Restenosis after directional coronary atherectomy: Differences between primary atheromatoes and restenosls lesions and influence of subintimal tissue resection

AbstractRates of restenosis were evaluated in 70 patients (74 lesions) after successful directional coronary atherectomy. The extent of vascular tissue resection was correlated with restenosis rates for coronary (n = 59) and vein bypass graft (n = 15) lesions.After 6 months, the overall restenosis rate was 50% (37 of 74 lesions); it was 42% (15 of 36 lesions) when intima alone was resected, 50% (7 of 14 lesions) when media was resected and 63% (15 of 24 lesions) when adventitia was resected. Subintimal tissue resection increased the restenosis rate for vein grafts (43% with intimal resection versus 100% with subintimal resection, p = 0.01) but not for coronary arteries (50% versus 48%). There was no overall difference in restenosis rates after atherectomy between primary lesions and restenosis lesions that occurred after balloon angioplasty (46% versus 54%). Among postballoon angioplasty restenosis lesions, a higher rate of restenosis after atherectomy was found with subintimal than with intimal resection (78% versus 32%, p = 0.01).Tissues from patients undergoing a second atherectomy for restenosis after initial atherectomy (n = 8) demonstrated neointimal hyperplasia that appeared histotogically identical to restenotic tissue developing after balloon angioplasty (n = 37).These data suggest that the cellular response to directional coronary atherectomy is characterized by neointimal proliferation similar to that which may develop after balloon angioplasty. The extent of fibrous hyperplasia appears to be related to the depth of tissue resection in vein graft lesions and coronary artery restenosis lesions that occur after balloon angioplasty but not in primary atheromatous coronary artery lesions

A Novel Test for Gene-Ancestry Interactions in Genome-Wide Association Data

Genome-wide association study (GWAS) data on a disease are increasingly available from multiple related populations. In this scenario, meta-analyses can improve power to detect homogeneous genetic associations, but if there exist ancestry-specific effects, via interactions on genetic background or with a causal effect that co-varies with genetic background, then these will typically be obscured. To address this issue, we have developed a robust statistical method for detecting susceptibility gene-ancestry interactions in multi-cohort GWAS based on closely-related populations. We use the leading principal components of the empirical genotype matrix to cluster individuals into “ancestry groups” and then look for evidence of heterogeneous genetic associations with disease or other trait across these clusters. Robustness is improved when there are multiple cohorts, as the signal from true gene-ancestry interactions can then be distinguished from gene-collection artefacts by comparing the observed interaction effect sizes in collection groups relative to ancestry groups. When applied to colorectal cancer, we identified a missense polymorphism in iron-absorption gene CYBRD1 that associated with disease in individuals of English, but not Scottish, ancestry. The association replicated in two additional, independently-collected data sets. Our method can be used to detect associations between genetic variants and disease that have been obscured by population genetic heterogeneity. It can be readily extended to the identification of genetic interactions on other covariates such as measured environmental exposures. We envisage our methodology being of particular interest to researchers with existing GWAS data, as ancestry groups can be easily defined and thus tested for interactions

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A field and video-annotation guide for baited remote underwater stereo-video surveys of demersal fish assemblages

Researchers TL, BG, JW, NB and JM were supported by the Marine Biodiversity Hub through funding from the Australian Government's National Environmental Science Program. Data validation scripts and GlobalArchive.org were supported by the Australian Research Data Commons, the Gorgon-Barrow Island Gorgon Barrow Island Net Conservation Benefits Fund, administered by the Government of Western Australia and the BHP/UWA Biodiversity and Societal Benefits of Restricted Access Areas collaboration.1. Baited remote underwater stereo-video systems (stereo-BRUVs) are a popular tool to sample demersal fish assemblages and gather data on their relative abundance and body-size structure in a robust, cost-effective, and non-invasive manner. Given the rapid uptake of the method, subtle differences have emerged in the way stereo-BRUVs are deployed and how the resulting imagery are annotated. These disparities limit the interoperability of datasets obtained across studies, preventing broad-scale insights into the dynamics of ecological systems. 2. We provide the first globally accepted guide for using stereo-BRUVs to survey demersal fish assemblages and associated benthic habitats. 3. Information on stereo-BRUV design, camera settings, field operations, and image annotation are outlined. Additionally, we provide links to protocols for data validation, archiving, and sharing. 4. Globally, the use of stereo-BRUVs is spreading rapidly. We provide a standardised protocol that will reduce methodological variation among researchers and encourage the use of Findable, Accessible, Interoperable, and Reproducible (FAIR) workflows to increase the ability to synthesise global datasets and answer a broad suite of ecological questions.Publisher PDFPeer reviewe

