Métabolisme énergétique et traumatisme crâniocérébral [Energy metabolism and craniocerebral injury]

Severe head injury induces major hormonal, humoral and metabolic changes, characterized by increases in stress hormone secretion, lymphokines production, associated with high lipid and protein catabolism as well as changes in energy expenditure (EE). Numerous factors influence EE in head-injured patients, particularly anthropometric data, body temperature, nutritional support, level of consciousness, muscular tone and activity. Resting EE is usually increased following brain trauma; however, normal or decreased metabolic rates can be observed in curarized patients on mechanical ventilation or in patients receiving high doses of barbiturates.

A new procedure to assess the energy requirements of lactation in Gambian women.

The combined 24-h energy expenditure (24-h EE) of mother and child was measured with a respiratory chamber (indirect calorimeter) in a group of 16 lactating Gambian women and was compared with that of a control group of 16 nonpregnant, nonlactating (NPNL) Gambian women. Breast-milk production (738 +/- 47 g/d: mean +/- SE) was adequate to allow a normal rate of growth of their 2-mo-old babies (28.0 +/- 2.4 g/d). The combined 24-h EE (mother and child) was higher (8381 +/- 180 kJ/d. P less than 0.001) than that of NPNL women (6092 +/- 121 kJ/d). Two-thirds of this differences could be attributed to the child's EE and one-third to a greater spontaneous physical activity of lactating women. The energy retained by the child for growth in conjunction with the calorimetric measurements allowed the calculation of the extra energy requirements for lactation, which were found to be 2100 kJ/d. These results confirm the values of the current dietary recommendations for lactation, based on the energy cost of milk production.

Protein energy malnutrition increases arginase activity in monocytes and macrophages.

BACKGROUND: Protein energy malnutrition is commonly associated with immune dysfunctions and is a major factor in susceptibility to infectious diseases. METHODS: In this study, we evaluated the impact of protein energy malnutrition on the capacity of monocytes and macrophages to upregulate arginase, an enzyme associated with immunosuppression and increased pathogen replication. RESULTS: Our results show that monocytes and macrophages are significantly increased in the bone marrow and blood of mice fed on a protein low diet. No alteration in the capacity of bone marrow derived macrophages isolated from malnourished mice to phagocytose particles, to produce the microbicidal molecule nitric oxide and to kill intracellular Leishmania parasites was detected. However, macrophages and monocytes from malnourished mice express significantly more arginase both in vitro and in vivo. Using an experimental model of visceral leishmaniasis, we show that following protein energy malnutrition, the increased parasite burden measured in the spleen of these mice coincided with increased arginase activity and that macrophages provide a more permissive environment for parasite growth. CONCLUSIONS: Taken together, these results identify a novel mechanism in protein energy malnutrition that might contributes to increased susceptibility to infectious diseases by upregulating arginase activity in myeloid cells.

Twenty-four-hour energy expenditure and basal metabolic rate measured in a whole-body indirect calorimeter in Gambian men.

By use of a respiration chamber, 24-hour energy expenditure (EE), diet-induced thermogenesis (DIT), and basal and sleeping EE were measured in 20 young rural Gambian men during the "hungry" season (weight, 60.8 +/- 1.4 kg) and in a group of 16 European men matched for body composition (weight, 66.9 +/- 1.9 kg). The 24-h EE was lower in Gambian than in European men (2047 +/- 46 vs 2635 +/- 74 kcal/d, p less than 0.001, respectively). Basal EE and sleeping EE were also lower in Gambian than in European men (1.05 +/- 0.02 vs 1.25 +/- 0.02 kcal/min and 1.0 +/- 0.02 vs 1.18 +/- 0.02 kcal/min, p less than 0.01, respectively). DIT was blunted in Gambian compared with European men (6.3 +/- 0.6% vs 12.1 +/- 0.5%, p less than 0.001 respectively). The net efficiency of walking was greater in Gambian than in European men (23.2 +/- 0.3% vs 20.1 +/- 0.4%, p less than 0.001, respectively). A low basal and sleeping EE, a reduced DIT, and a high work efficiency are important energy-sparing mechanisms in Gambian men, which allow them to cope with a marginal level of dietary intake during the hungry season.

Enteral versus parenteral nutrition: comparison of energy metabolism in lean and moderately obese women.

