On the Calibration of a Size-Structured Population Model from Experimental Data

The aim of this work is twofold. First, we survey the techniques developed in (Perthame, Zubelli, 2007) and (Doumic, Perthame, Zubelli, 2008) to reconstruct the division (birth) rate from the cell volume distribution data in certain structured population models. Secondly, we implement such techniques on experimental cell volume distributions available in the literature so as to validate the theoretical and numerical results. As a proof of concept, we use the data reported in the classical work of Kubitschek [3] concerning Escherichia coli in vitro experiments measured by means of a Coulter transducer-multichannel analyzer system (Coulter Electronics, Inc., Hialeah, Fla, USA.) Despite the rather old measurement technology, the reconstructed division rates still display potentially useful biological features

Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case-control study.

In malaria endemic areas anaemia is a usually silent condition that nevertheless places a considerable burden on health services. Cases of severe anaemia often require hospitalization and blood transfusions. The objective of this study was to assess risk factors for admission with anaemia to facilitate the design of anaemia control programmes. We conducted a prospective case-control study of children aged 2-59 months admitted to a district hospital in southern Tanzania. There were 216 cases of severe anaemia [packed cell volume (PCV) < 25%] and 234 age-matched controls (PCV > or = 25%). Most cases [55.6% (n = 120)] were < 1 year of age. Anaemia was significantly associated with the educational level of parents, type of accommodation, health-seeking behaviour, the child's nutritional status and recent and current medical history. Of these, the single most important factor was Plasmodium falciparum parasitaemia [OR 4.3, 95% confidence interval (CI) 2.9-6.5, P < 0.001]. Multivariate analysis showed that increased recent health expenditure [OR 2.2 (95% CI 1.3-3.9), P = 0.005], malnutrition [OR 2.4 (95%CI 1.3-4.3), P < 0.001], living > 10 km from the hospital [OR 3.0 (95% CI 1.9-4.9), P < 0.001], a history of previous blood transfusion [OR 3.8 (95% CI 1.7-9.1), P < 0.001] and P. falciparum parasitaemia [OR 9.5 (95% CI 4.3-21.3), P < 0.001] were independently related to risk of being admitted with anaemia. These findings are considered in terms of the pathophysiological pathway leading to anaemia. The concentration of anaemia in infants and problems of access to health services and adequate case management underline the need for targeted preventive strategies for anaemia control

Application of the PISA design model to monopiles embedded in layered soils

The PISA design model is a procedure for the analysis of monopile foundations for offshore wind turbine applications. This design model has been previously calibrated for homogeneous soils; this paper extends the modelling approach to the analysis of monopiles installed at sites where the soil profile is layered. The paper describes a computational study on monopiles embedded in layered soil configurations comprising selected combinations of soft and stiff clay and sand at a range of relative densities. The study comprises (a) analyses of monopile behaviour using detailed three-dimensional (3D) finite-element analysis, and (b) calculations employing the PISA design model. Results from the 3D analyses are used to explore the various influences that soil layering has on the performance of the monopile. The fidelity of the PISA design model is assessed by comparisons with data obtained from equivalent 3D finite-element analyses, demonstrating a good agreement in most cases. This comparative study demonstrates that the PISA design model can be applied successfully to layered soil configurations, except in certain cases involving combinations of very soft clay and very dense sand. </jats:p

PISA design methods for offshore wind turbine monopiles

Abstract This paper provides an overview of the PISA design model recently developed for laterally loaded offshore wind turbine monopiles through a major European joint-industry academic research project, the PISA Project. The focus was on large diameter, relatively rigid piles, with low length to diameter (L/D) ratios, embedded in clay soils of different strength characteristics, sand soils of different densities and in layered soils combining clays and sands. The resulting design model introduces new procedures for site specific calibration of soil reaction curves that can be applied within a one-dimensional (1D), Winkler-type, computational model. This paper summarises the results and key conclusions from PISA, including design methods for (a) stiff glacial clay till (Cowden till), (b) brittle stiff plastic clay (London clay), (c) soft clay (Bothkennar clay), (d) sand of varying densities (Dunkirk), and, (e) layered profiles (combining soils from (a) to (d)). The results indicate that the homogeneous soil reaction curves applied appropriately for layered profiles in the 1D PISA design model provide a very good fit to the three-dimensional finite element (3D FE) calculations, particularly for profiles relevant to current European offshore wind farm sites. Only a small number of cases, involving soft clay, very dense sand and L/D = 2 monopiles, would appear to require more detailed and bespoke analysis.</jats:p

PISA design model for monopiles for offshore wind turbines: Application to a marine sand

This paper describes a one-dimensional (1D) computational model for the analysis and design of laterally loaded monopile foundations for offshore wind turbine applications. The model represents the monopile as an embedded beam and specially formulated functions, referred to as soil reaction curves, are employed to represent the various components of soil reaction that are assumed to act on the pile. This design model was an outcome of a recently completed joint industry research project – known as PISA – on the development of new procedures for the design of monopile foundations for offshore wind applications. The overall framework of the model, and an application to a stiff glacial clay till soil, is described in a companion paper by Byrne and co-workers; the current paper describes an alternative formulation that has been developed for soil reaction curves that are applicable to monopiles installed at offshore homogeneous sand sites, for drained loading. The 1D model is calibrated using data from a set of three-dimensional finite-element analyses, conducted over a calibration space comprising pile geometries, loading configurations and soil relative densities that span typical design values. The performance of the model is demonstrated by the analysis of example design cases. The current form of the model is applicable to homogeneous soil and monotonic loading, although extensions to soil layering and cyclic loading are possible. </jats:p

Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis

In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing

Can an Integrated Approach Reduce Child Vulnerability to Anaemia? Evidence from Three African Countries.

Addressing the complex, multi-factorial causes of childhood anaemia is best done through integrated packages of interventions. We hypothesized that due to reduced child vulnerability, a "buffering" of risk associated with known causes of anaemia would be observed among children living in areas benefiting from a community-based health and nutrition program intervention. Cross-sectional data on the nutrition and health status of children 24-59 mo (N = 2405) were obtained in 2000 and 2004 from program evaluation surveys in Ghana, Malawi and Tanzania. Linear regression models estimated the association between haemoglobin and immediate, underlying and basic causes of child anaemia and variation in this association between years. Lower haemoglobin levels were observed in children assessed in 2000 compared to 2004 (difference -3.30 g/L), children from Tanzania (-9.15 g/L) and Malawi (-2.96 g/L) compared to Ghana, and the youngest (24-35 mo) compared to oldest age group (48-59 mo; -5.43 g/L). Children who were stunted, malaria positive and recently ill also had lower haemoglobin, independent of age, sex and other underlying and basic causes of anaemia. Despite ongoing morbidity, risk of lower haemoglobin decreased for children with malaria and recent illness, suggesting decreased vulnerability to their anaemia-producing effects. Stunting remained an independent and unbuffered risk factor. Reducing chronic undernutrition is required in order to further reduce child vulnerability and ensure maximum impact of anaemia control programs. Buffering the impact of child morbidity on haemoglobin levels, including malaria, may be achieved in certain settings

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.