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A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a reference nutrient intake (10 µg/d; 400 IU/d) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. Latest data indicate that UK population vitamin D intakes and status reamain relatively unchanged since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose–response and dietary modelling studies indicate dairy products, bread, hens’ eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: (i) need for ‘real-world’ cost information for use in modelling work; (ii) supportive food legislation; (iii) improved consumer and health professional understanding of vitamin D’s importance; (iv) clinical consequences of inadequate vitamin D status and (v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.

A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a reference nutrient intake (10 µg/d; 400 IU/d) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. Latest data indicate that UK population vitamin D intakes and status reamain relatively unchanged since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose–response and dietary modelling studies indicate dairy products, bread, hens’ eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: (i) need for ‘real-world’ cost information for use in modelling work; (ii) supportive food legislation; (iii) improved consumer and health professional understanding of vitamin D’s importance; (iv) clinical consequences of inadequate vitamin D status and (v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.

Sugar-sweetened beverage (SSB) consumption is independently associated with several non-communicable diseases, so policymakers are increasingly implementing measures, such as marketing regulation, to reduce intake. To help understand how such measures work, this study examined the association between SSB consumption and self-reported exposure to SSB promotions, both overall and by type of promotion, and whether these relationships vary between the UK, USA, Canada, Mexico, and Australia. Cross-sectional analysis of the online 2017 International Food Policy Study was performed (n = 15,515). Participants were grouped into 5265 (34%) non-, 5117 (33%) low-, and 5133 (33%) high-SSB consumers. Multinomial logistic regression models examined whether SSB consumption varied by exposure to total SSB promotion and by type: traditional, digital, recreational environment, and functional environment. Multiplicative interactions were included to investigate international variations. An additional unit of total self-reported SSB promotion exposure increased the likelihood of participants being low SSB consumers (relative risk ratio (RRR) = 1.08, 95% confidence interval (CI) = 1.06&ndash, 1.10) and high SSB consumers (RRR = 1.13, 95% CI = 1.11&ndash, 1.16). Only exposure to traditional and digital promotion increased the likelihood of participants being SSB consumers, though this may be explained by degree of exposure, which was not measured in this study. Some evidence illustrated international variation in these relationships.

Public Health England has set a definition for free sugars in the UK in order to estimate intakes of free sugars in the National Diet and Nutrition Survey. This follows the recommendation from the Scientific Advisory Committee on Nutrition in its 2015 report on Carbohydrates and Health that a definition of free sugars should be adopted. The definition of free sugars includes: all added sugars in any form; all sugars naturally present in fruit and vegetable juices, purées and pastes and similar products in which the structure has been broken down; all sugars in drinks (except for dairy-based drinks); and lactose and galactose added as ingredients. The sugars naturally present in milk and dairy products, fresh and most types of processed fruit and vegetables and in cereal grains, nuts and seeds are excluded from the definition.

This review aims to explore trends of early consumption of sugar-sweetened beverages (SSB) in sub-Saharan Africa (SSA), within the context of growing child and adolescent obesity and escalating type-2 diabetes prevalence. We explore efforts to mitigate these, drawing on examples from Africa and elsewhere. SSB, including carbonated drinks and fruit juices, play a contributory role in the development of obesity and associated non-communicable diseases (NCD). SSA is an attractive market for beverage companies owing to its rapid economic growth, growing middle class and youthful populations. SSB already contribute significantly to total sugar and energy consumption in SSA where a plethora of marketing techniques targeted at younger people are utilised to ensure brand recognition and influence purchasing and brand loyalty. Coupled with a general lack of nutrition knowledge or engagement with preventative health, this can lead to frequent consumption of sugary drinks at a young age. Public health efforts in many high income and some middle-income countries address increasing prevalence of obesity and type-2 diabetes by focusing on strategies to encourage reduction in sugar consumption via health policy and public education campaigns. However, similar efforts are not as developed or forthcoming in low-income countries. Health care systems across SSA are ill-prepared to cope with epidemic proportions of NCD, particularly when contextualised with the ongoing battle with infectious diseases. We conclude that greater efforts by governments and the nutrition community to educate the public on the health effects of increased and excessive consumption of SSB are necessary to help address this issue.

