Real-life adaptations in walking patterns in patients with established peripheral arterial disease assessed using a global positioning system in the community: A cohort study

Objective: Lower extremity peripheral arterial disease (PAD) is a chronic condition most commonly presenting with intermittent claudication (IC). IC limits walking ability and may negatively affect health-related quality of life. Treadmill assessment of maximal walking distance (MWD) is the gold standard to assess PAD symptom severity. Despite being a well-established and reproducible tool, it may be inappropriate (due to frailty or fear) for some patients and only describes maximal abilities for a single walk test. Global Positioning Systems (GPS) have been proposed as reliable and reproducible tool to measure total, mean and maximal walking distances in PAD patients, in the community setting. Using GPS our study attempted to explore what happens to the walking ability of patients with IC following no intervention under "real-life" conditions. Design and Methods: Using the GlobalSat DG100 GPS, forty-three patients (69±9yrs; 9 female; no invasive interventions or rehabilitation) undertook two 60-minute walking assessments, 6 months apart. Assessments took place in community spaces that had even terrain, no tall trees or buildings and were free from motorised vehicles. GPS-measured maximum walking distance was the main study outcome measure. Results: Over the 6-month period, patients demonstrated significantly shorter GPS-measured, mean (552m vs 334m; p=0.02) and maximum (714m vs 545m; p=0.04) walking distances, stopping also more frequently (9 v 5 times; p=0.03). Conclusions: Given the reported symptom progression we advocate early intervention (e.g. exercise interventions) combined with frequent patient monitoring in attempts to maintain or improve walking ability. Key Words: peripheral arterial disease; Global Position System; maximum walking distance; intermittent claudication; community assessments

STIS UV spectroscopy of early B supergiants in M31

We analyze STIS spectra in the 1150-1700 Angstrom wavelength range obtained for six early B supergiants in the neighboring galaxy M31. Because of their likely high (nearly solar) abundance, these stars were originally chosen to be directly comparable to their Galactic counterparts, and represent a much-needed addition to our current sample of B-type supergiants, in our efforts to study the dependence of the Wind Momentum-Luminosity Relationship on spectral type and metallicity. As a first step to determine wind momenta we fit the P-Cygni profiles of the resonance lines of N V, Si IV and C IV with standard methods, and derive terminal velocities for all of the STIS targets. From these lines we also derive ionic stellar wind column densities. Our results are compared with those obtained previously in Galactic supergiants, and confirm earlier claims of `normal' wind line intensities and terminal velocities in M31. For half of the sample we find evidence for an enhanced maximum turbulent velocity when compared to Galactic counterparts.Comment: 15 pages, 9 figures, 2 tables. Accepted for publication in The Astrophysical Journa

The TIGA technique for detecting gravitational waves with a spherical antenna

We report the results of a theoretical and experimental study of a spherical gravitational wave antenna. We show that it is possible to understand the data from a spherical antenna with 6 radial resonant transducers attached to the surface in the truncated icosahedral arrangement. We find that the errors associated with small deviations from the ideal case are small compared to other sources of error, such as a finite signal-to-noise ratio. An in situ measurement technique is developed along with a general algorithm that describes a procedure for determining the direction of an external force acting on the antenna, including the force from a gravitational wave, using a combination of the transducer responses. The practicality of these techniques was verified on a room-temperature prototype antenna.Comment: 15 pages, 14 figures, submitted to Physical Review

Imaging biomarkers of lung ventilation in interstitial lung disease from ¹²⁹Xe and oxygen enhanced ¹H MRI

PURPOSE: To compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. STUDY TYPE: Prospective longitudinal. POPULATION: Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. FIELD STRENGTH/SEQUENCE: MRI performed at 1.5 T. Inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. ASSESSMENT: Five 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. STATISTICAL TEST: To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. RESULTS: The global PFT tests could not distinguish ILD subtypes. Ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. DATA CONCLUSION: Neither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF

In silico and structural analyses demonstrate that intrinsic protein motions guide T cell receptor complementarity determining region loop flexibility

