Assessments of Arterial Stiffness and Endothelial Function Using Pulse Wave Analysis

Conventionally, the assessments of endothelial function and arterial stiffness require different sets of equipment, making the inclusion of both tests impractical for clinical and epidemiological studies. Pulse wave analysis (PWA) provides useful information regarding the mechanical properties of the arterial tree and can also be used to assess endothelial function. PWA is a simple, valid, reliable, and inexpensive technique, offering great clinical and epidemiological potential. The current paper will outline how to measure arterial stiffness and endothelial function using this technique and include discussion of validity and reliability

The Importance of Velocity Acceleration to Flow-Mediated Dilation

The validity of the flow-mediated dilation test has been questioned due to the lack of normalization to the primary stimulus, shear stress. Shear stress can be calculated using Poiseuille's law. However, little attention has been given to the most appropriate blood velocity parameter(s) for calculating shear stress. The pulsatile nature of blood flow exposes the endothelial cells to two distinct shear stimuli during the cardiac cycle: a large rate of change in shear at the onset of flow (velocity acceleration), followed by a steady component. The parameter typically entered into the Poiseuille's law equation to determine shear stress is time-averaged blood velocity, with no regard for flow pulsatility. This paper will discuss (1) the limitations of using Posieuille's law to estimate shear stress and (2) the importance of the velocity profile—with emphasis on velocity acceleration—to endothelial function and vascular tone

The Importance of Velocity Acceleration to Flow-Mediated Dilation

The validity of the flow-mediated dilation test has been questioned due to the lack of normalization to the primary stimulus, shear stress. Shear stress can be calculated using Poiseuille's law. However, little attention has been given to the most appropriate blood velocity parameter(s) for calculating shear stress. The pulsatile nature of blood flow exposes the endothelial cells to two distinct shear stimuli during the cardiac cycle: a large rate of change in shear at the onset of flow (velocity acceleration), followed by a steady component. The parameter typically entered into the Poiseuille's law equation to determine shear stress is time-averaged blood velocity, with no regard for flow pulsatility. This paper will discuss (1) the limitations of using Posieuille's law to estimate shear stress and (2) the importance of the velocity profile—with emphasis on velocity acceleration—to endothelial function and vascular tone

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The Importance of Velocity Acceleration to Flow-Mediated Dilation

The validity of the flow-mediated dilation test has been questioned due to the lack of normalization to the primary stimulus, shear stress. Shear stress can be calculated using Poiseuille's law. However, little attention has been given to the most appropriate blood velocity parameter(s) for calculating shear stress. The pulsatile nature of blood flow exposes the endothelial cells to two distinct shear stimuli during the cardiac cycle: a large rate of change in shear at the onset of flow (velocity acceleration), followed by a steady component. The parameter typically entered into the Poiseuille's law equation to determine shear stress is time-averaged blood velocity, with no regard for flow pulsatility. This paper will discuss (1) the limitations of using Posieuille's law to estimate shear stress and (2) the importance of the velocity profile—with emphasis on velocity acceleration—to endothelial function and vascular tone

Demarginalizing Interdisciplinarity in IS Research: Interdisciplinary Research in Marginalization

This paper reports on the second Workshop of a World University Network (WUN) Research Development Funded project on “The trans-nationalization of Indigenous movements: The role of digital technologies” at the University of Southampton, UK. The workshop explored interdisciplinarity and how interdisciplinary collaboration can help scholars study complex social phenomenon, such as the ways in which marginalized Indigenous communities use and shape digital technologies (such as social media) to enhance their cause. The workshop brought together scholars from diverse disciplines to engage in a critical debate. In addition to scholars from information systems, scholars from history, political science, geography, literature, arts, and anthropology came together to discuss how marginalized Indigenous communities can use digital media. The workshop highlighted the need for more interdisciplinary research and called for more critical approaches to bring such marginalized topics to the forefront of research in information systems. We consider three broad areas of inquiry in this paper: demarginalizing methodology for interdisciplinary research, interdisciplinary perspectives for demarginalization, and interdisciplinary contexts for demarginalization

Radionuclide Labeling and Evaluation of Candidate Radioligands for PET Imaging of Histone Deacetylase in the Brain