Background High sugar consumption contributes to the global obesity epidemic. Sugar-sweetened beverages (SSBs) constitute a significant proportion of sugar consumption and are independently associated with non-communicable diseases. Some equivocal evidence indicates the influence of marketing on sugary food and drink sales and consumption. However, little research has explored this relationship for SSBs, among adult samples, or using diverse marketing exposures. There are no cross-country comparisons of this relationship. Aim We aim to answer: Does SSB consumption vary according to self–reported exposure to sugary drink marketing? Does the relationship between SSB consumption and self–reported exposure to sugary drink marketing vary by country? Methods We analysed data from the 2017 International Food Policy Study (IFPS), a cross-sectional, online survey that sampled adults aged 18 to 64 years in Australia (n=3,767), UK (n=4,047), Mexico (n=4,057), USA (n=4,868), and Canada (n=2,139; aged 31 to 64 years). Surveys covered eating patterns, food environments, purchasing, knowledge of and attitudes to a range of policy measures. This included a seven-day Beverage Frequency Questionnaire. Dependent (SSB consumption) and independent variables (amount of self-reported sugary drinks marketing exposure) were computed, and potential confounders identified. A multinomial logistic regression model examined relative odds of non-, low- or high- weekly SSB consumption by marketing exposure, country, sex, age, and work status. The same model was reconstructed with interaction between marketing exposure and country, and a log likelihood test was used to compare the models. Results SSB consumption varied according to self-reported exposure to sugary drinks marketing. 57% of respondents consumed SSBs, and 72% self-reported exposure to sugary drinks marketing. Compared to those reporting no sugary drinks marketing exposure, those reporting greater exposure were more likely to have low- than no-SSB consumption and more likely to have high- than no-SSB consumption (ps Discussion SSB consumption was positively associated self-reported exposure to sugary drinks marketing in all countries, but this relationship varied by country. These analyses are cross-sectional, but the IFPS panel will be re-contacted annually enabling future longitudinal analyses. Improving understanding of the influence of marketing on SSB consumption could help policymakers to augment current strategies to reduce SSB consumption.

ObjectiveTo evaluate the impact on food purchasing behaviour of the ‘Change4Life Smart Swaps’ campaign to encourage families to make small changes to lower-fat or lower-sugar versions of commonly eaten foods and drinks.DesignQuasi-experimental study comparing the proportion of swaps made by an intervention group (267 families who had signed up to the ‘Smart Swaps’ campaign promoted through various media, including television and radio advertising in early 2014) and a comparison group (135 families resident in Wales, signed up for ‘Change4Life’ materials, but not directly exposed to the ‘Smart Swaps’ campaign). During weeks 1, 2 and 3 of the campaign participants were asked to record their purchases of dairy products, carbonated drinks and breakfast cereals, using a mobile phone app questionnaire, when making a purchase within the category.SettingEngland and Wales.SubjectsFamilies registered with ‘Change4Life’.ResultsIn weeks 2 and 3 a significantly higher percentage of the intervention group had made ‘smart swaps’ than the comparison group. After week 3, 58 % of participants had swapped to a lower-fat dairy product compared with 26 % of the comparison group (PP=0·01), and 24 % had made a change to a lower-sugar cereal compared with 12 % of the comparison group (P=0·009).ConclusionsIn the short term a national campaign to change purchase habits towards healthier products may have some merit but the sustainability of change requires further investigation.

Background In 2018, the UK government introduced a Soft Drinks Industry Levy (SDIL) to reduce the consumption of sugary drinks and their health consequences. Taxes on sugary drinks might prompt changes in associated marketing, but whether and how this happens, and the implications for health, are unclear. To inform exploration of changes in sugary drinks marketing that might result from the SDIL, we developed a theory of change by use of concept mapping and stakeholder interviews. Methods We used concept mapping, an inductive technique, to develop an initial theory. We then elaborated this theory on the basis of one-to-one telephone interviews with six representatives of each of industry, academia, and civil society (total n=18), who had experience of strategic decision-making or marketing by sugary drinks firms. Interviewees were recruited using seed and snowballing sampling. Interviews explored motivations for and manifestations of changes in soft drink marketing. Interviews were transcribed verbatim and thematically analysed. To maximise trustworthiness, four transcripts were double-coded, the revised theory was informally peer reviewed, three transcripts were excluded from initial coding to allow comparison with the revised theory, and the resultant theory was validated by interviewees. Findings The initial theory described strategic planning and decision-making followed by the analysis and selection of specific marketing responses. After analysis of interviews we developed this concept into an iterative and circular theory of marketing change. Briefly, firms change marketing by reviewing their internal and external context, identifying a catalyst, deciding their brand positioning, and then selecting a combination of strategies to enact this positioning. Resultant changes in purchasing feed back into factors internal and external to the firm. Ethics approval was granted by the University of Cambridge Humanities and Social Sciences Research Ethics Committee. Interpretation These findings extend understanding of industry responses to sugary drinks taxes and might be relevant for understanding of industry responses to fiscal interventions more generally. Our theory highlights that soft drinks firms are continually evolving, consider many external factors in addition to the SDIL, and think about marketing more broadly than just advertising. Our research was based on one case study of the SDIL; interviews were done 1 year after implementation of the levy. Future work should prospectively test our theory in alternative contexts. Funding JA and MW are funded by the Centre for Diet and Activity Research, a UK Clinical Research Collaboration Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. TP, JA and MW are funded by a grant from NIHR (16/130/01) to evaluate the UK Soft Drinks Industry Levy. HF receives funding for her PhD studentship from Public Health England and the Economic and Social Research Council. LL and FG are employed by Public Health England. MW holds an honorary consultant in public health contract with PHE. These funding sources had no direct role in the writing of the manuscript or decision to submit for publication.

