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Background: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer. However, most studies have used self-reported anthropometry which is prone to error.Methods: Among 363,094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of head and neck cancer. Head and neck cancer risk was examined in relation to body mass index (BMI) [lean: 2, normal weight (reference): 22.5–24.9 kg/m2, overweight 25–29.9 kg/m2, obese: ≥30 kg/m2], waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) using Cox proportional hazards models.Results: Among men, a BMI < 22.5 kg/m2 was associated with higher head and neck cancer risk [HR 1.62; 95% confidence interval (CI), 1.23–2.12)]; BMI was not associated with head and neck cancer among women. WC and WHR were associated with greater risk of head and neck cancer among women (WC per 5 cm: HR, 1.08; 95% CI, 1.02–1.15; WHR per 0.1 unit: HR, 1.64; 95% CI, 1.38–1.93). After stratification by smoking status, the association for WHR was present only among smokers (Pinteraction = 0.004). Among men, WC and WHR were associated with head and neck cancer only upon additional adjustment for BMI (WC per 5 cm: HR 1.16; 95% CI, 1.07–1.26; WHR per 0.1 unit: HR, 1.42; 95% CI, 1.21–1.65).Conclusions: Central adiposity, particularly among women, may have a stronger association with head and neck cancer risk than previously estimated.Impact: Strategies to reduce obesity may beneficially impact head and neck cancer incidence. Cancer Epidemiol Biomarkers Prev; 26(6); 895–904. ©2017 AACR.

Measures of adiposity and the risk of HNC among EPIC participants, by smoking status at baseline and second questionnaire

Scatterplots of the associations between BMI (kg/m2) and WC (Fig 1a) and between BMI (kg/m2) and WHR (Fig 1b).

Measures of adiposity and the risk of HNC in the EPIC study, excluding Oxford participants with calibrated self-reported anthropometry

Background: Individuals with higher blood 25-hydroxyvitamin D [25(OH)D] levels have a lower risk of developing colorectal cancer (CRC), but the influence of 25(OH)D on mortality after CRC diagnosis is unknown.Methods: The association between prediagnostic 25(OH)D levels and CRC-specific (N = 444) and overall mortality (N = 541) was prospectively examined among 1,202 participants diagnosed with CRC between 1992 and 2003 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95% CIs according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes. Potential dietary, lifestyle, and metabolic effect modifiers were also investigated.Results: There were 541 deaths, 444 (82%) due to CRC. Mean follow-up was 73 months. In multivariable analysis, higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific (Ptrend = 0.04) and overall mortality (Ptrend = 0.01). Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 (95% CI: 0.50–0.93) for CRC-specific mortality and 0.67 (95% CI: 0.50–0.88) for overall mortality, compared with the lowest quintile. Except for a possible interaction by prediagnostic dietary calcium intake (Pinteraction = 0.01), no other potential modifying factors related to CRC survival were noted. The VDR (FokI and BsmI) and CASR (rs1801725) genotypes were not associated with survival.Conclusions: High prediagnostic 25(OH)D levels are associated with improved survival of patients with CRC.Impact: Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before, at, and after CRC diagnosis on outcomes in CRC patients. Cancer Epidemiol Biomarkers Prev; 21(4); 582–93. ©2012 AACR.

Measures of adiposity and the risk of HNC among EPIC participants, including adjustment for weight change after baseline

Background Digital health technologies (DHTs), such as electronic health records and prescribing systems, are transforming health care delivery around the world. The quality of information in DHTs is key to the quality and safety of care. We developed a novel clinical information quality (CLIQ) framework to assess the quality of clinical information in DHTs. Objective This study explored clinicians’ perspectives on the relevance, definition, and assessment of information quality dimensions in the CLIQ framework. Methods We used a systematic and iterative eDelphi approach to engage clinicians who had information governance roles or personal interest in information governance; the clinicians were recruited through purposive and snowball sampling techniques. Data were collected using semistructured online questionnaires until consensus was reached on the information quality dimensions in the CLIQ framework. Responses on the relevance of the dimensions were summarized to inform decisions on retention of the dimensions according to prespecified rules. Thematic analysis of the free-text responses was used to revise definitions and the assessment of dimensions. Results Thirty-five clinicians from 10 countries participated in the study, which was concluded after the second round. Consensus was reached on all dimensions and categories in the CLIQ framework: informativeness (accuracy, completeness, interpretability, plausibility, provenance, and relevance), availability (accessibility, portability, security, and timeliness), and usability (conformance, consistency, and maintainability). A new dimension, searchability, was introduced in the availability category to account for the ease of finding needed information in the DHTs. Certain dimensions were renamed, and some definitions were rephrased to improve clarity. Conclusions The CLIQ framework reached a high expert consensus and clarity of language relating to the information quality dimensions. The framework can be used by health care managers and institutions as a pragmatic tool for identifying and forestalling information quality problems that could compromise patient safety and quality of care. International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2021-057430

BackgroundChildren and Young People (CYP) with acute illness require routine assessment of their physiological observations. There is no agreement as to what the standard reference ranges of vital signs in children and young people are. Existing reference ranges of vital signs that are currently used in clinical practice are minimally supported by empirical evidence. They are also sometimes conflicting.MethodsWe conducted a cross-sectional study using 66356 admission episodes to analyze routinely collected age-specific respiratory rate, heart rate, and blood pressure observations of CYP aged 0-19 years old at hospital discharge. Quantile regression with Restricted Cubic Splines was used to model age-specific centiles. These were then compared with standard reference ranges and literature.ResultsNew centile charts for vital signs are presented. Advanced Paediatric Life Support (APLS, 6th Ed.) reference ranges for respiratory rate and blood pressure poorly aligned to the centiles derived in this study although the centiles for heart rate align well. Variance was also demonstrated between the study centiles and those from the clinical papers, with the greatest differences seen in the upper centiles. Similarly, in comparison with APLS reference ranges, heart rate showed best alignment.ConclusionsThis is the first-time physiological observations of CYP in a UK Children’s hospital have been described and centile charts developed. Current widely used reference ranges especially those for Heart Rate and Respiratory Rate are not fit for purpose when evaluating whether the vital signs of a child are normal or otherwise.

