Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before ...and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate, or advanced disease, and inflammation was characterized through activation of pathways mediated by interferon (IFN), nuclear factor κB (NF-κB), glucocorticoid receptor, and signal transducer and activator of transcription 6 (STAT-6). Inflammation signatures revealed expression of genes and proteins induced by IFN and NF-κB in early-stage disease and genes and proteins induced by STAT-6 and glucocorticoid receptor activation in advanced-stage disease. The proresolving proteins FPR2/ALX and ChemR23 were increased in early-stage disease compared to intermediate- to advanced-stage disease. Patients who were pain-free after treatment had tendons with increased expression of CD206 and ALOX15 mRNA compared to tendons from patients who continued to experience pain after treatment, suggesting that these genes and their pathways may moderate tendon pain. Stromal cells from diseased tendons cultured in vitro showed increased expression of NF-κB and IFN target genes after treatment with lipopolysaccharide or IFNγ compared to stromal cells derived from healthy tendons. We identified 15-epi lipoxin A4, a stable lipoxin isoform derived from aspirin treatment, as potentially beneficial in the resolution of tendon inflammation.
In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial ...continuous-flow pump, at 6 months in patients with advanced heart failure.
In a randomized noninferiority and superiority trial, we compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal-flow pump group minus axial-flow pump group) was -10 percentage points.
Of 366 patients, 190 were assigned to the centrifugal-flow pump group and 176 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal-flow pump group, as compared with 106 (60.2%) in the axial-flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points P<0.001 for noninferiority; hazard ratio, 0.46; 95% confidence interval CI, 0.31 to 0.69 P<0.001 for superiority). Reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (3 patients 1.6% vs. 30 patients 17.0%; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal-flow pump group than in the axial-flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02).
In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).
Tristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the ...inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP.
The expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP.
TTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and co-localised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation.
The phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments.
Insect pollination underpins apple production but the extent to which different pollinator guilds supply this service, particularly across different apple varieties, is unknown. Such information is ...essential if appropriate orchard management practices are to be targeted and proportional to the potential benefits pollinator species may provide. Here we use a novel combination of pollinator effectiveness assays (floral visit effectiveness), orchard field surveys (flower visitation rate) and pollinator dependence manipulations (pollinator exclusion experiments) to quantify the supply of pollination services provided by four different pollinator guilds to the production of four commercial varieties of apple. We show that not all pollinators are equally effective at pollinating apples, with hoverflies being less effective than solitary bees and bumblebees, and the relative abundance of different pollinator guilds visiting apple flowers of different varieties varies significantly. Based on this, the taxa specific economic benefits to UK apple production have been established. The contribution of insect pollinators to the economic output in all varieties was estimated to be £92.1M across the UK, with contributions varying widely across taxa: solitary bees (£51.4M), honeybees (£21.4M), bumblebees (£18.6M) and hoverflies (£0.7M). This research highlights the differences in the economic benefits of four insect pollinator guilds to four major apple varieties in the UK. This information is essential to underpin appropriate investment in pollination services management and provides a model that can be used in other entomolophilous crops to improve our understanding of crop pollination ecology.
Abstract
We measured the mid-infrared (MIR) extinction using Spitzer photometry and spectroscopy (3.6–37
μ
m) for a sample of Milky Way sight lines (mostly) having measured ultraviolet extinction ...curves. We used the pair method to determine the MIR extinction that we then fit with a power law for the continuum and modified Drude profiles for the silicate features. We derived 16 extinction curves having a range of
A
(
V
) (1.8–5.5) and
R
(
V
) values (2.4–4.3). Our sample includes two dense sight lines that have 3
μ
m ice feature detections and weak 2175 Å bumps. The average
A
(
λ
)/
A
(
V
) diffuse sight-line extinction curve we calculate is lower than most previous literature measurements. This agrees better with literature diffuse dust grain models, though it is somewhat higher. The 10
μ
m silicate feature does not correlate with the 2175 Å bump, for the first time providing direct observational confirmation that these two features arise from different grain populations. The strength of the 10
μ
m silicate feature varies by ∼2.5 and is not correlated with
A
(
V
) or
R
(
V
). It is well fit by a modified Drude profile with strong correlations seen between the central wavelength, width, and asymmetry. We do not detect other features with limits in
A
(
λ
)/
A
(
V
) units of 0.0026 (5–10
μ
m), 0.004 (10–20
μ
m), and 0.008 (20–40
μ
m). We find that the standard prescription of estimating
R
(
V
) from
C
×
E
(
K
s
−
V
)/
E
(
B
−
V
) has
C
= −1.14 and a scatter of ∼7%. Using the IRAC 5.6
μ
m band instead of
K
s
gives
C
= −1.03 and the least scatter of ∼3%.
We report a quantum simulation of the deuteron binding energy on quantum processors accessed via cloud servers. We use a Hamiltonian from pionless effective field theory at leading order. We design a ...low-depth version of the unitary coupled-cluster ansatz, use the variational quantum eigensolver algorithm, and compute the binding energy to within a few percent. Our work is the first step towards scalable nuclear structure computations on a quantum processor via the cloud, and it sheds light on how to map scientific computing applications onto nascent quantum devices.
Resonant inelastic x-ray scattering is used to investigate the electronic origin of orbital polarization in nickelate heterostructures taking LaTiO_{3}-LaNiO_{3}-3×(LaAlO_{3}), a system with ...exceptionally large polarization, as a model system. We find that heterostructuring generates only minor changes in the Ni 3d orbital energy levels, contradicting the often-invoked picture in which changes in orbital energy levels generate orbital polarization. Instead, O K-edge x-ray absorption spectroscopy demonstrates that orbital polarization is caused by an anisotropic reconstruction of the oxygen ligand hole states. This provides an explanation for the limited success of theoretical predictions based on tuning orbital energy levels and implies that future theories should focus on anisotropic hybridization as the most effective means to drive large changes in electronic structure and realize novel emergent phenomena.
Peripheral arterial disease (PAD) represents a spectrum from asymptomatic stenosis to limb-threatening ischemia. The last decade has seen a tremendous increase in the variety of endovascular devices ...and techniques to treat occlusive disease. Like many evolving technologies, the literature surrounding therapy for endovascular arterial disease consists of mixed-quality manuscripts without clear standardization. Accordingly, critical evaluation of the reported results may be problematic. As such, providers and their patients make treatment decisions without the full benefit of a comparative effectiveness framework. The purpose of this document is to provide a summary for the reporting of endovascular revascularization techniques in the setting of chronic disease. Much of the work in this document is based on prior publications and standards proposed by the Society for Vascular Surgery. We have also made recommendations based on current literature and have attempted to acknowledge shortcomings and areas for future research. The various sections contain summaries of required reporting standards and should serve as a guide for the design of clinical trials and as reference for journal editors and reviewers when considering scientific work pertaining to endovascular therapy for chronic lower extremity arterial disease. An Appendix is provided with commonly used abbreviations in this document.
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