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Objective: Little information is available on the impact of abnormal glucose tolerance on mortality in South Asian and African populations in the developing world. We explored this issue in a large, multiethnic cohort from the developing nation of Mauritius.Research Design and Methods: Population-based surveys were undertaken in 1987, 1992, and 1998. The 9,559 participants (20-82 years old) comprised 66% South Asian (Indian), 27% Creole (African), and 7% Chinese descent. Mortality was ascertained in 2007.Results: Over a median 15.1-year follow-up, 1,557 participants died. Compared with those with normal glucose tolerance, the all-cause mortality hazard ratios (HR) for known diabetes, newly diagnosed diabetes, and impaired glucose tolerance were 3.35 (95% CI 2.77-4.04), 2.11 (1.73-2.57), and 1.53 (1.26-1.87) in South Asians and 2.14 (1.65-2.79), 1.41 (1.06-1.88), and 1.08 (0.83-1.40) in Africans, respectively. Those with impaired fasting glucose were not at increased risk in either ethnicity. In the Chinese, only those with known diabetes were at increased risk of mortality with HR 3.68 (1.87-7.25).Conclusions: This is the first study in a developing country of the impact of glucose intolerance on mortality in an African population, and one of the first studies of a South Asian population. It shows that the impact on mortality in these populations in Mauritius is comparable to that seen in developed countries. These results are important in a global context for future health policy in light of the impact of the rapid increase in prevalence of diabetes, especially in developing nations. [ABSTRACT FROM AUTHOR]

Objective: We investigated stroke mortality in individuals in different categories of glycemia and compared hazard ratios (HRs) corresponding to a 1-SD increase in 2-h plasma glucose and fasting plasma glucose (FPG) criteria.Research Design and Methods: We examined data from 2-h 75-g oral glucose tolerance tests taken from 13 European cohorts comprising 11,844 (55%) men and 9,862 (45%) women who were followed up for a median of 10.5 years. A multivariate adjusted Cox proportional hazards model was used to estimate HRs for stroke mortality.Results: In men and women without a prior history of diabetes, multivariate adjusted HRs for stroke mortality corresponding to a 1-SD increase in FPG were 1.02 (95% CI 0.83-1.25) and 1.52 (1.22-1.88) and those in 2-h plasma glucose 1.21 (1.06-1.38) and 1.31 (1.06-1.61), respectively. Addition of 2-h plasma glucose to the model with FPG significantly improved prediction of stroke mortality in men (chi2 = 10.12; P = 0.001) but not in women (chi2 = 0.01; P = 0.94), whereas addition of FPG to 2-h plasma glucose improved stroke mortality in women (chi2 = 4.08; P = 0.04) but not in men (chi2 = 3.29; P = 0.07).Conclusions: Diabetes defined by either FPG or 2-h plasma glucose increases the risk of stroke mortality. In individuals without a history of diabetes, elevated 2-h postchallenge glucose is a better predictor than elevated fasting glucose in men, whereas the latter is better than the former in women. [ABSTRACT FROM AUTHOR]

AIMS: Suboptimal maternal nutrition and catch-up growth in early childhood predispose to insulin resistance and other components of metabolic syndrome in later life. A central metabolic syndrome (CMS) has been identified comprising obesity, dyslipidaemia and insulin resistance. This study was designed to investigate determinants of risk for CMS. METHODS: Persons born in Newcastle in May and June 1947 (n = 358) were followed to 1996-1998. A lifecourse approach was used to estimate the proportion of variance in a summary measure of CMS at age 49-51 years accounted for by factors operating at different stages of life. RESULTS: After adjustment for other early life variables, childhood catch-up growth in men accounted for significant variation in the CMS score independent of adult lifestyle. In adulthood, exercise level in men and smoking in both genders were independently associated with CMS. Over two-thirds of explained variation in the CMS score in women, and almost half in men, was accounted for exclusively by factors measured in adulthood. CONCLUSIONS: While risk for CMS in men is compounded by early life disadvantage, promotion of a healthier adult lifestyle and a reduction in the number of people taking up smoking would appear to be the public health interventions most likely to reduce the prevalence of CMS in middle age. [ABSTRACT FROM AUTHOR]

Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options., Aim: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D., Methods: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee., Results: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI ≥40 kg/m 2 ) and in those with class II obesity (BMI 35.0-39.9 kg/m 2 ) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m 2 if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m 2 for Asian patients., Conclusions: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.

