Assessment of free-living physical activity in humans: an overview of currently available and proposed new measures.

The number of physical activity measures and indexes used in the human literature is large and may result in some difficulty for the average investigator to choose the most appropriate measure. Accordingly, this review is intended to provide information on the utility and limitations of the various measures. Its primary focus is the objective assessment of free-living physical activity in humans based on physiological and biomechanical methods. The physical activity measures have been classified into three categories: Measures based on energy expenditure or oxygen uptake, such as activity energy expenditure, activity-related time equivalent, physical activity level, physical activity ratio, metabolic equivalent, and a new index of potential interest, daytime physical activity level. Measures based on heart rate monitoring, such as net heart rate, physical activity ratio heart rate, physical activity level heart rate, activity-related time equivalent, and daytime physical activity level heart rate. Measures based on whole-body accelerometry (counts/U time). Quantification of the velocity and duration of displacement in outdoor conditions by satellites using the Differential Global Positioning System may constitute a surrogate for physical activity, because walking is the primary activity of man in free-living conditions. A general outline of the measures and indexes described above is presented in tabular form, along with their respective definition, usual applications, advantages, and shortcomings. A practical example is given with typical values in obese and non-obese subjects. The various factors to be considered in the selection of physical activity methods include experimental goals, sample size, budget, cultural and social/environmental factors, physical burden for the subject, and statistical factors, such as accuracy and precision. It is concluded that no single current technique is able to quantify all aspects of physical activity under free-living conditions, requiring the use of complementary methods. In the future, physical activity sensors, which are of low-cost, small-sized, and convenient for subjects, investigators, and clinicians, are needed to reliably monitor, during extended periods in free-living situations, small changes in movements and grade as well as duration and intensity of typical physical activities.

Effect of low-level pathogenic helminth infection on energy metabolism in Gambian children.

The aim of the present study was to determine whether an increase in resting energy expenditure (REE) contributes to the impaired nutritional status of Gambian children infected by a low level of infection with pathogenic helminths. The REE of 24 children infected with hookworm, Ascaris, Strongyloides, or Trichuris (mean +/- SEM age = 11.9 +/- 0.1 years) and eight controls without infection (mean +/- SEM age = 11.8 +/- 0.1 years) were measured by indirect calorimetry with a hood system (test A). This measurement was repeated after treatment with 400 mg of albendazole (patients) or a placebo (controls) (test B). When normalized for fat free mass, REE in test A was not different in the patients (177 +/- 2 kJ/kg x day) and in the controls (164 +/- 7 kJ/kg x day); furthermore, REE did not change significantly after treatment in the patients (173 +/- 3 kJ/kg x day) or in the controls (160 +/- 8 kJ/kg x day). There was no significant difference in the respiratory quotient between patients and controls, nor between tests A and B. It is concluded that a low level of helminth infection does not affect significantly the energy metabolism of Gambian children.

Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.

PURPOSE: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. RESULTS: In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. CONCLUSION: Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.

Effects of L-carnitine supplemented total parenteral nutrition on lipid and energy metabolism in postoperative stress.

During episodes of trauma carnitine-free total parenteral nutrition (TPN) may result in a reduction of the total body carnitine pool, leading to a diminished rate of fat oxidation. Sixteen patients undergoing esophagectomy were divided randomly in two equal isonitrogenous groups (0.2 g/kg.day). Both received TPN (35 kcal/kg.day; equally provided as long-chain triglycerides and glucose) over 11 days without (group A) and with (group B) L-carnitine supplementation (12 mg/kg.day = 75 mumol/kg.day). Compared with healthy controls, the total body carnitine pool prior to the operation was significantly reduced in both groups, suggesting a state of semistarvation and muscle wasting. In group A the plasma levels of total carnitine and its subfractions (free carnitine, short- and long-chain acylcarnitine) remained stable during the study whereas in group B the total plasma carnitine concentration rose mainly due to an increase in free carnitine. In group A the cumulative urinary carnitine losses were 11.5 +/- 2.6 mmol (= 15.5 +/- 3.1% of the estimated total body carnitine pool). In group B 3.1 +/- 1.9 mmol (= 11.1 +/- 7.6%) of the infused carnitine was retained in the immediate postoperative phase until day 6, but this amount was completely lost at completion of the study period. No significant differences in the respiratory quotient or in the plasma levels of triglycerides, free fatty acids, and ketone bodies were observed, between or within the groups, before the operation and after 11 days of treatment. It is concluded that the usefulness of carnitine supplementation during postoperative TPN was not apparent in the present patient material.

