Publications

ThrUMMS: A New View of the Molecular Milky Way

Abstract We present the Three-mm Ultimate Mopra Milky Way Survey, a new mm-wave molecular-line mapping survey of the southern Galactic Plane, and its first data releases and science results. ThrUMMS maps a 60° × 2° sector of our Galaxy's fourth quadrant, using a combination of fast mapping techniques with the Mopra radio telescope, simultaneously in the J = 1→0 lines of 12 CO, 13 CO, C 18 O, and CN near 112 GHz, at 1′.2 and 0.3 km s −1 resolution, with 1.2 K/ch sensitivity for 12 CO and 0.7 K/ch for the other transitions. The calibrated data cubes from these observations are made freely available to the community on the ThrUMMS website, http://www.astro.ufl.edu/thrumms , after processing through our pipeline. Here, we summarise the first science results, on global variations in the iso-CO line ratios and on a detailed multiwavelength study of the GMCs near l =333°.

Behaviour, finite element modelling and design of high strength steel homogeneous and hybrid welded I‐section beams

Abstract The behaviour and design of homogeneous and hybrid high strength steel (HSS) beams are addressed in the present study. Six in‐plane three‐point bending tests on three different welded I‐sections were first conducted. Following the experimental investigation, a finite element (FE) modelling programme was performed, which included a validation study confirming the accuracy of the developed FE models in replicating the flexural behaviour of HSS welded I‐section beams, and a parametric study generating additional FE data on HSS welded I‐section beams over a broader range of cross‐sectional slendernesses, steel grades and loading configurations. Then, the suitability of the current Eurocode 3 cross‐section slenderness limits for HSS homogeneous and hybrid welded I‐sections in bending were evaluated. It is shown that the current Eurocode Class 2 and Class 3 slenderness limits are suitable for the classification of the outstand flange (in compression) and internal web (in bending) elements of both HSS homogeneous and hybrid welded I‐sections subjected to major axis bending, while stricter Class 1 slenderness limits are considered necessary to achieve sufficient rotation capacity for plastic design. The findings indicate that plastic design can be used for HSS structures, provided the proposed stricter Class 1 slenderness limits are employed. Further work is underway to develop advanced design approaches using second‐order inelastic analysis with strain limits for HSS welded I‐section members.

Characterisation of the MALT90 Survey and the Mopra Telescope at 90 GHz

Abstract We characterise the Millimetre Astronomy Legacy Team 90 GHz Survey (MALT90) and the Mopra telescope at 90 GHz. We combine repeated position-switched observations of the source G300.968+01.145 with a map of the same source in order to estimate the pointing reliability of the position-switched observations and, by extension, the MALT90 survey; we estimate our pointing uncertainty to be 8 arcsec. We model the two strongest sources of systematic gain variability as functions of elevation and time-of-day and quantify the remaining absolute flux uncertainty. Corrections based on these two variables reduce the scatter in repeated observations from 12%–25% down to 10%–17%. We find no evidence for intrinsic source variability in G300.968+01.145. For certain applications, the corrections described herein will be integral for improving the absolute flux calibration of MALT90 maps and other observations using the Mopra telescope at 90 GHz.

Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial

Background Everolimus-eluting stent (EES) reduces the risk of restenosis in elective percutaneous coronary intervention. However, the use of drug-eluting stent in patients with ST-segment elevation myocardial infarction (STEMI) is still controversial. Data regarding the performance of second-generation EES in this setting are scarce. We report the 1-year result of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) trial, comparing EES with bare-metal stents (BMS) in patients with STEMI. Methods This multicentre, prospective, randomised, all-comer controlled trial was done in 12 medical centres in three countries. Between Dec 31, 2008, and May 15, 2010, we recruited patients with STEMI up to 48 h after the onset of symptoms requiring emergent percutaneous coronary intervention. Patients were randomly assigned (ratio 1:1) to receive EES or BMS. Randomisation was in blocks of four or six patients, stratified by centre and centralised by telephone. Patients were masked to treatment. The primary endpoint was the patient-oriented combined endpoint of all-cause death, any recurrent myocardial infarction, and any revascularisation at 1 year and was analysed by intention to treat. The secondary endpoints of the study included the device-oriented combined endpoint of cardiac death, target vessel myocardial infarction or target lesion revascularisation, and rates of all cause or cardiac death, recurrent myocardial infarction, target lesion or target vessel revascularisation, stent thrombosis, device and procedure success, and major and minor bleeding. This trial is registered with ClinicalTrials.gov, number NCT00828087. Findings Of the 1504 patients randomised, 1498 patients were randomly assigned to receive EES (n=751) or BMS (n=747). The primary endpoint was similar in both groups (89 [11·9%] of 751 patients in the EES group vs 106 [14·2%] of 747 patients in the BMS group; difference −2·34 [95% CI −5·75 to 1·07]; p=0·19). Device-oriented endpoint (44 [5·9%] in the EES group vs 63 [8·4%] in the BMS group; difference −2·57 [95% CI −5·18 to 0·03]; p=0·05) did not differ between groups, although rates of target lesion and vessel revascularisation were significantly lower in the EES group (16 [2·1%] vs 37 [5·0%], p=0·003, and 28 [3·7%] vs 51 [6·8%], p=0·0077, respectively). Rates of all cause (26 [3·5%] for EES vs 26 [3·5%] for BMS, p=1·00) or cardiac death (24 [3·2%] for EES vs 21 [2·8%] for BMS, p=0·76) or myocardial infarction (10 [1·3%] vs 15 [2·0%], p=0·32) did not differ between groups. Stent thrombosis rates were significantly lower in the EES group (4 [0·5%] patients with definite stent thrombosis in the EES group vs 14 [1·9%] in the BMS group and seven [0·9%] patients with definite or probable stent thrombosis in the EES group vs 19 [2·5%] in the BMS group, both p=0·019). Although device success rate was similar between groups, procedure success rate was significantly higher in the EES group (731 [97·5%] vs 705 [94·6%]; p=0·0050). Finally, Bleeding rates at 1 year were comparable between groups (29 [3·9%] patients in the EES group vs 39 [5·2%] in the BMS group; p=0·19). Interpretation The use of EES compared with BMS in the setting of STEMI did not lower the patient-oriented endpoint. However, at the stent level both rates of target lesion revascularisation and stent thrombosis were reduced in recipients of EES. Funding Spanish Heart Foundation.

CHALLENGES OF MYOGENESIS AND REPAIR OF THE HEART

A damaged myocardium cannot effectively regenerate and repair itself subsequent to either acute or chronic pathologic insult. The emerging field of cell transplantation has attempted to address some of the issues and has progressed from preclinical studies to proof-of-concept clinical studies conducted in humans. Different cell types are being researched, including autologous skeletal muscle-derived myoblasts, bone marrow-derived mesenchymal stem cells and autologous bone marrow-derived stem cells. Other ongoing efforts are seeking to promote homing of bone marrow-g g derived cells to convert to cardiomyocytes in the myocardium, enhancement of the ability of cardiomyocytes to replicate and efforts to derive pluripotent stem cells from human blastocysts. While a variety of other cell types such as embryonic cardiomyocytes and embryonic stem cells have been investigated through preclinical studies, they have not progressed to clinical applications, for logistic and ethical reasons. The goal of any such therapy is to restore both an angiogenic and a muscular component to the myocardium by replacing damaged, fibrous scar tissue with compliant, elastic muscle tissue that would convert an akinetic or dyskinetic scar into tissue that augments systolic and diastolic function. The unique ability of skeletal muscle-derived stem cells (myoblasts) to form myotubes within the infarcted zones of the heart has led to the promotion of early pilot studies in humans.1-5 A secondary benefit would be that the compliance of the scar would be modified such that the pathologic remodeling process would be altered and would progress towards the baseline normal state.6-8 The challenge of replacing a large amount of dysfunctional and necrotic tissue is immense, and the ability to deliver, retain and engraft cells into a mechanically disadvantaged and neurohormonally altered environment has yet to be adequately addressed.

Modulation of neurogenic inflammation: novel approaches to inflammatory disease

A comparison of the distribution of necrotic core in bifurcation and non-bifurcation coronary lesions: an in vivo assessment using intravascular ultrasound radiofrequency data analysis

