bluuebunny/crossref_metadata_2025 huggingface dataset:
New and emerging risk factors for CVD
Authors: Ferns Gordon A. A.
Published: April 2008

Morphological and immunocytochemical studies have elucidated the complex processes involved in atherogenesis. The notion of plaque instability has emerged from this work and underscored the importance of inflammation in determining clinical complications associated with atherosclerosis, such as acute coronary syndrome. Cells of the immune system have been detected within atherosclerotic lesions and auto-antibodies directed against modified LDL and heat-shock proteins have been identified in the blood of individuals with atherosclerosis. The use of risk ‘engines’, e.g. the Framingham coronary risk score, has facilitated the identification of individuals at high risk, but the constituent classical risk factors used in these algorithms do not adequately differentiate individuals at moderate risk. As age is a major component of the equations used in these algorithms they are not particularly useful in young adults, and their applicability to non-Caucasian populations has been questioned. Biomarkers of early disease and plaque instability have therefore both been sought. Although some of these markers have been shown individually to be associated with a significant hazard ratio, no substantial improvement in discrimination has been demonstrated when they are incorporated into a risk ‘engine’. The latter has generally been assessed by receiver operator characteristic curve analysis, although this approach has been criticised. Other modalities, including imaging and functional assessments of vascular function, are now being developed for clinical use.
A PERMUTATION-BASED ESTIMATOR FOR MONOTONE INDEX MODELS
Authors: Bhattacharya Debopam
Published: April 2008

This paper shows that the finite-dimensional parameters of a monotone-index model can be estimated by minimizing an objective function based on sorting the data. The key observation guiding this procedure is that the sum of distances between pairs of adjacent observations is minimized (over all possible permutations) when the observations are sorted by their values. The resulting estimator is a generalization of Cavanagh and Sherman's monotone rank estimator (MRE) (Cavanagh and Sherman, 1998, Journal of Econometrics 84, 351–381) and does not require a bandwidth choice. The estimator is
$\sqrt{n}$
-consistent and asymptotically normal with a consistently estimable covariance matrix. This least-squares estimator can also be used to estimate monotone-index panel data models. A Monte Carlo study is presented where the proposed estimator is seen to dominate the MRE in terms of mean-squared error and mean absolute deviation.
The influence of sleep and sleep loss upon food intake and metabolism
Authors: Crispim Cibele Aparecida , Zalcman Ioná , Dáttilo Murilo , Padilha Heloisa Guarita , Edwards Ben , Waterhouse Jim , Tufik Sérgio , de Mello Marco Túlio
Published: April 2008

The present review investigates the role of sleep and its alteration in triggering metabolic disorders. The reduction of the amount of time sleeping has become an endemic condition in modern society and the current literature has found important associations between sleep loss and alterations in nutritional and metabolic aspects. Studies suggest that individuals who sleep less have a higher probability of becoming obese. It can be related to the increase of ghrelin and decrease of leptin levels, generating an increase of appetite and hunger. Sleep loss has been closely associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and diabetes, and this disturbance may reflect decreased efficacy of the negative-feedback regulation of the hypothalamic–pituitary–adrenal axis. The period of sleep is also associated with an increase of blood lipid concentrations, which can be intensified under conditions of reduced sleep time, leading to disorders in fat metabolism. Based on a review of the literature, we conclude that sleep loss represents an important risk factor for weight gain, insulin resistance, type 2 diabetes and dyslipidaemia. Therefore, an adequate sleep pattern is fundamental for the nutritional balance of the body and should be encouraged by professionals in the area.
Tetsuro Yoshida (1894–1956) and architectural interchange between East and West
Authors: Kim Hyon-Sob
Published: April 2008

‘I have long been dreaming a dream: that I am a drop of dew on the leaf of a nameless plant deep in the valley of some far-off mountain range. The dewdrop rolls down into a little brook and mingles with its waters; the brook flows into a river which in turn discharges into the sea, and the waves of the sea in their turn lave the coasts of all the countries of the earth. Thus I picture to myself the cultural interchange of all peoples, and it has been my wish to take part, even if only as one little drop, in this important work.’

(Tetsuro Yoshida, 1955)
Unlocking Lutyens: a gateway to the hidden legacy of John Pell and Sir Christopher Wren
Authors: Radford Dennis , Cawthorne Douglas
Published: April 2008

The work and the life of the English architect Sir Edwin Landseer Lutyens (1869–1944) have been extensively documented over the past hundred years and clearly show a career with at least two phases. The first is characterised by the design of private country houses in the Arts and Crafts style and, in collaboration with the horticulturalist Gertrude Jekyll, the development of their gardens. The second begins around 1900 and reflects a shift towards Neo-Classicism, initially in country houses and later in a wider range of larger public buildings and monuments both in England and abroad. Lutyens developed his use of the Neo-Classical idiom throughout the latter part of his career into a unique style of design which Arthur Stanley George Butler has termed his ‘elemental mode’. This was characterised by a highly controlled use of form and mass, apparent adherence to rules of Classical proportioning and the sparing use of symbolic Classical motifs. However, very little is known with any certainty about how Lutyens actually achieved this style, in particular what role was attributable to intuition and good taste, as is often assumed, and how much may have been attributable to quantitative and formalised methods of design. Circumstantial evidence exists that strongly suggests that quantitative analytical methods may have been used in a method which drew upon his interest in puzzles and mathematics, his interests in architectural history (particularly English Neo-Classicism), his leanings towards mysticism and his exposure to Theosophy.
Low dietary calcium in European postmenopausal osteoporotic women
Authors: Bruyere Olivier , De Cock Caroline , Mottet Catherine , Neuprez Audrey , Malaise Olivier , Reginster Jean-Yves
Published: April 2008

Objective

The WHO recommends a daily Ca intake for postmenopausal women of 1300 mg. The objective of the present study was to assess the dietary Ca intake in European postmenopausal osteoporotic women.

Design, setting and subjects

Assessment of dietary Ca intake (food and supplements) was performed with a validated self-questionnaire in 8524 osteoporotic women from nine European countries (Belgium, Denmark, France, Germany, Hungary, Italy, Poland, Spain and the UK).

Results

Mean age of the patients was 74·2 (sd 7·1) years, mean BMI was 25·7 (sd 4·2) kg/m2. Of the study population, 37·2 % of the women took Ca supplements. The mean dietary intake of Ca was 930·7 (sd 422·9) mg/d. The lowest Ca intake was found in Hungary (586·7 (sd 319·1) mg/d) and the highest in Denmark (1145·6 (sd 463·0) mg/d). In the whole study population, only 19·1 % of the women had a dietary Ca intake >1300 mg/d. Only 17·1 % of women aged over 75 years achieved 1300 mg/d compared with 20·5 % of women aged less than 75 years (P = 0·0001 for the difference between the two groups).

Conclusion

Dietary intake of Ca is very low in European postmenopausal women. A greater awareness is needed to resolve this public health problem.
Impact of chewing betel-nut (Areca catechu) on liver cirrhosis and hepatocellular carcinoma: a population-based study from an area with a high prevalence of hepatitis B and C infections
Authors: Wu Grace Hui-Min , Boucher Barbara J , Chiu Yueh-Hsia , Liao Chao-Sheng , Chen Tony Hsiu-Hsi
Published: April 2008

Background

Chewing betel-nuts (Areca catechu) is carcinogenic but the risk for hepatocellular carcinoma (HCC) and liver cirrhosis (LC) is little considered. Worldwide 600 million people chew betel, including emigrants from palm-growing countries.

Objective

We aimed to assess the relationships and dose–response effects of betel chewing on LC and HCC risks, since habit cessation could reduce the increased risks of HCC and LC found in such communities.

Subjects

Screening 60 326 subjects aged 30–79 years in a population-based study in Taiwan identified LC in 588 and HCC in 131 subjects. Demographic features, hepatitis B/C infections, other risk factors and betel chewing were noted. Multiple Cox regression models were used to assess independent relationships, interactions and synergisms between age, betel chewing and hepatitis B/C.

Results

Betel chewing increased LC and HCC risk 4·25-fold (95 % CI 2·9, 6·2) in current chewers and 1·89-fold (95 % CI 1·13, 3·16) in ex-chewers v. never-chewers, with dose effects for quantity, duration and cumulative exposure in chewers. Subjects without hepatitis B/C infections had 5·0-fold (95 % CI 2·87, 9·03) increased risk of LC/HCC v. never-chewers, and betel chewing had an additive synergistic effect on hepatitis B/C-related risks. Risk reduction with betel habit cessation could exceed that expected from immunization programmes for hepatitis B and C.

Conclusion

Increased risks of cirrhosis and hepatocellular cancer were found in betel chewers free of hepatitis B/C infection, and these risks were synergistically additive to those of hepatitis B/C infections. Estimated risk reduction from effective anti-betel chewing programmes would be sizeable.
Demonstration of Robust Host Cell Protein Clearance in Biopharmaceutical Downstream Processes
Authors: Shukla Abhinav A. , Jiang Canping , Ma Junfen , Rubacha Michael , Flansburg Lisa , Lee Steven S.
Published: April 2008

Residual host cell protein impurities (HCPs) are a key component of biopharmaceutical process related impurities. These impurities need to be effectively cleared through chromatographic steps in the downstream purification process to produce safe and efficacious protein biopharmaceuticals. A variety of strategies to demonstrate robust host cell protein clearance using scale‐down studies are highlighted and compared. A common strategy is the “spiking” approach, which is widely employed in clearance studies for well‐defined impurities. For HCPs this approach involves spiking cell culture harvest, which is rich in host cell proteins, into the load material for all chromatographic steps to assess their clearance ability. However, for studying HCP clearance, this approach suffers from the significant disadvantage that the vast majority of host cell protein impurities in a cell culture harvest sample are not relevant for a chromatographic step that is downstream of the capture step in the process. Two alternative strategies are presented here to study HCP clearance such that relevance of those species for a given chromatographic step is taken into consideration. These include a “bypass” strategy, which assumes that some of the load material for a chromatographic step bypasses that step and makes it into the load for the subsequent step. The second is a “worst‐case” strategy, which utilizes information obtained from process characterization studies. This involves operating steps at a combination of their operating parameters within operating ranges that yield the poorest clearance of HCPs over that step. The eluate from the worst case run is carried forward to the next chromatographic step to assess its ability to clear HCPs. Both the bypass and worst‐case approaches offer significant advantages over the spiking approach with respect to process relevance of the HCP impurity species being studied. A combination of these small‐scale validation approaches with large‐scale HCP clearance data from clinical manufacturing and manufacturing consistency runs is used to demonstrate robust HCP clearance for the downstream purification process of an Fc fusion protein. The demonstration of robust HCP clearance through this comprehensive strategy can potentially be used to eliminate the need for routine analytical testing or for establishing acceptance criteria for these impurities as well as to demonstrate robust operation of the entire downstream purification process.
Topography growth drives stress rotations in the central Andes: Observations and models
Authors: Heidbach Oliver , Iaffaldano Giampiero , Bunge Hans‐Peter
Published: April 2008