Purpose This viewpoint paper provides an overview of lessons learnt throughout the whole cycle of development to exploitation of digital solutions in health and wellbeing settings. This paper aims to address learnings that can be applied to all digital health technologies, including assistive technologies, apps, wearables, medical devices and serious games. Design/methodology/approach Based on the knowledge and experiences of working within a multidisciplinary team, the authors discuss lessons learnt through research and consultancy projects in digital health and translate these into pragmatic suggestions and recommendations. Findings Firstly, the importance of collaborating and co-creating with multidisciplinary stakeholders and end users throughout the whole project lifecycle is emphasised. Secondly, digital health solutions are not a means to an end, nor a panacea; decisions should be evidence-based and needs-driven. Thirdly, whenever possible, research designs and tools need to be more adaptive and personalised. Fourthly, the use of a mixed-method system approach and continuous evaluation throughout the project’s lifecycle is recommended to build up the evidence base. Fifthly, to ensure successful exploitation and implementation, a business case and timely bottom-up approach is recommended. Finally, to prevent research waste, it is our shared responsibility to collaborate with existing consortia and create an awareness of existing solutions and approaches. Originality/value In conclusion, collaborating in the field of digital health offered insights into how to be more purposeful and effective in development, evaluation and exploitation of digital health solutions. Moving this diverse and dynamic field forward is challenging but will contribute to greater long-term impact on society.

Introduction: Digital health technologies (DHTs) such as electronic health records, clinical decision support systems and electronic prescribing systems are widely used in healthcare. While adoption of DHTs can improve healthcare delivery, information quality (IQ) problems associated with DHTs can compromise quality and safety of care. The clinical information quality (CLIQ) framework for digital health is a novel approach to assessing the quality of clinical information from DHTs. This study aims to appraise the CLIQ framework by exploring clinicians’ perspectives on the relevance, definition and assessment of IQ dimensions as defined in the framework. This study will adapt the CLIQ framework to the needs of clinical information users—the clinicians. The contextualised CLIQ framework will offer a pragmatic approach to assessing clinical information from DHTs and may help to forestall IQ problems that can compromise quality and safety of care. Methods and analysis: The electronic Delphi (eDelphi) approach will be used to engage a heterogeneous group of clinicians with patient-facing and/or information governance roles recruited through purposive and snowball sampling techniques. A semi-structured online questionnaire will be used to explore clinicians’ perspectives on relevance, definition and assessment of IQ dimensions in the CLIQ framework. Survey responses on the relevance of dimensions will be summarised using descriptive statistics to inform decisions on retention of dimensions and termination of the study, based on prespecified rules. Analysis of the free-text responses will be used to revise definition and assessment of dimensions. Ethics and dissemination: Ethics approval has been obtained from the Imperial College Research Governance and Integrity Team (Imperial College Research Ethics Committee (ICREC) Reference number: 20IC6396). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences. Published version This study is part of the doctoral research of the lead author (KPF) sponsored by the Federal Government of Nigeria. The study is independent research supported in part by the National Institute for Health Research (NIHR) Applied Research Collaboration Northwest London (NIHR200180).

Background: Health researchers may struggle to choose suitable validated dietary assessment tools (DATs) for their target population. The aim of this review was to identify and collate information on validated UK DATs and validation studies for inclusion on a website to support researchers to choose appropriate DATs.Design: A systematic review of reviews of DATs was undertaken. DATs validated in UK populations were extracted from the studies identified. A searchable website was designed to display these data. Additionally, mean differences and limits of agreement between test and comparison methods were summarized by a method, weighting by sample size.Results: Over 900 validation results covering 5 life stages, 18 nutrients, 6 dietary assessment methods, and 9 validation method types were extracted from 63 validated DATs which were identified from 68 reviews. These were incorporated into www.nutritools.org. Limits of agreement were determined for about half of validations. Thirty four DATs were FFQs. Only 17 DATs were validated against biomarkers, and only 19 DATs were validated in infant/children/adolescents.Conclusions: The interactive www.nutritools.org website holds extensive validation data identified from this review and can be used to guide researchers to critically compare and choose a suitable DAT for their research question, leading to improvement of nutritional epidemiology research.

Background Digital health technologies (DHTs) generate a large volume of information used in health care for administrative, educational, research, and clinical purposes. The clinical use of digital information for diagnostic, therapeutic, and prognostic purposes has multiple patient safety problems, some of which result from poor information quality (IQ). Objective This systematic review aims to synthesize an IQ framework that could be used to evaluate the extent to which digital health information is fit for clinical purposes. Methods The review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. We searched Embase, MEDLINE, PubMed, CINAHL, Maternity and Infant Care, PsycINFO, Global Health, ProQuest Dissertations and Theses Global, Scopus, and HMIC (the Health Management Information Consortium) from inception until October 2019. Multidimensional IQ frameworks for assessing DHTs used in the clinical context by health care professionals were included. A thematic synthesis approach was used to synthesize the Clinical Information Quality (CLIQ) framework for digital health. Results We identified 10 existing IQ frameworks from which we developed the CLIQ framework for digital health with 13 unique dimensions: accessibility, completeness, portability, security, timeliness, accuracy, interpretability, plausibility, provenance, relevance, conformance, consistency, and maintainability, which were categorized into 3 meaningful categories: availability, informativeness, and usability. Conclusions This systematic review highlights the importance of the IQ of DHTs and its relevance to patient safety. The CLIQ framework for digital health will be useful in evaluating and conceptualizing IQ issues associated with digital health, thus forestalling potential patient safety problems. Trial Registration PROSPERO International Prospective Register of Systematic Reviews CRD42018097142; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=97142 International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2018-024722