High-risk plaques are prone to develop at the site of coronary vessel bifurcations. The distribution of necrotic core at bifurcation lesions (BL) is known, however, little has been described on the necrotic core distribution in non-BLs. Therefore we compared the distribution of necrotic core between BL and non-BLs in coronary arteries using IVUS-VH imaging.A total of 129 patients (112 non-BL and 108 BL) were included. The lesions were divided into upstream and downstream segments according the location of the minimum lumen area (MLA) within the plaque. In BLs, compositional analysis showed no differences between the three segments. The necrotic core in contact with the lumen that was located in the downstream segment was significantly larger. While in non-BLs, this was not significantly different between segments. Plaque burden in BLs was 56.60±5.79% vs. 55.50±4.54% in non-BLs, p=0.04. Mean necrotic core area was larger in BLs 0.84±0.55mm2 vs. 0.70±0.49mm2, p=0.048. Mean percentage necrotic core was 15.48±8.02% vs. 14.51±7.64%, p=0.37. There was a trend towards a greater content of necrotic core in contact with the lumen in BLs. The percentage of frames with a major confluent pool of necrotic core in contact with the lumen >10% in BLs was 11.78±17.18 vs. 8.95±17.86 in non-BLs, p=0.065. There was a statistically significant difference in the frequency of IVUS derived thin capped fibroatheromas between bifurcation lesions 20 vs. 13 in non-bifurcation lesions, p=0.03.Bifurcation lesions appear to have a larger plaque burden with a different plaque composition compared to non-bifurcation lesions. This may partly explain the adverse outcomes seen following treatment of bifurcation lesions in contemporary practice.

Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis

The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.

Efficacy and safety profile of xanthines in COPD: a network meta-analysis

Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD. The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safety as a function of person-weeks. Data obtained from 998 COPD patients were selected from 14 studies and meta-analysed using a network approach. The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 s) and safety (risk of adverse events) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety). Considering the overall efficacy/safety profile of the investigated agents, the results of this quantitative synthesis suggest that doxofylline seems to be the best xanthine for the treatment of COPD.

MOLECULAR MECHANISM OF ACTION OF STEROIDS IN ASTHMA

Does prolonged clopidogrel therapy improve outcome in patients with drug-eluting or bare-metal stents?

No abstract is provided for this article.

Probing the stability landscape of prestressed stayed columns susceptible to mode interaction

Total occlusion trial with angioplasty by using laser guidewire. The TOTAL trial

Aims A randomized trial was performed to assess the safety and efficacy of a laser guidewire, in the treatment of chronic coronary occlusions. Methods and Results In 18 European centres, 303 patients with a chronic coronary occlusion were randomized to treatment with either the laser guidewire (n=144) or conventional guidewires (mechanical guidewire, n=159). The primary end-point of the study was treatment success, defined as reaching the true lumen distal to the occlusion by the allocated wire within 30min of fluoroscopic time: laser guidewire vs mechanical guidewire; 52·8% (n=76) vs 47·2% (n=75), P=0·33. Serious adverse events following the initial guidewire attempt were 0% (laser guidewire) and 0·6% (mechanical guidewire), respectively. Angioplasty (performed following successful guidewire crossing) was successful in 179 patients (91%, laser guidewire n=79, mechanical guidewire n=100), followed by stent implantation in 149 (79%). At the 6-month angiographic follow-up, the difference in binary restenosis rate (laser guidewire vs mechanical guidewire; 45·5% vs 38·3 %, P=0·72) or reocclusion rate (25·8% vs 16·1%, P=0·15) did not reach statistical significance. At 1, 6 and 12 months, angina and event-free survival were 69%, 35% and 24% (laser guidewire) vs 74%, 40% and 31% (mechanical guidewire). Conclusion Although laser guidewire technology was safe, the increase in crossing success did not reach statistical significance.

Design challenges for high current storage rings

Quantifying Proliferation of Cultured Human and Rabbit Airway Smooth Muscle Cells in Response to Serum and Platelet-derived Growth Factor

Development of suitable methods for the quantification of the proliferative response of airway smooth muscle (ASM) cells in culture will assist the investigation of the cellular mechanisms underlying the hyperplasia and hypertrophy of ASM as seen in asthmatic airways. In this study, two rapid and simple colorimetric assays have been modified to enable the growth of human bronchial and rabbit tracheal smooth muscle in culture to be assessed. One method depends upon the reduction by living cells of the tetrazolium salt MTT to form a blue formazan product, whereas the other relies on rapid binding of the dye Coomassie brilliant blue to protein at acidic pH. Experiments demonstrated the validity of both assays in quantifying the proliferative response of cultured human and rabbit ASM cells. The increase in optical density observed for each assay correlated directly, throughout the duration of culture, with the increase in cell number determined by hemocytometry in human and rabbit ASM cells proliferating in response to fetal calf serum (1.25 to 10%). This relationship held also for rabbit tracheal ASM cells proliferating in response to the heterodimer of platelet-derived growth factor (1 to 50 ng/ml). Application of these methods to adherent proliferating cultures of human and rabbit ASM cells demonstrated their adaptability to the generation of growth curves in response to serum and to a defined growth factor. These methods allow both total cellular protein and proliferation to be estimated in human and rabbit ASM cells in culture, using assays that are rapid, reproducible, inexpensive, and easy to perform while negating the use of radioisotopes. It is intended that these additional methods should be useful in delineating some of the mechanisms that might contribute to the proliferative response of these cells — particularly since there has been a resurgence in interest in culturing smooth muscle cells derived from the airways.

