A method for sensitivity analysis to assess the effects of measurement error in multiple exposure variables using external validation data

Measurement error in self-reported dietary intakes is known to bias the association between dietary intake and a health outcome of interest such as risk of a disease. The association can be distorted further by mismeasured confounders, leading to invalid results and conclusions. It is, however, difficult to adjust for the bias in the association when there is no internal validation data

Spin Reversal of a Quantum Hall Ferromagnet at a Landau Level Crossing

When Landau levels (LLs) become degenerate near the Fermi energy in the quantum Hall regime, interaction effects can drastically modify the electronic ground state. We study the quantum Hall ferromagnet formed in a two-dimensional hole gas around the LL filling factor $\nu=1$ in the vicinity of a LL crossing in the heave-hole valence band. Cavity spectroscopy in the strong-coupling regime allows us to optically extract the two-dimensional hole gas' spin polarization. By analyzing this polarization as a function of hole density and magnetic field, we observe a spin flip of the ferromagnet. Furthermore, the depolarization away from $\nu=1$ accelerates close to the LL crossing. This is indicative of an increase in the size of Skyrmion excitations as the effective Zeeman energy vanishes at the LL crossing

Food groups and risk of coronary heart disease, stroke and heart failure : a systematic review and dose-response meta-analysis of prospective studies

Background: Despite growing evidence for food-based dietary patterns' potential to reduce cardiovascular disease risk, knowledge about the amounts of food associated with the greatest change in risk of specific cardiovascular outcomes and about the quality of meta-evidence is limited. Therefore, the aim of this meta-analysis was to synthesize the knowledge about the relation between intake of 12 major food groups (whole grains, refined grains, vegetables, fruits, nuts, legumes, eggs, dairy, fish, red meat, processed meat, and sugar-sweetened beverages [SSB]) and the risk of coronary heart disease (CHD), stroke and heart failure (HF). Methods: We conducted a systematic search in PubMed and Embase up to March 2017 for prospective studies. Summary risk ratios (RRs) and 95% confidence intervals (95% CI) were estimated using a random effects model for highest versus lowest intake categories, as well as for linear and non-linear relationships. Results: Overall, 123 reports were included in the meta-analyses. An inverse association was present for whole grains (RRCHD: 0.95 (95% CI: 0.92-0.98), RRHF: 0.96 (0.95-0.97)), vegetables and fruits (RRCHD: 0.97 (0.96-0.99), and 0.94 (0.90-0.97); RRstroke: 0.92 (0.86-0.98), and 0.90 (0.84-0.97)), nuts (RRCHD: 0.67 (0.43-1.05)), and fish consumption (RRCHD: 0.88 (0.79-0.99), RRstroke: 0.86 (0.75-0.99), and RRHF: 0.80 (0.67-0.95)), while a positive association was present for egg (RRHF: 1.16 (1.03-1.31)), red meat (RRCHD: 1.15 (1.08-1.23), RRstroke: 1.12 (1.06-1.17), RRHF: 1.08 (1.02-1.14)), processed meat (RRCHD: 1.27 (1.09-1.49), RRstroke: 1.17 (1.02-1.34), RRHF: 1.12 (1.05-1.19)), and SSB consumption (RRCHD: 1.17 (1.11-1.23), RRstroke: 1.07 (1.02-1.12), RRHF: 1.08 (1.05-1.12)) in the linear dose-response meta-analysis. There were clear indications for non-linear dose-response relationships between whole grains, fruits, nuts, dairy, and red meat and CHD. Conclusion: An optimal intake of whole grains, vegetables, fruits, nuts, legumes, dairy, fish, red and processed meat, eggs and SSB showed an important lower risk of CHD, stroke, and HF

Combination of Conservative and Interventional Therapy Strategies for Intra- and Extrahepatic Cholangiocellular Carcinoma: A Retrospective Survival Analysis

Background. Due to the predominantly advanced stage at the time of diagnosis treatment of cholangiocarcinoma is difficult. Apart from surgical resection, interventional treatment strategies are increasingly used in advanced stage tumours. The aim of the study was a retrospective comparison of the effect of the various forms of treatment on morbidity and mortality. Method. A total of 195 patients, received either chemotherapy or a combination of photodynamic therapy (PDT) or transarterial chemoembolization (TACE) and chemotherapy. Results. The median survival rate for all patients was 15.6 months, 50.8% were still alive 1 year after diagnosis. Patients, who had previously undergone surgery, survived 17.1 months longer than those without surgical treatment (P < .01). Chemotherapy prolonged the survival by 9.2 months (P = .47). Palliative patients under combination of chemotherapy and PDT survived on average 1.8 months longer (P = .28), with chemotherapy and TACE 9.8 months longer (P = .04) compared to chemotherapy alone. Conclusions. It appears that surgical treatment and chemotherapy combined with PDT or TACE may prolong survival

Association between change in cardiovascular risk scores and future cardiovascular disease: analyses of data from the Whitehall II longitudinal, prospective cohort study

BACKGROUND: Evaluation of cardiovascular disease risk in primary care, which is recommended every 5 years in middle-aged and older adults (typical age range 40-75 years), is based on risk scores, such as the European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) and American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) algorithms. This evaluation currently uses only the most recent risk factor assessment. We aimed to examine whether 5-year changes in SCORE and ASCVD risk scores are associated with future cardiovascular disease risk. METHODS: We analysed data from the Whitehall II longitudinal, prospective cohort study for individuals with no history of stroke, myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, definite angina, heart failure, or peripheral artery disease. Participants underwent clinical examinations in 5-year intervals between Aug 7, 1991, and Dec 6, 2016, and were followed up for incident cardiovascular disease until Oct 2, 2019. Levels of, and 5-year changes in, cardiovascular disease risk were assessed using the SCORE and ASCVD risk scores and were analysed as predictors of cardiovascular disease. Harrell's C index, continuous net reclassification improvement, the Akaike information criterion, and calibration analysis were used to assess whether incorporating change in risk scores into a model including only a single risk score assessment improved the predictive performance. We assessed the levels of, and 5-year changes in, SCORE and ASCVD risk scores as predictors of cardiovascular disease and disease-free life-years using Cox proportional hazards and flexible parametric survival models. FINDINGS: 7574 participants (5233 [69·1%] men, 2341 [30·9%] women) aged 40-75 years were included in analyses of risk score change between April 24, 1997, and Oct 2, 2019. During a mean follow-up of 18·7 years (SD 5·5), 1441 (19·0%; 1042 [72·3%] men and 399 [27·7%] women) participants developed cardiovascular disease. Adding 5-year change in risk score to a model that included only a single risk score assessment improved model performance according to Harrell's C index (from 0·685 to 0·690, change 0·004 [95% CI 0·000 to 0·008] for SCORE; from 0·699 to 0·700, change 0·001 [0·000 to 0·003] for ASCVD), the Akaike information criterion (from 17 255 to 17 200, change -57 [95% CI -97 to -13] for SCORE; from 14 739 to 14 729, change -10 [-28 to 7] for ASCVD), and the continuous net reclassification index (0·353 [95% CI 0·234 to 0·447] for SCORE; 0·232 [0·030 to 0·344] for ASCVD). Both favourable and unfavourable changes in SCORE and ASCVD were associated with cardiovascular disease risk and disease-free life-years. The associations were seen in both sexes and all age groups up to the age of 75 years. At the age of 45 years, each 2-unit improvement in risk scores was associated with an additional 1·3 life-years (95% CI 0·4 to 2·2) free of cardiovascular disease for SCORE and an additional 0·9 life-years (95% CI 0·5 to 1·3) for ASCVD. At age 65 years, this same improvement was associated with an additional 0·4 life-years (95% CI 0·0 to 0·7) free of cardiovascular disease for SCORE and 0·3 life-years (95% CI 0·1 to 0·5) for ASCVD. These models were developed into an interactive calculator, which enables estimation of the number of cardiovascular disease-free life-years for an individual as a function of two risk score measurements. INTERPRETATION: Changes in the SCORE and ASCVD risk scores over time inform cardiovascular disease risk prediction beyond a single risk score assessment. Repeat data might allow more accurate cardiovascular risk stratification and strengthen the evidence base for decisions on preventive interventions. FUNDING: UK Medical Research Council, British Heart Foundation, Wellcome Trust, and US National Institute on Aging

Use of Two-Part Regression Calibration Model to Correct for Measurement Error in Episodically Consumed Foods in a Single-Replicate Study Design: EPIC Case Study

In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model

Eating out is different from eating at home among individuals who occasionally eat out. A cross-sectional study among middle-aged adults from eleven European countries

Eating out has been linked to the current obesity epidemic, but the evaluation of the extent to which out of home (OH) dietary intakes are different from those at home (AH) is limited. Data collected among 8849 men and 14 277 women aged 35–64 years from the general population of eleven European countries through 24-h dietary recalls or food diaries were analysed to: (1) compare food consumption OH to those AH; (2) describe the characteristics of substantial OH eaters, defined as those who consumed 25 % or more of their total daily energy intake at OH locations. Logistic regression models were fit to identify personal characteristics associated with eating out. In both sexes, beverages, sugar, desserts, sweet and savoury bakery products were consumed more OH than AH. In some countries, men reported higher intakes of fish OH than AH. Overall, substantial OH eating was more common among men, the younger and the more educated participants, but was weakly associated with total energy intake. The substantial OH eaters reported similar dietary intakes OH and AH. Individuals who were not identified as substantial OH eaters reported consuming proportionally higher quantities of sweet and savoury bakery products, soft drinks, juices and other non-alcoholic beverages OH than AH. The OH intakes were different from the AH ones, only among individuals who reported a relatively small contribution of OH eating to their daily intakes and this may partly explain the inconsistent findings relating eating out to the current obesity epidemic

Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study

Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors – healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. Results: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. Conclusions: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention. Electronic supplementary material The online version of this article (doi:10.1186/s12916-014-0168-4) contains supplementary material, which is available to authorized users