Mixed-effects models for modeling cardiac functions and treatment effects.

Mixed-effects model is an efficient tool for analyzing longitudinal data. The random effects in mixed-effects model can be used to capture the correlations among repeated measurements within a subject. The time points are not fixed and all available data can be used in mixed-effects model provided data are missing at random. For this reason, we focus on applying mixed-effects models to the repeated measurements of cardiac function including heart rate, left ventricle developed pressure, and coronary flow in the Glutathione-S-transferase P (GSTP) gene knockout and wild-type mice following ischemial/reperfusion injury performed in the isolated, Langendorff-perfused heart. Cardiac function is measured during three time periods: pre-ischemia, ischemia (no flow), and reperfusion. We developed piecewise nonlinear mixed-effects model to describe the different aspects of the cardiac function during each period. We applied nonlinear mixed-effects models and a changing point model to examine how cardiac function was altered by ischemial/reperfusion-induced injury and for comparison between mouse strains. These findings provide evidence of a new application for the mixed-effects model in physiological and pharmacological studies of the heart

China Market Entry Strategy Of Paris Baguette

This case study analyzes the global strategy of Paris Baguette, a leading bakery franchise in Korea. Because of stricter regulations in the local market, Paris Baguette has encouraged franchises to target overseas markets. The company made first inroads into the Chinese market in 2004 with a bakery cafe in Shanghai. The main point of Paris Baguette’s global strategy is summarized by high quality, style, diversification, and localization. Also, Paris Baguette directly operates its flagship store from headquarters, due to the poor legal environment in China. In this study, we analyze strategies of China market and suggest considerations for future business expansion

Liver Graft‐Versus‐Host Disease is associated with poor survival among allogeneic hematopoietic stem cell transplant recipients

Liver Graft‐versus‐host disease (GVHD) is common in patients with post‐transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post‐transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a “non‐liver GVHD” group, which consisted of other etiologies of post‐transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post‐transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the “non‐liver GVHD” group. The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time‐varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non‐relapse mortality, and adverse relapse‐free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151888/1/ajh25575.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151888/2/ajh25575_am.pd

Human Papillomavirus Infection and Cervical Dysplasia in a Subset of Arab American Women

Background: With limited health data on Arab Americans (AAs), we sought to describe the health-seeking behaviors, prevalence of abnormal cervical cytology and high-risk human papillomavirus (HPV) serotypes, and the relationship with socioeconomic factors among a subset of AA women. Methods: Retrospective observational cohort study of women undergoing routine cancer screening at the Arab-American Center for Economic and Social Services clinic. Data collected included demographics, tobacco use, gross monthly income, prior Papanicolaou (Pap) smear history, and results of cervical cytology and high-risk HPV testing. Results: Of 430 women, 74 (17%) reported that they had never had a Pap smear. Three hundred eighty-eight (90%) women had cervical cytology interpreted as negative for intraepithelial lesion, the remaining 42 (10%) women had abnormal results. Thirteen (3%) women reported prior abnormal Pap smear, which was significantly associated with additional abnormal Pap smear on multivariable analyses (odds ratio 65.46; 95% confidence interval [CI] 17.01-338.62; p \u3c 0.001). One hundred twenty-five (29%) women were tested for high-risk HPV serotypes; 106 (91%) had negative results, 4 (3%) were positive for HPV-16, 7 (6%) were positive for other high-risk serotypes, and 8 results were not recorded. A negative HPV screen was significantly associated with a negative Pap smear (Fisher\u27s exact test p = 0.006). There was no significant association between abnormal cervical cytology and evaluated socioeconomic factors. Conclusions: Additional population based-studies to determine cervical dysplasia/cancer and HPV prevalence in women of Middle Eastern descent are needed

Expression and subcellular localization of Discoidin Domain Receptor 1 (DDR1) define prostate cancer aggressiveness

Background: The Discoidin Domain Receptor 1 (DDR1) is one of the two members of a unique family of receptor tyrosine kinase receptors that signal in response to collagen, which has been implicated in cancer progression. Here, we examined the expression of DDR1 in prostate cancer (PCa), and assessed its potential value as a prognostic marker, as a function of grade, stage and other clinicopathologic parameters. Methods: We investigated the association between the expression level and subcellular localization of DDR1 protein and PCa aggressiveness by immunohistochemistry, using tissue microarrays (TMAs) encompassing 200 cases of PCa with various Gleason scores (GS) and pathologic stages with matched normal tissue, and a highly specific monoclonal antibody. Results: DDR1 was found to be localized in the membrane, cytoplasm, and nuclear compartments of both normal and cancerous prostate epithelial cells. Analyses of DDR1 expression in low GS (≤ 7[3 + 4]) vs high GS (≥ 7[4 + 3]) tissues showed no differences in nuclear or cytoplasmic DDR1in either cancerous or adjacent normal tissue cores. However, relative to normal-matched tissue, the percentage of cases with higher membranous DDR1 expression was significantly lower in high vs. low GS cancers. Although nuclear localization of DDR1 was consistently detected in our tissue samples and also in cultured human PCa and normal prostate-derived cell lines, its presence in that site could not be associated with disease aggressiveness. No associations between DDR1 expression and overall survival or biochemical recurrence were found in this cohort of patients. Conclusion: The data obtained through multivariate logistic regression model analysis suggest that the level of membranous DDR1 expression status may represent a potential biomarker of utility for better determination of PCa aggressiveness.This work was supported by the Department of Defense Prostate Cancer Research Program, DOD Award No W81XWH-15-1-0226 (to RF and RDB) and Awards No W81XWH-10-2-0056 and W81XWH-10-2-0046 Prostate Cancer Biorepository Network (PCBN)

