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High resolution photoemission study of SiOx/Si(111) interface disruption following in situ HfO₂deposition

We report on an in situ high resolution core level photoemission study of the early stages of interface formation between an ultrathin SiOx layer ( ∼ 0.3 nm) grown on the atomically clean Si(111) surface and a HfO2 dielectric layer. Si 2p core level spectra acquired at 130 eV photon energy reveal evidence of a chemically shifted component on the lower binding energy side of the substrate peak which is attributed to interface defect states resulting from the incorporation of silicon atoms from the substrate into the interfacial oxide at room temperature. This evidence of Si/SiOx interface disruption would be expected to increase charge carrier scattering mechanisms in the silicon and contribute to the generally observed mobility degradation in high-k stacks with ultrathin silicon oxide interface layers

Development of novel antibody-based diagnostics for the early and rapid detection of cardiac markers

The principal objective of this research was the production, characterisation and application of antibodies for the detection of both C-reactive protein (CRP) and Myeloperoxidase (MPO), two promising candidates in the field of cardiac diagnostics. CRP is a highly stable acute phase reactant, produced in the liver in response to interleukin (IL)-6. In January 2003 both the Centres for Disease Control and Prevention (CDC) and the American Heart Association (AHA) recommended CRP as the inflammatory marker of choice for assessment of cardiovascular risk. The other biomarker under investigation was MPO, a mediator enzyme secreted by inflammatory cells such as activated neutrophils and monocytes. High levels of MPO have been reported in atherosclerotic plaques and accumulating evidence indicates that MPO may have a causative role in plaque vulnerability. It has been suggested that these markers may even be complementary in the assessment of patient cardiac risk. As a marker of disease activity and vascular inflammation, CRP detection is associated with longterm risk stratification while MPO, being a marker of plaque instability and neutrophil activation, may be prove to be a key marker for short term stratification. A key feature of this work was to ensure the isolated antibodies had a sufficient level of both functional affinity and specificity for the development of novel diagnostic formats and assay platforms. Both classic polyclonal antibody generation and ‘state-of-the-art’ phage display technology were employed for the generation of CRP- and MPO-specific antibodies and recombinant fragments. The immune systems of mice, rabbits and chickens were investigated in this work, which allowed for the identification of the main advantages and disadvantages associated with each of the host immune systems and their capacity for generating specific and sensitive antibodies. It was observed that the avian immune system was found to be the most effective system for the generation of functional and soluble antibodies. The CRP-specific antibodies were incorporated into three novel biosensor platforms for their final characterisation. In addition, a novel lateral flow immunoassay (LFIA) for the rapid detection of MPO was developed, using a recombinant antibody isolated from a MPOimmune library. Spiked samples of depleted human serum were employed in both the biosensor and LFIA systems, thus validating the detection of the analytes in a realistic sample matri

Young athletes under pressure?

Regular participation in exercise has long been known to result in cardiovascular adaptation. Historically, the ‘athlete’s heart’ hypothesis has encouraged a dichotomised view of the heart’s adaptation to sport, depending on whether the physical activity was either of isotonic activity (runners and swimmers) resulting in ‘cardiomegaly’ or of isometric effort (wrestlers and shot putters, ie, ‘strength’ athletes) with clear peripheral adaptations and an ‘obvious increase in cardiac size’. Today, the classification of sports according to their physiological demands acknowledges a greater diversity of exposure, depending on the physical activity, with an emphasis on a ‘graded transition’ between the main categories: dynamic, static and impact. Still, our understanding of the determinants of structural and functional cardiovascular adaptation to exercise are limited, and the consequences for health remain a matter of debate

The effect of diabetes, ethnicity, impaired fasting glucose and exercise on arterial stiffness

The "first study" compared 3 methods of assessing arterial stiffness and found that: each method of assessment was comparable to the other and that reproducibility was similar throughout the systems. Since there are conflicting data associated with arterial stiffness and type-2 diabetes, the "second study" therefore assessed arterial stiffness, using pulse wave analysis and pulse wave velocity and found there to be increased arterial stiffness in a group of type-2 diabetics compared to healthy controls. The second study also found that South Asians had significantly lower arterial stiffness in the femoral vascular bed compared to the Caucasians. Although diabetes is known to increase arterial stiffness, the effect of impaired fasting glucose on arterial stiffness is unclear. The effect of impaired fasting glucose on arterial stiffness has therefore been investigated in the "third study" and the findings demonstrate that individuals with impaired fasting glucose have increased arterial stiffness compared to individuals with normal fasting glucose. Similar findings were observed when comparing diabetics and individuals with normoglycaemia. Finally, therapeutic intervention targeted at increased arterial stiffness should be of benefit in reducing the prevalence of cardiovascular disease. The "fourth study" has therefore also examined the effect of regular aerobic exercise on arterial stiffness and found that in older individuals, arterial stiffness was significantly lower in a group of individuals who exercised regularly compared to sedentary controls. Therefore, suggesting the potential benefit of aerobic exercise as a non-pharmacological intervention to decrease arterial stiffness and cardiovascular disease

CrossTalk proposal: Blood flow pulsatility in left ventricular assist device patients is essential to maintain normal brain physiology

For the first time in history, some humans live without a palpable pulse (Purohit et al. 2018). This remarkable physiology is the consequence of surgical implantation of a continuous‐flow left ventricular assist device (CF‐LVAD) in patients with end‐stage heart failure. Blood flow produced by CF‐LVADs has a low oscillatory profile in the aorta that results in significantly reduced pulsatility in all arterial compartments (Castagna et al. 2017; Fig. 1). Despite remarkable gains in quality of life and longevity, complications that affect not only morbidity, such as gastrointestinal bleeding, but also mortality, such as strokes, are still prevalent in CF‐LVAD patients. Low pulsatility has been proposed as a major culprit in contributing to these adverse events (Mancini & Colombo, 2015; Goldstein et al. 2018). In this CrossTalk proposal, we present the current arguments in favour of maintaining an appropriate amount of arterial pulsatility, in particular in the cerebral circulation, to lower risk in these patients

“Bionic Women and Men”: The Unique Physiology of Left Ventricular Assist Device Patients – Keep your finger on the pulse!

