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1.  Racial Variations in the Prevalence of Refractive Errors in the United States: The Multi-Ethnic Study of Atherosclerosis 
American journal of ophthalmology  2013;155(6):1129-1138.e1.
PURPOSE
To describe racial variations in the prevalence of refractive errors among adult white, Chinese, Hispanic, and black subjects in the United States.
DESIGN
Cross-sectional data from a prospective cohort study—the Multi-Ethnic Study of Atherosclerosis (MESA).
METHODS
A total of 6000 adults aged 45 to 84 years living in the United States participated in the study. Refractive error was assessed, without cycloplegia, in both eyes of all participants using an autorefractor. After excluding eyes with cataract, cataract surgery, or previous refractive surgery, the eye with the larger absolute spherical equivalent (SE) value for each participant was used to classify refractive error. Any myopia was defined as SE of −1.0 diopters (D) or less; high myopia was defined as SE of −5.0 D or less; any hyperopia was defined as SE of +1.0 D or more; clinically significant hyperopia was defined as SE of +3.0 D or more. Astigmatism was defined as a cylinder value of +1.0 D or more.
RESULTS
After excluding 508 participants with cataracts in both eyes, 838 participants with cataract surgery, 90 participants with laser refractive surgery, and 134 participants who refused to remove their contact lenses for the refraction measurement, 4430 adults with refractive error assessment in at least 1 eye contributed to the analysis. The prevalence of myopia among MESA participants was 25.1%, with lowest rates in Hispanic participants (14.2%), followed by black (21.5%) and white participants (31.0%), and highest rates in Chinese participants (37.2%). The overall rates of high myopia and astigmatism were 4.6% and 45.0%, respectively, with Chinese subjects also having the highest rates of high myopia (11.8%) and astigmatism (53.4%). The overall prevalence of any hyperopia was 38.2% and clinically significant hyperopia was 6.1%, with Hispanic participants having the highest rates of hyperopia (50.2%) and clinically significant hyperopia (8.8%). In multivariate analyses adjusting for age, sex, race, and study site, higher education level, being employed, and being taller were associated with a higher prevalence of myopia. In contrast, lower educational level and being shorter were associated with a higher prevalence of hyperopia.
CONCLUSIONS
Myopia and astigmatism were most prevalent in the Chinese population, with Chinese subjects having 3 times the prevalence of myopia as Hispanic subjects. Hyperopia was most common in Hispanic subjects. These findings provide further insights into variations in refractive errors among different racial groups and have important implications for the eye care services in the United States.
doi:10.1016/j.ajo.2013.01.009
PMCID: PMC3759975  PMID: 23453694
2.  Pulmonary Hyperinflation and Left Ventricular Mass 
Circulation  2013;127(14):1503-1511e6.
Background
Left ventricular (LV) mass is an important predictor of heart failure and cardiovascular mortality, yet determinants of LV mass are incompletely understood. Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) may contribute to changes in intrathoracic pressure that increase LV wall stress. We therefore hypothesized that residual lung volume in COPD would be associated with greater LV mass.
Methods and results
The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited smokers aged 50–79 years who were free of clinical cardiovascular disease. LV mass was measured by cardiac magnetic resonance. Pulmonary function testing was performed according to guidelines. Regression models were used to adjust for age, sex, body size, blood pressure and other cardiac risk factors.
Among 119 MESA COPD Study participants, mean age was 69±6 years, 55% were male and 65% had COPD, mostly of mild or moderate severity. Mean LV mass was 128±34 grams. Residual lung volume was independently associated with greater LV mass (7.2 grams per standard deviation increase in residual volume; 95% CI 2.2 to 12; P=0.004), and was similar in magnitude to that of systolic blood pressure (7.6 grams per standard deviation increase in systolic blood pressure, 95% CI 4.3 to 11 grams; p<0.001). Similar results were observed for LV mass to end-diastolic volume ratio (p=0.02) and with hyperinflation measured as residual volume to total lung capacity ratio (P=0.009).
Conclusions
Pulmonary hyperinflation, as measured by residual lung volume or residual lung volume to total lung capacity ratio, is associated with greater LV mass.
doi:10.1161/CIRCULATIONAHA.113.001653
PMCID: PMC4018203  PMID: 23493320
Left ventricular mass; hyperinflation; chronic obstructive pulmonary disease
3.  Pulse Pressure and Subclinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis 
American Journal of Hypertension  2013;26(5):636-642.
BACKGROUND
Brachial pulse pressure (PP) has been found to be associated with markers of subclinical cardiovascular disease, including carotid intima–media thickness and left-ventricular mass index (LVMI), but it is unclear whether these associations are independent of traditional cardiovascular risk factors and of the steady, nonpulsatile component of blood pressure (BP). Moreover, it is unknown whether these associations are modified by gender, age, or race/ethnicity.
METHODS
We used multivariate linear regression models to assess the relationship between brachial PP and three markers of subclinical cardiovascular disease (CVD) (common carotid intima–media thickness (CC-IMT), internal carotid intima–media thickness (IC-IMT), and LVMI) in four race/ethnic groups in the Multi-Ethnic Study of Atherosclerosis. The models were adjusted for traditional Framingham risk factors (age, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, diabetes, smoking status), use of lipid-lowering medication, use of antihypertensive medication, study site, and mean arterial pressure (MAP).
RESULTS
The assessment was done on 6,776 participants (2,612 non-Hispanic white, 1,870 African-American, 1,494 Hispanic, and 800 Chinese persons). The associations between brachial PP and CC-IMT, IC-IMT, and LVMI were significant in fully adjusted models. The three subclinical markers also showed significant interactions with gender (P < 0.0001), with stronger interactions in men. There was an interaction with age for LVMI (P = 0.004) and IC-IMT (P = 0.008). Race/ethnicity modified the association of PP with CC-IMT.
CONCLUSIONS
Brachial PP was independently associated with subclinical CVD after adjustment for cardiovascular risk factors and mean arterial pressure (MAP). The strength of the association differed significantly for strata of gender, age, and race/ethnicity.
doi:10.1093/ajh/hps092
PMCID: PMC3657481  PMID: 23388832
pulse pressare; subclinical cardiovascular disease; carotid intima–media thickness; left ventricular mass index; aging; hypertension; arterial stiffness; blood pressure.
4.  Ten-Year Trends in Coronary Calcification in Individuals without Clinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis 
PLoS ONE  2014;9(4):e94916.
Background
Coronary heart disease (CHD) incidence has declined significantly in the US, as have levels of major coronary risk factors, including LDL-cholesterol, hypertension and smoking, but whether trends in subclinical atherosclerosis mirror these trends is not known.
Methods and Findings
To describe recent secular trends in subclinical atherosclerosis as measured by serial evaluations of coronary artery calcification (CAC) prevalence in a population over 10 years, we measured CAC using computed tomography (CT) and CHD risk factors in five serial cross-sectional samples of men and women from four race/ethnic groups, aged 55–84 and without clinical cardiovascular disease, who were members of Multi-Ethnic Study of Atherosclerosis (MESA) cohort from 2000 to 2012. Sample sizes ranged from 1062 to 4837. After adjusting for age, gender, and CT scanner, the prevalence of CAC increased across exams among African Americans, whose prevalence of CAC was 52.4% in 2000–02, 50.4% in 2003–04, 60.0% is 2005–06, 57.4% in 2007–08, and 61.3% in 2010–12 (p for trend <0.001). The trend was strongest among African Americans aged 55–64 [prevalence ratio for 2010–12 vs. 2000–02, 1.59 (95% confidence interval 1.06, 2.39); p = 0.005 for trend across exams]. There were no consistent trends in any other ethnic group. Risk factors generally improved in the cohort, and adjustment for risk factors did not change trends in CAC prevalence.
Conclusions
There was a significant secular trend towards increased prevalence of CAC over 10 years among African Americans and no change in three other ethnic groups. Trends did not reflect concurrent general improvement in risk factors. The trend towards a higher prevalence of CAC in African Americans suggests that CHD risk in this population is not improving relative to other groups.
doi:10.1371/journal.pone.0094916
PMCID: PMC3990562  PMID: 24743658
5.  Mental and Physical Health Consequences of the September 11, 2001 (9/11) Attacks in Primary Care: A Longitudinal Study 
Journal of traumatic stress  2013;26(1):45-55.
The magnitude of the September 11, 2001 (9/11) attacks was without precedent in the United States, but long-term longitudinal research on its health consequences for primary care patients is limited. We assessed the prevalence and exposure-related determinants of mental disorders, functioning, general medical conditions and service utilization, 1 and 4 years after the 9/11 attacks, in an urban primary care cohort (N = 444) in Manhattan. Although the prevalence of posttraumatic stress disorder (PTSD) and levels of functional impairment declined over time, a substantial increase in suicidal ideation and missed work was observed. Most medical outcomes and service utilization indicators demonstrated a short-term increase after the 9/11 attacks (mean change of +20.3%), followed by a minor decrease in the subsequent year (mean change of −3.2%). Loss of a close person was associated with the highest risk for poor mental health and functional status over time. These findings highlight the importance of longitudinal assessments of mental, functional, and medical outcomes in urban populations exposed to mass trauma and terrorism.
doi:10.1002/jts.21767
PMCID: PMC3685149  PMID: 23319335
7.  Assessing Risk Prediction Models Using Individual Participant Data From Multiple Studies 
Pennells, Lisa | Kaptoge, Stephen | White, Ian R. | Thompson, Simon G. | Wood, Angela M. | Tipping, Robert W. | Folsom, Aaron R. | Couper, David J. | Ballantyne, Christie M. | Coresh, Josef | Goya Wannamethee, S. | Morris, Richard W. | Kiechl, Stefan | Willeit, Johann | Willeit, Peter | Schett, Georg | Ebrahim, Shah | Lawlor, Debbie A. | Yarnell, John W. | Gallacher, John | Cushman, Mary | Psaty, Bruce M. | Tracy, Russ | Tybjærg-Hansen, Anne | Price, Jackie F. | Lee, Amanda J. | McLachlan, Stela | Khaw, Kay-Tee | Wareham, Nicholas J. | Brenner, Hermann | Schöttker, Ben | Müller, Heiko | Jansson, Jan-Håkan | Wennberg, Patrik | Salomaa, Veikko | Harald, Kennet | Jousilahti, Pekka | Vartiainen, Erkki | Woodward, Mark | D'Agostino, Ralph B. | Bladbjerg, Else-Marie | Jørgensen, Torben | Kiyohara, Yutaka | Arima, Hisatomi | Doi, Yasufumi | Ninomiya, Toshiharu | Dekker, Jacqueline M. | Nijpels, Giel | Stehouwer, Coen D. A. | Kauhanen, Jussi | Salonen, Jukka T. | Meade, Tom W. | Cooper, Jackie A. | Cushman, Mary | Folsom, Aaron R. | Psaty, Bruce M. | Shea, Steven | Döring, Angela | Kuller, Lewis H. | Grandits, Greg | Gillum, Richard F. | Mussolino, Michael | Rimm, Eric B. | Hankinson, Sue E. | Manson, JoAnn E. | Pai, Jennifer K. | Kirkland, Susan | Shaffer, Jonathan A. | Shimbo, Daichi | Bakker, Stephan J. L. | Gansevoort, Ron T. | Hillege, Hans L. | Amouyel, Philippe | Arveiler, Dominique | Evans, Alun | Ferrières, Jean | Sattar, Naveed | Westendorp, Rudi G. | Buckley, Brendan M. | Cantin, Bernard | Lamarche, Benoît | Barrett-Connor, Elizabeth | Wingard, Deborah L. | Bettencourt, Richele | Gudnason, Vilmundur | Aspelund, Thor | Sigurdsson, Gunnar | Thorsson, Bolli | Kavousi, Maryam | Witteman, Jacqueline C. | Hofman, Albert | Franco, Oscar H. | Howard, Barbara V. | Zhang, Ying | Best, Lyle | Umans, Jason G. | Onat, Altan | Sundström, Johan | Michael Gaziano, J. | Stampfer, Meir | Ridker, Paul M. | Michael Gaziano, J. | Ridker, Paul M. | Marmot, Michael | Clarke, Robert | Collins, Rory | Fletcher, Astrid | Brunner, Eric | Shipley, Martin | Kivimäki, Mika | Ridker, Paul M. | Buring, Julie | Cook, Nancy | Ford, Ian | Shepherd, James | Cobbe, Stuart M. | Robertson, Michele | Walker, Matthew | Watson, Sarah | Alexander, Myriam | Butterworth, Adam S. | Angelantonio, Emanuele Di | Gao, Pei | Haycock, Philip | Kaptoge, Stephen | Pennells, Lisa | Thompson, Simon G. | Walker, Matthew | Watson, Sarah | White, Ian R. | Wood, Angela M. | Wormser, David | Danesh, John
American Journal of Epidemiology  2013;179(5):621-632.
