Afadin orients cell division to position the tubule lumen in developing renal tubules

In many types of tubules, continuity of the lumen is paramount to tubular function, yet how tubules generate lumen continuity in vivo is not known. We recently found the F-actin binding protein Afadin is required for lumen continuity in developing renal tubules, though its mechanism of action remains unknown. Here we demonstrate Afadin is required for lumen continuity by orienting the mitotic spindle during cell division. Using an in vitro 3D cyst model, we find Afadin localizes to the cell cortex adjacent to the spindle poles and orients the mitotic spindle. In tubules, cell division may be oriented relative to two axes, longitudinal and apical-basal. Unexpectedly, in vivo examination of early stage developing nephron tubules reveals cell division is not oriented in the longitudinal (or planar polarized) axis. However, cell division is oriented perpendicular to the apical-basal axis. Absence of Afadin in vivo leads to misorientation of apical-basal cell division in nephron tubules. Together these results support a model whereby Afadin determines lumen placement by directing apical-basal spindle orientation, which generates a continuous lumen and normal tubule morphogenesis

Spatial patterns and source attribution of urban methane in the Los Angeles Basin

Urban areas are increasingly recognized as a globally important source of methane to the atmosphere; however, the location of methane sources and relative contributions of source sectors are not well known. Recent atmospheric measurements in Los Angeles, California, USA, show that more than a third of the city's methane emissions are unaccounted for in inventories and suggest that fugitive fossil emissions are the unknown source. We made on-road measurements to quantify fine-scale structure of methane and a suite of complementary trace gases across the Los Angeles Basin in June 2013. Enhanced methane levels were observed across the basin but were unevenly distributed in space. We identified 213 methane hot spots from unknown emission sources. We made direct measurements of ethane to methane (C_2H_6/CH_4) ratios of known methane emission sources in the region, including cattle, geologic seeps, landfills, and compressed natural gas fueling stations, and used these ratios to determine the contribution of biogenic and fossil methane sources to unknown hot spots and to local urban background air. We found that 75% of hot spots were of fossil origin, 20% were biogenic, and 5% of indeterminate source. In regionally integrated air, we observed a wider range of C_2H_6/CH_4 values than observed previously. Fossil fuel sources accounted for 58–65% of methane emissions, with the range depending on the assumed C_2H_6/CH_4 ratio of source end-members and model structure. These surveys demonstrated the prevalence of fugitive methane emissions across the Los Angeles urban landscape and suggested that uninventoried methane sources were widely distributed and primarily of fossil origin

Let's Face It: Patient and Parent Perspectives on Incorporating a Facebook Group into a Multidisciplinary Weight Management Program

Background: Social media may have the potential to enhance weight management efforts. However, the acceptability of incorporating this entity into pediatrics is unknown. The objective of this project was to explore patients' and parents' perspectives about developing a Facebook group as a component of a pediatric weight management program. Methods: Semistructured interviews were performed between September, 2011, and February, 2012, with patients and parents in a multidisciplinary weight management program. Interviews explored participants' perceptions of potential benefits, concerns, and preferences related to a program-specific Facebook group. Transcripts were reviewed and themes identified. The study concluded when thematic saturation was achieved. Results: Participants (n=32) were largely enthusiastic about the idea of a program-specific Facebook group for adolescents. Most preferred a secret group, where only participants would know of the group's existence or group members' identity. No parents expressed concern about security or privacy related to a program-specific Facebook group; one parent expressed concern about undesirable advertisements. Participants endorsed a variety of ideas for inclusion on the page, including weight loss tips, live chats with providers, quizzes, and an incentive system where participants could gain points for making healthy choices. Many parents requested a separate parent-focused page, an idea that was supported by the adolescents. Conclusions: This study suggests that participants perceive potential benefits from incorporating social media interventions into pediatric weight management efforts. Privacy and security issues do not appear to be major parental concerns. Future work should explore the impact of program-specific social media interventions on outcomes for patients in weight management programs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140332/1/chi.2013.0047.pd

An Intervention to Reduce Environmental Tobacco Smoke Exposure Improves Pregnancy Outcomes

Objective—We tested the efficacy of a cognitive-behavioral intervention in reducing environmental tobacco smoke exposure (ETSE) and improving pregnancy outcomes among African-American women. Methods—We recruited 1,044 women to a randomized controlled trial during 2001-2004 in Washington, DC. Data on 691 women with self-reported ETSE were analyzed. A subset of 520 ETSE women and salivary cotinine levels (SCLs)/ml was also analyzed. Individually tailored counseling sessions adapted from evidence-based interventions for ETSE and other risks, were delivered to the intervention group. The usual care group received routine prenatal care as determined by their provider. Logistic regression models were used to predict ETSE before delivery and adverse pregnancy outcomes. Results—Women in the intervention were less likely to self-report ETSE before delivery when controlling for other covariates (OR=0.50, 95%CI=0.35-0.71). Medicaid recipients were more likely to have ETSE (OR=1.97, 95%CI=1.31-2.96). With advancing maternal age, the likelihood of ETSE was less (OR=0.96, 95%CI=0.93-0.99). For women in the intervention the rates of very low birth weight (VLBW) and very preterm birth (VPTB) were significantly improved (OR=0.11, 95%CI=0.01-0.86; OR=0.22, 95%CI=0.07-0.68, respectively). For women with SCL/ml, maternal age was not significant. Intimate partner violence at baseline significantly increased the chances of VLBW and VPTB (OR=3.75, 95%CI=1.02-13.81; OR=2.71, 95%CI=1.11-6.62, respectively). These results were true for mothers who reported ETSE overall and for those with SCL/ml. Conclusions—This is the first randomized clinical trial demonstrating efficacy of a cognitivebehavioral intervention targeting ETSE in pregnancy. We significantly reduced ETSE as well as VPTB and VLBW, leading causes of neonatal mortality and morbidity in minority populations. This intervention may reduce health disparities seen in reproductive outcomes

