment options. Additionally there should be a focus on promoting safer sex and injecting practices among drug users as well as the expansion of routine testing for HIV and HCV infections in this high risk population.^

Roadmap for implementing the Chronic Care Model for weight management: Healthcare Institution's Response to Obesity (HIRO)

Background. Excess weight and obesity are at epidemic proportions in the United States and place individuals at increased risk for a variety of chronic conditions. Rates of diabetes, high blood pressure, coronary artery disease, stroke, cancer, and arthritis are all influenced by the presence of obesity. Small reductions in excess weight can produce significant positive clinical outcomes. Healthcare organizations have a vital role to play in the identification and management of obesity. Currently, healthcare providers do not adequately diagnose and manage excess weight in patients. Lack of skill, time, and knowledge are commonly cited as reasons for non-adherence to recommended standards of care. The Chronic Care Model offers an approach to healthcare organizations for chronic disease management. The model consists of six elements that work together to empower both providers and patients to have more productive interactions: the community, the health system itself, self-management support, delivery system design, decision support, and clinical information systems. The model and its elements may offer a framework through which healthcare organizations can adapt to support, educate, and empower providers and patients in the management of excess weight and obesity. Successful management of excess weight will reduce morbidity and mortality of many chronic conditions. Purpose. The purpose of this review is to synthesize existing research on the effectiveness of the Chronic Care Model and its elements as they relate to weight management and behaviors associated with maintaining a healthy weight. Methods: A narrative review of the literature between November 1998 and November 2008 was conducted. The review focused on clinical trials, systematic reviews, and reports related to the chronic care model or its elements and weight management, physical activity, nutrition, or diabetes. Fifty-nine articles are included in the review. Results. This review highlights the use of the Chronic Care Model and its elements that can result in improved quality of care and clinical outcomes related to weight management, physical activity, nutrition, and diabetes. Conclusions. Healthcare organizations can use the Chronic Care Model framework to implement changes within their systems to successfully address overweight and obesity in their patient populations. Specific recommendations for operationalizing the Chronic Care Model elements for weight management are presented.^