Long reaction times are associated with delayed brain activity in Lewy body dementia

A significant symptom of Lewy body dementia (LBD) is slow cognitive processing or bradyphrenia. In a previous fMRI task-based study, we found slower responses in LBD, accompanied by greater deactivation in the default mode network. In this study, we investigated the timing and magnitude of the activations and deactivations with respect to reaction time to determine whether the slower responses in LBD were associated with delayed neuronal activity. Using fMRI, we examined the magnitude and latency of activations and deactivations during an event-related attention task in 32 patients with LBD and 23 healthy controls using predefined regions of interest. Default mode network deactivations did not significantly differ in their timing between groups or task conditions, while the task-related activations in the parietal, occipital, frontal, and motor cortex were all significantly later in the LBD group. Repeating the analysis with reaction time as a parametric modulator of activation magnitude produced similar findings, with the reaction time modulator being significant in a number of regions including the default mode network, suggesting that the increased deactivation in LBD is partly explained by slower task completion. Our data suggest that the default mode network deactivation is initiated at the start of the task, and remains deactivated until its end, with the increased magnitude of deactivation in LBD reflecting the more prolonged cognitive processing in these patients. These data add substantially to our understanding of the neural origins of bradyphrenia, which will be essential for determining optimum therapeutic strategies for cognitive impairment in LBD.Funded by: National Institute for Health Research, Newcastle Biomedical Research Unit based at Newcastle Hospitals NHS Foundation Trust, Newcastle University, Wellcome Trust. Grant Number: WT088441M

Improved characterisation and modelling of microbubbles in biomedical applications

Interest in coated microbubbles as agents for therapeutic and quantitative imaging applications in biomedical ultrasound has increased the need for their accurate modelling. However, effects such as gas diffusion, the properties of the coating and changes in bubble behaviour under repeated ultrasound pulses are still poorly understood. The work described in this thesis attempts to develop new theoretical descriptions of microbubble behaviour to address this challenge. In the first part of the thesis, a model of gas exchange into and out of bubbles in tissue under a varying external pressure is developed and applied to the computationally simpler problem of decompression diving. It is concluded that gas diffusion can explain bubble growth and the model validates current decompression algorithms. In the second part of the thesis, a revised equation of motion for microbubble oscillation is proposed that includes the effects of gas diffusion and a time-dependent surfactant surface concentration. This is subsequently incorporated into a nonlinear wave propagation model to account for these additional effects in the response of microbubble contrast agents to ultrasound excitation. Furthermore, the accuracy of a recently proposed computationally efficient method of modelling nonlinear propagation through a polydisperse bubble population is investigated. However, the approximation is concluded to be insufficiently accurate for parameter regimes corresponding to biomedical ultrasound. The results from the new model for microbubble dynamics indicate significant changes in both bubble behaviour and the character of the propagated pulse, demonstrating better agreement with experimental data than predictions from existing models. The results strongly suggest that changes in bubble dynamics are dominated both by surfactant shedding on ultrasonic timescales and gas diffusion over longer timescales between pulses. Incorporating such time-dependent phenomena in ultrasound imaging algorithms should lead to better quantitative agreement with experiment and guide future improvements in the clinical implementation of microbubble contrast agents

Ultrasound propagation through dilute polydisperse microbubble suspensions

In a fully nonlinear model of wave propagation through bubbly media, computational complexity arises when the medium contains a polydisperse bubble population. This is because a nonlinear ordinary differential equation governing the bubble response must be solved for the current radius of each bubble size present at every spatial location and at every time step. In biomedical ultrasound imaging, commercial contrast agents typically possess a wide range of bubble sizes that exhibit a variety of differing behaviours at ultrasound frequencies of clinical interest. Despite the advent of supercomputing resources, the simulation of ultrasound propagation through microbubble populations still represents a formidable numerical task. Consequently, efficient computational algorithms that have the potential to be implemented in real time on clinical scanners remain highly desirable. In this work, a numerical approach is investigated that computes only a single ordinary differential equation at each spatial location which can potentially reduce significantly the computational effort. It is demonstrated that, under certain parameter regimes, the approach replicates the fully nonlinear model of an incident ultrasound pulse propagating through a polydisperse population of bubbles with a high degree of accuracy

Estimating the incidence of acute infectious intestinal disease in the community in the UK:A retrospective telephone survey

Objectives: To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design. Design/Setting: A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days. Participants: 14,813 individuals for all of whom we had a legible recording of their agreement to participate Outcomes: Self-reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause. Results: The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135 – 2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377 – 778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time. Conclusions: The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates

Quantum states made to measure

Recent progress in manipulating quantum states of light and matter brings quantum-enhanced measurements closer to prospective applications. The current challenge is to make quantum metrologic strategies robust against imperfections.Comment: 4 pages, 3 figures, Commentary for Nature Photonic

On-chip manipulation of single photons from a diamond defect

Operating reconfigurable quantum circuits with single photon sources is a key goal of photonic quantum information science and technology. We use an integrated waveguide device containing directional couplers and a reconfigurable thermal phase controller to manipulate single photons emitted from a chromium related color center in diamond. Observation of both a wavelike interference pattern and particlelike sub-Poissionian autocorrelation functions demonstrates coherent manipulation of single photons emitted from the chromium related center and verifies wave particle duality. © 2013 American Physical Society

Validation protocols for blood pressure measuring devices: the impact of the European Society of Hypertension International Protocol and the development of a Universal Standard

In the last three decades protocols for the validation of blood pressure measuring devices have been developed by the US Association for the Advancement of Medical Instrumentation, the British Hypertension Society, the German Hypertension League, the European Society of Hypertension Working Group on blood pressure Monitoring and the International Organization for Standardization. The European Society of Hypertension International Protocol required much smaller sample size than the other protocols, aiming to reduce the time, resources and cost of validation studies and thereby increase the number of validated devices. Given its specifications, the European Society of Hypertension International Protocol was adequate for ‘high- and low-accuracy’ devices, yet assessment of ‘moderate accuracy’ devices had high uncertainty with resultant high rate of device failure. Thus, devices validated using the European Society of Hypertension International Protocol should be considered to be as accurate as those validated with the previous Association for the Advancement of Medical Instrumentation or British Hypertension Society protocols. However, the European Society of Hypertension International Protocol did not allow subgroup evaluation (arm sizes, special populations, etc). The mission of the European Society of Hypertension International Protocol to promote the concept of validation has been well achieved, as almost double studies have been published using it than all the other protocols together. However, the maintenance of different validation protocols is confusing and therefore experts from the Association for the Advancement of Medical Instrumentation, European Society of Hypertension International Protocol and International Organization for Standardization have now developed the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) as the recommended 21st-century procedure for worldwide application. The European Society of Hypertension Working Group has published a practical guide for using the Universal Standard. It is in the interests of all scientific bodies to propagate the Universal Standard and ensure its wide implementation