Individual participant time-to-event data from multiple prospective epidemiologic studies enable detailed investigation into the predictive ability of risk models. Here we address the challenges in appropriately combining such information across studies. Methods are exemplified by analyses of log C-reactive protein and conventional risk factors for coronary heart disease in the Emerging Risk Factors Collaboration, a collation of individual data from multiple prospective studies with an average follow-up duration of 9.8 years (dates varied). We derive risk prediction models using Cox proportional hazards regression analysis stratified by study and obtain estimates of risk discrimination, Harrell's concordance index, and Royston's discrimination measure within each study; we then combine the estimates across studies using a weighted meta-analysis. Various weighting approaches are compared and lead us to recommend using the number of events in each study. We also discuss the calculation of measures of reclassification for multiple studies. We further show that comparison of differences in predictive ability across subgroups should be based only on within-study information and that combining measures of risk discrimination from case-control studies and prospective studies is problematic. The concordance index and discrimination measure gave qualitatively similar results throughout. While the concordance index was very heterogeneous between studies, principally because of differing age ranges, the increments in the concordance index from adding log C-reactive protein to conventional risk factors were more homogeneous.
doi:10.1093/aje/kwt298
PMCID: PMC3927974  PMID: 24366051
C index; coronary heart disease; D measure; individual participant data; inverse variance; meta-analysis; risk prediction; weighting
8.  IS THERE A CIRCADIAN VARIATION OF EPILEPTIFORM ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY? 
Epilepsy & behavior : E&B  2009;16(3):10.1016/j.yebeh.2009.08.022.
Epileptiform abnormalities often occur at specific times of day or night, possibly attributable to state of consciousness (sleep vs. wake) and/or influences from the endogenous circadian pacemaker. In this pilot study we tested for the existence of circadian variation of interictal epileptiform discharges (IED), independent of changes in state, environment, or behavior. Five patients with generalized epilepsy underwent a protocol whereby their sleep/wake schedule was evenly distributed across the circadian cycle while undergoing full montage electroencephalography and hourly plasma melatonin measurements. Light was <8 lux to prevent circadian entrainment. All patients completed the protocol testifying to its feasibility. All patients had normal circadian rhythmicity of plasma melatonin relative to their habitual sleep times. In the three patients with sufficient IED to assess variability, most IED occurred during NREM (ratio NREM: Wake = 14:1; P<0.001). In both patients who had NREM at all circadian phases, there was apparent circadian variation in IED but with different phases relative to peak melatonin.
doi:10.1016/j.yebeh.2009.08.022
PMCID: PMC3861150  PMID: 19786369
circadian; epilepsy; idiopathic generalized epilepsy; sleep; nocturnal; interictal discharges; sleep/wake distribution
9.  Telemedicine Home Blood Pressure Measurements Predict Progression of Albuminuria in Elderly People with Diabetes 
Hypertension  2008;51(5):10.1161/HYPERTENSIONAHA.107.108589.
We assessed whether home blood pressure monitoring improved the prediction of progression of albuminuria when added to office measurements, and compared it to ambulatory blood pressure monitoring in a multiethnic cohort of older people (n=392) with diabetes mellitus, without macroalbuminuria, participating in the telemedicine arm of the Informatics for Diabetes Education and Telemedicine (IDEATel) study. Albuminuria was assessed by measuring the spot urine albumin-to-creatinine ratio at baseline and annually for three years. Ambulatory sleep/wake systolic blood pressure ratio was categorized as dipping (ratio≤0.9), non-dipping (ratio>0.9 -1), and nocturnal rise (ratio>1). In a repeated measures mixed linear model, after adjustment that included office pulse pressure, home pulse pressure was independently associated with higher follow-up albumin-to-creatinine ratio (p=0.001). That association persisted (p=0.01) after adjusting for 24-hour pulse pressure, and nocturnal rise, which were also independent predictors (p=0.02 and p=0.03, respectively). Cox proportional hazards models examined progression of albuminuria (n=74) as defined by cutoff values used by clinicians. After adjustment for office pulse pressure the hazards ratio (95% CI) per 10 mmHg increment of home pulse pressure was 1.34 (1.1-1.7), p=0.01. Home pulse pressure was not an independent predictor in the model including ambulatory monitoring data—a nocturnal rise was the only independent predictor (p=0.035). However, Cox models built separately for home pulse pressure and ambulatory monitoring exhibited similar calibration and discrimination. In conclusion, home blood pressure adds to office measurements and may substitute for ambulatory monitoring to predict worsening of albuminuria in elderly people with diabetes.
doi:10.1161/HYPERTENSIONAHA.107.108589
PMCID: PMC3855674  PMID: 18378859
Albuminuria; Diabetes mellitus; Home Blood Pressure; Ambulatory Blood Pressure
10.  Retinal Microvascular Signs and Risk of Stroke: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Background and Purpose
Small vessel disease contributes to the pathophysiology of stroke, and retinal microvascular signs have been linked to risk of stroke. We examined the relationship of retinal signs with incident stroke in a multi-ethnic cohort.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study that enrolled participants without clinical cardiovascular diseases from six United States communities between 2000–02. Of the participants, 4,849 (71.2%) had fundus photography performed in 2002–04. Retinopathy and retinal vessel caliber were assessed from retinal images. Stroke risk factors including high-sensitivity C-reactive protein (hsCRP), carotid artery intima-media thickness (IMT) and coronary artery calcium (CAC) were measured using standardized protocols. Incident stroke was confirmed from medical record review and death certificates.
Results
After 6 years of follow-up, there were 62 incident strokes. Narrower retinal arteriolar caliber was associated with increased risk of stroke after adjusting for conventional cardiovascular risk factors (adjusted incidence rate ratio [IRR] 2.83, 95% confidence interval [CI] 1.34–5.95, p=0.006; adjusted hazard ratio [HR] 3.01, 95% CI 1.29–6.99, p=0.011). Retinopathy in persons without diabetes was associated with increased risk of stroke (adjusted IRR 2.96, 95% CI 1.50–5.84, p=0.002; adjusted HR 3.07, 95%CI 1.17–8.09, p=0.023). These associations remained significant after adjusting for hsCRP, carotid IMT or CAC.
