Modeling epidemics on adaptively evolving networks: a data-mining perspective

The exploration of epidemic dynamics on dynamically evolving ("adaptive") networks poses nontrivial challenges to the modeler, such as the determination of a small number of informative statistics of the detailed network state (that is, a few "good observables") that usefully summarize the overall (macroscopic, systems level) behavior. Trying to obtain reduced, small size, accurate models in terms of these few statistical observables - that is, coarse-graining the full network epidemic model to a small but useful macroscopic one - is even more daunting. Here we describe a data-based approach to solving the first challenge: the detection of a few informative collective observables of the detailed epidemic dynamics. This will be accomplished through Diffusion Maps, a recently developed data-mining technique. We illustrate the approach through simulations of a simple mathematical model of epidemics on a network: a model known to exhibit complex temporal dynamics. We will discuss potential extensions of the approach, as well as possible shortcomings.Comment: 24 pages, 8 figures, submitted to Virulenc

Food Habits and Choices, Physical Activity, and Breastfeeding Among Overweight and Obese Postpartum Women.

Weight gain during pregnancy and weight retention 6 months postpartum are critical markers in predicting risk for life-long overweight in childbearing women. Pre-pregnancy weight, age, race, marital status, income, and parity are related to weight retention among postpartum women. Health behaviors, such as dietary intake, physical activity, and breastfeeding have also been associated with weight loss during the postpartum period. The purpose of this study was to 1.) describe food group servings, nutrient intake and quality, and meal and snack intake of exclusively breastfeeding (EB), mixed feeding (MF), or formula feeding (FF) women and 2.) determine how breastfeeding, food choices, and physical activity impact weight change by 6 months postpartum. In this sample of 450 women, the FF group consumed fewer calories and servings of grains, refined grains, and desserts. FF women were more likely to report dieting and not consume a multivitamin. All groups were at risk for vitamins A, E and C, calcium, folate and fiber inadequacies. MF women were also at risk for vitamins D, B-6, and zinc inadequacies, while FF women were also at risk for vitamin D inadequacy. Among 188 women, breastfeeding duration was related to weight loss (r = 0.23, P These findings suggest encouraging fruit, vegetable, dairy, grain, meat and beans, and healthy fat consumption may increase nutrients at risk for inadequacy in the diet. The behavioral factors significantly associated with weight gain were daily servings of soda, sweetened beverages, French fries, chips, desserts and sweets, and weekly fast food consumption. Decreasing these dietary behaviors may help promote weight loss during the postpartum period

Comparison of Serum Cotinine Concentration within and across Smokers of Menthol and Nonmenthol Cigarette Brands among Non-Hispanic Black and Non-Hispanic White U.S. Adult Smokers, 2001–2006

Background: The Food and Drug Administration (FDA) is examining options for regulating menthol content in cigarettes. There are many pharmacologic properties of menthol that may facilitate exposure to tobacco smoke, and it has been suggested that the preference for menthol cigarettes in black smokers accounts for their higher cotinine levels. Objective: To assess cigarettes smoked per day–adjusted cotinine levels in relation to smoking a menthol or nonmenthol cigarette brand among non-Hispanic black and white U.S. adult smokers under natural smoking conditions. Method: Serum cotinine concentrations were measured in 1,943 smokers participating in the 2001 to 2006 National Health and Nutrition Examination Surveys (NHANES). The effect of smoking a menthol brand on cigarettes smoked per day–adjusted serum cotinine levels in these two populations was modeled by adjusting for sex, age, number of smokers living in the home, body weight, time since last smoked, and FTC (Federal Trade Commission)-measured nicotine levels. The 8- or 12-digit Universal Product Code (UPC) on the cigarette label was used to determine the cigarette brand and whether it was menthol. Results: Smoking a menthol cigarette brand versus smoking a nonmenthol cigarette brand was not associated (P≥ 0.05) with mean serum cotinine concentration in either black or white smokers. Conclusions: The higher levels of cotinine observed in black smokers compared with white smokers are not explained by their higher preference for menthol cigarette brands. Impact: Further studies like ours are needed to improve our ability to understand health consequences of future changes in tobacco product design

Body Image and Body Satisfaction Differ by Race in Overweight Postpartum Mothers

Body image (BI) and body satisfaction may be important in understanding weight loss behaviors, particularly during the postpartum period. We assessed these constructs among African American and white overweight postpartum women

