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Background Ambient air pollution, detrimental built and social environments, social isolation (SI), low socioeconomic status (SES), and rural (versus urban) residence have been associated with cognitive decline and risk of Alzheimer’s disease and related dementias (ADRD). Research is needed to investigate the influence of ambient air pollution and built and social environments on SI and cognitive decline among rural, disadvantaged, ethnic minority communities. To address this gap, this cohort study will recruit an ethnoracially diverse, rural Florida sample in geographic proximity to seasonal agricultural burning. We will (1) examine contributions of smoke-related fine particulate matter (PM2.5) exposures to SI and cognitive function; (2) determine effects of built and social environments on SI and cognitive function; and (3) contextualize SI and cognitive function among residents from different ethnoracial groups during burn and non-burn seasons. Methods We will recruit 1,087 community-dwelling, dementia-free, ≥45-year-olds from five communities in Florida’s Lake Okeechobee region. Over 36 months, participants will complete baseline visits to collect demographics, health history, and health measurements (e.g., blood pressure, body mass index) and 6-month follow-ups assessing cognitive function and social isolation at each visit. A subsample of 120 participants representative of each community will wear smartwatches to collect sensor data (e.g., heart rate) and daily routine and predefined activities (e.g., GPS-captured travel, frequent destinations) over two months. Ecological momentary assessments (EMA) (e.g., whether smoke has bothered participant in last 30 minutes) will occur over two months during agricultural burning and non-burning months. PurpleAir monitors (36 total) will be installed in each community to continuously monitor outdoor PM2.5 levels. Discussion We expect to identify individual- and community-level factors that increase the risk for SI and cognitive decline in a vulnerable rural population.

Diet is key to the maintenance of health and crucial in the prevention and management of many diseases. Modified nutrient intake may become essential to prevent deficiency, optimise development and health or manage symptoms and disease progression. Adding to the complexity, disease and its treatment can also affect taste, appetite and ability to access and prepare foods. Coupled with this, individual requirements for energy, macronutrients and micronutrients are influenced by factors such as life stage (age, growth, pregnancy, etc.) and health status, which can affect the processes of consuming, digesting, absorbing, metabolising or excreting nutrients. First and foremost, dietary advice must be based on sound evidence if it is to achieve and maintain human health. Furthermore, the practice of nutrition and dietetics must integrate and apply the sciences of food, nutrition, biology, physiology, behaviour management, communication and must also recognise the context that society presents, including the plethora of often conflicting information on diet and health available via the internet and other media sources. A new Position Paper (Hickson et al., 2024) from the Academy of Nutrition Sciences (ANS) provides a state-of-the-art summary of how evidence-based practice is used to inform nutrition interventions for individuals, with a particular emphasis on research evaluation and using examples taken from the treatment of existing, clinically diagnosed disease. It is the third in a series of papers by the ANS that describe the nature of the scientific evidence and frameworks that underpin nutrition recommendations for health. It builds on the first ANS Position Paper that focussed on how dietary recommendations are formulated for populations for the prevention of non-communicable diseases (Williams et al., 2021a) and the second ANS Position Paper that examined the evidence used to support health claims for specific foods (Ashwell et al., 2022). Editorials that summarise these Position Papers and their recommendations have also been published to widen dissemination (Stanner et al., 2022a, 2022b; Williams et al., 2021b, 2021c), as is the case here with this editorial summarising the ANS Position Paper in relation to nutrition interventions for individuals (Hickson et al., 2024). A primary method through which research evidence is used to guide individualised nutrition interventions is the development of clinical practice guidelines, which are "systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances" (Institute of Medicine Committee to Advise the Public Health Service on Clinical Practice, 1990). Guidelines attempt to bridge the gap between research and clinical practice, guiding the practitioner and patient to implement treatments based on the best available evidence. Importantly, evidence-based practice recognises that research evidence is integrated with clinical expertise and patient preference, described as a 'three-legged stool' to emphasise that without one of these elements, evidence-based clinical decision-making collapses (Peterson et al., 2016). See Figure 1. Of major importance to evidence-based nutrition and dietetic practice is the ability to critically appraise the quality and certainty of research evidence in terms of: (i) whether an appropriate study design has been used to answer the clinical question; (ii) the methodological quality of the study (i.e. specific aspects of the methods); and (iii) the overall quality and certainty of the evidence as a basis for deriving recommendations, by applying GRADE (GRADE, 2013) or a similar framework. The Position Paper provides examples of critical appraisal tools for use with different study designs, including tools to assess the risk of bias within the study. There are a number of published guidelines that support the delivery of nutrition interventions by nutrition and dietetic professionals. The aim of a well-defined methodological process is to promote objectivity, transparency and reproducibility while minimising issues such as conflicts of interest. Examples include the Evidence Analysis Library (EAL) that is hosted and reviewed by the US Academy of Nutrition & Dietetics (Academy of Nutrition and Dietetics, 2022) and the Practice-based Evidence in Nutrition® (PEN), which is an online nutrition knowledge translation platform jointly managed by Dietitians of Canada, the British Dietetic Association and Dietitians Australia (Neale & Tapsell, 2019). The EAL and PEN illustrate different approaches in applying research evidence to individual clients, and the full Position Paper includes a useful table comparing the two clinical practice guideline development processes. The Position Paper identifies several challenges that require attention. Perhaps the most obvious of these is that, in addition to the increasing quantity and quality of robustly performed research studies, there is an abundance of conflicting information and misinformation that has to be navigated from diverse sources, including non-qualified practitioners, social media influencers and celebrities, the proliferation of fad diets and health products, and the tendency to use sensational headlines to attract more clicks, views and sales. See Box 1 for a summary of the challenges identified in the Position Paper. A number of strengths are recognised in the progress made to date, including: (i) implementation of research through transparent guidelines; (ii) defined processes for the development of national and international guidelines; and (iii) developments and collaborations in the form of EAL and PEN. To address the challenges identified in its Position Paper (Box 1), the ANS makes 10 consensus recommendations, addressed to three specific audiences. A summary of these 10 recommendations is provided in Boxes 2, 3, 4, but a detailed description of the recommendations, together with tools to support groups in the application of these (e.g. research glossary, list of critical appraisals etc) is available in the full paper (Hickson et al., 2024). Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Personalised dietary advice has become increasingly popular, currently however most approaches are based on an individual's genetic and phenotypic profile whilst largely ignoring other determinants such as socio economic and cognitive variables. This paper provides novel insights by testing the effectiveness of personalised healthy eating advice concurrently tailored to an individual's socio-demographic group, cognitive characteristics, and sensory preferences. We first used existing data to build a synthetic dataset based on information from 3654 households (Study 1a), and then developed a cluster model to identify individuals characterised by similar socio-demographic, cognitive, and sensory aspects (Study 1b). Finally, in Study 2 we used the characteristics of 8 clusters to build 8 separate personalised food choice advice and assess their ability to motivate the increased consumption of fruit and vegetables and decreased intakes of saturated fat and sugar. We presented 218 participants with either generic UK Government “EatWell” advice, advice that was tailored to their allocated cluster (matched personalised), or advice tailored to a different cluster (unmatched personalised). Results showed that, when compared to generic advice, participants that received matched personalised advice were significantly more likely to indicate they would change their diet. Participants were similarly motivated to increase vegetable consumption and decrease saturated fat intake when they received unmatched personalised advice, potentially highlighting the power of providing alternative food choices. Overall, this study demonstrated that the power of personalizing food choice advice, based on a combination of individual characteristics, can be more effective than current approaches in motivating dietary change. Our study also emphasizes the viability of addressing population health through automatically delivered web-based personalised advice.

