Meal-induced thermogenesis in lean and obese prepubertal children.

The resting metabolic rate (RMR) and the thermic effect of a meal (TEM) were measured in a group of 16 prepubertal (8.8 +/- 0.3 y) obese children (43.6 +/- 9.2 kg) and compared with a group of 10 age-matched (8.6 +/- 0.4 y), normal-weight children (31.0 +/- 6.0 kg). The RMR was higher in the obese than in the control children (4971 +/- 485 vs 4519 +/- 326 kJ/d, P < 0.05); after the RMR was adjusted for the effect of fat-free mass (FFM) the values were not significantly different (4887 +/- 389 vs 4686 +/- 389 kJ/d). The thermic response to a liquid mixed meal, expressed as a percentage of the energy content of the meal, was significantly lower in obese than in control children (4.4 +/- 1.2% vs 5.9 +/- 1.7%, P < 0.05). The blunted TEM shown by the obese children could favor weight gain and suggests that the defect in thermogenesis reported in certain obese adults may have already originated early in life.

Changes in insulin secretion and glucose metabolism induced by dexamethasone in lean and obese females

Résumé But: Chez les individus sveltes et en bonne santé, les modifications de la sensibilité à l'insuline secondaires à l'administration de dexaméthasone pendant deux jours sont compensées par une modification de la sécrétion d'insuline, permettant le maintien de l'homéostasie glucidique. Cette étude évalue les modifications du métabolisme glucidique et de la sécrétion d'insuline induites par une administration limitée de dexaméthasone chez les femmes obèses. Méthode de recherche: Onze femmes obèses ayant une tolérance au glucose normale ont été étudiées à deux reprises, 1° sans dexaméthasone et 2° après deux jours d'administration de dexaméthasone à faible dose. Un clamp hyperglycémique comportant deux plateaux (taux plasmatique de glucose à 7.5, respectivement 10 mM) avec du glucose marqué (6.6 ²H2 glc) a été utilisé pour déterminer la sécrétion d'insuline et le métabolisme du glucose du corps entier. Les résultats ont été comparés à ceux d'un groupe de huit femmes sveltes. Résultats : Sans dexaméthasone, les femmes obèses avaient un taux d'insuline plasmatique supérieur à jeun, durant le premier pic de sécrétion d'insuline, et aux deux plateaux hyperglycémiques. Elles avaient toutefois un métabolisme glucidique normal comparé à celui des femmes sveltes, ce qui indique une compensation adéquate. Après administration de la dexaméthasone, les femmes obèses avaient une augmentation du taux d'insuline plasmatique de 66 à 92%, mais une baisse de stockage du glucose de 15.4%. Ceci contrastait avec l'augmentation du taux d'insuline plasmatique de 91 à 113% chez les femmes sveltes et l'absence de changement de stockage du glucose du corps entier. Discussion : L'administration de dexaméthasone conduit à une baisse significative du stockage du glucose du corps entier pour une glycémie fixée chez les femmes obèses mais non chez les femmes sveltes. Ceci indique que les femmes obèses sont incapables d'accroître adéquatement leur sécrétion d'insuline. Abstract: Objective: In healthy lean individuals, changes in insulin sensitivity occurring as a consequence of a 2-day dexamethasone administration are compensated for by changes in insulin secretion, allowing glucose homeostasis to be maintained. This study evaluated the changes in glucose metabolism and insulin secretion induced by short-term dexamethasone administration in obese women. Research Methods and Procedures: Eleven obese women with normal glucose tolerance were studied on two occasions, without and after 2 days of low-dose dexamethasone administration. A two-step hyperglycemic clamp (7.5 and 10 mr1/1 glucose) with 6,6 2H2 glucose was used to assess insulin secretion and whole body glucose metabolism. Results were compared with those obtained in a group of eight lean women. Results: Without dexamethasone, obese women had higher plasma insulin concentrations in the fasting state, during the first phase of insulin secretion, and at the two hyperglycemic plateaus. However, they had normal whole body glucose metabolism compared with lean women, indicating adequate compensation. After dexamethasone, obese women had a 66% to 92% increase in plasma insulin concentrations but a 15.4% decrease in whole body glucose disposal. This contrasted with lean women, who had a 91% to 113% increase in plasma insulin concentrations, with no change in whole body glucose disposal. Discussion: Dexamethasone administration led to a significant reduction in whole body glucose disposal at fixed glycemia in obese but not lean women. This indicates that obese women are unable to increase their insulin secretion appropriately.

Effects of mental stress on insulin-mediated glucose metabolism and energy expenditure in lean and obese women.

