Louisiana State University System

BACKGROUND: Obesity is associated with increased mortality. Weight loss improves cardiovascular risk factors, but no prospective interventional studies have reported whether weight loss decreases overall mortality. In fact, many observational studies suggest that weight reduction is associated with increased mortality. METHODS: The prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects. Of these subjects, 2010 underwent bariatric surgery (surgery group) and 2037 received conventional treatment (matched control group). We report on overall mortality during an average of 10.9 years of follow-up. At the time of the analysis (November 1, 2005), vital status was known for all but three subjects (follow-up rate, 99.9%). RESULTS: The average weight change in control subjects was less than +/-2% during the period of up to 15 years during which weights were recorded. Maximum weight losses in the surgical subgroups were observed after 1 to 2 years: gastric bypass, 32%; vertical-banded gastroplasty, 25%; and banding, 20%. After 10 years, the weight losses from baseline were stabilized at 25%, 16%, and 14%, respectively. There were 129 deaths in the control group and 101 deaths in the surgery group. The unadjusted overall hazard ratio was 0.76 in the surgery group (P=0.04), as compared with the control group, and the hazard ratio adjusted for sex, age, and risk factors was 0.71 (P=0.01). The most common causes of death were myocardial infarction (control group, 25 subjects; surgery group, 13 subjects) and cancer (control group, 47; surgery group, 29). CONCLUSIONS: Bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.

BACKGROUND: Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS: We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS: At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P<0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS: In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.).

OBJECTIVE We examined the role of butyric acid, a short-chain fatty acid formed by fermentation in the large intestine, in the regulation of insulin sensitivity in mice fed a high-fat diet. RESEARCH DESIGN AND METHODS In dietary-obese C57BL/6J mice, sodium butyrate was administrated through diet supplementation at 5% wt/wt in the high-fat diet. Insulin sensitivity was examined with insulin tolerance testing and homeostasis model assessment for insulin resistance. Energy metabolism was monitored in a metabolic chamber. Mitochondrial function was investigated in brown adipocytes and skeletal muscle in the mice. RESULTS On the high-fat diet, supplementation of butyrate prevented development of insulin resistance and obesity in C57BL/6 mice. Fasting blood glucose, fasting insulin, and insulin tolerance were all preserved in the treated mice. Body fat content was maintained at 10% without a reduction in food intake. Adaptive thermogenesis and fatty acid oxidation were enhanced. An increase in mitochondrial function and biogenesis was observed in skeletal muscle and brown fat. The type I fiber was enriched in skeletal muscle. Peroxisome proliferator–activated receptor-γ coactivator-1α expression was elevated at mRNA and protein levels. AMP kinase and p38 activities were elevated. In the obese mice, supplementation of butyrate led to an increase in insulin sensitivity and a reduction in adiposity. CONCLUSIONS Dietary supplementation of butyrate can prevent and treat diet-induced insulin resistance in mouse. The mechanism of butyrate action is related to promotion of energy expenditure and induction of mitochondria function.

BACKGROUND: The possible advantage for weight loss of a diet that emphasizes protein, fat, or carbohydrates has not been established, and there are few studies that extend beyond 1 year. METHODS: We randomly assigned 811 overweight adults to one of four diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the four diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The diets consisted of similar foods and met guidelines for cardiovascular health. The participants were offered group and individual instructional sessions for 2 years. The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content. RESULTS: At 6 months, participants assigned to each diet had lost an average of 6 kg, which represented 7% of their initial weight; they began to regain weight after 12 months. By 2 years, weight loss remained similar in those who were assigned to a diet with 15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respectively); in those assigned to a diet with 20% fat and those assigned to a diet with 40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbohydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg, respectively) (P>0.20 for all comparisons). Among the 80% of participants who completed the trial, the average weight loss was 4 kg; 14 to 15% of the participants had a reduction of at least 10% of their initial body weight. Satiety, hunger, satisfaction with the diet, and attendance at group sessions were similar for all diets; attendance was strongly associated with weight loss (0.2 kg per session attended). The diets improved lipid-related risk factors and fasting insulin levels. CONCLUSIONS: Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize. (ClinicalTrials.gov number, NCT00072995.)

BACKGROUND: The true causes of the obesity epidemic are not well understood and there are few longitudinal population-based data published examining this issue. The objective of this analysis was to examine trends in occupational physical activity during the past 5 decades and explore how these trends relate to concurrent changes in body weight in the U.S. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of energy expenditure for occupations in U.S. private industry since 1960 using data from the U.S. Bureau of Labor Statistics. Mean body weight was derived from the U.S. National Health and Nutrition Examination Surveys (NHANES). In the early 1960's almost half the jobs in private industry in the U.S. required at least moderate intensity physical activity whereas now less than 20% demand this level of energy expenditure. Since 1960 the estimated mean daily energy expenditure due to work related physical activity has dropped by more than 100 calories in both women and men. Energy balance model predicted weights based on change in occupation-related daily energy expenditure since 1960 for each NHANES examination period closely matched the actual change in weight for 40-50 year old men and women. For example from 1960-62 to 2003-06 we estimated that the occupation-related daily energy expenditure decreased by 142 calories in men. Given a baseline weight of 76.9 kg in 1960-02, we estimated that a 142 calories reduction would result in an increase in mean weight to 89.7 kg, which closely matched the mean NHANES weight of 91.8 kg in 2003-06. The results were similar for women. CONCLUSION: Over the last 50 years in the U.S. we estimate that daily occupation-related energy expenditure has decreased by more than 100 calories, and this reduction in energy expenditure accounts for a significant portion of the increase in mean U.S. body weights for women and men.

Importance: The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. Objective: To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. Design, Setting, and Participants: Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes. Interventions: A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups. Main Outcomes and Measures: The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]). Results: Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3.3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%). Conclusions and Relevance: Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT03548987.

People with obesity commonly face a pervasive, resilient form of social stigma. They are often subject to discrimination in the workplace as well as in educational and healthcare settings. Research indicates that weight stigma can cause physical and psychological harm, and that affected individuals are less likely to receive adequate care. For these reasons, weight stigma damages health, undermines human and social rights, and is unacceptable in modern societies. To inform healthcare professionals, policymakers, and the public about this issue, a multidisciplinary group of international experts, including representatives of scientific organizations, reviewed available evidence on the causes and harms of weight stigma and, using a modified Delphi process, developed a joint consensus statement with recommendations to eliminate weight bias. Academic institutions, professional organizations, media, public-health authorities, and governments should encourage education about weight stigma to facilitate a new public narrative about obesity, coherent with modern scientific knowledge.

IMPORTANCE: Short-term studies show that bariatric surgery causes remission of diabetes. The long-term outcomes for remission and diabetes-related complications are not known. OBJECTIVES: To determine the long-term diabetes remission rates and the cumulative incidence of microvascular and macrovascular diabetes complications after bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS: The Swedish Obese Subjects (SOS) is a prospective matched cohort study conducted at 25 surgical departments and 480 primary health care centers in Sweden. Of patients recruited between September 1, 1987, and January 31, 2001, 260 of 2037 control patients and 343 of 2010 surgery patients had type 2 diabetes at baseline. For the current analysis, diabetes status was determined at SOS health examinations until May 22, 2013. Information on diabetes complications was obtained from national health registers until December 31, 2012. Participation rates at the 2-, 10-, and 15-year examinations were 81%, 58%, and 41% in the control group and 90%, 76%, and 47% in the surgery group. For diabetes assessment, the median follow-up time was 10 years (interquartile range [IQR], 2-15) and 10 years (IQR, 10-15) in the control and surgery groups, respectively. For diabetes complications, the median follow-up time was 17.6 years (IQR, 14.2-19.8) and 18.1 years (IQR, 15.2-21.1) in the control and surgery groups, respectively. INTERVENTIONS: Adjustable or nonadjustable banding (n = 61), vertical banded gastroplasty (n = 227), or gastric bypass (n = 55) procedures were performed in the surgery group, and usual obesity and diabetes care was provided to the control group. MAIN OUTCOMES AND MEASURES: Diabetes remission, relapse, and diabetes complications. Remission was defined as blood glucose <110 mg/dL and no diabetes medication. RESULTS: The diabetes remission rate 2 years after surgery was 16.4% (95% CI, 11.7%-22.2%; 34/207) for control patients and 72.3% (95% CI, 66.9%-77.2%; 219/303) for bariatric surgery patients (odds ratio [OR], 13.3; 95% CI, 8.5-20.7; P < .001). At 15 years, the diabetes remission rates decreased to 6.5% (4/62) for control patients and to 30.4% (35/115) for bariatric surgery patients (OR, 6.3; 95% CI, 2.1-18.9; P < .001). With long-term follow-up, the cumulative incidence of microvascular complications was 41.8 per 1000 person-years (95% CI, 35.3-49.5) for control patients and 20.6 per 1000 person-years (95% CI, 17.0-24.9) in the surgery group (hazard ratio [HR], 0.44; 95% CI, 0.34-0.56; P < .001). Macrovascular complications were observed in 44.2 per 1000 person-years (95% CI, 37.5-52.1) in control patients and 31.7 per 1000 person-years (95% CI, 27.0-37.2) for the surgical group (HR, 0.68; 95% CI, 0.54-0.85; P = .001). CONCLUSIONS AND RELEVANCE: In this very long-term follow-up observational study of obese patients with type 2 diabetes, bariatric surgery was associated with more frequent diabetes remission and fewer complications than usual care. These findings require confirmation in randomized trials. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01479452.

