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The vision sciences literature contains a large diversity of experimental and theoretical approaches to the study of visual attention. We argue that this diversity arises, at least in part, from the field's inability to unify differing theoretical perspectives. In particular, the field has been hindered by a lack of a principled formal framework for simultaneously thinking about both optimal attentional processing and capacity-limited attentional processing, where capacity is limited in a general, task-independent manner. Here, we supply such a framework based on rate-distortion theory (RDT) and optimal lossy compression. Our approach defines Bayes-optimal performance when an upper limit on information processing rate is imposed. In this article, we compare Bayesian and RDT accounts in both uncued and cued visual search tasks. We start by highlighting a typical shortcoming of unlimited-capacity Bayesian models that is not shared by RDT models, namely, that they often overestimate task performance when information-processing demands are increased. Next, we reexamine data from two cued-search experiments that have previously been modeled as the result of unlimited-capacity Bayesian inference and demonstrate that they can just as easily be explained as the result of optimal lossy compression. To model cued visual search, we introduce the concept of a “conditional communication channel.” This simple extension generalizes the lossy-compression framework such that it can, in principle, predict optimal attentional-shift behavior in any kind of perceptual task, even when inputs to the model are raw sensory data such as image pixels. To demonstrate this idea's viability, we compare our idealized model of cued search, which operates on a simplified abstraction of the stimulus, to a deep neural network version that performs approximately optimal lossy compression on the real (pixel-level) experimental stimuli.

Although deep neural networks (DNNs) are state-of-the-art artificial intelligence systems, it is unclear what insights, if any, they provide about human intelligence. We address this issue in the domain of visual perception. After briefly describing DNNs, we provide an overview of recent results comparing human visual representations and performance with those of DNNs. In many cases, DNNs acquire visual representations and processing strategies that are very different from those used by people. We conjecture that there are at least two factors preventing them from serving as better psychological models. First, DNNs are currently trained with impoverished data, such as data lacking important visual cues to three-dimensional structure, data lacking multisensory statistical regularities, and data in which stimuli are unconnected to an observer’s actions and goals. Second, DNNs typically lack adaptations to capacity limits, such as attentional mechanisms, visual working memory, and compressed mental representations biased toward preserving task-relevant abstractions.

Efficient data compression is essential for capacity-limited systems, such as biological perception and perceptual memory. We hypothesize that the need for efficient compression shapes biological systems in many of the same ways that it shapes engineered systems. If true, then the tools that engineers use to analyze and design systems, namely rate-distortion theory (RDT), can profitably be used to understand human perception and memory. The first portion of this article discusses how three general principles for efficient data compression provide accounts for many important behavioral phenomena and experimental results. We also discuss how these principles are embodied in RDT. The second portion notes that exact RDT methods are computationally feasible only in low-dimensional stimulus spaces. To date, researchers have used deep neural networks to approximately implement RDT in high-dimensional spaces, but these implementations have been limited to tasks in which the sole goal is compression with respect to reconstruction error. Here, we introduce a new deep neural network architecture that approximately implements RDT. An important property of our architecture is that it is trained "end-to-end," operating on raw perceptual input (e.g., pixel values) rather than intermediate levels of abstraction, as is the case with most psychological models. The article's final portion conjectures on how efficient compression can occur in memory over time, thereby providing motivations for multiple memory systems operating at different time scales, and on how efficient compression may explain some attentional phenomena such as RTs in visual search. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Humans can easily describe, imagine, and, crucially, predict a wide variety of behaviors of liquids—splashing, squirting, gushing, sloshing, soaking, dripping, draining, trickling, pooling, and pouring—despite tremendous variability in their material and dynamical properties. Here we propose and test a computational model of how people perceive and predict these liquid dynamics, based on coarse approximate simulations of fluids as collections of interacting particles. Our model is analogous to a “game engine in the head”, drawing on techniques for interactive simulations (as in video games) that optimize for efficiency and natural appearance rather than physical accuracy. In two behavioral experiments, we found that the model accurately captured people’s predictions about how liquids flow among complex solid obstacles, and was significantly better than several alternatives based on simple heuristics and deep neural networks. Our model was also able to explain how people’s predictions varied as a function of the liquids’ properties (e.g., viscosity and stickiness). Together, the model and empirical results extend the recent proposal that human physical scene understanding for the dynamics of rigid, solid objects can be supported by approximate probabilistic simulation, to the more complex and unexplored domain of fluid dynamics., Author summary Although most people struggle to learn physics in school, every human brain is a remarkable “intuitive physicist” when it comes to the quick, unconscious judgments we make in interacting with the world. Almost effortlessly, and with surprisingly high quantitative accuracy, we can judge when a plate placed near the edge of a table might be at risk of falling, or how far a partially filled glass of water can be tipped before the water is in danger of spilling. What kinds of computations in the brain support these abilities? We suggest an answer based on probabilistic inference operating over particle-based simulations, the same class of approximation methods used in video games to simulate convincing real-time interactions between objects in a virtual environment. This hypothesis can potentially account for people’s quantitative, graded judgments in diverse and novel situations including a wide array of materials and physical properties, without positing a large number of separate systems or heuristics. Here, we build on previous evidence that a system of approximate probabilistic simulation supports judgments about rigid objects (e.g. judging the stability of towers of blocks, as in the game Jenga), and ask whether people can also make systematic and accurate predictions about flowing and splashing liquids, such as water or honey. We show that it is possible to capture people’s quantitative predictions using a computational model that approximates the true underlying fluid dynamics to varying degrees of coarseness, and find that people’s responses are most consistent with a very coarse approximation; while typical engineering applications might use tens or hundreds of thousands of particles to simulate a fluid, the brain might get by with roughly a hundred particles. Furthermore, we find that people consistently underestimate the potential energy of a splashing liquid in our virtual scenes, and that our model captures this behavior.

Human brains are finite, and thus have bounded capacity. An efficient strategy for a capacity-limited agent is to continuously adapt by dynamically reallocating capacity in a task-dependent manner. Here we study this strategy in the context of visual working memory (VWM). People use their VWM stores to remember visual information over seconds or minutes. However, their memory performances are often error-prone, presumably due to VWM capacity limits. We hypothesize that people attempt to be flexible and robust by strategically reallocating their limited VWM capacity based on two factors: (a) the statistical regularities (e.g., stimulus feature means and variances) of the to-be-remembered items, and (b) the requirements of the task that they are attempting to perform. The latter specifies, for example, which types of errors are costly versus irrelevant for task performance. These hypotheses are formalized within a normative computational modeling framework based on rate-distortion theory, an extension of conventional Bayesian approaches that uses information theory to study rate-limited (or capacity-limited) processes. Using images of plants that are naturalistic and precisely controlled, we carried out two sets of experiments. Experiment 1 found that when a stimulus dimension (the widths of plants' leaves) was assigned a distribution, subjects adapted their VWM performances based on this distribution. Experiment 2 found that when one stimulus dimension (e.g., leaf width) was relevant for distinguishing plant categories but another dimension (leaf angle) was irrelevant, subjects' responses in a memory task became relatively more sensitive to the relevant stimulus dimension. Together, these results illustrate the task-dependent robustness of VWM, thereby highlighting the dependence of memory on learning.

Diet quality indices assess compliance with dietary guidelines and represent a measure of healthy dietary patterns. Few studies have compared different approaches to assessing diet quality in the same cohort. Our analysis was based on 972 participants of the British Diet and Nutrition Survey of people aged 65 y and older in 1994/1995 and who were followed-up for mortality status until 2008. Dietary intake was measured via a 4-d weighed food record. Three measures of diet quality were used: the Healthy Diet Score (HDS), the Recommended Food Score (RFS), and the Mediterranean Diet Score (MDS). HR for all-cause mortality were obtained using Cox regression adjusted for age, sex, energy intake, social class, region, smoking, physical activity, and BMI. After adjustment for confounders, the MDS was significantly associated with mortality [highest vs. lowest quartile; HR = 0.78 (95% CI = 0.62–0.98)]. Similarly, the RFS was also associated with mortality [HR = 0.67 (95 % CI = 0.52–0.86)]; however, there were no significant associations for the HDS [HR = 0.99 (95% CI = 0.79–1.24)]. The HDS was not a predictor of mortality is this population, whereas the RFS and the MDS were both associated with all-cause mortality. Simple measures of diet quality using food-based indicators can be useful predictors of longevity.