Conclusions
Narrower retinal arteriolar caliber and retinopathy in non-diabetic persons were associated with increased risk of stroke in this relatively healthy multi-ethnic cohort independent of traditional risk factors and measures of atherosclerosis. The association between narrower retinal arteriolar caliber and stroke warrants further investigation.
doi:10.1161/STROKEAHA.112.673335
PMCID: PMC3508325  PMID: 23111439
Stroke; Retinal microvascular signs; Retinopathy; Retinal vessel caliber
11.  Screening colonoscopy bowel preparation: experience in an urban minority population 
Methods:
Suboptimal bowel preparation, present in over 20% of colonoscopies, can severely compromise the effectiveness of the colonoscopy procedure. We surveyed 93 primarily urban minority men and women who underwent asymptomatic ‘screening’ colonoscopy regarding their precolonoscopy bowel-preparation experience.
Results:
Print materials alone (39.8%) and in-person verbal instructions alone (35.5%) were reportedly the most common modes of instruction from the gastroenterologists. Liquid-containing laxative (70.6%) was the most common laxative agent; a clear liquid diet (69.6%) the most common dietary restriction. Almost half of the participants mentioned ‘getting the laxative down’ as one of the hardest parts of the preparation; 40.9% mentioned dietary restrictions. The 24.7% who mentioned ‘understanding the instructions’ as one of the hardest parts were more likely to be non-US born and to have lower education and income. There was no relationship between difficulty in understanding instructions and mode of instruction or preparation protocol. One quarter suggested that a smaller volume and/or more palatable liquid would have made the preparation easier. Three quarters agreed that it would have been helpful to have someone to guide them through the preparation process.
Conclusions:
These findings suggest a variety of opportunities for both physician- and patient-directed educational interventions to promote higher rates of optimal colonoscopy bowel preparation.
doi:10.1177/1756283X13498661
PMCID: PMC3808570  PMID: 24179480
Colorectal cancer screening; colonoscopy; bowel preparation
12.  Image Corruption Detection in Diffusion Tensor Imaging for Post-Processing and Real-Time Monitoring 
PLoS ONE  2013;8(10):e49764.
Due to the high sensitivity of diffusion tensor imaging (DTI) to physiological motion, clinical DTI scans often suffer a significant amount of artifacts. Tensor-fitting-based, post-processing outlier rejection is often used to reduce the influence of motion artifacts. Although it is an effective approach, when there are multiple corrupted data, this method may no longer correctly identify and reject the corrupted data. In this paper, we introduce a new criterion called “corrected Inter-Slice Intensity Discontinuity” (cISID) to detect motion-induced artifacts. We compared the performance of algorithms using cISID and other existing methods with regard to artifact detection. The experimental results show that the integration of cISID into fitting-based methods significantly improves the retrospective detection performance at post-processing analysis. The performance of the cISID criterion, if used alone, was inferior to the fitting-based methods, but cISID could effectively identify severely corrupted images with a rapid calculation time. In the second part of this paper, an outlier rejection scheme was implemented on a scanner for real-time monitoring of image quality and reacquisition of the corrupted data. The real-time monitoring, based on cISID and followed by post-processing, fitting-based outlier rejection, could provide a robust environment for routine DTI studies.
doi:10.1371/journal.pone.0049764
PMCID: PMC3808367  PMID: 24204551
13.  Adult height and the risk of cause-specific death and vascular morbidity in 1 million people: individual participant meta-analysis 
Wormser, David | Angelantonio, Emanuele Di | Kaptoge, Stephen | Wood, Angela M | Gao, Pei | Sun, Qi | Walldius, Göran | Selmer, Randi | Verschuren, WM Monique | Bueno-de-Mesquita, H Bas | Engström, Gunnar | Ridker, Paul M | Njølstad, Inger | Iso, Hiroyasu | Holme, Ingar | Giampaoli, Simona | Tunstall-Pedoe, Hugh | Gaziano, J Michael | Brunner, Eric | Kee, Frank | Tosetto, Alberto | Meisinger, Christa | Brenner, Hermann | Ducimetiere, Pierre | Whincup, Peter H | Tipping, Robert W | Ford, Ian | Cremer, Peter | Hofman, Albert | Wilhelmsen, Lars | Clarke, Robert | de Boer, Ian H | Jukema, J Wouter | Ibañez, Alejandro Marín | Lawlor, Debbie A | D'Agostino, Ralph B | Rodriguez, Beatriz | Casiglia, Edoardo | Stehouwer, Coen DA | Simons, Leon A | Nietert, Paul J | Barrett-Connor, Elizabeth | Panagiotakos, Demosthenes B | Björkelund, Cecilia | Strandberg, Timo E | Wassertheil-Smoller, Sylvia | Blazer, Dan G | Meade, Tom W | Welin, Lennart | Svärdsudd, Kurt | Woodward, Mark | Nissinen, Aulikki | Kromhout, Daan | Jørgensen, Torben | Tilvis, Reijo S | Guralnik, Jack M | Rosengren, Annika | Taylor, James O | Kiechl, Stefan | Dagenais, Gilles R | Gerry, F | Fowkes, R | Wallace, Robert B | Khaw, Kay-Tee | Shaffer, Jonathan A | Visser, Marjolein | Kauhanen, Jussi | Salonen, Jukka T | Gallacher, John | Ben-Shlomo, Yoav | Kitamura, Akihiko | Sundström, Johan | Wennberg, Patrik | Kiyohara, Yutaka | Daimon, Makoto | de la Cámara, Agustin Gómez | Cooper, Jackie A | Onat, Altan | Devereux, Richard | Mukamal, Kenneth J | Dankner, Rachel | Knuiman, Matthew W | Crespo, Carlos J | Gansevoort, Ron T | Goldbourt, Uri | Nordestgaard, Børge G | Shaw, Jonathan E | Mussolino, Michael | Nakagawa, Hidaeki | Fletcher, Astrid | Kuller, Lewis H | Gillum, Richard F | Gudnason, Vilmundur | Assmann, Gerd | Wald, Nicholas | Jousilahti, Pekka R | Greenland, Philip | Trevisan, Maurizio | Ulmer, Hanno | Butterworth, Adam S | Folsom, Aaron R | Davey-Smith, George | Hu, Frank B | Danesh, John | Tipping, Robert W | Ford, Charles E | Simpson, Lara