Changes in BMI, Duration of Overweight and Obesity, and Glucose Metabolism: 45 Years of Follow-up of a Birth Cohort

OBJECTIVE: Long-term implications of childhood obesity and BMI change over the life course for risk of type 2 diabetes remain uncertain. The objective was to establish whether there are effects on adult glucose metabolism of 1) sensitive periods of BMI gain or 2) long duration of overweight and obesity. RESEARCH DESIGN AND METHODS: Participants in the 1958 British birth cohort with child to adult BMI and glycosylated hemoglobin (HbA(1c)) at 45 years (n = 7,855). RESULTS: Prevalence of type 2 diabetes or HbA(1c) ≥7 was 2%. BMI gains in child- and adulthood were associated with higher HbA(1c): for every SD of 5-year BMI increase from 0 to 7 years, there was a 75% (95% CI 1.42–2.16) increased risk of HbA(1c) ≥7, increasing to a 4.7-fold (3.12–7.00) risk for the interval 23–33 years. Associations for BMI gain in adulthood were related to attained BMI but were independent for the longer period birth (or 7 years) to 45 years. Duration of obesity was also associated with HbA(1c); compared with the never obese, those with childhood onset had a 23.9-fold risk (13.5–42.1) of HbA(1c) ≥7%; odds ratios were 16.0 (10.6–24.2) and 2.99 (1.77–5.03), respectively, for young and midadulthood onset. Similar trends by onset age were found in mean HbA(1c) levels and for onset of overweight. Those with the earliest age of onset had higher BMI and waist circumference at 45 years, which markedly explained the associations for onset age and HbA(1c). CONCLUSIONS: Excessive BMI gain across the life span and earlier onset of overweight/obesity are associated with impaired glucose metabolism, in part through attained adult BMI

Simple holographic models of black hole evaporation

Several recent papers have shown a close relationship between entanglement wedge reconstruction and the unitarity of black hole evaporation in AdS/CFT. The analysis of these papers however has a rather puzzling feature: all calculations are done using bulk dynamics which are essentially those Hawking used to predict information loss, but applying ideas from entanglement wedge reconstruction seems to suggest a Page curve which is consistent with information conservation. Why should two different calculations in the same model give different answers for the Page curve? In this note we present a new pair of models which clarify this situation. Our first model gives a holographic illustration of unitary black hole evaporation, in which the analogue of the Hawking radiation purifies itself as expected, and this purification is reproduced by the entanglement wedge analysis. Moreover a smooth black hole interior persists until the last stages the evaporation process. Our second model gives an alternative holographic interpretation of the situation where the bulk evolution leads to information loss: unlike in the models proposed so far, this bulk information loss is correctly reproduced by the entanglement wedge analysis. This serves as an illustration that quantum extremal surfaces are in some sense kinematic: the time-dependence of the entropy they compute depends on the choice of bulk dynamics. In both models no bulk quantum corrections need to be considered: classical extremal surfaces are enough to do the job. We argue that our first model is the one which gives the right analogy for what actually happens to evaporating black holes, but we also emphasize that any complete resolution of the information problem will require an understanding of non-perturbative bulk dynamics.Comment: 15 pages, 5 figures. v2: Improved the octopus picture. Also an expanded discussion of the motivation for and lessons from the model

The State of the Region: Hampton Roads 2004

This is Old Dominion University\u27s fifth annual State of the Region report. While it represents the work of many people connected in various ways to the university, the report does not constitute an official viewpoint of Old Dominion, or it\u27s president, Dr. Roseann Runte. The report maintains the goal of stimulating thought and discussion that ultimately will make Hampton Roads an even better place to live. We are proud of our region\u27s many successes, but realize that it is possible to improve our performance. In order to do so, we must have accurate information about where we are and a sound understanding of the policy options open to us.https://digitalcommons.odu.edu/economics_books/1014/thumbnail.jp

Skunk River Review September 1990, vol 2

https://openspace.dmacc.edu/skunkriver/1005/thumbnail.jp

The effect of asymmetries on stock index return value-at-risk estimates

It is widely accepted that equity return volatility increases more following negative shocks rather than positive shocks. However, much of value-at-risk (VaR) analysis relies on the assumption that returns are normally distributed (a symmetric distribution). This article considers the effect of asymmetries on the evaluation and accuracy of VaR by comparing estimates based on various models

pRb Inactivation in Mammary Cells Reveals Common Mechanisms for Tumor Initiation and Progression in Divergent Epithelia

Retinoblastoma 1 (pRb) and the related pocket proteins, retinoblastoma-like 1 (p107) and retinoblastoma-like 2 (p130) (pRb(f), collectively), play a pivotal role in regulating eukaryotic cell cycle progression, apoptosis, and terminal differentiation. While aberrations in the pRb-signaling pathway are common in human cancers, the consequence of pRb(f) loss in the mammary gland has not been directly assayed in vivo. We reported previously that inactivating these critical cell cycle regulators in divergent cell types, either brain epithelium or astrocytes, abrogates the cell cycle restriction point, leading to increased cell proliferation and apoptosis, and predisposing to cancer. Here we report that mouse mammary epithelium is similar in its requirements for pRb(f) function; Rb(f) inactivation by T(121), a fragment of SV40 T antigen that binds to and inactivates pRb(f) proteins, increases proliferation and apoptosis. Mammary adenocarcinomas form within 16 mo. Most apoptosis is regulated by p53, which has no impact on proliferation, and heterozygosity for a p53 null allele significantly shortens tumor latency. Most tumors in p53 heterozygous mice undergo loss of the wild-type p53 allele. We show that the mechanism of p53 loss of heterozygosity is not simply the consequence of Chromosome 11 aneuploidy and further that chromosomal instability subsequent to p53 loss is minimal. The mechanisms for pRb and p53 tumor suppression in the epithelia of two distinct tissues, mammary gland and brain, are indistinguishable. Further, this study has produced a highly penetrant breast cancer model based on aberrations commonly observed in the human disease