Fat-free mass index and fat mass index percentiles in Caucasians aged 18-98 y.

OBJECTIVE: To determine reference values for fat-free mass index (FFMI) and fat mass index (FMI) in a large Caucasian group of apparently healthy subjects, as a function of age and gender and to develop percentile distribution for these two parameters. DESIGN: Cross-sectional study in which bioelectrical impedance analysis (50 kHz) was measured (using tetrapolar electrodes and cross-validated formulae by dual-energy X-ray absorptiometry in order to calculate FFMI (fat-free mass/height squared) and FMI (fat mass/height squared). SUBJECTS: A total of 5635 apparently healthy adults from a mixed non-randomly selected Caucasian population in Switzerland (2986 men and 2649 women), varying in age from 24 to 98 y. RESULTS: The median FFMI (18-34 y) were 18.9 kg/m(2) in young males and 15.4 kg/m(2) in young females. No difference with age in males and a modest increase in females were observed. The median FMI was 4.0 kg/m(2) in males and 5.5 kg/m(2) in females. From young to elderly age categories, FMI progressively rose by an average of 55% in males and 62% in females, compared to an increase in body mass index (BMI) of 9 and 19% respectively. CONCLUSIONS: Reference intervals for FFMI and FMI could be of practical value for the clinical evaluation of a deficit in fat-free mass with or without excess fat mass (sarcopenic obesity) for a given age category, complementing the classical concept of body mass index (BMI) in a more qualitative manner. In contrast to BMI, similar reference ranges seems to be utilizable for FFMI with advancing age, in particular in men.

Assessment of Physical Activity and Energy Expenditure by GPS Combined With Accelerometry in Real-Life Conditions.

Background: Physical activity (PA) and related energy expenditure (EE) is often assessed by means of a single technique. Because of inherent limitations, single techniques may not allow for an accurate assessment both PA and related EE. The aim of this study was to develop a model to accurately assess common PA types and durations and thus EE in free-living conditions, combining data from global positioning system (GPS) and 2 accelerometers. Methods: Forty-one volunteers participated in the study. First, a model was developed and adjusted to measured EE with a first group of subjects (Protocol I, n = 12) who performed 6 structured and supervised PA. Then, the model was validated over 2 experimental phases with 2 groups (n = 12 and n = 17) performing scheduled (Protocol I) and spontaneous common activities in real-life condition (Protocol II). Predicted EE was compared with actual EE as measured by portable indirect calorimetry. Results: In protocol I, performed PA types could be recognized with little error. The duration of each PA type could be predicted with an accuracy below 1 minute. Measured and predicted EE were strongly associated (r = .97, P < .001). Conclusion: Combining GPS and 2 accelerometers allows for an accurate assessment of PA and EE in free-living situations.

Inferring ultraviolet anatomical exposure patterns while distinguishing the relative contribution of radiation components

Exposure to solar ultraviolet (UV) radiation is the main causative factor for skin cancer. UV exposure depends on environmental and individual factors, but individual exposure data remain scarce. While ground UV irradiance is monitored via different techniques, it is difficult to translate such observations into human UV exposure or dose because of confounding factors. A multi-disciplinary collaboration developed a model predicting the dose and distribution of UV exposure on the basis of ground irradiation and morphological data. Standard 3D computer graphics techniques were adapted to develop a simulation tool that estimates solar exposure of a virtual manikin depicted as a triangle mesh surface. The amount of solar energy received by various body locations is computed for direct, diffuse and reflected radiation separately. Dosimetric measurements obtained in field conditions were used to assess the model performance. The model predicted exposure to solar UV adequately with a symmetric mean absolute percentage error of 13% and half of the predictions within 17% range of the measurements. Using this tool, solar UV exposure patterns were investigated with respect to the relative contribution of the direct, diffuse and reflected radiation. Exposure doses for various body parts and exposure scenarios of a standing individual were assessed using erythemally-weighted UV ground irradiance data measured in 2009 at Payerne, Switzerland as input. For most anatomical sites, mean daily doses were high (typically 6.2-14.6 Standard Erythemal Dose, SED) and exceeded recommended exposure values. Direct exposure was important during specific periods (e. g. midday during summer), but contributed moderately to the annual dose, ranging from 15 to 24% for vertical and horizontal body parts, respectively. Diffuse irradiation explained about 80% of the cumulative annual exposure dose.

