Reconstructive Intracranial Vascular Surgery

It is scarcely less than two decades since the initial cautious explorations of reconstructive surgery for the prevention of cerebral infarction caused by extracranial vascular disease began. The next years recorded an accumulative experience in the field of vascular surgery. Early clinical investigations led to the discovery that extracranial vascular disease is a major cause of cerebral infarction or stroke. Estimates indicate, however, that only 30-40% of the patients with cerebrovascular insufficiency have significant extracranial occlusive disease. For this larger group of patients, previous surgical methods offer no hope. It is the purpose of this report to review the current status of our clinical explorations in the area of reconstructive intracranial vascular surgery

Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating

Sedentary aging results in a diminished rapid cutaneous vasodilator response to local heating. We investigated whether this diminished response was due to altered contributions of noradrenergic sympathetic nerves; assessing 1) the age-related decline and, 2) the effect of aerobic fitness. We measured skin blood flow (SkBF)(laser-Doppler flowmetry) in young (24±1 yr) and older (64±1 yr) endurance-trained and sedentary men (n=7 per group) at baseline and during 35 min of local skin heating to 42 °C at three forearm sites: 1) untreated; 2) bretylium tosylate (BT), preventing neurotransmitter release from noradrenergic sympathetic nerves; and 3) yohimbine and propranolol (YP), antagonising α- and β-adrenergic receptors. SkBF was converted to cutaneous vascular conductance (CVC) (SkBF/mean arterial pressure) and normalized to maximal CVC (%CVCmax) achieved by skin heating to 44 °C. Pharmacological agents were administered using microdialysis. In the young trained, the rapid vasodilator response was reduced at the BT and YP sites (P0.05) but treatment with BT did (P>0.05). Neither BT nor YP treatments affected the rapid vasodilator response in the older sedentary group (P>0.05). These data suggest that the age-related reduction in the rapid vasodilator response is due to an impairment of sympathetic-dependent mechanisms, which can be partly attenuated with habitual aerobic exercise. Rapid vasodilation involves noradrenergic neurotransmitters in young trained men, and non-adrenergic sympathetic cotransmitters (e.g., neuropeptide Y) in young sedentary and older trained men, possibly as a compensatory mechanism. Finally, in older sedentary men, the rapid vasodilation appears not to involve the sympathetic system

Limb-specific and cross-transfer effects of arm-crank exercise training

Arm cranking is a useful alternative exercise modality for improving walking performance in patients with intermittent claudication; however, the mechanisms of such an improvement are poorly understood. The main aim of the present study was to investigate the effects of arm-crank exercise training on lower-limb O 2 delivery in patients with intermittent claudication. A total of 57 patients with intermittent claudication (age, 70 + − 8 years; mean + − S.D.) were randomized to an arm-crank exercise group or a non-exercise control group. The exercise group trained twice weekly for 12 weeks. At baseline and 12 weeks, patients completed incremental tests to maximum exercise tolerance on both an arm-crank ergometer and a treadmill. Respiratory variables were measured breath-by-breath to determine peakVO 2 (O 2 uptake) and ventilatory threshold. Near-IR spectroscopy was used in the treadmill test to determine changes in calf muscle StO 2 (tissue O 2 saturation). Patients also completed a square-wave treadmill-walking protocol to determineVO 2 kinetics. A total of 51 patients completed the study. In the exercise group, higher maximum walking distances (from 496 + − 250 to 661 + − 324 m) and peakVO 2 values (from 17.2 + − 2.7 to 18.2 + − 3.4 ml · kg − 1 of body mass · min − 1 ) were recorded in the incremental treadmill test (P < 0.05). After training, there was also an increase in time to minimum StO 2 (from 268 + − 305 s to 410 + − 366 s), a speeding ofVO 2 kinetics (from 44.7 + − 10.4 to 41.3 + − 14.4 s) and an increase in submaximal StO 2 during treadmill walking (P < 0.05). There were no significant changes in the control group. The results suggest that the improvement in walking performance after arm-crank exercise training in patients with intermittent claudication is attributable, at least in part, to improved lower-limb O 2 delivery

The SISO CSPI PDG standard for commercial off-the-shelf simulation package interoperability reference models

For many years discrete-event simulation has been used to analyze production and logistics problems in manufactur-ing and defense. Commercial-off-the-shelf Simulation Packages (CSPs), visual interactive modelling environ-ments such as Arena, Anylogic, Flexsim, Simul8, Witness, etc., support the development, experimentation and visua-lization of simulation models. There have been various attempts to create distributed simulations with these CSPs and their tools, some with the High Level Architecture (HLA). These are complex and it is quite difficult to assess how a set of models/CSP are actually interoperating. As the first in a series of standards aimed at standardizing how the HLA is used to support CSP distributed simula-tions, the Simulation Interoperability Standards Organiza-tion’s (SISO) CSP Interoperability Product Development Group (CSPI PDG) has developed and standardized a set of Interoperability Reference Models (IRM) that are in-tended to clearly identify the interoperability capabilities of CSP distributed simulations

Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity. Methods/Design: Sixty patients with stable angina will be recruited and randomised 1: 1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases. Discussion: This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training

Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Article: Bourke, L., Tew, G.A., Milo, M. et Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. S T U D Y P R O T O C O L Open Access Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina Abstract Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity

Fc receptor-like 5 and anti-CD20 treatment response in granulomatosis with polyangiitis and microscopic polyangiitis

BACKGROUND. Baseline expression of FCRL5, a marker of naive and memory B cells, was shown to predict response to rituximab (RTX) in rheumatoid arthritis. This study investigated baseline expression of FCRL5 as a potential biomarker of clinical response to RTX in granulomatosis with polyangiitis (CPA) and microscopic polyangiitis (MPA). METHODS. A previously validated quantitative PCR-based (qPCR-based) platform was used to assess FCRL5 expression in patients with GPA/MPA (RAVE trial, NCT00104299). RESULTS. Baseline FCRL5 expression was significantly higher in patients achieving complete remission (CR) at 6,12, and 18 months, independent of other clinical and serological variables, among those randomized to RTX but not cyclophosphamide-azathioprine (CYC/AZA). Patients with baseline FCRL5 expression >= 0.01 expression units (termed FCRL5(hi)) exhibited significantly higher CR rates at 6,12, and 18 months as compared with FCRL5(lo) subjects (84% versus 57% [P = 0.016], 68% versus 40% [P = 0.02], and 68% versus 29% [P = 0.0009], respectively). CONCLUSION. Our data taken together suggest that FCRL5 is a biomarker of B cell lineage associated with increased achievement and maintenance of complete remission among patients treated with RTX and warrant further investigation in a prospective manner

Association Between Response to Etrolizumab and Expression of Integrin αE and Granzyme A in Colon Biopsies of Patients With Ulcerative Colitis

Background & AimsEtrolizumab is a humanized monoclonal antibody against the β7 integrin subunit that has shown efficacy vs placebo in patients with moderate to severely active ulcerative colitis (UC). Patients with colon tissues that expressed high levels of the integrin αE gene (ITGAE) appeared to have the best response. We compared differences in colonic expression of ITGAE and other genes between patients who achieved clinical remission with etrolizumab vs those who did.MethodsWe performed a retrospective analysis of data collected from 110 patients with UC who participated in a phase 2 placebo-controlled trial of etrolizumab, as well as from 21 patients with UC or without inflammatory bowel disease (controls) enrolled in an observational study at a separate site. Colon biopsies were collected from patients in both studies and analyzed by immunohistochemistry and gene expression profiling. Mononuclear cells were isolated and analyzed by flow cytometry. We identified biomarkers associated with response to etrolizumab. In the placebo-controlled trial, clinical remission was defined as total Mayo Clinic Score ≤2, with no individual subscore >1, and mucosal healing was defined as endoscopic score ≤1.ResultsColon tissues collected at baseline from patients who had a clinical response to etrolizumab expressed higher levels of T-cell−associated genes than patients who did not respond (P < .05). Colonic CD4+ integrin αE+ cells from patients with UC expressed higher levels of granzyme A messenger RNA (GZMA mRNA) than CD4+ αE− cells (P < .0001); granzyme A and integrin αE protein were detected in the same cells. Of patients receiving 100 mg etrolizumab, a higher proportion of those with high levels of GZMA mRNA (41%) or ITGAE mRNA (38%) than those with low levels of GZMA (6%) or ITGAE mRNA (13%) achieved clinical remission (P < .05) and mucosal healing (41% GZMAhigh vs 19% GZMAlow and 44% ITGAEhigh vs 19% ITGAElow). Compared with ITGAElow and GZMAlow patients, patients with ITGAEhigh and GZMAhigh had higher baseline numbers of epithelial crypt-associated integrin αE+ cells (P < .01 for both), but a smaller number of crypt-associated integrin αE+ cells after etrolizumab treatment (P < .05 for both). After 10 weeks of etrolizumab treatment, expression of genes associated with T-cell activation and genes encoding inflammatory cytokines decreased by 40%−80% from baseline (P < .05) in patients with colon tissues expressing high levels of GZMA at baseline.ConclusionsLevels of GZMA and ITGAE mRNAs in colon tissues can identify patients with UC who are most likely to benefit from etrolizumab; expression levels decrease with etrolizumab administration in biomarkerhigh patients. Larger, prospective studies of markers are needed to assess their clinical value

Sexual Size Dimorphism and Body Condition in the Australasian Gannet

Funding: The research was financially supported by the Holsworth Wildlife Research Endowment. Acknowledgments We thank the Victorian Marine Science Consortium, Sea All Dolphin Swim, Parks Victoria, and the Point Danger Management Committee for logistical support. We are grateful for the assistance of the many field volunteers involved in the study.Peer reviewedPublisher PD

Catalysis in flow: Operando study of Pd catalyst speciation and leaching

A custom-made plug flow reactor was designed and constructed to examine the behaviour of Pd catalysts during Suzuki-Miyaura cross-coupling reactions. Spatial-temporal resolution of catalyst activation, deactivation and leaching processes can be obtained by single-pass experiments. Subsequent deployment of the flow reactor in a XAS beam line revealed speciation of Pd along the catalyst bed