6650 Background: To date, economic analyses of tissue-based next generation sequencing genomic profiling (NGS) have required models with multiple assumptions, with little real-world evidence on overall survival (OS), clinical trial enrollment or end-of-life (EOL) quality of care. The OCTANE clinical trial (NCT02906943) is a prospective study evaluating the role of NGS for advanced solid tumors in Ontario, Canada. We performed a cost consequence analysis of OCTANE. Methods: We undertook a longitudinal, propensity score-matched retrospective cohort study using linked administrative data. OCTANE patients (pts) at Princess Margaret Cancer Centre from August 2016 until March 2019 undergoing NGS panel testing (555 or 163-gene panels) were matched with contemporary controls from across Ontario not enrolled in OCTANE. Patients were matched according to 19 variables including age, sex, place of residence, tumor site, symptom burden, income quintile, comorbidities and prior lines of systemic therapy. Primary outcomes were mean per capita health care costs (2019 Canadian dollars [CAD]) from the public payer’s perspective, OS, clinical trial enrollment and EOL quality metrics. Full 2-year follow-up data was available. Sensitivity analyses considered alternative matched cohort specifications. Results: There were 782 OCTANE pts with 782 matched controls. Variables were balanced after matching (standardized difference [std. diff.]<0.10). Most common tumor sites were: Ovary (30.4%), endometrium (15.0%) breast (12.3%) and colon (8.6%). OCTANE pts had higher mean healthcare costs than controls ($79,702 vs. $59,550), mainly due to costs of oncology visits ($33,165 vs. $26,197), outpatient clinic visits ($8,696 vs. $5,114) and emergency visits ($1,723 vs. $1,373) (all p<0.05). Publicly funded drug costs were less for OCTANE pts ($20,015 vs. $24,465). Overall, OCTANE enrollment was not associated with improved OS (restricted mean survival time (RMST) [standard error]: 1.50 (±0.03) vs. 1.44 (±0.03) years, log-rank p=0.153), but OCTANE was associated with longer OS in ovarian cancer (RMST: 1.69 (±0.05) vs. 1.45 (±0.06) years, p=0.011) and biliary tract tumors (RMST: 1.16 (±0.13) vs. 0.80 (±0.11) years, p=0.02). Importantly, OCTANE correlated with increased clinical trial enrollment (25.5% vs. 9.5%, p<0.001) and better EOL quality due to fewer deaths in hospital (10.2% vs 16.4%, p=0.003). Results were robust in sensitivity analysis. Conclusions: There was an increase in healthcare costs associated with NGS testing for advanced cancers. The impact on OS was not significant in the overall population, but varied across tumor types. OCTANE was associated with greater trial enrollment, lower publicly funded drug costs and fewer in hospital deaths suggesting important considerations in determining the value of NGS for advanced cancers. Clinical trial information: NCT02906943 .

Abstract Social isolation threatens the health of older adults, particularly those with Alzheimer’s disease and related dementias (ADRD). Our research uses measures of behavioral coordination to quantify the entrainment of an individual’s behavior to the collective dynamics of a group to which they belong, aiming to identify useful strategies to reduce social isolation for persons with ADRD in therapeutic group contexts. The present study is based on data collected during 27, 30-minute group therapy sessions conducted biweekly via WebEx by staff facilitators at a university-affiliated Memory and Wellness Center (MWC) in 2021, when CoViD-19 restrictions limited patients’ access to existing, in-person day programs. We study conversational entrainment among facilitators and participants in the recorded sessions using previously identified measures such as speech duration; voiced and voiceless interval durations; variations in pitch, intensity, and syllabic rate; and turn breaks. We present preliminary results identifying dynamical characteristics of sessions showing greater and lesser degrees of group social engagement before discussing possible strategies facilitators could use to enhance social coordination within therapy groups. The mental health benefits of professionally facilitated supportive group discussions for older adults with ADRD are well-accepted. Measuring conversational entrainment has the potential to provide quantitative evidence of cognitive benefits for persons with ADRD, and to help shape a therapeutic environment tailored to the needs of this vulnerable population.