Gold 2023: Highlights for primary care

Mechanical performance and design optimisation of metal honeycombs fabricated by laser powder bed fusion

Honeycomb structures have a wide range of applications, from medical implants to industrial components. In addition, honeycombs play a critical role when passive protection is required due to their low density and high energy absorption capabilities. With the transition of additive manufacturing from a rapid prototyping approach to a manufacturing process, this technology has recently offered designers and manufacturers the ability to fabricate and modify lattice structures such as honeycombs. The current study presents the application of laser powder bed fusion, a common additive manufacturing process for producing industrial metal components, for fabricating metal honeycombs. In addition, this study examines three modified designs that can only be practically fabricated using additive manufacturing and compares them with conventional honeycombs. For this purpose, quasi-static and dynamic compression tests are conducted to evaluate and compare the performance of the honeycomb structures. The results show that the structures produced by additive manufacturing have acceptable performance compared to conventional honeycomb structures, and laser powder bed fusion can be considered to be a reliable manufacturing method for honeycomb production. Furthermore, the honeycombs produced according to the modified designs generally outperformed their counterparts made from the typical hexagonal cells. Ultimately, the use of triangular cells as a design modification is proposed to produce honeycombs with promising performance characteristics in all of their principal axes and under various pressure scenarios, from quasi-static to dynamic loading rates. Finally, this study also investigates the applicability of a newly developed maraging steel for additive manufacturing of honeycombs. Microstructural analysis and quasi-static tensile tests have confirmed the material properties for this purpose.

The Role of IκB Kinase 2, but Not Activation of NF-κB, in the Release of CXCR3 Ligands from IFN-γ-Stimulated Human Bronchial Epithelial Cells

The severity of chronic obstructive pulmonary disease correlates with increased numbers of cytotoxic CD8(+) T lymphocytes in the lung parenchyma. CD8(+) T lymphocytes release IFN-gamma which stimulates airway epithelial cells to produce CXCR3 chemokines leading to further recruitment of CD8(+) T lymphocytes. To evaluate the signaling pathways involved in regulation of CXCR3 ligands, the human bronchial epithelial cell line BEAS-2B was stimulated with IFN-gamma and the release of the CXCR3 ligands was measured by ELISA. The release of CXCL9, CXCL10, and CXCL11 was inhibited by an IkappaB kinase 2 (IKK2) selective inhibitor 2-[(Aminocarbonyl)amino]-5-[4-fluorophenyl]-3-thiophenecarboxamide (TPCA-1) (EC(50) values were 0.50 +/- 0.03, 0.17 +/- 0.06, and 0.45 +/- 0.10 microM, respectively (n = 6)) and an IKK1/2 selective inhibitor 2-amino-6-(2'cyclopropylemethoxy-6'-hydroxy-phenyl)-4-piperidin-3-yl-pyridine-3-carbonitrile (EC(50) values 0.74 +/- 0.40, 0.27 +/- 0.06, and 0.88 +/- 0.29 microM, respectively (n = 6)). The glucocorticosteroid dexamethasone had no effect on CXCR3 ligand release. The release of CXCL10 was most sensitive to inhibition by IKK2 and a role for IKK2 in CXCL10 release was confirmed by overexpression of dominant-negative adenoviral constructs to IKK2 (68.2 +/- 8.3% n = 5), but not of IKK1. Neither phosphorylation of IkappaBalpha, translocation of p65 to the nucleus, or activation of a NF-kappaB-dependent reporter (Ad-NF-kappaB-luc) were detected following stimulation of BEAS-2B cells with IFN-gamma. These data suggest that IKK2 is also involved in the IFN-gamma-stimulated release of the CXCR3 ligands through a novel mechanism that is independent NF-kappaB.