The effects of the sympathetic activation elicited by a mental stress on insulin sensitivity and energy expenditure (VO(2)) were studied in 11 lean and 8 obese women during a hyperinsulinemic-euglycemic clamp. Six lean women were restudied under nonselective beta-adrenergic blockade with propranolol to determine the role of beta-adrenoceptors in the metabolic response to mental stress. In lean women, mental stress increased VO(2) by 20%, whole body glucose utilization ([6,6-(2)H(2)]glucose) by 34%, and cardiac index (thoracic bioimpedance) by 25%, whereas systemic vascular resistance decreased by 24%. In obese women, mental stress increased energy expenditure as in lean subjects, but it neither stimulated glucose uptake nor decreased systemic vascular resistance. In the six lean women who were restudied under propranolol, the rise in VO(2), glucose uptake, and cardiac output and the decrease in systemic vascular resistance during mental stress were all abolished. It is concluded that 1) in lean subjects, mental stress stimulates glucose uptake and energy expenditure and produces vasodilation; activation of beta-adrenoceptors is involved in these responses; and 2) in obese patients, the effects of mental stress on glucose uptake and systemic vascular resistance, but not on energy expenditure, are blunted.

Wave-height hazard analysis in Eastern Coast of Spain : Bayesian approach using generalized Pareto distribution

Standard practice of wave-height hazard analysis often pays little attention to the uncertainty of assessed return periods and occurrence probabilities. This fact favors the opinion that, when large events happen, the hazard assessment should change accordingly. However, uncertainty of the hazard estimates is normally able to hide the effect of those large events. This is illustrated using data from the Mediterranean coast of Spain, where the last years have been extremely disastrous. Thus, it is possible to compare the hazard assessment based on data previous to those years with the analysis including them. With our approach, no significant change is detected when the statistical uncertainty is taken into account. The hazard analysis is carried out with a standard model. Time-occurrence of events is assumed Poisson distributed. The wave-height of each event is modelled as a random variable which upper tail follows a Generalized Pareto Distribution (GPD). Moreover, wave-heights are assumed independent from event to event and also independent of their occurrence in time. A threshold for excesses is assessed empirically. The other three parameters (Poisson rate, shape and scale parameters of GPD) are jointly estimated using Bayes' theorem. Prior distribution accounts for physical features of ocean waves in the Mediterranean sea and experience with these phenomena. Posterior distribution of the parameters allows to obtain posterior distributions of other derived parameters like occurrence probabilities and return periods. Predictives are also available. Computations are carried out using the program BGPE v2.0

Comparison of aortic elasticity determined by cardiovascular magnetic resonance imaging in obese versus lean adults.

The vascular properties of large vessels in the obese have not been adequately studied. We used cardiovascular magnetic resonance imaging to quantify the cross-sectional area and elastic properties of the ascending thoracic and abdominal aorta in 21 clinically healthy obese young adult men and 25 men who were age-matched lean controls. Obese subjects had greater maximal cross-sectional area of the ascending thoracic aorta (984 +/- 252 vs 786 +/- 109 mm(2), p <0.01) and of the abdominal aorta (415 +/- 71 vs 374 +/- 51 mm(2), p <0.05). When indexed for height the differences persisted, but when indexed for body surface area, a significant difference between groups was found only for the maximal abdominal aortic cross-sectional area. The obese subjects also had decreased abdominal aortic elasticity, characterized by 24% lower compliance (0.0017 +/- 0.0004 vs 0.0021 +/- 0.0005 mm(2)/kPa/mm, p <0.01), 22% higher stiffness index beta (6.0 +/- 1.5 vs 4.9 +/- 0.7, p <0.005), and 41% greater pressure-strain elastic modulus (72 +/- 25 vs 51 +/- 9, p <0.005). At the ascending thoracic aorta, only the pressure-strain elastic modulus was different between obese and lean subjects (85 +/- 42 vs 65 +/- 26 kPa, respectively; p <0.05), corresponding to a 31% difference-but arterial compliance and stiffness index were not significantly different between groups. In clinically healthy young adult obese men, obesity is associated with increased cross-sectional aortic area and decreased aortic elasticity.

Work Organization Practices for Lean Production: A Study in Spanish and Brazilian Manufacturers

This work aims to discuss particular work organization practices in human resources reported as successful by companies adopting lean production principles, and investigate them through real examples observed on manufacturing plants in Spain and Brazil. A set of work organization practices was previously established by one of the authors, through interviews with practitioners of lean production and review of the literature. A series of visits and informal interviews at Spanish and Brazilian automotive parts manufacturers that follow lean production were conducted to verify that the set of policies are indeed practiced.

Beta-adrenergic blockade and intravenous nutrient-induced thermogenesis in lean and obese women.

Continuous respiratory exchange measurements were performed in nine obese and eight lean women for 1 h before, 3 h during, and 1 h after the intravenous administration of a nutrient mixture infused at twice the postabsorptive resting energy expenditure (REE). This experiment was conducted without or with beta-adrenergic blockade (iv propranolol). Propranolol administration did not change the postabsorptive REE [i.e., 1.03 +/- 0.07 before vs. 1.01 +/- 0.02 kcal/min after administration in lean women and 1.16 +/- 0.04 vs. 1.15 +/- 0.03 kcal/min (NS) in obese women]. The mean overall thermogenic response expressed as a percentage of the infused energy was similar in both groups and was not significantly blunted after propranolol infusion [6.9 +/- 0.4 vs. 5.9 +/- 0.6% in the lean women and 7.5 +/- 0.5 vs. 7.1 +/- 0.6% (NS) in the obese women]. During beta-adrenergic blockade the rate of lipid oxidation decreased in the lean group but was unchanged in the obese group and the glycemic response to nutrient administration was significantly higher in both groups than without propranolol. It is concluded that beta-adrenergic blockade has no effect on REE and on intravenous nutrient-induced thermogenesis in both lean and obese women.

Caracterización de la organización del trabajo bajo los principios del lean production: una propuesta de indicadores referidos a los trabajadores de planta.

La metodología lean production tiene una extensión creciente en todo el mundo. Las principalesobras sobre la metodología no definen en detalle las prácticas de organización del trabajo propia.Los objetivos finales del método se pueden resumir en conseguir la producción en flujo y en lamejora continua. Ambos fines necesitan una organización del trabajo apropiada. Se deducen de laliteratura siete principios que habrá de cumplir: estandarización y control, la formación, laparticipación y el empowermen, el trabajo en equipo, la polivalencia y la adaptabilidad, laimplicación con los valores de la empresa y remuneración y promociones que apoyen laimplantación del lean producción. Estos principios de concretan en políticas y prácticas que hande definir la concreción de esos principios. Finalmente, las políticas y prácticas se relacionan conindicadores. Ello ha de permitir valorar las características y el nivel de una determinadaimplantación del lean production. Se proponen posteriores investigaciones que han de suponer elanálisis de una o más factorías lean con el uso de los indicadores obtenidos.

Virtaviivainen LEAN-liiketoiminta

Työn tarkoituksena oli löytää ratkaisu omasta kokemuksesta nousseeseen tarpeeseen, kuinka LEAN-toimintaa tulisi ylläpitää ja organisoida yrityksessä. Samalla halusin ymmärtää, kuinka paljon suomalaisissa yrityksissä LEAN-toiminnasta ja sen johtamisesta tiedetään. Ensiksi kävin lävitse LEAN-teoriaa ja hukkia. Menetelmiä olen käsitellyt lähinnä siitä näkökulmasta, mitä niistä Abloy Oy:ssä voisi parhaiten käyttää yrityksen virtaviivaistamiseen. Työn empiirisessä osassa selvitetään haastattelututkimuksella ongelmakenttään liittyviä kysymyksiä. Merkittäväksi havainnoksi nousi se, että haastateltavat eivät nähneet LEAN-toimintaa erityisen hyvin johdetuksi alueeksi suomalaisissa yrityksissä. Haastatellut olivat sen sijaan melko yksimielisiä siitä, kuinka LEAN-toiminta tulisi organisoida yrityksessä, ja että sen tulisi raportoida korkealle yrityksen hierarkiassa. Tämän työn tulokset auttavat yrityksen LEAN-johtamistyötä. Selkeästi käy ilmi, että LEAN-johtajakoulutusta pitäisi organisoida. Abloy Oy:n johto on tullut tietoiseksi LEAN-toiminnan mahdollisuuksista ja merkityksestä monin tavoin. Ei riitä, että LEAN-työskentelyvain aloitetaan, se täytyy myös organisoida. Yrityksen korkeimman johdon on sitouduttava virtaviivaistamistyöhön. Tässä työssä annetut suositukset organisaation peruspiirteistä voivat edesauttaa yritysjohtoa LEAN-työskentelyn aloittamisessa.

Sankatuotannonkehittäminen Lean-menetelmin

Tämän diplomityön tavoitteena on selvittää kirjallisuuden avulla, mitä on lean-tuotanto ja implementoida lean-tuotantoon liittyviä tuotannon kehitysmenetelmiä. Työn aikana suunniteltiin lean-menetelmien avulla tuotantoa kehittäviä toimenpiteitä ja implementoitiin muutamia näistä. Näitä muutosten aiheuttamia seurauksia arvioitiin ja seurattiin. Lisäksi muutosten implementointia varten koulutettiin operaattoreita. Pääpaino on lean-menetelmiin tutustumisessa, pullonkaulan purkamisessa, pullonkaulakoneen asetuksen lyhentämisessä ja näiden vaikutusten tarkastelussa arvovirtakuvauksen ja asiakaskysynnän tahtiaikaan perustuen.

Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and pareto filters

Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the ethanol production in the fermentation of Saccharomyces cerevisiae.

Using Pareto optimality to explore the topology and dynamics of the human connectome.

Graph theory has provided a key mathematical framework to analyse the architecture of human brain networks. This architecture embodies an inherently complex relationship between connection topology, the spatial arrangement of network elements, and the resulting network cost and functional performance. An exploration of these interacting factors and driving forces may reveal salient network features that are critically important for shaping and constraining the brain's topological organization and its evolvability. Several studies have pointed to an economic balance between network cost and network efficiency with networks organized in an 'economical' small-world favouring high communication efficiency at a low wiring cost. In this study, we define and explore a network morphospace in order to characterize different aspects of communication efficiency in human brain networks. Using a multi-objective evolutionary approach that approximates a Pareto-optimal set within the morphospace, we investigate the capacity of anatomical brain networks to evolve towards topologies that exhibit optimal information processing features while preserving network cost. This approach allows us to investigate network topologies that emerge under specific selection pressures, thus providing some insight into the selectional forces that may have shaped the network architecture of existing human brains.