A model of oxygen dynamics in the cerebral microvasculature and the effects of morphology on flow and metabolism

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.The cerebral microvasculature plays a vital role in adequately supplying blood to the brain. Determining the health of the cerebral microvasculature is important during pathological conditions, such as stroke and dementia. Recent studies have shown the complex behaviour of cerebral metabolic rate with transit time distribution. In this paper, we extend a recently developed technique to solve for residue function and transit time distribution in an existing physiologically accurate model of the cerebral microvasculature to calculate cerebral metabolism. We present the mathematical theory based on solving the mass transport equation followed by results of the simulations. It is found that oxygen extraction fraction and cerebral metabolic rate are dependent on both mean and heterogeneity of the transit time distribution. For changes in cerebral blood flow, a positive correlation can be observed between mean transit time and oxygen extraction fraction, and a negative correlation between mean transit time and metabolic rate of oxygen. The metabolic rate is thus affected more significantly by cerebral blood flow than oxygen extraction fraction. A negative correlation can also be observed between transit time heterogeneity and the metabolic rate of oxygen for a constant cerebral blood flow. The heterogeneity of the transit time distribution also has an effect on the response of oxygen extraction fraction and cerebral metabolic rate to sudden changes. These results provide information on the role of the cerebral microvasculature and its effects on flow and metabolism. They thus open up the possibility of obtaining additional valuable clinical information for diagnosing and treating cerebrovascular diseases

Influence of the microvasculature on oxygen transport in human brain tissue

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.Two numerical methods are presented for simulating a micro-stroke: a discretised model and a continuum model, both developed for simulating coupled flow and oxygen transport to the microvasculature. The discrete model treats the microvasculature and the tissue perfusion as two coupled sub-systems governed by Poiseulle flow and mass transport equation respectively. The continuum model regards the blood passage as a porous media flow and deals with mass transport in terms of a two phase flow system. In our simulations, it has been shown that the microvascular structure has a strong influence on the localized oxygen transport behaviour, contributing to more complex patterns in the tissue oxygen concentration than those found by assuming continuum behaviour

A systematic review of the anxiety-attention relationship in far-aiming skills

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this recordTheoretical accounts of the anxiety and motor performance relationship cite disruptions to attention as a critical mediating factor. The aims of this paper were to (1) systematically review published research examining attentional mechanisms underpinning the anxiety–performance relationship in targeting skills, and (2) subsequently discuss these findings in relation to contemporary theoretical perspectives. Adhering to PRISMA guidelines, three electronic databases (PubMed, PsycInfo, and SPORTDiscus) were searched from inception until June 2017. Thirty-four articles satisfied the inclusion criteria. Overall, the research is of high methodological quality; however, there is a tendency to focus on the historical dichotomy between self-focus and distraction accounts, whereas empirical support for more contemporary theoretical perspectives is lacking. Whilst this review provides further support for the role of attentional disruptions in anxiety-induced performance degradation, the exact mechanisms still lack consensus. In addition, more innovative experimental designs and measures are required to progress our understanding of moderating variables

In silico investigation of the effect of particle diameter on deposition uniformity in pulmonary drug delivery

Systemic drug delivery via the pulmonary route has a critical limitation because dose uniformity is strongly dependent upon patient inhalation technique. The most frequent and critical errors in inhalation technique are overly forceful inspiration and insufficient breath-holding. In this study, response surface methodology was used with an in silico whole lung particle deposition model for bolus administration to investigate whether varying the inhaled drug particle size could reduce the dependence of deposition upon flow rate and/or breath-holding duration. The range of particle aerodynamic diameters studied was 0.1–10 µm for flow rates between 500–2000 mL/s and breath-holding duration between 0–15 seconds. Comparison with published experimental data showed that this modeling approach can accurately predict the lung deposition. The simulation results indicated that the deposition of particles with aerodynamic diameter in the range of 0.1–1.5 µm should be minimally affected by flow rate over the 500–2000 mL/s range. There was found to be no particle size whose deposition was completely independent of breath-holding duration. The smallest particles, whose deposition is diffusion-driven, were found to be the least sensitive to breath-holding time, but this size is of limited practical use. On the other hand, the simulations indicated that particles with a 1.5 µm diameter would provide acceptable consistency in dose reaching the acini region when the breath-holding duration was greater than 10 seconds. It is hoped that this finding could provide a means of improving dose uniformity for systemic delivery via the pulmonary route by facilitating simplified patient instructions

Speciation by host switch in brood parasitic indigobirds

A growing body of empirical and theoretical work supports the plausibility of sympatric speciation(1-3), but there remain few examples in which all the essential components of the process are well understood. The African indigobirds Vidua spp. are host-specific brood parasites. Indigobird nestlings are reared along with host young, and mimic the mouth markings of their respective hosts(4-6). As adults, male indigobirds mimic host song(4-7), whereas females use these songs to choose both their mates and the nests they parasitize(8). These behavioural mechanisms promote the cohesion of indigobird populations associated with a given host species, and provide a mechanism for reproductive isolation after a new host is colonized. Here we show that all indigobird species are similar genetically, but are significantly differentiated in both mitochondrial haplotype and nuclear allele frequencies. These data support a model of recent sympatric speciation. In contrast to the cuckoo Cuculus canorus, in which only female lineages are faithful to specific hosts(9,10), host switches have led to speciation in indigobirds because both males and females imprint on their hosts(8,11).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62510/1/nature01863.pd

Transferring research from a university to the United Kingdom National Health Service : The implications for impact

This is an Open Access article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.The aim of this article is to inform readers of the author's reflections on the experience of transferring universitybased research into the commercial sector, and of the processes and strategies employed when preparing for impact in so doing. Concepts for the transfer are illustrated by the author's reflection on aspects that arose during the birthing and subsequent start-up of a university spin-off, Pathways2Wellbeing, a form of reflection-on-action. This is the vehicle for the adaption required to transfer research into the delivery of a specialised clinic in the United Kingdom National Health Service for people with medically unexplained, persistent, bodily symptoms such as fibromyalgia, chronic fatigue and chronic pain. It is hoped that the article will provide readers with an insight into how knowledge transfer can take place through engagement with stakeholders to create an exchange of knowledges to result in impact on health service policy for service users, despite the challenges, and the enablers that facilitated this process. The reflections on the process of knowledge transfer and the implications for impact are underpinned by relevant theory.Peer reviewedFinal Published versio

Biliary stenting in patients with pancreatic cancer: results from a population-based cohort study

We aimed to describe management of biliary obstruction (BO) in the context of pancreatic cancer within a population-based cohort.We examined management of BO in 1863 patients diagnosed as having pancreatic cancer in 2010/2011. We used descriptive statistics and logistic regression to describe patterns of biliary stent usage, complications and duration of patency, associations between preoperative stenting and surgical outcomes, and between patient factors and management of jaundice.Almost half of the people in the cohort (n = 909) were jaundiced within 12 months of diagnosis. Two-thirds of these had at least 1 stent inserted. Preoperative stenting, mostly with plastic stents, occurred for 72% of patients who experienced jaundice prior to an attempted resection but was not associated with surgical outcomes. Seventy percent of the jaundiced patients who did not have an attempted resection were stented. Metal stents were less frequently replaced within 30 days than plastic (9% vs 42%). Living in a rural area was associated with reduced likelihood of having jaundice managed.Plastic stents were still used frequently, despite guidelines recommending metal in most contexts. Patients living in rural areas were less likely to have BO managed. This work highlights the need to monitor current practice

Modelling mixing within the dead space of the lung improves predictions of functional residual capacity

Routine estimation of functional residual capacity (FRC) in ventilated patients has been a long held goal, with many methods previously proposed, but none have been used in routine clinical practice. This paper proposes three models for determining FRC using the nitrous oxide concentration from the entire expired breath in order to improve the precision of the estimate. Of the three models proposed, a dead space with two mixing compartments provided the best results, reducing the mean limits of agreement with the FRC measured by whole body plethysmography by up to 41%. This moves away from traditional lung models, which do not account for mixing within the dead space. Compared to literature values for FRC, the results are similar to those obtained using helium dilution and better than the LUFU device (Dräger Medical, Lubeck, Germany), with significantly better limits of agreement compared to plethysmography