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First promulgated in 1959, the 3Rs of Replacement, Reduction and Refinement have evolved as fundamental principles underlying the use of animals and alternatives in science throughout the modern world. This review describes a contemporary approach to delivering the 3Rs through acknowledging the contribution of new technologies and emphasising that applying the 3Rs can be beneficial to good science as well as to animal welfare. This science-led approach moves the concept of the 3Rs out of an ethical silo where they were often considered by scientists to be an inconvenient obligation. On the contrary, relevant examples demonstrate the opportunity to practise better science using 3Rs technologies which deliver faster, more reproducible and more cost-effective results. Indeed, methods harnessing Replacement approaches may permit discoveries which are simply not feasible using animals and frequently are more flexible and agile since compliance with regulatory oversight requirements is simplified. Although the necessity for rigorous oversight is well recognised, it is important that the associated bureaucracy is not allowed to become prohibitive, causing scientists to avoid pursuing justifiable and important research involving animals. Public support for research is conditional – animals should not suffer unnecessarily and sufficient potential benefit should accrue from the research. However, society also actively seeks pioneering medical and scientific advances which can only be achieved through research. Therefore, a balance must be struck between safeguarding animal welfare whilst enabling high-quality science. It is this balance which promotes and sustains public confidence that animal based research is acceptable and being appropriately managed.

National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015. We mapped the most widely used list of causes amenable to personal health care developed by Nolte and McKee to 32 GBD causes. We accounted for variations in cause of death certification and misclassifications through the extensive data standardisation processes and redistribution algorithms developed for GBD. To isolate the effects of personal health-care access and quality, we risk-standardised cause-specific mortality rates for each geography-year by removing the joint effects of local environmental and behavioural risks, and adding back the global levels of risk exposure as estimated for GBD 2015. We employed principal component analysis to create a single, interpretable summary measure–the Healthcare Quality and Access (HAQ) Index–on a scale of 0 to 100. The HAQ Index showed strong convergence validity as compared with other health-system indicators, including health expenditure per capita (r=0·88), an index of 11 universal health coverage interventions (r=0·83), and human resources for health per 1000 (r=0·77). We used free disposal hull analysis with bootstrapping to produce a frontier based on the relationship between the HAQ Index and the Socio-demographic Index (SDI), a measure of overall development consisting of income per capita, average years of education, and total fertility rates. This frontier allowed us to better quantify the maximum levels of personal health-care access and quality achieved across the development spectrum, and pinpoint geographies where gaps between observed and potential levels have narrowed or widened over time. Between 1990 and 2015, nearly all countries and territories saw their HAQ Index values improve; nonetheless, the difference between the highest and lowest observed HAQ Index was larger in 2015 than in 1990, ranging from 28·6 to 94·6. Of 195 geographies, 167 had statistically significant increases in HAQ Index levels since 1990, with South Korea, Turkey, Peru, China, and the Maldives recording among the largest gains by 2015. Performance on the HAQ Index and individual causes showed distinct patterns by region and level of development, yet substantial heterogeneities emerged for several causes, including cancers in highest-SDI countries; chronic kidney disease, diabetes, diarrhoeal diseases, and lower respiratory infections among middle-SDI countries; and measles and tetanus among lowest-SDI countries. While the global HAQ Index average rose from 40·7 (95% uncertainty interval, 39·0–42·8) in 1990 to 53·7 (52·2–55·4) in 2015, far less progress occurred in narrowing the gap between observed HAQ Index values and maximum levels achieved; at the global level, the difference between the observed and frontier HAQ Index only decreased from 21·2 in 1990 to 20·1 in 2015. If every country and territory had achieved the highest observed HAQ Index by their corresponding level of SDI, the global average would have been 73·8 in 2015. Several countries, particularly in eastern and western sub-Saharan Africa, reached HAQ Index values similar to or beyond their development levels, whereas others, namely in southern sub-Saharan Africa, the Middle East, and south Asia, lagged behind what geographies of similar development attained between 1990 and 2015. This novel extension of the GBD Study shows the untapped potential for personal health-care access and quality improvement across the development spectrum. Amid substantive advances in personal health care at the national level, heterogeneous patterns for individual causes in given countries or territories suggest that few places have consistently achieved optimal health-care access and quality across health-system functions and therapeutic areas. This is especially evident in middle-SDI countries, many of which have recently undergone or are currently experiencing epidemiological transitions. The HAQ Index, if paired with other measures of health-system characteristics such as intervention coverage, could provide a robust avenue for tracking progress on universal health coverage and identifying local priorities for strengthening personal health-care quality and access throughout the world. Bill & Melinda Gates Foundation.

Obesity rates are increasing worldwide. Potential reasons include excessive consumption of sugary beverages and energy-dense foods instead of more nutrient-rich options. On a per kJ basis, energy-dense grains, added sugars and fats cost less, whereas lean meats, seafood, leafy greens and whole fruit generally cost more. Given that consumer food choices are often driven by price, the observed social inequities in diet quality and health can be explained, in part, by nutrition economics. Achieving a nutrient-rich diet at an affordable cost has become progressively more difficult within the constraints of global food supply. However, given the necessary metrics and educational tools, it may be possible to eat better for less. New metrics of nutrient density help consumers identify foods, processed and unprocessed, that are nutrient-rich, affordable and appealing. Affordability metrics, created by adding food prices to food composition data, permit calculations of both kJ and nutrients per penny, allowing for new studies on the economic drivers of food choice. Merging dietary intake data with local or national food prices permits the estimation of individual-level diet costs. New metrics of nutrient balance can help identify those food patterns that provide optimal nutritional value. Behavioural factors, including cooking at home, have been associated with nutrition resilience, defined as healthier diets at lower cost. Studies of the energy and nutrient costs of the global food supply and diverse food patterns will permit a better understanding of the socioeconomic determinants of health. Dietary advice ought to be accompanied by economic feasibility studies.

Background Recurrent diarrhea is common health and welfare problem in captive rhesus macaques ( Macaca mulatta ). Aside from infectious causes, dietary factors have been implicated in diarrhea. Therefore, the main objective of this study was to evaluate commercially available pelleted diets in rhesus macaques with chronic intermittent idiopathic diarrhea. The main differences between these diets were lactose and fiber content. A randomized cross-over diet study was conducted to investigate the influence of each diet on fecal consistency and defecation frequency as indicators of diarrhea. Nine animals with chronic intermittent diarrhea and four controls were included. Each diet was fed for approximately three months, with a similar wash-out period after each diet cycle. The fecal consistency was graded using the Waltham Faeces Scoring system, with a cutoff score of > 3.5 indicating diarrhea. Both groups and diets were compared by both mixed and fixed effect models. Results Descriptive data showed that the mean fecal consistency score was highest in the diarrhea group in the standard diet at 3.71 ± 0.456 whereas the lowest mean fecal consistency scores were observed for lactose-free and high fiber diet in both diarrhea (3.25 ± 0.423) and control group (3.04 ± 0.346). A significant improvement of the fecal consistency score was detected in the diarrhea group when fed lactose-free diets (-0.41(-0.65 – -0.16, P  < 0.01) and -0.47(-0.68 –—0.25, P  < 0.0002), respectively). Lactose-free and high fiber content showed the best outcome regarding improvement of the fecal consistency score -0.47(CL -0.68—- 0.25, P  < 0.0002). Defecation frequency increased in both groups with 1.21(CL 0.65 – 1.78, P  < 0.00001) per observation day when fed a lactose-free, high-fiber diet. Conclusions Lactose-free and high-fiber showed overall the best improvement of the fecal consistency in animals with diarrhea. Switching to commercially available lactose-free diets may decrease diarrhea incidence in rhesus macaques suffering from chronic intermittent idiopathic diarrhea. Nevertheless, additional nutritional research is warranted and establishing optimal nutritional requirements for captive macaques will add to our ability to understand and improve dietary interventions.

Few data on apparent pre-caecal digestibility (APCD) of crude protein (CP) and particularly amino acids (AA) are available from studies with horses. Protein bound in cell walls (i.e. neutral detergent insoluble CP (NDICP)) is unlikely to be decomposed by digestive enzymes in the small intestine. In contrast the corresponding analytical fraction of neutral detergent soluble CP (NDSCP) (NDSCP = CP−NDICP) is likely to be available for auto-enzymatic digestion. A literature analysis on the relationship between NDICP/NDSCP and pre-caecal indigestible/digestible CP was carried out. There was a strong positive relationship between NDICP and pre-caecal indigestible CP, which suggests that NDICP can be used to estimate the part of protein that is not available for digestion in the small intestine. There was also a correlation between NDSCP and pre-caecal digestible protein. The slope of the linear regression line between NDICP and pre-caecal digestible CP was 0·9, suggesting an APCD of NDSCP of 90 %. Thus pre-caecal digestible CP may be predicted by multiplying NDSCP by 0·9. Because the literature identifies a similar AA profile in NDICP and NDSCP within a given feed the presented concept may preliminarily be transferred to AA. The proposed system can at any time be adapted to the scientific progress without altering its structure. Such adaptations would be necessary particularly when new knowledge exist on the distribution of AA onto NDICP/NDSCP, the APCD of individual AA from NDSCP, and the impact of feed processing and chewing on particle sizes and protein digestibility.

The reason for the rarity of medieval maps is that few were drawn; the common practice was to give in words the spatial information that maps provide. It is estimated that we have about 200 English maps from the first half of the 16th century and perhaps 800 from the second half. Maps, and their value in setting out spatial relationships, had by then been general accepted. The pattern is similar in other parts of Europe where medieval local maps have been systematically studied. The pattern is consistent: few local maps were drawn before the end of the 15th century, after which their numbers rapidly increased in the 16th.

We investigated the effect of feeding a skin barrier function-augmenting diet early in dogs' lives on the appearance of clinical signs associated with canine atopic dermatitis. Pregnant bitches (starting 5 weeks after mating) and their subsequent litters (up to 1 year of age) were fed either supplemented or unsupplemented diets. Nutrients supplemented were nicotinamide, pantothenate, histidine, inositol and choline. Circulating IgE levels to dust mute allergens Der f and Der p were measured when the puppies were 6 and 12 months old. Two owner questionnaires were used to assess the occurrence of typical signs associated with atopic dermatitis when dogs were between the ages of 22 and 36, and 34 and 48 months. Using linear mixed models we observed higher levels of circulating anti-Der f (P = 0·021) and -Der p IgE (P = 0·01) during the first year in the dogs fed the unsupplemented than in those fed the supplemented diet. The owner-assessed incidence of atopic dermatitis signs amongst the dogs was significantly greater in the unsupplemented group at the time of the second follow-up questionnaire (10/33 dogs v. 2/24 dogs). These outcomes suggest that a nutritionally derived improvement to barrier function early in life may reduce the frequency of signs associated with atopic dermatitis. The effect is possibly the result of making the epidermis, now thought to be a major route of environmental allergen exposure, more resistant to penetration.

The effects of dietary carbohydrate and fat on feline health are not well understood. The effects of feeding diets moderately high in fat (HF; n 10; 30 % fat, 26 % carbohydrate as fed) or carbohydrate (HC; n 10; 11 % fat, 47 % carbohydrate), for 84 d, were investigated in healthy, adult cats (3·5 (sd 0·5) years). Data on indirect calorimetry, blood biomarkers, activity, play and cognition were collected at baseline, and at intervals throughout the study. Body composition was measured by dual-energy X-ray absorptiometry at baseline and on day 85. There were no significant main effects of diet on body weight and composition. When data were analysed over study day within diet, cats fed HF diets experienced a significant increase in body fat (P = 0·001) and body weight (P = 0·043) in contrast to cats consuming the HC diet that experienced no change in body fat or body weight (P = 0·762) throughout the study. Overall, energy expenditure was similar between diets (P = 0·356 (fasted), P = 0·086 (postprandial)) and respiratory quotient declined with exposure to the HF diet and increased with exposure to the HC diet (P < 0·001; fasted and postprandial). There was no difference in insulin sensitivity as an overall effect of diet (P = 0·266). Activity declined from baseline with exposure to both diets (HC: P = 0·002; HF: P = 0·01) but was not different between diets (P = 0·247). There was no effect of diet on play (P = 0·387) and cats consuming either the HF or HC diet did not successfully learn the cognitive test. Overall, cats adapt to dietary macronutrient content, and the implications of feeding HC and HF diets on risk for adiposity as driven by metabolic and behavioural mechanisms are discussed.

This paper is about re-using archived oral histories from two contrasting community oral history groups, Ambleside Oral History Group in the Lake District and Waltham Forest Oral History Workshop in London, to study family food practices during the First World War. Analysis of thirty-eight transcripts from the archives reveal themes relating to farming and food growing, hardship, food shortages, meals and self-sufficiency. We discuss some of the methodological opportunities, challenges and limitations of re-using oral histories in a social scientific study focusing on food and family life in hard times, such as the type, quality and accessibility of the interview data; co-construction; the interviewer's use of local knowledge and stories from previous interviews to steer interviews; and questions of temporality and context. We conclude that, despite the challenges and limitations of re-using oral histories, there is a wealth of sources in community oral history archives available for both social scientists and historians.