Objective To systematically review studies quantifying the associations of long term (clinic), mid-term (home), and short term (ambulatory) variability in blood pressure, independent of mean blood ...pressure, with cardiovascular disease events and mortality.Data sources Medline, Embase, Cinahl, and Web of Science, searched to 15 February 2016 for full text articles in English.Eligibility criteria for study selection Prospective cohort studies or clinical trials in adults, except those in patients receiving haemodialysis, where the condition may directly impact blood pressure variability. Standardised hazard ratios were extracted and, if there was little risk of confounding, combined using random effects meta-analysis in main analyses. Outcomes included all cause and cardiovascular disease mortality and cardiovascular disease events. Measures of variability included standard deviation, coefficient of variation, variation independent of mean, and average real variability, but not night dipping or day-night variation.Results 41 papers representing 19 observational cohort studies and 17 clinical trial cohorts, comprising 46 separate analyses were identified. Long term variability in blood pressure was studied in 24 papers, mid-term in four, and short-term in 15 (two studied both long term and short term variability). Results from 23 analyses were excluded from main analyses owing to high risks of confounding. Increased long term variability in systolic blood pressure was associated with risk of all cause mortality (hazard ratio 1.15, 95% confidence interval 1.09 to 1.22), cardiovascular disease mortality (1.18, 1.09 to 1.28), cardiovascular disease events (1.18, 1.07 to 1.30), coronary heart disease (1.10, 1.04 to 1.16), and stroke (1.15, 1.04 to 1.27). Increased mid-term and short term variability in daytime systolic blood pressure were also associated with all cause mortality (1.15, 1.06 to 1.26 and 1.10, 1.04 to 1.16, respectively).Conclusions Long term variability in blood pressure is associated with cardiovascular and mortality outcomes, over and above the effect of mean blood pressure. Associations are similar in magnitude to those of cholesterol measures with cardiovascular disease. Limited data for mid-term and short term variability showed similar associations. Future work should focus on the clinical implications of assessment of variability in blood pressure and avoid the common confounding pitfalls observed to date.Systematic review registration PROSPERO CRD42014015695.
Recombination is proposed to be critical for coronavirus (CoV) diversity and emergence of SARS-CoV-2 and other zoonotic CoVs. While RNA recombination is required during normal CoV replication, the ...mechanisms and determinants of CoV recombination are not known. CoVs encode an RNA proofreading exoribonuclease (nsp14-ExoN) that is distinct from the CoV polymerase and is responsible for high-fidelity RNA synthesis, resistance to nucleoside analogues, immune evasion, and virulence. Here, we demonstrate that CoVs, including SARS-CoV-2, MERS-CoV, and the model CoV murine hepatitis virus (MHV), generate extensive and diverse recombination products during replication in culture. We show that the MHV nsp14-ExoN is required for native recombination, and that inactivation of ExoN results in decreased recombination frequency and altered recombination products. These results add yet another critical function to nsp14-ExoN, highlight the uniqueness of the evolved coronavirus replicase, and further emphasize nsp14-ExoN as a central, completely conserved, and vulnerable target for inhibitors and attenuation of SARS-CoV-2 and future emerging zoonotic CoVs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Virtually all plants and animals, including humans, are home to symbiotic microorganisms. Symbiotic interactions can be neutral, harmful or have beneficial effects on the host organism. However, ...growing evidence suggests that microbial symbionts can evolve rapidly, resulting in drastic transitions along the parasite-mutualist continuum. In this Review, we integrate theoretical and empirical findings to discuss the mechanisms underpinning these evolutionary shifts, as well as the ecological drivers and why some host-microorganism interactions may be stuck at the end of the continuum. In addition to having biomedical consequences, understanding the dynamic life of microorganisms reveals how symbioses can shape an organism's biology and the entire community, particularly in a changing world.
The possible transition to the so-called ultimate regime, wherein both the bulk and the boundary layers are turbulent, has been an outstanding issue in thermal convection, since the seminal work by ...Kraichnan Phys. Fluids 5, 1374 (1962)PFLDAS0031-917110.1063/1.1706533. Yet, when this transition takes place and how the local flow induces it is not fully understood. Here, by performing two-dimensional simulations of Rayleigh-Bénard turbulence covering six decades in Rayleigh number Ra up to 10^{14} for Prandtl number Pr=1, for the first time in numerical simulations we find the transition to the ultimate regime, namely, at Ra^{*}=10^{13}. We reveal how the emission of thermal plumes enhances the global heat transport, leading to a steeper increase of the Nusselt number than the classical Malkus scaling Nu∼Ra^{1/3} Proc. R. Soc. A 225, 196 (1954)PRLAAZ1364-502110.1098/rspa.1954.0197. Beyond the transition, the mean velocity profiles are logarithmic throughout, indicating turbulent boundary layers. In contrast, the temperature profiles are only locally logarithmic, namely, within the regions where plumes are emitted, and where the local Nusselt number has an effective scaling Nu∼Ra^{0.38}, corresponding to the effective scaling in the ultimate regime.
