Simultaneous determination of wave speed and arrival time of reflected waves using the pressure-velocity loop

This is the post print version of the article. The official published version can be found at the link below.In a previous paper we demonstrated that the linear portion of the pressure–velocity loop (PU-loop) corresponding to early systole could be used to calculate the local wave speed. In this paper we extend this work to show that determination of the time at which the PU-loop first deviates from linearity provides a convenient way to determine the arrival time of reflected waves (Tr). We also present a new technique using the PU-loop that allows for the determination of wave speed and Tr simultaneously. We measured pressure and flow in elastic tubes of different diameters, where a strong reflection site existed at known distances away form the measurement site. We also measured pressure and flow in the ascending aorta of 11 anaesthetised dogs where a strong reflection site was produced through total arterial occlusion at four different sites. Wave speed was determined from the initial slope of the PU-loop and Tr was determined using a new algorithm that detects the sampling point at which the initial linear part of the PU-loop deviates from linearity. The results of the new technique for detecting Tr were comparable to those determined using the foot-to-foot and wave intensity analysis methods. In elastic tubes Tr detected using the new algorithm was almost identical to that detected using wave intensity analysis and foot-to-foot methods with a maximum difference of 2%. Tr detected using the PU-loop in vivo highly correlated with that detected using wave intensity analysis (r 2 = 0.83, P < 0.001). We conclude that the new technique described in this paper offers a convenient and objective method for detecting Tr, and allows for the dynamic determination of wave speed and Tr, simultaneously

On the Mechanics Underlying the Reservoir-Excess Separation in Systemic Arteries and their Implications for Pulse Wave Analysis

Several works have separated the pressure waveform p in systemic arteries into reservoir pr and excess pexc components, p = pr + pexc, to improve pulse wave analysis, using windkessel models to calculate the reservoir pressure. However, the mechanics underlying this separation and the physical meaning of pr and pexc have not yet been established. They are studied here using the time-domain, inviscid and linear one-dimensional (1-D) equations of blood flow in elastic vessels. Solution of these equations in a distributed model of the 55 larger human arteries shows that pr calculated using a two-element windkessel model is space-independent and well approximated by the compliance-weighted space-average pressure of the arterial network. When arterial junctions are well-matched for the propagation of forward-travelling waves, pr calculated using a three-element windkessel model is space-dependent in systole and early diastole and is made of all the reflected waves originated at the terminal (peripheral) reflection sites, whereas pexc is the sum of the rest of the waves, which are obtained by propagating the left ventricular flow ejection without any peripheral reflection. In addition, new definitions of the reservoir and excess pressures from simultaneous pressure and flow measurements at an arbitrary location are proposed here. They provide valuable information for pulse wave analysis and overcome the limitations of the current two- and three-element windkessel models to calculate pr

Identity Drift:The Multivocality of Ethical Identity in Islamic Financial Institution

In today’s neo-liberalist world, Islamic financial institutions (IFIs) face many difficulties combining contemporary financial thinking with Islamic, faith-based principles, on which their day-to-day operations ought to be based. Hence, IFI are likely to experience shifts/changes in organizational and ethical identity due to tensions that the combination of these principles invokes. We present an in-depth case study that focuses on these shifts in a major European based IFI across a 14-year period. We conceptualize identity change as drift, highlighting the multivocal nature of identity construction. The ethico-faith principles that were meant to serve as living codes of ethics guiding the IFI’s organizational culture, operational processes, and strategy formation turned out to mainly have been discursively rationalized to respond to regulatory, market and institutional imperatives. The company is aware that it needs to engage in a continuous dialogue with those who set these requirements. Its ethico-faith principles may consequently be adapted quite radically, especially in periods of turmoil and takeover, as we show across the analysed time period. The paper provides valuable insights for faith-inspired organizations to reflect on the extent to which they wish to engage in the discursive justification and legitimization of current market hegemonies, whilst they actively encourage their managers to behave ethically as well

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Synchrotron-based XPS studies of AlGaN and GaN surface chemistry and its relationship to ion sensor behaviour

Soft X-ray photoelectron spectroscopy was used to investigate the fundamental surface chemistry of both AlGaN and GaN surfaces in the context of understanding the behaviour of AlGaN/GaN heterostructures as chemical field-effect transistor (CHEMFET) ion sensors. AlGaN and GaN samples were subjected to different methods of oxide growth (native oxide and thermally grown oxide) and chemical treatment conditions. Our investigations indicate that the etching of the oxide layer is more pronounced with AlGaN compared to GaN. Also, we observed that chloride ions have a greater tendency to attach to the GaN surface relative to the AlGaN surface. Furthermore, chloride ions are comparatively more prevalent on surfaces treated with 5% HCl acid solution. The concentration of chloride ions is even higher on the HCl treated native oxide surface resulting in a very clear deconvolution of the Cl 2p1/2 and Cl 2p3/2 peaks. For GaN and AlGaN surfaces, a linear response (e.g. source-drain current) is typically seen with variation in pH of buffered solutions with constant reference electrode voltage at the surface gate; however, an inverted bath-tub type response (e.g. a maximum at neutral pH and lower values at pH values away from neutral) and a general tendency to negative charge selectivity has been also widely reported. We have shown that our XPS investigations are consistent with the different sensor response reported in the literature for these CHEMFET devices and may help to explain the differing response of these materials