Observational research, mainly prospective cohort studies (PCS), has represented a long-standing challenge for those attempting to draw up consistent policy recommendations in the area of diet and health. This has been due to the inherent limitations in ascribing causality from observed associations due to problems of confounding of the findings and publication and citation bias. Developments in nutritional epidemiology research over the past 20-30 years have enabled causal criteria to be derived from observational studies and the totality of the primary literature to be reviewed objectively, reducing previous focus on narrative accounts of individual studies. The gold standard approach to assessing causal relationships is via randomised controlled trials (RCT), but neither RCT nor PCS provide direct evidence for biological plausibility, which is a key criterion for assessing causality. Although extensive mechanistic data are available in the literature, a systematic approach to select and assess quality and relevance of published studies has not been available. This limits their use in the development of diet and health policy. Recent studies have investigated a proposed two-step framework and novel methodologies for integrating heterogeneous data from cell, animal and human studies. Pilot and feasibility studies have shown this to be a useful novel approach to studies of diet and cancer, but further refinements are required, including development of appropriate quality criteria which are less dependent on RCT designs. Future studies are needed to fully verify the approach and its potential for use in other diet-disease relationships.

Claims about the nutritional and health benefits of foods and drinks crop up all over the place. But are all claims authorised, thereby based on robust scientific evidence, and compliant with legislation? For example, such claims cannot be associated with alcoholic drinks (Advertising Standards Authority, 2022). And what regulatory processes exist to protect the public? The regulation of nutrition claims and health claims is the subject of a new Position Paper from the Academy of Nutrition Sciences (Ashwell et al., 2022). This article is protected by copyright. All rights reserved.

Dietary fat composition is an important modulator of vascular function. Non-esterified fatty acids (NEFA) enriched in saturated fatty acids (SFA) are thought to reduce vascular reactivity by attenuating insulin signalling via vasodilator pathways (phosphoinositide 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS)) and enhancing signalling via pro-inflammatory pathways. To examine the effects of fatty acids on these pathways, human aortic endothelial cells were incubated with single fatty acids, and mixtures of these fatty acids to mimic typical NEFA composition and concentrations achieved in our previous human study. RNA was extracted to determine gene expression using real-time RT-PCR and cell lysates prepared to assess protein phosphorylation by Western blotting. Oleic acid (OA, 100 µM) was shown to down regulate expression of the insulin receptor, PTEN and a PI3K catalytic (p110β) and regulatory (p85α) subunit compared to palmitic, linoleic and stearic acids (P < 0.04), and promote greater eNOS phosphorylation at Ser1177. Both concentration and composition of the SFA and SFA plus n-3 polyunsaturated fatty acids (PUFA) mixtures had significant effects on genes involved in the PI3K/Akt pathway. Greater up-regulation was found with 800 than 400 µM concentration (respective of concentrations in insulin resistant and normal individuals), whereas greater down-regulation was evident with SFA plus n-3 PUFA than SFA mixture alone. Our findings provide novel insights into the modulation of the PI3K/Akt/eNOS pathway by single fatty acids and fatty acid mixtures. In particular, OA appears to promote signalling via this pathway, with further work required to determine the primary molecular site(s) of action.

The regulation of health claims for foods by the Nutrition and Health Claims Regulation is intended, primarily, to protect consumers from unscrupulous claims by ensuring claims are accurate and substantiated with high quality scientific evidence. In this position paper, the Academy of Nutrition Sciences uniquely recognises the strengths of the transparent, rigorous scientific assessment by independent scientists of the evidence underpinning claims in Europe, an approach now independently adopted in UK. Further strengths are the separation of risk assessment from risk management, and the extensive guidance for those submitting claims. Nevertheless, four main challenges in assessing the scientific evidence and context remain: (i) defining a healthy population, (ii) undertaking efficacy trials for foods, (iii) developing clearly defined biomarkers for some trial outcomes and (iv) ensuring the composition of a food bearing a health claim is consistent with generally accepted nutrition principles. Although the Regulation aims to protect the consumer from harm, we identify some challenges from consumer research: (i) making the wording of some health claims more easily understood and (ii) understanding the implications of the misperceptions around products bearing nutrition or health claims. Recommendations are made to overcome these challenges. Further, the Academy recommends that a dialogue is developed with the relevant national bodies about Article 12(c) in the Regulation. This should further clarify the GB Guidance to avoid the current non-level playing field between health professionals and untrained 'influencers' who are not covered by this Article about the communication of authorised claims within commercial communications.

(1) Background: Spouse carers of persons with dementia (PwD) are particularly vulnerable to negative outcomes of care, yet research rarely focuses on their caregiving situation. This study explores factors associated with the positive value and negative impact of caregiving in spouse carers of PwD in Sweden. (2) Methods: The study was a cross-sectional questionnaire-based survey, with a convenience sample of spouse carers of PwD (n = 163). The questionnaire addressed: care situation, carer stress, health and social well-being, relationship quality and quality of support, and contained measures of positive value and negative impact of caregiving. (3) Results: Hierarchical regression models explained 63.4% variance in positive value and 63.2% variance in negative impact of caregiving. Three variables were significant in the model of positive value: mutuality, change in emotional closeness following dementia and quality of support. Six variables were significant in the model of negative impact: years in relationship, years as carer, behavioural stress, self-rated health, emotional loneliness and change in physical intimacy following dementia. (4) Conclusions: Support to spouse carers of PwD should address the carer–care-recipient relationship quality, although different aspects of the relationship should be addressed if both the positive value of caregiving is to be enhanced and the negative impact reduced.