International audience; We study mutual-aid games in which individuals choose to contribute to an informal mutual insurance pool. Individual coverage is determined by the aggregate level of contributions and a sharing rule. We analyze theoretically and experimentally the (ex ante) efficiency of equal and contribution-based coverage. The equal coverage mechanism leads to a unique no-insurance equilibrium while contribution-based coverage develops multiple equilibria and improves efficiency. Experimentally, the latter treatment reduces the amount of transfers from high contributors to low contributors and generates a \dual interior equilibrium". That dual equilibrium is consistent with the co-existence of different prior norms which correspond to notable equilibria derived in the theory. This results in asymmetric outcomes with a majority of high contributors less than fully reimbursing the global losses and a significant minority of low contributors less than fully defecting. Such behavioral heterogeneity may be attributed to risk attitudes (risk tolerance vs risk aversion) which is natural in a risky context.

International audience; We demonstrate evidences of electronic transport via topological Dirac surface states in a thin film of strained HgTe. At high perpendicular magnetic fields, we show that the electron transport reaches the quantum Hall regime with vanishing resistance. Furthermore, quantum Hall transport spectroscopy reveals energy splittings of relativistic Landau levels specific to coupled Dirac surface states. This study provides new insights in the quantum Hall effect of topological insulator (TI) slabs, in the cross-over regime between two- and three-dimensional TIs, and in the relevance of thin TI films to explore novel circuit functionalities in spintronics and quantum nanoelectronics.

Getting enough vitamin D to protect musculoskeletal health requires eating the right types of food and getting short bursts of daily sunshine in summer months. However, for many people this can be harder to achieve than it sounds, and some people will need to take supplements in autumn and winter. The Scientific Advisory Committee on Nutrition (SACN) reviewed previous recommendations1 in the light of public health advice to stay out of the sun and wear sunscreen and accumulation of new evidence on vitamin D. It has recommended a reference nutrient intake—the amount that is sufficient to meet the needs of 97.5% of the population—for vitamin D of 10 μg a day to protect musculoskeletal health in people aged 4 years or older.2 ### Population protection SACN based its recommendation on a review of the evidence on musculoskeletal health outcomes, concluding that there was insufficient evidence to make dietary recommendations on non-musculoskeletal outcomes and the risk of poor musculoskeletal health is increased at serum 25-hydroxyvitamin D concentrations below 25 nmol/L.2 This concentration is not diagnostic of disease but indicates the level below which risk of poor musculoskeletal health is increased; it represents a population protective level. On the basis of modelling work, SACN estimated that 10 μg/day is the amount of vitamin D needed for 97.5% of the population to maintain blood concentrations at or above 25 nmol/L when exposure to sunshine is minimal.2 SACN’s evaluation adhered to its framework for the evaluation of evidence,3 which is based on an evidence hierarchy used to judge the strength of each study according to design. Most weight is generally placed on randomised controlled trials since only this study type can demonstrate a causal relation between an intervention and …

Nutrition advice is devolved within each of the four UK countries, but share a common evidence base provided through the Scientific Advisory Committee on Nutrition (SACN). Current UK dietary recommendations to prevent cardiovascular disease (CVD) is based upon recommendations from SACN and its predecessor committee. Dietary advice in the UK has recently been revised in relation to intakes of free sugar and fibre. This paper highlights current UK recommendations for the prevention of CVD, in particular related to energy intake, saturated fat, free sugars, salt, fruit, vegetables, oily fish and fibre. It describes how this advice is promulgated including the refresh of the Eatwell Guide and wider action that will impact on CVD.

Summary There has been relatively little research on public health nutrition interventions for families and children, compared with, for example, work in schools. In Spring 2007, the UK Food Standards Agency held a multidisciplinary workshop on food choice in families and children, bringing together researchers from psychology, social sciences, public health and nutrition. The objectives of the workshop were to form an up-to-date view of the influences on children's and young people's food choice within the family, and identify future research needs. The participants identified six key areas for future research: multidisciplinary collaboration; using mixed research methods; developing new research methods; identifying family-related diversity and tailoring interventions towards this; understanding the effects of different parenting styles and the relevance of these to implementing interventions; and developing a more sophisticated understanding of barriers and motivators to food-related change in families.