Recent numerical models that couple global mantel circulation with lithosphere dynamics show that growth of the central Andes controls the 30% reduction of convergence velocity between the Nazca and South America plates observed over the past 10 Ma. The increase of gravitational potential energy due to topographic growth is also a major control on the stress pattern. Here we use numerical models which reproduce the Nazca/South America convergence history to predict the change of stress pattern in the central Andes for the past 10 Ma. Comparison of the modeled stress orientations at present‐day with the observed ones results in ±23.9° mean deviation. Based on this good agreement we attempt to predict paleostress orientations 10 Ma ago. Interestingly, the modeled stress orientations 3.2 Ma ago are very similar to the present‐day orientations. From this result we infer that stress rotations occurred between 10 and 3.2 Ma ago, when topography was considerably lower.
The impact of local sources and long‐range transport on aerosol properties over the northeast U.S. region during INTEX‐NA
Authors: Thornhill K. Lee , Chen Gao , Dibb Jack , Jordan Carolyn E. , Omar Ali , Winstead Edward L. , Schuster Greg , Clarke Antony , McNaughton Cameron , Scheuer Eric , Blake Donald , Sachse Glen , Huey L. G. , Singh H. B. , Anderson Bruce E.
Published: April 2008

We use data collected aboard the NASA DC‐8 aircraft during the summer 2004, Intercontinental Transport and Chemical Evolution Experiment over North America (INTEX‐NA) field campaign to examine the origin, composition, physical and optical properties of aerosols within air masses sampled over and downwind of the northeastern U.S. We note that aerosol concentrations within the region exhibited steep vertical gradients and significant variability in both time and space. An examination of air mass chemical signatures and backward trajectories indicates that transport from four, significantly different source regions contributed to the variability: the subtropical Atlantic Ocean (AO); the U.S. west coast and eastern Pacific (WCP); the U.S. east coast and Midwestern states (EC); and northwest Canada and Alaska (CA). AO air masses were typically confined to below 2 km altitude, exhibited low pollutant contents, contained enhanced levels of sea salt, and were typically observed when the Bermuda High strengthened. The most common air mass present in the upper troposphere, WCP air often contained weak dust and aged pollution enhances from convective input occurring over the central part of the continent. CA air exhibited enhancements in anthropogenic pollution tracers below 2 km and contained some black‐carbon rich haze layers between 3 and 5 km that could be traced to forest fires burning in western Canada and Alaska. EC air was prevalent at lower elevations throughout the study area and exhibited enhanced scattering along with elevated levels of sulfate aerosols and combustion tracers. There is an overall balance between the observed cations and anions for all cases, except EC air mass below 4 km.
Saharan mineral dust transport into the Caribbean: Observed atmospheric controls and trends
Authors: Doherty O. M. , Riemer N. , Hameed S.
Published: April 2008

Each summer large amounts of mineral dust from the Sahara are transported across the Atlantic and arrive at the Caribbean with far‐reaching implications for climate in this region. In this paper we analyze summer season interannual variability of North African mineral dust over the Caribbean using the Total Ozone Mapping Spectrometer (TOMS)/Nimbus 7 (1979–1992) and TOMS/Earth Probe (1998–2000) satellite aerosol data. We apply the “centers of action” approach to gain insight into the atmospheric controls on Saharan dust transport into the Caribbean and identify longitudinal displacement and pressure fluctuation of the Hawaiian High as well as longitudinal displacement of the Azores High as key players. In contrast, traditional indices such as the North Atlantic Oscillation and the Southern Oscillation are not correlated with the mineral dust variations over the Caribbean region. We utilize National Centers for Environmental Prediction/National Center for Atmospheric Research reanalysis to investigate the underlying physical mechanisms and to identify meteorological conditions that correspond to high and low dust loads. Our analysis shows that two different transport routes from distinct source regions are responsible for transporting mineral dust into the Caribbean: a northern mode in which dust mobilized from the Sahara travels westward controlled primarily by the Azores High and a southern mode in which intense dust clouds originating in the Sahel region travel over the Gulf of Guinea to reach the Caribbean. The latter is controlled primarily by teleconnections with the Hawaiian High.
Eocene biogenic silica accumulation rates at the Pacific equatorial divergence zone
Authors: Moore Ted C. , Jarrard Richard D. , Olivarez Lyle Annette , Lyle Mitch
Published: April 2008