The Haken-Kelso-Bunz (HKB) system of equations is a well-developed model for dyadic rhythmic coordination in biological systems. It captures ubiquitous empirical observations of bistability - the coexistence of in-phase and antiphase motion - in neural, behavioral, and social coordination. Recent work by Zhang and colleagues has generalized HKB to many oscillators to account for new empirical phenomena observed in multiagent interaction. Utilising this generalization, the present work examines how the coordination dynamics of a pair of oscillators can be augmented by virtue of their coupling to a third oscillator. We show that stable antiphase coordination emerges in pairs of oscillators even when their coupling parameters would have prohibited such coordination in their dyadic relation. We envision two lines of application for this theoretical work. In the social sciences, our model points toward the development of intervention strategies to support coordination behavior in heterogeneous groups (for instance in gerontology, when younger and older individuals interact). In neuroscience, our model will advance our understanding of how the direct functional connection of mesoscale or microscale neural ensembles might be switched by their changing coupling to other neural ensembles. Our findings illuminate a crucial property of complex systems: how the whole is different than the system's parts.

Nutrition BulletinVolume 46, Issue 1 p. 2-7 EditorialFree Access Synthesising nutrition science into dietary guidelines for populations amidst the challenge of fake news: Summary of an Academy of Nutrition Sciences position paper C. M. Williams, C. M. Williams c.m.williams@reading.ac.uk University of Reading, Reading, UK Academy of Nutrition Sciences, London, UKSearch for more papers by this authorJ. L. Buttriss, Corresponding Author J. L. Buttriss j.buttriss@nutrition.org.uk Academy of Nutrition Sciences, London, UK British Nutrition Foundation, London, UK Correspondence: Prof. Judith L. Buttriss, Director General, British Nutrition Foundation, New Derwent House, 69-73 Theobalds Road, London WC1X 8TA, UK. E-mail: j.buttriss@nutrition.org.ukSearch for more papers by this authorK. Whelan, K. Whelan kevin.whelan@kcl.ac.uk Academy of Nutrition Sciences, London, UK King's College London, London, UKSearch for more papers by this author C. M. Williams, C. M. Williams c.m.williams@reading.ac.uk University of Reading, Reading, UK Academy of Nutrition Sciences, London, UKSearch for more papers by this authorJ. L. Buttriss, Corresponding Author J. L. Buttriss j.buttriss@nutrition.org.uk Academy of Nutrition Sciences, London, UK British Nutrition Foundation, London, UK Correspondence: Prof. Judith L. Buttriss, Director General, British Nutrition Foundation, New Derwent House, 69-73 Theobalds Road, London WC1X 8TA, UK. E-mail: j.buttriss@nutrition.org.ukSearch for more papers by this authorK. Whelan, K. Whelan kevin.whelan@kcl.ac.uk Academy of Nutrition Sciences, London, UK King's College London, London, UKSearch for more papers by this author First published: 01 February 2021 https://doi.org/10.1111/nbu.12480Citations: 1AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat This editorial is published jointly with the Journal of Human Nutrition and Dietetics. Hardly a day goes by without headlines in the media about a new approach to weight loss or a major discovery of a diet that will prevent diabetes, heart diseases or even cancer. Social media in particular is awash with tales of foods, supplements and dietary treatments that are claimed to produce almost magical effects on health. If anything, matters have worsened during the COVID-19 pandemic, with a particular focus being on purported, but often unsubstantiated, benefits of foods, nutrients and supplements to the immune system (Lockyer 2020). In many cases, claims for efficacy in treating or preventing disease are based on limited scientific evaluation. Perversely, or perhaps consequently, dietary recommendations for health drawn up by expert panels, where all available scientific evidence is scrutinised using optimal and systematic methods to assess rigour and avoid bias, are often challenged. These challenges, which originate from the popular media and the scientific media and are rapidly disseminated in the digital age in which we live, include views that the evidence is inconsistent, is subject to publication or selection bias, that judgements lack independence from commercial interests, or interpretations are subject to ideological bias. This contrary situation fosters an environment that is not unique to diet and health, in which trust in science and in expert opinion is undermined, risking confusion and inertia in response to sound advice that has the potential to benefit health. On the one hand, insubstantial evidence for beneficial effects of particular treatments is followed with great fervour by those seeking to shortcut the need to review the evidence in detail, or by those wedded to a particular philosophy or agenda, whereas carefully evaluated bodies of evidence are sometimes regarded with suspicion even when the conclusions have stood the test of time. Nevertheless, it is also entirely appropriate that national dietary recommendations, which have the potential to affect the lives and wellbeing of large numbers of people, should be kept under review and open to scrutiny and challenge. This will help to ensure the evidence upon which recommendations are based is as strong as it can be. The continuing high rates of obesity, the co-existence of poor micronutrient density and excess energy in dietary patterns, and consistent evidence for adverse effects of diets high in fat, sugar or salt, provide compelling argument that more needs to be done to ensure evidence-based nutrition forms the bedrock of advice on diet delivered to populations and individuals. The Academy of Nutrition Sciences (ANS) was formed in 2019 as a joint initiative between the Association for Nutrition, the British Dietetic Association, the British Nutrition Foundation and the Nutrition Society. The objective of the ANS is to improve public health and wellbeing by supporting excellence in research, education and associated activities to advance the knowledge and application of evidence-based nutrition science (Academy of Nutrition Sciences 2020). The Trustees of the ANS agreed that action is required to reduce levels of misinformation about nutrition and health, to improve understanding of how evidence in nutrition is scrutinised to avoid bias and the way in which the totality of the evidence is evaluated to formulate dietary recommendations. The Academy agreed that a series of position papers should be published to consider the nature of the evidence base in specific areas of nutrition and health. The first of these, which has recently been published (Williams et al. 2020), addresses the evidence base underpinning dietary advice for populations for the prevention of non-communicable diseases such as cardiovascular disease and cancer. The position paper summarises the nature of the evidence base and the systematic processes used by expert panels to ensure rigour, relevance and consistency is brought to their conclusions. It also addresses some of the challenges inherent in studying diet–disease relationships and lessons learned over the past 45 years of evidence-based policy-making in dietary prevention of non-communicable diseases (Williams et al. 2020). The first national and global recommendations for dietary prevention of non-communicable diseases (NCD) were those published during the 1970s and early 1980s for the prevention of cardiovascular disease (CVD) (DHSS 1974; National Research Council (US) Committee on Diet Nutrition and Cancer 1982; World Health Organization 1982). These reports reflected the alarming rates of CVD morbidity and mortality in middle-aged men that were being reported at the time, mostly from Western countries. Although some of this increase was attributed to smoking, emerging evidence from observational epidemiology was pointing to diet as a contributory factor, with dietary fat considered to have an adverse effect on CVD through its ability to increase circulating concentrations of blood cholesterol (American Heart Association 1982). The first UK expert report on diet and CVD (DHSS 1974) published in 1974 considered the evidence at the time to be insufficient to allow specific recommendations to be made for CVD prevention, but suggested reductions in fat intake might help to alleviate rising prevalence of obesity (then 10% in UK adults). The UK panel advised that stronger lines of evidence from randomised controlled trials (RCTs) of dietary interventions on clinical outcomes (morbidity and mortality from CVD) and prospective cohort studies were needed to determine whether links between diet and CVD incidence were causal. As shown in the Academy's paper (Williams et al. 2020), as more evidence began to accumulate, subsequent recommendations from expert UK panels became stronger, allowing recommendations to be made for specified levels of intake of total, saturated and trans fats (Table 1). The recommendation that saturated fat intakes should be reduced to levels <10% of total energy intake has been a consistent UK recommendation since 1984, with the latest report from the Scientific Advisory Committee on Nutrition (SACN) in 2019 (SACN 2019) reaffirming this conclusion. Notwithstanding the UK recommendations, and the similar recommendation that had been made for US adults (United States Dietary Guidelines for Americans 2015–2020; USDA, 2015), many statements appeared in popular and social media questioning the benefits of reducing saturated fat intakes for heart health. Mostly, these statements were based on outcomes from individual studies with little account taken of the very large volume of evidence that had accumulated since the 1970s. In some cases, the scientific validity of statements made online was questionable. It is yet unclear whether these statements have had adverse effects on compliance with the recommendations, but the situation illustrates the challenges that face those concerned with communicating diet and health policy. Table 1. Recommendations for dietary fat intakes for the prevention of cardiovascular diseases COMA 1974 COMA 1984 COMA 1994 SACN 2020 COMA 1991 Dietary reference values Total fat and fatty acid intakes (% dietary energy) Total fat ↓ ↓35 ↓35 _ 35 Saturated fatty acids (SFA) ↓ ↓ 15† ↓10 ↓10** 10–11 Polyunsaturated fatty acids (PUFA), n-6 Not considered 3.5–6.8 6* ** 6.5* Long-chain polyunsaturated fatty acids, n-3 _ _ ↑ 0.2 g/d 0.2 Monounsaturated fatty acids _ _ 12 ** 12 Trans fatty acids (TFA) _ _ ↓ <2 ** <2 From the Committee on Medical Aspects of Food and Nutrition Policy (COMA) and Scientific Advisory Committee on Nutrition (SACN) reports, 1974–2019, for the UK. ↓ – reduce intake; ↑ – increase intake. Table adapted from Williams et al. (2020). COMA reports can be found at https://www.gov.uk/government/publications/coma-reports, SACN reports at https://www.gov.uk/government/collections/sacn-reports-and-position-statements. † Includes saturated and trans fatty acids (latter intakes were 4.8% in 1984). * Individual intakes of total PUFA should not exceed 10% of energy. ** SFA should be replaced by unsaturated fats; PUFA should not exceed 10% of energy; TFA should not exceed 2% of energy. Randomised controlled trials and non-communicable diseases Although RCTs are regarded as the gold standard for evaluating the effect of drug and other treatments on clinical disease, the ANS recognises that RCTs of clinical outcomes such as disease incidence or mortality has proved to be of lesser value in studying diet–disease relationships (Williams et al. 2020). To study the preventative effects of diets on disease outcomes, the trialled intervention needs to be conducted over a number of years, which in free-living settings results in poorer compliance and higher dropout rates than is observed with drug trials. Insufficient time allowed for follow-up of the outcome in study participants is a significant factor reducing the power of clinical outcome dietary trials. Decisions about what should be used for the control diet can also be challenging, whereas placebo drug treatments are straightforward. Where diet trials have been conducted in enclosed settings, for example long-stay homes, prisons or hospitals, the generalisability of the findings to whole populations has been criticised. The Academy's paper recognises that dietary RCTs are valuable for studying effects of diet on surrogate risk markers for non-communicable diseases, such as serum cholesterol concentration and blood pressure for CVD. Unlike RCTs studying impact on clinical outcomes, trials using surrogate markers of risk can be conducted over a few months, which makes them feasible to conduct on large numbers of representative groups with the achievement of good dietary compliance. Serum cholesterol is a strong risk factor for CVD and is responsive to dietary therapy, making it a suitable intermediate for studying the ability of diet to reduce risk of CVD. However, strong surrogate markers are not available for all non-communicable diseases, for example cancers, with the search for diet-responsive disease risk biomarkers continuing to be an active area of nutrition research. Prospective cohort studies The Academy's paper acknowledges that the significant investment in the design and conduct of prospective cohort studies over the past 20–30 years has substantially improved the quality of the evidence base concerning dietary prevention of non-communicable diseases. Large-scale cohort studies have been established in countries worldwide, with a number of these now having data from follow-up periods of 20–50 years; this allows accumulation of many thousands of cases, which provides greater statistical power. The development of standardised approaches for systematic reviews and meta- and pooled analyses has allowed detailed interrogation of summated data in subgroups of the study population, for example by gender. The ability of these large databases to evaluate criteria such as effect size, dose response, consistency, specificity and temporality has been an important advance, allowing causal relationships of diet–disease associations to be inferred, although not completely proven. These advances have to some extent alleviated concerns about the lack of valid RCT findings for diet and non-communicable diseases, although where these are available, meta-analyses of RCTs provide valuable input to expert panel scrutiny of the evidence. Expert panels These advances in nutritional epidemiology have been important in supporting the work of expert panels responsible for making dietary recommendations for the prevention of non-communicable diseases. The use of standardised frameworks and guidelines by panels has also provided transparent, systematic processes for identifying, selecting and interrogating the available evidence base (Fig. 1). Figure 1Open in figure viewerPowerPoint Schematic representation of the processes used to structure assessment of the evidence underpinning dietary recommendations (Williams et al. 2020) Standardised frameworks ensure there is less focus on narrative accounts of individual studies, with reduced risk of selection and publication bias that can arise from over-reliance on highly cited reports. Summation of prospective cohort data via meta- and pooled analyses allows the causal characteristics of the summated data to be interrogated for evidence of causality for diet–disease relationships. Most panels now use grading criteria to decide on the quality of the overall evidence and whether it is sufficiently strong to conclude that the relationship between diet and the disease in question is a causal one. The World Cancer Research Fund Continuous Update Project (WCRF CUP) uses a 10-year cycle of updating and selection of the evidence; expert panel interrogation; and grading of the evidence. Dietary recommendations are then made on the basis of the grading achieved for the relevant cancer site for specific foods, drinks or measures of nutritional status. The evidence is graded within five categories from the lowest (substantial effect on risk unlikely) to the top two highest [probable and convincing (highest)]. Where evidence is graded as probable or convincing, the panel considers the evidence sufficient to make dietary recommendations for the prevention of cancer at that site. Table 2 shows the gradings for risk of colon cancer and specific diet and anthropometric characteristics assessed by WCRF CUP in 2017/2018, illustrating how the approach enables dietary recommendations to change over time to reflect the available evidence. Table 2. Grading for strength of the evidence for causal relationship between specific dietary components or anthropometric measures and risk of colorectal cancer, WCRF† WCRF 1997 WCRF 2007 WCRF 2018 Red meat Convincing Convincing Probable ‡ Processed meat Convincing Convincing Convincing Alcoholic drinks Convincing (men) Probable (women) Convincing (men) Probable (women) Convincing (men and women) Body fatness Convincing Convincing Convincing Abdominal fatness Convincing Convincing Convincing Adult attained height Convincing Convincing Convincing † Strength classified as: convincing; probable; limited – suggestive; limited – no conclusion; substantial effect on risk unlikely. ‡ Includes beef, lamb, pork and