Fibroblast migration and collagen deposition during dermal wound healing: mathematical modelling and clinical implications,

The extent to which collagen alignment occurs during dermal wound healing determines the severity of scar tissue formation. We have modelled this using a multiscale approach, in which extracellular materials, for example collagen and fibrin, are modelled as continua, while fibroblasts are considered as discrete units. Within this model framework, we have explored the effects that different parameters have on the alignment process, and we have used the model to investigate how manipulation of transforming growth factor-β levels can reduce scar tissue formation. We briefly review this body of work, then extend the modelling framework to investigate the role played by leucocyte signalling in wound repair. To this end, fibroblast migration and collagen deposition within both the wound region and healthy peripheral tissue are considered. Trajectories of individual fibroblasts are determined as they migrate towards the wound region under the combined influence of collagen/fibrin alignment and gradients in a paracrine chemoattractant produced by leucocytes. The effects of a number of different physiological and cellular parameters upon the collagen alignment and repair integrity are assessed. These parameters include fibroblast concentration, cellular speed, fibroblast sensitivity to chemoattractant concentration and chemoattractant diffusion coefficient. Our results show that chemoattractant gradients lead to increased collagen alignment at the interface between the wound and the healthy tissue. Results show that there is a trade-off between wound integrity and the degree of scarring. The former is found to be optimized under conditions of a large chemoattractant diffusion coefficient, while the latter can be minimized when repair takes place in the presence of a competitive inhibitor to chemoattractants

Prediction of outcome after paraquat poisoning by measurement of the plasma paraquat concentration

Background: Paraquat is a herbicide with a good occupational safety record, but a high mortality after intentional ingestion that has proved refractory to treatment. For nearly three decades paraquat concentration-time data have been used to predict the outcome following ingestion. However, none of the published methods has been independently or prospectively validated. We aimed to use prospectively collected data to test the published predictive methods and to determine if any is superior. Methods: Plasma paraquat concentrations were measured on admission for 451 patients in 10 hospitals in Sri Lanka as part of large prospective cohort study. All deaths in hospital were recorded; patients surviving to hospital discharge were followed up after 3 months to detect delayed deaths. Five prediction methods that are based on paraquat concentration-time data were then evaluated in all eligible patients. Results: All methods showed comparable performance within their range of application. For example, between 4- and 24-h prediction of prognosis was most variable between Sawada and Proudfoot methods but these differences were relatively small [specificity 0.96 (95% CI: 0.90-0.99) vs. 0.89 (0.82-0.95); sensitivity 0.57 vs. 0.79, positive and negative likelihood ratios 14.8 vs. 7.40 and 0.44 vs. 0.23 and positive predictive values 0.96 vs. 0.92, respectively]. Conclusions: All five published methods were better at predicting death than survival. These predictions may also serve as tools to identify patients who need treatment and for some assessment to be made of new treatments that are trialled without a control grou

Numerical and experimental investigations of three-dimensional container filling with Newtonian viscous fluids

This work employs numerical and experimental approaches to investigate three-dimensional container filling with Newtonian viscous fluids. For this purpose, a computer code developed for simulating three-dimensional free surface flows has been used. The CFD Freeflow3D code was specifically designed to deal with unsteady three-dimensional flows possessing multiple moving free surfaces. An experimental apparatus that allows the visualization of the various phenomena that can occur during the filling of containers has been constructed and employed. Experiments on container filling were carried out by varying the fluid velocity at the injection nozzle. This paper presents a computational study on container filling with Newtonian viscous fluids and employs the experimental results to validate the software. The experimental observations were compared with the predictions from the Freeflow3D code and good agreement between the two sets of results is observed. Moreover, the code predictions showed that it is capable of capturing the most relevant phenomena observed in the experiments.The Brazilian authors would like to acknowledge the financial support given by the funding agencies: CNPq - Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Grant Nos. 302631/2010-0, 301408/2009-2, 472514/2011-3), FAPESP - Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (Grant No. 2011/13930-0) and CAPES Grant Nos. BEX 2844/10-9 and 226/09 (CAPES-FCT). This work is part of the activities developed within the CEPID-CeMEAI FAPESP project Grant No. 2013/07375 - 0 and also benefits from the early collaboration within the framework of the University of Sao Paulo (Brazil) and University of Porto (Portugal) research agreements. The Portuguese authors gratefully acknowledge funding from Fundacao para a Ciencia e Tecnologia (FCT) under the project PEst-C/CTM/LA0025/2013 (Strategic Project - LA 25-2013-2014), project PTDC/MAT/121185/2010 and FEDER, via FCT

The views of five participating undergraduate students of the Student Associates Scheme in England

This paper reports findings from a study which explored undergraduate perceptions of the Student Associates Scheme in England (SAS). The scheme was established by the Training and Development Agency for Schools in an attempt to increase the number of graduates entering the teaching profession, particularly in shortage subjects such as the physical sciences and mathematics. The scheme places undergraduate students on short-term placements in secondary schools throughout England to provide them with experiences that may encourage them to consider teaching as a career option. Findings show that the SAS school placements were a positive experience for the students participating in this study. However, a question emerged as to whether or not the scheme is targeting students who have yet to decide upon teaching as a career or just reinforcing the existing aspirations of students who have already decided to teach. As the scheme is attempting to increase the number of teachers entering the profession this question has important implications for this study and further work which will focus on undergraduates who think that their career ambitions would not be fulfilled by teaching

Cosmological Models with Fractional Derivatives and Fractional Action Functional

Cosmological models of a scalar field with dynamical equations containing fractional derivatives or derived from the Einstein-Hilbert action of fractional order, are constructed. A number of exact solutions to those equations of fractional cosmological models in both cases is given.Comment: 14 page

Prediction of outcome after paraquat poisoning by measurement of the plasma paraquat concentration

Background: Paraquat is a herbicide with a good occupational safety record, but a high mortality after intentional ingestion that has proved refractory to treatment. For nearly three decades paraquat concentration–time data have been used to predict the outcome following ingestion. However, none of the published methods has been independently or prospectively validated. We aimed to use prospectively collected data to test the published predictive methods and to determine if any is superior

Meridional Circulation and Global Solar Oscillations

We investigate the influence of large-scale meridional circulation on solar p-modes by quasi-degenerate perturbation theory, as proposed by \cite{lavely92}. As an input flow we use various models of stationary meridional circulation obeying the continuity equation. This flow perturbs the eigenmodes of an equilibrium model of the Sun. We derive the signatures of the meridional circulation in the frequency multiplets of solar p-modes. In most cases the meridional circulation leads to negative average frequency shifts of the multiplets. Further possible observable effects are briefly discussed.Comment: 14 pages, 5 figures, submittted to Solar Physics Topical Issue "HELAS

Diagnostic and medical needs for therapeutic drug monitoring of antibiotics

Therapeutic drug monitoring (TDM) of antibiotics has been practiced for more than half a century, but it is still not widely applied for infected patients. It has a traditional focus on limiting toxicity of specific classes of antibiotics such as aminoglycosides and vancomycin. With more patients in critical care with higher levels of sickness severity and immunosuppression as well as an increasingly obese and ageing population, an increasing risk of suboptimal antibiotic exposure continues to escalate. As such, the value of TDM continues to expand, especially for beta-lactams which constitute the most frequently used antibiotic class. To date, the minimum inhibitory concentration (MIC) of infectious microbes rather than classification in terms of susceptible and resistant can be reported. In parallel, increasingly sophisticated TDM technology is becoming available ensuring that TDM is feasible and can deliver personalized antibiotic dosing schemes. There is an obvious need for extensive studies that will quantify the improvements in clinical outcome of individual TDM-guided dosing. We suggest that a broad diagnostic and medical investigation of the TDM arena, including marke

From Atiyah Classes to Homotopy Leibniz Algebras

A celebrated theorem of Kapranov states that the Atiyah class of the tangent bundle of a complex manifold $X$ makes $T_X[-1]$ into a Lie algebra object in $D^+(X)$, the bounded below derived category of coherent sheaves on $X$. Furthermore Kapranov proved that, for a K\"ahler manifold $X$, the Dolbeault resolution $\Omega^{\bullet-1}(T_X^{1,0})$ of $T_X[-1]$ is an $L_\infty$ algebra. In this paper, we prove that Kapranov's theorem holds in much wider generality for vector bundles over Lie pairs. Given a Lie pair $(L,A)$, i.e. a Lie algebroid $L$ together with a Lie subalgebroid $A$, we define the Atiyah class $\alpha_E$ of an $A$-module $E$ (relative to $L$) as the obstruction to the existence of an $A$-compatible $L$-connection on $E$. We prove that the Atiyah classes $\alpha_{L/A}$ and $\alpha_E$ respectively make $L/A[-1]$ and $E[-1]$ into a Lie algebra and a Lie algebra module in the bounded below derived category $D^+(\mathcal{A})$, where $\mathcal{A}$ is the abelian category of left $\mathcal{U}(A)$-modules and $\mathcal{U}(A)$ is the universal enveloping algebra of $A$. Moreover, we produce a homotopy Leibniz algebra and a homotopy Leibniz module stemming from the Atiyah classes of $L/A$ and $E$, and inducing the aforesaid Lie structures in $D^+(\mathcal{A})$.Comment: 36 page