The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

Normal values for pancreatic stone protein in different age groups.

BACKGROUND: Pancreatic stone protein (PSP) has been identified as a promising sepsis marker in adults, children and neonates. However, data on population-based reference values are lacking. This study aimed to establish age-specific reference values for PSP. METHODS: PSP was determined using a specific ELISA. PSP serum concentrations were determined in 372 healthy subjects including 217 neonates, 94 infants and children up to 16 years, and 61 adults. The adjacent categories method was used to determine which age categories had significantly different PSP concentrations. RESULTS: PSP circulating levels were not gender-dependent and ranged from 1.0 to 99.4 ng/ml with a median of 9.2 ng/ml. PSP increased significantly between the age categories, from a median of 2.6 ng/ml in very preterm newborns, to 6.3 ng/ml in term newborns, to 16.1 ng/ml in older children (p < 0.001). PSP levels were higher on postnatal day three compared to levels measured immediately post delivery (p < 0.001). Paired umbilical artery and umbilical vein samples were strongly correlated (p < 0.001). Simultaneously obtained capillary heel-prick versus venous samples showed a good level of agreement for PSP (Rho 0.89, bias 19 %). CONCLUSIONS: This study provides age-specific normal values that may be used to define cut-offs for future trials on PSP. We demonstrate an age-dependent increase of PSP from birth to childhood.

Feather mercury levels in seabirds at South Georgia: Influences of trophic position, sex and age

We studied the mercury contamination of 13 species of seabirds breeding on Bird Island, South Georgia, in 1998. Total mercury concentrations in body feather samples of birds caught at their breeding colonies were determined. Among the species, grey-headed albatross (8933 ng g-1) and southern giant petrel (7774 ng g-1) showed the highest, and gentoo penguin (948 ng g-1) the lowest body feather mercury concentrations. Mercury levels were negatively correlated with the proportion of crustaceans (mainly krill) in the species¹ diets, suggesting that the trophic level is the most important factor in explaining the variation of mercury concentrations in Antarctic seabirds. In 4 species studied for age effects among adult birds (grey-headed and black-browed albatross, northern and southern giant petrel), no age-dependent variation in mercury levels was found. Sex differences were also assessed: female gentoo penguins had lower mercury levels than males, which may be related to the elimination of part of the mercury body burden by females into eggs. In contrast, northern giant petrel males had lower levels than females, which may be related to a higher consumption by males of carrion from Antarctic fur seals. In grey-headed albatrosses, mercury levels were 113% higher than in 1989, when this species was investigated at the same site, indicating a possible increase in mercury pollution of the Southern Ocean during the last decade.

Maternal age and Down syndrome in Southeastern Brazil

The proportion of maternal-age-independent patients estimated among 200 Brazilian Down syndrome children (59.6%) was significantly larger than that of maternal-age-dependent cases (40.4%). The latter proportion is the smallest observed in pertinent literature and due basically to the low mean maternal age of the population analyzed. Based on the remarkable correlation (r = 0.95) between the proportion of maternal-age-dependent patients and the mean maternal age of the general population, a simple predictive equation to estimate the proportion of maternal-age-dependent Down syndrome patients based on the mean maternal age of the general population is suggested in situations where reliable data on the incidence of this syndrome according to maternal age is not available.

Successful IFRS standard change implementation process after the initial IFRS implementation

The main objective of the study was to form a strategic process model and project management tool to help IFRS change implementation projects in the future. These research results were designed based on the theoretical framework of Total Quality Management and leaning on the facts that were collected during the empirical case study of IAS 17 change. The us-age of the process oriented approach in IFRS standard change implementation after the initial IFRS implementation is rationalized with the following arguments: 1) well designed process tools lead to optimization of resources 2) With the help of process stages and related tasks it is easy to ensure the efficient way of working and managing the project as well as make sure to include all necessary stakeholders to the change process. This research is following the qualitative approach and the analysis is in describing format. The first part of the study is a literature review and the latter part has been conducted as a case study. The data has been col-lected in the case company with interviews and observation. The main findings are a process model for IFRS standard change process and a check-list formatted management tool for up-coming IFRS standard change projects. The process flow follows the main cornerstones in IASB’s standard setting process and the management tool has been divided to stages accordingly.

Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

Loss of Y-chromosome has been correlated with older age in males. Furthermore, current evidence indicates that Y-chromosome loss also occurs in several human tumors, including head and neck carcinomas. However, the association between Y nullisomy and the occurrence of neoplasias in elderly men has not been well established. In the present study, the association between Y-chromosome loss and head and neck carcinomas was evaluated by comparison to cells from peripheral blood lymphocytes and normal mucosa of cancer-free individuals matched for age using dual-color fluorescence in situ hybridization. Twenty-one patients ranging in age from 28 to 68 years were divided into five-year groups for comparison with 16 cancer-free individuals matched for age. The medical records of all patients were examined to obtain clinical and histopathological data. None of the patients had undergone radiotherapy or chemotherapy before surgery. In all groups, the frequency of Y-chromosome loss was higher among patients than among normal reference subjects (P < 0.0001) and was not age-dependent. These data suggest that Y-chromosome loss is a tumor-specific alteration not associated with advanced age in head and neck carcinomas.

Neural substrates and functional connectivity associated with sleep-dependent and independent consolidation of new motor skills

La mémoire n’est pas un processus unitaire et est souvent divisée en deux catégories majeures: la mémoire déclarative (pour les faits) et procédurale (pour les habitudes et habiletés motrices). Pour perdurer, une trace mnésique doit passer par la consolidation, un processus par lequel elle devient plus robuste et moins susceptible à l’interférence. Le sommeil est connu comme jouant un rôle clé pour permettre le processus de consolidation, particulièrement pour la mémoire déclarative. Depuis plusieurs années cependant, son rôle est aussi reconnu pour la mémoire procédurale. Il est par contre intéressant de noter que ce ne sont pas tous les types de mémoire procédurale qui requiert le sommeil afin d’être consolidée. Entre autres, le sommeil semble nécessaire pour consolider un apprentissage de séquences motrices (s’apparentant à l’apprentissage du piano), mais pas un apprentissage d’adaptation visuomotrice (tel qu’apprendre à rouler à bicyclette). Parallèlement, l’apprentissage à long terme de ces deux types d’habiletés semble également sous-tendu par des circuits neuronaux distincts; c’est-à-dire un réseau cortico-striatal et cortico-cérébelleux respectivement. Toutefois, l’implication de ces réseaux dans le processus de consolidation comme tel demeure incertain. Le but de cette thèse est donc de mieux comprendre le rôle du sommeil, en contrôlant pour le simple passage du temps, dans la consolidation de ces deux types d’apprentissage, à l’aide de l’imagerie par résonnance magnétique fonctionnelle et d’analyses de connectivité cérébrale. Nos résultats comportementaux supportent l’idée que seul l’apprentissage séquentiel requiert le sommeil pour déclencher le processus de consolidation. Nous suggérons de plus que le putamen est fortement associé à ce processus. En revanche, les performances d’un apprentissage visuomoteur s’améliorent indépendamment du sommeil et sont de plus corrélées à une plus grande activation du cervelet. Finalement, en explorant l’effet du sommeil sur la connectivité cérébrale, nos résultats démontrent qu’en fait, un système cortico-striatal semble être plus intégré suite à la consolidation. C’est-à-dire que l’interaction au sein des régions du système est plus forte lorsque la consolidation a eu lieu, après une nuit de sommeil. En opposition, le simple passage du temps semble nuire à l’intégration de ce réseau cortico-striatal. En somme, nous avons pu élargir les connaissances quant au rôle du sommeil pour la mémoire procédurale, notamment en démontrant que ce ne sont pas tous les types d’apprentissages qui requièrent le sommeil pour amorcer le processus de consolidation. D’ailleurs, nous avons également démontré que cette dissociation de l’effet du sommeil est également reflétée par l’implication de deux réseaux cérébraux distincts. À savoir, un réseau cortico-striatal et un réseau cortico-cérébelleux pour la consolidation respective de l’apprentissage de séquence et d’adaptation visuomotrice. Enfin, nous suggérons que la consolidation durant le sommeil permet de protéger et favoriser une meilleure cohésion au sein du réseau cortico-striatal associé à notre tâche; un phénomène qui, s’il est retrouvé avec d’autres types d’apprentissage, pourrait être considéré comme un nouveau marqueur de la consolidation.

Social networks: evolving graphs with memory dependent edges

The plethora, and mass take up, of digital communication tech- nologies has resulted in a wealth of interest in social network data collection and analysis in recent years. Within many such networks the interactions are transient: thus those networks evolve over time. In this paper we introduce a class of models for such networks using evolving graphs with memory dependent edges, which may appear and disappear according to their recent history. We consider time discrete and time continuous variants of the model. We consider the long term asymptotic behaviour as a function of parameters controlling the memory dependence. In particular we show that such networks may continue evolving forever, or else may quench and become static (containing immortal and/or extinct edges). This depends on the ex- istence or otherwise of certain infinite products and series involving age dependent model parameters. To test these ideas we show how model parameters may be calibrated based on limited samples of time dependent data, and we apply these concepts to three real networks: summary data on mobile phone use from a developing region; online social-business network data from China; and disaggregated mobile phone communications data from a reality mining experiment in the US. In each case we show that there is evidence for memory dependent dynamics, such as that embodied within the class of models proposed here.