Age-related skeletal muscle loss, sarcopenia, cachexia and wider malnutrition (under nutrition) are complex in aetiology with interaction of clinical, social and economic factors. Weight loss and loss of skeletal muscle mass in older people are associated with increased morbidity and mortality with implications for increasing health and social care costs. There is insufficient evidence to identify the ideal treatment options. However, preventing weight loss and loss of skeletal muscle in older age will be keys to reducing morbidity and mortality. This will require all those coming into contact with older people to identify and address weight loss early, including through diet, improving physical activity and increasing social interaction. Public health messages on diet should, in the main, continue to focus on older people achieving current UK dietary recommendations for their age as visually depicted in the eatwell plate together with associated messages regarding dietary supplements where appropriate.

The Nutrition Division of the Food Standards Agency (FSA) held a seminar in November 2001 to discuss results from research projects related to encouraging good diets and identifying needs to ensure an integrated approach within schools. The principle aim of the seminar was to discuss the results from school-based interventions designed to increase fruit and vegetable consumption by young people and, in particular, to disseminate results from four FSA-commissioned interventions to interested parties. Six presentations on a range of school-based interventions were given in the morning; four discussion workshops, arranged such that participants provided a mixture of perspectives in each group, were held in the afternoon. Participants identified common issues of interest and concern as a result of discussing topics related to school-based nutrition, namely: What works to encourage fruit and vegetable consumption? What doesn't work? What impedes progress? and Where do we go from here? A general feeling was tha...

International audience; Topological insulator materials like HgTe exhibit unique electronic properties at their interfaces and so peculiar attention has to be paid concerning the growth optimization. Molecular beam epitaxy of tensile strained HgTe/CdTe is investigated as a function of the growth temperature. Crystal quality is checked by using high resolution X-rays diffraction. By combining several material characterization techniques such as scanning transmission electronic microscopy, time-of-flight secondary ion mass spectroscopy and X-rays reflectivity, we report sharp interface morphology with nanometer-scale Hg/Cd diffusion lengths. (C) 2015 Elsevier B.V. All rights reserved.

Current concepts of the inflammatory process include the formation of oxidation products which have the ability to damage tissue. In a few selected inflammation models which included irritant and immunologic stimulus, some representative compounds with antioxidant activity were studied. A diverse set of responses were obtained, but consistently DPPD and ethoxyquin exhibited antiinflammatory activity. Although it cannot be categorically stated that antioxidant capability leads to antiinflammatory activity, it appears that these data provide a theoretical basis for modulating the inflammatory process.

Only native products of Mycobacterium leprae , whether cell wall, cytosol, or membrane derived, can confer protective immunity against challenge in the mouse footpad. Previously, recombinant proteins were shown to be ineffective. The cell wall skeleton—the mycolyl-arabinogalactan-peptidoglycan complex—devoid of proteins is not protective.

Drug are generally screened for activity against Mycobacterium leprae by administration to M. leprae -infected mice, and the efficacy of a chemotherapeutic regimen is assessed by inoculating mice with M. leprae recovered from the skin-biopsy specimens obtained at intervals during treatment. Both methods are expensive and time consuming. Although a number of methods has been proposed for the rapid distinction between viable and non viable M. leprae , none has found wide acceptance. Earlier work had shown that the ratios of the intrabacterial concentrations of Na + and K + (Na + ,K + -ratio) of individual bacterial cells, measured by means of laser microprobe mass analysis, are a sensitive indicator of the viability of cultivable organisms. Assuming that the maximal value (the “limiting value”) of the Na + ,K + -ratio of viable cultivable organisms is valid for non-cultivable species, the degree of correspondence between intrabacterial Na + ,K + -ratios of M. lepraemurium after treatment in vivo with isoniazid, streptomycin and clofazimine, and the ability of these organisms to multiply in mice were examined. A linear relationship between the proportion of viable organisms, calculated from the limiting value of the Na + ,K + -ratio, and that calculated from ID 50 was found, suggesting that, at least for M. lepraemurium , the intrabacterial Na + ,K + -ratio predicts the effect of drugs measured by the much more demanding technique of mouse inoculation.

Excerpt CASE REPORT J. G., white male, aged 12 years, was admitted on December 10, 1944 with a chief complaint of generalized swelling. Nine days previously the patient had developed a "cold" which...

