How do brochures encourage walking in natural environments in the UK? A content analysis.

Although walking for leisure can support health, there has been little systematic attempt to consider how recreational walking is best promoted. In the UK, local authorities create promotional materials for walking networks, but little is known about whether they effectively encourage walking through persuasive messaging. Many of these materials pertain to walks in natural environments which evidence suggests are generally visited less frequently by physically inactive individuals. Consequently the present study explores whether and how recreational walking brochures use persuasive messages in their promotion of walks in natural environments. A coding taxonomy was developed to classify text in recreational walking brochures according to five behavioural content areas and 87 categories of potentially persuasive messages. Reliability of the taxonomy was ascertained and a quantitative content analysis was applied to 26 brochures collected from Devon, UK. Brochures often provided information about an advertised route, highlighted cultural and aesthetic points of interest, and provided directions. Brochures did not use many potentially effective messages. Text seldom prompted behaviour change or built confidence for walking. Social norm related information was rarely provided and there was a general lack of information on physical activity and its benefits for health and well-being. The limited range of message strategies used in recreational walking brochures may not optimally facilitate walking in natural environments for inactive people. Future research should examine the effects of theory-informed brochures on walking intentions and behaviour. The taxonomy could be adapted to suit different media and practices surrounding physical activity in natural environments

Label-free infrared spectroscopy and imaging of single phospholipid bilayers with nanoscale resolution

Mid-infrared absorption spectroscopy has been used extensively to study the molecular properties of cell membranes and model systems. Most of these studies have been carried out on macroscopic samples or on samples a few micrometers in size, due to constraints on sensitivity and spatial resolution with conventional instruments that rely on far-field optics. Properties of membranes on the scale of nanometers, such as in-plane heterogeneity, have to date eluded investigation by this technique. In the present work, we demonstrate the capability to study single bilayers of phospholipids with near-field mid-infrared spectroscopy and imaging and achieve a spatial resolution of at least 40 nm, corresponding to a sample size of the order of a thousand molecules. The quality of the data and the observed spectral features are consistent with those reported from measurements of macroscopic samples and allow detailed analysis of molecular properties, including orientation and ordering of phospholipids. The work opens the way to the nanoscale characterization of the biological membranes for which phospholipid bilayers serve as a model

Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial.

Importance: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. Objective: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. Design, Setting, and Participants: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF ( Interventions: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. Main Outcomes and Measures: The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). Results: Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P \u3e .05. Conclusions and Relevance: Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. Trial Registration: clinicaltrials.gov Identifier: NCT02188784

A fully (3+1)-D Regge calculus model of the Kasner cosmology

We describe the first discrete-time 4-dimensional numerical application of Regge calculus. The spacetime is represented as a complex of 4-dimensional simplices, and the geometry interior to each 4-simplex is flat Minkowski spacetime. This simplicial spacetime is constructed so as to be foliated with a one parameter family of spacelike hypersurfaces built of tetrahedra. We implement a novel two-surface initial-data prescription for Regge calculus, and provide the first fully 4-dimensional application of an implicit decoupled evolution scheme (the ``Sorkin evolution scheme''). We benchmark this code on the Kasner cosmology --- a cosmology which embodies generic features of the collapse of many cosmological models. We (1) reproduce the continuum solution with a fractional error in the 3-volume of 10^{-5} after 10000 evolution steps, (2) demonstrate stable evolution, (3) preserve the standard deviation of spatial homogeneity to less than 10^{-10} and (4) explicitly display the existence of diffeomorphism freedom in Regge calculus. We also present the second-order convergence properties of the solution to the continuum.Comment: 22 pages, 5 eps figures, LaTeX. Updated and expanded versio

Quantifying mesoscale-driven nitrate supply: a case study

The supply of nitrate to surface waters plays a crucial role in maintaining marine life. Physical processes at the mesoscale (~10-100?km) and smaller have been advocated to provide a major fraction of the global supply. Whilst observational studies have focussed on well-defined features, such as isolated eddies, the vertical circulation and nutrient supply in a typical 100-200?km square of ocean will involve a turbulent spectrum of interacting, evolving and decaying features. A crucial step in closing the ocean nitrogen budget is to be able to rank the importance of mesoscale fluxes against other sources of nitrate for surface waters for a representative area of open ocean. While this has been done using models, the vital observational equivalent is still lacking.To illustrate the difficulties that prevent us from putting a global estimate on the significance of the mesoscale observationally, we use data from a cruise in the Iceland Basin where vertical velocity and nitrate observations were made simultaneously at the same high spatial resolution. Local mesoscale nitrate flux is found to be an order of magnitude greater than that due to small-scale vertical mixing and exceeds coincident nitrate uptake rates and estimates of nitrate supply due to winter convection. However, a non-zero net vertical velocity for the region introduces a significant bias in regional estimates of the mesoscale vertical nitrate transport. The need for synopticity means that a more accurate estimate can not be simply found by using a larger survey area. It is argued that time-series, rather than spatial surveys, may be the best means to quantify the contribution of mesoscale processes to the nitrate budget of the surface ocean

