Microalbuminuria could improve risk stratification in patients with TIA and minor stroke.

Published onlineJournal ArticleThis is the final version of the article. Available from Wiley Open Access via the DOI in this record.OBJECTIVE: Transient ischemic attacks (TIA) and minor strokes are important risk factors for recurrent strokes. Current stroke risk prediction scores such as ABCD2, although widely used, lack optimal sensitivity and specificity. Elevated urinary albumin excretion predicts cardiovascular disease, stroke, and mortality. We explored the role of microalbuminuria (using albumin creatinine ratio (ACR)) in predicting recurrence risk in patients with TIA and minor stroke. METHODS: Urinary ACR was measured on a spot sample in 150 patients attending a daily stroke clinic with TIA or minor stroke. Patients were followed up at day 7, 30, and 90 to determine recurrent stroke, cardiovascular events, or death. Eligible patients had a carotid ultrasound Doppler investigation. High-risk patients were defined as those who had an event within 90 days or had >50% internal carotid artery (ICA) stenosis. RESULTS: Fourteen (9.8%) recurrent events were reported by day 90 including two deaths. Fifteen patients had severe ICA stenosis. In total, 26 patients were identified as high risk. These patients had a higher frequency of previous stroke or hypercholesterolemia compared to low-risk patients (P = 0.04). ACR was higher in high-risk patients (3.4 [95% CI 2.2-5.2] vs. 1.7 [1.5-2.1] mg/mmol, P = 0.004), independent of age, sex, blood pressure, diabetes, and previous stroke. An ACR greater than 1.5 mg/mmol predicted high-risk patients (Cox proportional hazard ratio 3.5 (95% CI 1.3-9.5, P = 0.01). INTERPRETATION: After TIA or minor stroke, a higher ACR predicted recurrent events and significant ICA stenosis. Incorporation of urinary ACR from a spot sample in the acute setting could improve risk stratification in patients with TIA and minor stroke.This article presents independent research supported by the NIHR Exeter Clinical Research Facility and the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR Exeter Clinical Research Facility, the NHS, the NIHR or the Department of Health in England. We also acknowledge and thank the South West Stroke Research Network for their help with patient recruitment and follow-up, and Mrs. Audrey Peters and Mr. Frank Summers for performing the carotid Doppler scans

South Asians have elevated postexercise blood pressure and myocardial oxygen consumption compared to Europeans despite equivalent resting pressure

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Stroke mortality rate is higher in South Asians than in Europeans, despite equivalent or lower resting blood pressure (BP). Elevated recovery BP after exercise predicts stroke, independently of resting values. We hypothesized that South Asians would have adverse postexercise hemodynamics and sought explanations for this. METHODS AND RESULTS: A population-based sample of 147 European and 145 South Asian middle-aged men and women performed the Dundee 3-minute step test. Cardiovascular risk factors were measured. BP, heart rate, and rate-pressure product, a measure of myocardial oxygen consumption, were compared. With 90% power and 5% significance, we could detect a difference of 0.38 of a standard deviation in any outcome measure. Resting systolic BP was similar in South Asians (144 mm Hg) and Europeans (142 mm Hg) (P=0.2), as was exercise BP (P=0.4). However, recovery systolic BP at 3 minutes after exercise was higher in South Asians by 4.3 mm Hg (95% confidence interval [CI], 0.2 to 8.3 mm Hg; P=0.04). This effect persisted when adjusted for exercise BP and work effort (5.4 mm Hg [95% CI, 2.2 to 8.7 mm Hg; P=0.001]). Adjustment for baroreflex insensitivity and greater aortic stiffness in South Asians contributes greatly to attenuating this ethnic difference (1.9 mm Hg [95% CI, -0.9 to 4.6 mm Hg; P=0.4]). Similarly, rate-pressure product recovery after exercise was impaired in South Asians by 735 mm Hg/min (95% CI, 137 to 1334 mm Hg/min; P=0.02); again, adjustment for baroreflex insensitivity and aortic stiffness attenuated this difference (261 mm Hg/min [95% CI, -39 to 561 mm Hg/min; P=0.3]). CONCLUSION: Postexercise recovery of BP and rate-pressure product is impaired in South Asians compared to Europeans even though resting and exercise BP are similar. This is associated with the autonomic dysfunction and aortic stiffness in South Asians.The British Heart Foundation funded this project. Drs Chaturvedi, Kooner, John Chambers, and Hughes received support from the NIHR (UK National Institute for Health Research) Biomedical Research Centre. Dr Shore received support from the Peninsula NIHR Clinical Research Facility