Excerpt In 1926 von Willebrand1described a familial bleeding tendency affecting both sexes and characterized by a prolonged bleeding time, accompanied by a normal coagulation time and platelet coun...

The Tennessee Self Concept Scale was adminsitered to 243 insitutionalized delinquent males and females to determine (1) if there were significant differences between the self concepts of non-delinquents and confined delinquents and (2) if there are significant differences in the self concepts of the subjects according to months of institutional confinement, age, and sex. Analyses indicated that the subjects have abnormally lower self concepts than non-delinquents and that females and the youngest subjects have significantly lower self concepts than their male and older counter-parts. Subjects confined from 13 through 24 months are significantly more critical of themselves indicating a willingness to recognize what they perceive as negative attributes. Age and sex were the only significant predictors of Total Self Concept, and age was also a significant predictor of perceived Behavior. Sex was a significant predictor of Personal and Family Self scores. Scores indicated that most of the subjects held themse...

Fear, denial, and the avoidance of death and dying appear to be products of life in modern society. While society insulates most people from contact with the death and dying of others, there are professions that come into repeated contact with dying individuals. The present study uses the Collett‐Lester Fear of Death Scale to analyze the Fear of Death and Dying for Self and Others (four subscales) among a sample of registered nurses (BA level). Over a 10‐year period, nurses’ fears concerning death and dying were measured at three points—before a course on death and dying (Pretest), after the course (Posttest), and at a point in their professional nursing practice (Retest). The results suggest that these nurses’ fears of death for self and others change at a statistically significant level over the Pretest and Posttest observations; however, the changes are temporary. The Fear of Dying for Self and Others tends to decline significantly over the Pretest and Retest observations. Age, religion, religiosity, a...

Fluorine-19 nuclear magnetic resonance (NMR) studies of cells and perfused organs loaded with fluorinated ion chelators represent a new approach to determining cytosolic free calcium levels in situ. The molecular basis for this approach and the relative advantages and disadvantages of the NMR technique are discussed in this paper. Results obtained on perfused normoxic and ischemic rat hearts are presented, indicating that ischemia is associated with an elevation in the level of cytosolic free calcium before the onset of irreversible cell injury. The results are therefore consistent with this elevation playing a causative role in the mediation of myocardial cell injury resulting from ischemia.

ObjectiveTo describe the Food Standards Agency's (FSA) Food Acceptability & Choice and Food Choice Inequalities research programmes and the context for the FSA seminar on peer-led approaches to dietary change held in July 2006.ResultsThe aims of the FSA's food choice research programmes are to identify the social, psychological and physical barriers to achieving a healthier diet and how they might be addressed. Results of the research provide the scientific basis for some FSA advice on healthy eating. An important element of both programmes is the output of practical tools and resources that can be used by health professionals, nutritionists, teachers and others to encourage people to eat a healthy diet. The FSA held a seminar in July 2006 in order to identify the specific and general learning points from three peer-led intervention studies and to discuss how these could best be communicated to various audiences, including practitioners, researchers and policy-makers.ConclusionsThe seminar provided a useful forum for discussion. The FSA will ensure that lessons learned from these peer-led intervention studies are taken account of in the planning, appraisal and management of future research projects, in the communication of project results and in the dissemination of resources.

Although multiplication of Mycobacterium leprae in the foot pads of immune-competent mice is limited, and no leprosy-like lesions are produced in these animals, the mouse foot-pad system represents the first truly useful and reproducible animal model of M. leprae infection. Its employment has enabled research into basic questions with respect to the microbiology of M. leprae, and the epidemiology, treatment and control of leprosy. The mouse foot-pad technique is labour-intensive and time-consuming, and is expensive in terms of the costs of animal purchase and maintenance. In addition, the technique appears to be rather imprecise and insensitive, compared with the techniques employed in working with cultivable micro-organisms. For these reasons, and also as a by-product of the success of multi-drug therapy, the technique has been abandoned in many research centres. Nevertheless, until a more simple and sensitive technique for demonstrating the viability of M. leprae is developed, the mouse foot-pad system remains an essential tool for leprosy research. In this review, we discuss the mouse foot-pad technique in detail, analyse its precision, point out its shortcomings, describe its most important applications, and prescribe a method by which to assess the ability of an alternative technique to serve in place of this established technique.