M | Walldius, Göran | Jungner, Ingmar | Folsom, Aaron R | Demerath, Ellen W | Franceschini, Nora | Lutsey, Pamela L | Panagiotakos, Demosthenes B | Pitsavos, Christos | Chrysohoou, Christina | Stefanadis, Christodoulos | Shaw, Jonathan E | Atkins, Robert | Zimmet, Paul Z | Barr, Elizabeth LM | Knuiman, Matthew W | Whincup, Peter H | Wannamethee, S Goya | Morris, Richard W | Willeit, Johann | Kiechl, Stefan | Weger, Siegfried | Oberhollenzer, Friedrich | Wald, Nicholas | Ebrahim, Shah | Lawlor, Debbie A | Gallacher, John | Ben-Shlomo, Yoav | Yarnell, John WG | Casiglia, Edoardo | Tikhonoff, Valérie | Greenland, Philip | Shay, Christina M | Garside, Daniel B | Nietert, Paul J | Sutherland, Susan E | Bachman, David L | Keil, Julian E | de Boer, Ian H | Kizer, Jorge R | Psaty, Bruce M | Mukamal, Kenneth J | Nordestgaard, Børge G | Tybjærg-Hansen, Anne | Jensen, Gorm B | Schnohr, Peter | Giampaoli, Simona | Palmieri, Luigi | Panico, Salvatore | Pilotto, Lorenza | Vanuzzo, Diego | de la Cámara, Agustin Gómez | Simons, Leon A | Simons, Judith | McCallum, John | Friedlander, Yechiel | Gerry, F | Fowkes, R | Price, Jackie F | Lee, Amanda J | Taylor, James O | Guralnik, Jack M | Phillips, Caroline L | Wallace, Robert B | Kohout, Frank J | Cornoni-Huntley, Joan C | Guralnik, Jack M | Blazer, Dan G | Guralnik, Jack M | Phillips, Caroline L | Phillips, Caroline L | Guralnik, Jack M | Khaw, Kay-Tee | Wareham, Nicholas J | Brenner, Hermann | Schöttker, Ben | Müller, Heiko | Rothenbacher, Dietrich | Wennberg, Patrik | Jansson, Jan-Håkan | Nissinen, Aulikki | Donfrancesco, Chiara | Giampaoli, Simona | Woodward, Mark | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | D'Agostino, Ralph B | Vasan, Ramachandran S | Fox, Caroline S | Pencina, Michael J | Daimon, Makoto | Oizumi, Toshihide | Kayama, Takamasa | Kato, Takeo | Bladbjerg, Else-Marie | Jørgensen, Torben | Møller, Lars | Jespersen, Jørgen | Dankner, Rachel | Chetrit, Angela | Lubin, Flora | Svärdsudd, Kurt | Eriksson, Henry | Welin, Lennart | Lappas, Georgios | Rosengren, Annika | Lappas, Georgios | Welin, Lennart | Svärdsudd, Kurt | Eriksson, Henry | Lappas, Georgios | Bengtsson, Calle | Lissner, Lauren | Björkelund, Cecilia | Cremer, Peter | Nagel, Dorothea | Strandberg, Timo E | Salomaa, Veikko | Tilvis, Reijo S | Miettinen, Tatu A | Tilvis, Reijo S | Strandberg, Timo E | Kiyohara, Yutaka | Arima, Hisatomi | Doi, Yasufumi | Ninomiya, Toshiharu | Rodriguez, Beatriz | Dekker, Jacqueline M | Nijpels, Giel | Stehouwer, Coen DA | Hu, Frank B | Sun, Qi | Rimm, Eric B | Willett, Walter C | Iso, Hiroyasu | Kitamura, Akihiko | Yamagishi, Kazumasa | Noda, Hiroyuki | Goldbourt, Uri | Vartiainen, Erkki | Jousilahti, Pekka R | Harald, Kennet | Salomaa, Veikko | Kauhanen, Jussi | Salonen, Jukka T | Kurl, Sudhir | Tuomainen, Tomi-Pekka | Poppelaars, Jan L | Deeg, Dorly JH | Visser, Marjolein | Meade, Tom W | De Stavola, Bianca Lucia | Hedblad, Bo | Nilsson, Peter | Engström, Gunnar | Verschuren, WM Monique | Blokstra, Anneke | de Boer, Ian H | Shea, Steven J | Meisinger, Christa | Thorand, Barbara | Koenig, Wolfgang | Döring, Angela | Verschuren, WM Monique | Blokstra, Anneke | Bueno-de-Mesquita, H Bas | Wilhelmsen, Lars | Rosengren, Annika | Lappas, Georgios | Fletcher, Astrid | Nitsch, Dorothea | Kuller, Lewis H | Grandits, Greg | Tverdal, Aage | Selmer, Randi | Nystad, Wenche | Mussolino, Michael | Gillum, Richard F | Hu, Frank B | Sun, Qi | Manson, JoAnn E | Rimm, Eric B | Hankinson, Susan E | Meade, Tom W | De Stavola, Bianca Lucia | Cooper, Jackie A | Bauer, Kenneth A | Davidson, Karina W | Kirkland, Susan | Shaffer, Jonathan A | Shimbo, Daichi | Kitamura, Akihiko | Iso, Hiroyasu | Sato, Shinichi | Holme, Ingar | Selmer, Randi | Tverdal, Aage | Nystad, Wenche | Nakagawa, Hidaeki | Miura, Katsuyuki | Sakurai, Masaru | Ducimetiere, Pierre | Jouven, Xavier | Bakker, Stephan JL | Gansevoort, Ron T | van der Harst, Pim | Hillege, Hans L | Crespo, Carlos J | Garcia-Palmieri, Mario R | Kee, Frank | Amouyel, Philippe | Arveiler, Dominique | Ferrières, Jean | Schulte, Helmut | Assmann, Gerd | Jukema, J Wouter | de Craen, Anton JM | Sattar, Naveed | Stott, David J | Cantin, Bernard | Lamarche, Benoît | Després, Jean-Pierre | Dagenais, Gilles R | Barrett-Connor, Elizabeth | Bergstrom, Jaclyn | Bettencourt, Richele R | Buisson, Catherine | Gudnason, Vilmundur | Aspelund, Thor | Sigurdsson, Gunnar | Thorsson, Bolli | Trevisan, Maurizio | Hofman, Albert | Ikram, M Arfan | Tiemeier, Henning | Witteman, Jacqueline CM | Tunstall-Pedoe, Hugh | Tavendale, Roger | Lowe, Gordon DO | Woodward, Mark | Devereux, Richard | Yeh, Jeun-Liang | Ali, Tauqeer | Calhoun, Darren | Ben-Shlomo, Yoav | Davey-Smith, George | Onat, Altan | Can, Günay | Nakagawa, Hidaeki | Sakurai, Masaru | Nakamura, Koshi | Morikawa, Yuko | Njølstad, Inger | Mathiesen, Ellisiv B | Løchen, Maja-Lisa | Wilsgaard, Tom | Sundström, Johan | Ingelsson, Erik | Michaëlsson, Karl | Cederholm, Tommy | Gaziano, J Michael | Buring, Julie | Ridker, Paul M | Gaziano, J Michael | Ridker, Paul M | Ulmer, Hanno | Diem, Günter | Concin, Hans | Rodeghiero, Francesco | Tosetto, Alberto | Wassertheil-Smoller, Sylvia | Manson, JoAnn E | Marmot, Michael | Clarke, Robert | Fletcher, Astrid | Brunner, Eric | Shipley, Martin | Kivimaki, Mika | Ridker, Paul M | Buring, Julie | Ford, Ian | Robertson, Michele | Ibañez, Alejandro Marín | Feskens, Edith | Geleijnse, Johanna M | Kromhout, Daan | Walker, Matthew | Watson, Sarah | Alexander, Myriam | Butterworth, Adam S | Angelantonio, Emanuele Di | Franco, Oscar H | Gao, Pei | Gobin, Reeta | Haycock, Philip | Kaptoge, Stephen | Seshasai, Sreenivasa R Kondapally | Lewington, Sarah | Pennells, Lisa | Rapsomaniki, Eleni | Sarwar, Nadeem | Thompson, Alexander | Thompson, Simon G | Walker, Matthew | Watson, Sarah | White, Ian R | Wood, Angela M | Wormser, David | Zhao, Xiaohui | Danesh, John
Background The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.