Influence of age on the development of immunological lung response in intrauterine undernourishment

Objective: We investigated the effect of intrauterine undernourishment on some features of asthma using a model of allergic lung inflammation in rats. The effects of age at which the rats were challenged (5 and 9 wk) were also evaluated. Methods: Intrauterine undernourished offspring were obtained from dams that were fed 50% of the nourished diet of counterparts and were immunized at 5 and 9 wk of age. They were tested for immunoglobulin E anti-ova titers (by passive cutaneous anaphylaxis), cell count in the bronchoal-veolar fluid, leukotriene concentration, airway reactivity, mucus production, and blood corticosterone and leptin concentrations 21 d, after immunologic challenge. Results: Intrauterine undernourishment significantly reduced the antigen-specific immunoglobulin E production, inflammatory cell infiltration into airways, mucus secretion, and production of leukotrienes B-4/C-4 in the lungs in both age groups compared with respective nourished rats. The increased reactivity to methacholine that follows antigen challenge was not affected by intrauterine undernourishment. Corticosterone levels increased with age in the undernourished rats` offspring, but not in the nourished rats` offspring. Undernourished offspring already presented high levels of corticosterone before inflammatory stimulus and were not modified by antigen challenge. Leptin levels increased with challenge in the nourished rats but not in the undernourished rats and could not be related to corticosterone levels in the. undernourished rats. Conclusion: Intrauterine undernourishment has a striking and age-dependent effect on the off spring, reducing lung allergic inflammation. (C) 2008 Elsevier Inc. All rights reserved.

Undersampled Critical Branching Processes on Small-World and Random Networks Fail to Reproduce the Statistics of Spike Avalanches

The power-law size distributions obtained experimentally for neuronal avalanches are an important evidence of criticality in the brain. This evidence is supported by the fact that a critical branching process exhibits the same exponent t~3=2. Models at criticality have been employed to mimic avalanche propagation and explain the statistics observed experimentally. However, a crucial aspect of neuronal recordings has been almost completely neglected in the models: undersampling. While in a typical multielectrode array hundreds of neurons are recorded, in the same area of neuronal tissue tens of thousands of neurons can be found. Here we investigate the consequences of undersampling in models with three different topologies (two-dimensional, small-world and random network) and three different dynamical regimes (subcritical, critical and supercritical). We found that undersampling modifies avalanche size distributions, extinguishing the power laws observed in critical systems. Distributions from subcritical systems are also modified, but the shape of the undersampled distributions is more similar to that of a fully sampled system. Undersampled supercritical systems can recover the general characteristics of the fully sampled version, provided that enough neurons are measured. Undersampling in two-dimensional and small-world networks leads to similar effects, while the random network is insensitive to sampling density due to the lack of a well-defined neighborhood. We conjecture that neuronal avalanches recorded from local field potentials avoid undersampling effects due to the nature of this signal, but the same does not hold for spike avalanches. We conclude that undersampled branching-process-like models in these topologies fail to reproduce the statistics of spike avalanches.

Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Metabolic syndrome and dementia associated with Parkinson's disease: impact of age and hypertension

Objective: To determine correlations between age and metabolic disorders in Parkinson's disease (PD) patients. Methods: This observational cross-sectional study included brief tests for dementia and the Mattis test. Signals of metabolic syndrome were evaluated. Results: There was no significant effect from the presence of hypertension (OR=2.36 for patients under 65 years old and OR=0.64 for patients over 65), diabetes or hypercholesterolemia regarding occurrences of dementia associated with PD (24% of the patients). The study demonstrated that each year of age increased the estimated risk of dementia in PD patients by 9% (OR=1.09; 95%Cl: 1.01-1.17). Conclusion: There was no evidence to correlate the presence of metabolic syndrome with the risk of dementia that was associated with PD. The study confirmed that dementia in PD is age dependent and not related to disease duration.

An explanatory mechanism for the different decline in limb strength in older women

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Interactions of age and leg muscle fatigue on unobstructed walking and obstacle crossing

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Budding Process During the Organogenesis of the Ventral Prostatic Lobe in Mongolian Gerbil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)