Objectively measured physical capability levels and mortality: systematic review and meta-analysis

Objective: To do a quantitative systematic review, including published and unpublished data, examining the associations between individual objective measures of physical capability (grip strength, walking speed, chair rising, and standing balance times) and mortality in community dwelling populations. Design: Systematic review and meta-analysis. Data sources: Relevant studies published by May 2009 identified through literature searches using Embase (from 1980) and Medline (from 1950) and manual searching of reference lists; unpublished results were obtained from study investigators. Study selection: Eligible observational studies were those done in community dwelling people of any age that examined the association of at least one of the specified measures of physical capability (grip strength, walking speed, chair rises, or standing balance) with mortality. Data synthesis: Effect estimates obtained were pooled by using random effects meta-analysis models with heterogeneity between studies investigated. Results: Although heterogeneity was detected, consistent evidence was found of associations between all four measures of physical capability and mortality; those people who performed less well in these tests were found to be at higher risk of all cause mortality. For example, the summary hazard ratio for mortality comparing the weakest with the strongest quarter of grip strength (14 studies, 53 476 participants) was 1.67 (95% confidence interval 1.45 to 1.93) after adjustment for age, sex, and body size (I2=84.0%, 95% confidence interval 74% to 90%; P from Q statistic <0.001). The summary hazard ratio for mortality comparing the slowest with the fastest quarter of walking speed (five studies, 14 692 participants) was 2.87 (2.22 to 3.72) (I2=25.2%, 0% to 70%; P=0.25) after similar adjustments. Whereas studies of the associations of walking speed, chair rising, and standing balance with mortality have only been done in older populations (average age over 70 years), the association of grip strength with mortality was also found in younger populations (five studies had an average age under 60 years). Conclusions: Objective measures of physical capability are predictors of all cause mortality in older community dwelling populations. Such measures may therefore provide useful tools for identifying older people at higher risk of death. With Contributions from Dr P.A. Bath, University of Sheffiel

Centre-level variation in speech outcome and interventions, and factors associated with poor speech outcomes in 5-year-old children with non-syndromic unilateral cleft lip and palate:the Cleft Care UK study. Part 4

Objectives: To investigate centre-level variation in speech intervention and outcome and factors associated with a speech disorder in children in Cleft Care UK (CCUK). Setting and Sample Population: Two hundred and sixty-eight 5-year-old British children with non-syndromic unilateral cleft lip and palate recruited to CCUK. Materials and Methods: Centre-based therapists undertook audio-video recordings. Perceptual analysis was undertaken using the CAPS-A tool. Speech outcomes were based on structural and articulation scores, and intelligibility/distinctiveness. Between-centre variation in treatment and outcomes were examined using multilevel models. These models were extended to estimate the association between a range of factors (hearing loss, speech intervention, fistula, secondary speech surgery for velopharyngeal insufficiency, socio-economic status, gender, and parental happiness with speech) and speech outcomes. Results: There was centre-level variation in secondary speech surgery, speech intervention, structure and intelligibility outcomes. Children with a history of speech intervention had a lower odds of poor intelligibility/distinctiveness, 0.1 (95% CI: 0.0-0.4). Parental concern was associated with a higher odds of poor intelligibility/distinctiveness, 13.2 (95% CI: 4.9-35.1). Poor speech outcomes were associated with a fistula, secondary speech surgery and history of hearing loss. Conclusions: Within the centralized service there is centre-level variation in secondary speech surgery, intervention and speech outcomes. These findings support the importance of early management of fistulae, effective management of velopharyngeal insufficiency and hearing impairment, and most importantly speech intervention in the preschool years. Parental concern about speech is a good indicator of speech status

Centralization of cleft care in the UK. Part 6:a tale of two studies

OBJECTIVES: We summarize and critique the methodology and outcomes from a substantial study which has investigated the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after the UK government started to implement the centralization of cleft care in response to an earlier survey in 1998, the Clinical Standards Advisory Group (CSAG). SETTING AND SAMPLE POPULATION: A UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Data were collected from children born in the UK with a unilateral cleft lip and palate between 1 April 2005 and 31 March 2007. MATERIALS AND METHODS: We discuss and contextualize the outcomes from speech recordings, hearing, photographs, models, oral health and psychosocial factors in the current study. We refer to the earlier survey and other relevant studies. RESULTS: We present arguments for centralization of cleft care in healthcare systems, and we evidence this with improvements seen over a period of 15 years in the UK. We also make recommendations on how future audit and research may configure. CONCLUSIONS: Outcomes for children with a unilateral cleft lip and palate have improved after the introduction of a centralized multidisciplinary service, and other countries may benefit from this model. Predictors of early outcomes are still needed, and repeated cross-sectional studies, larger longitudinal studies and adequately powered trials are required to create a research-led evidence-based (centralized) service

A cross-sectional survey of 5-year-old children with non-syndromic unilateral cleft lip and palate:the Cleft Care UK study. Part 1: background and methodology