Abstract
We use very long baseline interferometry to measure the proper motions of three black hole X-ray binaries (BHXBs). Using these results together with data from the literature and Gaia DR2 to ...collate the best available constraints on proper motion, parallax, distance, and systemic radial velocity of 16 BHXBs, we determined their three-dimensional Galactocentric orbits. We extended this analysis to estimate the probability distribution for the potential kick velocity (PKV) a BHXB system could have received on formation. Constraining the kicks imparted to BHXBs provides insight into the birth mechanism of black holes (BHs). Kicks also have a significant effect on BH–BH merger rates, merger sites, and binary evolution, and can be responsible for spin–orbit misalignment in BH binary systems. 75 per cent of our systems have potential kicks $\gt 70\, \rm {km\,s^{-1}}$. This suggests that strong kicks and hence spin–orbit misalignment might be common among BHXBs, in agreement with the observed quasi-periodic X-ray variability in their power density spectra. We used a Bayesian hierarchical methodology to analyse the PKV distribution of the BHXB population, and suggest that a unimodal Gaussian model with a mean of 107 $\pm \,\,16\, \rm {km\,s^{-1}}$ is a statistically favourable fit. Such relatively high PKVs would also reduce the number of BHs likely to be retained in globular clusters. We found no significant correlation between the BH mass and PKV, suggesting a lack of correlation between BH mass and the BH birth mechanism. Our python code allows the estimation of the PKV for any system with sufficient observational constraints.
The logarithmic law for the mean velocity in turbulent boundary layers has long provided a valuable and robust reference for comparison with theories, models and large-eddy simulations (LES) of ...wall-bounded turbulence. More recently, analysis of high-Reynolds-number experimental boundary-layer data has shown that also the variance and higher-order moments of the streamwise velocity fluctuations
$\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}u^{\prime +}$
display logarithmic laws. Such experimental observations motivate the question whether LES can accurately reproduce the variance and the higher-order moments, in particular their logarithmic dependency on distance to the wall. In this study we perform LES of very high-Reynolds-number wall-modelled channel flow and focus on profiles of variance and higher-order moments of the streamwise velocity fluctuations. In agreement with the experimental data, we observe an approximately logarithmic law for the variance in the LES, with a ‘Townsend–Perry’ constant of
$A_1\approx 1.25$
. The LES also yields approximate logarithmic laws for the higher-order moments of the streamwise velocity. Good agreement is found between
$A_p$
, the generalized ‘Townsend–Perry’ constants for moments of order
$2p$
, from experiments and simulations. Both are indicative of sub-Gaussian behaviour of the streamwise velocity fluctuations. The near-wall behaviour of the variance, the ranges of validity of the logarithmic law and in particular possible dependencies on characteristic length scales such as the roughness length
$z_0$
, the LES grid scale
$\Delta $
, and subgrid scale mixing length
$C_s\Delta $
are examined. We also present LES results on moments of spanwise and wall-normal fluctuations of velocity.
The unifying theory of scaling in thermal convection (Grossmann & Lohse, J. Fluid. Mech., vol. 407, 2000, pp. 27–56; henceforth the GL theory) suggests that there are no pure power laws for the ...Nusselt and Reynolds numbers as function of the Rayleigh and Prandtl numbers in the experimentally accessible parameter regime. In Grossmann & Lohse (Phys. Rev. Lett., vol. 86, 2001, pp. 3316–3319) the dimensionless parameters of the theory were fitted to 155 experimental data points by Ahlers & Xu (Phys. Rev. Lett., vol. 86, 2001, pp. 3320–3323) in the regime
$3\times 1{0}^{7} \leq \mathit{Ra}\leq 3\times 1{0}^{9} $
and
$4\leq \mathit{Pr}\leq 34$
and Grossmann & Lohse (Phys. Rev. E, vol. 66, 2002, p. 016305) used the experimental data point from Qiu & Tong (Phys. Rev. E, vol. 64, 2001, p. 036304) and the fact that
$\mathit{Nu}(\mathit{Ra}, \mathit{Pr})$
is independent of the parameter
$a$
, which relates the dimensionless kinetic boundary thickness with the square root of the wind Reynolds number, to fix the Reynolds number dependence. Meanwhile the theory is, on the one hand, well-confirmed through various new experiments and numerical simulations; on the other hand, these new data points provide the basis for an updated fit in a much larger parameter space. Here we pick four well-established (and sufficiently distant)
$\mathit{Nu}(\mathit{Ra}, \mathit{Pr})$
data points and show that the resulting
$\mathit{Nu}(\mathit{Ra}, \mathit{Pr})$
function is in agreement with almost all established experimental and numerical data up to the ultimate regime of thermal convection, whose onset also follows from the theory. One extra
$\mathit{Re}(\mathit{Ra}, \mathit{Pr})$
data point is used to fix
$\mathit{Re}(\mathit{Ra}, \mathit{Pr})$
. As
$\mathit{Re}$
can depend on the definition and the aspect ratio, the transformation properties of the GL equations are discussed in order to show how the GL coefficients can easily be adapted to new Reynolds number data while keeping
$\mathit{Nu}(\mathit{Ra}, \mathit{Pr})$
unchanged.
Animals live in symbiosis with numerous microbe species. While some can protect hosts from infection and benefit host health, components of the microbiota or changes to the microbial landscape have ...the potential to facilitate infections and worsen disease severity. Pathogens and pathobionts can exploit microbiota metabolites, or can take advantage of a depletion in host defences and changing conditions within a host, to cause opportunistic infection. The microbiota might also favour a more virulent evolutionary trajectory for invading pathogens. In this review, we consider the ways in which a host microbiota contributes to infectious disease throughout the host's life and potentially across evolutionary time. We further discuss the implications of these negative outcomes for microbiota manipulation and engineering in disease management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
We examined age- and sex-specific hip fracture hospitalization rates among people aged 65 and older using 1990–2010 National Hospital Discharge Survey data. Trends calculated using Joinpoint ...regression analysis suggest that future increases in hip fractures due to the aging population will be largely offset by decreasing hip fracture rates among women. However, this trend will be counterbalanced by rising numbers of hip fractures among men.
Introduction
From 1990 to 2006, age-adjusted U.S. hip fracture rates among people aged 65 years and older declined significantly. We wanted to determine whether decreasing age group-specific hip fracture rates might offset increases in hip fractures among the aging population over the next two decades.
Methods
This study used data from the National Hospital Discharge Survey, a national probability survey of inpatient discharges from nonfederal U.S. hospitals, to analyze hip fracture hospitalizations, defined as cases with first diagnosis coded ICD-9 CM 820. We analyzed trends in rates by sex and 10-year age groups using Joinpoint analysis software and used the results and projected population estimates to obtain the expected number of hip fractures in 2020 and 2050.
Results
Based on current age- and sex-specific trends in hip fracture hospitalization rates, the number of hip fractures is projected to rise 11.9 %—from 258,000 in 2010 to 289,000 (Projection Interval PI = 193,000–419,000) in 2030. The number of hip fractures among men is expected to increase 51.8 % (PI = 15.9–119.4 %) while the number among women is expected to decrease 3.5 % (PI = −44.3–37.3 %). These trends will affect the future distribution of hip fractures among the older population.
Conclusions
Although the number of older people in the U.S.A. will increase appreciably over the next 20 years, the expected increase in the total number of hip fractures will be largely offset by decreasing hip fracture rates among women. However, this trend will be counterbalanced by rising numbers of hip fractures among men.
Recently, a comparison between the locations of 6.7-GHz methanol masers and dust continuum emission has renewed speculation that these masers can be associated with evolved stars. The implication of ...such a scenario would be profound, especially for the interpretation of large surveys for 6.7-GHz masers, individual studies where high-mass star formation has been inferred from the presence of 6.7-GHz methanol masers and for the pumping mechanisms of these masers. We have investigated the two instances where 6.7-GHz methanol masers have been explicitly suggested to be associated with evolved stars, and we find the first to be associated with a standard high-mass star formation region, and the second to be a spurious detection. We also find no evidence to suggest that the methanol maser action can be supported in the environments of evolved stars. We thereby confirm their exclusive association with high-mass star formation regions.
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