The mission of the American Diabetes Association is “to prevent and cure diabetes and to improve the lives of all people affected by diabetes.” Increasingly, scientific and medical articles ( 1) and commentaries ( 2) about diabetes interventions use the terms “remission” and “cure” as possible outcomes. Several approved or experimental treatments for type 1 and type 2 diabetes (e.g., pancreas or islet transplants, immunomodulation, bariatric/metabolic surgery) are of curative intent or have been portrayed in the media as a possible cure. However, defining remission or cure of diabetes is not as straightforward as it may seem. Unlike “dichotomous” diseases such as many malignancies, diabetes is defined by hyperglycemia, which exists on a continuum and may be impacted over a short time frame by everyday treatment or events (medications, diet, activity, intercurrent illness). The distinction between successful treatment and cure is blurred in the case of diabetes. Presumably improved or normalized glycemia must be part of the definition of remission or cure. Glycemic measures below diagnostic cut points for diabetes can occur with ongoing medications (e.g., antihyperglycemic drugs, immunosuppressive medications after a transplant), major efforts at lifestyle change, a history of bariatric/metabolic surgery, or ongoing procedures (such as repeated replacements of endoluminal devices). Do we use the terms remission or cure for all patients with normal glycemic measures, regardless of how this is achieved?

CONTEXT: Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination. OBJECTIVE: To examine the benefits of aerobic training alone, resistance training alone, and a combination of both on hemoglobin A(1c) (HbA(1c)) in individuals with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c) levels of 6.5% or higher were enrolled in the 9-month exercise program between April 2007 and August 2009. INTERVENTION: Forty-one participants were assigned to the nonexercise control group, 73 to resistance training 3 days a week, 72 to aerobic exercise in which they expended 12 kcal/kg per week; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week. Main Outcome Change in HbA(1c) level. Secondary outcomes included measures of anthropometry and fitness. RESULTS: The study included 63.0% women and 47.3% nonwhite participants who were a mean (SD) age of 55.8 years (8.7 years) with a baseline HbA(1c) level of 7.7% (1.0%). Compared with the control group, the absolute mean change in HbA(1c) in the combination training exercise group was -0.34% (95% confidence interval [CI], -0.64% to -0.03%; P = .03). The mean changes in HbA(1c) were not statistically significant in either the resistance training (-0.16%; 95% CI, -0.46% to 0.15%; P = .32) or the aerobic (-0.24%; 95% CI, -0.55% to 0.07%; P = .14) groups compared with the control group. Only the combination exercise group improved maximum oxygen consumption (mean, 1.0 mL/kg per min; 95% CI, 0.5-1.5, P < .05) compared with the control group. All exercise groups reduced waist circumference from -1.9 to -2.8 cm compared with the control group. The resistance training group lost a mean of -1.4 kg fat mass (95% CI, -2.0 to -0.7 kg; P < .05) and combination training group lost a mean of -1.7 (-2.3 to -1.1 kg; P < .05) compared with the control group. CONCLUSIONS: Among patients with type 2 diabetes mellitus, a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c) levels. This was not achieved by aerobic or resistance training alone. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00458133.

