Weak Pinning and Long-Range Anticorrelated Motion of Phase Boundaries in Driven Diffusive Systems.

We show that domain walls separating coexisting extremal current phases in driven diffusive systems exhibit complex stochastic dynamics with a subdiffusive temporal growth of position fluctuations due to long-range anticorrelated current fluctuations and a weak pinning at long times. This weak pinning manifests itself in a saturated width of the domain wall position fluctuations that increases sublinearly with the system size. As a function of time t and system size L, the width w(t,L) has a scaling behavior w(t,L)=L^{3/4}f(t/L^{9/4}), with f(u) constant for u≫1 and f(u)∼u^{1/3} for u≪1. An Orstein-Uhlenbeck process with long-range anticorrelated noise is shown to capture this scaling behavior. The exponent 9/4 is a new dynamical exponent for relaxation processes in driven diffusive systems.

Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR. RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) ß, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk. CONCLUSIONS: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.

Metabolically defined body size and body shape phenotypes and risk of postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Excess body fatness and hyperinsulinemia are both associated with an increased risk of postmenopausal breast cancer. However, whether women with high body fatness but normal insulin levels or those with normal body fatness and high levels of insulin are at elevated risk of breast cancer is not known. We investigated the associations of metabolically defined body size and shape phenotypes with the risk of postmenopausal breast cancer in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. METHODS: Concentrations of C-peptide-a marker for insulin secretion-were measured at inclusion prior to cancer diagnosis in serum from 610 incident postmenopausal breast cancer cases and 1130 matched controls. C-peptide concentrations among the control participants were used to define metabolically healthy (MH; in first tertile) and metabolically unhealthy (MU; >1st tertile) status. We created four metabolic health/body size phenotype categories by combining the metabolic health definitions with normal weight (NW; BMI < 25 kg/m2 , or WC < 80 cm, or WHR < 0.8) and overweight or obese (OW/OB; BMI ≥ 25 kg/m2 , or WC ≥ 80 cm, or WHR ≥ 0.8) status for each of the three anthropometric measures separately: (1) MHNW, (2) MHOW/OB, (3) MUNW, and (4) MUOW/OB. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Women classified as MUOW/OB were at higher risk of postmenopausal breast cancer compared to MHNW women considering BMI (OR = 1.58, 95% CI = 1.14-2.19) and WC (OR = 1.51, 95% CI = 1.09-2.08) cut points and there was also a suggestive increased risk for the WHR (OR = 1.29, 95% CI = 0.94-1.77) definition. Conversely, women with the MHOW/OB and MUNW were not at statistically significant elevated risk of postmenopausal breast cancer risk compared to MHNW women. CONCLUSION: These findings suggest that being overweight or obese and metabolically unhealthy raises risk of postmenopausal breast cancer while overweight or obese women with normal insulin levels are not at higher risk. Additional research should consider the combined utility of anthropometric measures with metabolic parameters in predicting breast cancer risk.

Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. RESULTS: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. CONCLUSION: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.

Stochastic thermodynamics and modes of operation of a ribosome: A network theoretic perspective.

The ribosome is one of the largest and most complex macromolecular machines in living cells. It polymerizes a protein in a step-by-step manner as directed by the corresponding nucleotide sequence on the template messenger RNA (mRNA) and this process is referred to as "translation" of the genetic message encoded in the sequence of mRNA transcript. In each successful chemomechanical cycle during the (protein) elongation stage, the ribosome elongates the protein by a single subunit, called amino acid, and steps forward on the template mRNA by three nucleotides called a codon. Therefore, a ribosome is also regarded as a molecular motor for which the mRNA serves as the track, its step size is that of a codon and two molecules of GTP and one molecule of ATP hydrolyzed in that cycle serve as its fuel. What adds further complexity is the existence of competing pathways leading to distinct cycles, branched pathways in each cycle, and futile consumption of fuel that leads neither to elongation of the nascent protein nor forward stepping of the ribosome on its track. We investigate a model formulated in terms of the network of discrete chemomechanical states of a ribosome during the elongation stage of translation. The model is analyzed using a combination of stochastic thermodynamic and kinetic analysis based on a graph-theoretic approach. We derive the exact solution of the corresponding master equations. We represent the steady state in terms of the cycles of the underlying network and discuss the energy transduction processes. We identify the various possible modes of operation of a ribosome in terms of its average velocity and mean rate of GTP hydrolysis. We also compute entropy production as functions of the rates of the interstate transitions and the thermodynamic cost for accuracy of the translation process.

Insulin-like growth factor-1, insulin-like growth factor-binding protein-3, and breast cancer risk: observational and Mendelian randomization analyses with ∼430 000 women.