A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin

J.H. is funded by The Anonymous Trust and Cunningham Trust. GD is funded by ARUK, DR received a University of St Andrews Research Internship. JAA is funded by the Carnegie Trust.A key pathology of Alzheimer’s disease (AD) is amyloid β (Aβ) accumulation which triggers synaptic impairments and neuronal death. Metabolic disruption is common in AD and recent evidence implicates impaired leptin function in AD. Thus the leptin system may be a novel therapeutic target in AD. Indeed, leptin has cognitive enhancing properties and it prevents the aberrant effects of Aβ on hippocampal synaptic function and neuronal viability. However as leptin is a large peptide, development of smaller leptin-mimetics may be the best therapeutic approach. Thus, we have examined the cognitive enhancing and neuroprotective properties of known bioactive leptin fragments. Here we show that the leptin (116-130) fragment, but not leptin (22-56), mirrored the ability of leptin to promote AMPA receptor trafficking to synapses and facilitate activity-dependent hippocampal synaptic plasticity. Administration of leptin (116-130) also mirrored the cognitive enhancing effects of leptin as it enhanced performance in episodic-like memory tests. Moreover, leptin (116-130) prevented hippocampal synaptic disruption and neuronal cell death in models of amyloid toxicity. These findings establish further the importance of the leptin system as a therapeutic target in AD.PostprintPeer reviewe

CCR9 interactions support ovarian cancer cell survival and resistance to cisplatin-induced apoptosis in a PI3K-dependent and FAK-independent fashion

<p>Abstract</p> <p>Background</p> <p>Cisplatin is more often used to treat ovarian cancer (OvCa), which provides modest survival advantage primarily due to chemo-resistance and up regulated anti-apoptotic machineries in OvCa cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in OvCa cell may improve therapeutic outcomes. We have shown that ovarian cancer cells express CC chemokine receptor-9 (CCR9). Others have also shown that CCL25, the only natural ligand for CCR9, up regulates anti-apoptotic proteins in immature T lymphocytes. Hence, it is plausible that CCR9-mediated cell signals might be involved in OvCa cell survival and inhibition of cisplatin-induced apoptosis. In this study, we investigated the potential role and molecular mechanisms of CCR9-mediated inhibition of cisplatin-induced apoptosis in OvCa cells.</p> <p>Methods</p> <p>Cell proliferation, vibrant apoptosis, and TUNEL assays were performed with or without cisplatin treatment in presence or absence of CCL25 to determine the role of the CCR9-CCL25 axis in cisplatin resistance. In situ Fast Activated cell-based ELISA (FACE) assays were performed to determine anti-apoptotic signaling molecules responsible for CCL25-CCR9 mediated survival.</p> <p>Results</p> <p>Our results show interactions between CCR9 and CCL25 increased anti-apoptotic signaling cascades in OvCa cells, which rescued cells from cisplatin-induced cell death. Specifically, CCL25-CCR9 interactions mediated Akt, activation as well as GSK-3β and FKHR phosphorylation in a PI3K-dependent and FAK-independent fashion.</p> <p>Conclusions</p> <p>Our results suggest the CCR9-CCL25 axis plays an important role in reducing cisplatin-induced apoptosis of OvCa cells.</p

CCL25-CCR9 interaction modulates ovarian cancer cell migration, metalloproteinase expression, and invasion

<p>Abstract</p> <p>Background</p> <p>Ovarian carcinoma (OvCa) is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells and its only natural ligand, CCL25, is largely expressed in the thymus, which involutes with age. Other than the thymus, CCL25 is expressed by the small bowel. Interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for OvCa cells. The current study shows OvCa tissue and cells significantly express CCR9, which interacts with CCL25 to support carcinoma cell migration and invasion.</p> <p>Methods</p> <p>RT-PCR and flow cytometry techniques were used to quantify the expression CCR9 by OvCa cells. OvCa tissue microarrays (TMA) was used to confirm CCR9 expression in clinical samples. The Aperio ScanScope scanning system was used to quantify immunohistochemical staining. Cell invasion and migration assays were performed using cell migration and matrigel invasion chambers. Matrix metalloproteinase (MMP) mRNAs were quantified by RT-PCR and active MMPs were quantified by ELISA.</p> <p>Results</p> <p>Our results show significantly (<it>p </it>< 0.001) higher expression of CCR9 by mucinous adenocarcinoma, papillary serous carcinoma, and endometriod ovarian carcinoma cases, than compared to non-neoplastic ovarian tissue. Furthermore, CCR9 expression was significantly elevated in OvCa cell lines (OVCAR-3 and CAOV-3) in comparison to normal adult ovarian epithelial cell mRNA. OvCa cells showed higher migratory and invasive potential towards chemotactic gradients of CCL25, which was inhibited by anti-CCR9 antibodies. Expression of collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), and stromelysins (MMP-3, -10, and -11) by OvCa cells were modulated by CCL25 in a CCR9-dependent fashion.</p> <p>Conclusions</p> <p>These results demonstrate both biological significance and clinical relevance of CCL25 and CCR9 interactions in OvCa cell metastasis.</p