A synthesis of Eocene biogenic silica accumulation rates in the equatorial zone of the Pacific shows several relatively broad maxima spaced a few million years apart and extending from the uppermost Eocene into the lower Eocene. There is a distinct, step‐like decrease in biogenic silica mass accumulation rate at 38.5 Ma (just below the top of C18n.1n),which appears to be related to changes in oceanographic conditions in the eastern equatorial region. Eocene biogenic silica accumulation rates in the equatorial Pacific are distinctly lower than those in the Neogene. A comparison of Eocene accumulation rates and known areas of open ocean biogenic silica deposition with those in the more modern world leads us to conclude that there is no need to call upon an increased supply of dissolved silica to the world ocean to account for the siliceous‐rich deposits of the Eocene.
Calibration of transient groundwater models using time series analysis and moment matching
Authors: Bakker Mark , Maas Kees , Von Asmuth Jos R.
Published: April 2008

A comprehensive and efficient approach is presented for the calibration of transient groundwater models. The approach starts with the time series analysis of the measured heads in observation wells using all active stresses as input series, which may include rainfall, evaporation, surface water levels, and pumping. The time series analysis results in the impulse response function of each stress at the observation well. For each impulse response function, the temporal moments M0 and M1 may be computed. Both moments fulfill differential equations that are equivalent to the differential equation for steady groundwater flow, with known values along physical boundaries. The model of M0 may be calibrated for the transmissivity, as it does not depend on the storage coefficient; the computed values of M0 at the observation wells are used for calibration. The model of M1 may be calibrated for the storage coefficient, once the transmissivity is known from the M0 model; the computed values of M1 at the observation wells are used for calibration. The approach is intended for systems that may be approximated as linear. In summary, our proposed calibration process for transient models reduces to the calibration of only two steady models. Several examples are given to demonstrate the accuracy and efficiency of the proposed approach.
Global Impacts of the 1600 Eruption of Peru's Huaynaputina Volcano
Authors: Verosub Kenneth L. , Lippman Jake
Published: April 2008

The human impacts of the 1815 eruption of Tambora volcano in eastern Indonesia are well known. The sulfur injected into the stratosphere by that eruption produced a veil of sunlight‐reflecting sulfate aerosols. The following year, often called the “year without a summer,” was marked by significant global cooling, resulting in crop failures, famine, and social unrest as well as by a broad array of climatic impacts [Oppenheimer, 2003]. Over the past 10,000 years, there have been many other volcanic eruptions of comparable (and greater) magnitude than Tambora, and at least some of these must have had similar effects. However, Tambora is the only major eruption whose global climatic and human impacts have been comprehensively documented.
Collecting Spatial Data: Optimal Design of Experiments for Random Fields, Third Edition
Authors: Manton Michael
Published: April 2008

Any technical book that reaches its third edition in 10 years is fulfilling a role for the scientific community over an extended period. Thus, the publication of the third edition of Collecting Spatial Data signifies that this monograph is continuing to provide an effective summary of the state of the art of the design of spatial networks.

Measuring of spatially varying quantities, such as geological strata or daily rainfall, is a critical problem both for research and for the operation of a modern society. To monitor the state of the environment, manage our use of the environment, and set future policies for the environment, we need to know the spatial and temporal distribution of a wide range of variables on land, in the ocean, and in the atmosphere. At the same time that communities are keen to gather information about the environment, they are also reluctant to spend a lot of money on such apparently mundane activities. Thus, efficiency is invariably a key factor in designing a spatial network for such monitoring.
Aeolian dust in East Antarctica (EPICA‐Dome C and Vostok): Provenance during glacial ages over the last 800 kyr
Authors: Delmonte B. , Andersson P. S. , Hansson M. , Schöberg H. , Petit J. R. , Basile‐Doelsch I. , Maggi V.
Published: April 2008

Aeolian mineral dust archived in Antarctic ice cores represents a key proxy for Quaternary climate evolution. The longest and most detailed dust and climate sequences from polar ice are provided today by the Vostok and by the EPICA‐Dome C (EDC) ice cores. Here we investigate the geographic provenance of dust windborne to East Antarctica during Early and Middle Pleistocene glacial ages using strontium and neodymium isotopes as tracers. The isotopic signature of Antarctic dust points towards a dominant South American origin during Marine Isotopic Stage (MIS) 8, 10, 12, and back to MIS 16 and 20 as deduced from EDC core. Data provide evidence for a persistent overall westerly circulation pattern allowing efficient transfer of dust from South America to the interior of Antarctica over the last 800 kyr. Some small but significant dissimilarity between old and recent glacial ages suggests a slightly reduced Patagonian contribution during ancient glaciations.
Probing in vivo dendritic cell functions by conditional cell ablation
Authors: Sapoznikov Anita , Jung Steffen
Published: April 2008

Dendritic cells (DCs) play a central role in T‐cell activation and the control of the inherent autoreactivity of the T‐cell compartment. Pleiotropic DC functions are likely associated with discrete DC subsets. However, the latter remain largely defined by phenotype and unique anatomic location, rather than function. The investigation of DC involvement in complex phenomena that rely on multicellular interactions, such as immuno‐stimulation and tolerization calls for an assessment of DC functions within physiological context. Given the highly dynamic DC compartment, the method of choice to study in vivo DC functions is their conditional ablation in the intact organism. Here, we summarize the recent progress in this field highlighting pitfalls and prospects of the approach.
The Human Obesity Gene Map: The 1999 Update
Authors: Chagnon Yvon C. , Pérusse Louis , Weisnagel S. John , Rankinen Tuomo , Bouchard Claude
Published: April 2008