Diabetes mellitus is one of the most important public health challenges of the twenty-first century. Until the past decade, it has been seriously underrated as a global health threat. Major gaps exist in efforts to comprehend the burden nationally and globally, especially in developing nations, due to a lack of accurate data for monitoring and surveillance. Early attempts to obtain accurate data, discussed in this article, seem to have been cast aside so, at present, these needs remain unmet. Existing international efforts to assemble information fall far short of requirements. Current estimates are imprecise, only providing a rough picture, and probably underestimate the disease burden. The methodologies that are currently used, and that are discussed in this Perspectives article, are inadequate for providing a complete and accurate assessment of the prevalence of diabetes mellitus. International consensus on uniform standards and criteria for reporting national data on diabetes mellitus prevalence as well as for common complications of diabetes mellitus and mortality need to be developed.

Background: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options., Aim: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D., Methods: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee., Results: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI≥40 kg/m(2)) and in those with class II obesity (BMI 35.0-39.9 kg/m(2)) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m(2) if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m(2) for Asian patients., Conclusions: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies., (Copyright © 2016. Published by Elsevier Inc.)

The number of people with diabetes worldwide has more than doubled during the past 20 years. One of the most worrying features of this rapid increase is the emergence of type 2 diabetes in children, adolescents, and young adults. Although the role of traditional risk factors for type 2 diabetes, such as genetic, lifestyle, and behavioral risk factors, has been given attention, recent research has focused on identifying the contributions of epigenetic mechanisms and the effect of the intrauterine environment. Epidemiological data predict an inexorable and unsustainable increase in global health expenditure attributable to diabetes, so disease prevention should be given high priority. An integrated approach is needed to prevent type 2 diabetes and must recognize its heterogeneity. Future research needs to be directed at improved understanding of the potential role of determinants, such as the maternal environment and other early life factors, as well as changing trends in global demography, to help shape disease prevention programs. Equally important is a better understanding of the role of metabolic surgery in helping to address the management both of persons with type 2 diabetes and of those persons in the community who are at higher risk for type 2 diabetes, particularly in emerging nations where the diabetes epidemic is in full flight., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Aims: Developing countries face a high and growing burden of type 2 diabetes. We surveyed physicians in a diverse range of countries in the Middle East and Africa (Egypt, Kingdom of Saudi Arabia, United Arab Emirates, South Africa and Lebanon) with regard to their perceptions of barriers to type 2 diabetes care identified as potentially important in the literature and by the authors., Methods: One thousand and eighty-two physicians completed a questionnaire developed by the authors., Results: Most physicians enrolled in the study employed guideline-driven care; 80-100% of physicians prescribed metformin (with lifestyle intervention, where there are no contraindications) for newly diagnosed type 2 diabetes, with lifestyle intervention alone used where metformin was not prescribed. Sulfonylureas were prescribed widely, consistent with the poor economic status of many patients. About one quarter of physicians were not undertaking any form of continuing medical education, and relatively low proportions of practices had their own diabetes educators, dieticians or diabetic foot specialists. Physicians identified the deficiencies of their patients (unhealthy lifestyles, lack of education and poor diet) as the most important barriers to optimal diabetes care. Low-treatment compliance was not ranked highly. Access to physicians did not appear to be a problem, as most patients were seen multiple times per year., Conclusions: Physicians in the Middle East and South Africa identified limitations relating to their patients as the main barrier to delivering care for diabetes, without giving high priority to issues relating to processes of care delivery. Further study would be needed to ascertain whether these findings reflect an unduly physician-centred view of their practice. More effective provision of services relating to the prevention of complications and improved lifestyles may be needed., (© 2013 John Wiley & Sons Ltd.)

Background: Type 2 diabetes can often be prevented by lifestyle modification; however, successful lifestyle intervention programmes are labour intensive. Mobile phone messaging is an inexpensive alternative way to deliver educational and motivational advice about lifestyle modification. We aimed to assess whether mobile phone messaging that encouraged lifestyle change could reduce incident type 2 diabetes in Indian Asian men with impaired glucose tolerance., Methods: We did a prospective, parallel-group, randomised controlled trial between Aug 10, 2009, and Nov 30, 2012, at ten sites in southeast India. Working Indian men (aged 35-55 years) with impaired glucose tolerance were randomly assigned (1:1) with a computer-generated randomisation sequence to a mobile phone messaging intervention or standard care (control group). Participants in the intervention group received frequent mobile phone messages compared with controls who received standard lifestyle modification advice at baseline only. Field staff and participants were, by necessity, not masked to study group assignment, but allocation was concealed from laboratory personnel as well as principal and co-investigators. The primary outcome was incidence of type 2 diabetes, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00819455., Results: We assessed 8741 participants for eligibility. 537 patients were randomly assigned to either the mobile phone messaging intervention (n=271) or standard care (n=266). The cumulative incidence of type 2 diabetes was lower in those who received mobile phone messages than in controls: 50 (18%) participants in the intervention group developed type 2 diabetes compared with 73 (27%) in the control group (hazard ratio 0·64, 95% CI 0·45-0·92; p=0·015). The number needed to treat to prevent one case of type 2 diabetes was 11 (95% CI 6-55). One patient in the control group died suddenly at the end of the first year. We recorded no other serious adverse events., Interpretation: Mobile phone messaging is an effective and acceptable method to deliver advice and support towards lifestyle modification to prevent type 2 diabetes in men at high risk., Funding: The UK India Education and Research Initiative, the World Diabetes Foundation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To determine whether glucose-independent differences in HbA1c exist between people of African, South Asian, and Chinese ethnicities., Research Design and Methods: Data from 6,701 people aged 19-78 years, without known diabetes, from Mauritius, and participating in the population-based Non-Communicable Disease Surveys of the main island and the island of Rodrigues were included. Participants were African (n = 1,219 from main island, n = 1,505 from Rodrigues), South Asian (n = 3,820), and Chinese (n = 157). Survey data included HbA1c, plasma glucose during oral glucose tolerance testing (OGTT), anthropometry, demographics, and medical and lifestyle history., Results: Mean HbA1c, after adjustment for fasting and 2-h plasma glucose and other factors known to influence HbA1c, was higher in Africans from Rodrigues (6.1%) than in South Asians (5.7%, P < 0.001), Chinese (5.7%, P < 0.001), or Africans from the main island of Mauritius (5.7%, P < 0.001). The age-standardized prevalence of diabetes among Africans from Rodrigues differed substantially depending on the diagnostic criteria used [OGTT 7.9% (95% CI 5.8-10.0); HbA1c 17.3% (15.3-19.2)]. Changing diagnostic criteria resulted in no significant change in the prevalence of diabetes within the other ethnic groups., Conclusions: People of African ethnicity from Rodrigues have higher HbA1c than those of South Asian or African ethnicity from the main island of Mauritius for reasons not explained by plasma glucose during an OGTT or traditional factors known to affect glycemia. Further research should be directed at determining the mechanism behind this disparity and its relevance to clinical outcomes.

Background: This study aimed to identify correlates of case fatality within an incident stroke population in rural Tanzania., Methods: Stroke patients, identified by the Tanzanian Stroke Incidence Project, underwent a full examination and assessment around the time of incident stroke. Records were made of demographic data, blood pressure, pulse rate and rhythm, physical function (Barthel index), neurological status (communication, swallowing, vision, muscle activity, sensation), echocardiogram, chest X-ray and computed tomography (CT) head scan. Cases were followed up over the next 3 - 6 years., Results: In 130 incident cases included in this study, speech, language and swallowing problems, reduced muscle power, and reduced physical function were all significantly correlated with case fatality at 28 days and 3 years. Age was significantly correlated with case fatality at 3 years, but not at 28 days post-stroke. Smoking history was the only significant correlate of case fatality at 28 days that pre-dated the incident stroke. All other significant correlates were measures of neurological recovery from stroke., Conclusions: This is the first published study of the correlates of post-stroke case fatality in sub-Saharan Africa (SSA) from an incident stroke population. Case fatality was correlated with the various motor impairments resulting from the incident stroke. Improving poststroke care may help to reduce stroke case fatality in SSA.

