Modified alternating direction methods for solving a two-dimensional non-continuous seepage flow with fractional derivatives

In this paper, a two-dimensional non-continuous seepage flow with fractional derivatives (2D-NCSF-FD) in uniform media is considered, which has modified the well known Darcy law. Using the relationship between Riemann-Liouville and Grunwald-Letnikov fractional derivatives, two modified alternating direction methods: a modified alternating direction implicit Euler method and a modified Peaceman-Rachford method, are proposed for solving the 2D-NCSF-FD in uniform media. The stability and consistency, thus convergence of the two methods in a bounded domain are discussed. Finally, numerical results are given.

Glycaemic load is associated with insulin resistance in older Australian women

Background: Diets with a high postprandial glycemic response may contribute to long-term development of insulin resistance and diabetes, however previous epidemiological studies are conflicting on whether glycemic index (GI) or glycemic load (GL) are dietary factors associated with the progression. Our objectives were to estimate GI and GL in a group of older women, and evaluate cross-sectional associations with insulin resistance. Subjects and Methods: Subjects were 329 Australian women aged 42-81 years participating in year three of the Longitudinal Assessment of Ageing in Women (LAW). Dietary intakes were assessed by diet history interviews and analysed using a customised GI database. Insulin resistance was defined as a homeostasis model assessment (HOMA) value of >3.99, based on fasting blood glucose and insulin concentrations. Results: GL was significantly higher in the 26 subjects who were classified as insulin resistant compared to subjects who were not (134±33 versus 114±24, P<0.001). In a logistic regression model, an increment of 15 GL units increased the odds of insulin resistance by 2.09 (95%CI 1.55, 2.80, P<0.001) independently of potential confounding variables. No significant associations were found when insulin resistance was assessed as a continuous variable. Conclusions: Results of this cross-sectional study support the concept that diets with a higher GL are associated with increased risk of insulin resistance. Further studies are required to investigate whether reducing glycemic intake, by either consuming lower GI foods and/or smaller serves of carbohydrate, can contribute to a reduction in development of insulin resistance and long-term risk of type 2 diabetes.

An experimental and finite element investigation of the biomechanics of vertebral compression fractures

Osteoporosis is a disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis affects over 200 million people worldwide, with an estimated 1.5 million fractures annually in the United States alone, and with attendant costs exceeding $10 billion dollars per annum. Osteoporosis reduces bone density through a series of structural changes to the honeycomb-like trabecular bone structure (micro-structure). The reduced bone density, coupled with the microstructural changes, results in significant loss of bone strength and increased fracture risk. Vertebral compression fractures are the most common type of osteoporotic fracture and are associated with pain, increased thoracic curvature, reduced mobility, and difficulty with self care. Surgical interventions, such as kyphoplasty or vertebroplasty, are used to treat osteoporotic vertebral fractures by restoring vertebral stability and alleviating pain. These minimally invasive procedures involve injecting bone cement into the fractured vertebrae. The techniques are still relatively new and while initial results are promising, with the procedures relieving pain in 70-95% of cases, medium-term investigations are now indicating an increased risk of adjacent level fracture following the procedure. With the aging population, understanding and treatment of osteoporosis is an increasingly important public health issue in developed Western countries. The aim of this study was to investigate the biomechanics of spinal osteoporosis and osteoporotic vertebral compression fractures by developing multi-scale computational, Finite Element (FE) models of both healthy and osteoporotic vertebral bodies. The multi-scale approach included the overall vertebral body anatomy, as well as a detailed representation of the internal trabecular microstructure. This novel, multi-scale approach overcame limitations of previous investigations by allowing simultaneous investigation of the mechanics of the trabecular micro-structure as well as overall vertebral body mechanics. The models were used to simulate the progression of osteoporosis, the effect of different loading conditions on vertebral strength and stiffness, and the effects of vertebroplasty on vertebral and trabecular mechanics. The model development process began with the development of an individual trabecular strut model using 3D beam elements, which was used as the building block for lattice-type, structural trabecular bone models, which were in turn incorporated into the vertebral body models. At each stage of model development, model predictions were compared to analytical solutions and in-vitro data from existing literature. The incremental process provided confidence in the predictions of each model before incorporation into the overall vertebral body model. The trabecular bone model, vertebral body model and vertebroplasty models were validated against in-vitro data from a series of compression tests performed using human cadaveric vertebral bodies. Firstly, trabecular bone samples were acquired and morphological parameters for each sample were measured using high resolution micro-computed tomography (CT). Apparent mechanical properties for each sample were then determined using uni-axial compression tests. Bone tissue properties were inversely determined using voxel-based FE models based on the micro-CT data. Specimen specific trabecular bone models were developed and the predicted apparent stiffness and strength were compared to the experimentally measured apparent stiffness and strength of the corresponding specimen. Following the trabecular specimen tests, a series of 12 whole cadaveric vertebrae were then divided into treated and non-treated groups and vertebroplasty performed on the specimens of the treated group. The vertebrae in both groups underwent clinical-CT scanning and destructive uniaxial compression testing. Specimen specific FE vertebral body models were developed and the predicted mechanical response compared to the experimentally measured responses. The validation process demonstrated that the multi-scale FE models comprising a lattice network of beam elements were able to accurately capture the failure mechanics of trabecular bone; and a trabecular core represented with beam elements enclosed in a layer of shell elements to represent the cortical shell was able to adequately represent the failure mechanics of intact vertebral bodies with varying degrees of osteoporosis. Following model development and validation, the models were used to investigate the effects of progressive osteoporosis on vertebral body mechanics and trabecular bone mechanics. These simulations showed that overall failure of the osteoporotic vertebral body is initiated by failure of the trabecular core, and the failure mechanism of the trabeculae varies with the progression of osteoporosis; from tissue yield in healthy trabecular bone, to failure due to instability (buckling) in osteoporotic bone with its thinner trabecular struts. The mechanical response of the vertebral body under load is highly dependent on the ability of the endplates to deform to transmit the load to the underlying trabecular bone. The ability of the endplate to evenly transfer the load through the core diminishes with osteoporosis. Investigation into the effect of different loading conditions on the vertebral body found that, because the trabecular bone structural changes which occur in osteoporosis result in a structure that is highly aligned with the loading direction, the vertebral body is consequently less able to withstand non-uniform loading states such as occurs in forward flexion. Changes in vertebral body loading due to disc degeneration were simulated, but proved to have little effect on osteoporotic vertebra mechanics. Conversely, differences in vertebral body loading between simulated invivo (uniform endplate pressure) and in-vitro conditions (where the vertebral endplates are rigidly cemented) had a dramatic effect on the predicted vertebral mechanics. This investigation suggested that in-vitro loading using bone cement potting of both endplates has major limitations in its ability to represent vertebral body mechanics in-vivo. And lastly, FE investigation into the biomechanical effect of vertebroplasty was performed. The results of this investigation demonstrated that the effect of vertebroplasty on overall vertebra mechanics is strongly governed by the cement distribution achieved within the trabecular core. In agreement with a recent study, the models predicted that vertebroplasty cement distributions which do not form one continuous mass which contacts both endplates have little effect on vertebral body stiffness or strength. In summary, this work presents the development of a novel, multi-scale Finite Element model of the osteoporotic vertebral body, which provides a powerful new tool for investigating the mechanics of osteoporotic vertebral compression fractures at the trabecular bone micro-structural level, and at the vertebral body level.

Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer

Although systemic androgen deprivation prolongs life in advanced prostate cancer, remissions are temporary because patients almost uniformly progress to a state of a castration-resistant prostate cancer (CRPC) as indicated by recurring PSA. This complex process of progression does not seem to be stochastic as the timing and phenotype are highly predictable, including the observation that most androgen-regulated genes are reactivated despite castrate levels of serum androgens. Recent evidence indicates that intraprostatic levels of androgens remain moderately high following systemic androgen deprivation therapy, whereas the androgen receptor (AR) remains functional, and silencing the AR expression following castration suppresses tumor growth and blocks the expression of genes known to be regulated by androgens. From these observations, we hypothesized that CRPC progression is not independent of androgen-driven activity and that androgens may be synthesized de novo in CRPC tumors leading to AR activation. Using the LNCaP xenograft model, we showed that tumor androgens increase during CRPC progression in correlation to PSA up-regulation. We show here that all enzymes necessary for androgen synthesis are expressed in prostate cancer tumors and some seem to be up-regulated during CRPC progression. Using an ex vivo radiotracing assays coupled to high-performance liquid chromatography-radiometric/mass spectrometry detection, we show that tumor explants isolated from CRPC progression are capable of de novo conversion of [(14)C]acetic acid to dihydrotestosterone and uptake of [(3)H]progesterone allows detection of the production of six other steroids upstream of dihydrotestosterone. This evidence suggests that de novo androgen synthesis may be a driving mechanism leading to CRPC progression following castration.

Supply chain collaboration : capabilities for continuous innovation

Purpose – The purpose of this study is to investigate how collaborative relationships enhance continuous innovation in the supply chain using case studies. Design/methodology/approach – The data were collected from semi-structured interviews with 23 managers in ten case studies. The main intention was to comprehend how these firms engaged in collaborative relationships and their importance for successful innovation. The study adopted a qualitative approach to investigating these factors. Findings – The findings demonstrate how differing relationships can impact on the operation of firms and their capacities to innovate. The ability to work together with partners has enabled firms to integrate and link operations for increased effectiveness as well as embark on both radical and incremental innovation. Research limitations/implications – The research into the initiatives and strategies for collaboration was essentially exploratory. A qualitative approach using case studies acknowledged that the responses from managers were difficult to quantify or gauge the extent of these factors. Practical implications – The findings have shown various methods where firms integrated with customers and suppliers in the supply chain. This was evident in the views of managers across all the firms examined, supporting the importance of collaboration and efficient allocation of resources throughout the supply chain. They were able to set procedures in their dealings with partners, sharing knowledge and processes, and subsequently joint-planning and investing with them for better operations, systems and processes in the supply chain. Originality/value – The case studies serve as examples for managers in logistics organisation who are contemplating strategies and issues on collaborative relationships. The study provides important lessons on how such relationships can impact on the operation of firms and their capability to innovate. Keywords Supply chain management, Innovation, Relationship marketing

Examining the role of human resource management in continuous improvement

The objective of this paper is to take a first step in developing a theoretical framework describing the role of HRM in successful CI, based on the current literature from both fields. To this end, elements from the CI Maturity Model and a framework depicting the role of HRM in innovation serve as a foundation for examining how specific bundles of HRM practices utilised during different phases of the CI implementation process may contribute to sustained organisational and enhanced operational performance. The primary contribution of this paper is theoretical; however, the framework has practical value in that it suggests important relationships between HRM practices and behaviours necessary for successful CI. A preliminary test of the framework in an empirical setting is summarised at the conclusion of this paper, where a number of possible research avenues are also suggested.

Exploration and exploitation : the interplay between knowledge and continuous innovation

In rapidly changing environments, organisations require dynamic capabilities to integrate, build and reconfigure resources and competencies to achieve continuous innovation. Although tangible resources are important to promoting the firm’s ability to act, capabilities fundamentally rest in the knowledge created and accumulated by the firm through human capital, organisational routines, processes, practices and norms. The exploration for new ideas, technologies and knowledge – to one side – and – on the other one – the exploitation of existing and new knowledge is essential for continuous innovation. Firms need to decide how best to allocate their scarce resources for both activities and at the same time build dynamic capabilities to keep up with changing market conditions. This in turn, is influenced by the absorptive capacity of the firm to assimilate knowledge. This paper presents a case study that investigates the sources of knowledge in an engineering firm in Australia, and how it is organised and processed. As information pervades the firm from both internal and external sources, individuals integrate knowledge using both exploration and exploitation approaches. The findings illustrate that absorptive capacity can encourage greater leverage for exploration potential leading to radical innovation; and reconfiguring exploitable knowledge for incremental improvements. This study provides an insight for managers in quest of improving knowledge strategies and continuous innovation. It also makes significant theoretical contributions to the literature through extending the concepts of

Performance measurement and continuous improvement : are they linked to manufacturing strategy?

To maintain or achieve competitiveness and profitability, a manufacturing firm or enterprise must respond to a range of challenges, including rapid improvements in technology; declining employment and output; globalisation of markets and environmental requirements. In addition, substantial changes in government policy have had important impacts in many countries, as have the increasing levels of global trade. Manufacturing enterprises need to have a clear understanding of what their customers want and why customers purchase their products rather than purchase from their competitors. They need to fully understand the aims of the business in terms of its customers, market segments, product attributes, geographical markets and performance. Continuous Improvement (CI) methods have become widely adopted and regarded as providing an important component of increased company competitiveness. This article examines the extent to which continuous improvement activities have contributed to the different areas of business performance.

Learning barriers in continuous product innovation

In today's dynamic and turbulent environment companies are required to increase their effectiveness and efficiency, exploit synergy and learn product innovation processes in order to build competitive advantage. To be able to stimulate and facilitate learning in product innovation, it is necessary to gain an insight into factors that hinder learning and to design effective intervention strategies that may help remove barriers to learning. This article reports on learning barriers identified by product innovation managers in over 70 companies in the UK, Ireland, Italy, Netherlands, Sweden and Australia. The results show that the majority of the barriers identified can be labelled as organisational defensive routines leading to a chain of behaviours; lack of resources leads to under-appreciation of the value of valid information, absence of informed choice and lack of personal responsibility. An intervention theory is required which enables individuals and organisations to interrupt defensive patterns in ways that prevents them from recurring.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections : clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin–clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of β-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin–clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3–12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin–clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

Experience mapping : producing spatially continuous environment representations using RatSLAM

RatSLAM is a system for vision-based Simultaneous Localisation and Mapping (SLAM) inspired by models of the rodent hippocampus. The system can produce stable representations of large complex environments during robot experiments in both indoor and outdoor environments. These representations are both topological and metric in nature, and can involve multiple representations of the same place as well as discontinuities. In this paper we describe a new technique known as experience mapping that can be used online with the RatSLAM system to produce world representations known as experience maps. These maps group together multiple place representations and are spatially continuous. A number of experiments have been conducted in simulation and a real world office environment. These experiments demonstrate the high degree to which experience maps are representative of the spatial arrangement of the environment.