This report constitutes the sixth update of the human obesity gene map incorporating published results up to the end of October 1999. Evidence from the rodent and human obesity cases caused by single gene mutations, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTL) uncovered in human genome‐wide scans and in crossbreeding experiments with mouse, rat, pig and chicken models, association and linkage studies with candidate genes and other markers is reviewed. Twenty‐five human cases of obesity can now be explained by variation in five genes. Twenty Mendelian disorders exhibiting obesity as one of their clinical manifestations have now been mapped. The number of different QTLs reported from animal models reaches now 98. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 89 reports of positive associations pertaining to 40 candidate genes. Finally, 44 loci have linked to obesity indicators in genomic scans and other linkage study designs. The obesity gene map depicted in Figure 1 reveals that putative loci affecting obesity‐related phenotypes can be found on all autosomes, with chromosomes 14 and 21 showing each one locus only. The number of genes, markers, and chromosomal regions that have been associated or linked with human obesity phenotypes continues to increase and is now well above 200.

The 1999 human obesity gene map. The map includes all putative obesity‐related phenotypes identified from the various lines of evidence reviewed in the article. The chromosomes and their regions are from the Gene Map of the Human Genome web site hosted by the National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD (URL:http:www.ncbi.nlm.nih.gov). The chromosome number and the size of each chromosome in megabases (Mb) are given at the top and bottom of the chromosomes, respectively. Loci abbreviations and full names are given in the Appendix. The abbreviations for QTLs are given in Table 4.

imageimage
Use of Tape‐Recorded Food Records in Assessing Children's Dietary Intake
Authors: Lindquist Christine H. , Cummings Tina , Goran Michael I.
Published: April 2008

Background: Dietary assessment among children is particularly problematic when techniques are dependent on memory skills or advanced cognitive development.

Objective: The current study explored the use of self‐report by tape recorders to document children's dietary intake immediately upon consumption, and compared this method with the traditional, interviewer‐guided recall technique. In addition, the influence of body fatness and sociodemographic characteristics on the accuracy of recall and tape‐recorded food records was determined.

Research Methods and Procedures: The sample included 30 black and white children aged 6.5 to 11.6 years (x¯ = 9.5). Energy intake (EI), measured by six 24‐hour food records (three for each method), was compared with total energy expenditure calculated by the doubly labeled water technique. Paired t tests, correlation analyses, and multiple re‐gression analyses were performed.

Results: The analyses revealed poor validity of the tape recorder method (x¯ misreporting score = −1.13 ± 2.62 MJ/day, r for total energy expenditure and EI = −0.06, p = 0.74). Estimates of EI differed significantly between the tape recorder and recall methods (p < 0.01). The traditional recall method was confirmed as a valid estimate of energy intake (x¯ misreporting score = 0.04 ± 2.38 MJ/day), although demonstrating a modest correlation with TEE (r = 0.32, p = 0.08). Although no significant predictors of misreporting using the recall method were identified in the multivariate analyses, older children and children with higher adiposity were more likely to misreport using the tape recorder method.

Discussion: The results suggest that the use of the tape recorder for estimating EI does not result in accurate assessments among children, although this techniquemay be useful for specific subgroups (i.e., younger and leaner children).
Low Plasma Leptin Concentration and Low Rates of Fat Oxidation in Weight‐Stable Post‐Obese Subjects
Authors: Filozof Claudia M. , Murúa Carlos , Sanchez Marta P. , Brailovsky Carlos , Perman Mario , Gonzalez Claudio D. , Ravussin Eric
Published: April 2008

Objective: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post‐obese adults (2 males and 6 females; 48.9 ± 12.2 years; body mass index [BMI]: 24.5 ± 1.0 kg/m2; body fat 33 ± 5%; mean ± SD) who lost 27.1 ± 21.3 kg (16 to 79 kg) and had maintained this weight loss for ≥2 months (2 to 9 months) to eight age‐ and BMI‐matched control never‐obese subjects (1 male and 7 females; 49.1 ± 5.2 years; BMI 24.4 ± 1.0 kg/m2; body fat 33 ± 7%).

Research Methods and Procedures: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10‐hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48‐hour period in free living conditions.

Results: After adjustment for fat mass and fat‐free mass, post‐obese subjects had, compared with controls, similar levels of physical activity (4185 ± 205 vs. 4295 ± 204 counts) and similar RMR (1383 ± 268 vs. 1430 ± 104 kcal/day) but higher RQ (0.86 ± 0.04 vs. 0.81 ± 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat‐free mass, was lower in post‐obese than in control subjects (4.5 ± 2.1 vs. 11.6 ± 7.9 ng/mL, p < 0.05).

Discussion: The low fat oxidation and low plasma leptin concentrations observed in post‐obese individuals may, in part, explain their propensity to relapse.
Sequence Variation within the Neuropeptide Y Gene and Obesity in Mexican Americans
Authors: Bray Molly S. , Boerwinkle Eric , Hanis Craig L.
Published: April 2008

Objective: Recently, we reported evidence for linkage between neuropeptide Y (NPY) and both obesity and several obesity‐related quantitative measures in a sample of Mexican Americans from Starr County, Texas. The purpose of this study was to investigate putative variation within the coding and promoter regions of NPY.

