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Background An accumulating body of evidence suggests that the number of apolipoprotein B-containing particles (ApoB-P) is more predictive of cardiovascular risk than their lipid content. However, it is unclear if this association is consistent across different lipoprotein types and sizes. Purpose We aimed to evaluate if particle type and size are associated with incident myocardial infarction (MI) beyond ApoB-P count. Moreover, we aimed to determine if the risk associated with lipoprotein(a) is additive to that of ApoB-P. Methods This prospective cohort study included 96,126 participants without prior history of stroke, coronary or peripheral artery disease or use of lipid-lowering medication from the UK Biobank. Count and size of VLDL, IDL, LDL, and HDL, as well as ApoB level and total ApoB-P count were measured in non-fasting plasma samples by nuclear magnetic resonance platform. Lipoprotein(a) was measured by immunoturbidimetric assay. We explored associations between these lipoprotein markers and incident MI using Cox proportional hazard models adjusted sequentially for clinical covariates, HDL count and size, and ApoB-P. Results Over a median follow-up of 12.1 years, 1702 participants had incident MI. In unadjusted models, 1-SD increases in ApoB-P count, ratio of VLDL to (LDL+IDL) particle counts, VLDL size and lipoprotein(a) were associated with a higher risk of MI, while LDL size was associated with a lower risk of MI (Table 1). When adjusting for clinical covariates and lipid parameters, only ApoB-P and lipoprotein(a) remained significantly associated with a higher risk of MI (HR: 1.40 [1.32; 1.48] and 1.20 [1.14; 1.27], respectively). Adjusted restricted cubic splines confirmed findings from linear trend Cox models (Figure 1). ApoB-P count was highly correlated with ApoB level (r=0.99), and replication of analyses replacing one for another revealed no change in results. Conclusion The risk of MI is independently associated with the total particle count of all ApoB-P, and not the size or type of these lipoproteins. ApoB level can be used as a very accurate surrogate of ApoB-P count in the clinical setting. Lipoprotein(a) is associated with MI risk independently of total particle count, and therefore, the combination of ApoB and lipoprotein(a) may provide the optimal clinical evaluation of lipid-mediated MI risk. Funding Acknowledgement Type of funding sources: None.

Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.

For starting and shifting processes of dual-clutch transmission vehicle, the combined starting control strategy for dual clutches is proposed to reduce temperature rise of clutch and the dynamics simulation model of starting and shifting is built. For the two different downshift modes during inertia phase, the work and power of sliding friction are comparatively analysed. The results can provide boundary conditions of heat source for thermal equilibrium analysis under two typical starting conditions. During the benchmark test, the extreme starting condition under full load and large gradient and the three typical shifting conditions are set. Then, the sliding friction test is executed. The transmitted torque of wet dual clutches and the speed of driving and driven plates of dual clutches are measured to calculate work and power of sliding friction, and the corresponding temperature rise of wet dual clutches is obtained. Furthermore, the heat generation and heat dissipation conditions under different sliding friction modes are analysed. The corresponding influences on clutch control and temperature rise of cooling oil are also discussed. Based on the simulation and test results, the thermal equilibrium of clutches is analysed. The evaluation indexes of sliding friction work are calculated, and then the starting and shift control strategies are optimized.

Cet article fait le point sur les effets satietogenes des hydrates de carbone consommes sous forme solide ou liquide sur, et sur leur role eventuel dans la pathogenese de l’obesite. Plusieurs etudes recentes ont evalue le role des fibres alimentaires, de l’index glycemique des aliments, ou de la charge glycemique sur la satiete et sur la prise alimentaire spontanee. Les resultats restent cependant equivoques. L’ingestion d’hydrates de carbone sous forme liquide, principalement sous forme de boissons sucrees, a augmente de maniere importante au cours des dernieres decennies tant chez l’adolescent que chez l’adulte. De maniere generale, il apparait que les hydrates de carbones ingeres sous forme liquide produisent une satiete moindre que lorsqu’ils sont ingeres avec des aliments solides. La consommation d’hydrates de carbone sous forme liquide est de ce fait incompletement compensee par une reduction des apports alimentaires lors des repas suivants, et s’accompagne d’une augmentation des apports energetiques totaux. En conclusions, la satiete est un phenomene complexe, dans lequel intervient la forme physique des aliments. Il apparait vraisemblable que les hydrates de carbone ingeres sous forme liquide produisent un sentiment de satiete moindre que les hydrates de carbone ingeres sous forme d’aliments solides

The prognostic role of phosphatase and tensin homolog (PTEN) in non-small cell lung cancer (NSCLC) has been controversial.In this study, levels of PTEN expression were investigated in NSCLC patients and their prognostic value in NSCLC was assessed. PTEN expression in tumor tissues from 68 NSCLC patients was analyzed using immunohistochemistry and confocal microscopy. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis.NSCLC patients classified as expressers of high levels of PTEN (n = 46) had better prognoses than those classified as expressers of low levels (mean survival 17.1 versus 12.9 months, log-rank p = 0.038). In patients with adenocarcinoma (AC), high PTEN expression (n = 9) was associated with significantly longer survival than low PTEN expression (mean survival 23.50 versus 15.54 months, log-rank p = 0.043). High levels of PTEN expression resulted in 43% reduction in risk for all NSCLC patients (HR = 0.57, 95% CI: 0.33-0.98, p = 0.041). PTEN expression and clinical stage remained significantly associated with survival after adjustment for age, sex and tumor type (HR = 0.56, 95% CI: 0.32-0.99; p = 0.048; HR = 0.54, 95% CI: 0.36-0.97; p = 0.045). No significant difference in continuous PTEN expression levels was observed among groups with different clinical or pathological characteristics (p0.17). When levels of PTEN expression were binarized using the optimal cutpoint, higher levels of PTEN expression were observed in patients with T1/T2 than in those with T3/T4 (80% and 58% respectively, p = 0.049) and in patients with AC than in those with squamous-cell carcinoma (SCC) (78% and 58% respectively, p = 0.08). No significant difference in binarized PTEN expression levels was found among groups with any other clinical/pathologic characteristic (p0.28).Our results suggest that high levels of PTEN expression may be favorable prognostic marker in NSCLC patients.

The aim of this study was to assess the association between obesity and the risk of intensive care unit (ICU) admission and death among patients hospitalized for influenza A (H1N1) viral infection. A systematic review of the Medline and Cochrane databases using 'obesity', 'hospitalization', 'influenza A viral infection', various synonyms, and reference lists of retrieved articles from January 2009 to January 2010. Studies comparing the prevalence of obesity among patients with confirmed infection for influenza A virus and who were either hospitalized or admitted to ICU/died were included. A total of 3059 subjects from six cross-sectional studies, who were hospitalized for influenza A (H1N1) viral infection, were included in this meta-analysis. Severely obese H1N1 patients (body mass index ≥ 40 kg m(-2), n = 804) were as twice as likely to be admitted to ICU or die (odds ration: 2.01, 95% confidence interval: 1.29-3.14, P0.002) compared with H1N1 patients who were not severely obese. Having a body mass index ≥ 30 kg m(-2) was similarly associated with a more than twofold increased risk of ICU admission or death although this did not reach statistical significance (2.14, 0.92-4.99, P0.07). This meta-analysis supports the view that obesity is associated with higher risks of ICU admission or death in patients with influenza A (H1N1) infection. Therefore, morbid obese patients should be monitored more intensively when hospitalized.

Fuelled by rapid urbanization and changes in dietary and lifestyle choices, chronic diseases have emerged as a critical public health issue in China. The Healthy China 2020 programme recently announced by the Chinese government has set an overarching goal of promoting public health and making health care accessible and affordable for all Chinese citizens by year 2020. One of important components of the programme is to reduce chronic diseases by promoting healthy eating and active lifestyles. Chronic diseases not only affect health and quality of life, but also have economical and social consequences. With a limited infrastructure for chronic disease care, China is ill-equipped to deal with the escalating chronic disease epidemic, which threatens to reverse the gains of economic development in recent decades. Population-based intervention studies conducted in China and elsewhere have demonstrated the efficacy and effectiveness of several preventive strategies to reduce risk of chronic diseases in high-risk individuals and the general population. However, translating these findings into practice requires changes in health systems and public policies. To achieve the goals set by the Healthy China 2020 programme, prevention of chronic diseases should be elevated to a national public policy priority.