T-cell immunity is controlled by T cell receptor (TCR) binding to peptide major histocompatibility complexes (pMHCs). The nature of the interaction between these two proteins has been the subject of many investigations because of its central role in immunity against pathogens, cancer, in autoimmunity, and during organ transplant rejection. Crystal structures comparing unbound and pMHC-bound TCRs have revealed flexibility at the interaction interface, particularly from the perspective of the TCR. However, crystal structures represent only a snapshot of protein conformation that could be influenced through biologically irrelevant crystal lattice contacts and other factors. Here, we solved the structures of three unbound TCRs from multiple crystals. Superposition of identical TCR structures from different crystals revealed some conformation differences of up to 5 Å in individual complementarity determining region (CDR) loops that are similar to those that have previously been attributed to antigen engagement. We then used a combination of rigidity analysis and simulations of protein motion to reveal the theoretical potential of TCR CDR loop flexibility in unbound state. These simulations of protein motion support the notion that crystal structures may only offer an artifactual indication of TCR flexibility, influenced by crystallization conditions and crystal packing that is inconsistent with the theoretical potential of intrinsic TCR motions

Airway microstructure in idiopathic pulmonary fibrosis: assessment at hyperpolarized 3He diffusion-weighted MRI

Background MRI with inhaled hyperpolarized helium 3 (3He) allows for functional and structural imaging of the lungs. Hyperpolarized gas diffusion-weighted (DW) MRI provides noninvasive and quantitative assessment of microstructural acinar changes in the lungs. Purpose To investigate whether microstructural imaging metrics from in-vivo hyperpolarized 3He DW MRI are sensitive to longitudinal changes in a cohort of participants with idiopathic pulmonary fibrosis (IPF) and to evaluate the reproducibility of these metrics and their correlation with existing clinical measures of IPF disease severity. Materials and Methods In this prospective study, 18 participants with IPF underwent 3He DW MRI at 1.5 T and 11 participants underwent an identical same-day examination for reproducibility assessment. Thirteen participants returned for 6- and 12-month follow-up examinations. Pulmonary function tests, including diffusing capacity of the lungs for carbon monoxide and forced vital capacity, were performed at each examination. The apparent diffusion coefficient (ADC) and stretched exponential model–derived mean diffusive length scale (LmD) from DW MRI was compared with baseline CT fibrosis scores and pulmonary function tests by using Spearman rank correlation coefficient. Longitudinal changes in DW MRI and pulmonary function test measurements were assessed with Friedman tests and post hoc Dunn test. Results 3He ADC and LmD were reproducible (mean Bland-Altman analysis bias, 0.002 cm2 · sec-1 and −1.5 μm, respectively). Elevated ADC and LmD regions qualitatively corresponded to fibrotic regions at CT. ADC and LmD correlated with diffusing capacity of the lungs for carbon monoxide (respectively: r = −0.56, P = .017; and r = −0.54, P = .02) and CT fibrosis score (respectively: r = 0.71, P = .001; and r = 0.65, P = .003). LmD increased by 12 μm after 12 months (P = .001) whereas mean ADC (P = .17), forced vital capacity (P = .12), and diffusing capacity of the lungs for carbon monoxide (P > .99) were not statistically different between examinations. Conclusion Helium 3 diffusion-weighted MRI-derived mean diffusive length scale demonstrates longitudinal changes in lungs affected by idiopathic pulmonary fibrosis

Roles of the ocean mesoscale in the horizontal supply of mass, heat, carbon and nutrients to the Northern Hemisphere subtropical gyres

Horizontal transport at the boundaries of the subtropical gyres plays a crucial role in providing the nutrients that fuel gyre primary productivity, the heat that helps restratify the surface mixed layer, and the dissolved inorganic carbon (DIC) that influences air‐sea carbon exchange. Mesoscale eddies may be an important component of these horizontal transports; however, previous studies have not quantified the horizontal tracer transport due to eddies across the subtropical gyre boundaries. Here we assess the physical mechanisms that control the horizontal transport of mass, heat, nutrients and carbon across the North Pacific and North Atlantic subtropical gyre boundaries using the eddy‐rich ocean component of a climate model (GFDL's CM2.6) coupled to a simple biogeochemical model (mini‐BLING). Our results suggest that horizontal transport across the gyre boundaries supplies a substantial amount of mass and tracers to the ventilated layer of both Northern Hemisphere subtropical gyres, with the Kuroshio and Gulf Stream acting as main exchange gateways. Mass, heat, and DIC supply is principally driven by the time‐mean circulation, whereas nutrient transport differs markedly from the other tracers, as nutrients are mainly supplied to both subtropical gyres by down‐gradient eddy mixing across gyre boundaries. A budget analysis further reveals that the horizontal nutrient transport, combining the roles of both mean and eddy components, is responsible for more than three quarters of the total nutrient supply into the subtropical gyres, surpassing a recent estimate based on a coarse resolution model and thus further highlighting the importance of horizontal nutrient transport