goat. Table adapted from Williams et al. (2020). As shown in the adapted table from the Academy's paper, evidence for a causal relationship between red meat and colon cancer was found to be weaker in the evaluation for the 2018 report than in the 1997 or 2007 reports. This reflected new evidence that had become available after 2007, which resulted in revision to the previous 'convincing' categorisation for red meat and risk of colon cancer in earlier reports. For the relationship between colon cancer risk and consumption of alcoholic drinks in women, evidence had become stronger and was revised from probable to convincing. These data demonstrate that new findings can influence the strength of the existing evidence and that processes are sufficiently flexible to allow this. Importantly, the new data is considered alongside the existing data, as part of systematic reviews and meta-analysis, so that its relevance and impact on the totality of the evidence can be scrutinised. The Academy concluded that the increasingly open nature of the work of expert groups and the systematic methods, processes and criteria used by expert groups to interpret complex data sets and to make dietary recommendations for population health were as rigorous in the area of diet and health as in other areas of science, medicine and health. Further, the frameworks used to allow updates, whether in the form of regular cycles or as and when additional data become available, were considered to be important. Remaining challenges Although the Academy's position paper considers the developments in nutritional epidemiology and the processes used by expert panels to have been important in strengthening recommendations for health, it recognises there are some important areas where the evidence base has been insufficiently deployed or where methodological limitations remain of concern. In particular, it is concluded that experimental studies that investigate biological mechanisms underlying diet–disease relationships have not been sufficiently exploited in the area of diet, nutrition and health (Williams et al. 2020). Observational and mechanistic findings contribute complementary information that can strengthen the evidence for causal relationships. As has been the case with advances made in epidemiology, the position paper recommends that a more systematic approach to this part of the evidence base, including clear criteria for selection of studies based on quality and relevance, should enable discrimination of those studies that can usefully address current diet and health questions, from those that cannot (Williams et al. 2020). Dietary assessment, in other words estimating food and nutrient intake, has long been acknowledged as a challenging aspect of epidemiological investigation because the potential for confounding by other variables and bias is greater for diet than for many other exposures. However, the Academy considers that certain challenges have increased substantially since the latter part of the 20th century. These include the wide variety of new products and frequent compositional changes associated with reformulation of manufactured foods; high prevalence and extent of underreporting of energy intakes; and confounding due to changes in population background diets over time. Underreporting of energy intakes in diet records of volunteers has been repeatedly demonstrated using the method of doubly labelled water. Methods to overcome this potential for systematic bias due to underreporting in prospective cohort studies have yet to be identified, and this remains an area of active research. The Academy considers national nutrition surveillance programmes such as the UK's National Diet and Nutrition Survey and the US National Health and Nutrition Examination Survey to provide essential independent measures of diet and nutritional status that help ensure national context to global research findings. These rolling survey programmes provide information on temporal trends in food and nutrient intakes in a variety of population subgroups, determined by age, sex and socio-economic status, which can be taken into account when interpreting findings from long-term cohort studies in which dietary data derive from countries other than the UK. Of course, making judgements and recommendations based on the available scientific evidence is just one step in the process of achieving beneficial change in dietary behaviours. Also of considerable importance are using this assessment to drive policy change and ensuring that the associated diet-related messages are communicated and acted upon despite all the competing messaging from other sources. The possibility that confusion about the principles of healthy eating could undermine attempts to achieve desirable population changes in diet is a serious consideration for the Academy, and the position paper examines evidence that might support the contention that dietary recommendations are frequently changing or inconsistent, that is the argument that 'the experts keep changing their minds…'. For two of the main diseases for which diet has been causally implicated, cardiovascular diseases and colon cancer, the Academy found that the main dietary recommendations for reducing disease risk had not substantially changed over time. The recommendations for saturated fat and CVD have been finessed over time as evidence has accumulated but have remained broadly consistent for 35–45 years and for diet and colon cancer for at least 20 years. The Academy considers that frequent reporting of individual studies in the media may have contributed to the perception of frequent changes in dietary recommendations. Some reports in the media proffer a degree of certainty and level of significance for findings from small insubstantial studies that are not warranted, perhaps reflecting the need, generally, for better understanding of the concepts of uncertainty and risk in a scientific context. The Academy considers the nutrition science profession, including registered dietitians, registered nutritionists and registered public health nutritionists, could do far more to communicate the rigorous quality-driven selection processes involved in making dietary recommendations and the remaining challenges that underlie studies of diet–disease relationships. Audience-specific communications are needed, including messaging for different categories of health professionals, the media, other scientists and lay audiences. This is work that the Academy, in collaboration with its founding member organisations – the Association for Nutrition, the British Dietetic Association, the British Nutrition Foundation and the Nutrition Society, will be prioritising as part of its work over the next few years. References Academy of Nutrition Sciences (2020) The Academy of Nutrition Sciences. Available at: https://www.academynutritionsciences.org.uk/ (accessed 21 December 2020). American Heart Association (1982) Rationale of the diet-heart statement of the American Heart Association. Report of the AHA Nutrition Committee. Arteriosclerosis 2: 177– 91. DHSS (Department of Health and Social Security) (1974) Diet and coronary heart disease. Report of the Advisory Panel of the Committee on Medical Aspects of Food Policy (Nutrition) on Diet in relation to Cardiovascular and Cerebrovascular Disease. Available at: https://www.gov.uk/government/publications/coma-reports (accessed 21 December 2020). Lockyer SL (2020) Effects of diets, foods and nutrients on immunity: implications for COVID-19. Nutrition Bulletin 45: 456– 73. National Research Council (US) Committee on Diet Nutrition and Cancer (1982) Diet, Nutrition, and Cancer. National Academies Press: Washington, DC. SACN (Scientific Advisory Committee on Nutrition) (2019) Saturated fats and health. Public Health England. Available at: www.gov.uk/government/publications/saturated-fats-and-health-sacn-report (accessed 21 December 2020). USDA (United States Department of Agriculture) (2015) United States Dietary Guidelines for Americans 2015–2020. Available at: https://health.gov/sites/default/files/2019-09/2015-2020_Dietary_Guidelines.pdf (accessed 21 December 2020). Williams CM, Ashwell M, Prentice A et al. (2020) Nature of the evidence base and frameworks underpinning dietary recommendations for prevention of non-communicable diseases: a position paper from the Academy of Nutrition Sciences. British Journal of Nutrition, Accepted manuscript 1– 30. https://doi.org/10.1017/S0007114520005000 World Health Organization (1982) Prevention of Coronary Heart Disease: Report of a WHO Expert Committee (Technical report series: no 678). World Health Organization: Geneva. Citing Literature Volume46, Issue1March 2021Pages 2-7 FiguresReferencesRelatedInformation

Objective:We evaluated components of an integrated, mobile health-based intervention "Activate for Life" (AFL) on health outcomes in lower-income older adults (≥ 60 years). Methods:AFL incorporates balance (Otago; OG), physical strength (Gentle Yoga and yogic Breathing; GYYB), and mental engagement (Behavioral Activation; BA) components. Thirty participants were randomly allocated to one of three study arms (n=10): OG (Arm 1), OG+GYYB (Arm 2), or OG+GYYB+BA (Arm 3; a.k.a. "full AFL"). Participants were evaluated for physical, functional, and physiological endpoints at baseline and post-intervention (12-weeks and/or 3-month follow up). Results:Improvements in pain interference and 1,5- anhydroglucitol biomarker levels over time were noted for all arms. No significant changes were observed for other physical, functional, or physiological measures. Discussion:This study illustrates potential benefits of the AFL intervention on the health of lower-income older adults. Lessons learned from this pilot trial will inform design improvements for a large-scale randomized controlled trial.

This study compares methods of imputing genetic markers, given a typed GWAS scaffold from the Long Life Family Study (LLFS) and latest reference panel of 1000-Genomes. We examined two programs for pre-phasing haplotypes MACH/SHAPEIT2 and MINIMAC/IMPUTE2 for imputation. SHAPEIT2 is advantageous for haplotype pre-phasing. MINIMAC and IMPUTE2 produced similar imputation quality. We used a 4MB region on chromosome 2 of LLFS and in the Supplement, we compared methods using chromosome 19 data from the Genetic Analysis Workshop-19. IMPUTE2 had the advantage of using two references 1000G and a sequence for a subset of subjects. SHAPEIT2 and IMPUTE2 were used to finalise the full LLFS autosome imputation. In LLFS, 44% of ~80M autosomal imputed variants showed good imputation quality (info ≥ 0.30). Low imputation quality was associated with a predominantly low allele frequency in 1000-Genomes. New emerging large-scale sequences and enhanced imputation methodologies will further improve imputation quality.

