CCQM-K90, formaldehyde in nitrogen, 2 μmol mol− 1 Final report

The CCQM-K90 comparison is designed to evaluate the level of comparability of national metrology institutes (NMI) or designated institutes (DI) measurement capabilities for formaldehyde in nitrogen at a nominal mole fraction of 2 μmol mol−1. The comparison was organised by the BIPM using a suite of gas mixtures prepared by a producer of specialty calibration gases. The BIPM assigned the formaldehyde mole fraction in the mixtures by comparison with primary mixtures generated dynamically by permeation coupled with continuous weighing in a magnetic suspension balance. The BIPM developed two dynamic sources of formaldehyde in nitrogen that provide two independent values of the formaldehyde mole fraction: the first one based on diffusion of trioxane followed by thermal conversion to formaldehyde, the second one based on permeation of formaldehyde from paraformaldehyde contained in a permeation tube. Two independent analytical methods, based on cavity ring down spectroscopy (CRDS) and Fourier transform infrared spectroscopy (FTIR) were used for the assignment procedure. Each participating institute was provided with one transfer standard and value assigned the formaldehyde mole fraction in the standard based on its own measurement capabilities. The stability of the formaldehyde mole fraction in transfer standards was deduced from repeated measurements performed at the BIPM before and after measurements performed at participating institutes. In addition, 5 control standards were kept at the BIPM for regular measurements during the course of the comparison. Temporal trends that approximately describe the linear decrease of the amount-of-substance fraction of formaldehyde in nitrogen in the transfer standards over time were estimated by two different mathematical treatments, the outcomes of which were proposed to participants. The two treatments also differed in the way measurement uncertainties arising from measurements performed at the BIPM were propagated to the uncertainty of the trend parameters, as well as how the dispersion of the dates when measurements were made by the participants was taken into account. Upon decision of the participants, the Key Comparison Reference Values were assigned by the BIPM using the largest uncertainty for measurements performed at the BIPM, linear regression without weight to calculate the trend parameters, and not taking into account the dispersion of dates for measurements made by the participant. Each transfer standard was assigned its own reference value and associated expanded uncertainty. An expression for the degree of equivalence between each participating institute and the KCRV was calculated from the comparison results and measurement uncertainties submitted by participating laboratories. Results of the alternative mathematical treatment are presented in annex of this report

High frequency operation of an integrated electro-absorption modulator onto a vertical-cavity surface-emitting laser

We present in this paper the vertical integration of an electro-absorption modulator (EAM) onto a vertical-cavity surface-emitting laser (VCSEL). We discuss the design, fabrication, and measured characteristics of the combined VCSEL and EAM. We previously demonstrated a standalone EAM with an optical bandwidth around 30 GHz. In this paper we present for the first time an optical bandwidth of 30 GHz for an EAM integrated onto a VCSEL. This device exhibits single-mode operation and a very low chirp, below 0.1 nm, even with a modulation depth of 70% which makes this device very competitive for high-speed communications in data centers

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

Serum procalcitonin and CRP levels in non-alcoholic fatty liver disease: a case control study

<p>Abstract</p> <p>Background</p> <p>Both C reactive protein (CRP) and procalcitonin (PCT) are well known acute phase reactant proteins. CRP was reported to increase in metabolic syndrome and type-2 diabetes. Similarly altered level of serum PCT was found in chronic liver diseases and cirrhosis. The liver is considered the main source of CRP and a source of PCT, however, the serum PCT and CRP levels in non-alcoholic fatty liver disease (NAFLD) were not compared previously. Therefore we aimed to study the diagnostic and discriminative role of serum PCT and CRP in NAFLD.</p> <p>Methods</p> <p>Fifty NAFLD cases and 50 healthy controls were included to the study. Liver function tests were measured, body mass index was calculated, and insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Serum CRP was measured with nephalometric method. Serum PCT was measured with Kryptor based system.</p> <p>Results</p> <p>Serum PCT levels were similar in steatohepatitis (n 20) and simple steatosis (n 27) patients, and were not different than the control group (0.06 ± 0.01, 0.04 ± 0.01 versus 0.06 ± 0.01 ng/ml respectively). Serum CRP levels were significantly higher in simple steatosis, and steatohepatitis groups compared to healthy controls (7.5 ± 1.6 and 5.2 ± 2.5 versus 2.9 ± 0.5 mg/dl respectively p < 0.01). CRP could not differentiate steatohepatitis from simple steatosis. Beside, three patients with focal fatty liver disease had normal serum CRP levels.</p> <p>Conclusion</p> <p>Serum PCT was within normal ranges in patients with simple steatosis or steatohepatitis and has no diagnostic value. Serum CRP level was increased in NAFLD compared to controls. CRP can be used as an additional marker for diagnosis of NAFLD but it has no value in discrimination of steatohepatitis from simple steatosis.</p

Food processing and cancer risk in Europe: results from the prospective EPIC cohort study