Summary Follow-up of a British national survey of older people found that in men, all-cause mortality was predicted by baseline plasma concentrations of phosphorus, albumin, creatinine and α1-antichymotrypsin, and food energy intake and in women by plasma alkaline phosphatase, creatinine, α1-antichymotrypsin, 25-hydroxy-vitamin D (marginally), and phosphorus intake. Introduction Predictive power, for all-cause mortality, of bone-related vitamin and mineral indices and intakes, measured at baseline (primary objective), was studied in the British National Diet and Nutrition Survey (community-living subset) of People Aged 65 Years and Over. A secondary objective was to identify cross-sectional relationships between indices at baseline to help explain mortality predictions. Methods Mortality status was recorded for 1,054 (mean age 76.6 ± 7.4 years, 49.0% female) participants from baseline survey in 1994/1995 until September 2008. Seventy-four per cent of male and 62% of female participants died. Cox proportional hazards models were used to relate baseline nutrient and risk marker estimates to subsequent survival. Results below 1.0 signified lower risk at greater nutrient (status or intake) values and vice versa. Results In both sexes, all-cause mortality was significantly predicted by body weight and mid-upper arm circumference. In men, it was predicted by baseline plasma concentrations (per SD) of: phosphorus (hazard ratio 1.18, 95% confidence interval (CI) = 1.06–1.30), albumin (hazard ratio 0.84, 95% CI = 0.74–0.94), creatinine (hazard ratio 1.20, 95% CI = 1.08–1.33) and α1-antichymotrypsin (hazard ratio 1.21, 95% CI = 1.11–1.33). In women, it was predicted by plasma albumin (hazard ratio 0.83, 95% CI = 0.72–0.96), alkaline phosphatase (hazard ratio 1.08, 95% CI = 1.01–1.16), creatinine (hazard ratio 1.37, 95% CI = 1.13–1.66), α1-antichymotrypsin (hazard ratio 1.27, 95% CI = 1.11–1.45) and marginally by 25-hydroxy-vitamin D (hazard ratio 0.87, 95% CI = 0.75–1.00). In men, it was predicted by dietary intake (per SD) of food energy; in women, by intake of phosphorus. Adjustment for plasma α1-antichymotrypsin or plasma creatinine reduced the significance of plasma phosphorus in men. Conclusion Mortality prediction by higher plasma phosphorus in older British men may imply impaired renal function and/or acute phase status. Further studies are needed on which associations are causal and modifiable.

The predictive power, for total, vascular, cancer and respiratory mortality, of selected redox-modulatory (vitamin and mineral nutrient) indices measured at baseline, was studied in the British National Diet and Nutrition Survey (community-living subset) of people aged 65 years and over. Mortality status and its primary and underlying causes were recorded for 1054 (mean age 76·6 (sd 7·4) years and 49·0 % female) participants, from the baseline survey in 1994–5 until September 2008. During this interval, 74 % of the male and 62 % of the female participants died. Total mortality was significantly predicted by baseline plasma concentrations (per sd) of vitamin C (hazard ratio (HR) 0·81; 95 % CI 0·74, 0·88), α-carotene (HR 0·90; 95 % CI 0·81, 0·99), Se (HR 0·76; 95 % CI 0·69, 0·84), Zn (HR 0·79; 95 % CI 0·72, 0·87), Cu (HR 1·27; 95 % CI 1·14, 1·42) and Fe (HR 0·81; 95 % CI 0·74, 0·89). Total mortality was also significantly predicted by baseline dietary intakes (per sd) of food energy (HR 0·86; 95 % CI 0·79, 0·94), vitamin C (HR 0·88; 95 % CI 0·80, 0·94), carotenoids (HR 0·89; 95 % CI 0·83, 0·96), Zn (HR 0·89; 95 % CI 0·82, 0·96) and Cu (HR 0·91; 95 % CI 0·84, 1·00). Prediction patterns and significance for primary vascular, cancer and respiratory mortality differed in certain respects, but not fundamentally. Model adjustment for known disease or mortality risk predictors resulted in loss of significance for some of the indices; however, plasma Se and Zn, and food energy remained significant predictors. We conclude that total and primary vascular, cancer and respiratory mortality in older British people of both sexes is predicted by several biochemical indices of redox-modulatory nutrients, some of which may reflect the respondents' acute-phase status at baseline, whereas others may reflect the healthiness of their lifestyle.

There is variability in the association between dietary intake and health outcomes across different countries, especially among the elderly. We used the gold standard dietary assessment method, a weighed food record, to examine the association between dietary pattern and mortality in a representative sample of community dwelling participants from Great Britain aged 65 years and older. Dietary intake was recorded at baseline in 1017 elderly participants (520 men, 497 women, mean age 76.3±7.4 years). Exploratory factor analysis was performed to examine dietary patterns and participants were followed up over an average of 9.2 years for mortality. The factor analysis revealed four interpretable principal components accounting for approximately 9.8% of the total variance, with similar patterns across sex. A ‘Mediterranean-style’ dietary pattern explained the greatest proportion of the variance (3.7%), followed by ‘health-aware’ (2.2%), ‘traditional’ (2.0%) and ‘sweet and fat’ (1.9%) factors. There were a total of 683 deaths through follow-up. After adjustment for potential confounders, only the Mediterranean-style dietary pattern remained associated with mortality (highest vs lowest tertile; hazard ratio=0.82, 95% CI, 0.68–1.00). The benefits of the Mediterranean-style diet were only observed among women (hazard ratio=0.71, 95% CI 0.52–0.96) although in men the traditional diet was a risk factor for mortality (hazard ratio=1.30, 95% CI 1.00–1.71). Using a gold standard approach, our results confirm previous evidence that dietary patterns are important in longevity among the elderly.

Objective Our objective was to examine associations among plasma homocysteine concentrations (tHcy), the tHcy-cofactors (folate, vitamins B6 and B12), and multiple domains of cognitive performance, with statistical adjustment for possible confounds, including cardiovascular disease risk factors (CVD-RF) and cardiovascular disease (CVD). Methods Subjects were 812 participants (58% women) of the Maine-Syracuse study who were free of dementia and stroke. Employing a cross-sectional design and multiple regression analyses, fasting concentrations of tHcy and its vitamin cofactors (folate, B6, and B12) were related to multiple domains of cognitive performance. Results With adjustment for age, education, gender, ethnicity, and the vitamins, tHcy was inversely associated with visual-spatial organization, working memory, scanning-tracking, and abstract reasoning. The same results were found with adjustment for age, education, gender, ethnicity, CVD-RF, and CVD. Vitamin cofactors were positively related to cognitive performance, but with adjustment for CVD-RF and CVD, only vitamin B6 was related to multiple cognitive domains. Conclusions The inverse association of tHcy with multiple domains of cognitive functioning is not necessarily dependent on vitamin levels, vitamin deficiency, prevalent CVD risk factors, and manifest CVD. Serum folate, serum B12, and plasma B6 vitamin concentrations are positively associated with cognitive performance. Investigation of other possible mechanisms (e.g., tHcy neurotoxicity) mediating tHcy associations with cognitive performance is important, as are clinical trials examining the efficacy of folate, vitamin B6, and vitamin B12 for maintenance of cognitive functioning.

ObjectivesTo describe the selection and modification of an appropriate diet score to assess diet quality in early old age.Design and settingCross-sectional analyses of the Boyd Orr cohort – a long-term follow-up of men and women whose families took part in a survey of diet and health in pre-war Britain. Dietary data were obtained from a 113-item food-frequency questionnaire. A nine-item Healthy Diet Indicator (HDI) developed by Huijbregts and colleagues was identified from the literature and modified because some dietary variables were unavailable and to accord more closely with recommendations of the UK Committee on Medical Aspects of Food Policy.SubjectsIn total, 1475 traced, surviving cohort members aged 60 years and over.ResultsModification resulted in a 12-item Healthy Diet Score (HDS). We found that about half the variation in the HDS was explained by variation in the HDI (r = 0.71). There was, however, little misclassification of subjects (r = −0.57), red meat (r = −0.46), dietary fibre (r = 0.58), fruit and vegetables (r = 0.54) and percentage energy from carbohydrates (r = 0.51). Modifying existing items had greater impact on agreement between HDI and HDS than the addition of new items.ConclusionsThe selection and modification of diet scores is more complicated than often assumed. Furthermore, modest changes to an existing score can produce a score that is different from the original, and although it was not possible to test this issue, it may no longer predict subsequent health experience.

