Mostrando recursos 1 - 20 de 2.719

  1. Family history of diabetes and its relationship with insulin secretion and insulin sensitivity in Iraqi immigrants and native Swedes: a population-based cohort study

    Bennet, Louise; Franks, Paul W.; Zöller, Bengt; Groop, Leif
    Aims Middle Eastern immigrants to western countries are at high risk of developing type 2 diabetes. However, the heritability and impact of first-degree family history (FH) of type 2 diabetes on insulin secretion and action have not been adequately described. Methods: Citizens of Malmö, Sweden, aged 30–75 years born in Iraq or Sweden were invited to participate in this population-based study. Insulin secretion (corrected insulin response and oral disposition index) and action (insulin sensitivity index) were assessed by oral glucose tolerance tests. Results: In total, 45.7% of Iraqis (616/1348) and 27.4% of native Swedes (201/733) had FH in parent(s), sibling(s)...

  2. RankProd 2.0: a refactored bioconductor package for detecting differentially expressed features in molecular profiling datasets

    Del Carratore, Francesco; Jankevics, Andris; Eisinga, Rob; Heskes, Tom; Hong, Fangxin; Breitling, Rainer
    Abstract Motivation: The Rank Product (RP) is a statistical technique widely used to detect differentially expressed features in molecular profiling experiments such as transcriptomics, metabolomics and proteomics studies. An implementation of the RP and the closely related Rank Sum (RS) statistics has been available in the RankProd Bioconductor package for several years. However, several recent advances in the understanding of the statistical foundations of the method have made a complete refactoring of the existing package desirable. Results: We implemented a completely refactored version of the RankProd package, which provides a more principled implementation of the statistics for unpaired datasets. Moreover,...

  3. Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects

    Peak, Corey M.; Reilly, Amanda L.; Azman, Andrew S.; Buckee, Caroline O.
    Background: Oral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings. However, vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy. As the supply and utilization of oral cholera vaccines grows, critical questions related to herd immunity are emerging, including: who should be targeted; when should revaccination be performed; and why have cholera outbreaks occurred in recently vaccinated populations? Methods and findings We use mathematical models to simulate routine and mass oral cholera vaccination in populations with varying degrees of migration, transmission intensity,...

  4. Fried food intake and risk of nonfatal acute myocardial infarction in the Costa Rica Heart Study

    Hu, Peter; Li, Yanping; Campos, Hannia
    Economic development in middle-income countries has led to a noticeable rise in the availability of commercial deep fried foods and lifestyles that require eating meals “on the go” and outside of the home. Yet, data from these countries where fried foods were traditionally prepared at home are scarce, despite several studies showing the potential adverse effects of fried food consumption on risk for heart disease. We aimed to examine whether consumption of fried foods inside or outside of the home is associated with an increased risk of myocardial infarction (MI) among Hispanic/Latinos living in Costa Rica. Participants were incident cases...

  5. 1609Plasma markers of immune activation likely reflect related but distinct processes of cellular immune activation in HIV-infected persons before and after suppression of viremia by antiretroviral therapy: ACTG 5260

    Kelesidis, Theodoros; Moser, Carlee; Mccomsey, Grace A.; Brown, Todd; Ribaudo, Heather; Tran, Thuy Tien T; Yang, Otto; Stein, James; Currier, Judith

  6. Social integration and healthy aging among U.S. women

    Li, Shanshan; Hagan, Kaitlin; Grodstein, Francine; VanderWeele, Tyler J.
    Background: Social integration has been related to risk of chronic diseases and mental health conditions. Purpose We investigated the association between social integration in midlife with subsequent health and well-being in aging. Methods: We included women from the Nurses' Health Study in the United States, who had no major chronic diseases in 1996 when we assessed social integration, using the Berkman-Syme Social Network Index. We defined healthy aging after 16 years of follow-up, when women ranged from 66 to 91 years, on the basis of survival along with 4 health criteria, assessed in 2012: no history of major chronic disease...

  7. Treatment Outcomes Among Older Human Immunodeficiency Virus-Infected Adults in Nigeria

    Agaba, Patricia A.; Meloni, Seema T.; Sule, Halima M.; Agbaji, Oche O.; Sagay, Atiene S.; Okonkwo, Prosper; Idoko, John A.; Kanki, Phyllis J.
    Abstract Background. Older age at initiation of combination antiretroviral therapy (cART) has been associated with poorer clinical outcomes. Our objectives were to compare outcomes between older and younger patients in our clinical cohort in Jos, Nigeria. Methods. This retrospective cohort study evaluated patients enrolled on cART at the Jos University Teaching Hospital, Nigeria between 2004 and 2012. We compared baseline and treatment differences between older (≥50 years) and younger (15–49 years) patients. Kaplan-Meier analysis and Cox proportional hazard models estimated survival and loss to follow-up (LTFU) and determined factors associated with these outcomes at 24 months. Results. Of 8352 patients,...