By reporting his satisfaction with his job or any other experience, an individual does not communicate the number of utils that he feels. Instead, he expresses his posterior preference over available alternatives conditional on acquired knowledge of the past. This new interpretation of reported job satisfaction restores the power of microeconomic theory without denying the essential role of discrepancies between one’s situation and available opportunities. Posterior human wealth discrepancies are found to be the best predictor of reported job satisfaction. Static models of relative utility and other subjective well-being assumptions are all unambiguously rejected by the data, as well as an \"economic\" model in which job satisfaction is a measure of posterior human wealth. The \"posterior choice\" model readily explains why so many people usually report themselves as happy or satisfied, why both younger and older age groups are insensitive to current earning discrepancies, and why the past weighs more heavily than the present and the future., En rapportant sa satisfaction vis-à-vis son travail ou toute autre expérience, un individu ne communique pas le nombre d’unités d’utilité qu’il ressent. Plutôt, conditionnellement à ses expériences antérieures, il exprime a posteriori sa préférence relativement à d’autres emplois ou situations alternatives. Cette nouvelle interprétation de la satisfaction révélée rend à la théorie microéconomique son pouvoir explicatif tout en reconnaissant le rôle essentiel joué par la différence entre la situation d’une personne et les opportunités. Les différences a posteriori dans la richesse humaine sont les meilleurs prédicteurs de la satisfaction révélée. Les modèles statiques de l’utilité relative et ceux d’utilité subjective sont tous rejetés par les données, de même que le modèle économique où la satisfaction de l’emploi est une mesure de la richesse humaine a posteriori. Le modèle de choix a posteriori explique pourquoi, dans les enquêtes, une grande majorité de personnes expriment leur bonheur ou leur satisfaction, pourquoi les jeunes et les vieux ne réagissent pas aux différentielles de revenus courants et pourquoi le passé joue davantage que la situation présente ou future.

124 Background: Despite the Institute of Medicine’s recommendation that all cancer survivors be provided with a survivorship care plan (SCP), there is limited information as to whether SCPs improve knowledge. The purpose of this study was to examine the impact of SCPs on patient knowledge regarding tumor stage, cancer treatment and potential risk of long-term side effects, surveillance recommendations, and perceived knowledge of their therapy. Methods: 75 English-speaking women over the age of 18 were enrolled in this prospective study. The participants’ treatment progress was tracked through the electronic medical record and used to create the SCP, which was given to them at the completion of treatment (defined as the time patients had completed radiation and/or chemotherapy treatments and initiated on hormonal therapy, if applicable). Knowledge of stage, treatments, potential side effects, and surveillance recommendations were assessed before receiving the SCP and again two months later. Accuracy of responses was compared using the McNemar test. Results: The median patient age was 56.8 ± 12.5 and 47.1% were stage I, 37.3% were stage II, and 15.7% were stage III. Participants were statistically more accurate in identifying their stage after receiving their SCP than at baseline (72.6% vs. 92.2%, p = 0.0016). While many patients were more accurate in the identification of the cancer treatment they received after SCP, the only significant improvement was in identifying 5-Fluorouracil as chemotherapy received (65.5% vs. 89.7%, p=0.0196). Patients were more accurate in identifying potential side effects but were only statistically more accurate at identifying leukemia as a risk factor (36.0% vs. 46.9%, p=0.0348). At baseline and follow up patients perceived that they had a high level of understanding as it related to their cancer stage (60.4%, and 66.7%), treatment (69.4%, and 71.4%), and surveillance recommendations (61.4%, and 54.6%). Conclusions: SCPs appear to improve patient knowledge in several important areas including basic and specific treatment details, surveillance recommendations, and potential side effects. Delivery of a SCPs is one strategy to improve knowledge of treatments received.

Lévy Michel Louis. Richesse et population. Une notice de René Carmille sur Alfred Sauvy(1943). In: Population, 50ᵉ année, n°4-5, 1995. pp. 1247-1249.

Tyrosinemia type I, the most severe disease of the tyrosine catabolic pathway is caused by a deficiency in fumarylacetoacetate hydrolase (FAH). A patient showing few of the symptoms associated with the disease, was found to be a compound heterozygote for a splice mutation, IVS6-1g->t, and a putative missense mutation, Q279R. Analysis of FAH expression in liver sections obtained after resection for hepatocellular carcinoma revealed a mosaic pattern of expression. No FAH was found in tumor regions while a healthy region contained enzyme-expressing nodules. Analysis of DNA from a FAH expressing region showed that the expression of the protein was due to correction of the Q279R mutation. RT-PCR was used to assess if Q279R RNA was produced in the liver cells and in fibroblasts from the patient. Normal mRNA was found in the liver region where the mutation had reverted while splicing intermediates were found in non-expressing regions suggesting that the Q279R mutation acted as a splicing mutation in vivo. Sequence of transcripts showed skipping of exon 8 alone or together with exon 9. Using minigenes in transfection assays, the Q279R mutation was shown to induce skipping of exon 9 when placed in a constitutive splicing environment. These data suggest that the putative missense mutation Q279R in the FAH gene acts as a splicing mutation in vivo. Moreover FAH expression can be partially restored in certain liver cells as a result of a reversion of the Q279R mutation and expansion of the corrected cells.

Consistent with our previously reported findings, chronic ingestion of cadmium chloride in drinking water by mice caused a decrease in the rate of circulation clearance of 51Cr-labeled sheep red blood cells (E) and IgG-coated E (E-IgG) due to a decrease in the localization of E and E-IgG in the liver. These decreases reached their nadirs after 15 weeks of cadmium ingestion and remained relatively constant for up to one year during continued ingestion of cadmium. Replacement of the drinking water containing cadmium with regular tap water resulted within 8 days in an improvement in the ability of the mice to clear E and E-IgG. Mice also had a decreased ability to develop delayed-type hypersensitivity reactions while being given cadmium; this abnormality also returned toward normal after withdrawal of cadmium. The return of these two responses toward control levels occurred while there was still a large organ burden of cadmium that was not measurably different from that at cessation of cadmium ingestion.

In the course of a clinical trial of acedapsone therapy in 17 patients with lepromatous leprosy, the rate of response to therapy was measured by inoculation of mice with Mycobacterium leprae recovered from biopsy specimens of skin lesions obtained before treatment and at intervals of 4, 12, and 24 weeks after institution of treatment. The susceptibility of each isolate of M. leprae to dapsone (4,4′-diaminodiphenylsulfone [DDS]) was measured by passaging organisms that had multiplied in mice to new groups of untreated mice and to mice treated with DDS incorporated in the mouse chow in concentrations of 10 −5 , 3 × 10 −5 , and 10 −4 g/100 ml. The rate of response to acedapsone therapy and the susceptibility of patient strains of M. leprae to DDS varied widely among patients. All isolates were inhibited from multiplication by treatment of mice with 10 −4 g of DDS per 100 ml; all but two isolates were susceptible to 3 × 10 −5 g of DDS per 100 ml; and 17 of 36 isolates, representing nine patient strains, were susceptible to 10 −5 g of DDS per 100 ml. Plasma levels of DDS measured in the mice administered these diets show that the minimal inhibitory concentration of DDS for M. leprae isolated from untreated patients is about 3 ng/ml. No relationship could be demonstrated between DDS susceptibility of pretreatment isolates of M. leprae and the rate at which patients responded to acedapsone therapy. Neither acedapsone treatment of patients nor DDS treatment of mice appeared to select genotypically more resistant M. leprae .

SummaryMethimazole, an antithyroid drug, and thiambutosine, an antimicrobial active against M. leprae in the mouse, were both found to inhibit multiplication of M. leprae in the mouse foot pad when administered in concentrations too small to inhibit thyroid function of the mice. Moreover, methimazole inhibited multiplication in vitro of a number of cultivable Mycobacteria. Although the antimicrobial and the antithyroid effects may be exerted through a common mechanism, it appears that methimazole nevertheless possesses direct antimicrobial properties.

SummaryFour female dogs receiving 1.0 mg dapsone (DDS)/kg iv exhibited logarithmic decline of plasma levels of DDS with a mean half-time of disappearance (T1/2) of 11.7 hr. No evidence of acetylation of DDS to monoacetyl DDS (MADDS) was found. An equimolar dose of MADDS was deacetylated slowly to DDS by the same dogs. The mean T1/2 of MADDS was 6.5 hr, significantly less than that of DDS. In 2-hr plasma samples after these doses of drugs, protein-binding of DDS and MADDS averaged 71 and 84%, respectively. Tests of protein-binding of the two drugs in vitro confirmed the observations in vivo.

In 22 lepromatous Filipino patients receiving their first injection of 225 mg acedapsone (DADDS), dapsone (DDS), and monoacetyl DDS (MADDS) were present in plasma in approximately equal quantities. Peak levels of parent drug, DDS, and MADDS occurred between 22 and 35 days. The half-times of disappearance (T1/2) from plasma were 43 days for DDS and MADDS and 46 days for DADDS. Acetylator phenotyping with sulfamethazine (SMZ) and DDS showed that 17 patients were rapid and 5 patients were slow acetylators. Correlations between acetylation of SMZ and DDS after DDS and of acetylation of DDS after DDS and DADDS were highly significant. However, acetylation of DDS after DADDS did not differentiate the patients into acetylator phenotypes. The T1/2 of DDS after DDS in the patients was directly related to the minimum levels of DDS at 77 days after DADDS treatment. These minimum levels were 8-fold higher than the minimum inhibitory concentration (MIC) of DDS for Mycobacterium leprae in mice and rats, but not all patients responded satisfactorily. No relationship could be demonstrated between the bacteriologic response and any of the pharmacologic parameters examined in these Filipino patients. In a companion study, minimum levels of DADDS, MADDS, and DDS were determined in 447 leprosy patients of all disease types from the Karimui District of Papua New Guinea who had been receiving 225 mg DADDS every 70 to 80 days for the past 5 years. All patients exhibited DDS levels above the MIC of DDS for M. leprae, no significant differences in plasma sulfone levels were found among disease types, no relationship between rate of healing in paucibacillary patients and sulfone levels were found, and type of response in multibacillary patients and sulfone levels were unrelated. No substantial accumulation of the sulfones in the Karimui patients receiving continuous therapy with DADDS for 5 years was indicated from a comparison with the levels in the Filipino patients following a single injection of DADDS.