Vitamin C (ascorbate) is essential for hydroxylation of prolyl and lysyl residues in nascent collagen, the failure of which leads to connective tissue lesions of scurvy. Of the pyridinium-type cross-links in mature collagen, pyridinoline requires more hydroxylysyl residues than does deoxypyridinoline. Our study tested the hypothesis that pyridinoline:deoxypyridinoline ratios in urinary degradation products may vary with ascorbate status in man. These ratios were compared between British and Gambian prepubertal boys, mean age 8·3 years, and in Gambian boys between two seasons with contrasting ascorbate availability. The mean cross-links ratio in 216 British boys was 4·36 (sd 0·71), significantly greater (P7 weeks. If confirmed, the putative association between ascorbate and collagen cross-link ratios in man could become the basis for a functional test for adequacy of ascorbate status.

Background: Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular diseases (CVD). HHCY may interact with hypertension (HTEN) and an unfavorable cholesterol profile (UNFAVCHOL) to alter the risk of CVD. Objectives: To estimate the prevalences of HHCY (1) isolated and (2) in combination with UNFAVCHOL and/or HTEN in different age categories. To provide information that may improve the screening and treatment of subjects at risk of CVD. Design: Cross-sectional data on 12 541 men and 12 948 women aged 20 + y were used from nine European studies. Results: The prevalence of isolated HHCY was 8.5% in subjects aged 20-40 y, 4.7% in subjects aged 40-60 y and 5.9% in subjects aged over 60 y. When combining all age groups, 5.3% had isolated HHCY and an additional 5.6% had HHCY in combination with HTEN and/or UNFAVCHOL. The combinations of risk factors increased with age and, except for HHCY&UNFAVCHOL, were more prevalent than predicted by chance. Of the young subjects (20-40 y), 24% suffered from one or more of the investigated CVD risk factors. This figure was 75.1% in the old subjects (60 + years). Conclusions: A substantial number of subjects in selected European populations have HHCY (10.9%). In half of these cases, subjects suffer also from other CVD risk factors like UNFAVCHOL and HTEN. Older people in particular tend to have more than one risk factor. Healthcare professionals should be aware of this when screening and treating older people not only for the conventional CVD risk factors like UNFAVCHOL and HTEN but also HHCY, as this can easily be reduced through increased intake of folic acid via supplement or foods fortified with folic acid. © 2005 Nature Publishing Group All rights reserved.

Objective: To examine zinc and vitamin A intake and status and associated dietary, socio-demographic, lifestyle and physiological factors in British young people. Design: National Diet and Nutrition Survey of young people aged 4–18 y. Setting: Great Britain, 1997. Subjects: Complete 7-day weighed dietary records were provided by 1520 participants, while 1193 provided blood samples. Results: A total of 13 and 11% of participants respectively reported low dietary intakes of zinc and vitamin A (retinol equivalents), relative to the UK lower reference nutrient intake. These percentages were not altered significantly by including contributions to intake from supplements, mainly containing vitamin A (as retinol). Likelihood of low zinc and/or vitamin A intake was more often associated with age, sex and likely under-reporting of food consumption than with other socio-demographic and lifestyle factors. Low zinc and vitamin A intakes were generally less likely in those with higher consumption of dairy foods (mainly milk). Zinc and vitamin A status (assessed by plasma zinc and retinol concentrations) were adequate in almost all participants. Plasma zinc concentration was not significantly associated with zinc intake. Plasma retinol concentration was correlated with vitamin A intake (overall r=0.17, P

Objective:To examine the prevalence and dietary, sociodemographic and lifestyle risk factors of low iron intake and poor iron status in British young people.Design:National Diet and Nutrition Survey of young people aged 4–18 years.Setting:Great Britain, 1997.Subjects:In total, 1699 young people provided 7-day weighed dietary records, of which 11% were excluded because the participant reported being unwell with eating habits affected. Blood was obtained from 1193 participants, with iron status indicated by haemoglobin, serum ferritin and transferrin saturation.Results:Iron intakes were generally adequate in most young people aged 4–18 years. However, low iron intakes (below the Lower Reference Nutrient Intake) occurred in 44% of adolescent girls (11–18 years), being less prevalent with high consumption of breakfast cereals. Low haemoglobin concentration (−1, 4–12 years; −1, 13+ years for girls and boys, respectively) was observed in 9% of children aged 4–6 years, pubertal boys (11–14 years) and older girls (15–18 years). Adolescent girls who were non-Caucasians or vegetarians had significantly poorer iron status than Caucasians or meat eaters, independent of other risk factors. The three iron status indices were correlated significantly with haem, but not non-haem, iron intake.Conclusions:Adolescent girls showed the highest prevalence of low iron intake and poor iron status, with the latter independently associated with non-Caucasian ethnicity and vegetarianism. Risk of poor iron status may be reduced by consuming (particularly lean red) meat or enhancers of non-haem iron absorption (e.g. fruit or fruit juice) in vegetarians.

Mild-to-moderate vitamin C depletion in weanling guinea-pigs affects pyridinoline:deoxypyridinoline (collagen cross-link) ratios in femur shaft and urine, attributed to impairment of hydroxylation of collagen lysine. We investigated: (1) whether the picture at two time points is compatible with progressive accumulation of abnormal collagen; (2) whether any changes are seen in skin, where little deoxypyridinoline occurs; (3) whether total food restriction has similar effects. Male weanling Dunkin–Hartley guinea-pigs were fed diets containing either 0·5 (vitamin C-restricted) or 160·0–320·0 (vitamin C-adequate) mg vitamin /. Two groups receiving the vitamin C-adequate diet received itad libitum. Two other groups received the vitamin C-adequate diet in a restricted amount, limited to that which permitted nearly the same growth rate as in the vitamin C-restricted groups. Animals were fed for 4 or 8 weeks; urine was collected, and vitamin C and collagen indices were measured. In the femur shaft, the hydroxyproline content per unit weight was unaffected by vitamin C restriction or by total food restriction. Deoxypyridinoline was increased and the pyridinoline:deoxypyridinoline ratio was decreased in vitamin C-restricted groups, but not in food-restricted groups. Changes in the value of the ratio were greater after 8 than after 4 weeks. Urine indices mirrored bone indices. In skin, the main effect of vitamin C restriction was to reduce hydroxyproline. Here, the cross-link ratios changed less markedly than in bone, and there was less deoxypyridinoline. We conclude that the picture at two time points is compatible with a progressive accumulation of pyridinoline-enriched collagen in vitamin C-deprived animals, that the picture in skin differs from that of bone and urine, and that cross-link changes are not produced by total food restriction.

Intake and sources of phylloquinone (vitamin K1) were examined according to socio-demographic and lifestyle factors in free-living British people aged 65 years and over, from the 1994-5 National Diet and Nutrition Survey. Complete 4-d weighed dietary records were obtained from 1152 participants living in private households. Using newly-available, mainly UK-specific food content data, the weighted geometric mean intake of phylloquinone was estimated at 65 (95 % CI 62, 67) microg/d for all participants, with higher intakes in men than in women (70 v. 61 microg/d respectively, P

Plasma phylloquinone (vitamin K1) concentration was examined according to season, socio-demographic and lifestyle factors and phylloquinone intake in a nationally representative sample of British people aged 65 years and over from the 1994–5 National Diet and Nutrition Survey. Values for both plasma phylloquinone concentration and phylloquinone intake were available from 1076 participants (561 men, 515 women). Eight hundred and thirty-four were living in private households, 242 in residential or nursing homes. Weighted geometric mean plasma phylloquinone concentrations were 0·36 (95 % CI 0·06, 2·01) and 0·24 (95 % CI 0·06, 0·96) nmol/l in free-living and institution samples respectively. Plasma phylloquinone concentrations did not generally differ between men and women, although values in free-living people were significantly lower during autumn and winter (October to March). Plasma phylloquinone concentration was not significantly associated with age. Plasma phylloquinone concentrations were positively correlated with phylloquinone intake in free-living men and women (r0·18 and 0·30 respectively, bothPP

Plasma total homocysteine (tHcy), cysteine and cysteinyl-glycine were measured in a representative sample of 922 young people aged 4–18 years, participating in the National Diet and Nutrition Survey in mainland Britain in 1997. Both tHcy and cysteine increased markedly with age; cysteinyl-glycine less so. Neither tHcy nor cysteine differed between genders; cysteinyl-glycine was higher in males. tHcy concentrations were lowest in the winter; cysteine and cysteinyl-glycine varied only slightly with season. In respondents aged >15 years, tHcy was higher in smokers, but in respondents aged 7–11 years, tHcy was higher in those whose mothers smoked. tHcy was inversely correlated with serum folate, serum vitamin B12and vitamin B6status, but neither cysteine nor cysteinyl-glycine shared these relationships. The relationships between tHcy and B-vitamin status indices ran parallel with those of the 65 years and over survey, but at much lower tHcy concentrations for any given B-vitamin concentration. Age-adjusted tHcy was not correlated with anthropometric indices, blood pressure, haematology, plasma creatinine, urea or cholesterol, but was directly correlated with fasting triacylglycerol. We conclude that disease-risk indices, like tHcy and perhaps cysteine, if established during early life, may be modulated by diet and lifestyle, thereby providing an opportunity for public health intervention.

To the Editor: An accumulating body of evidence has demonstrated the health benefit of certain behaviors, including moderate physical activity,1 not -smoking,2 low to moderate alcohol intake,3 and consumption of fruit and vegetables.4 Despite this, adherence to a healthy lifestyle pattern has decreased during the last 18 years.5 Because multiple health risk behaviors are known to cluster, the effect of combined health behavior on health outcomes may be important. This research may be helpful to inform policy-makers about the efficacy of multibehavior interventions as opposed to single-behavior interventions, but there is limited information about the effects of combined health behaviors on mortality in representative samples of older adults, which formed the rationale for the present study. Data were derived from the National Diet and Nutrition Survey (NDNS) of people living in the community aged 65 and older from mainland Britain.6 Ethical approval for the survey was obtained from the local research ethics committees for each of the 80 randomly-selected post code sectors included in the survey (20 per “wave”) and from the Ethics Committee of the Medical Research Council (MRC) Dunn Nutrition Unit. The survey was linked to National Health Service administrative mortality data up to September 2008. Self-reported physical activity, smoking, and alcohol use were recorded. Plasma vitamin C was used as a marker of plant food intake, with a value of 50 mU or greater used to indicate daily intake of at least five servings of fruit and vegetables, as previously defined.7 This measure was verified against estimated vitamin C intake from a 4-day weighed food record.6 A combined health behavior score was derived by giving 1 point for each of the following: nonsmoking, moderate alcohol consumption (1–21 units for men, 1–14 units for women), regular moderate to vigorous physical activity, and vitamin C (≥ 50 mU). Thus, the combined health behavior scores ranged from 0 to 4. The survey response rate was 85%; from the eligible sample of 2,172 participants, 72% provided full interview data and 59% provided full diet records. The present analysis consisted of 1,062 participants (539 men, 523 women, mean age, 76.5 ± 7.5, range 65–99) who consented to follow-up. Approximately 15.0% of the sample adhered to all four behaviors. Participants adhering to more healthy behaviors were younger, more likely to be female, and more highly educated and had better self-rated health. There were 714 all-cause deaths over an average of 9.2 years of follow-up. The results demonstrate a linear inverse association between the combined health behavior score and mortality risk, which persisted after adjustment for possible confounding factors (Table 1). All of the individual health behaviors were associated with lower risk of mortality: physical activity (multivariate-adjusted hazard ratio (HR)=0.83, 95% confidence interval (CI)=0.69–1.00), smoking (HR=0.73, 95% CI=0.59–0.90), moderate alcohol (HR=0.81, 95% CI=0.70–0.94), and vitamin C intake of 50 mU or greater (HR=0.88, 95% CI=0.74–1.05). None of the health behaviors individually was as powerful as the combined effects, which lowered the all-cause mortality rate 58%. When estimated dietary vitamin C intake was used instead of plasma vitamin C, the results were identical when using a cut-point of 40 mg/d to represent the U.K. recommended intake. Table 1 Cox Proportional Hazards Models for the Association Between Combined Health Behavior and Mortality over 9 Years of Follow-Up The present study demonstrated that adherence to healthy behaviors, including not smoking, moderate alcohol consumption, regular moderate to vigorous physical activity, and adequate vitamin C intake (a marker of fruit and vegetable consumption) was associated with lower risk of mortality in a representative sample of older participants from the United Kingdom. Approximately 15% of the sample met the criteria for all four healthy behaviors, which is comparable with a German cohort, in which 9% met the same criteria.8 Although a number of previous studies have examined associations between combined health behavior and disease end points, far less work has specifically considered the elderly population. In a cohort of elderly European men and women, adherence to the four key health behaviors lowered all-cause mortality 65%,9 which is similar to the results of the current study, which demonstrate a 51% lower risk after adjustment for possible confounders. In the Cardiovascular Health Study, the rate of incident diabetes mellitus was 35% lower for each additional low-risk lifestyle factor in participants aged 65 and older.10 Strengths of the present study include the nationally representative sample of community-dwelling adults, the prospective design, and the rigorous methods of outcome ascertainment. The exposure measures were based on self-report, which represents a limitation. In summary, healthy behaviors confer benefit for survival in older adults.

ObjectiveTo examine risk factors for poor iron status in British toddlers.DesignNational Diet and Nutrition Survey (NDNS) of children aged 1.5–4.5 years.SettingMainland Britain, 1992/93.SubjectsOf the 1859 children whose parents or guardians were interviewed, a weighed dietary intake was provided for 1675, and a blood sample obtained from 1003.ResultsMean haemoglobin (Hb) and ferritin levels were significantly lower in younger (1.5–2.5 years) than in older (3.5–4.5 years) children, with boys having significantly lower ferritin levels than girls. Poor iron status (Hb>110 g l−1, ferritin >10 μg l−1, or low values for both indices) was associated with lower socioeconomic and employment status. Iron status was directly associated with meat and fruit consumption and inversely with that of milk and milk products, after adjustment for age and gender. The latter association remained significant after further adjustment for sociodemographic variables, energy intake and body weight. Children consuming −1of milk and cream were less likely to consume foods in other groups, with those also consuming little meat, fish, fruit and nuts at greatest risk of poor iron status. Few associations were observed between poor iron status and individual nutrient intakes, and iron status was not associated with either iron intake or with consumption of a vegetarian diet.ConclusionsOverdependence on milk, where it displaces iron-rich or iron-enhancing foods, may put toddlers at increased risk of poor iron status. However, this becomes non-significant when moderate-to-high amounts of foods known to enhance iron status (e.g. meat and/or fruit) are also consumed. Milk consumption in this age group should ideally be part of a mixed and balanced diet including all food groups, and particularly lean meat (or other iron-rich or fortified foods) and fruit. This is particularly relevant for households of lower socioeconomic and employment status.

Objectives: To determine the patterns and possible explanations for gender differences in food choices, nutrient intakes and status indices, especially for micronutrients, in a representative sample of older people living in Britain, who participated in the National Diet and Nutrition Survey of people aged 65 y and over during 1994–95. Design: The Survey procedures included a health-and-lifestyle interview, a four-day weighed diet record, anthropometric measurements and a fasting blood sample for biochemical indices. Setting: Eighty randomly-selected postcode sectors from mainland Britain. Subjects: Of 1556 older people not living in institutions who were interviewed, 80% agreed to provide a complete four-day diet record and 63% agreed to give a blood sample for status index measurements. Interventions: None. Main result: The most highly significant gender differences in food choices were that women ate more butter, full-fat milk and certain beverages, cakes, apples, pears and bananas, whereas men ate more eggs, sugar, certain meat products and drank more alcoholic drinks, especially beer and lager. When adjusted for energy intakes, the younger women (65–79 y) had higher intakes than the younger men, of fat, retinol, vitamin C and calcium. The older women (80+y) had higher intakes than older men, of fat and vitamin E, but lower intakes of protein, zinc and β-carotene. The younger women had better status indices than the younger men: for α- and β-carotenes, β-cryptoxanthin and vitamin C. Women had higher plasma concentrations of cholesterol and HDL cholesterol, phosphate and copper, but lower indices of iron and vitamin D status, than men. These gender differences in status were not altered by inclusion of the corresponding nutrient intakes in the model. Conclusions: There are gender differences in food choices, in energy and nutrient intakes and in nutritional blood status indices in older British people, especially those aged 65–79 y. Some of the status differences are attenuated in the age group of 80 y and older, whereas others are enhanced. The relationships between the quantity and type of foods or nutrients consumed, and nutrient status, are complex. With respect to suspected risk and protective factors for vascular disease, women aged 65–79 y had significantly better status for plasma α-and β-carotene, ascorbate, HDL-cholesterol and homocysteine; but, in contrast, they had lower blood haemoglobin concentrations and higher concentrations of total and non-HDL-cholesterol. Sponsorship: The British National Diet and Nutrition Survey series is funded by the Ministry of Agriculture, Fisheries and Food and the Department of Health, and this survey was conducted by Social and Community Planning Research in conjunction with MRC Human Nutrition Research (formerly MRC Dunn Nutritional Laboratory).

The aims of the National Diet and Nutrition Survey series are summarized, and the new National Diet and Nutrition Survey of people aged 65 years and over is explored, with particular emphasis on micronutrient intakes and status indices. Mean nutrient intakes were generally satisfactory for most micronutrients, but intakes of vitamin D, Mg, K and Cu were low. Intakes of vitamin D were far below the reference nutrient intake for people aged 65 years and over, and there was also biochemical evidence of vitamin D deficiency, for 8 % of free-living and 37 % of institution participants, attributed partly to limited exposure to sunlight. A substantial proportion of people living in institutions had inadequate biochemical status indices, notably for vitamin C, Fe and folate. Relationships between intake and status were close for vitamins. Mineral intakes did not correlate well with currently used status indices. Some intakes and indices, especially those of vitamin C, carotenoids, Na and K, were strongly correlated with socio-economic status and with north–south gradients in Britain. Future research challenges should address the functional and health significance of low intakes and sub-optimal biochemical indices for certain micronutrients, especially for people living in institutions; the shortcomings of mineral status indices especially as indicators of mineral intake; the social and geographical inequalities of micronutrient intakes and status, and why micronutrient status deteriorates with increasing age. The answers to these questions will help to define the characteristics of nutritional risk for older people in Britain, and to clarify future needs for education and intervention.

Objective:To compare vitamin B6status indices with each other and with potential confounding factors, in the datasets from two national British surveys and associated studies.Design:Vitamin B6status was measured by plasma pyridoxal phosphate (PLP) and plasma pyridoxic acid (PA) in both surveys, and also by erythrocyte aspartate aminotransferase activation coefficient (EAATAC) in one of the surveys. Plasma α1-antichymotrypsin was measured as an index of acute phase status; plasma creatinine was measured as an index of renal function; and plasma total alkaline phosphatase activity was measured as a proxy for PLP hydrolase activity.Setting:The survey of people aged 65 years and over was carried out in 80 postcode sectors across mainland Britain during 1994–95 and the survey of young people was carried out in 132 postcode sectors across mainland Britain during 1997.Subjects:Blood samples fromc. 1000 subjects of both sexes in each survey permitted measurements of plasma PLP and PA. There were also measurements of EAATAC in the young people's survey.Results:According to published limits of normality, only 5% or less of the young people had unacceptable vitamin B6status as measured by plasma PLP. About half had apparently unacceptable status by EAATAC, but this observation is difficult to interpret. The young people had considerably higher plasma concentrations of PLP and lower concentrations of PA than the older people. In both surveys, plasma PLP was strongly correlated with plasma PA and in the young persons’ survey it was also correlated, although much less strongly, with the basal activity and activation coefficient of aspartate aminotransferase. Both plasma PLP and EAATAC (but not PA nor basal aspartate aminotransferase activity) were influenced by acute phase status in young people, as indicated by significant correlations with α1-antichymotrypsin. In people aged 65 years and over, PA (but not PLP) was correlated with renal function, as indicated by its relation with plasma creatinine; however PLP (but not PA) was correlated with plasma alkaline phosphatase activity.Conclusions:Several potential confounders — acute phase reaction, kidney malfunction and hydrolase activity — may influence vitamin B6status indices, although differently for different indices and different age groups. Since older people have relatively poor vitamin B6status, which may have important health implications for them, more reliable vitamin B6status indices are needed.

Objectives: To examine seasonality of 25-hydroxyvitamin D (25OH-D) levels in British preschool children and the effect of vitamin D supplementation on this. Design: The National Diet and Nutrition Survey of children aged 1.5–4.5 y in Britain during 1992–3 measured dietary intakes and blood status indices, including those for vitamin D, during all four seasons. The present study addresses the seasonal dependence of the relation between vitamin D intake and status. Setting: 100 randomly selected postcode sectors throughout Britain, whose locations were classified as (a) Scotland; (b) Northern England; (c) Central, Wales, South+SW; (d) London+SE. Subjects: Of 1859 whose parents or guardians were interviewed, 1675 provided a weighed diet estimate, and blood vitamin D status (25OH-D) was measured in 756, with approximately equal numbers in each season. Results: Vitamin D status is highly dependent on season: moreover, the relation between vitamin D intake and status is also seasonally dependent, being strong in the winter and negligible in the summer. During the winter, those children who had relatively low 25OH-D concentrations generally were those not receiving vitamin D supplements. Vitamin D intakes and supplement use were lower in the north than in the south of Britain. Conclusions: For British preschool children, dietary vitamin D is of much greater importance in the winter than in the summer. There is evidence of regional inequality, with lesser use of supplements in the north. Supplements are needed in the winter, to achieve satisfactory vitamin D status and minimise the risk of rickets and of poor bone health, especially in high-risk groups. Sponsorship: This study was part of the National Diet and Nutrition Survey of Children Aged 1.5–4.5 y, which was funded jointly by the Ministry of Agriculture, Fisheries and Food and the Department of Health, and was conducted by the Social Survey Division of the Office of Population Censuses and Surveys (now the Office for National Statistics) and the MRC Dunn Nutritional Laboratory (now MRC Human Nutrition Research).

ObjectivesTo examine the relationship between cigarette smoking and a range of nutrient intakes and blood status indices in older people.DesignNational Diet and Nutrition Survey: cross-sectional survey of nationally representative sample of people aged 65 years and over.SettingMainland Britain during 1994/95.Subjects1191 people (619 male, 572 female) aged 65 years and over, of whom 920 were living in private households and 271 were living in institutions.ResultsCigarette smoking was inversely correlated with intakes of antioxidants and other micronutrients after adjustment for age, sex and domicile. Cigarette smoking was also inversely correlated with a number of antioxidant micronutrient status indices including plasma vitamin C and the carotenoids (but not vitamin E status indices), and with other micronutrient status indices, including plasma pyridoxal phosphate, red cell and serum folate, after adjustment for age, sex, domicile and the corresponding nutrient intake. Previous cigarette smoking or cigar/pipe smoking was not generally associated with lower nutrient intakes or status indices, however, both current and previous cigarette smoking was associated with increased concentrations of acute phase indicators. Further adjustment for total energy intake and/or sociodemographic, health and drug usage variables attenuated only a few of the associations observed.ConclusionOlder people who smoke cigarettes are at increased risk of suboptimal antioxidant and other micronutrient intakes and status, but the lower intakes found in cigarette smokers only partly explain their reduced blood indices.

Objective:To describe the extent of use of medicines by older people living in Britain, and to explore relationships with vitamin status indices.Design:The National Diet and Nutrition Survey of people aged 65 years and over collected data from a British sample during 1994–95. The present study has made novel use of it, to relate medicine use with biochemical indices of vitamin status.Setting:Eighty postcode areas, selected randomly from mainland Britain.Subjects:1506 people, 65 years and over gave information about use of medication, and a 4-day weighed food record. Three-quarters gave blood for status indices.Results:78% of those living in the community and 93% of those in institutions were using medication. Certain vitamin status indices: plasma retinol, erythrocyte folate and riboflavin, paradoxically suggested better status in users than in non-users of antihypertensive, gastrointestinal, central nervous system, corticosteroid or diabetic drugs. There was evidence of a link with renal insufficiency, especially for plasma retinol, but neither this nor increased nutrient intake, acute phase effects or haemoconcentration could explain the paradoxical associations.Conclusions:Caution is needed in interpreting certain vitamin status indices, especially in older people who are extensively using medicines. New vitamin indices are needed, to avoid confounding interferences.

During an epidemic outbreak of neuropathy in Cuba during 1992-1993, blood and urine samples were collected from 107 persons with confirmed neuropathy, from 106 control subjects without clinical abnormality who were broadly matched with the affected persons by age and domicile, and from 537 unmatched subjects, also free from clinical abnormality. The unmatched subjects lived in two locations in Cuba ; at each location they were drawn from two age ranges : 14-15-y-old secondary school students and 16-64-y-old adults. Measurements of urinary thiamine and blood transketolase and its activation with thiamine pyrophosphate were made. For the neuropathy subjects, these measurements were repeated after 3 wk of rehabilitation. All groups showed biochemical evidence of thiamine depletion affecting 30-70% of their members, which is a high prevalence. Severity of biochemical depletion was, however, no greater in the neuropathy subjects than in the control subjects (P > 0.05). However, it was greater in Pinar del Rio, where the incidence of disease was higher, than in the city of Havana, where less disease was seen. Although the majority of the affected subjects responded biochemically to a daily oral multivitamin supplement containing thiamine (P < 0.001), in some cases normal biochemical status was not achieved even after 3 wk of intensive treatment. In the affected group, thiamine status was inversely correlated with the amount of alcohol consumed (P = 0.007). Thiamine status at the outset was correlated with clinical outcome after treatment. Although neither thiamine depletion nor alcohol abuse were likely to have been the sole cause of the neuropathy epidemic, they may have been contributory factors. Thiamine supplementation or food fortification may therefore be necessary in Cuba.