Bayesian lead time estimation for the Johns Hopkins Lung Project data

Problem statement: Lung cancer screening using X-rays has been controversial for many years. A major concern is whether lung cancer screening really brings any survival benefits, which depends on effective treatment after early detection. The problem was analyzed from a different point of view and estimates were presented of the projected lead time for participants in a lung cancer screening program using the Johns Hopkins Lung Project (JHLP) data. Method: The newly developed method of lead time estimation was applied where the lifetime T was treated as a random variable rather than a fixed value, resulting in the number of future screenings for a given individual is a random variable. Using the actuarial life table available from the United States Social Security Administration, the lifetime distribution was first obtained, then the lead time distribution was projected using the JHLP data. Results: The data analysis with the JHLP data shows that, for a male heavy smoker with initial screening ages at 50, 60, and 70, the probability of no-early-detection with semiannual screens will be 32.16%, 32.45%, and 33.17%, respectively; while the mean lead time is 1.36, 1.33 and 1.23 years. The probability of no-early-detection increases monotonically when the screening interval increases, and it increases slightly as the initial age increases for the same screening interval. The mean lead time and its standard error decrease when the screening interval increases for all age groups, and both decrease when initial age increases with the same screening interval. Conclusion: The overall mean lead time estimated with a random lifetime T is slightly less than that with a fixed value of T. This result is hoped to be of benefit to improve current screening programs

The Effect of Binocular Disparities on the Space Distortion

When one pair of dots is located in an object, the perceived space between those two dots is larger than the space of two dots which have same interval and are placed out of object. This is space distortion. Two experiments were performed to investigate the effect of binocular disparities on space distortion. The depth plane of surrounding object (in experiment 1) and of two pairs of dots (in experiment 2) was manipulated. The results showed that when objects or dots were perceived on a different depth plane from an original depth plane, the strength of space distortion was reduced. These results imply that space distortion is more related to early visual processing than attention

The Effects of Novelty and Familiarity on Beauty Perception

In order to investigate how novelty and familiarity affect beauty perception, fractal images were presented five times over 14 weeks. Fractal images are unfamiliar to people, hence used in this study to control their previous experience. a total of 800 fractal images were divided into five groups (160 images X 5 group), and three groups of images were presented to participants each time for five times. The results showed that while beauty perception is decreased until the third exposure, it is increased from third to fifth exposure. These results suggest that a certain level of repeated exposure is necessary for subjects to become familiar, which in turn affect beauty perception

Changes in Human Electroencephalographic Activity in Response to <i>Agastache rugosa</i> Essential Oil Exposure

Agastache rugosa (Korean mint) is an important medicinal and aromatic plant and its aerial parts have a pleasant fragrance. A. rugosa leaves are used as an ingredient in salads and soups for enhancing the aroma and taste of foods in Korea. However, there is no report on the influence of the aroma of A. rugosa on human psychophysiological activity. Therefore, the present study aimed to investigate the effect of exposure to the essential oil of Korean A. rugosa on human electroencephalographic (EEG) activity. The essential oil of A. rugosa was isolated using steam distillation extraction and its composition was determined by gas chromatography and mass spectrometry (GC–MS) analysis. In the EEG study, 38 healthy volunteers (19 men and 19 women) participated. The EEG readings were analyzed for 25 EEG indices from 29 electrodes placed on the scalp according to the international 10–20 system. The major component in the essential oil of A. rugosa was estragole (89.49%) followed by D-limonene (3.40%), menthone (1.80%), and pulegone (1.86%). In the EEG study, significant decreases in absolute theta (AT) and relative theta (RT) power spectra were observed during the exposure to A. rugosa essential oil when compared to that of no odor exposure. Whereas relative alpha (RA), relative slow alpha (RSA), spectral edge frequency 50% (SEF50), and spectral edge frequency 50% of alpha (ASEF) power spectra values significantly increased. These results reveal that the EEG power spectra changes incurred during the exposure to the essential oil of A. rugosa may be associated with the enhancement of freshness and concentration states of the human brain