Energy expenditure during walking and running in obese and nonobese prepubertal children.

We measured body composition and energy expenditure during walking and running on a treadmill in 40 prepubertal children: 23 obese children (9.3 +/- 1.1 years of age; 46 +/- 10 kg (mean +/- SD)) and 17 nonobese matched control children (9.2 +/- 0.6 years of age; 30 +/- 5 kg). Energy expenditure was assessed by indirect calorimetry with a standard open-circuit method. At the same speed of exercise, the energy expenditure was significantly (p < 0.01) greater in obese than in control children, in both boys and girls. Expressed per kilogram of body weight or per kilogram of fat-free mass, the energy expenditure was comparable in the two groups. Obese children had a significantly (p < 0.01) larger pulmonary ventilatory response to exercise than did control children. Heart rate was comparable in boys and girls combined but significantly higher (p < 0.05) in obese subjects, if boys and girls were analyzed separately. These data indicate that walking and running are energetically more expensive for obese children than for children of normal body weight. The knowledge of these energy costs could be useful in devising a physical activity program to be used in the treatment of obese children.

Energy expenditure before and during energy restriction in obese patients.

Twenty-four hour energy expenditure (24 EE), resting metabolic rate (RMR), spontaneous physical activity and body composition were determined in 7 obese patients (5 females, 2 males, 174 +/- 9% IBW, 38 +/- 2% fat mass) on 2 different occasions: before weight reduction, and after 10 to 16 weeks on a hypocaloric diet as outpatients, the recommended energy intake varying from 3500 to 4700 kJ/day depending on the subject. Mean body weight loss was 12.6 +/- 1.9 kg, ie 13% of initial body weight, 72% being fat. Twenty-four hour energy expenditure (24 EE) was measured in a respiration chamber with all the subjects receiving 10418 kJ/d before weight reduction and an average of 3360 +/- 205 kJ/d while on the diet. When expressed in absolute values, both 24 EE and RMR decreased during the hypocaloric diet from 9819 +/- 442 to 8229 +/- 444 and from 7262 +/- 583 to 6591 +/- 547 kJ/d respectively. On the basis of fat-free-mass (FFM), 24 EE decreased from 168 +/- 6 to 148 +/- 5 kJ/kg FFM/d whereas RMR was unchanged (approximately 120 kJ/kg FFM/d). Approximately one half of the 24 EE reduction (1590 kJ/d) was accounted for by a decrease in RMR, the latter being mainly accounted for by a reduction in FFM. Most of the remaining decline in 24 EE can be explained by a decreased thermic effect of food, and by the reduced cost of physical activity mainly due to a lower body weight. Therefore, there seems little reason to evoke additional mechanisms to explain the decline in energy expenditure during dieting.

A model for physical activity, bahaviour and energy expenditure assessment in real-life condition