BACKGROUND: Epidemiological evidence supports a positive association between circulating insulin-like growth factor-1 (IGF-1) concentrations and breast cancer risk, but both the magnitude and causality of this relationship are uncertain. We conducted observational analyses with adjustment for regression dilution bias, and Mendelian randomization (MR) analyses allowed for causal inference. PATIENTS AND METHODS: We investigated the associations between circulating IGF-1 concentrations and incident breast cancer risk in 206 263 women in the UK Biobank. Multivariable hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. HRs were corrected for regression dilution using repeat IGF-1 measures available in a subsample of 6711 women. For the MR analyses, genetic variants associated with circulating IGF-1 and IGF-binding protein-3 (IGFBP-3) levels were identified and their association with breast cancer was examined with two-sample MR methods using genome-wide data from 122 977 cases and 105 974 controls. RESULTS: In the UK Biobank, after a median follow-up of 7.1 years, 4360 incident breast cancer cases occurred. In the multivariable-adjusted models corrected for regression dilution, higher IGF-1 concentrations were associated with a greater risk of breast cancer (HR per 5 nmol/l increment of IGF-1 = 1.11, 95% CI = 1.07-1.16). Similar positive associations were found by follow-up time, menopausal status, body mass index, and other risk factors. In the MR analyses, a 5 nmol/l increment in genetically-predicted IGF-1 concentration was associated with a greater breast cancer risk (odds ratio = 1.05, 95% CI = 1.01-1.10; P = 0.02), with a similar effect estimate for estrogen-positive (ER+) tumours, but no effect found for estrogen-negative (ER-) tumours. Genetically-predicted IGFBP-3 concentrations were not associated with breast cancer risk (odds ratio per 1-standard deviation increment = 1.00, 95% CI = 0.97-1.04; P = 0.98). CONCLUSION: Our results support a probable causal relationship between circulating IGF-1 concentrations and breast cancer, suggesting that interventions targeting the IGF pathway may be beneficial in preventing breast tumorigenesis.

Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults.

PURPOSE: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up. METHODS: A total of 255,170 participants aged 25-70 years were recruited in ten European countries (1992-2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC-MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. RESULTS: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087-0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041-0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. CONCLUSION: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

Kardar-Parisi-Zhang universality of the Nagel-Schreckenberg model.

Dynamical universality classes are distinguished by their dynamical exponent z and unique scaling functions encoding space-time asymmetry for, e.g., slow-relaxation modes or the distribution of time-integrated currents. So far the universality class of the Nagel-Schreckenberg (NaSch) model, which is a paradigmatic model for traffic flow on highways, was not known. Only the special case v_{max}=1, where the model corresponds to the totally asymmetric simple exclusion process, is known to belong to the superdiffusive Kardar-Parisi-Zhang (KPZ) class with z=3/2. In this paper, we show that the NaSch model also belongs to the KPZ class for general maximum velocities v_{max}>1. Using nonlinear fluctuating hydrodynamics theory we calculate the nonuniversal coefficients, fixing the exact asymptotic solutions for the dynamical structure function and the distribution of time-integrated currents. The results of large-scale Monte Carlo simulations match the exact asymptotic KPZ solutions without any fitting parameter left. Additionally, we find that nonuniversal early-time effects or the choice of initial conditions might have a strong impact on the numerical determination of the dynamical exponent and therefore lead to inconclusive results. We also show that the universality class is not changed by extending the model to a two-lane NaSch model with lane-changing rules.

Social Support to Reduce Uncertainty in Childhood Cancer in South Texas: A Case Study.

PURPOSE: To determine if supportive measures are found to be most helpful and feasible for families of children with cancer by obtaining in-depth perspectives of uncertainty and adaptation. HYPOTHESES: Traditional methods of psychosocial support do not meet the needs of parents and families dealing with cancer. Participants prefer more informal meetings and gatherings that are more social in nature. METHOD: A descriptive single embedded case study was used to study uncertainty and social support for families with children treated at a pediatric hematology/oncology department in south Texas. The sample included members of the health care team in a pediatric cancer/bone marrow transplant unit and parents of children diagnosed with cancer. Data were gathered through audio-recorded interviews. DATA ANALYSIS: Data were transcribed and analyzed through thematic content and pattern matching using computer software. RESULTS: Four themes were identified: meaning of uncertainty in parents and members of the health care team, facilitators of parental adaptation, education and psychosocial support, and patient/family obstacles hindering successful adaptation. These demonstrated aspects of care interventions, clarifying what uncertainty means and how it affects the ability of parents to adapt to life with pediatric cancer, perceptions regarding the helpfulness of education and support interventions or lack thereof, and what internal and external obstacles hinder the family's adaptation. IMPLICATIONS FOR PRACTICE: Improving patient education through individualization and delivery time frame as well as providing opportunities for informal sharing and community building are key to reducing uncertainty and improving family adaptation to life with childhood cancer.

Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study.

BACKGROUND: There is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features. RESULTS: After correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with qval = 0.029 and qval = 0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL. CONCLUSIONS: Alcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses indicated that dietary folate and alcohol intake may be associated with genomic regions with tumor suppressor activity such as the GSDMD and HOXA5 genes. These results were in line with the hypothesis that epigenetic mechanisms play a role in the association between folate and alcohol, although further studies are warranted to clarify the importance of these mechanisms in cancer.

Meeting report from the joint IARC-NCI international cancer seminar series: a focus on colorectal cancer.

Despite significant progress in our understanding of the etiology, biology and genetics of colorectal cancer, as well as important clinical advances, it remains the third most frequently diagnosed cancer worldwide and is the second leading cause of cancer death. Based on demographic projections, the global burden of colorectal cancer would be expected to rise by 72% from 1.8 million new cases in 2018 to over 3 million in 2040 with substantial increases anticipated in low- and middle-income countries. In this meeting report, we summarize the content of a joint workshop led by the National Cancer Institute and the International Agency for Research on Cancer, which was held to summarize the important achievements that have been made in our understanding of colorectal cancer etiology, genetics, early detection and treatment and to identify key research questions that remain to be addressed.

Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.

A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study.

BACKGROUND: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting. MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours. RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor. CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

Autoantibodies Against Glycoprotein 2 Isoforms in Pediatric Patients with Inflammatory Bowel Disease.

BACKGROUND: Anti-Glycoprotein 2 (GP2) antibodies are associated with a more complicated course of Crohn's disease (CD) in adults. Four different GP2 isoforms with different length and antibody-binding sites have been identified so far but not been explored in serological studies. We aimed to investigate the diagnostic utility of autoantibodies against all 4 isoforms of GP2 in an exclusively pediatric population for the first time. METHODS: We included 278 children and adolescents with inflammatory bowel disease: 164 with CD, 114 with ulcerative colitis, 83 disease controls (acute gastrointestinal infection, nonspecific gastrointestinal functional disorders), and 219 healthy controls. Sera were tested for anti-GP2 antibodies using 4 different isoforms of GP2 for anti-Saccharomyces cerevisiae antibodies, antineutrophil cytoplasmic antibodies, and pancreatic antibodies. RESULTS: Anti-GP2 antibodies were significantly more prevalent in patients with CD than in ulcerative colitis and controls. We found a sensitivity of 38% (with a specificity of 95%) for anti-GP2 IgG against isoform 4 in CD. Anti-GP2 IgA against isoform 1 and anti-GP2 IgG against isoform 4 possessed the best diagnostic values for identification of CD. For the differentiation of CD from ulcerative colitis anti-GP2 IgG against isoforms 3 and 4 proved to be most accurate markers. Anti-GP2 antibodies were associated with a more complicated disease behavior and bowel surgery in CD. In a subgroup of patients with CD, anti-GP2 IgG against isoform 4 proved to be a relatively stable marker over time independent of disease activity. CONCLUSIONS: Anti-GP2 antibodies against different isoforms are specific markers for CD and for different phenotypes in pediatric inflammatory bowel disease.

Prevalence of vitamin D deficiency and association with metabolic syndrome in a Qatari population.

OBJECTIVES: Despite long hours of sunlight in Qatar and other regions of the Middle East, vitamin D deficiency has been rising. In parallel, the prevalence of metabolic syndrome has also been increasing in Qatar. Vitamin D levels have been associated with metabolic syndrome but the data are inconsistent and no studies have addressed these inter-relationships in a Middle Eastern population where the prevalence of these conditions is high. The objective is to investigate the prevalence of vitamin D deficiency and its association with metabolic syndrome and its components in the Qatar Biobank population. METHODS: A cross-sectional study of 1205 participants (702 women and 503 men) from the Qatar Biobank, comprising Qataris and non-Qataris between the ages of 18 and 80 years, was used to perform multivariate linear regression analyses to examine the association between metabolic syndrome and prevalence of vitamin D deficiency (defined as <20 ng ml-1 serum vitamin D levels) adjusting for age, sex, ethnicity, season of blood collection, physical activity and education. Odds ratios and 95% confidence intervals were calculated for all analyses. RESULTS: Approximately 64% of participants were vitamin D deficient (<20 ng ml-1) with more men being deficient (68.6%) than women (61.3%). Serum vitamin D was 8% lower in individuals with metabolic syndrome (RR: 0.92, 95%CI: 0.87-0.98, P-value: 0.01) compared to individuals without metabolic syndrome. Waist circumference and HDL as well as high triglyceride levels were also significantly positively associated with vitamin D deficiency. No association was found between the other components of metabolic syndrome or diabetes and the presence of vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency is prevalent in this Qatari population. Presence of metabolic syndrome was associated with presence of vitamin D deficiency. Future prospective studies need to be conducted to investigate the potential for causality.

