Reconciling transport models across scales: the role of volume exclusion

Diffusive transport is a universal phenomenon, throughout both biological and physical sciences, and models of diffusion are routinely used to interrogate diffusion-driven processes. However, most models neglect to take into account the role of volume exclusion, which can significantly alter diffusive transport, particularly within biological systems where the diffusing particles might occupy a significant fraction of the available space. In this work we use a random walk approach to provide a means to reconcile models that incorporate crowding effects on different spatial scales. Our work demonstrates that coarse-grained models incorporating simplified descriptions of excluded volume can be used in many circumstances, but that care must be taken in pushing the coarse-graining process too far

Investigation of Superconducting Gap Structure in TbFeAsO0.9_{0.9}F0.1_{0.1} using Point Contact Andreev Reflection

Bulk samples of TbFeAsO$_{0.9}$F$_{0.1}$ (T$_{c}$(on) = 50K) were measured by point contact Andreev reflection spectroscopy. The spectra show unambiguous evidence for multiple gap-like features plus the presence of high bias shoulders. By measuring the spectra as a function of temperature with both gold and superconducting niobium tips, we establish that the gap-like features are associated with superconducting order parameter in this material. We discuss whether the well defined zero bias conductance peak that we observe infrequently is associated with a nodal superconducting order parameter.Comment: 11 pages, 5 figures, published versio

The influence of cognitive-perceptual variables on patterns of change over time in rural midlife and older women\u27s healthy eating.

Although studies demonstrate that dietary interventions for healthy adults can result in beneficial dietary changes, few studies examine when and how people change in response to these interventions, particularly in rural populations. The purpose of this study was to examine patterns of change over time in healthy eating behaviors in midlife and older women in response to a one-year health-promoting intervention, and to examine what predictors (perceived benefits, barriers, self-efficacy, and family support for healthy eating) influence the changes during the intervention and follow-up. Data for this secondary analysis were from the Wellness for Women community-based trial. Women (N = 225) between the ages of 50-69 in rural Nebraska, U.S.A., were recruited. A repeated-measures experimental design was used with randomization of two rural counties to intervention (tailored newsletter) or comparison (standard newsletter) groups. Eating behavior was measured by the Healthy Eating Index. The predictor variables were assessed using standard measures. Data analysis was done using latent growth curve modeling. The tailored newsletter group was successful in improving their healthy eating behavior compared to the standard newsletter group during the one-year intervention, at the end of the intervention, and during the follow-up phase. Family support at the end of the intervention was positively associated with healthy eating at the end of the intervention. Perceived barriers had the strongest impact on healthy eating behavior at all time points. Compared to participants in the standard newsletter group, those in the tailored newsletter group perceived more family support and fewer barriers for healthy eating at the end of the intervention (mediation effects). Based on these findings, both family support and perceived barriers should be central components of interventions focused on healthy eating behavior in rural midlife and older women

The influence of cognitive-perceptual variables on patterns of change over time in rural midlife and older women\u27s healthy eating

Although studies demonstrate that dietary interventions for healthy adults can result in beneficial dietary changes, few studies examine when and how people change in response to these interventions, particularly in rural populations. The purpose of this study was to examine patterns of change over time in healthy eating behaviors in midlife and older women in response to a one-year health-promoting intervention, and to examine what predictors (perceived benefits, barriers, self-efficacy, and family support for healthy eating) influence the changes during the intervention and follow-up. Data for this secondary analysis were from the Wellness for Women community-based trial. Women (N ¼ 225) between the ages of 50e69 in rural Nebraska, U.S.A., were recruited. A repeated-measures experimental design was used with randomization of two rural counties to intervention (tailored newsletter) or comparison (standard newsletter) groups. Eating behavior was measured by the Healthy Eating Index. The predictor variables were assessed using standard measures. Data analysis was done using latent growth curve modeling. The tailored newsletter group was successful in improving their healthy eating behavior compared to the standard newsletter group during the one-year intervention, at the end of the intervention, and during the follow-up phase. Family support at the end of the intervention was positively associated with healthy eating at the end of the intervention. Perceived barriers had the strongest impact on healthy eating behavior at all time points. Compared to participants in the standard newsletter group, those in the tailored newsletter group perceived more family support and fewer barriers for healthy eating at the end of the intervention (mediation effects). Based on these findings, both family support and perceived barriers should be central components of interventions focused on healthy eating behavior in rural midlife and older women

Near-infrared and optical imaging of Q2345+007: the largest gravitationally lensed QSO system?