BACKGROUND Digital health technologies (DHTs) generate a large volume of information used in health care for administrative, educational, research, and clinical purposes. The clinical use of digital information for diagnostic, therapeutic, and prognostic purposes has multiple patient safety problems, some of which result from poor information quality (IQ). OBJECTIVE This systematic review aims to synthesize an IQ framework that could be used to evaluate the extent to which digital health information is fit for clinical purposes. METHODS The review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. We searched Embase, MEDLINE, PubMed, CINAHL, Maternity and Infant Care, PsycINFO, Global Health, ProQuest Dissertations and Theses Global, Scopus, and HMIC (the Health Management Information Consortium) from inception until October 2019. Multidimensional IQ frameworks for assessing DHTs used in the clinical context by health care professionals were included. A thematic synthesis approach was used to synthesize the Clinical Information Quality (CLIQ) framework for digital health. RESULTS We identified 10 existing IQ frameworks from which we developed the CLIQ framework for digital health with 13 unique dimensions: accessibility, completeness, portability, security, timeliness, accuracy, interpretability, plausibility, provenance, relevance, conformance, consistency, and maintainability, which were categorized into 3 meaningful categories: availability, informativeness, and usability. CONCLUSIONS This systematic review highlights the importance of the IQ of DHTs and its relevance to patient safety. The CLIQ framework for digital health will be useful in evaluating and conceptualizing IQ issues associated with digital health, thus forestalling potential patient safety problems. CLINICALTRIAL PROSPERO International Prospective Register of Systematic Reviews CRD42018097142; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=97142 INTERNATIONAL REGISTERED REPORT RR2-10.1136/bmjopen-2018-024722

Online dietary assessment tools can reduce administrative costs and facilitate repeated dietary assessment during follow-up in large-scale prospective studies. We developed an online 24-h recall (myfood24) with automated estimation of associated nutrient intake, and assessed validity against reference recovery, predictive and concentration biomarkers. Validity of the online tool was then compared with that of traditional interviewer-administered multiple-pass 24-h recalls and presented as the expected attenuation of any diet-disease associations estimated with the tool.Metabolically stable adults were recruited and completed the new online dietary recall, a traditional interviewer-based multiple-pass recall and provided samples of blood and urine for a range of reference biomarkers. Longer-term dietary intake was estimated from up to three recalls taken two weeks apart. Estimated intakes of protein, total sugars, potassium and sodium were compared with urinary biomarker concentrations. Estimated energy intake was compared with energy expenditure measured by three-plane accelerometry and open-circuit indirect calorimetry. Validity against these biomarkers was also compared to that estimated for traditional interviewer-administered multiple-pass 24-hour recalls.At least one biomarker sample was received from each of 212 participants. Compared to reference biomarkers, both the online 24-hour recall and interviewer-based recall led to attenuation of diet-disease associations. The online tool resulted in attenuation factors of around 0.2–0.3 which could have important effects on estimated risks. For example, if the true relative risk of a diet-disease association was 2.0, an attenuation factor of 0.3 would reduce the relative risk to 1.23. Ranking using intakes against repeated biomarkers as an estimate of truth, resulted in higher attenuation factors of approximately 0.3–0.4, with a smaller impact on risk estimates. Attenuation improved substantially on repeated application of the tool. Validity of the interviewer-based recall found similar attenuation factors, but it was more administratively burdensome and expensive to implement. The online tool typically provided 10–20% lower nutrient estimates compared to the interviewer-administered tool.Our findings show that, whilst results from both automated online and traditional interviewer-based dietary recalls are attenuated compared to objective biomarker measures, the myfood24 online 24-hour recall is comparable to the more time-consuming and costly traditional interviewer-based 24-hour recall across a wide range of measures. The less burdensome implementation of the online tool, with automated nutrient coding and easy replication over a longer time period with associated gains in precision, makes it well-placed for repeated use in large-scale prospective studies.

Background Measuring dietary intake in children and adolescents can be challenging due to misreporting, difficulties in establishing portion size and reliance on recording dietary data via proxy reporters. The aim of this review was to present results from a recent systematic review of reviews reporting and comparing validated dietary assessment tools used in younger populations in the UK. Methods Validation data for dietary assessment tools used in younger populations (≤18 years) were extracted and summarised using results from a systematic review of reviews of validated dietary assessment tools. Mean differences and Bland-Altman limits of agreement (LOA) between the test and reference tool were extracted or calculated and compared for energy, macronutrients and micronutrients. Results Seventeen studies which reported validation of 14 dietary assessment tools (DATs) were identified with relevant nutrition information. The most commonly validated nutrients were energy, carbohydrate, protein, fat, calcium, iron, folate and vitamin C. There were no validated DATs reporting assessment of zinc, iodine or selenium intake. The most frequently used reference method was the weighed food diary, followed by doubly labelled water and 24 h recall. Summary plots were created to facilitate comparison between tools. On average, the test tools reported higher mean intakes than the reference methods with some studies consistently reporting wide LOA. Out of the 14 DATs, absolute values for LOA and mean difference were obtained for 11 DATs for EI. From the 24 validation results assessing EI, 16 (67%) reported higher mean intakes than the reference. Of the seven (29%) validation studies using doubly labelled water (DLW) as the reference, results for the test DATs were not substantially better or worse than those using other reference measures. Further information on the studies from this review is available on the www.nutritools.org website. Conclusions Validated dietary assessment tools for use with children and adolescents in the UK have been identified and compared. Whilst tools are generally validated for macronutrient intakes, micronutrients are poorly evaluated. Validation studies that include estimates of zinc, selenium, dietary fibre, sugars and sodium are needed.