Methods We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual–participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.
Results For people born between 1900 and 1960, mean adult height increased 0.5–1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96–0.99) for death from any cause, 0.94 (0.93–0.96) for death from vascular causes, 1.04 (1.03–1.06) for death from cancer and 0.92 (0.90–0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12–1.42) for risk of melanoma death to 0.84 (0.80–0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.
Conclusion Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
doi:10.1093/ije/dys086
PMCID: PMC3465767  PMID: 22825588
Height; cardiovascular disease; cancer; cause-specific mortality; epidemiological study; meta-analysis
14.  Adiponectin and All-Cause Mortality in Elderly People With Type 2 Diabetes 
Diabetes Care  2012;35(9):1858-1863.
OBJECTIVE
To assess the association between serum adiponectin level and all-cause mortality in people with type 2 diabetes. Because of the insulin-sensitizing, anti-inflammatory, and antiatherogenic effects of adiponectin, we hypothesized that higher adiponectin level would be associated with lower all-cause mortality.
RESEARCH DESIGN AND METHODS
A total of 609 men and women aged 72 ± 6.3 years with type 2 diabetes and information on total and high molecular weight adiponectin were followed for a median of 5 years. The longitudinal association between adiponectin and all-cause mortality was analyzed with Cox proportional hazards models with time from adiponectin measurement to death as the time-to-event variable. Analyses were adjusted for demographic variables and significant diabetes parameters, significant cardiovascular parameters, and significant diabetes medications.
RESULTS
Total and high molecular weight adiponectin were highly correlated. The highest adiponectin quartile was strongly associated with higher all-cause mortality compared with the lowest quartile (hazard ratio = 4.0 [95% CI: 1.7–9.2]) in the fully adjusted model. These results did not change in analyses stratified by sex and thiazolidinedione use, after exclusion of people who died within one year of adiponectin measurement, or when change in weight before adiponectin measurement was considered.
CONCLUSIONS
Contrary to our hypothesis, higher adiponectin level was related to higher all-cause mortality. This association was not explained by confounding by other characteristics, including medications or preceding weight loss.
doi:10.2337/dc11-2215
PMCID: PMC3424994  PMID: 22773703
15.  The Internal Circadian Clock Increases Hunger and Appetite in the Evening Independent of Food Intake and Other Behaviors 
Obesity (Silver Spring, Md.)  2013;21(3):421-423.
Objective
Despite the extended overnight fast, paradoxically, people are typically not ravenous in the morning and breakfast is typically the smallest meal of the day. Here we assessed whether this paradox could be explained by an endogenous circadian influence on appetite with a morning trough, while controlling for sleep/wake and fasting/feeding effects.
Design and Methods
We studied 12 healthy non-obese adults (6 male; age, 20–42 year) throughout a 13-day laboratory protocol that balanced all behaviors, including eucaloric meals and sleep periods, evenly across the endogenous circadian cycle. Participants rated their appetite and food preferences by visual analog scales.
Results
There was a large endogenous circadian rhythm in hunger, with the trough in the biological morning (8 AM) and peak in the biological evening (8 PM; peak-to-trough amplitude=17%; P=0.004). Similarly phased significant endogenous circadian rhythms were present in appetite for sweets, salty and starchy foods, fruits, meats/poultry, food overall, and for estimates of how much food participants could eat (amplitudes 14–25%; all P < 0.05).
Conclusions
In people who sleep at night, the intrinsic circadian evening peak in appetite may promote larger meals before the fasting period necessitated by sleep. Furthermore, the circadian decline in hunger across the night would theoretically counteract the fasting-induced hunger increase that could otherwise disrupt sleep.
doi:10.1002/oby.20351
PMCID: PMC3655529  PMID: 23456944
Appetite; Circadian; Energy Balance; Hunger; Metabolism
16.  Noninvasive fractal biomarker of clock neurotransmitter disturbance in humans with dementia 
Scientific Reports  2013;3:2229.
Human motor activity has a robust, intrinsic fractal structure with similar patterns from minutes to hours. The fractal activity patterns appear to be physiologically important because the patterns persist under different environmental conditions but are significantly altered/reduced with aging and Alzheimer's disease (AD). Here, we report that dementia patients, known to have disrupted circadian rhythmicity, also have disrupted fractal activity patterns and that the disruption is more pronounced in patients with more amyloid plaques (a marker of AD severity). Moreover, the degree of fractal activity disruption is strongly associated with vasopressinergic and neurotensinergic neurons (two major circadian neurotransmitters) in postmortem suprachiasmatic nucleus (SCN), and can better predict changes of the two neurotransmitters than traditional circadian measures. These findings suggest that the SCN impacts human activity regulation at multiple time scales and that disrupted fractal activity may serve as a non-invasive biomarker of SCN neurodegeneration in dementia.
doi:10.1038/srep02229
PMCID: PMC3714649  PMID: 23863985
17.  Gender Differences in Posttraumatic Stress Disorder Among Primary Care Patients After the World Trade Center Attack of September 11, 2001 
Gender medicine  2005;2(2):76-87.