There are accumulating data describing the association between diabetes and cancer mortality from Westernised populations. There are no data describing the relationship between diabetes and cancer mortality in African or South Asian populations from developing countries. We explored the relationship of abnormal glucose tolerance and diabetes on cancer mortality risk in a large, multi-ethnic cohort from the developing nation of Mauritius. Population-based surveys were undertaken in 1987, 1992 and 1998. The 9559 participants comprised 66% of South Asian (Indian), 27% of African (Creole), and 7% of Chinese descent. Cox's proportional hazards model with time varying covariates was used to obtain hazard ratios (HRs) and 95% confidence intervals (95% CI) for risk of cancer mortality, after adjustment for confounding factors. In men, but not women, cancer mortality risk increased with rising 2h-PG levels with HR for the top versus bottom quintile of 2.77 (95%CI: 1.28 to 5.98). South Asian men with known diabetes had a significantly greater risk of cancer mortality than those with normal glucose tolerance (NGT) HR: 2.74 (95%CI: 1.00-7.56). Overall, impaired glucose tolerance was associated with an elevated risk of cancer mortality compared to NGT (HR: 1.47, 95% CI: 0.98-2.19), though this was not significant. We have shown that the association between abnormal glucose tolerance and cancer extends to those of African and South Asian descent. These results highlight the importance of understanding this relationship in a global context to direct future health policy given the rapid increase in type 2 diabetes, especially in developing nations., (Copyright © 2012 UICC.)

Background: Higher waist circumference and lower hip circumference are both associated with increased cardiovascular disease (CVD) risk, despite being directly correlated. The real effects of visceral obesity may therefore be underestimated when hip circumference is not fully taken into account. We hypothesized that adding waist and hip circumference to traditional risk factors would significantly improve CVD risk prediction., Methods: In a population-based survey among South Asian and African Mauritians (n = 7978), 1241 deaths occurred during 15 years of follow-up. In a model that included variables used in previous CVD risk calculations (a Framingham-type model), the association between waist circumference and mortality was examined before and after adjustment for hip circumference. The percentage with an increase in estimated 10-year cumulative mortality of >25% and a decrease of >20% after waist and hip circumference were added to the model was calculated., Results: Waist circumference was strongly related to mortality only after adjustment for hip circumference and vice versa. Adding waist and hip circumference to a Framingham-type model increased estimated 10-year cumulative CVD mortality by >25% for 23.7% of those who died and 15.7% of those censored. Cumulative mortality decreased by >20% for 4.5% of those who died and 14.8% of those censored., Conclusions: The effect of central obesity on mortality risk is seriously underestimated without adjustment for hip circumference. Adding waist and hip circumference to a Framingham-type model for CVD mortality substantially increased predictive power. Both may be important inclusions in CVD risk prediction models.

Objective: Secular trends in the epidemiology of diabetes are best described by studying the same population over time, but few such studies exist. Using surveys from Mauritius in 1987 and 2009, we examined 1) the change in the prevalence of diabetes, 2) the extent to which changes in traditional diabetes risk factors explained the increase, and 3) the change in the distribution of plasma glucose levels over time., Research Design and Methods: Independent population-based surveys were undertaken in Mauritius in 1987 and 2009 using similar methodology in adults aged 20-74 years. Physical measurements and fasting blood samples were taken, and an oral glucose tolerance test was performed at both surveys., Results: The age-standardized prevalence of diabetes in 2009 was 22.3% (95% CI 20.0-24.6) among men and 20.2% (18.3-22.3) among women, representing an increase since 1987 of 64 and 62% among men and women, respectively. Concurrent changes in the distribution of age, ethnicity, waist circumference, BMI, physical activity, smoking, family history of diabetes, and hypertension explained more of the increase in the prevalence of diabetes in men than in women. Increases in plasma glucose (especially fasting glucose) were seen across the population but were greater at the upper levels., Conclusions: In Mauritius, there has been a marked increase in diabetes prevalence over 22 years. This mainly results from changes in traditional risk factors, leading to population-wide increases in plasma glucose levels. Interventions to control this escalation of diabetes should focus on population-wide strategies.

Background: Previous studies suggest that over-nutrition in early infancy may programme long-term susceptibility to insulin resistance., Objective: To assess the association of breast milk and quantity of infant formula and cows' milk intake during infancy with insulin resistance measures in early adulthood., Design: Long-term follow-up of the Barry Caerphilly Growth cohort, into which mothers and their offspring had originally been randomly assigned, between 1972-1974, to receive milk supplementation or not. Participants were the offspring, aged 23-27 years at follow-up (n = 679). Breastfeeding and formula/cows' milk intake was recorded prospectively by nurses. The main outcomes were insulin sensitivity (ISI(0)) and insulin secretion (CIR(30))., Results: 573 (84%) individuals had valid glucose and insulin results and complete covariate information. There was little evidence of associations of breastfeeding versus any formula/cows' milk feeding or of increasing quartiles of formula/cows' milk consumption during infancy (<3 months) with any outcome measure in young adulthood. In fully adjusted models, the differences in outcomes between breastfeeding versus formula/cows' milk feeding at 3 months were: fasting glucose (-0.07 mmol/l; 95% CI: -0.19, 0.05); fasting insulin (8.0%; -8.7, 27.6); ISI(0) (-6.1%; -11.3, 12.1) and CIR(30) (3.8%; -19.0, 32.8). There was also little evidence that increasing intakes of formula/cows' milk at 3 months were associated with fasting glucose (increase per quartile of formula/cows' milk intake = 0.00 mmol/l; -0.03, 0.03); fasting insulin (0.8%; -3.2, 5.1); ISI (0) (-0.9%; -5.1, 3.5) and CIR(30) (-2.6%; -8.4, 3.6)., Conclusions: We found no evidence that increasing consumption of formula/cows' milk in early infancy was associated with insulin resistance in young adulthood.

Type 2 diabetes (T2D) and obesity are both complex and chronic medical disorders, each with an escalating worldwide prevalence. When obesity is severe, and/or available medical therapies fail to control the diabetes, bariatric surgery becomes a cost-effective therapy for T2D. When there are other major comorbidities and cardiovascular risk, the option of bariatric surgery becomes even more worthy of consideration. National guidelines for bariatric surgery need to be developed and implemented for people with T2D. With this in mind, the International Diabetes Federation convened a multidisciplinary working group to develop a position statement. The key recommendations cover describing those eligible for surgery and who should be prioritized, incorporating bariatric surgery into T2D treatment algorithms, performing surgery in centers with multidisciplinary teams that are experienced in the management of both obesity and diabetes, and developing bariatric surgery registries and reporting standards., (© 2011 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.)

The International Diabetes Federation Taskforce on Epidemiology and Prevention of Diabetes convened a consensus working group of diabetologists, endocrinologists, surgeons and public health experts to review the appropriate role of surgery and other gastrointestinal interventions in the treatment and prevention of Type 2 diabetes. The specific goals were: to develop practical recommendations for clinicians on patient selection; to identify barriers to surgical access and suggest interventions for health policy changes that ensure equitable access to surgery when indicated; and to identify priorities for research. Bariatric surgery can significantly improve glycaemic control in severely obese patients with Type 2 diabetes. It is an effective, safe and cost-effective therapy for obese Type 2 diabetes. Surgery can be considered an appropriate treatment for people with Type 2 diabetes and obesity not achieving recommended treatment targets with medical therapies, especially in the presence of other major co-morbidities. The procedures must be performed within accepted guidelines and require appropriate multidisciplinary assessment for the procedure, comprehensive patient education and ongoing care, as well as safe and standardized surgical procedures. National guidelines for bariatric surgery need to be developed for people with Type 2 diabetes and a BMI of 35 kg/m(2) or more., (Copyright © 2011 J.B. Dixon, P. Zimmet, K.G. Alberti & F. Rubino. Reprinted from Diabetic Medicine, Volume 28, Issue 6, pages 628-642, June 2011, Wiley-Blackwell. Published by Elsevier Inc. All rights reserved.)