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

Plasma concentrations and intakes of amino acids in male meat-eaters, fish-eaters, vegetarians and vegans: a cross-sectional analysis in the EPIC-Oxford cohort.

BACKGROUND/OBJECTIVES: We aimed to investigate the differences in plasma concentrations and in intakes of amino acids between male meat-eaters, fish-eaters, vegetarians and vegans in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. SUBJECTS/METHODS: This cross-sectional analysis included 392 men, aged 30-49 years. Plasma amino acid concentrations were measured with a targeted metabolomic approach using mass spectrometry, and dietary intake was assessed using a food frequency questionnaire. Differences between diet groups in mean plasma concentrations and intakes of amino acids were examined using analysis of variance, controlling for potential confounding factors and multiple testing. RESULTS: In plasma, concentrations of 6 out of 21 amino acids varied significantly by diet group, with differences of -13% to +16% between meat-eaters and vegans. Concentrations of methionine, tryptophan and tyrosine were highest in fish-eaters and vegetarians, followed by meat-eaters, and lowest in vegans. A broadly similar pattern was seen for lysine, whereas alanine concentration was highest in fish-eaters and lowest in meat-eaters. For glycine, vegans had the highest concentration and meat-eaters the lowest. Intakes of all 18 dietary amino acids differed by diet group; for the majority of these, intake was highest in meat-eaters followed by fish-eaters, then vegetarians and lowest in vegans (up to 47% lower than in meat-eaters). CONCLUSIONS: Men belonging to different habitual diet groups have significantly different plasma concentrations of lysine, methionine, tryptophan, alanine, glycine and tyrosine. However, the differences in plasma concentrations were less marked than and did not necessarily mirror those seen for amino acid intakes.

Fibonacci family of dynamical universality classes.

Universality is a well-established central concept of equilibrium physics. However, in systems far away from equilibrium, a deeper understanding of its underlying principles is still lacking. Up to now, a few classes have been identified. Besides the diffusive universality class with dynamical exponent [Formula: see text], another prominent example is the superdiffusive Kardar-Parisi-Zhang (KPZ) class with [Formula: see text]. It appears, e.g., in low-dimensional dynamical phenomena far from thermal equilibrium that exhibit some conservation law. Here we show that both classes are only part of an infinite discrete family of nonequilibrium universality classes. Remarkably, their dynamical exponents [Formula: see text] are given by ratios of neighboring Fibonacci numbers, starting with either [Formula: see text] (if a KPZ mode exist) or [Formula: see text] (if a diffusive mode is present). If neither a diffusive nor a KPZ mode is present, all dynamical modes have the Golden Mean [Formula: see text] as dynamical exponent. The universal scaling functions of these Fibonacci modes are asymmetric Lévy distributions that are completely fixed by the macroscopic current density relation and compressibility matrix of the system and hence accessible to experimental measurement.

Reproductive and hormonal factors and mortality among women with colorectal cancer in the NIH-AARP Diet and Health Study.

BACKGROUND: Although use of menopausal hormone therapy (MHT) and some reproductive factors have been associated with colorectal cancer (CRC) risk, relations between these factors and survival after CRC diagnosis are unclear. METHODS: Among 2053 post-menopausal women diagnosed with incident CRC in the NIH-AARP Diet and Health Study, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using multivariable Cox proportional hazards regression to test associations between oral contraceptive (OC) use, menarche age, age at first birth, parity, menopausal age, and MHT use with all-cause and CRC-specific mortality. RESULTS: There were 759 deaths (332 CRC-related deaths) over a median follow-up of 7.7 years. We observed no statistically significant associations between OC use, menarche age, age at first birth, parity, menopausal age, and mortality. Compared with never MHT use, former use was not associated with mortality, but we found an inverse association among baseline current users, for both all-cause (HR=0.79, 95% CI 0.66-0.94) and CRC mortality (0.76, 0.59-0.99). CONCLUSION: Future studies should further focus on the mechanisms by which exogenous oestrogen exposure might affect tumour progression and CRC survival.

An epidemiologic risk prediction model for ovarian cancer in Europe: the EPIC study.

BACKGROUND: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. METHODS: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202,206 women in the European Prospective Investigation into Cancer and Nutrition study. RESULTS: Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration. CONCLUSION: Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.