Measurement of Wall Shear Stress Exerted by Flowing Blood in the Human Carotid Artery: Ultrasound Doppler Velocimetry and Echo Particle Image Velocimetry

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordVascular endothelial cells lining the arteries are sensitive to wall shear stress (WSS) exerted by flowing blood. An important component of the pathophysiology of vascular diseases, WSS is commonly estimated by centerline ultrasound Doppler velocimetry (UDV). However, the accuracy of this method is uncertain. We have previously validated the use of a novel, ultrasound-based, particle image velocimetry technique (echo PIV) to compute 2-D velocity vector fields, which can easily be converted into WSS data. We compared WSS data derived from UDV and echo PIV in the common carotid artery of 27 healthy participants. Compared with echo PIV, time-averaged WSS was lower using UDV (28 ± 35%). Echo PIV revealed that this was due to considerable spatiotemporal variation in the flow velocity profile, contrary to the assumption that flow is steady and the velocity profile is parabolic throughout the cardiac cycle. The largest WSS underestimation by UDV was found during peak systole (118 ± 16%) and the smallest during mid-diastole (4.3± 46%). The UDV method underestimated WSS for the accelerating and decelerating systolic measurements (68 ± 30% and 24 ± 51%), whereas WSS was overestimated for end-diastolic measurements (−44 ± 55%). Our data indicate that UDV estimates of WSS provided limited and largely inaccurate information about WSS and that the complex spatiotemporal flow patterns do not fit well with traditional assumptions about blood flow in arteries. Echo PIV-derived WSS provides detailed information about this important but poorly understood stimulus that influences vascular endothelial pathophysiology.National Institute of HealthNational Institute for Health Research (NIHR

Associations between interarm differences in blood pressure and cardiovascular disease outcomes: protocol for an individual patient data meta-analysis and development of a prognostic algorithm

This is the final version of the article. Available on open access from BMJ Publishing Group via the DOI in this record.There is another record for this publication in ORE: http://hdl.handle.net/10871/32190INTRODUCTION: Individual cohort studies in various populations and study-level meta-analyses have shown interarm differences (IAD) in blood pressure to be associated with increased cardiovascular and all-cause mortality. However, key questions remain, such as follows: (1) What is the additional contribution of IAD to prognostic risk estimation for cardiovascular and all-cause mortality? (2) What is the minimum cut-off value for IAD that defines elevated risk? (3) Is there a prognostic value of IAD and do different methods of IAD measurement impact on the prognostic value of IAD? We aim to address these questions by conducting an individual patient data (IPD) meta-analysis. METHODS AND ANALYSIS: This study will identify prospective cohort studies that measured blood pressure in both arms during recruitment, and invite authors to contribute IPD datasets to this collaboration. All patient data received will be combined into a single dataset. Using one-stage meta-analysis, we will undertake multivariable time-to-event regression modelling, with the aim of developing a new prognostic model for cardiovascular risk estimation that includes IAD. We will explore variations in risk contribution of IAD across predefined population subgroups (eg, hypertensives, diabetics), establish the lower limit of IAD that is associated with additional cardiovascular risk and assess the impact of different methods of IAD measurement on risk prediction. ETHICS AND DISSEMINATION: This study will not include any patient identifiable data. Included datasets will already have ethical approval and consent from their sponsors. Findings will be presented to international conferences and published in peer reviewed journals, and we have a comprehensive dissemination strategy in place with integrated patient and public involvement. PROSPERO REGISTRATION NUMBER: CRD42015031227.National Institute for Health Research (NIHR