A multi-decade record of high quality fCO2 data in version 3 of the Surface Ocean CO2 Atlas (SOCAT)

The Surface Ocean CO2 Atlas (SOCAT) is a synthesis of quality-controlled fCO2 (fugacity of carbon dioxide) values for the global surface oceans and coastal seas with regular updates. Version 3 of SOCAT has 14.7 million fCO2 values from 3646 data sets covering the years 1957 to 2014. This latest version has an additional 4.6 million fCO2 values relative to version 2 and extends the record from 2011 to 2014. Version 3 also significantly increases the data availability for 2005 to 2013. SOCAT has an average of approximately 1.2 million surface water fCO2 values per year for the years 2006 to 2012. Quality and documentation of the data has improved. A new feature is the data set quality control (QC) flag of E for data from alternative sensors and platforms. The accuracy of surface water fCO2 has been defined for all data set QC flags. Automated range checking has been carried out for all data sets during their upload into SOCAT. The upgrade of the interactive Data Set Viewer (previously known as the Cruise Data Viewer) allows better interrogation of the SOCAT data collection and rapid creation of high-quality figures for scientific presentations. Automated data upload has been launched for version 4 and will enable more frequent SOCAT releases in the future. High-profile scientific applications of SOCAT include quantification of the ocean sink for atmospheric carbon dioxide and its long-term variation, detection of ocean acidification, as well as evaluation of coupled-climate and ocean-only biogeochemical models. Users of SOCAT data products are urged to acknowledge the contribution of data providers, as stated in the SOCAT Fair Data Use Statement. This ESSD (Earth System Science Data) “living data” publication documents the methods and data sets used for the assembly of this new version of the SOCAT data collection and compares these with those used for earlier versions of the data collection (Pfeil et al., 2013; Sabine et al., 2013; Bakker et al., 2014). Individual data set files, included in the synthesis product, can be downloaded here: doi:10.1594/PANGAEA.849770. The gridded products are available here: doi:10.3334/CDIAC/OTG.SOCAT_V3_GRID

Implementable Deep Learning for Multi-sequence Proton MRI Lung Segmentation:A Multi-center, Multi-vendor, and Multi-disease Study

Background: Recently, deep learning via convolutional neural networks (CNNs) has largely superseded conventional methods for proton (1H)-MRI lung segmentation. However, previous deep learning studies have utilized single-center data and limited acquisition parameters.Purpose: Develop a generalizable CNN for lung segmentation in 1H-MRI, robust to pathology, acquisition protocol, vendor, and center.Study type: Retrospective.Population: A total of 809 1H-MRI scans from 258 participants with various pulmonary pathologies (median age (range): 57 (6–85); 42% females) and 31 healthy participants (median age (range): 34 (23–76); 34% females) that were split into training (593 scans (74%); 157 participants (55%)), testing (50 scans (6%); 50 participants (17%)) and external validation (164 scans (20%); 82 participants (28%)) sets.Field Strength/Sequence: 1.5-T and 3-T/3D spoiled-gradient recalled and ultrashort echo-time 1H-MRI.Assessment: 2D and 3D CNNs, trained on single-center, multi-sequence data, and the conventional spatial fuzzy c-means (SFCM) method were compared to manually delineated expert segmentations. Each method was validated on external data originating from several centers. Dice similarity coefficient (DSC), average boundary Hausdorff distance (Average HD), and relative error (XOR) metrics to assess segmentation performance.Statistical Tests: Kruskal–Wallis tests assessed significances of differences between acquisitions in the testing set. Friedman tests with post hoc multiple comparisons assessed differences between the 2D CNN, 3D CNN, and SFCM. Bland–Altman analyses assessed agreement with manually derived lung volumes. A P value of &lt;0.05 was considered statistically significant.Results: The 3D CNN significantly outperformed its 2D analog and SFCM, yielding a median (range) DSC of 0.961 (0.880–0.987), Average HD of 1.63 mm (0.65–5.45) and XOR of 0.079 (0.025–0.240) on the testing set and a DSC of 0.973 (0.866–0.987), Average HD of 1.11 mm (0.47–8.13) and XOR of 0.054 (0.026–0.255) on external validation data.Data Conclusion: The 3D CNN generated accurate 1H-MRI lung segmentations on a heterogenous dataset, demonstrating robustness to disease pathology, sequence, vendor, and center.Evidence Level: 4.Technical Efficacy: Stage 1.</p