Structural studies suggest aggregation as one of the modes of action for teixobactin

Teixobactin is a new promising antibiotic that targets cell wall biosynthesis by binding to lipid II and has no detectable resistance thanks to its unique but yet not fully understood mechanism of operation. To aid in the structure-based design of teixobactin analogues with improved pharmacological properties, we present a 3D structure of native teixobactin in membrane mimetics and characterise its binding to lipid II through a combination of solution NMR and fast (90 kHz) magic angle spinning solid state NMR. In NMR titrations, we observe a pattern strongly suggesting interactions between the backbone of the C-terminal “cage” and the pyrophosphate moiety in lipid II. We find that the N-terminal part of teixobactin does not only act as a membrane anchor, as previously thought, but is actively involved in binding. Moreover, teixobactin forms a well-structured and specific complex with lipid II, where the N-terminal part of teixobactin assumes a b conformation that is highly prone to aggregation, which likely contributes to the antibiotic's high bactericidal efficiency. Overall, our study provides several new clues to teixobactin's modes of action

Diminished Self-Chaperoning Activity of the ΔF508 Mutant of CFTR Results in Protein Misfolding

The absence of a functional ATP Binding Cassette (ABC) protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) from apical membranes of epithelial cells is responsible for cystic fibrosis (CF). Over 90% of CF patients carry at least one mutant allele with deletion of phenylalanine at position 508 located in the N-terminal nucleotide binding domain (NBD1). Biochemical and cell biological studies show that the ΔF508 mutant exhibits inefficient biosynthetic maturation and susceptibility to degradation probably due to misfolding of NBD1 and the resultant misassembly of other domains. However, little is known about the direct effect of the Phe508 deletion on the NBD1 folding, which is essential for rational design strategies of cystic fibrosis treatment. Here we show that the deletion of Phe508 alters the folding dynamics and kinetics of NBD1, thus possibly affecting the assembly of the complete CFTR. Using molecular dynamics simulations, we find that meta-stable intermediate states appearing on wild type and mutant folding pathways are populated differently and that their kinetic accessibilities are distinct. The structural basis of the increased misfolding propensity of the ΔF508 NBD1 mutant is the perturbation of interactions in residue pairs Q493/P574 and F575/F578 found in loop S7-H6. As a proof-of-principle that the S7-H6 loop conformation can modulate the folding kinetics of NBD1, we virtually design rescue mutations in the identified critical interactions to force the S7-H6 loop into the wild type conformation. Two redesigned NBD1-ΔF508 variants exhibited significantly higher folding probabilities than the original NBD1-ΔF508, thereby partially rescuing folding ability of the NBD1-ΔF508 mutant. We propose that these observed defects in folding kinetics of mutant NBD1 may also be modulated by structures separate from the 508 site. The identified structural determinants of increased misfolding propensity of NBD1-ΔF508 are essential information in correcting this pathogenic mutant

Baryon Acoustic Oscillations in the Sloan Digital Sky Survey Data Release 7 Galaxy Sample

The spectroscopic Sloan Digital Sky Survey (SDSS) Data Release 7 (DR7) galaxy sample represents the final set of galaxies observed using the original SDSS target selection criteria. We analyse the clustering of galaxies within this sample, including both the Luminous Red Galaxy (LRG) and Main samples, and also include the 2-degree Field Galaxy Redshift Survey (2dFGRS) data. Baryon Acoustic Oscillations are observed in power spectra measured for different slices in redshift; this allows us to constrain the distance--redshift relation at multiple epochs. We achieve a distance measure at redshift z=0.275, of r_s(z_d)/D_V(0.275)=0.1390+/-0.0037 (2.7% accuracy), where r_s(z_d) is the comoving sound horizon at the baryon drag epoch, D_V(z)=[(1+z)^2D_A^2cz/H(z)]^(1/3), D_A(z) is the angular diameter distance and H(z) is the Hubble parameter. We find an almost independent constraint on the ratio of distances D_V(0.35)/D_V(0.2)=1.736+/-0.065, which is consistent at the 1.1sigma level with the best fit Lambda-CDM model obtained when combining our z=0.275 distance constraint with the WMAP 5-year data. The offset is similar to that found in previous analyses of the SDSS DR5 sample, but the discrepancy is now of lower significance, a change caused by a revised error analysis and a change in the methodology adopted, as well as the addition of more data. Using WMAP5 constraints on Omega_bh^2 and Omega_ch^2, and combining our BAO distance measurements with those from the Union Supernova sample, places a tight constraint on Omega_m=0.286+/-0.018 and H_0 = 68.2+/-2.2km/s/Mpc that is robust to allowing curvature and non-Lambda dark energy. This result is independent of the behaviour of dark energy at redshifts greater than those probed by the BAO and supernova measurements. (abridged)Comment: 22 pages, 16 figures, minor changes to match version published in MNRA