RésuméL'origine de l'obésité, qui atteint des proportions épidémiques, est complexe. Elle est liée au mode de vie et au comportement des individus par rapport à l'activité physique, expression des choix individuels et de l'interaction avec l'environnement. Les mesures du comportement au niveau de l'activité physique des individus face à leur environnement, la répartition des types d'activité physique, la durée, la fréquence, l'intensité, et la dépense énergétique sont d'une grande importance. Aujourd'hui, il y a un manque de méthodes permettant une évaluation précise et objective de l'activité physique et du comportement des individus. Afin de compléter les recherches relatives à l'activité physique, à l'obésité et à certaines maladies, le premier objectif du travail de thèse était de développer un modèle pour l'identification objective des types d'activité physique dans des conditions de vie réelles et l'estimation de la dépense énergétique basée sur une combinaison de 2 accéléromètres et 1 GPS. Le modèle prend en compte qu'une activité donnée peut être accomplie de différentes façons dans la vie réelle. Les activités quotidiennes ont pu être classées en 8 catégories, de sédentaires à actives, avec une précision de 1 min. La dépense énergétique a pu peut être prédite avec précision par le modèle. Après validation du modèle, le comportement des individus de l'activité physique a été évalué dans une seconde étude. Nous avons émis l'hypothèse que, dans un environnement caractérisé par les pentes, les personnes obèses sont tentées d'éviter les pentes raides et de diminuer la vitesse de marche au cours d'une activité physique spontanée, ainsi que pendant les exercices prescrits et structurés. Nous avons donc caractérisé, par moyen du modèle développé, le comportement des individus obèses dans un environnement vallonné urbain. La façon dont on aborde un environnement valloné dans les déplacements quotidiens devrait également être considérée lors de la prescription de marche supplémentaire afin d'augmenter l'activité physique.SummaryOrigin of obesity, that reached epidemic proportion, is complex and may be linked to different lifestyle and physical activity behaviour. Measurement of physical activity behaviour of individuals towards their environment, the distribution of physical activity in terms of physical activity type, volume, duration, frequency, intensity, and energy expenditure is of great importance. Nowadays, there is a lack of methods for accurate and objective assessment of physical activity and of individuals' physical activity behaviour. In order to complement the research relating physical activity to obesity and related diseases, the first aim of the thesis work was to develop a model for objective identification of physical activity types in real-life condition and energy expenditure based on a combination of 2 accelerometers and 1 GPS device. The model takes into account that a given activity can be achieved in many different ways in real life condition. Daily activities could be classified in 8 categories, as sedentary to active physical activity, within 1 min accuracy, and physical activity patterns determined. The energy expenditure could be predicted accurately with an accuracy below 10%. Furthermore, individuals' physical activity behaviour is expression of individual choices and their interaction with the neighbourhood environment. In a second study, we hypothesized that, in an environment characterized by inclines, obese individuals are tempted to avoid steep positive slopes and to decrease walking speed during spontaneous outdoor physical activity, as well as during prescribed structured bouts of exercise. Finally, we characterized, by mean of the developed model, the physical activity behaviour of obese individuals in a hilly urban environment. Quantifying how one tackles hilly environment or avoids slope in their everyday displacements should be also considered while prescribing extra walking in free-living conditions in order to increase physical activity.

Characterization and simulation of a CdTe detector for use in PET

The Voxel Imaging PET (VIP) Path nder project got the 4 year European Research Council FP7 grant in 2010 to prove the feasibility of using CdTe detectors in a novel conceptual design of PET scanner. The work presented in this thesis is a part of the VIP project and consists of, on the one hand, the characterization of a CdTe detector in terms of energy resolution and coincidence time resolution and, on the other hand, the simulation of the setup with the single detector in order to extend the results to the full PET scanner. An energy resolution of 0.98% at 511 keV with a bias voltage of 1000 V/mm has been measured at low temperature T=-8 ºC. The coincidence time distribution of two twin detectors has been found to be as low as 6 ns FWHM for events with energies above 500 keV under the same temperature and bias conditions. The measured energy and time resolution values are compatible with similar ndings available in the literature and prove the excellent potential of CdTe for PET applications. This results have been presented in form of a poster contribution at the IEEE NSS/MIC & RTSD 2011 conference in October 2011 in Valencia and at the iWoRID 2012 conference in July 2012 in Coimbra, Portugal. They have been also submitted for publication to "Journal of Instrumentation (JINST)" in September 2012.