Inter- and intra-molecular interactions of Arabidopsis thaliana DELLA protein RGL1

The phytohormone gibberellin and the DELLA proteins act together to control key aspects of plant development. Gibberellin induces degradation of DELLA proteins by recruitment of an F-box protein using a molecular switch: a gibberellin-bound nuclear receptor interacts with the N-terminal domain of DELLA proteins, and this event primes the DELLA C-terminal domain for interaction with the F-box protein. However, the mechanism of signalling between the N- and C-terminal domains of DELLA proteins is unresolved. In the present study, we used in vivo and in vitro approaches to characterize di- and tri-partite interactions of the DELLA protein RGL1 (REPRESSOR OF GA1-3-LIKE 1) of Arabidopsis thaliana with the gibberellin receptor GID1A (GIBBERELLIC ACID-INSENSITIVE DWARF-1A) and the F-box protein SLY1 (SLEEPY1). Deuterium-exchange MS unequivocally showed that the entire N-terminal domain of RGL1 is disordered prior to interaction with the GID1A; furthermore, association/dissociation kinetics, determined by surface plasmon resonance, predicts a two-state conformational change of the RGL1 N-terminal domain upon interaction with GID1A. Additionally, competition assays with monoclonal antibodies revealed that contacts mediated by the short helix Asp-Glu-Leu-Leu of the hallmark DELLA motif are not essential for the GID1A–RGL1 N-terminal domain interaction. Finally, yeast two- and three-hybrid experiments determined that unabated communication between N- and C-terminal domains of RGL1 is required for recruitment of the F-box protein SLY1

Australia\u27s health 2000 : the seventh biennial report of the Australian Institute of Health and Welfare

Australia\u27s Health 2000 is the seventh biennial health report of the Australian Institute of Health and Welfare. It is the nation\u27s authoritative source of information on patterns of health and illness, determinants of health, the supply and use of health services, and health services costs and performance.This 2000 edition serves as a summary of Australia\u27s health record at the end of the twentieth century. In addition, a special chapter is presented on changes in Australia\u27s disease profile over the last 100 years.Australia\u27s Health 2000 is an essential reference and information source for all Australians with an interest in health

Preface paper to the Semi-Arid Land-Surface-Atmosphere (SALSA) Program special issue

The Semi-Arid Land-Surface-Atmosphere Program (SALSA) is a multi-agency, multi-national research effort that seeks to evaluate the consequences of natural and human-induced environmental change in semi-arid regions. The ultimate goal of SALSA is to advance scientific understanding of the semi-arid portion of the hydrosphere–biosphere interface in order to provide reliable information for environmental decision making. SALSA approaches this goal through a program of long-term, integrated observations, process research, modeling, assessment, and information management that is sustained by cooperation among scientists and information users. In this preface to the SALSA special issue, general program background information and the critical nature of semi-arid regions is presented. A brief description of the Upper San Pedro River Basin, the initial location for focused SALSA research follows. Several overarching research objectives under which much of the interdisciplinary research contained in the special issue was undertaken are discussed. Principal methods, primary research sites and data collection used by numerous investigators during 1997–1999 are then presented. Scientists from about 20 US, five European (four French and one Dutch), and three Mexican agencies and institutions have collaborated closely to make the research leading to this special issue a reality. The SALSA Program has served as a model of interagency cooperation by breaking new ground in the approach to large scale interdisciplinary science with relatively limited resources

Biological clustering supports both "Dutch'' and "British'' hypotheses of asthma and chronic obstructive pulmonary disease

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. OBJECTIVE: We sought to determine, in terms of their sputum cellular and mediator profiles, the extent to which they represent distinct or overlapping conditions supporting either the "British" or "Dutch" hypotheses of airway disease pathogenesis. METHODS: We compared the clinical and physiological characteristics and sputum mediators between 86 subjects with severe asthma and 75 with moderate-to-severe COPD. Biological subgroups were determined using factor and cluster analyses on 18 sputum cytokines. The subgroups were validated on independent severe asthma (n = 166) and COPD (n = 58) cohorts. Two techniques were used to assign the validation subjects to subgroups: linear discriminant analysis, or the best identified discriminator (single cytokine) in combination with subject disease status (asthma or COPD). RESULTS: Discriminant analysis distinguished severe asthma from COPD completely using a combination of clinical and biological variables. Factor and cluster analyses of the sputum cytokine profiles revealed 3 biological clusters: cluster 1: asthma predominant, eosinophilic, high TH2 cytokines; cluster 2: asthma and COPD overlap, neutrophilic; cluster 3: COPD predominant, mixed eosinophilic and neutrophilic. Validation subjects were classified into 3 subgroups using discriminant analysis, or disease status with a binary assessment of sputum IL-1β expression. Sputum cellular and cytokine profiles of the validation subgroups were similar to the subgroups from the test study. CONCLUSIONS: Sputum cytokine profiling can determine distinct and overlapping groups of subjects with asthma and COPD, supporting both the British and Dutch hypotheses. These findings may contribute to improved patient classification to enable stratified medicine