Body composition, IGF1 status, and physical functionality in nonagenarians: implications for osteosarcopenia

OBJECTIVES: Body composition alterations occur during aging. The purpose of the present analysis was to explore the functional consequences of the overlap of sarcopenia and osteoporosis, and the potential role of insulin-like growth factor 1 (IGF1) in their development in the oldest old. SETTING AND PARTICIPANTS: Eighty-seven nonagenarians from the Louisiana Healthy Aging Study were included. MEASURES: The definition of sarcopenia was based on appendicular lean mass (ALM). Osteoporosis was diagnosed based on bone mineral density (BMD) T score. Four phenotypes were compared: (1) healthy body composition, that is, nonosteoporotic nonsarcopenic (CO, control group), (2) osteoporotic (O, low BMD T score), (3) sarcopenic (S, low ALM), and (4) osteosarcopenic (OS, low BMD T score and low ALM). Sex- and age-specific IGF1-Standard Deviation Scores (SDS) were calculated. The Continuous Scale-Physical Functional Performance (CS-PFP) test was performed. RESULTS: In OS men, IGF1-SDS values (-0.61 ±0.37 vs -0.04 ± 0.52, P = .02) were lower than those in CO males (control group), whereas IGF1-SDS were similar in the 4 body composition phenotypes in women. In men only, ALM was positively associated with IGF1-SDS values (P = .01) independent of age and C-reactive protein concentration. Regarding bone health, we found no association between IGF1-SDS values and BMD. IGF1-SDS was not associated with functional performance (CS-PFP) in men and women. CONCLUSIONS/IMPLICATIONS: IGF1 sensitivity in skeletal muscle and bone may differ by sex in the oldest old. IGF1 status did not appear to affect physical functionality. Determinants and clinical and functional characteristics of osteosarcopenia need to be further investigated in order to define conclusive diagnostic criteria

A time-domain control signal detection technique for OFDM

Transmission of system-critical control information plays a key role in efficient management of limited wireless network resources and successful reception of payload data information. This paper uses an orthogonal frequency division multiplexing (OFDM) architecture to investigate the detection performance of a time-domain approach used to detect deterministic control signalling information. It considers a type of control information chosen from a finite set of information, which is known at both transmitting and receiving wireless terminals. Unlike the maximum likelihood (ML) estimation method, which is often used, the time-domain detection technique requires no channel estimation and no pilots as it uses a form of time-domain correlation as the means of detection. Results show that when compared with the ML method, the time-domain approach improves detection performance even in the presence of synchronisation error caused by carrier frequency offset

Theories of behaviour change synthesised into a set of theoretical groupings: Introducing a thematic series on the Theoretical Domains Framework

Behaviour change is key to increasing the uptake of evidence into healthcare practice. Designing behaviour-change interventions first requires problem analysis, ideally informed by theory. Yet the large number of partly overlapping theories of behaviour makes it difficult to select the most appropriate theory. The need for an overarching theoretical framework of behaviour change was addressed in research in which 128 explanatory constructs from 33 theories of behaviour were identified and grouped. The resulting Theoretical Domains Framework (TDF) appears to be a helpful basis for investigating implementation problems. Research groups in several countries have conducted TDF-based studies. It seems timely to bring together the experience of these teams in a thematic series to demonstrate further applications and to report key developments. This overview article describes the TDF, provides a brief critique of the framework, and introduces this thematic series. In a brief review to assess the extent of TDF-based research, we identified 133 papers that cite the framework. Of these, 17 used the TDF as the basis for empirical studies to explore health professionals’ behaviour. The identified papers provide evidence of the impact of the TDF on implementation research. Two major strengths of the framework are its theoretical coverage and its capacity to elicit beliefs that could signify key mediators of behaviour change. The TDF provides a useful conceptual basis for assessing implementation problems, designing interventions to enhance healthcare practice, and understanding behaviour-change processes. We discuss limitations and research challenges and introduce papers in this series

Next-to-leading order QCD predictions for Z0H0+jetZ^0 H^0 + {\rm jet} production at LHC

We calculate the complete next-to-leading order (NLO) QCD corrections to the $Z^0H^0$ production in association with a jet at the LHC. We study the impacts of the NLO QCD radiative corrections to the integrated and differential cross sections and the dependence of the cross section on the factorization/renormalization scale. We present the transverse momentum distributions of the final $Z^0$-, Higgs-boson and leading-jet. We find that the NLO QCD corrections significantly modify the physical observables, and obviously reduce the scale uncertainty of the LO cross section. The QCD K-factors can be 1.183 and 1.180 at the $\sqrt{s}=14 TeV$ and $\sqrt{s}=7 TeV$ LHC respectively, when we adopt the inclusive event selection scheme with $p_{T,j}^{cut}=50 GeV$, $m_H=120 GeV$ and $\mu=\mu_r=\mu_f=\mu_0 \equiv 1/2(m_Z+m_H)$. Furthermore, we make the comparison between the two scale choices, $\mu=\mu_0$ and $\mu=\mu_1=1/2(E_{T}^{Z}+E_{T}^{H}+ \sum_{j}E_{T}^{jet})$, and find the scale choice $\mu=\mu_1$ seems to be more appropriate than the fixed scale $\mu=\mu_0$.Comment: 18 pages, 7 figure

The role of sociocultural perspectives in eating disorder treatment: A study of health professionals

Eating disorders are now often approached as biopsychosocial problems, because they are widely recognised as multifactorial in origin. However, it has been suggested that there is a substantial and unwarranted imbalance within this biopsychosocial framework, with the ‘social’ aspects of the equation relegated to secondary or facilitating factors within treatment contexts. Drawing on data from 12 qualitative interviews with health professionals in a UK region, this article examines the extent to which sociocultural perspectives on eating disorders are valued and explored in eating disorder treatment, with a particular focus on the relationship between eating disorders and gender. As girls/women are widely acknowledged to be disproportionately affected by eating problems, the article draws on feminist perspectives on eating disorders to explore whether the relationships between cultural constructions of femininity and experiences of body/eating distress are actively addressed within treatment. The study reveals high levels of inconsistency in this regard, as while some participants see such issues as central to treatment, others have ‘never really considered’ them before. In addition, the study examines the potential limitations of how such sociocultural issues are conceptualised and addressed, as well as why they might be marginalised in the current climate of evidence-based eating disorder treatment. The article then considers the implications of the findings for thinking about feminist perspectives on eating disorders – and the significance of gender in treatment – at the level of both research and practice

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR