From lab-based to in-line: Analytical tools for the characterization of whey protein denaturation and aggregation-A review.

Whey protein denaturation and aggregation have long been areas of research interest to the dairy industry, having significant implications for process performance and final product functionality and quality. As such, a significant number of analytical techniques have been developed or adapted to assess and characterize levels of whey protein denaturation and aggregation, to either maximize processing efficiency or create products with enhanced functionality (both technological and biological). This review aims to collate and critique these approaches based on their analytical principles and outline their application for the assessment of denaturation and aggregation. This review also provides insights into recent developments in process analytical technologies relating to whey protein denaturation and aggregation, whereby some of the analytical methods have been adapted to enable measurements in-line. Developments in this area will enable more live, in-process data to be generated, which will subsequently allow more adaptive processing, enabling improved product quality and processing efficiency. Along with the applicability of these techniques for the assessment of whey protein denaturation and aggregation, limitations are also presented to help assess the suitability of each analytical technique for specific areas of interest.

Features from the photoplethysmogram and the electrocardiogram for estimating changes in blood pressure.

There is a growing emphasis being placed on the potential for cuffless blood pressure (BP) estimation through modelling of morphological features from the photoplethysmogram (PPG) and electrocardiogram (ECG). However, the appropriate features and models to use remain unclear. We investigated the best features available from the PPG and ECG for BP estimation using both linear and non-linear machine learning models. We conducted a clinical study in which changes in BP ([Formula: see text]BP) were induced by an infusion of phenylephrine in 30 healthy volunteers (53.8% female, 28.0 (9.0) years old). We extracted a large and diverse set of features from both the PPG and the ECG and assessed their individual importance for estimating [Formula: see text]BP through Shapley additive explanation values and a ranking coefficient. We trained, tuned, and evaluated linear (ordinary least squares, OLS) and non-linear (random forest, RF) machine learning models to estimate [Formula: see text]BP in a nested leave-one-subject-out cross-validation framework. We reported the results as correlation coefficient ([Formula: see text]), root mean squared error (RMSE), and mean absolute error (MAE). The non-linear RF model significantly ([Formula: see text]) outperformed the linear OLS model using both the PPG and the ECG signals across all performance metrics. Estimating [Formula: see text]SBP using the PPG alone ([Formula: see text] = 0.86 (0.23), RMSE = 5.66 (4.76) mmHg, MAE = 4.86 (4.29) mmHg) performed significantly better than using the ECG alone ([Formula: see text] = 0.69 (0.45), RMSE = 6.79 (4.76) mmHg, MAE = 5.28 (4.57) mmHg), all [Formula: see text]. The highest ranking features from the PPG largely modelled increasing reflected wave interference driven by changes in arterial stiffness. This finding was supported by changes observed in the PPG waveform in response to the phenylephrine infusion. However, a large number of features were required for accurate BP estimation, highlighting the high complexity of the problem. We conclude that the PPG alone may be further explored as a potential single source, cuffless, blood pressure estimator. The use of the ECG alone is not justified. Non-linear models may perform better as they are able to incorporate interactions between feature values and demographics. However, demographics may not adequately account for the unique and individualised relationship between the extracted features and BP.

Classifying nocturnal blood pressure patterns using photoplethysmogram features.

Circadian rhythms in blood pressure (BP) may in some cases be indicative of an increased risk of adverse cardiovascular events. However, current methods for assessing these rhythms can be disruptive to sleep, work, and daily activities. Features of the photoplethysmogram (PPG), which can be non-invasively and unobtrusively recorded, have been suggested as surrogate measures of BP. This work investigates the presence of a circadian rhythm in these features and evaluates their potential to classify nocturnal BP patterns. 742 patients who were discharged home from the ICU were selected from the MIMIC-III database. Our results show that a number of PPG features exhibit a clear and observable circadian rhythm. Of the 19 features evaluated, the circadian rhythms of 5 features outperformed heart rate (HR) in terms of correlation with the circadian rhythm of SBP ( ). We also present evidence that a metric combining the PPG features significantly improves BP phenotype classification accuracy. Clinical Relevance-This work suggests that a combined metric of PPG features may be able to accurately assess an individual's circadian rhythm of BP.