Results from analysis of 24 h urine collections, verified for completeness with para-amino benzoic acid, and blood samples collected over 1 year were compared with 16 d weighed records of all food consumed collected over the year, and with results from 24 h recalls, food-frequency questionnaires and estimated food records in 160 women. Using the weighed records, individuals were sorted into quintiles of the distribution of the urine N excretion: dietary N intake ratio (UN:DN). UN exceeded DN in the top quintile of this ratio; mean ratio UN:DN = 1·13 Individuals in this top quintile were heavier, had significantly greater body mass indices, were reportedly more restrained eaters, had significantly lower energy intake:basal metabolic rate ratios (EI:BMR), and had correlated ratios of UN:DN and EI:BMR (r- 0·62). Those in the top quintile reported lower intakes of energy and energy-yielding nutrients, Ca, fats, cakes, breakfast cereals, milk and sugars than individuals in the other quintiles but not lower intakes of non-starch polysaccharides, vitamin C, vegetables, potatoes or meat. Correlations between dietary intake from weighed records and 24 h urine K were 0·74 and 0·82, and between dietary vitamin C and β-carotene and plasma vitamin C and β-carotene 0·86 and 0·48. Correlations between dietary N intake from weighed records and 24 h urine excretion were high (0·78–0·87). Those between N from estimated food records and urine N werer0·60–0·70. Correlations between urine N and 24 h recalls and food-frequency questionnaires were in the order of 0·01 to 0·5. Despite problems of underreporting in overweight individuals in 20% of this sample, weighed records remained the most accurate method of dietary assessment, and only an estimated 7 d diary was able to approach this accuracy.

We describe studies of nanoparticle synthesis using oligonucleotides as capping ligands. The oligonucleotides nucleate, grow, and stabilize near-infrared fluorescent, approximately uniform PbS nanocrystals in an aqueous environment. The properties of the resulting particles strongly depend upon the sequences as well as synthesis conditions. Fourier Transform infrared measurements suggest that functional groups on the nucleobases such as carbonyl and amine moieties are responsible for surface passivation, while the phosphate backbone is strained to accommodate nucleobase bonding, preventing irreversible aggregation and thereby stabilizing the colloids. Our theoretical model indicates that oligonucleotide-mediated particle growth relies on the chemical reactivity of the oligonucleotide ligands that saturate dangling bonds of growing clusters, and favorable sequences are those that have the highest surface reactivity with growing particles. The oligonucleotide template approach is facile and versatile, offering a route to produce a range of material compositions for other chalcogenide semiconductor quantum dots and metal oxide nanoparticles.

Children growing up in poor versus affluent neighborhoods are more likely to spend time in prison, develop health problems and die at an early age. The question of how neighborhood conditions influence our behavior and health has attracted the attention of public health officials and scholars for generations. Online tools are now providing new opportunities to measure neighborhood features and may provide a cost effective way to advance our understanding of neighborhood effects on child health.A virtual systematic social observation (SSO) study was conducted to test whether Google Street View could be used to reliably capture the neighborhood conditions of families participating in the Environmental-Risk (E-Risk) Longitudinal Twin Study. Multiple raters coded a subsample of 120 neighborhoods and convergent and discriminant validity was evaluated on the full sample of over 1,000 neighborhoods by linking virtual SSO measures to: (a) consumer based geo-demographic classifications of deprivation and health, (b) local resident surveys of disorder and safety, and (c) parent and teacher assessments of children's antisocial behavior, prosocial behavior, and body mass index.High levels of observed agreement were documented for signs of physical disorder, physical decay, dangerousness and street safety. Inter-rater agreement estimates fell within the moderate to substantial range for all of the scales (ICCs ranged from .48 to .91). Negative neighborhood features, including SSO-rated disorder and decay and dangerousness corresponded with local resident reports, demonstrated a graded relationship with census-defined indices of socioeconomic status, and predicted higher levels of antisocial behavior among local children. In addition, positive neighborhood features, including SSO-rated street safety and the percentage of green space, were associated with higher prosocial behavior and healthy weight status among children.Our results support the use of Google Street View as a reliable and cost effective tool for measuring both negative and positive features of local neighborhoods.

Predictive power, for total and vascular mortality, of selected indices measured at baseline in the British National Diet and Nutrition Survey (community-living subset) of People Aged 65 Years and Over was tested. Mortality status and its primary and underlying causes were recorded for 1100 (mean age 76·7 (sd7·5) years, 50·2 % females) respondents from the baseline survey in 1994–5 until September 2008. Follow-up data analyses focussed especially on known predictors of vascular disease risk, together with intakes and status indices of selected nutrients known to affect, or to be affected by, these predictors. Total mortality was significantly predicted by hazard ratios of baseline plasma concentrations (persd) of total homocysteine (tHcy) (95 % CI) 1·19 (1·11, 1·27), pyridoxal phosphate 0·90 (0·81, 1·00), pyridoxic acid 1·10 (1·03, 1·19), α1-antichymotrypsin 1·21 (1·13, 1·29), fibrinogen 1·14 (1·05, 1·23), creatinine 1·20 (1·10, 1·31) and glycosylated Hb 1·23 (1·14, 1·32), and by dietary intakes of energy 0·87 (0·80, 0·96) and protein 0·86 (0·77, 0·97). Prediction patterns and significance were similar for primary-cause vascular mortality. The traditional risk predictors plasma total and HDL cholesterol were not significant mortality predictors in this age group, nor were the known tHcy-regulating nutrients, folate and vitamin B12(intakes and status indices). Model adjustment for known risk predictors resulted in the loss of significance for some of the afore-mentioned indices; however, tHcy 1·34 (1·04, 1·73) remained a significant predictor for vascular mortality. Thus, total and primary vascular mortality is predicted by energy and protein intakes, and by biochemical indices including tHcy, independent of serum folate or vitamin B12.

Marginally vitamin C-deficient guinea-pigs treated with the diabetogenic agent streptozotocin were compared with those liberally supplied with vitamin C, for functional indices of vitamin C status, particularly in the eye lens. Weanling male Dunkin–Hartley guinea-pigs were fed on diets with 0.1 g vitamin C/kg (marginally deficient), or 5 g/kg (liberally supplied), and some received intraperitoneal streptozotocin (two doses of 150 mg/kg body-weight). About half the streptozotocin-treated animals had high urinary glucose following an oral glucose dose; these animals also grew more slowly than the others. At 4 months after streptozotocin the animals were killed for measurement of tissue vitamin C, glucose and sorbitol. Streptozotocin moderately increased the concentration of glucose in plasma, lens and aqueous humour. Lens sorbitol levels increased only in the group exposed to streptozotocin plus marginal vitamin C. There was a significant (P < 0.02) positive correlation between urinary glucose and lens sorbitol levels overall. Liberal vitamin C intake may thus counteract the effect of streptozotocin diabetes on lens sorbitol, suggesting a new function of vitamin C, possibly related to cataractogenesis and to the biochemical lesions associated with diabetes.

Background: Iron-related genes and iron status may independently contribute to variable HIVoutcomes. The nature of the biologically plausible gene-nutrient interaction remains unknown. Objectives: The objectives were to investigate whether iron-related genotypes and clinically abnormal iron status independently predict mortality in HIV and whether a gene-nutrient interaction exists. Design: Baseline plasma, DNA, and clinical data were obtained from 1362 HIV-seropositive Gambian adults followed for 11.5 y to ascertain all-cause mortality. Iron status was estimated on the basis of plasma iron, soluble transferrin receptor (sTfR), ferritin, transferrin, transferrin index, and log(sTfR/ferritin). One haptoglobin (HP) and 5 SLC11A1 (NRAMP1) polymorphisms were genotyped. Results: SLC11A1-SLC3 and CAAA polymorphisms were the best independent genetic predictors of mortality [adjusted mortality rate ratio (95% CI)]: SLC3:G/C = 0.59 (95% CI: 0.45, 0.85), CAAA:del/ ins = 1.51 (95% CI: 1.10, 2.07). In an adjusted model that included all polymorphisms, SLC1:199/199, SLC1:other/other, SLC6a:A/A, and CAAA:del/ins were associated with significantly greater mortality, whereas Hp 2‐1 and SLC3:G/C were protective. In unadjusted analyses, all biomarker concentrations were significantly associated with mortality. Extending previous findings, both low and elevated iron states were associated with mortality, but the nature of the risk was variable, with linear, inversely linear, and U-shaped associations depending on the biomarker. Mortality was significantly lower in HIV-2 than in HIV-1 infection in the presence of abnormal (low or elevated) iron status. A gene-iron interaction was detected (likelihood-ratio test P = 0.018); however, subject numbers restricted category-specific interpretation. Conclusions: Iron-related genes, iron status, and their interaction predict mortality in HIV. These findings illustrate the complexity and uncertainty surrounding best practice for managing abnormal iron status and anemia during HIV infection and in regions with a high risk of infection. Am J Clin Nutr 2009;90:1‐9.