Prediction of Birth Weight By Cotinine Levels During Pregnancy in a Population of African American Smokers

Objective—The goal was to investigate the association between maternal salivary cotinine levels (SCLs) and pregnancy outcome among African Americans smokers Methods—In a randomized controlled trial conducted in 2001-2004 in Washington, D.C. 714 women (126 active smokers (18%)) were tested for SCLs at the time of recruitment and later in pregnancy. Sociodemographic health risks and pregnancy outcomes were recorded. Results—Birth weights were significantly lower for infants born to mothers with baseline SCLs of ≥20 ng/ml compared to/ml (p=0.024), ≥50 ng/ml compared to/ml (p=0.002), ≥100 ng/ml compared to/ml (p=0.002), in bivariate analyses. In linear regression analyses adjusting for sociodemographic and medical factors, SCLs of ≥20 ng/ml were associated with a reduction in birth weight of 88 grams when SCLs were measured at baseline (p=0.042) and 205 grams when SCLs were measured immediately before delivery (p Conclusions—Elevated SCLs early in pregnancy or before delivery were associated with reductions in birth weight. At any cutoff level, birth weight reduction was more significant for the same SCL measured late in pregnancy. Maintaining lower levels of smoking for women who are unable to quit may be beneficial

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Portraying the nature of corruption: Using an explorative case-study design

What is the nature of corruption in Western democracies? To answer this research question, the authors study 10 Dutch corruption cases in depth, looking at confidential criminal files. The cases allow them to sketch a general profile of a corruption case. The authors offer nine propositions to portray the nature of corruption. They conclude that corruption usually takes place within enduring relationships, that the process of becoming corrupt can be characterized as a slippery slope, and that important motives for corruption, aside from material gain, include friendship or love, status, and the desire to impress others. The explorative multiple case study methodology helps to expand our understanding of the way in which officials become corrupt. © 2008 The American Society for Public Administration

Assessing the genetic architecture of epithelial ovarian cancer histological subtypes.

Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The Nurses’ Health Studies would like to thank the participants and staff of the Nurses' Health Study and Nurses' Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. Funding of the constituent studies was provided by the California Cancer Research Program (00-01389V-20170, N01-CN25403, 2II0200); the Canadian Institutes of Health Research (MOP-86727); Cancer Australia; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124); the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; the L & S Milken Foundation; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); the Roswell Park Cancer Institute Alliance Foundation; the US National Cancer Institute (K07-CA095666, K07-CA80668, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC67001, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA072720, P30-CA15083, P30-CA008748, P50-CA159981, P50-CA105009, P50-CA136393, R01-CA149429, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063678, R01-CA063682, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA080978, R01-CA083918, R01-CA087538, R01-CA092044, R01-CA095023, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R03-CA113148, R03-CA115195, U01-CA069417, U01-CA071966, UM1-CA186107, UM1-CA176726 and Intramural research funds); the NIH/National Center for Research Resources/General Clinical Research Center (MO1-RR000056); the US Army Medical Research and Material Command (DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-07-0449, W81XWH-10-1-02802); the US Public Health Service (PSA-042205); the National Health and Medical Research Council of Australia (199600 and 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01GB 9401); the State of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P.685); the German Cancer Research Center; the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; Eve Appeal; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital ‘Womens Health Theme’ and the Royal Marsden Hospital; and WorkSafeBC 14. Investigator-specific funding: G.C.P receives scholarship support from the University of Queensland and QIMR Berghofer. Y.L. was supported by the NHMRC Early Career Fellowship. G.C.T. is supported by the National Health and Medical Research Council. S.M. was supported by an ARC Future Fellowship

Environmental Tobacco Smoke Avoidance Among Pregnant African-American Nonsmokers

Background—Environmental tobacco smoke (ETS) exposure during pregnancy contributes to adverse infant health outcomes. Limited previous research has focused on identifying correlates of ETS avoidance. This study sought to identify proximal and more distal correlates of ETS avoidance early in pregnancy among African-American women. Methods—From a sample of low-income, black women (n=1044) recruited in six urban, prenatal care clinics (July 2001–October 2003), cotinine-confirmed nonsmokers with partners, household/ family members, or friends who smoked (n=450) were identified and divided into two groups: any past-7-day ETS exposure and cotinine-confirmed ETS avoidance. Bivariate and multivariate logistic regression analyses identified factors associated with ETS avoidance. Data were initially analyzed in 2004. Final models were reviewed and revised in 2007 and 2008. Results—Twenty-seven percent of pregnant nonsmokers were confirmed as ETS avoiders. In multivariate logistic regression analysis, the odds of ETS avoidance were increased among women who reported household smoking bans (OR=2.96; 95% CI=1.83, 4.77; p Conclusions—Social contextual factors were the strongest determinants of ETS avoidance during pregnancy. Results highlight the importance of prenatal screening to identify pregnant nonsmokers at risk, encouraging household smoking bans, gaining support from significant others, and fully understanding the interpersonal context of a woman’s pregnancy before providing behavioral counseling and advice to prevent ETS exposure