A variable-stepsize Jacobian-free exponential integrator for simulating transport in heterogeneous porous media : application to wood drying

A Jacobian-free variable-stepsize method is developed for the numerical integration of the large, stiff systems of differential equations encountered when simulating transport in heterogeneous porous media. Our method utilises the exponential Rosenbrock-Euler method, which is explicit in nature and requires a matrix-vector product involving the exponential of the Jacobian matrix at each step of the integration process. These products can be approximated using Krylov subspace methods, which permit a large integration stepsize to be utilised without having to precondition the iterations. This means that our method is truly "Jacobian-free" - the Jacobian need never be formed or factored during the simulation. We assess the performance of the new algorithm for simulating the drying of softwood. Numerical experiments conducted for both low and high temperature drying demonstrates that the new approach outperforms (in terms of accuracy and efficiency) existing simulation codes that utilise the backward Euler method via a preconditioned Newton-Krylov strategy.

Food for thought : designing for critical reflection on food practices

This workshop is a continuation and extension to the successful past workshops including [4, 5, 6]. The workshop addresses the opportunities and challenges for the design of digital interactive systems that engage individuals in critical reflection on their everyday food practices - including designing for engagement in more environmentally aware, socially inclusive, and healthier behaviour. These three themes represent the focus of much recent HCI work related to food. The workshop aims to further the conversation on these themes through understanding specifically how the process of critical reflection can be encouraged by interactive technology. While the focus will be on food as an application area, the intention is to also explore, more generally, how the process of critical reflection can be facilitated through interactive technology. The workshop provides a unique forum to discuss existing theoretical and pragmatic approaches, and to envision novel ways to design technology that encourages sustained critical reflection.

Standardising practices improves clinical diabetic foot management: the Queensland Diabetic Foot Innovation Project, 2006-09

Objective. The aim of this paper is to report the clinical practice changes resulting from strategies to standardise diabetic foot clinical management in three diverse ambulatory service sites in Queensland, Australia. Methods. Multifaceted strategies were implemented in 2008, including: multidisciplinary teams, clinical pathways, clinical training, clinical indicators, and telehealth support. Prior to the intervention, none of the aforementioned strategies were used, except one site had a basic multidisciplinary team. A retrospective audit of consecutive patient records from July 2006 to June 2007 determined baseline clinical activity (n = 101).Aclinical pathway teleform was implemented as a clinical activity analyser in 2008 (n = 327) and followed up in 2009 (n = 406). Pre- and post-implementation data were analysed using Chi-square tests with a significance level set at P < 0.05. Results. There was an improvement in surveillance of the high risk population of 34% in 2008 and 19% in 2009, and treating according to risk of 15% in 2009 (P < 0.05). The documentation of all best-practice clinical activities performed improved 13–66% (P < 0.03). Conclusion. These findings support the use of multifaceted strategies to standardise practice and improve diabetic foot complications management in diverse ambulatory services.

Standardising practices improves ambulatory diabetic foot management and reduces amputations : the Queensland Diabetic Foot Innovation Project, 2006 – 2009

Background Diabetic foot complications are recognised as the most common reason for diabetic related hospitalisation and lower extremity amputations. Multi-faceted strategies to reduce diabetic foot hospitalisation and amputation rates have been successful. However, most diabetic foot ulcers are managed in ambulatory settings where data availability is poor and studies limited. The project aimed to develop and evaluate strategies to improve the management of diabetic foot complications in three diverse ambulatory settings and measure the subsequent impact on ospitalisation and amputation. Methods Multifaceted strategies were implemented in 2008, including: multi-disciplinary teams, clinical pathways and training, clinical indicators, telehealth support and surveys. A retrospective audit of consecutive patient records from July 2006 – June 2007 determined baseline clinical indicators (n = 101). A clinical pathway teleform was implemented as a clinical record and clinical indicator analyser in all sites in 2008 (n = 327) and followed up in 2009 (n = 406). Results Prior to the intervention, clinical pathways were not used and multi-disciplinary teams were limited. There was an absolute improvement in treating according to risk of 15% in 2009 and surveillance of the high risk population of 34% and 19% in 2008 and 2009 respectively (p < 0.001). Improvements of 13 – 66% (p < 0.001) were recorded in 2008 for individual clinical activities to a performance > 92% in perfusion, ulcer depth, infection assessment and management, offloading and education. Hospitalisation impacts recorded reductions of up to 64% in amputation rates / 100,000 population (p < 0.001) and 24% average length of stay (p < 0.001) Conclusion These findings support the use of multi-faceted strategies in diverse ambulatory services to standardise practice, improve diabetic foot complications management and positively impact on hospitalisation outcomes. As of October 2010, these strategies had been rolled out to over 25 ambulatory sites, representing 66% of Queensland Health districts, managing 1,820 patients and 13,380 occasions of service, including 543 healed ulcer patients. It is expected that this number will rise dramatically as an incentive payment for the use of the teleform is expanded.