Capillary pressure may predict preclinical changes in the eye

This is the final version. Available on open access from Springer Verlag via the DOI in this recordAIMS/HYPOTHESIS: Microvascular dysfunction is associated with end-organ damage. Macular oedema is an important component of diabetic retinopathy. Macular thickness can be accurately quantified by optical coherence tomography (OCT), enabling accurate assessment of the macular prior to clinically apparent abnormalities. We investigated whether macular (fovea) thickness in non-diabetic individuals is related to the microvascular variables controlling fluid filtration across a blood vessel wall, in particular capillary pressure and the microvascular filtration capacity (Kf). METHODS: We recruited 50 non-diabetic individuals (25 men, 25 women; age range: 26-78 years; BMI range: 20-46 kg/m(2)). Fovea thickness was assessed by OCT. Microvascular assessments included: finger nailfold capillary pressure; Kf; microvascular structural assessments, i.e. skin vasodilatory capacity, minimum vascular resistance (MVR) and microvascular distensibility; and endothelial function. RESULTS: At 214.6 (19.9) microm (mean [SD]), fovea thickness was within normal range. Capillary pressure, adjusted for BMI, was associated with fovea thickness (standardised beta 0.573, p = 0.006, linear regression). Fovea thickness was not associated with Kf, microvascular structural assessments or endothelial function. Capillary pressure was still associated with fovea thickness when adjusted for microvascular variables (Kf, vasodilatory capacity, MVR, microvascular distensibility or endothelial function), or for risk factors for diabetes (systemic blood pressure, insulin sensitivity, inflammation, glycaemic status and lipids) and age. CONCLUSIONS/INTERPRETATION: Capillary pressure, a key determinant of movement of fluid across a blood vessel wall, is associated with fovea thickness in non-diabetic individuals. This suggests that with regard to potential preventative or therapeutic targets, attention should be directed at the mechanisms determining retinal microvascular pressure.Diabetes UKNational Institute for Health Research (NIHR

Utilization of Raman spectroscopy to identify breast cancer from the water content in surgical samples containing blue dye

This is the final version. Available on open access from Wiley via the DOI in this record. Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.Breast conserving surgery (BCS) for breast cancer aims for optimal oncological results with minimal tissue excision. Positive margins due to insufficient resection results in significant numbers of patients requiring re‐excision, which could be resolved with intra‐operative margin analysis (IMA). High wavenumber (HWN) Raman Spectroscopy (RS) examines the difference in protein/lipid environment and water content in tissues. Fluorescence from haemoglobin and blue dye surgical pigments (commonly present in excised breast tissue) can confound HWN RS. We present a Raman system with 785 nm excitation laser and indium gallium arsenide camera capable of quantifying changes in water content in different environments (protein‐rich and lipid‐rich) by measuring the water/total area ratio (W/TAR) of the HWN spectrum. We demonstrate that haemoglobin and blue dye do not adversely affect water content analysis by the W/TAR calculation. Measurement of paired tumour/non‐tumour human breast tissue specimens showed the biochemical differences between tissues, and spectral analysis with W/TAR demonstrated large differences in water content and that our Raman system can accurately differentiate between tumour and non‐tumour tissue, even in the presence of surgical pigments. This provides proof of principle that this Raman system is suitable for further investigation with a view to providing IMA in the clinical environment.National Institute for Health Research (NIHR)Engineering and Physical Sciences Research Council (EPSRC

Advances in Screening, Early Diagnosis and Accurate Staging of Diabetic Neuropathy

This is the final version. Available on open access from Frontiers Media via the DOI in this recordThe incidence of both type 1 and type 2 diabetes is increasing worldwide. Diabetic peripheral neuropathy (DPN) is among the most distressing and costly of all the chronic complications of diabetes and is a cause of significant disability and poor quality of life. This incurs a significant burden on health care costs and society, especially as these young people enter their peak working and earning capacity at the time when diabetes-related complications most often first occur. DPN is often asymptomatic during the early stages; however, once symptoms and overt deficits have developed, it cannot be reversed. Therefore, early diagnosis and timely intervention are essential to prevent the development and progression of diabetic neuropathy. The diagnosis of DPN, the determination of the global prevalence, and incidence rates of DPN remain challenging. The opinions vary about the effectiveness of the expansion of screenings to enable early diagnosis and treatment initiation before disease onset and progression. Although research has evolved over the years, DPN still represents an enormous burden for clinicians and health systems worldwide due to its difficult diagnosis, high costs related to treatment, and the multidisciplinary approach required for effective management. Therefore, there is an unmet need for reliable surrogate biomarkers to monitor the onset and progression of early neuropathic changes in DPN and facilitate drug discovery. In this review paper, the aim was to assess the currently available tests for DPN’s sensitivity and performance.National Institute for Health Research (NIHR

Brachial artery vasodilatory response and wall shear rate determined by multi-gate Doppler in a healthy young cohort