Two complementary molecular energy decomposition schemes: the Mayer and Ziegler-Rauk methods in comparison

In the present paper we discuss and compare two different energy decomposition schemes: Mayer's Hartree-Fock energy decomposition into diatomic and monoatomic contributions [Chem. Phys. Lett. 382, 265 (2003)], and the Ziegler-Rauk dissociation energy decomposition [Inorg. Chem. 18, 1558 (1979)]. The Ziegler-Rauk scheme is based on a separation of a molecule into fragments, while Mayer's scheme can be used in the cases where a fragmentation of the system in clearly separable parts is not possible. In the Mayer scheme, the density of a free atom is deformed to give the one-atom Mulliken density that subsequently interacts to give rise to the diatomic interaction energy. We give a detailed analysis of the diatomic energy contributions in the Mayer scheme and a close look onto the one-atom Mulliken densities. The Mulliken density ρA has a single large maximum around the nuclear position of the atom A, but exhibits slightly negative values in the vicinity of neighboring atoms. The main connecting point between both analysis schemes is the electrostatic energy. Both decomposition schemes utilize the same electrostatic energy expression, but differ in how fragment densities are defined. In the Mayer scheme, the electrostatic component originates from the interaction of the Mulliken densities, while in the Ziegler-Rauk scheme, the undisturbed fragment densities interact. The values of the electrostatic energy resulting from the two schemes differ significantly but typically have the same order of magnitude. Both methods are useful and complementary since Mayer's decomposition focuses on the energy of the finally formed molecule, whereas the Ziegler-Rauk scheme describes the bond formation starting from undeformed fragment densities

Orthotropic active strain models for the numerical simulation of cardiac biomechanics

An active strain formulation for orthotropic constitutive laws arising in cardiac mechanics modeling is introduced and studied. The passive mechanical properties of the tissue are described by the Holzapfel-Ogden relation. In the active strain formulation, the Euler-Lagrange equations for minimizing the total energy are written in terms of active and passive deformation factors, where the active part is assumed to depend, at the cell level, on the electrodynamics and on the specific orientation of the cardiac cells. The well-posedness of the linear system derived from a generic Newton iteration of the original problem is analyzed and different mechanical activation functions are considered. In addition, the active strain formulation is compared with the classical active stress formulation from both numerical and modeling perspectives. Taylor-Hood and MINI finite elements are employed to discretize the mechanical problem. The results of several numerical experiments show that the proposed formulation is mathematically consistent and is able to represent the main key features of the phenomenon, while allowing savings in computational costs.

Temporal diffeomorphic free-form deformation: application to motion and strain estimation from 3D echocardiography

This paper presents a new registration algorithm, called Temporal Di eomorphic Free Form Deformation (TDFFD), and its application to motion and strain quanti cation from a sequence of 3D ultrasound (US) images. The originality of our approach resides in enforcing time consistency by representing the 4D velocity eld as the sum of continuous spatiotemporal B-Spline kernels. The spatiotemporal displacement eld is then recovered through forward Eulerian integration of the non-stationary velocity eld. The strain tensor iscomputed locally using the spatial derivatives of the reconstructed displacement eld. The energy functional considered in this paper weighs two terms: the image similarity and a regularization term. The image similarity metric is the sum of squared di erences between the intensities of each frame and a reference one. Any frame in the sequence can be chosen as reference. The regularization term is based on theincompressibility of myocardial tissue. TDFFD was compared to pairwise 3D FFD and 3D+t FFD, bothon displacement and velocity elds, on a set of synthetic 3D US images with di erent noise levels. TDFFDshowed increased robustness to noise compared to these two state-of-the-art algorithms. TDFFD also proved to be more resistant to a reduced temporal resolution when decimating this synthetic sequence. Finally, this synthetic dataset was used to determine optimal settings of the TDFFD algorithm. Subsequently, TDFFDwas applied to a database of cardiac 3D US images of the left ventricle acquired from 9 healthy volunteers and 13 patients treated by Cardiac Resynchronization Therapy (CRT). On healthy cases, uniform strain patterns were observed over all myocardial segments, as physiologically expected. On all CRT patients, theimprovement in synchrony of regional longitudinal strain correlated with CRT clinical outcome as quanti ed by the reduction of end-systolic left ventricular volume at follow-up (6 and 12 months), showing the potential of the proposed algorithm for the assessment of CRT.

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.