Tocotrienol as potential anticancer agent

Vitamin E is composed of two structurally similar compounds: tocopherols (TPs) and tocotrienols (T3). Despite being overshadowed by TP over the past few decades, T3 is now considered to be a promising anticancer agent due to its potent effects against a wide range of cancers. A growing body of evidence suggests that in addition to its antioxidative and pro-apoptotic functions, T3 possesses a number of anticancer properties that make it superior to TP. These include the inhibition of epithelial-to-mesenchymal transitions, the suppression of vascular endothelial growth factor tumor angiogenic pathway and the induction of antitumor immunity. More recently, T3, but not TP, has been shown to have chemosensitization and anti-cancer stem cell effects, further demonstrating the potential of T3 as an effective anticancer therapeutic agent. With most of the previous clinical studies on TP producing disappointing results, research has now focused on testing T3 as the next generation vitamin E for chemoprevention and cancer treatment. This review will summarize recent developments in the understanding of the anticancer effects of T3. We will also discuss current progress in clinical trials involving T3 as an adjuvant to conventional cancer therapy.

S-allylmercaptocysteine reduces carbon tetrachloride-induced hepatic oxidative stress and necroinflammation via nuclear factor kappa B-dependent pathways in mice.

Purpose To study the protective effects and underlying molecular mechanisms of SAMC on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in the mouse model. Methods Mice were intraperitoneally injected with CCl4 (50 μl/kg; single dose) to induce acute hepatotoxicity with or without a 2-h pre-treatment of SAMC intraperitoneal injection (200 mg/kg; single dose). After 8 h, the blood serum and liver samples of mice were collected and subjected to measurements of histological and molecular parameters of hepatotoxicity. Results SAMC reduced CCl4-triggered cellular necrosis and inflammation in the liver under histological analysis. Since co-treatment of SAMC and CCl4 enhanced the expressions of antioxidant enzymes, reduced the nitric oxide (NO)-dependent oxidative stress, and inhibited lipid peroxidation induced by CCl4. SAMC played an essential antioxidative role during CCl4-induced hepatotoxicity. Administration of SAMC also ameliorated hepatic inflammation induced by CCl4 via inhibiting the activity of NF-κB subunits p50 and p65, thus reducing the expressions of pro-inflammatory cytokines, mediators, and chemokines, as well as promoting pro-regenerative factors at both transcriptional and translational levels. Conclusions Our results indicate that SAMC mitigates cellular damage, oxidative stress, and inflammation in CCl4-induced acute hepatotoxicity mouse model through regulation of NF-κB. Garlic or garlic derivatives may therefore be a potential food supplement in the prevention of liver damage.

More is not necessarily better. A biomechanical study on distal screw numbers in volar locking distal radius plates

INTRODUCTION: Currently available volar locking plates for the treatment of distal radius fractures incorporate at least two distal screw rows for fixation of the metaphyseal fragment and have a variable-angle locking mechanism which allows placement of the screws in various directions There is, however no evidence that these plates translate into better outcomes or have superior biomechanical properties to first generation plates, which had a single distal screw row and fixed-angle locking. The aim of our biomechanical study was to compare fixed-angle single-row plates with variable-angle multi-row plates to clarify the optimal number of locking screws. MATERIALS AND METHODS: Five different plate-screw combinations of three different manufacturers were tested, each group consisting of five synthetic fourth generation distal radius bones. An AO type C2 fracture was created and the fractures were plated according to each manufacturer's recommendations. The specimens then underwent cyclic and load-to-failure testing. An optical motion analysis system was used to detect displacement of fragments. RESULTS: No significant differences were detected after cyclic loading as well as after load-to-failure testing, neither in regard to axial deformation, implant rigidity or maximum displacement. The fixed-angle single-row plate showed the highest pre-test rigidity, least increase in post-testing rigidity and highest load-to-failure rigidity and least radial shortening. The radial shortening of plates with two distal screw rows was 3.1 and 4.3 times higher, respectively, than that of the fixed-angle single-row plate. CONCLUSION: The results of our study indicate that two distal screw rows do not add to construct rigidity and resistance against loss of reduction. Well conducted clinical studies based on the findings of biomechanical studies are necessary to determine the optimal number of screws necessary to achieve reproducibly good results in the treatment of distal radius fractures.