The objective was to comprehensively assess iron status and determine whether elevated iron status like anemia predicts mortality. We followed 1362 Gambian adults (53% female) in an HIV-seroprevalent clinic-based cohort over 11.5 years to ascertain all-cause mortality. Baseline iron status (iron soluble transferrin receptor [sTfR] transferrin ferritin transferrin saturation log [transferrin receptor: ferritin]) age gender ethnicity hemoglobin body mass index HIV type absolute CD4 count malaria status and a-1-antichymotrypsin were measured. The mortality rate was 25.9/100 person-years. Elevated iron universally predicted greater mortality compared to normal iron status for all iron status indices with the exception of sTfR in unadjusted models. In fully adjusted models transferrin (elevated vs. normal hazard ratio [HR]: 1.77; 95% confidence interval [CI]: 1.30 to 2.42; P less than 0.001) ferritin (elevated vs. normal HR: 1.40; 95% CI: 1.07 to 1.83; P = 0.014) and the combined iron status index (highly elevated vs. normal HR: 2.20; 95% CI: 1.16 to 4.18; P = 0.016) remained significant predictors. As expected hemoglobin (Hb) concentration and absolute CD4 counts were each inversely associated with mortality. Elevated iron status predicts mortality in HIV infection even after adjustment for immunosuppression and other confounders. This finding has implications in the clinical monitoring of disease progression and for iron-supplementation practices in areas of high HIV prevalence. (authors)

The disease risk indicator plasma total homocysteine (tHcy) is influenced by genetic and environmental factors, including folate and vitamin B(12) status. Little is known about the determinants of tHcy in rural West Africa. We explored the hypothesis that tHcy in rural Gambian adults might vary between the sexes and physiological groups, and/or with folate and vitamin B(12) status. Comparisons were made with a British national survey. Non-pregnant Gambian women (n 158) had tHcy concentrations (geometric mean 9.0 micromol/l) similar to those of non-pregnant UK women (n 449; 9.4 micromol/l), whereas pregnant Gambian women (n 12) had significantly lower values (6.2 micromol/l). Gambian men (n 22) had significantly higher values (14.7 micromol/l) than British men (n 354; 10.8 micromol/l). Gambian lactating women and British men and women exhibited significant inverse relationships between log(e)(tHcy) and folate status; however, only the British subjects exhibited significant inverse relationships between loge(tHcy) and vitamin B(12) status. In the British sample, and in Gambian lactating women, folate and vitamin B(12) status variations together accounted for 20-25 % of the variation in log(e)(tHcy). Within the UK, black-skinned adults had folate and tHcy levels similar to those of their white-skinned counterparts, but significantly higher vitamin B(12) values. We conclude that, whereas folate and vitamin B(12) status are similar between British and rural Gambian populations, tHcy is higher in Gambian men and lower in pregnant Gambian women, and that serum vitamin B(12) values appear to be higher in black-skinned than white-skinned British subjects. Possible reasons are discussed.

Previous studies of vitamin C absorption in man using stable isotope probes have given results which cannot easily be reconciled with those obtained using non-isotope measurement. In order to investigate some of the apparent paradoxes we have conducted a study using two consecutive doses of vitamin C, one labelled and one unlabelled, given 90 min apart. Compatibility of the experimental results with two feasible models was investigated. In Model 1, ingested vitamin C enters a pre-existing pool before absorption, which occurs only when a threshold is exceeded; in Model 2, ingested vitamin C is exchanged with a pre-existing flux before absorption. The key difference between these two models lies in the predicted profile of labelled material in plasma. Model 1 predicts that the second unlabelled dose will produce a secondary release of labelled vitamin C which will not be observed on the basis of Model 2. In all subjects Model 1 failed to predict the observed plasma concentration profiles for labelled and unlabelled vitamin C, but Model 2 fitted the experimental observations. We speculate on possible physiological explanations for this behaviour, but from the limited information available cannot unequivocally confirm the model structure by identifying the source of the supposed flux.

Relationships between vitamin E status (alpha and gamma-tocopherol and their ratio in plasma), anthropometric and biochemical indices, and food and nutrient intakes, were studied in four British National Diet and Nutrition Surveys: children aged 1.5-4.5 years, young people aged 4.0-18.0 years, adults 19.0-64.0 years and adults aged > or = 65.0 years. gamma-Tocopherol:alpha-tocopherol ratio declined with age. In older women gamma-tocopherol and gamma-tocopherol:alpha-tocopherol ratios were directly related to indices of obesity. In young men alpha- and gamma-tocopherols were directly correlated with obesity, but gamma-tocopherol:alpha-tocopherol ratio was not. For young people and toddlers, fewer obesity indices were available and relationships were weaker. Other fat- and water-soluble vitamin indices correlated directly with alpha-tocopherol and inversely with gamma-tocopherol and gamma-tocopherol:alpha-tocopherol ratio. Whereas alpha-tocopherol correlated directly with 'healthy' nutrient choices (such as intrinsic sugars, dietary fibre, vitamins and potassium) and inversely with 'unhealthy' choices (extrinsic sugars and monounsaturated fats, i.e. avoidance of polyunsaturated fat), gamma-tocopherol and the gamma-tocopherol:alpha-tocopherol ratio related inversely with 'healthy' choices. Food groups had analogous relationships; thus, alpha-tocopherol related directly to use of polyunsaturated fats, fresh fruits and fruit juices, and inversely to non-polyunsaturated fats and extrinsic sugar. The reverse was true for gamma-tocopherol and gamma-tocopherol:alpha-tocopherol ratio. Although the mechanisms underlying these relationships are obscure, the gamma-tocopherol:alpha-tocopherol ratio may reveal poor dietary choices, status predictors and a propensity for obesity in later life, especially in women.

Factors affecting absorption of physiological doses of vitamin C in man have not been widely studied, partly because few suitable tools exist to distinguish recently absorbed vitamin C from endogenous vitamin. Stable isotope-labelled vitamin C provides such a tool. Fifteen healthy non-smoking subjects aged 26–59 years were studied. Each received 30 mg L-[1-13C]ascorbic acid orally on two occasions, 3–4 weeks apart. The ascorbate was given alone or with Fe (100 mg as ferrous fumarate) or with red grape juice, which is rich in polyphenols. Blood was collected at frequent intervals for 1 h, and then each hour for a further 3 h. Total concentration of vitamin C was measured fluorometrically and its13C-isotope enrichment was measured by GC–MS after conversion to volatile trimethylsilyl esters. Peak plasma enrichment occurred within 25–50 min. No kinetic variables were significantly altered by the iron fumarate supplement. Grape juice attenuated vitamin C absorption, reaching significance at the 20 min time point. There were weak correlations between isotope enrichment and body weight or endogenous ascorbate concentration. The increment in total plasma ascorbate was smaller if calculated from isotope enrichment than from vitamin C concentration increase. The dilution pool was much larger than the plasma ascorbate pool. Further studies are needed to resolve these paradoxes. Stable isotope-labelled ascorbate is potentially useful for measurement of vitamin C absorption by human subjects.

Objective: Assessment of consumption of raw and processed tomatoes, plasma lycopene concentration and their interrelationship in a nationally representative sample of elderly British people. Setting: A 1994–1995 National Diet and Nutrition Survey: a nationwide cross-sectional sample of people aged 65 y and over living in mainland Britain, either in the community (‘free-living’, n=1275) or in institutions such as nursing homes (n=412). Methods: Consumption of raw and processed tomatoes (including those in tomato-containing composite foods) was recorded by a 4-day dietary record for each participant. Plasma lycopene concentration was assayed by HPLC. Sociodemographic and lifestyle information was recorded by trained interviewers. Results: In all, 29% of free-living people and 24% of those living in institutions did not consume any raw or processed tomatoes during the 4-day recording period. Free-living participants were more likely to consume raw tomatoes (26 vs 16%). Plasma lycopene concentration was positively associated with the weight of raw and processed tomatoes consumed, especially with processed tomatoes and their products, alcohol consumption and with plasma total (as well as HDL and non-HDL) cholesterol concentrations. Among free-living participants, increased age, cigarette smoking habit and manual occupational social class were all associated with lower plasma lycopene concentration. Conclusions: In the current population, consumption of raw and processed tomatoes varied by sociodemographic and lifestyle characteristics, and made a significant contribution to plasma lycopene concentration. Determinants of plasma lycopene concentration were age, plasma cholesterol concentration and smoking habit.

Supplementation with carotene-rich fruits may be an effective and sustainable approach to prevent vitamin A deficiency. To test the effectiveness of mango supplementation, 176 Gambian children, aged 2 to 7 y, were randomly assigned to one of four treatments: 75 g of dried mango containing approximately 150 micro g retinol activity equivalents with (MF) or without (M) 5 g of fat, 5 d/wk for 4 mo or 60,000 micro g of vitamin A (A) or placebo (P) capsule at baseline. After 4 mo, plasma beta-carotene was greater in both the M (P < 0.05) and MF (P = 0.07) groups compared with the P group. After controlling for baseline plasma retinol, elevated acute phase proteins and age, plasma retinol concentrations in the A and MF, but not M, groups were higher than in the P group at the end of the study (P < 0.01). Increases in retinol concentrations, however, were small in both groups. These results support the use of dietary supplementation with dried mangoes and a source of fat as one of several concurrent strategies that can be used to help maintain vitamin A status of children in developing countries where there is a severe seasonal shortage of carotenoid-rich foods.

Assessment of functional vitamin B(12) status in a subset of the respondents in the British National Diet and Nutrition Survey of people aged 65 y and over.National Diet and Nutrition Survey: a British nationwide cross-sectional sample of people aged 65 y and over, living either in the community or in institutions such as nursing homes, during one calendar year spanning 1994-1995.Methylmalonic acid (MMA) concentrations were measured in plasma samples from 313 subjects (ca 14% of those originally enrolled in the survey). The results were compared with those for serum vitamin B(12), vitamin B(12) intakes and other status and intake estimates and with socio-demographic indices.Of the NDNS participants overall, 20% had serum vitamin B(12) concentrations150 pmol/l. In the subset studied here, 24% of free-living and 46% of institution-living participants had MMA0.5 micromol/l. Geometric mean MMA increased with age, from 0.25 micro mol/l in people aged 65-74 y to 0.38 micro mol/l in people aged 85+y. There was little evidence for any gender difference in MMA. It was inversely correlated with serum vitamin B(12) and with red blood cell folate; it was positively correlated directly with total homocysteine, but not significantly with serum folate or with vitamin B(12) intake. Among respondents with high MMA, a subgroup had normal serum vitamin B(12) but higher-than-average plasma urea and creatinine. Socio-demographic co-variates of MMA included receipt of State income benefits, social class of head of household, and educational attainment. These indices were not correlated with serum vitamin B(12).The progressive increase in MMA with age is metabolic evidence for increasing risk of functional vitamin B(12) deficiency with increasing age in older people. There is evidence that renal function is linked to high MMA in some older people. Age and renal function are thus both important when establishing upper reference limits for MMA. The socio-demographic observations suggest a link between poverty and poor functional vitamin B(12) status in older British people.

BACKGROUND—Despite the fact that visual function has an important role in the quality of life in later years, very few studies have measured visual acuity in population based nationwide samples of British elderly people. Such measurements were carried out in the context of the national diet and nutrition survey of people aged 65 years or over (NDNS). METHODS—NDNS participants, who were living in 80 different randomly selected postcode areas of mainland Britain, were visited at their home by a nurse who measured visual acuity at 3 metres, using the Glasgow acuity card (GAC) method. In addition, a brief questionnaire related to ocular health was administered. RESULTS—Visual acuity was measured in 1362 NDNS participants who were not classified as mentally impaired. Visual impairment (using the WHO low vision criteria) was measured in 195 (14.3%) subjects. Prevalence of visual impairment increased significantly with age (65-74 years 3.1%; 75-84 years 11.6%; 85+ years 35.5%, p

OBJECTIVES: To provide a reference range for plasma total homocysteine (tHcy), an independent risk factor for vascular disease, and to explore relationships with nutritional indices for people aged 65 y and over, in the UK National Diet and Nutrition Survey (NDNS). DESIGN: The survey procedures described in the National Diet and Nutrition Survey Report (1997) included a health-and-lifestyle interview, a four-day weighed diet record, anthropometric and blood pressure measurements and a fasting blood sample for biochemical indices, including tHcy. SETTING: Eighty randomly selected postcode sectors from mainland Britain during 1995-1996. SUBJECTS: Of 2060 people interviewed, 1527 were visited by the nurse, 1276 gave a blood sample and 972 had tHcy measured. About 80% were in their own homes and the remainder were in nursing homes or similar institutions. RESULTS: Significant cross-sectional relationships, both univariate and multivariate were found between tHcy and index concentrations of folate and vitamin B12 (P < 0.0001), and between tHcy and plasma creatinine, urea, calcium, zinc, alpha 1-antichymotrypsin, lutein and cysteine (P = 0.013 to < 0.0001). Dietary nutrient analyses showed an association with folate intake. tHcy was also correlated with age and with domicile (free-living or institution), with history of vascular disease and with use of four classes of drugs, two of which are prescribed for vascular diseases. There was a north-south gradient in tHcy (P = 0.005), and also in food choices, blood micronutrient indices and vascular disease prevalence. CONCLUSIONS: The concentrations of tHcy found in this study provide a reference range for people aged 65 y and over, in mainland Britain. tHcy is a valuable functional index of micronutrient status and intakes for British people aged 65 y and over, which can assist the development of health-promotion strategies.

To investigate the sensitivity of guinea pig tissues to ascorbic acid depletion, as distinct from inanition, young male guinea pigs were maintained with either ascorbic acid restriction or total diet restriction for 8 weeks. One group (A) received no ascorbic acid for 3 weeks, then 0·5 mg/d for 5 weeks; one group (B) was weight-matched by restricted food intake to the first group; a third (marginally deficient) group (C) received 1 mg ascorbic acid/d throughout; a fourth was weight-matched to this group (D); and a fifth group received the control dietad lib.(E). Both of the groups with restricted ascorbic acid intakes (A and C) developed very low tissue ascorbic acid contents, but only the first group (severely deficient group A) also exhibited a severely reduced growth rate. This group also exhibited reduced femur calcium and hydroxyproline contents and reduced skin hydroxyproline content. These changes were not seen in the corresponding weight-matched group (B). Neither plasma alkaline phosphatase (EC3.1.3.1) activity, nor a variety of indices of vitamin D status exhibited changes which could be attributed specifically to reduced ascorbic acid intake and hence to lowered tissue ascorbic acid content. It is concluded that low tissue ascorbic acid levels in guinea pigs clearly alter the connective tissue composition of growing femur and skin, but do not necessarily produce a major, specific effect on vitamin D status. Moreover, the control of inanition is crucial to permit interpretation of the changes in metabolism that are caused by ascorbic acid deficiency.

Ninety preselected children, aged between 8 and 14 years, living in two rural West African (Gambian) villages, were randomly divided into three groups, matched for age and sex. One group received a placebo (lactose) tablet, one received riboflavin (5 mg) on 5 d every week, which was sufficient to correct an endemic riboflavin deficiency, and one received a multivitamin supplement (Protovit; Hoffmann La Roche), on 5 d every week, together with FeSO4(200 mg) once weekly, and the supplements were given for 1 year. Neuromuscular tests, including arm tremor and manipulative skills, were performed on three occasions: once just before the introduction of the supplements; again 6 weeks after commencing the supplements; and again 1 year later. Venous blood samples were collected at the same time as the first two sets of neuromuscular tests. These samples were used for haematology and nutrient status indices: plasma ferritin, ascorbic acid, cyanocobalamin and pyridoxal phosphate, and erythrocyte tests for folate status, for riboflavin status (erythrocyte glutathionc reductase activation coefficient) and thiamine status (erythrocyte transketolase activation coefficient). The riboflavin in both supplements achieved a clear-cut response in biochemical status, which was dose-dependent. The pyridoxine, ascorbic acid and Fe components of the multivitamin also affected the associated biochemical indices. Although overall the arm tremor and related neuromuscular function tests did not respond significantly to the supplements, significant improvement was seen in the boys for the arm-tremor test in both the supplemented groups.