Background
Debate surrounds the nature of gender differences in rates of posttraumatic stress disorder (PTSD).
Objective
The goal of this study was to quantify and explore the reasons for gender differences in rates of PTSD in low income, primary care patients after the World Trade Center (WTC) attack of September 11, 2001.
Methods
A survey was conducted at a large primary care practice in New York City 7 to 16 months after the WTC attack. The study involved a systematic sample of primary care patients aged 18 to 70 years. The main outcome measures were the Life Events Checklist, the Posttraumatic Stress Disorder Checklist–Civilian Version, and the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, all administered by a bilingual research staff.
Results
A total of 3807 patients were approached at the primary care clinic. Of the 1347 who met eligibility criteria, 1157 (85.9%) consented to participate. After the addition of the WTC/PTSD supplement to the study, the total number of patients was 992, of whom 982 (99.0%) completed the survey. Both sexes had high rates of direct exposure to the WTC attack and high rates of lifetime exposure to stressful life events. Overall, females had lower rates of exposure to the attack compared with males (P < 0.05). Hispanic females had the highest rate of PTSD in the full sample. Gender differences in rates of PTSD were largely accounted for by differences in marital status and education. The rate of current major depressive disorder (MDD) was higher in females than in males (P < 0.001), and the reverse was true for substance abuse (P < 0.001). Gender differences for MDD and substance abuse persisted even after adjustments for demographic differences between the sexes.
Conclusions
The increased rate of PTSD in women attending a primary care clinic was mediated by their social and economic circumstances, such as living alone without a permanent relationship and with little education or income. The increased rate of MDD in women appeared to be less dependent on these circumstances. These findings have implications for the treatment of women with PTSD in primary care and for research on gender differences in rates of psychiatric disorders.
PMCID: PMC3683844  PMID: 16115602
posttraumatic stress disorder; gender; World Trade Center; primary care
18.  Metabolic Consequences in Humans of Prolonged Sleep Restriction Combined with Circadian Disruption 
Science translational medicine  2012;4(129):129ra43.
Epidemiological studies link short sleep and circadian disruption with risk of metabolic syndrome and diabetes. We tested the hypotheses that prolonged sleep restriction with concurrent circadian disruption, as can occur with shift work, impairs glucose regulation and metabolism. Healthy adults spent >5 weeks in controlled laboratory conditions including: sleep extension (baseline), 3-week sleep restriction (5.6 h sleep/24 h) combined with circadian disruption (recurring 28-h ‘days’), and 9-day recovery sleep with circadian re-entrainment. Prolonged sleep restriction with concurrent circadian disruption significantly decreased resting metabolic rate, and increased postprandial plasma via inadequate pancreatic beta cell responsivity; these normalized with 9 days of recovery sleep and stable circadian reentrainment. Thus, in humans, prolonged sleep restriction with concurrent circadian disruption alters metabolism and could increase risk of obesity and diabetes.
doi:10.1126/scitranslmed.3003200
PMCID: PMC3678519  PMID: 22496545
19.  Positive Screens for Psychiatric Disorders in Primary Care: A Long-Term Follow-Up of Patients Who Were Not in Treatment 
Objective
Screening for psychiatric disorders has gained acceptance in some general medical settings, but critics argue about its value. The purpose of this study was to determine the clinical utility of screening by conducting a long-term follow-up of patients who screened positive for psychiatric disorders but who were initially not in treatment.
Methods
A cohort of 519 low-income, adult primary care patients were screened for major depression and bipolar, anxiety, and substance use disorders and reassessed with the Structured Clinical Interview for DSM-IV after a mean of 3.7 years by a clinician blind to the initial screen. Data on treatment utilization was obtained through hospital records. The sample consisted of 348 patients who had not received psychiatric care in the year before screening.
Results
Among 39 patients who screened positive for major depression, 62% (95% confidence interval=45.5%–77.6%) met criteria for current major depressive disorder at follow-up. Those who screened positive reported significantly poorer mental and social functioning and worse general health at follow-up than the screen-negative patients and were more likely to have visited the emergency department for psychiatric reasons (12.1% and 3.0%, odds ratio [OR]=6.4) and to have major depression (OR=7.6). Generally similar results were observed for patients who screened positive for other disorders.
Conclusions
Commonly used screening methods identified patients with psychiatric disorders; about four years later, those not initially in treatment were likely to have enduring symptoms and to use emergency psychiatric services. Screening should be followed up by clinical diagnostic assessment in the context of available mental health treatment.
doi:10.1176/appi.ps.61.2.151
PMCID: PMC3670116  PMID: 20123820
20.  The Mental Health Consequences of Disaster-Related Loss: Findings from Primary Care One Year After the 9/11 Terrorist Attacks 
Psychiatry  2008;71(4):339-348.
This study examines the long-term psychiatric consequences, pain interference in daily activities, work loss, and functional impairment associated with 9/11-related loss among low-income, minority primary care patients in New York City. A systematic sample of 929 adult patients completed a survey that included a sociodemographic questionnaire, the PTSD Checklist, the PRIME-MD Patient Health Questionnaire, and the Medical Outcomes Study Short Form-12 (SF-12).
Approximately one-quarter of the sample reported knowing someone who was killed in the attacks of 9/11, and these patients were sociodemographically similar to the rest of the sample. Compared to patients who had not experienced 9/11-related loss, patients who experienced loss were roughly twice as likely (OR = 1.97, 95%; CI = 1.40, 2.77) to screen positive for at least one mental disorder, including major depressive disorder (MDD; 29.2%), generalized anxiety disorder (GAD; 19.4%), and posttraumatic stress disorder (PTSD; 17.1%). After controlling for pre-9/11 trauma, 9/11-related loss was significantly related to extreme pain interference, work loss, and functional impairment. The results suggest that disaster-related mental health care in this clinical population should emphasize evidence-based treatments for mood and anxiety disorders.
doi:10.1521/psyc.2008.71.4.339
PMCID: PMC3653136  PMID: 19152283
21.  Trauma exposure and posttraumatic stress disorder among primary care patients with bipolar spectrum disorder 
Bipolar disorders  2008;10(4):503-510.
Objective
To examine relationships between exposure to trauma, bipolar spectrum disorder (BD) and posttraumatic stress disorder (PTSD) in a sample of primary care patients.
Methods
A systematic sample (n = 977) of adult primary care patients from an urban general medicine practice were interviewed with measures including the Mood Disorders Questionnaire, the PTSD Checklist–Civilian Version, and the Medical Outcomes Study 12-Item Short Form Health Survey.