Nitrate ion detection using AlGaN/GaN heterostructure-based devices without a reference electrode

AlGaN/GaN heterostructure-based devices can be engineered through heterostructure design to have a high transconductance near zero gate–drain voltage, potentially enabling high sensitivity, reference electrode free, ion sensing. As a proof of concept, these devices were coated with a PVC-based membrane containing a plasticizer and an ionophore to detect nitrate ions in solution. The sensor response is measured as a change in conductivity across two contacts using a Kelvin probe (or four-contact) geometry, with the current between the two outer contacts kept constant. We show that this sensor for nitrate is sensitive and stable with a rapid response time (i.e. less than 60 s). The detection limit remains consistently low over multiple runs/days. In a 0.1 M KH2PO4 ion buffer, a detection limit of less than 1 × 10-6 M and a linear response range of 10-6–10-3 M were achieved. Furthermore, detection limits of approximately 10-6 M and 10-4 M in 0.1 M K2SO4 and 0.1 M KCl ion buffers, respectively, were demonstrated. In a 0.1 M KH2PO4 ion buffer, there was minimal change in sensor response upon addition of KOH increasing the pH from approximately 4–11. As a control, devices without a PVC membrane coating were tested under identical conditions and exhibited negligible response to nitrate ion exposure. Furthermore, using transistor theory, we show that the apparent gate response is near-Nenrstian under a variety of conditions. The success of this study paves the way for extending this technology to selectively sensing multiple ions in water through incorporation of the appropriate polymer based membranes on arrays of devices

Stiffening and ventricular-arterial interaction in the ascending aorta using MRI: ageing effects in healthy humans

OBJECTIVES: The aim of this study was to investigate the effect of age and sex on nPWV and ndI in the ascending aorta of healthy humans. BACKGROUND: Local pulse wave velocity (nPWV) and wave intensity (ndI) in the human ascending aorta have not been studied adequately, because of the need for invasive pressure measurements. However, a recently developed technique made the noninvasive determination of nPWV and ndI possible using measurements of flow velocity and arterial diameter. METHODS: Diameter and flow velocity were measured at the level of the ascending aorta in 144 healthy participants (aged 20-77 years, 66 men), using MRI. nPWV, ndI parameters; forward (FCW); backward (BCW) compression waves, forward decompression wave (FDW), local aortic distensibility (nDs) and reflection index (nRI) were calculated. RESULTS: nPWV increased significantly with age from 4.7 ± 0.3 m/s for those 20-30 years to 6.4 ± 0.2 m/s for those 70-80 years (P < 0.001) and did not differ between sexes. nDs decreased with age (5.3 ± 0.5 vs. 2.6 ± 0.2 10 1/Pa, P < 0.001) and nRI increased with age (0.17 ± 0.03 vs. 0.39 ± 0.06, P < 0.01) for those 20-30 and 70-80 years, respectively. FCW, BCW and FDW decreased significantly with age by 86.3, 71.3 and 74.2%, respectively (P < 0.001), all compared to the lowest age-band. CONCLUSION: In healthy humans, ageing results in stiffer ascending aorta, with increase in nPWV and decrease in nDs. A decrease in FCW and FDW indicates decline in left ventricular early and late systolic functions with age in healthy humans with no differences between sexes. nRI is more sensitive than BCW in establishing the effects of ageing on reflected waves measured in the ascending aorta

Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported. However, whether these families constitute MEN 1 variants or separate entities remains speculative as the genetic bases for these diseases are unclear. The gene for MEN 1 has recently been cloned and characterized. Using single strand conformation analysis (SSCA) and sequencing, we performed mutation analysis in: a) a total of 55 MEN 1 families from 7 countries, b) 13 isolated MEN 1 cases without family history of the disease, c) 8 acromegaly families, and d) 4 FIHP families. Mutations were identified in 27 MEN 1 families and 9 isolated cases. The 22 different mutations spread across most of the 9 translated exons and included frameshift (11), nonsense (6), splice (2), missense mutations (2), and in-frame deletions (1). Among the 19 Finnish MEN 1 probands, a 1466del12 mutation was identified in 6 families with identical 11q13 haplotypes and in 2 isolated cases indicating a common founder. One frameshift mutation caused by 359del4 (GTCT) was found in 1 isolated case and 4 kindreds of different origin and haplotypes; this mutation therefore represents a common "warm" spot in the MEN1 gene. By analyzing the DNA of the parents of an isolated case one mutation was confirmed to be de novo. No mutation was found in any of the acromegaly and small FIHP families, suggesting that genetic defects other than the MEN1 gene might be involved and that additional such families need to be analyzed