Recent studies indicate transcription factor hepatocyte nuclear factor 4 alpha (HNF-4 alpha, HNF4A) modulates the transcription of the pancreatic B-cell ATP-sensitive K+ (KATP) channel subunit Kir6.2 gene (KCNJ11). Both HNF4A and KCNJ11 have previously been associated with diabetes risk but little is known whether the variations in these genes interact with each other.We conducted a prospective, nested case-control study of 714 incident cases of Type 2 diabetes and 1120 control subjects from the Nurses' Health Study.KCNJ11 E23K was significantly associated with an increased diabetes risk (odds ratio 1.26, 95% CI 1.03-1.53) while HNF4A P2 promoter polymorphisms were associated with a moderately increased risk at borderline significance. By using a logistic regression model, we found significant interactions between HNF4A rs2144908, rs4810424 and rs1884613 and KCNJ11 E23K (P for interaction = 0.017, 0.012 and 0.004, respectively). Carrying the minor alleles of the three HNF4A polymorphisms was associated with significantly greater diabetes risk in women carrying the KCNJ11 allele 23K, but not in those who did not carry this allele. Analyses using the multifactor dimensionality reduction (MDR) method confirmed the gene-gene interaction. We identified that the best interaction model included HNF4A rs2144908 and KCNJ11 E23K. Such a two-locus model showed the maximum cross-validation consistency of 10 out of 10 and a significant prediction accuracy of 54.2% (P = 0.01) on the basis of 1000-fold permutation testing.Our data indicate that HNF4A P2 promoter polymorphisms may interact with KCNJ11 E23K in predicting Type 2 diabetes in women.

This chapter discusses the contributions of the Nurses' Health Study (NHS) and Health Professionals' Follow-up Study (HPFS) to the nutritional epidemiology of coronary heart disease (CHD). Compelling evidence from these studies indicates that CHD is heavily influenced by dietary and lifestyle factors. Replacing saturated and trans fats with unsaturated fats, including sources of n-3 fatty acids, substituting whole grain forms of carbohydrate for refined grains and potatoes, consuming an abundance of fruits and vegetables, and controlling body weight will dramatically reduce the risk of CHD. The magnitude of benefit achievable through diet and lifestyle is large and substantially greater than that due to drug treatment of blood cholesterol or hypertension.

Our aim was to study the broader eating patterns that potentially reflect many dietary exposures working together in their association with breast cancer risk. Using data from a prospective study of 61,463 women with an average follow-up of 9.6 years and 1,328 incident cases of breast cancer, we conducted a factor analysis to identify major dietary patterns. Proportional hazards regression was used to estimate hazard ratios. We found no association between the "Western" dietary pattern (characterized by such foods as red and processed meats, refined grains, fat, and sweets) or the "healthy" dietary pattern (fruit and vegetables, fish and poultry, low-fat dairy, and whole grains) and breast cancer risk. However, women who were in the highest category of the "drinker" dietary pattern (wine, beer, and spirits) had a moderately increased risk (rate ratio = 1.27; 95% confidence interval, 1.06-1.52; P for trend, 0.002). The positive association was somewhat weaker among women below 50 years of age, a finding not inconsistent with chance. Our results are in agreement with the majority of previous studies that show alcohol consumption moderately increases the risk of breast cancer, but our results do not support any association between breast cancer risk and the "Western" or "healthy" dietary patterns.

To assess the relationship between cigarette smoking and mortality among women with type 2 diabetes in the Nurses' Health Study cohort.The Nurses' Health Study, a prospective cohort of U.S. female registered nurses, included 7,401 women with type 2 diabetes diagnosed at baseline or during follow-up from 1976 to 1996. Total and cause-specific mortality of these diabetic women were the outcomes of interest.We documented 724 deaths during 20 years of follow-up (67,420 person-years) among women with type 2 diabetes. In multivariate analyses, adjusting for age, history of high blood pressure and high cholesterol, and other cardiovascular risk factors, compared with never smokers, the RRs of mortality were 1.31 (95% CI 1.11-1.55) for past smokers, 1.43 (0.96-2.14) for current smokers of 1-14 cigarettes/day, 1.64 (1.24-2.17) for current smokers of 15-34 cigarettes/day, and 2.19 (1.32-3.65) for current smokers ofor =35 cigarettes/day (P for trend = 0.0002). Women with type 2 diabetes who had stopped smoking foror =10 years had a mortality RR of 1.11 (0.92-1.35) compared with diabetic women who were never smokers.Cigarette smoking is associated in a dose-response manner with an increased mortality among women with type 2 diabetes. Furthermore, quitting smoking appears to decrease this excess risk substantially. Diabetes patients should be strongly advised against smoking.