Importance: Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management. Objective: To compare the efficacy and adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg (both with diet and physical activity), in people with overweight or obesity. Design, Setting, and Participants: Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: September 11-November 26) to May 2021 (end of follow-up: May 11) in adults with body mass index of 30 or greater or 27 or greater with 1 or more weight-related comorbidities, without diabetes (N = 338). Interventions: Participants were randomized (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4 mg (16-week escalation; n = 126), or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg (4-week escalation; n = 127), or matching placebo, plus diet and physical activity. Participants unable to tolerate 2.4 mg of semaglutide could receive 1.7 mg; participants unable to tolerate 3.0 mg of liraglutide discontinued treatment and could restart the 4-week titration. Placebo groups were pooled (n = 85). Main Outcomes and Measures: The primary end point was percentage change in body weight, and confirmatory secondary end points were achievement of 10% or more, 15% or more, and 20% or more weight loss, assessed for semaglutide vs liraglutide at week 68. Semaglutide vs liraglutide comparisons were open-label, with active treatment groups double-blinded against matched placebo groups. Comparisons of active treatments vs pooled placebo were supportive secondary end points. Results: Of 338 randomized participants (mean [SD] age, 49 [13] years; 265 women [78.4%]; mean [SD] body weight, 104.5 [23.8] kg; mean [SD] body mass index, 37.5 [6.8]), 319 (94.4%) completed the trial, and 271 (80.2%) completed treatment. The mean weight change from baseline was -15.8% with semaglutide vs -6.4% with liraglutide (difference, -9.4 percentage points [95% CI, -12.0 to -6.8]; P < .001); weight change with pooled placebo was -1.9%. Participants had significantly greater odds of achieving 10% or more, 15% or more, and 20% or more weight loss with semaglutide vs liraglutide (70.9% of participants vs 25.6% [odds ratio, 6.3 {95% CI, 3.5 to 11.2}], 55.6% vs 12.0% [odds ratio, 7.9 {95% CI, 4.1 to 15.4}], and 38.5% vs 6.0% [odds ratio, 8.2 {95% CI, 3.5 to 19.1}], respectively; all P < .001). Proportions of participants discontinuing treatment for any reason were 13.5% with semaglutide and 27.6% with liraglutide. Gastrointestinal adverse events were reported by 84.1% with semaglutide and 82.7% with liraglutide. Conclusions and Relevance: Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT04074161.

CONTEXT: Low levels of cardiorespiratory fitness are associated with high risk of mortality, and improvements in fitness are associated with reduced mortality risk. However, a poor understanding of the physical activity-fitness dose response relation remains. OBJECTIVE: To examine the effect of 50%, 100%, and 150% of the NIH Consensus Development Panel recommended physical activity dose on fitness in women. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of 464 sedentary, postmenopausal overweight or obese women whose body mass index ranged from 25.0 to 43.0 and whose systolic blood pressure ranged from 120.0 to 159.9 mm Hg. Enrollment took place between April 2001 and June 2005 in the Dallas, Tex, area. INTERVENTION: Participants were randomly assigned to 1 of 4 groups: 102 to the nonexercise control group and 155 to the 4-kcal/kg, 104 to the 8-kcal/kg, and 103 to the 12-kcal/kg per week energy-expenditure groups for the 6-month intervention period. Target training intensity was the heart rate associated with 50% of each woman's peak Vo2. MAIN OUTCOME MEASURE: The primary outcome was aerobic fitness assessed on a cycle ergometer and quantified as peak absolute oxygen consumption (Vo2abs, L/min). RESULTS: The mean (SD) baseline Vo2abs values were 1.30 (0.25) L/min. The mean (SD) minutes of exercising per week were 72.2 (12.3) for the 4-kcal/kg, 135.8 (19.5) for the 8-kcal/kg, and 191.7 (33.7) for the 12-kcal/kg per week exercise groups. After adjustment for age, race/ethnicity, weight, and peak heart rate, the exercise groups increased their Vo2abs compared with the control group by 4.2% in the 4-kcal/kg, 6.0% in the 8-kcal/kg, and 8.2% in the 12-kcal/kg per week groups (P<.001 for each vs control; P for trend <.001). There was no treatment x subgroup interaction for age, body mass index, weight, baseline Vo2abs, race/ethnicity, or baseline hormone therapy use. There were no significant changes in systolic or diastolic blood pressure values from baseline to 6 months in any of the exercise groups vs the control group. CONCLUSION: In this study, previously sedentary, overweight or obese postmenopausal women experienced a graded dose-response change in fitness across levels of exercise training. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00011193.

The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic.

Abstract Fire is a powerful ecological and evolutionary force that regulates organismal traits, population sizes, species interactions, community composition, carbon and nutrient cycling and ecosystem function. It also presents a rapidly growing societal challenge, due to both increasingly destructive wildfires and fire exclusion in fire‐dependent ecosystems. As an ecological process, fire integrates complex feedbacks among biological, social and geophysical processes, requiring coordination across several fields and scales of study. Here, we describe the diversity of ways in which fire operates as a fundamental ecological and evolutionary process on Earth. We explore research priorities in six categories of fire ecology: (a) characteristics of fire regimes, (b) changing fire regimes, (c) fire effects on above‐ground ecology, (d) fire effects on below‐ground ecology, (e) fire behaviour and (f) fire ecology modelling. We identify three emergent themes: the need to study fire across temporal scales, to assess the mechanisms underlying a variety of ecological feedbacks involving fire and to improve representation of fire in a range of modelling contexts. Synthesis : As fire regimes and our relationships with fire continue to change, prioritizing these research areas will facilitate understanding of the ecological causes and consequences of future fires and rethinking fire management alternatives.