Automatic particle picking of biological molecules imaged by electron microscopy

One of the next great challenges of cell biology is the determination of the enormous number of protein structures encoded in genomes. In recent years, advances in electron cryo-microscopy and high-resolution single particle analysis have developed to the point where they now provide a methodology for high resolution structure determination. Using this approach, images of randomly oriented single particles are aligned computationally to reconstruct 3-D structures of proteins and even whole viruses. One of the limiting factors in obtaining high-resolution reconstructions is obtaining a large enough representative dataset ($>100,000$ particles). Traditionally particles have been manually picked which is an extremely labour intensive process. The problem is made especially difficult by the low signal-to-noise ratio of the images. This paper describes the development of automatic particle picking software, which has been tested with both negatively stained and cryo-electron micrographs. This algorithm has been shown to be capable of selecting most of the particles, with few false positives. Further work will involve extending the software to detect differently shaped and oriented particles.

A generic implementation framework for stereo matching algorithms

Traditional area-based matching techniques make use of similarity metrics such as the Sum of Absolute Differences(SAD), Sum of Squared Differences (SSD) and Normalised Cross Correlation (NCC). Non-parametric matching algorithms such as the rank and census rely on the relative ordering of pixel values rather than the pixels themselves as a similarity measure. Both traditional area-based and non-parametric stereo matching techniques have an algorithmic structure which is amenable to fast hardware realisation. This investigation undertakes a performance assessment of these two families of algorithms for robustness to radiometric distortion and random noise. A generic implementation framework is presented for the stereo matching problem and the relative hardware requirements for the various metrics investigated.

The Growing Pains of Data Breach Notification Law

Mandatory data breach notification laws are a novel statutory solution in relation to organizational protections of personal information. They require organizations which have suffered a breach of security involving personal information to notif'y those persons whose information may have been affected. These laws originated in the state based legislatures of the United States during the last decade and have subsequently garnered worldwide legislative interest. Despite their perceived utility, mandatory data breach notification laws have several conceptual and practical concems that limit the scope of their applicability, particularly in relation to existing information privacy law regimes. We outline these concerns, and in doing so, we contend that while mandatory data breach notification laws have many useful facets, their utility as an 'add-on' to enhance the failings of current information privacy law frameworks should not necessarily be taken for granted.

Selective cleavage of human sex hormone-binding globulin by kallikrein-related peptidases and effects on androgen action in LNCaP prostate cancer cells

Stimulation of the androgen receptor via bioavailable androgens, including testosterone and testosterone metabolites, is a key driver of prostate development and the early stages of prostate cancer. Androgens are hydrophobic and as such require carrier proteins, including sex hormone-binding globulin (SHBG), to enable efficient distribution from sites of biosynthesis to target tissues. The similarly hydrophobic corticosteroids also require a carrier protein whose affinity for steroid is modulated by proteolysis. However, proteolytic mechanisms regulating the SHBG/androgen complex have not been reported. Here, we show that the cancer-associated serine proteases, kallikrein-related peptidase (KLK)4 and KLK14, bind strongly to SHBG in glutathione S-transferase interaction analyses. Further, we demonstrate that active KLK4 and KLK14 cleave human SHBG at unique sites and in an androgen-dependent manner. KLK4 separated androgen-free SHBG into its two laminin G-like (LG) domains that were subsequently proteolytically stable even after prolonged digestion, whereas a catalytically equivalent amount of KLK14 reduced SHBG to small peptide fragments over the same period. Conversely, proteolysis of 5α-dihydrotestosterone (DHT)-bound SHBG was similar for both KLKs and left the steroid binding LG4 domain intact. Characterization of this proteolysis fragment by [(3)H]-labeled DHT binding assays revealed that it retained identical affinity for androgen compared with full-length SHBG (dissociation constant = 1.92 nM). Consistent with this, both full-length SHBG and SHBG-LG4 significantly increased DHT-mediated transcriptional activity of the androgen receptor compared with DHT delivered without carrier protein. Collectively, these data provide the first evidence that SHBG is a target for proteolysis and demonstrate that a stable fragment derived from proteolysis of steroid-bound SHBG retains binding function in vitro.

Markers of cutaneous human papillomavirus infection in individuals with tumor-free skin, actinic keratoses, and squamous cell carcinoma

Separately, actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) have been associated with cutaneous human papillomavirus (HPV) infections. To further explore the association between HPV infection and SCC development, we determined markers of cutaneous HPV infection within a single population in persons with precursor lesions (AK), cancerous lesions (SCC), and without. Serum and plucked eyebrow hairs were collected from 57 tumor-free controls, 126 AK, and 64 SCC cases. Presence of HPV L1 and E6 seroreactivity and viral DNA were determined for HPV types 5, 8, 15, 16, 20, 24, and 38. Significant positive associations with increasing severity of the lesions (controls, AK, and SCC, respectively) were observed for overall HPV L1 seropositivity (13%, 26%, and 37%) and for HPV8 (4%, 17%, and 30%). In parallel, the proportion of L1 seropositive individuals against multiple HPV types increased from 14% to 39% and 45%. The overall E6 seroreactivity, however, tended to decline with AK and SCC, especially for HPV8 (21%, 11%, and 2%). HPV DNA positivity was most prevalent in the AK cases (54%) compared with the SCC cases (44%) and the tumor-free controls (40%). Among all participants, there was a positive trend between overall HPV DNA positivity and L1 seropositivity, but not E6 seropositivity. Taken together, our data suggest that cutaneous HPV infections accompanied by detectable HPV DNA in eyebrow hairs and HPV L1 seropositivity, but not E6 seropositivity, are associated with an increased risk of AK and SCC.

Custom digital workflows : a new framework for design analysis integration

Flexible information exchange is critical to successful design-analysis integration, but current top-down, standards-based and model-oriented strategies impose restrictions that contradicts this flexibility. In this article we present a bottom-up, user-controlled and process-oriented approach to linking design and analysis applications that is more responsive to the varied needs of designers and design teams. Drawing on research into scientific workflows, we present a framework for integration that capitalises on advances in cloud computing to connect discrete tools via flexible and distributed process networks. We then discuss how a shared mapping process that is flexible and user friendly supports non-programmers in creating these custom connections. Adopting a services-oriented system architecture, we propose a web-based platform that enables data, semantics and models to be shared on the fly. We then discuss potential challenges and opportunities for its development as a flexible, visual, collaborative, scalable and open system.

Custom digital workflows : a new framework for design analysis integration

Flexible information exchange is critical to successful design integration, but current top-down, standards-based and model-oriented strategies impose restrictions that are contradictory to this flexibility. In this paper we present a bottom-up, user-controlled and process-oriented approach to linking design and analysis applications that is more responsive to the varied needs of designers and design teams. Drawing on research into scientific workflows, we present a framework for integration that capitalises on advances in cloud computing to connect discrete tools via flexible and distributed process networks. Adopting a services-oriented system architecture, we propose a web-based platform that enables data, semantics and models to be shared on the fly. We discuss potential challenges and opportunities for the development thereof as a flexible, visual, collaborative, scalable and open system.

Data transformations in custom digital workflows : property graphs as a data model for user-defined mappings

This paper describes the use of property graphs for mapping data between AEC software tools, which are not linked by common data formats and/or other interoperability measures. The intention of introducing this in practice, education and research is to facilitate the use of diverse, non-integrated design and analysis applications by a variety of users who need to create customised digital workflows, including those who are not expert programmers. Data model types are examined by way of supporting the choice of directed, attributed, multi-relational graphs for such data transformation tasks. A brief exemplar design scenario is also presented to illustrate the concepts and methods proposed, and conclusions are drawn regarding the feasibility of this approach and directions for further research.