Abstract Multiple causes converge for older adults to shed social relationships. Lost opportunities for social engagement are tied to weakened cognitive reserve and under-optimal aging in health and disease. For example, a woman, 75, regularly strolls with younger friends. At 80, her reduced motor fitness makes it hard to keep pace and she withdraws her participation. With same-age peers, she might continue this healthy physical and social activity a few more years by unobtrusively shortening the outing or by slowing her pace. A man, 85, loves to debate politics with family, but his turn at talks diminish: his hearing loss (sensory) prevents quick grasp of the discussion; his slower verbal fluency (cognitive) hamper quick-witted replies. Both examples illustrate that social aging is not only a ¬¬¬property of the aging individual. Social context plays an important role. Our recently formed interdisciplinary group (geropsychiatric nurse, mathematical physicist and complexity scientist) is studying the systemic complexities of social aging with experiments and mathematical models. Our aim is to present our model and aging-focused hypotheses, as well as empirical validation in younger adults. Four key variables are group size and heterogeneity, and the strength and adaptability of social coordination. Our current results show that people coordinate better with others like them in pace, but they lose the ability to coordinate with people whose pace is different. We anticipate that our program of research will deliver evidence-based recommendations on social-engineering of activities that maximize opportunities for sustained interactions among older adults.

This Position Paper from the Academy of Nutrition Sciences is the first in a series which describe the nature of the scientific evidence and frameworks that underpin nutrition recommendations for health. This first paper focuses on evidence which underpins dietary recommendations for prevention of non-communicable diseases. It considers methodological advances made in nutritional epidemiology and frameworks used by expert groups to support objective, rigorous and transparent translation of the evidence into dietary recommendations. The flexibility of these processes allows updating of recommendations as new evidence becomes available. For CVD and some cancers, the paper has highlighted the long-term consistency of a number of recommendations. The innate challenges in this complex area of science include those relating to dietary assessment, misreporting and the confounding of dietary associations due to changes in exposures over time. A large body of experimental data is available that has the potential to support epidemiological findings, but many of the studies have not been designed to allow their extrapolation to dietary recommendations for humans. Systematic criteria that would allow objective selection of these data based on rigour and relevance to human nutrition would significantly add to the translational value of this area of nutrition science. The Academy makes three recommendations: (i) the development of methodologies and criteria for selection of relevant experimental data, (ii) further development of innovative approaches for measuring human dietary intake and reducing confounding in long-term cohort studies and (iii) retention of national nutrition surveillance programmes needed for extrapolating global research findings to UK populations.

e19303 Background: There is limited real-world evidence of impact of large clinical panel sequencing on treatment-matching for patients with advanced solid tumors. The province of Ontario has a single payer, publicly funded health care system. We linked genomic testing results from a prospective province-wide trial, OCTANE (Ontario-Wide Cancer TArgeted Nucleic Acid Evaluation), to administrative data to determine the feasibility of this approach for evaluating survival and the impact of sequencing on treatment matching. Methods: We linked all Ontario patients from Princess Margaret (PM) with panel testing results (tumor-only 555-gene panel) to province-wide administrative data on treatments and outcomes. Patients were recruited from August 2016 to August 2018. Only clinically actionable variants based upon OncoKB annotation (Level 1 and 2) were assessed for genotype-informed treatment matching. Results: All 888 eligible patients were successfully linked to administrative data. Mean age was 58 (±13) years, 635 (71.5%) were female. Most common disease sites were ovary (26.4%), uterus (14.0%), colorectal (11.8%) and breast (9.5%). Administrative data vital status was more complete than trial collected data with 262 of 476 deaths only recorded in administrative data. Median survival was 1.70 years (95% confidence interval 1.50-1.91). 247 (27.8%) had actionable mutations, most commonly PIK3CA (54.7%), BRCA1 (15.8%), BRCA2 (15.0%) and BRAF (8.9%). 37 (15.0%) and 42 (17.0%) patients with actionable mutations received targeted therapy within 6 and 12 months of test report date, respectively. Conclusions: This is the first known feasibility study of linked administrative data to measure outcomes of large clinical panel sequencing for patients with advanced solid tumors. Vital status was more complete with administrative data compared to trial-collected data, and treatment data was successfully linked. About one in twenty-one enrolled patients received genome-informed treatments within 12 months, or about one in six of all patients with actionable mutations. This may be due to short interval follow up, trial and drug access, successful standard of care treatments, early patient deterioration or limited alterations covered by the panel, among other causes.