Investigation of bovine serum albumin denaturation using ultrasonic spectroscopy

This is the author’s version of a work that was accepted for publication in the journal Food Hydrocolloids. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published at: http://dx.doi.org/10.1016/j.foodhyd.2010.11.011The ability of ultrasound spectroscopy to characterise protein denaturation at relatively high concentrations and under conditions found in foods, is examined. Measurement of longitudinal sound velocity against concentration and frequency (20-160 MHz) for the bovine serum albumin monomer at pH 7.0 gave a frequency independent value for molecular compressibility of at 25 °C, corresponding to a sound velocity for the BSA molecule of 1920 ms-1. At 160 MHz, the longitudinal sound attenuation in BSA molecules is ~5200 Npm-1, a factor of 10 higher than in water. The excess attenuation of the solution over water was nearly 90 Npm-1 at the highest measured volume fraction of 0.03 (or 3% v/v). Concentration-dependent ultrasound velocity (20 - 160 MHz) and attenuation (2 - 120 MHz) spectra were obtained over time for heated bovine serum albumin (BSA) solutions up to 40 mg/mL at neutral pH and at 25 °C. An acoustic scattering model was used which considered the solute molecules as scatterers of ultrasound, to determine the molecules' sound velocity, compressibility, and attenuation properties. Mild heat treatment caused the molecule to organise into dimers and trimers, without change in sound velocity; implying that there is little or no change in secondary structure. Changes in attenuation spectra correlated with estimated molecular weight as determined through DLS and SEC measurements. During oligomerisation, the BSA molecules continue to behave acoustically as monomers. Under severe heat treatment, BSA rapidly suffered irreversible denaturation and gelation occurred which affected both ultrasound attenuation spectra and the velocity of sound, consistent with significant molecular conformation changes and/or molecule-molecule interactions

Global Spatial Risk Assessment of Sharks Under the Footprint of Fisheries

Effective ocean management and conservation of highly migratory species depends on resolving overlap between animal movements and distributions and fishing effort. Yet, this information is lacking at a global scale. Here we show, using a big-data approach combining satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively) and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of high-seas fishing effort. Results demonstrate an urgent need for conservation and management measures at high-seas shark hotspots and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real time, dynamic management

Composition and Function of Haemolymphatic Tissues in the European Common Shrew

BACKGROUND: Studies of wild animals responding to their native parasites are essential if we are to understand how the immune system functions in the natural environment. While immune defence may bring increased survival, this may come at a resource cost to other physiological traits, including reproduction. Here, we tested the hypothesis that wild common shrews (Sorex araneus), which produce large numbers of offspring during the one breeding season of their short life span, forgo investment in immunity and immune system maintenance, as increased longevity is unlikely to bring further opportunities for mating. In particular, we predicted that adult shrews, with shorter expected lifespans, would not respond as effectively as young animals to infection. METHODOLOGY/PRINCIPAL FINDINGS: We examined haemolymphatic tissues from wild-caught common shrews using light and transmission electron microscopy, applied in conjunction with immunohistology. We compared composition and function of these tissues in shrews of different ages, and the extent and type of inflammatory reactions observed in response to natural parasitic infections. All ages seemed able to mount systemic, specific immune responses, but adult shrews showed some signs of lymphatic tissue exhaustion: lymphatic follicles in adults (n = 21) were both smaller than those in sub-adults (n = 18; Wald = 11.1, p<0.05) and exhibited greater levels of depletion (Wald = 13.3, p<0.05). CONCLUSIONS/SIGNIFICANCE: Contrary to our expectations, shrews respond effectively to their natural parasites, and show little indication of immunosenescence as adults. The pancreas of Aselli, a unique lymphoid organ, may aid in providing efficient immune responses through the storage of large numbers of plasma cells. This may allow older animals to react effectively to previously encountered parasites, but infection by novel agents, and eventual depletion of plasma cell reserves, could both still be factors in the near-synchronous mortality of adult shrews observed shortly after breeding

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio