Modelling mucociliary clearance

Mathematical modelling of the fluid mechanics of mucociliary clearance (MCC) is reviewed and future challenges for researchers are discussed. The morphology of the bronchial and tracheal airway surface liquid (ASL) and ciliated epithelium are briefly introduced. The cilia beat cycle, beat frequency and metachronal coordination are described, along with the rheology of the mucous layer. Theoretical modelling of MCC from the late 1960s onwards is reviewed, and distinctions between ‘phenomenological’, ‘slender body theory’ and recent ‘fluid–structure interaction’ models are explained.\ud \ud The ASL consists of two layers, an overlying mucous layer and underlying watery periciliary layer (PCL) which bathes the cilia. Previous models have predicted very little transport of fluid in the PCL compared with the mucous layer. Fluorescent tracer transport experiments on human airway cultures conducted by Matsui et al. [Matsui, H., Randell, S.H., Peretti, S.W., Davis, C.W., Boucher, R.C., 1998. Coordinated clearance of periciliary liquid and mucus from airway surfaces. J. Clin. Invest. 102 (6), 1125–1131] apparently showed equal transport in both the PCL and mucous layer. Recent attempts to resolve this discrepancy by the present authors are reviewed, along with associated modelling findings. These findings have suggested new insights into the interaction of cilia with mucus due to pressure gradients associated with the flat PCL/mucus interface. This phenomenon complements previously known mechanisms for ciliary propulsion. Modelling results are related to clinical findings, in particular the increased MCC observed in patients with pseudohypoaldosteronism. Recent important advances by several groups in modelling the fluid–structure interaction by which the cilia movement and fluid transport emerge from specification of internal mechanics, viscous and elastic forces are reviewed. Finally, we discuss the limitations of existing work, and the challenges for the next generation of models, which may provide further insight into this complex and vital system

The Role of Ecosystem Services in Community Well-Being

Natural ecosystems provide services to humans that make life possible. Life, as well as the economy, is dependent upon these ecosystem goods and services (EGS). These services also contribute to a “good” or “quality life” by influencing the well-being of individuals and communities. Understanding the relationships among EGS that contribute to and shape well-being is an important task for researchers, decision makers and policy makers. In the past, these relationships were almost completely dependent upon income and consumption of goods. Today, the relationships are based on a more holistic perception including environmental and social attributes. The importance of ecosystem services to community well-being and their interactions are described through examples of communities’ perceptions of the importance of various attributes of well-being and the role of ecosystem services in defining public health

The neural correlates of visual imagery vividness - an fMRI study and literature review

This is the final version of the article. Available from Elsevier via the DOI in this record.Using the Vividness of Visual Imagery Questionnaire we selected 14 high-scoring and 15 low-scoring healthy participants from an initial sample of 111 undergraduates. The two groups were matched on measures of age, IQ, memory and mood but differed significantly in imagery vividness. We used fMRI to examine brain activation while participants looked at, or later imagined, famous faces and famous buildings. Group comparison revealed that the low-vividness group activated a more widespread set of brain regions while visualising than the high-vividness group. Parametric analysis of brain activation in relation to imagery vividness across the entire group of participants revealed distinct patterns of positive and negative correlation. In particular, several posterior cortical regions show a positive correlation with imagery vividness: regions of the fusiform gyrus, posterior cingulate and parahippocampal gyri (BAs 19, 29, 31 and 36) displayed exclusively positive correlations. By contrast several frontal regions including parts of anterior cingulate cortex (BA 24) and inferior frontal gyrus (BAs 44 and 47), as well as the insula (BA 13), auditory cortex (BA 41) and early visual cortices (BAs 17 and 18) displayed exclusively negative correlations. We discuss these results in relation to a previous, functional imaging study of a clinical case of ‘blind imagination’, and to the existing literature on the functional imaging correlates of imagery vividness and related phenomena in visual and other domains.Jonathan Fulford’s salary was supported via an NIHR grant

Discrete cilia modelling with singularity distributions

We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system

Production and temperature sensitivity of long chain alkenones in the cultured haptophyte Pseudoisochrysis paradoxa

The alkenone unsaturation index (U<sub>37</sub><sup>K</sup> or U<sub>37</sub><sup>K′</sup>) serves as a critical tool for reconstructing temperature in marine environments. Lacustrine haptophyte algae are genetically distinct from their ubiquitous and well studied marine counterparts, and the unknown species-specific genetic imprints on long chain alkenone production by lacustrine species have hindered the widespread application of the U37<sup>K</sup> temperature proxy to lake sediment records. The haptophyte Pseudoisochrysis paradoxa produces alkenones but its U37<sup>K</sup> calibration has never been determined. It has an alkenone fingerprint abundant in tetraunsaturated alkenones, a hallmark of lacustrine environments. We present here the first calibration of the U37<sup>K</sup> index to temperature for a culture of P. paradoxa. We found that the U37<sup>K</sup> index accurately captured the alkenone response to temperature whereas the U37<sup>K′</sup> index failed to do so, with U37<sup>K′</sup> values below 0.08 projecting to two different temperature values. Our results add a fifth species-specific U37<sup>K</sup> calibration and provide another line of evidence that different haptophyte species require different U37<sup>K</sup> calibrations. The findings also highlight the necessary inclusion of the C<sub>37:4</sub> alkenone when reconstructing temperatures from P. paradoxa-derived alkenone records

Costs of fragility hip fractures globally:a systematic review and meta-regression analysis

Purpose – To systematically review the costs of hip fractures globally and identify drivers of differences in costs. Methods – A systematic review was conducted to identify studies reporting patient level fragility hip fracture costs between 1990 and 2015. We extracted data on the participants and costs from these studies. Cost data concerning the index hospitalisation were pooled and a meta-regression was used to examine its potential drivers. We also pooled data on the first year costs following hip fracture and considered healthcare, social care as well as other cost categories if reported by studies. Results – 113 studies reported costs of hip fracture based on patient level data. Patients developing complications as well as patients enrolled in intervention arms of comparative studies were found to have significantly higher costs compared to the controls. The pooled estimate of the cost for the index hospitalisation was $10,075. Health and social care costs at 12 months were$43,669 with inpatient costs being their major driver. Meta-regression analysis identified age, gender and geographic region as being significantly associated with the differences in costs for the index hospitalisation. Conclusions – Hip fracture poses a significant economic burden and variation exists in their costs across different regions. We found that there was a considerable variation across studies in terms of study design, methodology, follow up period, costs considered and results reported that highlights the need for more standardisation in this area of research. </p

The defended Vici of Roman Britain: recent research and new agendas

The evidence of the character and purpose of settlements previously described as defended ‘small towns’ is reviewed in the light of knowledge accrued since the implementation of Planning Policy Guidance 16 in 1990, the same year as the publication of Burnham and Wacher's survey, The ‘Small Towns’ of Roman Britain. This review focuses on four of the more extensively excavated settlements: Alcester, Cambridge, Godmanchester and Worcester. In the absence of convincing urban attributes, it is suggested that this category of settlement should more appropriately be regarded as defended villages (vici). These cluster in and around the West Anglian plain and on Ermine Street, suggesting a strategic function to protect grain and other food supplies and their movement, potentially either to the northern frontier or south to London and, perhaps, export to the Continent

Estimation of changes in the force of infection for intestinal and urogenital schistosomiasis in countries with Schistosomiasis Control Initiative-assisted programmes

The last decade has seen an expansion of national schistosomiasis control programmes in Africa based on large-scale preventative chemotherapy. In many areas this has resulted in considerable reductions in infection and morbidity levels in treated individuals. In this paper, we quantify changes in the force of infection (FOI), defined here as the per (human) host parasite establishment rate, to ascertain the impact on transmission of some of these programmes under the umbrella of the Schistosomiasis Control Initiative (SCI)