  8. High‐sensitivity C‐reactive protein, low‐density lipoprotein cholesterol and cardiovascular outcomes in patients with type 2 diabetes in the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial

    Hwang, You‐Cheol; Morrow, David A.; Cannon, Christopher P.; Liu, Yuyin; Bergenstal, Richard; Heller, Simon; Mehta, Cyrus; Cushman, William; Bakris, George L.; Zannad, Faiez; White, William B.
    Aims We sought to assess the risk of major adverse cardiovascular events (MACE) by utilizing high‐sensitivity C‐reactive protein (hsCRP) level and low‐density lipoprotein cholesterol (LDL‐C) in patients with type 2 diabetes and recent acute coronary syndrome. Materials and methods Study participants enrolled in the EXAMINE trial (Clinical trials registration number: NCT00968708) and were stratified by baseline hsCRP levels (<1, 1‐3 and >3 mg/L). They were also sub‐divided into 4 groups according to baseline hsCRP (≤3 or >3 mg/L) and achieved LDL‐C (<70 or ≥70 mg/dL) levels. Among 5380 patients, the MACE rate, a composite of cardiovascular death, non‐fatal acute myocardial...

  9. Does Type of Residential Housing Matter for Depressive Symptoms in the Aftermath of a Disaster? Insights From the Great East Japan Earthquake and Tsunami

    Sasaki, Yuri; Aida, Jun; Tsuji, Taishi; Miyaguni, Yasuhiro; Tani, Yukako; Koyama, Shihoko; Matsuyama, Yusuke; Sato, Yukihiro; Tsuboya, Toru; Nagamine, Yuiko; Kameda, Yoshihito; Saito, Tami; Kakimoto, Kazuhiro; Kondo, Katsunori; Kawachi, Ichiro
    Abstract The 2011 Great East Japan Earthquake and Tsunami resulted in widespread property destruction and over 250,000 displaced residents. We sought to examine whether the type of housing arrangement available to the affected victims was associated with a differential incidence of depressive symptoms. In this prospective cohort study, which comprised participants aged ≥65 years from Iwanuma as a part of the Japan Gerontological Evaluation Study, we had information about the residents’ mental health both before the disaster in 2010 and 2.5 years afterward. The Geriatric Depression Scale was used. Type of accommodation after the disaster was divided into 5 categories:...

  10. lme4qtl: linear mixed models with flexible covariance structure for genetic studies of related individuals

    Ziyatdinov, Andrey; Vázquez-Santiago, Miquel; Brunel, Helena; Martinez-Perez, Angel; Aschard, Hugues; Soria, Jose Manuel
    Background: Quantitative trait locus (QTL) mapping in genetic data often involves analysis of correlated observations, which need to be accounted for to avoid false association signals. This is commonly performed by modeling such correlations as random effects in linear mixed models (LMMs). The R package lme4 is a well-established tool that implements major LMM features using sparse matrix methods; however, it is not fully adapted for QTL mapping association and linkage studies. In particular, two LMM features are lacking in the base version of lme4: the definition of random effects by custom covariance matrices; and parameter constraints, which are essential...

  11. Lrp1 in osteoblasts controls osteoclast activity and protects against osteoporosis by limiting PDGF–RANKL signaling

    Bartelt, Alexander; Behler-Janbeck, Friederike; Beil, F. Timo; Koehne, Till; Müller, Brigitte; Schmidt, Tobias; Heine, Markus; Ochs, Laura; Yilmaz, Tayfun; Dietrich, Martin; Tuckermann, Jan P.; Amling, Michael; Herz, Joachim; Schinke, Thorsten; Heeren, Joerg; Niemeier, Andreas
    Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1 (Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass. Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption. Osteoblast Lrp1...

  12. ARMMs as a versatile platform for intracellular delivery of macromolecules

    Wang, Qiyu; Yu, Jiujiu; Kadungure, Tatenda; Beyene, Joseph; Zhang, Hong; Lu, Quan
    Majority of disease-modifying therapeutic targets are restricted to the intracellular space and are therefore not druggable using existing biologic modalities. The ability to efficiently deliver macromolecules inside target cells or tissues would greatly expand the current landscape of therapeutic targets for future generations of biologic drugs, but remains challenging. Here we report the use of extracellular vesicles, known as arrestin domain containing protein 1 [ARRDC1]-mediated microvesicles (ARMMs), for packaging and intracellular delivery of a myriad of macromolecules, including the tumor suppressor p53 protein, RNAs, and the genome-editing CRISPR-Cas9/guide RNA complex. We demonstrate selective recruitment of these macromolecules into ARMMs. When...