Continuous respiratory-exchange measurements were performed on ten moderately obese and ten lean young women for 1 h before, 3 h during, and 3 h after either parenteral (IV) or intragastric (IG) administration of a nutrient mixture infused at twice the postabsorptive, resting energy expenditure (REE). REE rose significantly from 0.98 +/- 0.02 to 1.13 +/- 0.03 kcal/min (IV) and from 0.99 +/- 0.02 to 1.13 +/- 0.02 kcal/min (IG) in the lean group; from 1.10 +/- 0.02 to 1.27 +/- 0.03 kcal/min (IV) and from 1.11 +/- 0.02 to 1.29 +/- 0.03 (IG) in the obese group. These increases resulted in similar nutrient-induced thermogenesis of 10.0 +/- 0.7% (IV) and 9.3 +/- 0.9% (IG) in the lean group; of 9.2 +/- 0.7% (IV) and 10.1 +/- 0.8% (IG) in the obese. Nutrient utilization was comparable in both groups and in both routes of administration, although the response time to IG feeding was delayed. These results showed no significant difference in both the thermogenic response and nutrient utilization between moderately obese and control groups using acute IV or IG feeding.

Evidence-based Economic Policy - Three Essays in Applied Microeconometrics

Over thirty years ago, Leamer (1983) - among many others - expressed doubts about the quality and usefulness of empirical analyses for the economic profession by stating that "hardly anyone takes data analyses seriously. Or perhaps more accurately, hardly anyone takes anyone else's data analyses seriously" (p.37). Improvements in data quality, more robust estimation methods and the evolution of better research designs seem to make that assertion no longer justifiable (see Angrist and Pischke (2010) for a recent response to Leamer's essay). The economic profes- sion and policy makers alike often rely on empirical evidence as a means to investigate policy relevant questions. The approach of using scientifically rigorous and systematic evidence to identify policies and programs that are capable of improving policy-relevant outcomes is known under the increasingly popular notion of evidence-based policy. Evidence-based economic policy often relies on randomized or quasi-natural experiments in order to identify causal effects of policies. These can require relatively strong assumptions or raise concerns of external validity. In the context of this thesis, potential concerns are for example endogeneity of policy reforms with respect to the business cycle in the first chapter, the trade-off between precision and bias in the regression-discontinuity setting in chapter 2 or non-representativeness of the sample due to self-selection in chapter 3. While the identification strategies are very useful to gain insights into the causal effects of specific policy questions, transforming the evidence into concrete policy conclusions can be challenging. Policy develop- ment should therefore rely on the systematic evidence of a whole body of research on a specific policy question rather than on a single analysis. In this sense, this thesis cannot and should not be viewed as a comprehensive analysis of specific policy issues but rather as a first step towards a better understanding of certain aspects of a policy question. The thesis applies new and innovative identification strategies to policy-relevant and topical questions in the fields of labor economics and behavioral environmental economics. Each chapter relies on a different identification strategy. In the first chapter, we employ a difference- in-differences approach to exploit the quasi-experimental change in the entitlement of the max- imum unemployment benefit duration to identify the medium-run effects of reduced benefit durations on post-unemployment outcomes. Shortening benefit duration carries a double- dividend: It generates fiscal benefits without deteriorating the quality of job-matches. On the contrary, shortened benefit durations improve medium-run earnings and employment possibly through containing the negative effects of skill depreciation or stigmatization. While the first chapter provides only indirect evidence on the underlying behavioral channels, in the second chapter I develop a novel approach that allows to learn about the relative impor- tance of the two key margins of job search - reservation wage choice and search effort. In the framework of a standard non-stationary job search model, I show how the exit rate from un- employment can be decomposed in a way that is informative on reservation wage movements over the unemployment spell. The empirical analysis relies on a sharp discontinuity in unem- ployment benefit entitlement, which can be exploited in a regression-discontinuity approach to identify the effects of extended benefit durations on unemployment and survivor functions. I find evidence that calls for an important role of reservation wage choices for job search be- havior. This can have direct implications for the optimal design of unemployment insurance policies. The third chapter - while thematically detached from the other chapters - addresses one of the major policy challenges of the 21st century: climate change and resource consumption. Many governments have recently put energy efficiency on top of their agendas. While pricing instru- ments aimed at regulating the energy demand have often been found to be short-lived and difficult to enforce politically, the focus of energy conservation programs has shifted towards behavioral approaches - such as provision of information or social norm feedback. The third chapter describes a randomized controlled field experiment in which we discuss the effective- ness of different types of feedback on residential electricity consumption. We find that detailed and real-time feedback caused persistent electricity reductions on the order of 3 to 5 % of daily electricity consumption. Also social norm information can generate substantial electricity sav- ings when designed appropriately. The findings suggest that behavioral approaches constitute effective and relatively cheap way of improving residential energy-efficiency.

Energy requirements during reproduction and reproductive effort in shrews (Soricidae)

The energy requirements of reproducing and non-reproducing females of three species of Crocidura (C. russula, C. viaria, C. olivieri), and two species of Sorex (S. coronatus, S. minutus) were measured. Members of these two genera show different rates of metabolism and reproductive strategies (extreme altriciality and larger litter size in Sorex). During pregnancy, the daily energy intake (on either an absolute or a mass-specific basis) remained close to the non-reproductive value in all species. The absolute energy intake increased strongly after parturition and was influenced by the litter size. Peak energy intake of lactating females was extremely high, typically between 100% and 200% above the non-reproductive requirements in the Crocidura and about 300% above the non-reproductive intake in the Sorex. The mass-specific daily energy intake was reduced during lactation in the three smaller species but not in C. viaria and C. olivieri. This decrease probably involves the different thermoregulatory abilities and/or basal rate of metabolism of the pups. Average reproductive effort was about 50%, in the Crocidura species and above 150% in the Sorex species. The higher effort in the latter is partly due to a larger litter size. But in addition, extreme altriciality in the Sorex leads to an earlier increase in the energy requirements and thus is an energetically more expensive reproductive mode. The present results support the hypothesis that a higher basal rate of metabolism is associated with a higher reproductive effort in shrews.

Adipose tissue integrity as a prerequisite for systemic energy balance: a critical role for peroxisome proliferator-activated receptor gamma.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is an essential regulator of adipocyte differentiation, maintenance, and survival. Deregulations of its functions are associated with metabolic diseases. We show here that deletion of one PPARgamma allele not only affected lipid storage but, more surprisingly, also the expression of genes involved in glucose uptake and utilization, the pentose phosphate pathway, fatty acid synthesis, lipolysis, and glycerol export as well as in IR/IGF-1 signaling. These deregulations led to reduced circulating adiponectin levels and an energy crisis in the WAT, reflected in a decrease to nearly half of its intracellular ATP content. In addition, there was a decrease in the metabolic rate and physical activity of the PPARgamma(+/-) mice, which was abolished by thiazolidinedione treatment, thereby linking regulation of the metabolic rate and physical activity to PPARgamma. It is likely that the PPARgamma(+/-) phenotype was due to the observed WAT dysfunction, since the gene expression profiles associated with metabolic pathways were not affected either in the liver or the skeletal muscle. These findings highlight novel roles of PPARgamma in the adipose tissue and underscore the multifaceted action of this receptor in the functional fine tuning of a tissue that is crucial for maintaining the organism in good health.

Society, politcs and nuclear energy in Switzerland

After the Fukushima accident, the Swiss Federal Council opted for withdrawal from nuclear energy in the horizon 2035. Considering that this decision cannot be studied in historical isolation, this article describes the evolution of the relationship between nuclear energy and the Swiss society by highlighting four distinctive periods: the social mobilisation of the seventies and eighties, the turning point of the nineties, the nuclear revival in the late 2000s and the Fukushima accident. To describe this relationship, we will analyse social mobilisation and the results of initiatives and empirical studies related to nuclear energy in Switzerland.

Opinions on tobacco control policies in Lausanne, Switzerland, 2003-2006.

OBJECTIVE: To assess the determinants of opinions regarding tobacco control policies in the Swiss general population. METHODS: Cross-sectional study conducted between 2003 and 2006 on a random sample of adult residents of Lausanne, Switzerland, aged 35-75 years (2601 women and 2398 men). Nine questions on smoking policies were applied. RESULTS: Ninety-five percent of responders supported policies that would help smokers to quit, 92% no selling of tobacco to subjects aged less than 16 years, 87% a smoking ban in public places and 86% a national campaign against smoking. A further 77% supported a total ban on tobacco advertising, 74% the reimbursement of nicotine replacement therapies and 70% an increase in the price of cigarettes. A lower support was found for two non-evidence-based interventions total ban of tobacco sales (35%) and promotion of light cigarettes (22%). Never smokers, women, physically active subjects, teetotallers and subjects with lower educational level were more likely to favour stronger measures while no differences were found between age groups. Reimbursement of nicotine replacement therapies was favoured more by current smokers and inactive subjects. CONCLUSION: The vast majority of responders supported the recommended tobacco control policies. Opinions regarding specific interventions vary according to the policy and subjects' characteristics.

Sex differences in obesity and the regulation of energy homeostasis.

Obesity prevalence is generally higher in women than in men, and there is also a sex difference in body fat distribution. Sex differences in obesity can be explained in part by the influence of gonadal steroids on body composition and appetite; however, behavioural, socio-cultural and chromosomal factors may also play a role. This review, which evolved from the 2008 Stock Conference on sex differences in obesity, summarizes current research and recommendations related to hormonal and neuroendocrine influences on energy balance and fat distribution. A number of important gaps in the research are identified, including a need for more studies on chromosomal sex effects on energy balance, the role of socio-cultural (i.e. gender) factors in obesity and the potential deleterious effects of high-fat diets during pregnancy on the foetus. Furthermore, there is a paucity of clinical trials examining sex-specific approaches and outcomes of obesity treatment (lifestyle-based or pharmacological), and research is urgently needed to determine whether current weight loss programmes, largely developed and tested on women, are appropriate for men. Last, it is important that both animal and clinical research on obesity be designed and analysed in such a way that data can be separately examined in both men and women.

Dietary obesity-associated Hif1α activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system.

Dietary obesity is a major factor in the development of type 2 diabetes and is associated with intra-adipose tissue hypoxia and activation of hypoxia-inducible factor 1α (HIF1α). Here we report that, in mice, Hif1α activation in visceral white adipocytes is critical to maintain dietary obesity and associated pathologies, including glucose intolerance, insulin resistance, and cardiomyopathy. This function of Hif1α is linked to its capacity to suppress β-oxidation, in part, through transcriptional repression of sirtuin 2 (Sirt2) NAD(+)-dependent deacetylase. Reduced Sirt2 function directly translates into diminished deacetylation of PPARγ coactivator 1α (Pgc1α) and expression of β-oxidation and mitochondrial genes. Importantly, visceral adipose tissue from human obese subjects is characterized by high levels of HIF1α and low levels of SIRT2. Thus, by negatively regulating the Sirt2-Pgc1α regulatory axis, Hif1α negates adipocyte-intrinsic pathways of fatty acid catabolism, thereby creating a metabolic state supporting the development of obesity.

Continuous versus single bolus enteral nutrition: comparison of energy metabolism in humans.

Continuous respiratory exchange measurements were performed on five women and five men for 1 h before and 6 h after the administration of a milkshake (53% carbohydrates, 30% lipid, and 17% protein energy) given either as a single bolus dose or continuously during 3 h using a nasogastric tube. The energy administered corresponded to 2.3 times the postabsorptive resting energy expenditure. Resting energy expenditure, respiratory quotient, plasma glucose, and insulin concentrations increased sooner and steeper, and plasma free fatty acids levels decreased earlier with the meal ingested as a single dose than with continuous administration. The magnitude of nutrient-induced thermogenesis was greater (P less than 0.01) with the single dose (means +/- SE, 10.0 +/- 0.6%) than with the continuous administration (8.1 +/- 0.5%). The overall (6 h) substrate balances were not significantly different between the two modes of administration. It is concluded that the mode of enteral nutrient administration influences the immediate thermogenic response as well as changes in respiratory quotient, glycemia, and insulinemia; however, the overall nutrient balance was not affected by the mode of enteral nutrient administration.

Effect of obesity onset on pendular energy transduction at spontaneous walking speed: Prader-Willi versus nonsyndromal obese individuals.

OBJECTIVE: To compare the mechanical external work (Wext ) and pendular energy transduction (Rstep ) at spontaneous walking speed (Ss ) in individuals with Prader-Willi syndrome (PWS) versus subjects with nonsyndromal obesity (OB) to investigate whether the early onset of obesity allows PWS subjects to adopt energy conserving gait mechanics. DESIGN AND METHODS: Wext and Rstep were computed using kinematic data acquired by an optoelectronic system and compared in 15 PWS (BMI = 39.5 ± 1.8 kg m(-2) ; 26.7 ± 1.5 year) and 15 OB (BMI = 39.3 ± 1.0 kg m(-2) ; 28.7 ± 1.9 year) adults matched for gender, age and BMI and walking at Ss . RESULTS: Ss was significantly lower in PWS (0.98 ± 0.03 m s(-1) ) than in OB (1.20 ± 0.02 m s(-1) ; P < 0.001). There were no significant differences in Wext per kilogram between groups (PWS: 0.37 ± 0.04 J kg(-1) m(-1) ; OB: 0.40 ± 0.05 J kg(-1) m(-1) ; P = 0.66) and in Rstep (PWS: 69.9 ± 2.9%; OB: 67.7 ± 2.4%; P = 0.56). However, Rstep normalized to Froude number (Rstep /Fr) was significantly greater in PWS (6.0 ± 0.6) than in OB (3.8 ± 0.2; P = 0.001). Moreover, Rstep /Fr was inversely correlated with age of obesity onset (r = -0.49; P = 0.006) and positively correlated with obesity duration (r = 0.38; P = 0.036). CONCLUSION: Individuals with PWS seem to alter their gait to improve pendular energy transduction as a result of precocious and chronic adaptation to loading.