Despite spending more than any other nation on medical care per person, the United States ranks behind other industrialized nations in key health performance measures. A main cause is the deep disparities in access to care and health outcomes. Federal programs such as the designations of Medically Underserved Areas/Populations and Health Professional Shortage Areas are designed to boost the number of health professionals serving these areas and to help alleviate the access problem. Their effectiveness relies first and foremost on an accurate measure of accessibility so that resources can be allocated to truly needy areas. Various measures of accessibility need to be integrated into one framework for comparison and evaluation. Optimization methods can be used to improve the distribution and supply of health care providers to maximize service coverage, minimize travel needs of patients, limit the number of facilities, and maximize health or access equality. Inequality in health care access comes at a personal and societal price, evidenced in disparities in health outcomes, including late-stage cancer diagnosis. This review surveys recent literature on the three named issues with emphasis on methodological advancements and implications for public policy.

Food intake and energy expenditure are controlled by complex, redundant, and distributed neural systems that reflect the fundamental biological importance of adequate nutrient supply and energy balance. Much progress has been made in identifying the various hormonal and neural mechanisms by which the brain informs itself about availability of ingested and stored nutrients and, in turn, generates behavioral, autonomic, and endocrine output. While hypothalamus and caudal brainstem play crucial roles in this homeostatic function, areas in the cortex and limbic system are important for processing information regarding prior experience with food, reward, and emotion, as well as social and environmental context. Most vertebrates can store a considerable amount of energy as fat for later use, and this ability has now become one of the major health risks for many human populations. The predisposition to develop obesity can theoretically result from any pathological malfunction or lack of adaptation to changing environments of this highly complex system.

The workshop entitled 'Interventions to Slow Aging in Humans: Are We Ready?' was held in Erice, Italy, on October 8-13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR-S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting.

I test the hypothesis that short debt maturity attenuates the negative effect of growth opportunities on leverage. Using simultaneous equations with leverage and maturity endogenous, I find strong support for an economically significant attenuation effect. The negative effect of growth opportunities on leverage for firms with all shorter-term debt is less than one-sixth as large as the effect for firms with all longer-term debt. Short maturity also increases liquidity risk, however, which negatively affects leverage. The results suggest that firms trade off the cost of underinvestment problems against the cost of liquidity risk when choosing short maturity.

OBJECTIVE: We sought to provide guidelines for the nutritional and endocrine management of adults after bariatric surgery, including those with diabetes mellitus. The focus is on the immediate postoperative period and long-term management to prevent complications, weight regain, and progression of obesity-associated comorbidities. The treatment of specific disorders is only summarized. PARTICIPANTS: The Task Force was composed of a chair, five additional experts, a methodologist, and a medical writer. It received no corporate funding or remuneration. CONCLUSIONS: Bariatric surgery is not a guarantee of successful weight loss and maintenance. Increasingly, patients regain weight, especially those undergoing restrictive surgeries such as laparoscopic banding rather than malabsorptive surgeries such as Roux-en-Y bypass. Active nutritional patient education and clinical management to prevent and detect nutritional deficiencies are recommended for all patients undergoing bariatric surgery. Management of potential nutritional deficiencies is particularly important for patients undergoing malabsorptive procedures, and strategies should be employed to compensate for food intolerance in patients who have had a malabsorptive procedure to reduce the risk for clinically important nutritional deficiencies. To enhance the transition to life after bariatric surgery and to prevent weight regain and nutritional complications, all patients should receive care from a multidisciplinary team including an experienced primary care physician, endocrinologist, or gastroenterologist and consider enrolling postoperatively in a comprehensive program for nutrition and lifestyle management. Future research should address the effectiveness of intensive postoperative nutritional and endocrine care in reducing morbidity and mortality from obesity-associated chronic diseases.

The relationship between bone and fat formation within the bone marrow microenvironment is complex and remains an area of active investigation. Classical in vitro and in vivo studies strongly support an inverse relationship between the commitment of bone marrow-derived mesenchymal stem cells or stromal cells to the adipocyte and osteoblast lineage pathways. In this review, we focus on the recent literature exploring the mechanisms underlying these differentiation events and discuss their implications relevant to osteoporosis and regenerative medicine.