Background Food processing has been hypothesised to play a role in cancer development; however, data from large-scale epidemiological studies are scarce. This study investigated the association between dietary intake according to amount of food processing and risk of cancer at 25 anatomical sites using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods This study used data from the prospective EPIC cohort study, which recruited participants between March 18, 1991, and July 2, 2001, from 23 centres in ten European countries. Participant eligibility within each cohort was based on geographical or administrative boundaries. Participants were excluded if they had a cancer diagnosis before recruitment, had missing information for the NOVA food processing classification, or were within the top and bottom 1% for ratio of energy intake to energy requirement. Validated dietary questionnaires were used to obtain information on food and drink consumption. Participants with cancer were identified using cancer registries or during follow-up from a combination of sources, including cancer and pathology centres, health insurance records, and active follow-up of participants. We performed a substitution analysis to assess the effect of replacing 10% of processed foods and ultra-processed foods with 10% of minimally processed foods on cancer risk at 25 anatomical sites using Cox proportional hazard models. Findings 521 324 participants were recruited into EPIC, and 450 111 were included in this analysis (318 686 [70·8%] participants were female individuals and 131 425 [29·2%] were male individuals). In a multivariate model adjusted for sex, smoking, education, physical activity, height, and diabetes, a substitution of 10% of processed foods with an equal amount of minimally processed foods was associated with reduced risk of overall cancer (hazard ratio 0·96, 95% CI 0·95–0·97), head and neck cancers (0·80, 0·75–0·85), oesophageal squamous cell carcinoma (0·57, 0·51–0·64), colon cancer (0·88, 0·85–0·92), rectal cancer (0·90, 0·85–0·94), hepatocellular carcinoma (0·77, 0·68–0·87), and postmenopausal breast cancer (0·93, 0·90–0·97). The substitution of 10% of ultra-processed foods with 10% of minimally processed foods was associated with a reduced risk of head and neck cancers (0·80, 0·74–0·88), colon cancer (0·93, 0·89–0·97), and hepatocellular carcinoma (0·73, 0·62–0·86). Most of these associations remained significant when models were additionally adjusted for BMI, alcohol and dietary intake, and quality. Interpretation This study suggests that the replacement of processed and ultra-processed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types. Funding Cancer Research UK, l'Institut National du Cancer, and World Cancer Research Fund International

Determinants of blood acylcarnitine concentrations in healthy individuals of the European Prospective Investigation into cancer and nutrition

Background & aims: Circulating levels of acylcarnitines (ACs) have been associated with the risk of various diseases such as cancer and type 2 diabetes. Diet and lifestyle factors have been shown to influence AC concentrations but a better understanding of their biological, lifestyle and metabolic determinants is needed. Methods: Circulating ACs were measured in blood by targeted (15 ACs) and untargeted metabolomics (50 ACs) in 7770 and 395 healthy participants of the European Prospective Investigation into Cancer and Nutrition (EPIC), respectively. Associations with biological and lifestyle characteristics, dietary patterns, self-reported intake of individual foods, estimated intake of carnitine and fatty acids, and fatty acids in plasma phospholipid fraction and amino acids in blood were assessed. Results: Age, sex and fasting status were associated with the largest proportion of AC variability (partial-r up to 0.19, 0.18 and 0.16, respectively). Some AC species of medium or long-chain fatty acid moiety were associated with the corresponding fatty acids in plasma (partial-r = 0.24) or with intake of specific foods such as dairy foods containing the same fatty acid. ACs of short-chain fatty acid moiety (propionylcarnitine and valerylcarnitine) were moderately associated with concentrations of branched-chain amino acids (partial-r = 0.5). Intake of most other foods and of carnitine showed little association with AC levels. Conclusions: Our results show that determinants of ACs in blood vary according to their fatty acid moiety, and that their concentrations are related to age, sex, diet, and fasting status. Knowledge on their potential determinants may help interpret associations of ACs with disease risk and inform on potential dietary and lifestyle factors that might be modified for disease prevention

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 q(val)=0.029 and q(val)=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

Consumption of ultra-processed foods and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study

Background It is currently unknown whether ultra-processed foods (UPFs) consumption is associated with a higher incidence of multimorbidity. We examined the relationship of total and subgroup consumption of UPFs with the risk of multimorbidity defined as the co-occurrence of at least two chronic diseases in an individual among first cancer at any site, cardiovascular disease, and type 2 diabetes. Methods This was a prospective cohort study including 266,666 participants (60% women) free of cancer, cardiovascular disease, and type 2 diabetes at recruitment from seven European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Foods and drinks consumed over the previous 12 months were assessed at baseline by food-frequency questionnaires and classified according to their degree of processing using Nova classification. We used multistate modelling based on Cox regression to estimate cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations of total and subgroups of UPFs with the risk of multimorbidity of cancer and cardiometabolic diseases. Findings After a median of 11.2 years of follow-up, 4461 participants (39% women) developed multimorbidity of cancer and cardiometabolic diseases. Higher UPF consumption (per 1 standard deviation increment, ∼260 g/day without alcoholic drinks) was associated with an increased risk of multimorbidity of cancer and cardiometabolic diseases (HR: 1.09, 95% CI: 1.05, 1.12). Among UPF subgroups, associations were most notable for animal-based products (HR: 1.09, 95% CI: 1.05, 1.12), and artificially and sugar-sweetened beverages (HR: 1.09, 95% CI: 1.06, 1.12). Other subgroups such as ultra-processed breads and cereals (HR: 0.97, 95% CI: 0.94, 1.00) or plant-based alternatives (HR: 0.97, 95% CI: 0.91, 1.02) were not associated with risk. Interpretation Our findings suggest that higher consumption of UPFs increases the risk of cancer and cardiometabolic multimorbidity. Funding Austrian Academy of Sciences, Fondation de France, Cancer Research UK, World Cancer Research Fund International, and the Institut National du Cancer