We have taken K, R, V, and B band images of Q 2345+007, which has been claimed to be the gravitationally lensed quasar with the widest separation between the two images (≈ 7″), although the lens remains to be identified. The K band image extends the observations to longer wavelengths, and in conjunction with the published data and our new results at shorter wavelengths show that the colors of the two components do not differ markedly over the wavelength range 0.4-2.2 µm, though it is possible that the weaker component is slightly redder. From a comparison of our V and B band images with published images we find that the intensities of both components have declined substantially over the past decade. This opens up the possibility of testing the lensing hypothesis by measuring a temporal offset between the light curves of the two components

An IP-10 (CXCL10)-derived peptide inhibits angiogenesis

Angiogenesis plays a critical role in processes such as organ development, wound healing, and tumor growth. It requires well-orchestrated integration of soluble and matrix factors and timely recognition of such signals to regulate this process. Previous work has shown that newly forming vessels express the chemokine receptor CXC receptor 3 (CXCR3) and, activation by its ligand IP-10 (CXCL10), both inhibits development of new vasculature and causes regression of newly formed vessels. To identify and develop new therapeutic agents to limit or reverse pathological angiogenesis, we identified a 21 amino acid fragment of IP-10, spanning the α-helical domain residues 77-98, that mimic the actions of the whole IP-10 molecule on endothelial cells. Treatment of the endothelial cells with the 22 amino acid fragment referred to as IP-10p significantly inhibited VEGF-induced endothelial motility and tube formation in vitro, properties critical for angiogenesis. Using a Matrigel plug assay in vivo, we demonstrate that IP-10p both prevented vessel formation and induced involution of nascent vessels. CXCR3 neutralizing antibody was able to block the inhibitory effects of the IP-10p, demonstrating specificity of the peptide. Inhibition of endothelial function by IP-10p was similar to that described for IP-10, secondary to CXCR3-mediated increase in cAMP production, activation of PKA inhibiting cell migration, and inhibition of VEGF-mediated m-calpain activation. IP-10p provides a novel therapeutic agent that inhibits endothelial cell function thus, allowing for the modulation of angiogenesis. © 2012 Yates-Binder et al

Objective cough frequency, airway inflammation, and disease control in asthma

Background Cough is recognized as an important troublesome symptom in the diagnosis and monitoring of asthma. Asthma control is thought to be determined by the degree of airway inflammation and hyperresponsiveness but how these factors relate to cough frequency is unclear. The goal of this study was to investigate the relationships between objective cough frequency, disease control, airflow obstruction, and airway inflammation in asthma. Methods Participants with asthma underwent 24-h ambulatory cough monitoring and assessment of exhaled nitric oxide, spirometry, methacholine challenge, and sputum induction (cell counts and inflammatory mediator levels). Asthma control was assessed by using the Global Initiative for Asthma (GINA) classification and the Asthma Control Questionnaire (ACQ). The number of cough sounds was manually counted and expressed as coughs per hour (c/h). Results Eighty-nine subjects with asthma (mean ± SD age, 57 ± 12 years; 57% female) were recruited. According to GINA criteria, 18 (20.2%) patients were classified as controlled, 39 (43.8%) partly controlled, and 32 (36%) uncontrolled; the median ACQ score was 1 (range, 0.0-4.4). The 6-item ACQ correlated with 24-h cough frequency (r = 0.40; P < .001), and patients with uncontrolled asthma (per GINA criteria) had higher median 24-h cough frequency (4.2 c/h; range, 0.3-27.6) compared with partially controlled asthma (1.8 c/h; range, 0.2-25.3; P = .01) and controlled asthma (1.7 c/h; range, 0.3-6.7; P = .002). Measures of airway inflammation were not significantly different between GINA categories and were not correlated with ACQ. In multivariate analyses, increasing cough frequency and worsening FEV1 independently predicted measures of asthma control. Conclusions Ambulatory cough frequency monitoring provides an objective assessment of asthma symptoms that correlates with standard measures of asthma control but not airflow obstruction or airway inflammation. Moreover, cough frequency and airflow obstruction represent independent dimensions of asthma control

Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study

Background: The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented. However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease. Methods: TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers). To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ³ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937). Results: Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4,29) in GOLD stage IV. SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage. Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV. The rates of adverse events were similar across treatment arms and increased with disease severity. Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages. Conclusion: In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages. Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease. The effects were similar to those reported for the study as a whole. Thus, SFC is an effective treatment option for patients with GOLD stage II COPD

Presacral malakoplakia presenting as foot drop: a case report

Background: Malakoplakia is a rare condition characterized by inflammatory masses with specific histological characteristics. These soft tissue masses can mimic tumors and tend to develop in association with chronic or recurrent infections, typically of the urinary tract. A specific defect in innate immunity has been described. In the absence of randomized controlled trials, management is based on an understanding of the biology and on case reports. Case presentation: Here we describe a case of presacral malakoplakia in a British Indian woman in her late 30s, presenting with complex unilateral foot drop. Four years earlier, she had suffered a protracted episode of intrapelvic sepsis following a caesarean delivery. Resection of her presacral soft tissue mass was not possible. She received empiric antibiotics, a cholinergic agonist, and ascorbic acid. She responded well to medical management both when first treated and following a recurrence of symptoms after completing an initial 8 months of therapy. Whole exome sequencing of the patient and her parents was undertaken but no clear causal variant was identified. Conclusions: Malakoplakia is uncommon but the diagnosis should be considered where soft tissue masses develop at the site of chronic or recurrent infections. Obtaining tissue for histological examination is key to making the diagnosis. This case suggests that surgical resection is not always needed to achieve a good clinical and radiological outcome