The Oxford WebQ is an online 24-hour dietary questionnaire that is appropriate for repeated administration in large-scale prospective studies, including the UK Biobank study and the Million Women Study. We compared the performance of the Oxford WebQ and a traditional interviewer-administered multiple-pass 24-hour dietary recall against biomarkers for protein, potassium, and total sugar intake and total energy expenditure estimated by accelerometry. We recruited 160 participants in London, United Kingdom, between 2014 and 2016 and measured their biomarker levels at 3 nonconsecutive time points. The measurement error model simultaneously compared all 3 methods. Attenuation factors for protein, potassium, total sugar, and total energy intakes estimated as the mean of 2 applications of the Oxford WebQ were 0.37, 0.42, 0.45, and 0.31, respectively, with performance improving incrementally for the mean of more measures. Correlation between the mean value from 2 Oxford WebQs and estimated true intakes, reflecting attenuation when intake is categorized or ranked, was 0.47, 0.39, 0.40, and 0.38, respectively, also improving with repeated administration. These correlations were similar to those of the more administratively burdensome interviewer-based recall. Using objective biomarkers as the standard, the Oxford WebQ performs well across key nutrients in comparison with more administratively burdensome interviewer-based 24-hour recalls. Attenuation improves when the average value is taken over repeated administrations, reducing measurement error bias in assessment of diet-disease associations.

This study examined the feasibility of including myfood24, an online 24-hour dietary recall tool, in a cohort studies of older adults. Participants (n = 319) were recruited during follow-up visits for the CHARIOT-Pro Sub-study, a prospective study of cognitively healthy adults aged 60&ndash, 85 years at baseline. Email invitations were sent over three consecutive months, with weekly reminders. Multivariable regression models were applied to examine the number of recalls completed in relation to technology readiness (TR) scores and demographic characteristics. Ninety-four percent of people agreed to participate. Among participants, 67% completed at least one recall, and 48% completed two or more. Participants who completed multiple recalls reported higher self-confidence with technology and received a higher TR score than those who did not complete any recalls. A one-point higher TR score was associated with higher odds of completing three recalls compared to zero recalls (OR 1.70, 95% CI 0.96&ndash, 3.01), this association was further attenuated after adjustment for demographic and other TR-related covariates (OR 1.35, 95% CI 0.63&ndash, 2.88). This study demonstrates reasonable participation rates for a single myfood24 recall among older adults participating in a cohort study but suggests that further support may be required to obtain multiple recalls in this population.

Objective: Evaluate a method for the estimation of the nocturnal systolic blood pressure dip from 24-hour blood pressure trends using a wrist-worn Photoplethysmography (PPG) sensor and a deep neural network in free-living individuals, comparing the deep neural network to traditional machine learning and non-machine learning baselines. Approach: A wrist-worn PPG sensor was worn by 106 healthy individuals for 226 days during which 5111 reference values for blood pressure were obtained with a 24-hour ambulatory blood pressure monitor as ground truth and matched with the PPG sensor data. Features based on heart rate variability and pulse morphology were extracted from the PPG waveforms. Machine learning models (linear regression, random forests, dense neural networks and long- and short-term memory neural networks) were then trained and evaluated in their capability of tracking trends in systolic and diastolic blood pressure, as well as the estimation of the nocturnal systolic blood pressure dip. Main results Best performance was obtained with a deep long- and shortterm memory neural network with a Root Mean Squared Error (RMSE) of 3.12±2.20 ∆mmHg and a correlation of 0.69 (p = 3 ∗ 10−5) with the ground truth Systolic Blood Pressure (SBP) dip. This dip was derived from trend estimates of blood pressure which had an RMSE of 8.22±1.49 mmHg for systolic and 6.55±1.39 mmHg for diastolic blood pressure. The random forest model showed slightly lower average error magnitude for SBP trends (7.86±1.57 mmHg), however Bland-Altmann analysis revealed systematic problems in its predictions that were less present in the long- and short-term memory model. Significance The work provides first evidence for the unobtrusive estimation of the nocturnal blood pressure dip, a highly prognostic clinical parameter. It is also the first to evaluate unobtrusive blood pressure measurement in a large data set of unconstrained 24-hour measurements in free-living individuals and provides evidence for the utility of long- and short-term models in this domain.

Alcohol intake has been related to an increased risk of breast cancer (BC) while dietary fiber intake has been inversely associated to BC risk. A beneficial effect of fibers on ethanol carcinogenes ...

International audience; Engagement in electronic health (eHealth) and mobile health (mHealth) behavior change interventions is thought to be important for intervention effectiveness, though what constitutes engagement and how it enhances efficacy has been somewhat unclear in the literature. Recently published detailed definitions and conceptual models of engagement have helped to build consensus around a definition of engagement and improve our understanding of how engagement may influence effectiveness. This work has helped to establish a clearer research agenda. However, to test the hypotheses generated by the conceptual modules, we need to know how to measure engagement in a valid and reliable way. The aim of this viewpoint is to provide an overview of engagement measurement options that can be employed in eHealth and mHealth behavior change intervention evaluations, discuss methodological considerations, and provide direction for future research. To identify measures, we used snowball sampling, starting from systematic reviews of engagement research as well as those utilized in studies known to the authors. A wide range of methods to measure engagement were identified, including qualitative measures, self-report questionnaires, ecological momentary assessments, system usage data, sensor data, social media data, and psychophysiological measures. Each measurement method is appraised and examples are provided to illustrate possible use in eHealth and mHealth behavior change research. Recommendations for future research are provided, based on the limitations of current methods and the heavy reliance on system usage data as the sole assessment of engagement. The validation and adoption of a wider range of engagement measurements and their thoughtful application to the study of engagement are encouraged.

Background Online dietary assessment tools can reduce administrative costs and facilitate repeated dietary assessment during follow-up in large-scale studies. However, information on bias due to measurement error of such tools is limited. We developed an online 24-h recall (myfood24) and compared its performance with a traditional interviewer-administered multiple-pass 24-h recall, assessing both against biomarkers. Methods Metabolically stable adults were recruited and completed the new online dietary recall, an interviewer-based multiple pass recall and a suite of reference measures. Longer-term dietary intake was estimated from up to 3 × 24-h recalls taken 2 weeks apart. Estimated intakes of protein, potassium and sodium were compared with urinary biomarker concentrations. Estimated total sugar intake was compared with a predictive biomarker and estimated energy intake compared with energy expenditure measured by accelerometry and calorimetry. Nutrient intakes were also compared to those derived from an interviewer-administered multiple-pass 24-h recall. Results Biomarker samples were received from 212 participants on at least one occasion. Both self-reported dietary assessment tools led to attenuation compared to biomarkers. The online tools resulted in attenuation factors of around 0.2–0.3 and partial correlation coefficients, reflecting ranking intakes, of approximately 0.3–0.4. This was broadly similar to the more administratively burdensome interviewer-based tool. Other nutrient estimates derived from myfood24 were around 10–20% lower than those from the interviewer-based tool, with wide limits of agreement. Intraclass correlation coefficients were approximately 0.4–0.5, indicating consistent moderate agreement. Conclusions Our findings show that, whilst results from both measures of self-reported diet are attenuated compared to biomarker measures, the myfood24 online 24-h recall is comparable to the more time-consuming and costly interviewer-based 24-h recall across a range of measures. Electronic supplementary material The online version of this article (10.1186/s12916-018-1113-8) contains supplementary material, which is available to authorized users.

Objective Monitoring of physical activity and sedentary behaviours by mobile phone applications (apps) and wearable technology (wearables) may improve these health behaviours. This systematic review aims to synthesise the qualitative literature on the barriers and facilitators of using apps and wearables for monitoring physical activity and/or sedentary behaviour in adults. Methods This review protocol is registered in PROSPERO (CRD42017070194). Scientific databases including CINAHL Complete, MEDLINE, PsycINFO, SPORTDiscus, Cochrane Library and Scopus will be searched for relevant studies published from 1 January 2012 to the date the searches are conducted. Studies will be included if they incorporated adults who used an app or wearable for monitoring physical activity and/or sedentary behaviour; explored the barriers and/or facilitators of using an app and/or wearable; and were published in English. Following duplicate screening of titles and abstracts, full texts of potentially eligible papers will be screened to identify studies using qualitative approaches to explore barriers and facilitators of using apps and/or wearables for monitoring physical activity and/or sedentary behaviour. Discrepancies will be resolved through consensus or by consulting a third screener. Relevant excerpts (quotes and text) from the included papers will be extracted and analysed thematically. The Critical Appraisal Skills Programme Qualitative Research Checklist will be used to appraise included studies. Conclusion The results of this work will be useful for those intending to monitor physical activity and/or sedentary behaviour using these technologies.

Accurate diet measurement is challenging and strategies to support researchers in selecting the most appropriate dietary assessment tools (DATs) are required. DIET@NET (DIETary Assessment tools NETwork) partnership aimed to create an online resource that provides guidelines for selecting tools with access to validated DATs. The Nutritools website(1) (www.nutritools.org), was developed using 3 approaches. 1) Creation of Best Practice Guidelines(2), enabling researchers to choose the most appropriate DAT for their work. These were generated using the Delphi method which enabled integration of expert views. 2) Creating an interactive DAT e-library, with the DATs being identified through a systematic review of systematic reviews(3). Bubble charts and summary plots are used to compare DATs. 3) Development of a Food Questionnaire Creator (FQC), an online interface between food tables and the DATs which allows users to create their own food questionnaires. This work was overseen by the DIET@NET partnership. Other useful information includes links to food composition databases and a detailed glossary of terms. Results from the systematic review of reviews generated information for Nutritools. The website includes 127 international validated tools, of which 63 tools were validated in the UK (with 45 validated from year 2000 onwards). The majority (n = 34) of the validated tools were food frequency questionnaires, developed from 1981 to 2016. Numbers of foods included ranged from 8–692 items. Five of the 12 dietary recalls included were web-based. Tools were usually validated against another self-reported dietary assessment method, mainly weighed food diaries. More than 1500 papers with non-UK tools were identified, of these, data on 64 international tools and their validation studies were added to Nutritools. The FQC allows for food questionnaires to be created using data from the UK National Diet and Nutrition Survey (NDNS) Year 6 and the Composition of Foods Integrated Dataset. Results from the NDNS can be used to formulate food questions that capture a large proportion of the nutrients of interest and to inform portion sizes. In conclusion, Nutritools (www.nutritools.org), is an online platform that hosts international validated and interactive DATs. Researchers can use the interactive Best Practice Guidelines and features in the selection of the most appropriate DAT for their study, and the Food Questionnaire Creator to develop their own online food questionnaires. This project was funded by the Medical Research Council (MRC) (ref: MR/L02019X/1). 1. Warthon-Medina M, Hooson J, Hancock N, et al. (2017) The Lancet 390, pS94. 2. Cade JE, Warthon-Medina M, Albar S, et al. (2017) BMC Medicine 15(1), p202. 3. Hooson J, Hancock N, Greenwood DC, et al. (2016) Proc Nutr Soc 75(OCE3).

Background: Electronic health (eHealth) and mobile health (mHealth) approaches to address low physical activity levels, sedentary behavior, and unhealthy diets have received significant research attention. However, attempts to systematically map the entirety of the research field are lacking. This gap can be filled with a bibliometric study, where publication-specific data such as citations, journals, authors, and keywords are used to provide a systematic overview of a specific field. Such analyses will help researchers better position their work. Objective: The objective of this review was to use bibliometric data to provide an overview of the eHealth and mHealth research field related to physical activity, sedentary behavior, and diet Methods: The Web of Science (WoS) Core Collection was searched to retrieve all existing and highly cited (as defined by WoS) physical activity, sedentary behavior, and diet related eHealth and mHealth research papers published in English between January 1, 2000 and December 31, 2016. Retrieved titles were screened for eligibility, using the abstract and full-text where needed. We described publication trends over time, which included journals, authors, and countries of eligible papers, as well as their keywords and subject categories. Citations of eligible papers were compared with those expected based on published data. Additionally, we described highly-cited papers of the field (ie, top ranked 1%). Results: The search identified 4805 hits, of which 1712 (including 42 highly-cited papers) were included in the analyses. Publication output increased on an average of 26% per year since 2000, with 49.00% (839/1712) of papers being published between 2014 and 2016. Overall and throughout the years, eHealth and mHealth papers related to physical activity, sedentary behavior, and diet received more citations than expected compared with papers in the same WoS subject categories. The Journal of Medical Internet Research published most papers in the field (9.58%, 164/1712). Most papers originated from high-income countries (96.90%, 1659/1717), in particular the United States (48.83%, 836/1712). Most papers were trials and studied physical activity. Beginning in 2013, research on Generation 2 technologies (eg, smartphones, wearables) sharply increased, while research on Generation 1 (eg, text messages) technologies increased at a reduced pace. Reviews accounted for 20 of the 42 highly-cited papers (n=19 systematic reviews). Social media, smartphone apps, and wearable activity trackers used to encourage physical activity, less sedentary behavior, and/or healthy eating were the focus of 14 highly-cited papers. Conclusions: This study highlighted the rapid growth of the eHealth and mHealth physical activity, sedentary behavior, and diet research field, emphasized the sizeable contribution of research from high-income countries, and pointed to the increased research interest in Generation 2 technologies. It is expected that the field will grow and diversify further and that reviews and research on most recent technologies will continue to strongly impact the field. Refereed/Peer-reviewed

Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10 g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7-5.8%). Taking 0 to 5 g/day as reference, alcohol intake of >5 to 15 g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1-11%). Significant increasing trends were observed between alcohol intake and ER+/PR+, ER-/PR-, HER2- and ER-/PR-HER2- tumors. Breast cancer risk was stronger among women who started drinking prior to first full-time pregnancy. Overall, our results confirm the association between alcohol intake and both hormone receptor positive and hormone receptor negative breast tumors, suggesting that timing of exposure to alcohol drinking may affect the risk. Therefore, women should be advised to control their alcohol consumption.

UNSTRUCTURED Engagement in electronic health (eHealth) and mobile health (mHealth) behavior change interventions is thought to be important for intervention effectiveness, though what constitutes engagement and how it enhances efficacy has been somewhat unclear in the literature. Recently published detailed definitions and conceptual models of engagement have helped to build consensus around a definition of engagement and improve our understanding of how engagement may influence effectiveness. This work has helped to establish a clearer research agenda. However, to test the hypotheses generated by the conceptual modules, we need to know how to measure engagement in a valid and reliable way. The aim of this viewpoint is to provide an overview of engagement measurement options that can be employed in eHealth and mHealth behavior change intervention evaluations, discuss methodological considerations, and provide direction for future research. To identify measures, we used snowball sampling, starting from systematic reviews of engagement research as well as those utilized in studies known to the authors. A wide range of methods to measure engagement were identified, including qualitative measures, self-report questionnaires, ecological momentary assessments, system usage data, sensor data, social media data, and psychophysiological measures. Each measurement method is appraised and examples are provided to illustrate possible use in eHealth and mHealth behavior change research. Recommendations for future research are provided, based on the limitations of current methods and the heavy reliance on system usage data as the sole assessment of engagement. The validation and adoption of a wider range of engagement measurements and their thoughtful application to the study of engagement are encouraged.

Background Measuring dietary intake is difficult and strategies which enable researchers to select the most appropriate dietary assessment tools (DATs) are needed. The DIET@NET partnership aimed to create a central resource to improve the quality, consistency and comparability of dietary data. Methods Development of the Nutritools website was divided into 3 strands. 1) Creating Best Practice Guidelines (BPG) which enables researchers to choose the most appropriate DAT for their work. These were generated using the Delphi method which enabled integration of expert views. 2) Creating an interactive DAT e-library, with the DATs being identified through a systematic review of reviews. 3) Creating an online interface (Food Questionnaire Creator (FQC)) between food tables and DATs. Results The main features of the Nutritools website, includes the interactive Dietary Assessment Guidelines comprising of 43 BPG and a summary of the strengths and weaknesses of the dietary assessment methods. The DAT e-library provides in-depth information regarding the tools and validation study characteristics, and results. This information is also provided visually through bubble and summary plots, which allows easier comparison between the DATs. Finally, the FQC allows researchers to create new online food questionnaires or use existing DATs identified from the systematic review. Users can map their questionnaire to the latest food composition databases. Currently the FQC only provides UK DATs and databases but it has the capability to allow for international databases and tools to be added. Conclusions DIET@NET partnership has created the state-of-the-art Nutritools website, www.nutritools.org, which provides guidance to researchers undertaking studies that require dietary assessment. By providing guidance and access to validated DATs, the quality, consistency and comparability of dietary assessment in research can be improved. Key messages: •The Nutritools website, www.nutritools.org provides a central resource for researchers undertaking studies which require dietary measurement. •The Nutritools website, www.nutritools.org provides guidance and access to validated dietary assessment tools.

BACKGROUND Electronic health (eHealth) and mobile health (mHealth) approaches to address low physical activity levels, sedentary behavior, and unhealthy diets have received significant research attention. However, attempts to systematically map the entirety of the research field are lacking. This gap can be filled with a bibliometric study, where publication-specific data such as citations, journals, authors, and keywords are used to provide a systematic overview of a specific field. Such analyses will help researchers better position their work. OBJECTIVE The objective of this review was to use bibliometric data to provide an overview of the eHealth and mHealth research field related to physical activity, sedentary behavior, and diet. METHODS The Web of Science (WoS) Core Collection was searched to retrieve all existing and highly cited (as defined by WoS) physical activity, sedentary behavior, and diet related eHealth and mHealth research papers published in English between January 1, 2000 and December 31, 2016. Retrieved titles were screened for eligibility, using the abstract and full-text where needed. We described publication trends over time, which included journals, authors, and countries of eligible papers, as well as their keywords and subject categories. Citations of eligible papers were compared with those expected based on published data. Additionally, we described highly-cited papers of the field (ie, top ranked 1%). RESULTS The search identified 4805 hits, of which 1712 (including 42 highly-cited papers) were included in the analyses. Publication output increased on an average of 26% per year since 2000, with 49.00% (839/1712) of papers being published between 2014 and 2016. Overall and throughout the years, eHealth and mHealth papers related to physical activity, sedentary behavior, and diet received more citations than expected compared with papers in the same WoS subject categories. The Journal of Medical Internet Research published most papers in the field (9.58%, 164/1712). Most papers originated from high-income countries (96.90%, 1659/1717), in particular the United States (48.83%, 836/1712). Most papers were trials and studied physical activity. Beginning in 2013, research on Generation 2 technologies (eg, smartphones, wearables) sharply increased, while research on Generation 1 (eg, text messages) technologies increased at a reduced pace. Reviews accounted for 20 of the 42 highly-cited papers (n=19 systematic reviews). Social media, smartphone apps, and wearable activity trackers used to encourage physical activity, less sedentary behavior, and/or healthy eating were the focus of 14 highly-cited papers. CONCLUSIONS This study highlighted the rapid growth of the eHealth and mHealth physical activity, sedentary behavior, and diet research field, emphasized the sizeable contribution of research from high-income countries, and pointed to the increased research interest in Generation 2 technologies. It is expected that the field will grow and diversify further and that reviews and research on most recent technologies will continue to strongly impact the field.

BACKGROUND: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer (HNC). However, most studies have used self-reported anthropometry which is prone to error. METHODS: Among 363 094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of HNC. HNC risk was examined in relation to body mass index (BMI) [lean: < 22.5 kg/m², normal weight (reference): 22.5-24.9 kg/m², overweight 25-29.9 kg/m², obese: > 30 kg/m²], waist circumference (WC), hip circumference (HC) and waist to hip ratio (WHR) using Cox proportional hazards models. RESULTS: Among men, a BMI < 22.5 kg/m² was associated with higher HNC risk [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.23 - 2.12)]; BMI was not associated with HNC among women. WC and WHR were associated with greater risk of HNC among women, (WC per 5 cm: HR 1.08, 95% CI 1.02 - 1.15; WHR per 0.1 unit: HR 1.64, 95% CI 1.38 - 1.93). After stratification by smoking status, the association for WHR was present only among smokers (p interaction 0.004). Among men, WC and WHR were associated with HNC only upon additional adjustment for BMI (WC per 5 cm: HR 1.16, 95% CI 1.07 - 1.26; WHR per 0.1 unit: HR 1.42, 95% CI 1.21 - 1.65). CONCLUSION: Central adiposity, particularly among women, may have a stronger association with HNC risk than previously estimated. IMPACT: Strategies to reduce obesity may beneficially impact HNC incidence., The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC- 2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; , PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to K.T. Khaw, N.J. Wareham; C570/A16491 to R.C. Travis and C8221/A19170 to Tim Key (EPIC-Oxford), Medical Research Council (1000143 to K.T. Khaw, N.J. Wareham, MR/M012190/1 to Tim Key (EPIC-Oxford)) (United Kingdom).

BACKGROUND: The consumption of sweet beverages has been associated with greater risk of type 2 diabetes and obesity, which may be involved in the development of pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may increase pancreatic cancer risk as well.OBJECTIVE: We examined the association between sweet-beverage consumption (including total, sugar-sweetened, and artificially sweetened soft drink and juice and nectar consumption) and pancreatic cancer risk.DESIGN: The study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 477,199 participants (70.2% women) with a mean age of 51 y at baseline were included, and 865 exocrine pancreatic cancers were diagnosed after a median follow-up of 11.60 y (IQR: 10.10-12.60 y). Sweet-beverage consumption was assessed with the use of validated dietary questionnaires at baseline. HRs and 95% CIs were obtained with the use of multivariable Cox regression models that were stratified by age, sex, and center and adjusted for educational level, physical activity, smoking status, and alcohol consumption. Associations with total soft-drink consumption were adjusted for juice and nectar consumption and vice versa.RESULTS: Total soft-drink consumption (HR per 100 g/d: 1.03; 95% CI: 0.99, 1.07), sugar-sweetened soft-drink consumption (HR per 100 g/d: 1.02; 95% CI: 0.97, 1.08), and artificially sweetened soft-drink consumption (HR per 100 g/d: 1.04; 95% CI: 0.98, 1.10) were not associated with pancreatic cancer risk. Juice and nectar consumption was inversely associated with pancreatic cancer risk (HR per 100 g/d: 0.91; 95% CI: 0.84, 0.99); this association remained statistically significant after adjustment for body size, type 2 diabetes, and energy intake.CONCLUSIONS: Soft-drink consumption does not seem to be associated with pancreatic cancer risk. Juice and nectar consumption might be associated with a modest decreased pancreatic cancer risk. Additional studies with specific information on juice and nectar subtypes are warranted to clarify these results.

Source at https://doi.org/10.1371/journal.pone.0173117 Adult height and sitting height may reflect genetic and environmental factors, including early life nutrition, physical and social environments. Previous studies have reported divergent associations for height and chronic disease mortality, with positive associations observed for cancer mortality but inverse associations for circulatory disease mortality. Sitting height might be more strongly associated with insulin resistance; however, data on sitting height and mortality is sparse. Using the European Prospective Investigation into Cancer and Nutrition study, a prospective cohort of 409,748 individuals, we examined adult height and sitting height in relation to all-cause and cause-specific mortality. Height was measured in the majority of participants; sitting height was measured in ~253,000 participants. During an average of 12.5 years of follow-up, 29,810 deaths (11,931 from cancer and 7,346 from circulatory disease) were identified. Hazard ratios (HR) with 95% confidence intervals (CI) for death were calculated using multivariable Cox regression within quintiles of height. Height was positively associated with cancer mortality (men: HRQ5 vs. Q1 = 1.11, 95%CI = 1.00–1.24; women: HRQ5 vs. Q1 = 1.17, 95%CI = 1.07–1.28). In contrast, height was inversely associated with circulatory disease mortality (men: HRQ5 vs. Q1 = 0.63, 95%CI = 0.56–0.71; women: HRQ5 vs. Q1 = 0.81, 95%CI = 0.70–0.93). Although sitting height was not associated with cancer mortality, it was inversely associated with circulatory disease (men: HRQ5 vs. Q1 = 0.64, 95%CI = 0.55–0.75; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.49–0.74) and respiratory disease mortality (men: HRQ5 vs. Q1 = 0.45, 95%CI = 0.28–0.71; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.40–0.89). We observed opposing effects of height on cancer and circulatory disease mortality. Sitting height was inversely associated with circulatory disease and respiratory disease mortality.

Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (α- and β-carotene, canthaxanthin, β-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (α-, β- and γ- and δ-tocopherol) and dietary consumption of β-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary β-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties.

BackgroundRapid medical assessment and treatment of patients with transient ischemic attack (TIA) or stroke significantly reduces the risk of recurrent stroke. Previous research has shown that delays to initial medical assessment are due to lack of an urgent response to symptoms. In comparison to other communities living within the UK, South Asians have a higher risk of stroke/TIA. Therefore, it is critically important to explore stroke/TIA knowledge and anticipated response to symptoms, within this community.AimThis study aims to provide preliminary evidence of stroke knowledge and awareness of the relaunched ‘Act FAST’ campaign in the South Asian community and to provide evidence of successful participant recruitment from ‘hard to engage’ groups.MethodA pilot mixed methods study, incorporating focus group discussions and a short ‘tick box’ style paper survey, designed to assess and explore participant knowledge of stroke/TIA symptoms, and awareness of the relaunched ‘Act FAST’ campaign. Barriers and facilitators to stroke education and the suitability of mass-media campaigns are also discussed during the focus groups. All participants were recruited from places of worship.ResultsThe authors will present highlights from the ‘on-going’ study including; the recruitment strategy, barriers and facilitators to recruitment in Sikh temples and preliminary findings from 68 completed surveys. Highlights from the focus group discussions will be presented, alongside participant suggested methods to improve stroke/TIA knowledge in Indian communities.ConclusionPreliminary findings suggest awareness of stroke symptoms in the Indian community, but less awareness of TIA. Non-English speakers may be less aware of ‘Act FAST’.

OBJECTIVE Younger age at menarche, a marker of pubertal timing in girls, is associated with higher risk of later type 2 diabetes. We aimed to confirm this association and to examine whether it is explained by adiposity. RESEARCH DESIGN AND METHODS The prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from 26 research centers across eight European countries. We tested the association between age at menarche and incident type 2 diabetes using Prentice-weighted Cox regression in 15,168 women (n = 5,995 cases). Models were adjusted in a sequential manner for potential confounding and mediating factors, including adult BMI. RESULTS Mean menarcheal age ranged from 12.6 to 13.6 years across InterAct countries. Each year later menarche was associated with 0.32 kg/m2 lower adult BMI. Women in the earliest menarche quintile (8–11 years, n = 2,418) had 70% higher incidence of type 2 diabetes compared with those in the middle quintile (13 years, n = 3,634), adjusting for age at recruitment, research center, and a range of lifestyle and reproductive factors (hazard ratio [HR], 1.70; 95% CI, 1.49–1.94; P < 0.001). Adjustment for BMI partially attenuated this association (HR, 1.42; 95% CI, 1.18–1.71; P < 0.001). Later menarche beyond the median age was not protective against type 2 diabetes. CONCLUSIONS Women with history of early menarche have higher risk of type 2 diabetes in adulthood. Less than half of this association appears to be mediated by higher adult BMI, suggesting that early pubertal development also may directly increase type 2 diabetes risk.