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.Wall shear rate (WSR) is an important stimulus for the brachial artery flow-mediated dilation (FMD) response. However, WSR estimation near the arterial wall by conventional Doppler is inherently difficult. To overcome this limitation, we utilised multi-gate Doppler to accurately determine the WSR stimulus near the vessel wall simultaneously with the FMD response using an integrated FMD system [Ultrasound Advanced Open Platform (ULA-OP)]. Using the system, we aimed to perform a detailed analysis of WSR-FMD response and establish novel WSR parameters in a healthy young population. Data from 33 young healthy individuals (27.5±4.9yrs, 19F) were analysed. FMD was assessed with reactive hyperemia using ULA-OP. All acquired raw data were post-processed using custom-designed software to obtain WSR and diameter parameters. The acquired velocity data revealed that non-parabolic flow-profiles within the cardiac cycle and under different flow-states, with heterogeneity between participants. We also identified seven WSR magnitude and four WSR time-course parameters. Among them, WSR area under the curve until its return to baseline was the strongest predictor of the absolute (R2 =0.25) and percentage (R2 =0.31) diameter changes in response to reactive hyperemia. For the first time, we identified mono- and biphasic WSR stimulus patterns within our cohort that produced different magnitudes of FMD response [absolute diameter change: 0.24±0.10mm (monophasic) vs 0.17±0.09mm (biphasic), p<0.05]. We concluded that accurate and detailed measurement of the WSR stimulus is important to comprehensively understand the FMD response and that this advance in current FMD technology could be important to better understand vascular physiology and pathology.This study was supported by the European Union’s Seventh Framework Programme (FP7/2007-2013) for the Innovative Medicine Initiative under grant agreement number IMI/115006 (the SUMMIT consortium), in part by the National Institute of Health Research (NIHR) Exeter Clinical Research Facility, and by the Italian Ministry of University and Research (MIUR, Project PRIN 2010-2011)

Diets of European polecat Mustela putorius in Great Britain during fifty years of population recovery

This is the final version. Available from Springer via the DOI in this record. Following nineteenth-century declines, polecats Mustela putorius are recolonising Great Britain. Polecat diet relates to two potential risks to recovery. First, rabbits Oryctolagus cuniculus, which are important prey for polecats, have experienced extreme population fluctuations, with near extirpation due to myxomatosis in the 1950s, recovery in 1960s–1990s and declines in 1990s–2010s. Second, polecats are secondarily exposed to anticoagulant rodenticides by eating contaminated rodents, and the frequency of polecat exposure to rodenticides is increasing. We analysed stomach contents from 99 polecats collected in 2012–2016 and compared results with earlier studies. Lagomorphs were the most abundant prey (66% frequency of occurrence, 95% confidence interval 53–74%), followed by other mammals (12%, 4–18%), amphibians (10%, 3–16%) and birds (7%, 1–13%). Diet varied seasonally; lagomorph occurrence was highest in spring and summer and lowest in autumn. Dietary niche breadth was greater in the 1960s, when rabbits were scarce, than in other decades, but did not differ between the 1990s and 2010s, indicating that diets have not diversified with recent rabbit declines. This may be because rabbit abundance is not yet low enough to cause dietary diversification or because polecats were collected in areas where rabbits were still abundant. Rodents did not increase in diet between the 1990s and 2010s and still occur with < 10% frequency, indicating that rodents need not contribute much to diet to expose polecats to rodenticides. This potentially limits the effectiveness of management actions designed to minimise polecat exposure to contaminated rodent prey.Vincent Wildlife TrustUniversity of Exete

Global Symmetries and D-Terms in Supersymmetric Field Theories

We study the role of D-terms in supersymmetry (SUSY) breaking. By carefully analyzing the SUSY multiplets containing various conserved currents in theories with global symmetries, we obtain a number of constraints on the renormalization group flow in supersymmetric field theories. Under broad assumptions, these results imply that there are no SUSY-breaking vacua, not even metastable ones, with parametrically large D-terms. This explains the absence of such D-terms in models of dynamical SUSY-breaking. There is, however, a rich class of calculable models which generate comparable D-terms and F-terms through a variety of non-perturbative effects; these D-terms can be non-abelian. We give several explicit examples of such models, one of which is a new calculable limit of the 3-2 model.Comment: 34 pages, 2 figures; reference added, minor change