A pharmacologic study of clofazimine (B663) was carried out in mice and human subjects to provide information needed for interpretation of data from studies of drug action in the two species. The quantities of B663 in mouse carcasses were measured to determine the half-time of disappearance (t ½) of the drug and the absorption of the drug after oral administration. The antimicrobial activity of orally-administered B663 was studied in mice infected with Mycobacterium leprae and correlated with the quantity of B663 in the carcass. Published studies of the effect of the drug in murine infections with M. leprae and M. tuberculosis were reinterpreted. The t ½ of B663 is about 1 week in male BALB/c mice. The antimicrobial effect of the drug appears to require a concentration in the mouse carcass smaller than 1 mg/kg for M. leprae and greater than 5 to 10 mg/kg for M. tuberculosis. The concentration of B663 was also measured in the plasma, urine and feces of volunteers and leprosy patients. The t ½ of the drug is at least 70 days in man. The disposition of the drug thus differs greatly between the two species, making difficult the transfer of information from laboratory to clinic.

Contrary to the results of an earlier study in which polyinosinic-polycytidylic acid [poly(I:C)] administered intraperitoneally to mice had no effect on multiplication of Mycobacterium leprae in the mouse footpad, the local administration of poly(I:C) every 12 h for 15 doses during logarithmic multiplication was found both to inhibit bacterial multiplication and to produce high tissue levels of interferon (IF). Local administration of poly(I) alone inhibited multiplication of M. leprae to almost as great a degree without at the same time producing a measurable IF titer in the footpad tissues. Mouse IF and “mock” IF both inhibited bacterial multiplication to the same degree, but administration of only the former resulted in a measurable IF titer. Polyadenylic-polyuridylic acid administered locally neither inhibited multiplication nor induced IF; fetal calf serum, administered in the same concentration as found in the preparations of IF and mock IF, was modestly inhibitory, without inducing IF. Thus, the local administration of poly(I:C) appears to have inhibited multiplication of M. leprae independently of IF induction.

Cyclophosphamide (CPA)-induced bladder toxicity and lethality were inhibited by N -acetylcysteine (NAC) when given systemically at a 4 : 1 ratio prior to CPA. This dose of NAC did not affect the production or the formation of free alkylating agents from CPA in vivo or in vitro . The immunosuppressive effect of CPA against T cell response systems, such as graft vs host reaction, antibody to sheep red blood cells and (PHA) phytohemagglutin stimulation was unaffected by NAC. It is concluded that the metabolic products of CPA for cytotoxicity as expressed as cystitis and lethality are different from the alkylating agents, which appear to affect immunological phenomena.

Female Buffalo and Lewis rats receiving 1.0 mg DDS/kg ip exhibited higher plasma levels of DDS and its monoacetylated metabolite, MADDS, than did male rats of each strain receiving the same dose. The fraction of the total measured drug in plasma as MADDS at 8 hr in female rats of both strains ranged from 43 to 62% compared with a range of 28-31% in male rats. Plasma half times of disappearance (T1/2) of DDS ranged from 5.0 to 6.8 hr and were not different among sexes and strains. Deacetylation of MADDS to DDS occurred when equimolar doses of MADDS were administered. An approach to a steady state of acetylation-deacetylation was indicated by comparing the percentage MADDS of the total drug in plasma in the respective sexes and strains receiving both drugs. T1/2 values of MADDS were significantly lower than values for DDS in Lewis rats. They were not different in Buffalo rats. Protein binding studies in plasma from rats receiving 5.0 mg DDS or 5.8 mg MADDS/kg showed 67-72% binding of DDS and 91% binding of MADDS. These in vivo observations were confirmed by in vitro binding studies. Comparison of these results with those of earlier studies in mice and man indicates that the rat is a better model of man than is the mouse for studies on the disposition of DDS.