Research Methods and Procedures: Five young, obese individuals (body mass index [BMI] 33 to 45 kg/m2, age 14 to 30 years); five adult, lean individuals (BMI 20 to 26 kg/m2, age 39 to 65 years); and five sibling pairs sharing no alleles that were identical by descent at a marker locus proximal to NPYwere selected for fluorescence‐based sequencing of approximately 1100 base pairs (bp) immediately 5′ from the start site and all four exons of NPY. We identified a total of eight variant sites, including a 2‐bp insertion/deletion (I/D) within a putative negative regulatory region (−880I/D) and a 17‐bp deletion at the exon 1/intron 1 junction (69I/D). The −880I/D and 69I/D variants were typed in a separate random sample of Mexican Americans (N = 914) from Starr County, Texas.

Results: Analyses of variance resulted in a significant association between −880I/D and waist‐to‐hip ratio (p = 0.041) in the entire sample and between −880I/D and BMI (p = 0.031), abdominal circumference (p = 0.044), and waist‐to‐hip ratio (p = 0.041) in a non‐obese subsample (BMI < 30 kg/m2, n = 594). The 69I/D variant was observed in only one pedigree and does not appear to segregate with obesity within this pedigree.

Discussion: This study reports newly identified common human sequence variation within the regulatory and coding sequence of NPY. Several variants were observed, and of those tested, the −880I/D promoter region variant may influence body fat patterning in non‐obese individuals but does not appear to play a major role in the etiology of common forms of obesity in this population.
Rapamycin Inhibits Human Adipocyte Differentiation in Primary Culture
Authors: Bell Andrea , Grunder Laura , Sorisky Alexander
Published: April 2008

Objective: The immunosuppressant drug rapamycin, has been reported to inhibit 3T3‐L1 adipocyte differentiation by interfering with critical postconfluent mitoses that are required early on for successful differentiation of this cell line (clonal expansion phase). In contrast to the murine 3T3‐L1 preadipocyte cell line, human preadipocytes in primary culture do not undergo clonal expansion during differentiation. We investigated whether rapamycin could inhibit human adipocyte differentiation.

Research Methods and Procedures: The effect of rapamycin on the induction of differentiation of human preadipocytes in primary culture into adipocytes was measured using Oil Red O staining and glycerol phosphate dehydrogenase activity.

Results: We have observed that rapamycin severely curtails human adipocyte differentiation of both omental and abdominal subcutaneous preadipocytes (to 14% and 19% of standard differentiation, respectively). The rapamycin‐mediated inhibition of human adipocyte differentiation could be reversed in the presence of excess amounts of FK‐506, which displaces rapamycin from its intracellular receptor, FKPB12. Measurement of cytosolic protein and [3H]thymidine incorporation into DNA confirmed the absence of proliferation during differentiation of human preadipocytes in primary culture.

Discussion: Our data indicate that rapamycin exerts important negative regulatory effects on adipogenesis in human preadipocytes, through a mechanism that does not depend on interruption of clonal expansion.
Heart Rate Variability in Obese Children: Relations to Total Body and Visceral Adiposity, and Changes with Physical Training and Detraining
Authors: Gutin Bernard , Barbeau Paule , Litaker Mark S. , Ferguson Michael , Owens Scott
Published: April 2008

Objective: Heart rate variability provides non‐invasive information about cardiac parasympathetic activity (PSA). We determined in obese children: (1) relations of baseline PSA to body composition and hemodynamics; (2) effects of physical training (PT) and cessation of PT; and (3) which factors explained individual differences in responsivity of PSA to the PT.

Research Methods and Procedures: The root mean square of successive differences (RMSSD) was the index of PSA. Obese children (n = 79) were randomly assigned to groups that participated in PT during the first or second 4‐month periods of the study.

Results: Baseline RMSSD was significantly (p < 0.05) associated with lower levels of: fat mass, fat‐free mass, subcutaneous abdominal adipose tissue, resting heart rate (HR), resting systolic blood pressure, and exercise HR. Stepwise multiple regression produced a final model (R2 = 0.36) that included only resting HR. The analysis of changes over the three time points of the study found a significant (p = 0.026) time by group interaction, such that RMSSD increased during periods of PT and decreased following cessation of PT. Greater individual increases in response to the PT (p < 0.05) were seen in those who had lower pre‐PT RMSSD levels, showed the greatest decreases in resting HR, and increased most in vigorous physical activity. The final regression model retained only the change in resting HR as a significant predictor of the changes in the RMSSD (R2 = 0.23).

Discussion: Regular exercise that improved fitness and body composition had a favorable effect on PSA in obese children.
Inheritance of the Waist‐to‐Hip Ratio in the National Heart, Lung, and Blood Institute Family Heart Study
Authors: Feitosa Mary F. , Borecki Ingrid , Hunt Steven C. , Arnett Donna K. , Rao D. C. , Province Michael
Published: April 2008

Objective: Considering that waist‐to‐hip ratio (WHR) is a simple anthropometric measure of obesity and is a better predictor of coronary heart disease than body mass index (BMI), the genetic underpinnings of WHR are of interest. The inheritance pattern of WHR, before and after adjustment for BMI (WHR‐BMI), was investigated in 2713 individuals from 1038 nuclear families in the National Heart, Lung, and Blood Institute Family Heart Study (NHLBI‐FHS).

Research Methods and Procedures: Waist and hip measurements were taken twice, and the means of the measurements were used to calculate the WHR. Adjustments for age were carried out separately by sex, using stepwise multiple regression procedures for WHR and WHR‐BMI phenotypes. Segregation analysis was applied using the unified model as implemented in the computer program POINTER.