Histone deacetylases (HDACs) regulate gene expression by inducing conformational changes in chromatin. Ever since the discovery of a naturally occurring HDAC inhibitor, trichostatin A (TSA) stimulated the recent development of suberoylanilide (SAHA, Zolinza®), HDAC has become an important molecular target for drug development. This has created the need to develop specific in vivo radioligands to study epigenetic regulation and HDAC engagement for drug development for diseases including cancer and psychiatric disorders. 6-([18F]Fluoroacetamido)-1-hexanoicanilide ([18F]FAHA) was recently developed as a HDAC substrate and shows moderate blood–brain barrier (BBB) permeability and specific signal (by metabolic trapping/or deacetylation) but rapid metabolism. Here, we report the radiosynthesis of two carbon-11 labeled candidate radiotracers (substrate- and inhibitor-based radioligand) for HDAC and their evaluation in non-human primate brain. PET studies showed very low brain uptake and rapid metabolism of both labeled compounds but revealed a surprising enhancement of brain penetration by F for H substitution when comparing one of these to [18F]FAHA. Further structural refinement is needed for the development of brain-penetrant, metabolically stable HDAC radiotracers and to understand the role of fluorine substitution on brain penetration.Chemistry and Chemical Biolog

The utility of presentation and 4-hour high sensitivity troponin I to rule-out acute myocardial infarction in the emergency department

Objectives: International guidance recommends that early serial sampling of high sensitivity troponin be used to accurately identify acute myocardial infarction (AMI) in chest pain patients. The background evidence for this approach is limited. We evaluated whether on presentation and 4-hour high-sensitivity troponin I (hs-cTnI) could be used to accurately rule-out AMI. Design and methods: hs-cTnI was measured on presentation and at 4-hours in adult patients attending an emergency department with possible acute coronary syndrome. We determined the sensitivity for AMI for at least one hs-cTnI above the 99th percentile for a healthy population or alone or in combination with new ischemic ECG changes. Both overall and sex-specific 99th percentiles were assessed. Patients with negative tests were designated low-risk. Results: 63 (17.1%) of 368 patients had AMI. The median (interquartile range) time from symptom onset to first blood sampling was 4.8. h (2.8-8.6). The sensitivity of the presentation and 4. h hs-cTnI using the overall 99th percentile was 92.1% (95% CI 82.4% to 97.4%) and negative predictive value 95.4% (92.3% to 97.4%) with 78.3% low-risk. Applying the sex-specific 99th percentile did not change the sensitivity. The addition of ECG did not change the sensitivity. Conclusion: Hs-cTnI >. 99th percentile thresholds measured on presentation and at 4-hours was not a safe strategy to rule-out AMI in this clinical setting irrespective of whether sex-specific 99th percentiles were used, or whether hs-cTnI was combined with ECG results

Heart Fatty Acid Binding Protein and cardiac troponin: development of an optimal rule-out strategy for acute myocardial infarction

Background: Improved ability to rapidly rule-out Acute Myocardial Infarction (AMI) in patients presenting with chest pain will promote decongestion of the Emergency Department (ED) and reduce unnecessary hospital admissions. We assessed a new commercial Heart Fatty Acid Binding Protein (H-FABP) assay for additional diagnostic value when combined with cardiac troponin (using a high sensitivity assay). Methods: H-FABP and high-sensitivity troponins I (hs-cTnI) and T (hs-cTnT) were measured in samples taken on-presentation from patients, attending the ED, with symptoms triggering investigation for possible acute coronary syndrome. The optimal combination of H-FABP with each hs-cTn was defined as that which maximized the proportion of patients with a negative test (low-risk) whilst maintaining at least 99 % sensitivity for AMI. A negative test comprised both H-FABP and hs-cTn below the chosen threshold in the absence of ischemic changes on the ECG. Results: One thousand seventy-nine patients were recruited including 248 with AMI. H-FABP 99 % sensitivity for AMI whilst classifying 40.9 % of patients as low-risk. The combination of H-FABP < 3.9 ng/mL and hs-cTnT < 7.6 ng/L with a negative ECG maintained the same sensitivity whilst classifying 32.1 % of patients as low risk. Conclusions: In patients requiring rule-out of AMI, the addition of H-FABP to hs-cTn at presentation (in the absence of new ischaemic ECG findings) may accelerate clinical diagnostic decision making by identifying up to 40 % of such patients as low-risk for AMI on the basis of blood tests performed on presentation. If implemented this has the potential to significantly accelerate triaging of patients for early discharge from the ED