Stimulation of tumour growth by wound-derived growth factors

The goal of this work was to determine the molecular basis for the induction of tumour vascularization and progression by injury. Magnetic resonance imaging (MRI) studies demonstrated that administration of wound fluid derived from cutaneous injuries in pigs reduced the lag for vascularization and initiation of growth of C6 glioma spheroids, implanted in nude mice, and accelerated tumour doubling time. The former effect can be attributed to the angiogenic capacity of wound fluid as detected in vivo by MRI, and in vitro in promoting endothelial cell proliferation. The latter effect, namely the induced rate of tumour growth, is consistent with the angiogenic activity of wound fluid as well as with the finding that wound fluid was directly mitogenic to the tumour cells, and accelerated growth of C6 glioma in spheroid culture. Of the multiple growth factors present in wound fluid, two key factors, heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) and platelet-derived growth factor (PDGF), were identified as the dominant mitogens for C6 glioma, and inhibition of their activity using specific neutralizing antibodies suppressed the mitogenic effect of wound fluid on DNA synthesis in C6 glioma. This study suggests that the stimulatory effect of injury on tumour progression can possibly be attenuated by therapeutic targeting directed against a limited number of specific growth factors. © 1999 Cancer Research Campaig

Estimating past hepatitis C infection risk from reported risk factor histories: implications for imputing age of infection and modeling fibrosis progression

BackgroundChronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates.MethodsWe analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women’s Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use.ResultsAlthough injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before.ConclusionsIn studies of fibrosis progression, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression

Overweight at age two years in a multi-ethnic cohort (ABCD study): the role of prenatal factors, birth outcomes and postnatal factors

<p>Abstract</p> <p>Background</p> <p>Childhood overweight/obesity is a major public health problem worldwide which disproportionally affects specific ethnic groups. Little is known about whether such differences already exist at an early age and which factors contribute to these ethnic differences. Therefore, the present study assessed possible ethnic differences in overweight at age 2 years, and the potential explanatory role of prenatal factors, birth outcomes and postnatal factors.</p> <p>Methods</p> <p>Data were derived from a multi-ethnic cohort in the Netherlands (the ABCD study). Weight and height data of 3,156 singleton infants at age 2 years were used. Five ethnic populations were distinguished: Dutch native (n = 1,718), African descent (n = 238), Turkish (n = 162), Moroccan (n = 245) and other non-Dutch (n = 793). Overweight status was defined by the International Obesity Task Force guidelines. The explanatory role of prenatal factors, birth outcomes and postnatal factors in ethnic disparities in overweight (including obesity) was assessed by logistic regression analysis.</p> <p>Results</p> <p>Compared to the native Dutch (7.1%), prevalence of overweight was higher in the Turkish (19.8%) and Moroccan (16.7%) group, whereas the prevalence was not increased in the African descent (9.2%) and other non-Dutch (8.8%) group. Although maternal pre-pregnancy body mass index partly explained the ethnic differences, the odds ratio (OR) of being overweight remained higher in the Turkish (OR: 2.66; 95%CI: 1.56-4.53) and Moroccan (OR: 2.11; 95%CI: 1.31-3.38) groups after adjusting for prenatal factors. The remaining differences were largely accounted for by weight gain during the first 6 months of life (postnatal factor). Maternal height, birth weight and gender were independent predictors for overweight at age 2 years, but did not explain the ethnic differences.</p> <p>Conclusion</p> <p>Turkish and Moroccan children in the Netherlands have 2- to 3-fold higher odds for being overweight at age 2 years, which is largely attributed to maternal pre-pregnancy BMI and weight gain during the first 6 months of life. Further study on the underlying factors of this early weight gain is required to tackle ethnic differences in overweight among these children.</p

DETORQUEO, QUIRKY, and ZERZAUST Represent Novel Components Involved in Organ Development Mediated by the Receptor-Like Kinase STRUBBELIG in Arabidopsis thaliana

Intercellular signaling plays an important role in controlling cellular behavior in apical meristems and developing organs in plants. One prominent example in Arabidopsis is the regulation of floral organ shape, ovule integument morphogenesis, the cell division plane, and root hair patterning by the leucine-rich repeat receptor-like kinase STRUBBELIG (SUB). Interestingly, kinase activity of SUB is not essential for its in vivo function, indicating that SUB may be an atypical or inactive receptor-like kinase. Since little is known about signaling by atypical receptor-like kinases, we used forward genetics to identify genes that potentially function in SUB-dependent processes and found recessive mutations in three genes that result in a sub-like phenotype. Plants with a defect in DETORQEO (DOQ), QUIRKY (QKY), and ZERZAUST (ZET) show corresponding defects in outer integument development, floral organ shape, and stem twisting. The mutants also show sub-like cellular defects in the floral meristem and in root hair patterning. Thus, SUB, DOQ, QKY, and ZET define the STRUBBELIG-LIKE MUTANT (SLM) class of genes. Molecular cloning of QKY identified a putative transmembrane protein carrying four C2 domains, suggesting that QKY may function in membrane trafficking in a Ca2+-dependent fashion. Morphological analysis of single and all pair-wise double-mutant combinations indicated that SLM genes have overlapping, but also distinct, functions in plant organogenesis. This notion was supported by a systematic comparison of whole-genome transcript profiles during floral development, which molecularly defined common and distinct sets of affected processes in slm mutants. Further analysis indicated that many SLM-responsive genes have functions in cell wall biology, hormone signaling, and various stress responses. Taken together, our data suggest that DOQ, QKY, and ZET contribute to SUB-dependent organogenesis and shed light on the mechanisms, which are dependent on signaling through the atypical receptor-like kinase SUB

Breastfeeding Offers Protection Against Obesity in Children of Recently Immigrated Latina Women

Breastfeeding has been found to have a protective effect on subsequent development of obesity in childhood, particularly in white, non-Hispanic populations. The protective effect of nursing for more than 12 months in children of Latina women is less clear, which may be due to differences in levels of acculturation in previously studied populations. We evaluated the association between breastfeeding for 12 months or more and risk for obesity in a cohort of children of recently immigrated relatively unacculturated Latina mothers. Maternal characteristics at birth, including length of stay in the United States, breastfeeding habits at 4–6 weeks of age, 6 months, and 1 year, and anthropometric measurements were obtained for a cohort of 196 children participating in a prospective study. At 1 year of age 39.0 % of infants were being breastfed. Being breastfed at 1 year of age was associated with a decreased risk of obesity in both univariate (odds ratio (OR) 0.49, 95 % confidence interval (CI) 0.21–0.83) and multivariate models (OR 0.39, 95 % CI 0.02–0.93) adjusting for maternal BMI, marital status, education level, country of origin, age, years of living in the United States, and child's birth weight at 3 years of age, regardless of mother's acculturation status using length of stay in the United States as a proxy for acculturation. The association with breastfeeding persisted at 4 years of age as a protective factor for obesity (OR 0.29, 95 % CI 0.11–0.80). Breastfeeding for longer than 12 months provides a significant protective effect on the development of obesity in early childhood in a cohort of children of high-risk recently immigrated Latina women in San Francisco who were relatively unacculturated to the United States

Big data analytics for supply chain management: A literature review and research agenda

The main objective of this study is to provide a literature review of big data analytics for supply chain management. A review of articles related to the topics was done within SCOPUS, the largest abstract and citation database of peer-reviewed literature. Our search found 17 articles. The distribution of articles per year of publication, subject area, and affiliation, as well as a summary of each paper are presented. We conclude by highlighting future research directions where the deployment of big data analytics is likely to transform supply chain management practices