Results: For age‐adjusted WHR, the segregation results suggested an additive major gene that accounts for 35% of the phenotypic variance, and approximately 30% of the sample are homozygous for the “high” genotype. The results for age‐ and BMI‐adjusted WHR were also compatible with a major gene; however, the multifactorial model provided the most parsimonious fit to the data.

Discussion: Although the genetic mechanisms for several obesity traits have been studied, tests of Mendelian segregation on this simple anthropometric measure (WHR) have not been reported previously. This study provides evidence for the presence of a major gene for age‐adjusted WHR, suggesting that it is an appropriate trait for further genetic analysis, especially because it has strong predictive value and probably relates biologically to cardiovascular risk.
The Effect of Repeated Episodes of Dietary Restriction and Refeeding on Systolic Blood Pressure and Food Intake in Exercise‐Trained Normotensive Rats
Authors: Miller Gary D. , Dimond Alison G. , Stern Judith S.
Published: April 2008

Objective: To explore the effects of weight cycling and exercise on blood pressure and macronutrient intake in Sprague‐Dawley rats.

Research Methods and Procedures: Female Sprague‐Dawley rats (n = 62; 5 months old) were assigned to an ad libitum (Con) or weight‐cycled (Cyc) group. They were either sedentary (Con‐Sed and Cyc‐Sed) or exercise‐trained (Con‐Ex and Cyc‐Ex) on a motorized treadmill (20 m/minute; 60 minutes/day; 6 days/week). The Cyc groups underwent 2 cycles of 3 weeks of 60% food restriction followed by 5 weeks of ad libitum refeeding using a macronutrient self‐selection diet. Body mass and food intake were analyzed weekly. Systolic blood pressure (SBP) was measured at baseline and during the first and fifth weeks of each refeeding.

Results: For both cycling periods, SBP was elevated in Cyc vs. Con groups at Week 1 of refeeding, but was similar among groups by Week 5 of refeeding. Both Con groups had greater total energy intake than the Cyc groups for both cycling periods (Cycle 1: 2882.2 ± 75.1, Con‐Sed; 2916.1 ± 67.1, Con‐Ex; 2692.2 ± 58.7, Cyc‐Sed; and 2780.5 ± 52.4 kcal, Cyc‐Ex) (Cycle 2: 2815.8 ± 75.1, Con‐Sed; 2938.8 ± 49.4, Con‐Ex; 2577.1 ± 60.5, Cyc‐Sed; and 2643.5 ± 65.9 kcal, Cyc‐Ex). Relative fat intake (percentage of total kcal/week) was significantly less for Con‐Ex and Cyc‐Ex than Con‐Sed and Cyc‐Sed throughout both refeeding periods.

Discussion: Weight cycling failed to produce significant sustained effects on SBP, body mass, or food intake. Exercise training, irrespective of diet, lowered dietary fat intake.
Predictors of Weight Change in Middle‐aged and Old Men
Authors: Fogelholm Mikael , Kujala Urho , Kaprio Jaakko , Sarna Seppo
Published: April 2008

Objective: Studies on weight change and mortality have yielded inconclusive results. This 10‐year prospective study was undertaken to improve understanding of factors affecting weight change.

Research Methods and Procedures: The subjects were 1143 men, aged 36 to 88 years (mean, 53.3 years) at entry. A questionnaire was filled in at entry and at the end of the follow‐up with queries on weight, height, weight at the age of 20, physician‐diagnosed diseases, smoking, alcohol use, dietary habits, leisure physical activity, occupation, present occupational activity, living conditions (living alone or cohabiting), and former athletic status. Further information on morbidity was obtained from selected national registers. Factors predicting weight change during the study were identified by stepwise linear multiple regression analysis.

Results: The mean 10‐year weight change was 0.8 (range, −29 to +24) kg. Age at entry (β‐coefficient, −0.17, SE 0.02), weight at entry (β, −0.03, SE 0.01), diabetes at entry (β, −3.55, SE 1.02), diabetes diagnosed after entry (β, −3.94, SE 0.96), malignant cancer (β, −1.60, SE 0.70), being a smoker (β, −1.59, SE 0.48), and increased physical activity (β, −1.27, SE 0.54) were significantly (p < 0.05) associated with weight loss in the final model. The model explained 13% of the variance of weight change.

Discussion: The results emphasize the complexity of weight change. Some factors associated with weight change are apparently negatively, and some positively, associated with health. This could explain the equivocal findings on weight change and mortality in the literature.
Obesity Management: Australian General Practitioners’ Attitudes and Practices
Authors: Campbell Karen , Engel Helen , Timperio Anna , Cooper Catherine , Crawford David
Published: April 2008

Objectives: To document general practitioners’ (GPs) attitudes and practices regarding the prevention and management of overweight and obesity.

Research Methods and Procedures: A cross‐sectional survey of a randomly selected sample of 1500 Australian GPs was conducted, of which 752 questionnaires were returned. The measures included views on weight management, definitions of success, views regarding the usefulness of drugs, approaches to and strategies recommended for weight management, and problems and frustrations in managing overweight and obesity.

Results: GPs view weight management as important and feel they have an important role to play. Although they consider themselves to be well prepared to treat overweight patients, they believe that they have limited efficacy in weight management and find it professionally unrewarding. GPs view the assessment of a patient's dietary and physical activity habits and the provision of dietary and physical activity advice as very important. The approaches least likely to be considered important and/or least likely to be practiced were those that would support the patient in achieving and maintaining lifestyle change.

Discussion: There remains considerable opportunity to improve the practice of GPs in their management of overweight and obesity. Although education is fundamental, it is important to acknowledge the constraints of the GPs’ existing working environment.
Usefulness of Anthropometry and DXA in Predicting Intra‐abdominal Fat in Obese Men and Women
Authors: Kamel Emad G. , McNeill Geraldine , van Wijk Marlene C. W.
Published: April 2008

Objective: To investigate the usefulness of anthropometry and DXA in predicting intra‐abdominal fat (IAF) in obese men and women.

Research Methods and Procedures: Observational, cross sectional study of 22 women and 18 men with a body mass index of 30 or above. IAF from 20 cm above and 10 cm below the L4 to L5 intervertebral disc was measured by magnetic resonance imaging (MRI) as a reference method. Central abdominal fat was measured from the upper border of L2 to the lower border of L4 by DXA. Waist and hip circumferences were also measured.

Results: In obese women DXA, waist circumference and waist‐hip ratio were equally well correlated with IAF (r = 0.74, 0.75, and 0.70, respectively). In obese men DXA was moderately correlated with IAF measured by MRI (r = 0.46), whereas waist circumference and waist‐hip ratio were not significantly correlated with IAF.

Discussion: The prediction of IAF in obese subjects was highly dependent on sex more than in non‐obese persons. Anthropometry and DXA were equally useful in obese women, whereas anthropometry had no predictive power and DXA was the only acceptable predictor of IAF in obese men.
Effect of One Morning Meal and a Bolus of Dexamethasone on 24‐Hour Variation of Serum Leptin Levels in Humans
Authors: Laferrère Blandine , Fried Susan K. , Osborne Tom , Pi‐Sunyer F. Xavier
Published: April 2008

Objective: We have previously shown that morning administration of dexamethasone in combination with food induces a doubling of serum leptin levels starting at 7 hours after dexamethasone administration, with a maximum effect at 10 hours, the latest time point that we have studied. However, dexamethasone given in the absence of food had no effect on serum leptin at 10 hours. The present experiment was undertaken to determine the duration of the effect of dexamethasone on 24‐hour serum leptin under fasted and fed conditions in humans.

Research Methods and Procedures: Six healthy non‐obese male volunteers were studied under the following four conditions: 1) dexamethasone (2 mg intravenously, given at 0900 hours) with fasting; 2) dexamethasone with food (1700 kcal, 55% carbohydrate, 15% protein, and 30% fat, given in one meal 2 hours after dexamethasone administration at 1100 hours); 3) saline with food (same meal); 4) saline with fasting. Serum leptin, glucose, insulin, and cortisol were monitored every 30 minutes for 24 hours.

Results: 1) Under the fasting condition, dexamethasone increased leptin nocturnal secretion between 2100 and 2400 hours. 2) A single meal (1700 kcal) at 1100 hours increased nocturnal leptin secretion when compared with the fasting condition. The peak increase of leptin was 123% over baseline between 2100 and 2400 hours, 10 to 14 hours after the meal. 3) In the fed + dexamethasone condition, leptin levels increased from baseline starting 8 hours after dexamethasone injection, reached a maximum increase of 260% between 2100 and 2400 hours, then decreased thereafter, remaining elevated compared to baseline for 16 hours. There was a correlation between 24‐hour leptin secretion and insulin secretion after a single morning meal.

Discussion: A single bolus of dexamethasone, given before a single large meal, produces a delayed (6‐hour) but long‐lasting increase in serum leptin (over 16 hours). Under fasted conditions, dexamethasone does not increase daytime leptin but does increase leptin during the night.
Zinc‐Induced Hyperleptinemia Relates to the Amelioration of Sucrose‐Induced Obesity with Zinc Repletion
Authors: Chen Ming‐Der , Lin Pi‐Yao
Published: April 2008

Objective: Dietary zinc repletion can ameliorate sucrose‐induced obesity. A positive correlation between zinc and leptin has been recently noted, and both are known as important mediators in appetite control. In this study, we examined whether the reported amelioration of sucrose‐induced obesity by zinc repletion was consequent on the changes in circulating leptin levels.

Research Methods and Procedures: Mice with obesity that was induced by giving a 32% sucrose solution in addition to a semipurified diet were divided into two groups based on whether they had 20 mg/liter zinc supplementation in their drinking water.

Results: As expected, the mice with sucrose‐induced obesity had hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia, and hypozincemia when compared with the mice given the diet alone. Body weight gain, body fat content, and food and sucrose intake tended to decrease but not with statistical significance in sucrose‐fed obese mice with zinc supplementation. Nevertheless, some serum variables (glucose, insulin, triglycerides, and zinc) in sucrose‐fed obese mice with zinc treatment were approximate to those values of the mice given the diet alone. Moreover, sucrose‐fed obese mice with zinc supplementation had the highest serum values of leptin.

Discussion: This study indicates that the amelioration of sucrose‐induced obesity by zinc repletion may be partly attributable to the hyperleptinemia induced by the mineral.