Across many countries in the world, advanced heart failure patients who are eligible for a heart transplant face the same dilemma: there are not enough donor hearts available for all. The current next-best alternative to a heart transplant is the surgical implantation of a left ventricular assist device (LVAD). Although the purpose of the LVAD is to relieve the overloaded left ventricle of heart failure patients and restore a normal cardiac output, patients have presented with high levels of stroke gastrointestinal bleeding and right-heart failure. One potential reason for this increased risk is the continuous flow of the implanted LVAD. As a result, the majority of LVAD patients do not have a palpable pulse (Purohit et al., 2018), creating a unique arterial biology in these humans (Castagna et al., 2017). Perhaps surprising is the superior health outcome of patients supported with continuous-flow (CF) compared with pulsatile-flow LVADs. In addition, the reduced/absent pulsatility in these CF-LVAD patients (see figure 1.) enables the investigation of unique arterial physiology and cardiovascular regulation, which has already revealed some unexpected observations. For example, continuous-flow patients appear to have a higher sympathetic activity (Cornwell et al., 2015), and suffer complications above a low systolic blood pressure of ~100 mmHg, atypical of non-LVAD populations in whom hypertension (>140 mmHg) is a predictor of stroke (Pinsino et al., 2019). Thus, the medical debate whether continuous flow is truly better for the health of advanced heart failure patients also necessitates a more generic, fundamental discussion into ‘normal’ arterial physiology & health. The comprehensive study investigating the detailed cardiovascular response and adaptations to drastically altered haemodynamics in heart failure, with and without LVAD support, at rest, during physical activity and in combination with cardiovascular acting medication, is essential. This unique area of research presents an opportunity to significantly increase our fundamental physiological understanding of the interaction between cardiac dynamics (volume, force, ejection pattern) and arterial regulation (flow, blood pressure, sympathetic activity, endothelial function, pulsatility). Therefore, the symposium entitled “Bionic women and men – Physiology lessons from implantable cardiac devices” held at the 2019 Annual Meeting of The Physiological Society in Aberdeen, UK, brought together clinicians and scientists from a previous CrossTalk debate (Cornwell et al., 2019; Stöhr et al., 2019) to review the current knowledge of LVAD patients and identify outstanding questions in the field. In total, four presentations were given and each of them have been published as symposium reports in this edition of Experimental Physiology

Aortic Pulse Wave Velocity as a Measure of Cardiovascular Risk in Chronic Obstructive Pulmonary Disease: Two-Year Follow-Up Data from the ARCADE Study

Background and objectives: Cardiovascular (CV) disease is a major cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD). Patients with COPD have increased arterial stiffness, which may predict future CV risk. However, the development of arterial stiffness in COPD has not yet been studied prospectively. The Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE) is a longitudinal study of CV risk and other comorbidities in COPD. The aims of this analysis were to explore factors associated with aortic pulse wave velocity (aPWV) at baseline and to describe the progression of aPWV in patients with COPD and comparators over two years. Materials and methods: At baseline, 520 patients with COPD (confirmed by spirometry) and 150 comparators free from respiratory disease were assessed for body composition, blood pressure, aPWV, noninvasive measures of cardiac output, inflammatory biomarkers, and exercise capacity. This was repeated after two years, and mortality cases and causes were also recorded. Results: At baseline, aPWV was greater in COPD patients 9.8 (95% confidence interval (CI) 9.7–10) versus comparators 8.7 (8.5–9.1) m/s (p < 0.01) after adjustments for age, mean arterial pressure (MAP), and heart rate. Mean blood pressure was 98 ± 11 in COPD patients and 95 ± 10 mmHg in comparators at baseline (p = 0.004). After two years, 301 patients and 105 comparators were fully reassessed. The mean (95% CI) aPWV increased similarly in patients 0.44 (0.25–0.63) and comparators 0.46 (0.23–0.69) m/s, without a change in blood pressure. At the two-year follow-up, there were 29 (6%) deaths in COPD patients, with the majority due to respiratory causes, with an overall dropout of 43% of patients with COPD and 30% of comparators. Conclusions: This was the first large longitudinal study of CV risk in COPD patients, and we confirmed greater aPWV in COPD patients than comparators after adjustments for confounding factors. After two years, patients and comparators had a similar increase of almost 0.5 m/s aPWV

Biosecurity on poultry farms from on-farm fluidized bed combustion and energy recovery from poultry litter

peer-reviewedThe spreading of poultry litter in recent years has led to a serious increase in levels of eutrophication, nitrate leaching, high Biological Oxygen Demand (BOD), ammonia toxicity, high chlorine concentrations and pathogen contamination. The review presented here details the optimum standards that should be met when storing litter for On-Farm Fluidized Bed Combustion. Storage conditions are paramount to a fuel combusting to its highest possible potential. Safety measures such as the prevention of leaching and spontaneous combustion must be adhered to, so too should the prevention and containment of possible diseases and pathogens to minimize the effects of contamination