In the last decade, our understanding of the nutrients and foods most likely to promote cardiac health has improved substantially, owing in part to the data from several large and carefully conducted prospective cohort studies, including the Nurses' Health Study (NHS) and Health Professionals' Follow-up Study (HPFS). Using more refined dietary assessment tools and multiple measurements, the NHS and HPFS have provided a wealth of information not only on major types of fat and different classes of fatty acids, but also other aspects of diet, including antioxidants, folate, fiber, dietary glycemic load, and overall dietary patterns. These studies, along with metabolic, clinical and other epidemiological studies, have provided strong evidence for a major role of dietary modification in the prevention of coronary heart disease (CHD).

The co-twin control design has been widely used in studying the effects of environmental factors on the development of diseases. For binary outcomes that arise from co-twin control studies, the conditional likelihood method is commonly used. This approach, however, does not readily extend to ordinal response data because the standard conditional likelihood does not exist for cumulative logit or proportional odds models. In this paper, we investigate the applicability of the random-effects and GEE approaches in analysing ordinal response data from co-twin control studies. Using both approaches, we re-analyse data from a co-twin control study of the impact of military services during the Vietnam era on post-traumatic stress disorders (PTSD). The ordinal models have considerably increased power in detecting the effects of exposure when compared to the analyses using a dichotomized response. We discuss the interpretation of the estimates from GEE and random-effect models in the context of the twin data.

Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6. However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available.To examine intakes of folate and vitamin B6 in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD.Prospective cohort study.In 1980, a total of 80082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B6.Nonfatal MI and fatal CHD confirmed by World Health Organization criteria.During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD. After controlling for cardiovascular risk factors, including smoking and hypertension and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence interval [CI], 0.55-0.87) for folate (median intake, 696 microg/d vs 158 microg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B6 (median intake, 4.6 mg/d vs 1.1 mg/d). Controlling for the same variables, the RR was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B6 intake compared with the opposite extreme. Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95% CI, 0.65-0.90), the major source of folate and vitamin B6, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B6. In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI, 0.13-0.58).These results suggest that intake of folate and vitamin B6 above the current recommended dietary allowance may be important in the primary prevention of CHD among women.

This study describes the patterns and predictors of smokeless tobacco (ST) use in a large sample of urban public school students in Los Angeles and San Diego. The use of ST is more common among men than women and among Caucasians than African Americans, Hispanics, and others. Approximately 20% of the male respondents and 5% of the female respondents reported use of ST at least once, and 10.1% of male students and 3.1% of female students who had never tried ST by seventh grade started to use it by eighth grade. Among Caucasians, about 30% of boys reported trying ST at least once and 13.7% of those who had never used ST by seventh grade initiated experimentation by eighth grade. These data are used to examine the family, peer, and intrapersonal predictors of ST onset. The family risk factors for ST onset include living with a single parent, parent-child conflicts, and parental alcohol use. The peer risk factors for ST use include peer drug use and activities with friends, such as parties and participation in sports. The intrapersonal risk factors include poor grades in school, risk taking, and stress. The study also shows that those who use cigarettes, alcohol, or marijuana are at higher risk of using ST and vice versa. This study supports a problem-prone behavior perspective of ST use and cigarette smoking. We suggest that both products be targeted because the same programs are likely to apply to both products to counteract problem-prone type variables. Medical Subject Headings (MeSH): tobacco, smokeless chewing tobacco, adolescent behavior.

Smoking-related behaviors and attitudes of significant others (especially friends and parents) are among the most consistent predictors of adolescent smoking. However, theorists remain divided on whether the behaviors of significant others influence adolescent smoking directly or indirectly, and the relative influence of parental and peer smoking on adolescents' own smoking is still a matter of debate. In addition, little research has examined the role of significant others' behavior on different stages of smoking onset. In particular, not much information is available regarding gender and ethnic differences in social influences on smoking behavior. We use structural equation modeling to address these issues. Different theoretical perspectives from cognitive-affective theories (Ajzen 1985; Ajzen and Fishbein 1980) and social learning theories (Akers et al. 1979; Bandura 1969, 1982, 1986) have been integrated into a structural model of smoking influence. The results show that friends' smoking affects adolescent initiation into smoking both directly and indirectly, whereas parental smoking influences smoking initiation only indirectly. The data also show that friends' and parents' smoking affect smoking escalation only indirectly. In general, friends' smoking has a stronger effect on adolescents' smoking behavior, particularly on initiation. Multiple group comparisons of the structural models predicting smoking initiation among males and females reveal that parental approval of smoking plays a significant mediating role for females, but not for males. Comparisons of Whites, Blacks, Hispanics, and other ethnic groups reveal that there are some significant differences in the pathways of friends' influences among the four groups.