A three species model to simulate application of hyperbaric oxygen therapy to chronic wounds

Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the costeffectiveness of this therapy.

An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers

Background: To directly assess tumor oxygenation in resectable non - small cell lung cancers (NSCLC) and to correlate tumor pO2 and the selected gene and protein expression to treatment outcomes. Methods: Twenty patients with resectable NSCLC were enrolled. Intraoperative measurements of normal lung and tumor pO2 were done with the Eppendorf polarographic electrode. All patients had plasma osteopontin measurements by ELISA. Carbonic anhydrase-IX (CA IX) staining of tumor sections was done in the majority of patients (n = 16), as was gene expression profiling (n = 12) using cDNA microarrays. Tumor pO2 was correlated with CA IX staining, osteopontin levels, and treatment outcomes. Results: The median tumor pO2 ranged from 0.7 to 46 mm Hg (median, 16.6) and was lower than normal lung pO2 in all but one patient. Because both variables were affected by the completeness of lung deflation during measurement, we used the ratio of tumor/normal lung (T/L) pO2 as a reflection of tumor oxygenation. The median T/L pO 2 was 0.13. T/L pO2 correlated significantly with plasma osteopontin levels (r = 0.53, P = 0.02) and CA IX expression (P = 0.006). Gene expression profiling showed that high CD44 expression was a predictor for relapse, which was confirmed by tissue staining of CD44 variant 6 protein. Other variables associated with the risk of relapse were T stage (P = 0.02), T/L pO2 (P = 0.04), and osteopontin levels (P = 0.001). Conclusions: Tumor hypoxia exists in resectable NSCLC and is associated with elevated expression of osteopontin and CA IX. Tumor hypoxia and elevated osteopontin levels and CD44 expression correlated with poor prognosis. A larger study is needed to confirm the prognostic significance of these factors. © 2006 American Association for Cancer Research.

Kinetics of the initial stage of silicon surface oxidation : Deal–Grove or surface nucleation?

The nucleation-initiated oxidation of a Si surface at very low temperatures in plasmas is demonstrated experimentally, in contrast to the Deal-Grove mechanism, which predicts Si oxidation at a Si/SiO interface and cannot adequately describe the formation of SiO nanodots and oxidation rates at very low (several nanometers) oxide thickness. Based on the experimental results, an alternative oxidation scenario is proposed and supported by multiscale numerical simulations suggesting that saturation of micro- and nanohillocks with oxygen is a trigger mechanism for initiation of Si surface oxidation. This approach is generic and can be applied to describe the kinetics of low-temperature oxidation of other materials. © 2009 American Institute of Physics.

Body composition and components of energy expenditure in children with end-stage liver disease

Background: Better understanding of body composition and energy metabolism in pediatric liver disease may provide a scientific basis for improved medical therapy aimed at achieving optimal nutrition, slowing progression to end-stage liver disease (ESLD), and improving the outcome of liver transplantation. Methods: Twenty-one children less than 2 years of age with ESLD awaiting liver transplantation and 15 healthy, aged-matched controls had body compartment analysis using a four compartment model (body cell mass, fat mass, extracellular water, and extracellular solids). Subjects also had measurements of resting energy expenditure (REE) and respiratory quotient (RQ) by indirect calorimetry. Nine patients and 15 control subjects also had measurements of total energy expenditure (TEE) using doubly labelled water. Results: Mean weights and heights were similar in the two groups. Compared with control subjects, children with ESLD had higher relative mean body cell mass (33 ± 2% vs 29 ± 1% of body weight, P < 0.05), but had similar fat mass, extracellular water, and extracellular solid compartments (18% vs 20%, 41% vs 38%, and 7% vs 13% of body weight respectively). Compared with control subjects, children with ESLD had 27% higher mean REE/body weight (0.285 ± 0.013 vs 0.218. ± 0.013 mJ/kg/24h, P < 0.001), 16% higher REE/unit cell mass (P < 0.05); and lower mean RQ (P < 0.05). Mean TEE of patients was 4.70 ± 0.49 mJ/24h vs 3.19 ± 0.76 in controls, (P < 0.01). Conclusions: In children, ESLD is a hypermetabolic state adversely affecting the relationship between metabolic and non-metabolic body compartments. There is increased metabolic activity within the body cell mass with excess lipid oxidation during fasting and at rest. These findings have implications for the design of appropriate nutritional therapy.

Oxygen transport in a three-dimensional microvascular network incorporated with early tumour growth and preexisting vessel cooption: Numerical simulation study

We propose a dynamic mathematical model of tissue oxygen transport by a preexisting three-dimensional microvascular network which provides nutrients for an in situ cancer at the very early stage of primary microtumour growth. The expanding tumour consumes oxygen during its invasion to the surrounding tissues and cooption of host vessels. The preexisting vessel cooption, remodelling and collapse are modelled by the changes of haemodynamic conditions due to the growing tumour. A detailed computational model of oxygen transport in tumour tissue is developed by considering (a) the time-varying oxygen advection diffusion equation within the microvessel segments, (b) the oxygen flux across the vessel walls, and (c) the oxygen diffusion and consumption with in the tumour and surrounding healthy tissue. The results show the oxygen concentration distribution at different time points of early tumour growth. In addition, the influence of preexisting vessel density on the oxygen transport has been discussed. The proposed model not only provides a quantitative approach for investigating the interactions between tumour growth and oxygen delivery, but also is extendable to model other molecules or chemotherapeutic drug transport in the future study.

In Situ Observation of the Thermal Decomposition of Weddelite by Heating Stage Environmental Scanning Electron Microscopy

The morphological and chemical changes occurring during the thermal decomposition of weddelite, CaC2O4·2H2O, have been followed in real time in a heating stage attached to an Environmental Scanning Electron Microscope operating at a pressure of 2 Torr, with a heating rate of 10 °C/min and an equilibration time of approximately 10 min. The dehydration step around 120 °C and the loss of CO around 425 °C do not involve changes in morphology, but changes in the composition were observed. The final reaction of CaCO3 to CaO while evolving CO2 around 600 °C involved the formation of chains of very small oxide particles pseudomorphic to the original oxalate crystals. The change in chemical composition could only be observed after cooling the sample to 350 °C because of the effects of thermal radiation.

Experiences with an Object-Oriented, Multi-Stage Language

Metaphor is a multi-stage programming language extension to an imperative, object-oriented language in the style of C# or Java. This paper discusses some issues we faced when applying multi-stage language design concepts to an imperative base language and run-time environment. The issues range from dealing with pervasive references and open code to garbage collection and implementing cross-stage persistence.

Particle and gaseous emissions from commercial aircraft at each stage of the landing and takeoff cycle

A novel technique was used to measure emission factors for commonly used commercial aircraft including a range of Boeing and Airbus airframes under real world conditions. Engine exhaust emission factors for particles in terms of particle number and mass (PM2.5), along with those for CO2, and NOx were measured for over 280 individual aircraft during the various modes of landing/takeoff (LTO) cycle. Results from this study show that particle number, and NOx emission factors are dependant on aircraft engine thrust level. Minimum and maximum emissions factors for particle number, PM2.5, and NOx emissions were found to be in the range of 4.16×1015-5.42×1016 kg-1, 0.03-0.72 g.kg-1, and 3.25-37.94 g.kg-1 respectively for all measured airframes and LTO cycle modes. Number size distributions of emitted particles for the naturally diluted aircraft plumes in each mode of LTO cycle showed that particles were predominantly in the range of 4 to 100 nm in diameter in all cases. In general, size distributions exhibit similar modality during all phases of the LTO cycle. A very distinct nucleation mode was observed in all particle size distributions, except for taxiing and landing of A320 aircraft. Accumulation modes were also observed in all particle size distributions. Analysis of aircraft engine emissions during LTO cycle showed that aircraft thrust level is considerably higher during taxiing than idling suggesting that International Civil Aviation Organization (ICAO) standards need to be modified as the thrust levels for taxi and idle are considered to be the same (7% of total thrust) [1].

User-designer collaboration during the early stage of the product development process

As an understanding of users' tacit knowledge and latent needs embedded in user experience has played a critical role in product development, users’ direct involvement in design has become a necessary part of the design process. Various ways of accessing users' tacit knowledge and latent needs have been explored in the field of user-centred design, participatory design, and design for experiencing. User-designer collaboration has been used unconsciously by traditional designers to facilitate the transfer of users' tacit knowledge and to elicit new knowledge. However, what makes user-designer collaboration an effective strategy has rarely been reported on or explored. Therefore, interaction patterns between the users and the designers in three industry-supported user involvement cases were studied. In order to develop a coding system, collaboration was defined as a set of coordinated and joint problem solving activities, measured by the elicitation of new knowledge from collaboration. The analysis of interaction patterns in the user involvement cases revealed that allowing users to challenge or modify their contextual experiences facilitates the transfer of knowledge and new knowledge generation. It was concluded that users can be more effectively integrated into the product development process by employing collaboration strategies to intensify the depth of user involvement.

The impact of perceived stage of cancer on carers’ anxiety and depression during the patients’ final year of life

Objective: This paper explores the effects of perceived stage of cancer (PSOC) on carers' anxiety and depression during the patients' final year. Methods: A consecutive sample of patients and carers (N=98) were surveyed at regular intervals regarding PSOC, and anxiety and depression using the Hospital Anxiety and Depression Scale. Means were compared by gender using the Mann-Whitney U-test. The chi-square was used to analyse categorical data. Agreement between carers' and patients' PSOC was estimated using kappa statistics. Correlations between carers' PSOC and their anxiety and depression were calculated using the Spearman's rank correlation. Results: Over time, an increasing proportion of carers reported that the cancer was advanced, culminating at 43% near death. Agreement regarding PSOC was fair (kappa=0.29-0.34) until near death (kappa=0.21). Carers' anxiety increased over the year; depression increased in the final 6 months. Females were more anxious (p=0.049, 6 months; p=0.009, 3 months) than males, and more depressed until 1 month to death. The proportion of carers reporting moderate-severe anxiety almost doubled over the year to 27%, with more females in this category at 6 months (p=0.05). Carers with moderate-severe depression increased from 6 to 15% over the year. Increased PSOC was weakly correlated with increased anxiety and depression. Conclusions: Carers' anxiety exceeded depression in severity during advanced cancer. Females generally experienced greater anxiety and depression. Carers were more realistic than patients regarding the ultimate outcome, which was reflected in their declining mental health, particularly near the end.

Parametric building development during early design stage

Objectives The objectives of this project were two-fold: • Assess the ease with which current architectural CAD systems supported the use ofparametric descriptions in defining building shape, engineering system performance and cost at the early stages of building design; • Assess the feasibility of implementing a software decision support system that allowed designers to trade-off the characteristics and configuration of various engineering systems to move towards a “global optimum” rather than considering each system in isolation and expecting humans to weigh up all of the costs and benefits. The first stage of the project consisted of using four different CAD systems to define building shells (envelopes) with different usages. These models were then exported into a shared database using the IFC information exchange specifications. The second stage involved the implementation of small computer programs that were able to estimate relevant system parameters based on performance requirements and the constraints imposed by the other systems. These are presented in a unified user interface that extracts the appropriate building shape parameters from the shared database Note that the term parametric in this context refers to the relationships among and between all elements of the building model - not just geometric associations - which will enable the desired coordination.