  13. Treatment gaps and potential cardiovascular risk reduction from expanded statin use in the US and England

    Ueda, Peter; Lung, Thomas Wai-Chun; Lu, Yuan; Salomon, Joshua A.; Rahimi, Kazem; Clarke, Philip; Danaei, Goodarz
    Background: The updated national guidelines for cardiovascular risk assessment and lipid modification in the UK and US expand the indications for statin therapy in primary prevention to adults with moderate risk of cardiovascular disease (CVD) but many adults at high CVD risk remain untreated in both countries. We set out to identify treatment gaps in English and American adults at moderate and high risk of cardiovascular disease (CVD), and to estimate the number of CVD events that would be prevented from expanding statin therapy to those who are currently untreated. Methods: We used nationally representative samples of 10,375 English adults...

  14. Dietary patterns in an elderly population and their relation with bone mineral density: the Rotterdam Study

    de Jonge, Ester A. L.; Rivadeneira, Fernando; Erler, Nicole S.; Hofman, Albert; Uitterlinden, André G.; Franco, Oscar H.; Kiefte-de Jong, Jessica C.
    Purpose Our aim was to identify dietary patterns that are associated with bone mineral density (BMD) against a background of relatively high dairy intake in elderly Dutch subjects. Methods: Participants were 55 years of age and older (n = 5144) who were enrolled in The Rotterdam Study, a population-based prospective cohort study. Baseline intake of 28 pre-defined food groups was determined using a validated food frequency questionnaire. Dietary patterns were identified using principal component analysis. BMD was measured using dual-energy X-ray absorptiometry at baseline and at three subsequent visits (between 1993 and 2004). Linear mixed modelling was used to longitudinally...

  15. Commentary: The value of life course epidemiology in low- and middle-income countries: an ageing perspective

    Tollman, Stephen M; Norris, Shane A; Berkman, Lisa F

  16. Income inequality and cardiovascular disease risk factors in a highly unequal country: a fixed-effects analysis from South Africa

    Adjaye-Gbewonyo, Kafui; Kawachi, Ichiro; Subramanian, S. V.; Avendano, Mauricio
    Background: Chronic stress associated with high income inequality has been hypothesized to increase CVD risk and other adverse health outcomes. However, most evidence comes from high-income countries, and there is limited evidence on the link between income inequality and biomarkers of chronic stress and risk for CVD. This study examines how changes in income inequality over recent years relate to changes in CVD risk factors in South Africa, home to some of the highest levels of income inequality globally. Methods: We linked longitudinal data from 9356 individuals interviewed in the 2008 and 2012 National Income Dynamics Study to district-level Gini...

  17. Role of survey response rates on valid inference: an application to HIV prevalence estimates

    Marino, Miguel; Pagano, Marcello
    Background: Nationally-representative surveys suggest that females have a higher prevalence of HIV than males in most African countries. Unfortunately, these results are made on the basis of surveys with non-ignorable missing data. This study evaluates the impact that differential survey nonresponse rates between males and females can have on the point estimate of the HIV prevalence ratio of these two classifiers. Methods: We study 29 Demographic and Health Surveys (DHS) from 2001 to 2010. Instead of employing often used multiple imputation models with a Missing at Random assumption that may not hold in this setting, we assess the effect of...

  18. Quantifying Transmission Heterogeneity Using Both Pathogen Phylogenies and Incidence Time Series

    Li, Lucy M.; Grassly, Nicholas C.; Fraser, Christophe
    Abstract Heterogeneity in individual-level transmissibility can be quantified by the dispersion parameter k of the offspring distribution. Quantifying heterogeneity is important as it affects other parameter estimates, it modulates the degree of unpredictability of an epidemic, and it needs to be accounted for in models of infection control. Aggregated data such as incidence time series are often not sufficiently informative to estimate k. Incorporating phylogenetic analysis can help to estimate k concurrently with other epidemiological parameters. We have developed an inference framework that uses particle Markov Chain Monte Carlo to estimate k and other epidemiological parameters using both incidence time...

  19. Antiretroviral Therapy Enrollment Characteristics and Outcomes Among HIV-Infected Adolescents and Young Adults Compared with Older Adults — Seven African Countries, 2004–2013

    Auld, Andrew F.; Agolory, Simon G.; Shiraishi, Ray W.; Wabwire-Mangen, Fred; Kwesigabo, Gideon; Mulenga, Modest; Hachizovu, Sebastian; Asadu, Emeka; Tuho, Moise Zanga; Ettiegne-Traore, Virginie; Mbofana, Francisco; Okello, Velephi; Azih, Charles; Denison, Julie A.; Tsui, Sharon; Koole, Olivier; Kamiru, Harrison; Nuwagaba-Biribonwoha, Harriet; Alfredo, Charity; Jobarteh, Kebba; Odafe, Solomon; Onotu, Dennis; Ekra, Kunomboa A.; Kouakou, Joseph S.; Ehrenkranz, Peter; Bicego, George; Torpey, Kwasi; Mukadi, Ya Diul; van Praag, Eric; Menten, Joris; Mastro, Timothy; Hamilton, Carol Dukes; Swaminathan, Mahesh; Dokubo, E. Kainne; Baughman, Andrew L.; Spira, Thomas; Colebunders, Robert; Bangsberg, David; Marlink, Richard; Zee, Aaron; Kaplan, Jonathan; Ellerbrock, Tedd V.

  20. Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

    Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B.; Barrowdale, Daniel; Dennis, Joe; McGuffog, Lesley; Soucy, Penny; Leslie, Goska; Rizzolo, Piera; Navazio, Anna Sara; Valentini, Virginia; Zelli, Veronica; Lee, Andrew; Amin Al Olama, Ali; Tyrer, Jonathan P.; Southey, Melissa; John, Esther M.; Conner, Thomas A.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Steele, Linda; Ding, Yuan Chun; Neuhausen, Susan L.; Hansen, Thomas V.O.; Osorio, Ana; Weitzel, Jeffrey N.; Toss, Angela; Medici, Veronica; Cortesi, Laura; Zanna, Ines; Palli, Domenico; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Azzollini, Jacopo; Viel, Alessandra; Cini, Giulia; Damante, Giuseppe; Tommasi, Stefania; Peterlongo, Paolo; Fostira, Florentia; Hamann, Ute; Evans, D. Gareth; Henderson, Alex; Brewer, Carole; Eccles, Diana; Cook, Jackie; Ong, Kai-ren; Walker, Lisa; Side, Lucy E.; Porteous, Mary E.; Davidson, Rosemarie; Hodgson, Shirley; Frost, Debra; Adlard, Julian; Izatt, Louise; Eeles, Ros; Ellis, Steve; Tischkowitz, Marc; Godwin, Andrew K.; Meindl, Alfons; Gehrig, Andrea; Dworniczak, Bernd; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Hauke, Jan; Rhiem, Kerstin; Kast, Karin; Arnold, Norbert; Ditsch, Nina; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Wand, Dorothea; Lasset, Christine; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Damiola, Francesca; Barjhoux, Laure; Mazoyer, Sylvie; Van Heetvelde, Mattias; Poppe, Bruce; De Leeneer, Kim; Claes, Kathleen B.M.; de la Hoya, Miguel; Garcia-Barberan, Vanesa; Caldes, Trinidad; Perez Segura, Pedro; Kiiski, Johanna I.; Aittomäki, Kristiina; Khan, Sofia; Nevanlinna, Heli; van Asperen, Christi J.; Vaszko, Tibor; Kasler, Miklos; Olah, Edith; Balmaña, Judith; Gutiérrez-Enríquez, Sara; Diez, Orland; Teulé, Alex; Izquierdo, Angel; Darder, Esther; Brunet, Joan; Del Valle, Jesús; Feliubadalo, Lidia; Pujana, Miquel Angel; Lazaro, Conxi; Arason, Adalgeir; Agnarsson, Bjarni A.; Johannsson, Oskar Th.; Barkardottir, Rosa B.; Alducci, Elisa; Tognazzo, Silvia; Montagna, Marco; Teixeira, Manuel R.; Pinto, Pedro; Spurdle, Amanda B.; Holland, Helene; Lee, Jong Won; Lee, Min Hyuk; Lee, Jihyoun; Kim, Sung-Won; Kang, Eunyoung; Kim, Zisun; Sharma, Priyanka; Rebbeck, Timothy R.; Vijai, Joseph; Robson, Mark; Lincoln, Anne; Musinsky, Jacob; Gaddam, Pragna; Tan, Yen Y.; Berger, Andreas; Singer, Christian F.; Loud, Jennifer T.; Greene, Mark H.; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L.; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Nielsen, Henriette Roed; Skytte, Anne-Bine; Sunde, Lone; Jensen, Uffe Birk; Pedersen, Inge Sokilde; Krogh, Lotte; Kruse, Torben A.; Caligo, Maria A.; Yoon, Sook-Yee; Teo, Soo-Hwang; von Wachenfeldt, Anna; Huo, Dezheng; Nielsen, Sarah M.; Olopade, Olufunmilayo I.; Nathanson, Katherine L.; Domchek, Susan M.; Lorenchick, Christa; Jankowitz, Rachel C.; Campbell, Ian; James, Paul; Mitchell, Gillian; Orr, Nick; Park, Sue Kyung; Thomassen, Mads; Offit, Kenneth; Couch, Fergus J.; Simard, Jacques; Easton, Douglas F.; Chenevix-Trench, Georgia; Schmutzler, Rita K.; Antoniou, Antonis C.; Ottini, Laura
    Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated—for the first time to our knowledge—associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers...

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