The presence of a circadian rhythm in pulse arrival time and its application for classifying blood pressure night-time dip.

Circadian rhythms of blood pressure (BP) have key diagnostic significance in the assessment of hypertension. The night-time dip or rise in BP (10-20% decrease or increase compared to daytime BP), for example, has been shown to be a strong indicator for cardiovascular disease. However, current methods for assessing the circadian rhythms of BP can be disruptive to sleep, work, and daily activities. Pulse arrival time (PAT) has been suggested as a surrogate measure of BP. This work investigates the presence of a circadian rhythm in PAT and evaluates its application to classify nocturnal BP dip or rise. 769 patients who were discharged home from the ICU were selected from the MIMIC database. Our results show a clear and observable circadian rhythm of PAT that is strongly inversely correlated with BP (r = -0.89). The ratios between nocturnal and diurnal changes in PAT accurately classifies an individual as a nocturnal BP dipper (AUC = 0.72) or a riser (AUC = 0.71).Clinical Relevance-This work shows that you can accurately assess an individuals's circadian rhythm of BP using PAT.

Pulse arrival time as a surrogate of blood pressure.

Various models have been proposed for the estimation of blood pressure (BP) from pulse transit time (PTT). PTT is defined as the time delay of the pressure wave, produced by left ventricular contraction, measured between a proximal and a distal site along the arterial tree. Most researchers, when they measure the time difference between the peak of the R-wave in the electrocardiogram signal (corresponding to left ventricular depolarisation) and a fiducial point in the photoplethysmogram waveform (as measured by a pulse oximeter attached to the fingertip), describe this erroneously as the PTT. In fact, this is the pulse arrival time (PAT), which includes not only PTT, but also the time delay between the electrical depolarisation of the heart's left ventricle and the opening of the aortic valve, known as pre-ejection period (PEP). PEP has been suggested to present a significant limitation to BP estimation using PAT. This work investigates the impact of PEP on PAT, leading to a discussion on the best models for BP estimation using PAT or PTT. We conducted a clinical study involving 30 healthy volunteers (53.3% female, 30.9 ± 9.35 years old, with a body mass index of 22.7 ± 3.2 kg/m[Formula: see text]). Each session lasted on average 27.9 ± 0.6 min and BP was varied by an infusion of phenylephrine (a medication that causes venous and arterial vasoconstriction). We introduced new processing steps for the analysis of PAT and PEP signals. Various population-based models (Poon, Gesche and Fung) and a posteriori models (inverse linear, inverse squared and logarithm) for estimation of BP from PTT or PAT were evaluated. Across the cohort, PEP was found to increase by 5.5 ms ± 4.5 ms from its baseline value. Variations in PTT were significantly larger in amplitude, - 16.8 ms ± 7.5 ms. We suggest, therefore, that for infusions of phenylephrine, the contribution of PEP on PAT can be neglected. All population-based models produced large BP estimation errors, suggesting that they are insufficient for modelling the complex pathways relating changes in PTT or PAT to changes in BP. Although PAT is inversely correlated with systolic blood pressure (SBP), the gradient of this relationship varies significantly from individual to individual, from - 2946 to - 470.64 mmHg/s in our dataset. For the a posteriori inverse squared model, the root mean squared errors (RMSE) for systolic and diastolic blood pressure (DBP) estimation from PAT were 5.49 mmHg and 3.82 mmHg, respectively. The RMSEs for SBP and DBP estimation by PTT were 4.51 mmHg and 3.53 mmHg, respectively. These models take into account individual calibration curves required for accurate blood pressure estimation. The best performing population-based model (Poon) reported error values around double that of the a posteriori inverse squared model, and so the use of population-based models is not justified.

Day-to-day progression of vital-sign circadian rhythms in the intensive care unit.

BACKGROUND: Disrupted vital-sign circadian rhythms in the intensive care unit (ICU) are associated with complications such as immune system disruption, delirium and increased patient mortality. However, the prevalence and extent of this disruption is not well understood. Tools for its detection are currently limited. METHODS: This paper evaluated and compared vital-sign circadian rhythms in systolic blood pressure, heart rate, respiratory rate and temperature. Comparisons were made between the cohort of patients who recovered from the ICU and those who did not, across three large, publicly available clinical databases. This comparison included a qualitative assessment of rhythm profiles, as well as quantitative metrics such as peak-nadir excursions and correlation to a demographically matched 'recovered' profile. RESULTS: Circadian rhythms were present at the cohort level in all vital signs throughout an ICU stay. Peak-nadir excursions and correlation to a 'recovered' profile were typically greater throughout an ICU stay in the cohort of patients who recovered, compared to the cohort of patients who did not. CONCLUSIONS: These results suggest that vital-sign circadian rhythms are typically present at the cohort level throughout an ICU stay and that quantitative assessment of these rhythms may provide information of prognostic use in the ICU.

Non-Contact Assessment of Peripheral Artery Haemodynamics Using Infrared Video Thermography.

Skin temperature has long been used as a natural indicator of vascular diseases in the extremities. Considerable correlation between oscillations in skin surface temperature and oscillations of skin blood flow has previously been demonstrated. We hypothesised that the impairment of blood flow in stenotic (subcutaneous) peripheral arteries would influence cutaneous temperature such that, by measuring gradients in the temperature distribution over skin surfaces, one may be able to diagnose or quantify the progression of vascular conditions in whose pathogenesis a reduction in subcutaneous blood perfusion plays a critical role (e.g. peripheral artery disease). As proof of principle, this study investigates the local changes in the skin temperature of healthy humans (15 male, [Formula: see text] years old, BMI [Formula: see text] kg/m 2) undergoing two physical challenges designed to vary their haemodynamic status. Skin temperature was measured in four central regions (forehead, neck, chest, and left shoulder) and four peripheral regions (left upper arm, forearm, wrist, and hand) using an infrared thermal camera. We compare inter-region patterns. Median temperature over the peripheral regions decreased from baseline after both challenges (maximum decrease: [Formula: see text] °C at 60 s after exercise; [Formula: see text] and [Formula: see text] °C at 180 s of cold-water immersion; [Formula: see text]). Median temperature over the central regions showed no significant changes. Our results show that the non-contact measurement of perfusion-related changes in peripheral temperature from infrared video data is feasible. Further research will be directed towards the thermographic study of patients with symptomatic peripheral vascular disease.

Study protocol for an exploratory interventional study investigating the feasibility of video-based non-contact physiological monitoring in healthy volunteers by Mapping Of Lower Limb skIn pErfusion (MOLLIE).

INTRODUCTION: Skin perfusion varies in response to changes in the circulatory status. Blood flow to skin is reduced during haemodynamic collapse secondary to peripheral vasoconstriction, whereas increased skin perfusion is frequently observed when haemodynamics improve with resuscitation. These changes in perfusion may be monitored using non-contact image-based methods. Previous camera-derived physiological measurements have focused on accurate vital signs monitoring and extraction of physiological signals from environmental noise. One of the biggest challenges of camera-derived monitoring is artefacts from motion, which limits our understanding of what parameters may be derived from skin. In this study, we use phenylephrine and glyceryl trinitrate (GTN) to cause vasoconstriction and vasodilation in stationary healthy volunteers to describe directional changes in skin perfusion pattern. METHODS AND ANALYSIS: We aim to recruit 30 healthy volunteers who will undergo protocolised infusions of phenylephrine and GTN, followed by the monitored and timed release of a thigh tourniquet. The experimental timeline will be identical for all participants. Measurements of traditionally used haemodynamic markers (heart rate, blood pressure and stroke volume) and camera-derived measurements will be taken concurrently throughout the experimental period. The parameters of interest from the image data are skin colour and pattern, skin surface temperature, pulsatile signal detected at the skin surface and skin perfusion index. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Oxford University Research and Ethics Committee and Clinical Trials and Research Governance teams (R63796/RE001). The results of this study will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN10417167.