Results
Compared with patients who screened negative for BD (n = 881), those who screened positive (n = 96) were 2.6 times [95% confidence interval (CI): 1.6–4.2] as likely to report physical or sexual assault, and 2.9 times (95% CI: 1.6–5.1) as likely to screen positive for current PTSD. Among those screening positive for BD, comorbid PTSD was associated with significantly worse social functioning. These results controlled for selected background characteristics, current major depressive episode, and current alcohol/drug use disorder.
Conclusion
In an urban general medicine setting, trauma exposure was related to BD, and the frequency of PTSD among patients with BD appears to be common and clinically significant. These results suggest an unmet need for mental health care in this specific population and are especially important in view of available treatments for BD and PTSD.
doi:10.1111/j.1399-5618.2008.00589.x
PMCID: PMC3633108  PMID: 18452446
bipolar disorder; posttraumatic stress disorder; primary care; trauma exposure
22.  Posttraumatic stress disorder in primary care one year after the 9/11 attacks☆ 
General hospital psychiatry  2006;28(3):213-222.
Objective
To screen for posttraumatic stress disorder (PTSD) in primary care patients 7–16 months after 9/11 attacks and to examine its comorbidity, clinical presentation and relationships with mental health treatment and service utilization.
Method
A systematic sample (n = 930) of adult primary care patients who were seeking primary care at an urban general medicine clinic were interviewed using the PTSD Checklist: the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire and the Medical Outcome Study 12-Item Short Form Health Survey (SF-12). Health care utilization data were obtained by a cross linkage to the administrative computerized database.
Results
Prevalence estimates of current 9/11-related probable PTSD ranged from 4.7% (based on a cutoff PCL-C score of 50 and over) to 10.2% (based on the DSM-IV criteria). A comorbid mental disorder was more common among patients with PTSD than patients without PTSD (80% vs. 30%). Patients with PTSD were more functionally impaired and reported increased use of mental health medication as compared to patients without PTSD (70% vs. 18%). Among patients with PTSD there was no increase in hospital and emergency room (ER) admissions or outpatient care during the first year after the attacks.
Conclusions
In an urban general medicine setting, 1 year after 9/11, the frequency of probable PTSD appears to be common and clinically significant. These results suggest an unmet need for mental health care in this clinical population and are especially important in view of available treatments for PTSD.
doi:10.1016/j.genhosppsych.2006.02.002
PMCID: PMC3622521  PMID: 16675364
Primary care; Posttraumatic stress disorder; 9/11 attacks
23.  Adiposity is Associated with Endothelial Activation in Healthy 2- to 3-Year-Old Children 
Adiposity is associated with C-reactive protein level in healthy 2–3 year old children and with other markers of endothelial activation adults, but data are lacking in very young children. Data from 491 healthy Hispanic children were analyzed. Mean age was 2.7 years (S.D. 0.5, range 2 to 3 years); mean body mass index (BMI) was 17.2 kg/m2 (S.D. 1.9) among boys and 17.1 kg/m2 (S.D. 2.1) among girls. E-selectin level was associated with BMI (R =0.11; p < 0.02), ponderal index (p < 0.02), waist circumference (p = 0.02), fasting insulin (p < 0.02), and insulin resistance (p ≤ 0.05); these associations remained significant after adjustment for age, sex and fasting glucose. sVCAM was also associated with BMI (R = 0.12; P<0.05). These observations indicate that adiposity is associated with inflammation and endothelial activation in very early childhood.
PMCID: PMC3603688  PMID: 20020578
children; adiposity; E-selectin; sICAM; sVAM
24.  Klf15 orchestrates circadian nitrogen homeostasis 
Cell Metabolism  2012;15(3):311-323.
SUMMARY
Diurnal variation in nitrogen homeostasis is observed across phylogeny. But whether these are endogenous rhythms, and if so, molecular mechanisms that link nitrogen homeostasis to the circadian clock remain unknown. Here, we provide evidence that a clock-dependent peripheral oscillator, Krüppel-like factor15 transcriptionally coordinates rhythmic expression of multiple enzymes involved in mammalian nitrogen homeostasis. In particular, Krüppel-like factor15-deficient mice exhibit no discernable amino acid rhythm, and the rhythmicity of ammonia to urea detoxification is impaired. Of the external cues, feeding plays a dominant role in modulating Krüppel-like factor15 rhythm and nitrogen homeostasis. Further, when all behavioral, environmental and dietary cues were controlled in humans, nitrogen homeostasis still expressed endogenous circadian rhythmicity. Thus, in mammals, nitrogen homeostasis exhibits circadian rhythmicity, and is orchestrated by Krüppel-like factor15.
doi:10.1016/j.cmet.2012.01.020
PMCID: PMC3299986  PMID: 22405069
25.  Retinal microvascular calibre and risk of incident diabetes: The multi-ethnic study of atherosclerosis 
Aim
To prospectively examine the association of retinal microvascular signs with incident diabetes and impaired fasting glucose (IFG) in a multi-ethnic population-based cohort.
Methods
The multi-ethnic study of atherosclerosis comprised Caucasians, African-Americans, Hispanics and Chinese aged 45–84 years. Retinal vascular calibre and retinopathy were quantified from baseline retinal photographs. Incident diabetes and IFG were ascertained prospectively.
Results
After a median follow-up of 3 years, 243 (4.9%) people developed diabetes and 565 (15.0%) developed IFG. After adjusting for known risk factors, participants with wider retinal arteriolar calibre had a higher risk of developing diabetes [HR: 1.60; 95% CI: 1.12–2.29, p = 0.011 comparing highest with lowest arteriolar calibre tertile]. In ethnic subgroup analysis, the association between wider retinal arteriolar calibre and incident diabetes was stronger and statistically significant only in Caucasians [HR: 2.78; 95% CI: 1.37–5.62, p = 0.005]. Retinal venular calibre and retinopathy signs were not related to risk of diabetes or IFG.
Conclusion
Wider retinal arteriolar calibre is independently associated with an increased risk of diabetes, supporting a possible role for early arteriolar changes in diabetes development. This effect was largely seen in Caucasians, and not in other ethnic groups, and may reflect ethnic differences in susceptibility to diabetes from microvascular pathways.
doi:10.1016/j.diabres.2011.10.027
PMCID: PMC3269503  PMID: 22088792
Retinal microvascular calibre; Retinopathy; Diabetes; Impaired fasting glucose

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