OBJECTIVES: We describe the methodology for a major study investigating the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after an initial survey, detailed in the Clinical Standards Advisory Group (CSAG) report in 1998, had informed government recommendations on centralization. SETTING AND SAMPLE POPULATION: This is a UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Children born between 1 April 2005 and 31 March 2007 were seen in cleft centre audit clinics. MATERIALS AND METHODS: Consent was obtained for the collection of routine clinical measures (speech recordings, hearing, photographs, models, oral health, psychosocial factors) and anthropometric measures (height, weight, head circumference). The methodology for each clinical measure followed those of the earlier survey as closely as possible. RESULTS: We identified 359 eligible children and recruited 268 (74.7%) to the study. Eleven separate records for each child were collected at the audit clinics. In total, 2666 (90.4%) were collected from a potential 2948 records. The response rates for the self-reported questionnaires, completed at home, were 52.6% for the Health and Lifestyle Questionnaire and 52.2% for the Satisfaction with Service Questionnaire. CONCLUSIONS: Response rates and measures were similar to those achieved in the previous survey. There are practical, administrative and methodological challenges in repeating cross-sectional surveys 15 years apart and producing comparable data

Detailed electronic structure studies on superconducting MgB2_2 and related compounds

In order to understand the unexpected superconducting behavior of MgB$_2$ compound we have made electronic structure calculations for MgB$_2$ and closely related systems. Our calculated Debye temperature from the elastic properties indicate that the average phonon frequency is very large in MgB$_2$ compared with other superconducting intermetallics and the exceptionally high $T_c$ in this material can be explained through BCS mechanism only if phonon softening occurs or the phonon modes are highly anisotropic. We identified a doubly-degenerate quasi-two dimensional key-energy band in the vicinity of $E_{F}$ along $\Gamma$-A direction of BZ which play an important role in deciding the superconducting behavior of this material. Based on this result, we have searched for similar kinds of electronic feature in a series of isoelectronic compounds such as BeB$_2$, CaB$_2$, SrB$_2$, LiBC and MgB$_2$C$_2$ and found that MgB$_2$C$_2$ is one potential material from the superconductivity point of view. There are contradictory experimental results regarding the anisotropy in the elastic properties of MgB$_2$ ranging from isotropic, moderately anisotropic to highly anisotropic. In order to settle this issue we have calculated the single crystal elastic constants for MgB$_2$ by the accurate full-potential method and derived the directional dependent linear compressibility, Young's modulus, shear modulus and relevant elastic properties. We have observed large anisotropy in the elastic properties. Our calculated polarized optical dielectric tensor shows highly anisotropic behavior even though it possesses isotropic transport property. MgB$_2$ possesses a mixed bonding character and this has been verified from density of states, charge density and crystal orbital Hamiltonian population analyses

Black Hole, Jet, and Disk: The Universal Engine

In this paper I review the results of our ongoing project to investigate the coupling between accretion disk and radio jet in galactic nuclei and stellar mass black holes. We find a good correlation between the UV bump luminosity and the radio luminosities of AGN, which improves upon the usual [OIII]/radio correlations. Taking mass and energy conservation in the jet/disk system into account we can successfully model the correlation for radio-loud and radio-weak quasars. We find that jets are comparable in power to the accretion disk luminosity, and the difference between radio-loud and radio-weak may correspond to two natural stages of the relativistic electron distribution -- assuming that radio weak quasars have jets as well. The distribution of flat- and steep-spectrum sources is explained by bulk Lorentz factors gamma_j ~ 5-10. The absence of radio-loud quasars below a critical optical luminosity coincides with the FR I/FR II break and could be explained by a powerdependent, ``closing'' torus. This points towards a different type of obscuring torus in radio-loud host galaxies which might be a consequence of past mergers (e.g. by the temporary formation of a binary black-hole). Interaction of the jet with the closing torus might in principle also help to make a jet radio-loud. Turning to stellar-mass black holes we find that galactic jet sources can be described with the same coupled jet/disk model as AGN which is suggestive of some kind of universal coupling between jet and accretion disk around compact objects.Comment: to appear in ``Jets from Stars and Galactic Nuclei'', Springer Lecture Notes, plain TeX, 16 pages, also at http://www.astro.umd.edu/~hfalcke/publications.htm

A Density Functional Study of Atomic Hydrogen Adsorption on Plutonium Layers

Hydrogen adsorption on delta-Pu (100) and (111) surfaces using the generalized gradient approximation of the density functional theory with Perdew and Wang functionals have been studied at both the spin-polarized level and the non-spin-polarized level. For the (100) surface at the non-spin-polarized level, we find that the center position of the (100) surface is the most favorable site with a chemisorption energy of 2.762 eV and an optimum distance of the hydrogen adatom to the Pu surface of 1.07 A. For the spin-polarized (100) surface, the center site is again the preferred site with a chemisorption energy of 3.467 eV and an optimum hydrogen distance of 1.13 A. For the non-spin-polarized (111) surface, the center position is also the preferred site, but with slightly lower chemisorption energy, namely 2.756 eV and a higher hydrogen distance, 1.40 A, compared to the (100) center site. The center site is also the preferred site for the spin-polarized (111) surface, with a chemisorption energy of 3.450 eV and a hydrogen distance of 1.42 A. Also, for the spin-polarized calculations, the over all net magnetic moments of the (111) surface changed significantly due to the hydrogen adsorption. The 5f orbitals are delocalized, especially as one approaches the Fermi level. However, the degree of localization decreases for spin-polarized calculations. The coordination numbers have a significant role in the chemical bonding process. Mulliken charge distribution analysis indicates that the interaction of Pu with H mainly takes place in the first layer and that the other two layers are only slightly affected. Work functions, in general, tend to increase due to the presence of a hydrogen adatom.Comment: The introduction is extended to include a short review of delta-P

A genome-wide association study of total child psychiatric problems scores

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.</p

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease