Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

The obesity epidemic : both energy intake and physical activity contribute

Recent data from Australia, the United States and Europe show increased self-reported energy intake associated with obesity, in contrast to earlier suggestions that the obesity epidemic has occurred despite minimal or no increase in per capita energy intake from food. The effect of increased energy intake is compounded by sedentary lifestyles. Both physical activity and nutrition must be addressed to reduce the prevalence of obesity and improve the health of Australians.

A phase II study of Caelyx, liposomal doxorubicin : lack of activity in patients with advanced gastric cancer

Purpose A phase II study was designed to assess the efficacy and safety of Caelyx (liposomal doxorubicin) in patients with advanced or metastatic gastric cancer. Methods A total of 25 patients with gastric adenocarcinoma were treated with Caelyx 45 mg/m2 every 28 days as first-line therapy for advanced disease. Patients were treated until tumour progression or unacceptable toxicity. Results One patient was withdrawn from the study after experiencing a severe infusion reaction. Of the 24 evaluable patients, 1 had a partial response, 7 had stable disease and the others progressed. Side effects, in particular palmar-plantar erythrodysaesthesia and haematological toxicity, were minor. Conclusions We conclude that while this dose and schedule of Caelyx in this patient group is acceptable, further studies with this regimen cannot be recommended due to the lack of antitumour activity seen.

Biomechanical characteristics of peripheral diabetic neuropathy : a systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure

Background: Diabetic peripheral neuropathy is an important cause of foot ulceration and limb loss. This systematic review and meta-analysis investigated the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and dynamic plantar pressures. Methods: Electronic databases were searched systematically for articles reporting the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and plantar pressures. Searches were restricted to articles published between January 2000 and April 2012. Outcome measures assessed included spatiotemporal parameters, lower limb kinematics, kinetics, muscle activation and plantar pressure. Meta-analyses were carried out on all outcome measures reported by ≥3 studies. Findings: Sixteen studies were included consisting of 382 neuropathy participants, 216 diabetes controls without neuropathy and 207 healthy controls. Meta-analysis was performed on 11 gait variables. A high level of heterogeneity was noted between studies. Meta-analysis results suggested a longer stance time and moderately higher plantar pressures in diabetic peripheral neuropathy patients at the rearfoot, midfoot and forefoot compared to controls. Systematic review of studies suggested potential differences in the biomechanical characteristics (kinematics, kinetics, EMG) of diabetic neuropathy patients. However these findings were inconsistent and limited by small sample sizes.; Interpretation: Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies. Interpretation: Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies.

Fine tuning of elasticity via crosslinking collagen-based materials to mediate mechanotransduction and stability using corona treatment

The common goal of tissue engineering is to develop substitutes that can closely mimic the structure of extracellular matrix (ECM). However, similarly important is the intensive material properties which have often been overlooked, in particular, for soft tissues that are not to bear load assumingly. The mechanostructural properties determine not only the structural stability of biomaterials but also their physiological functionality by directing cellular activity and regulating cell fate decision. The aim here is to emphasize that cells could sense intensive material properties like elasticity and reside, proliferate, migrate and differentiate accordinglyno matter if the construct is from a natural source like cartilage, skin etc. or of synthetic one. Meanwhile, the very objective of this work is to provide a tunable scheme for manipulating the elasticity of collagen-based constructs to be used to demonstrate how to engineer cell behavior and regulate mechanotransduction. Articular cartilage was chosen as it represents one of the most complex hierarchical arrangements of collagen meshwork in both connective tissues and ECM-like biomaterials. Corona discharge treatment was used to produce constructs with varying density of crosslinked collagen and stiffness accordingly. The results demonstrated that elastic modulus increased up to 33% for samples treated up to one minute as crosslink density was found to increase with exposure time. According to the thermal analysis, longer exposure to corona increased crosslink density as the denaturation enthalpy increased. However the spectroscopy results suggested that despite the stabilization of the collagen structure the integrity of the triple helical structure remained intact. The in vitro superficial culture of heterologous chondrocytes also determined that the corona treatment can modulate migration with increased focal adhesion of cells due to enhanced stiffness, without cytotoxicity effects, and providing the basis for reinforcing three-dimensional collagen-based biomaterials in order to direct cell function and mediate mechanotransduction.

Physical activity and health-related quality of life among physiotherapists : a cross sectional survey in an Australian hospital and health service

Background Physiotherapists are a professional group with a high rate of attrition and at high risk of musculoskeletal disorders. The purpose of this investigation was to examine the physical activity levels and health-related quality of life of physiotherapists working in metropolitan clinical settings in an Australian hospital and health service. It was hypothesized that practicing physiotherapists would report excellent health-related quality of life and would already be physically active. Such a finding would add weight to a claim that general physical activity conditioning strategies may not be useful for preventing musculoskeletal disorders among active healthy physiotherapists, but rather, future investigations should focus on the development and evaluation of role specific conditioning strategies. Methods A questionnaire was completed by 44 physiotherapists from three inpatient units and three ambulatory clinics (63.7% response rate). Physical activity levels were reported using the Active Australia Survey. Health-related quality of life was examined using the EQ-5D instrument. Physical activity and EQ-5D data were examined using conventional descriptive statistics; with domain responses for the EQ-5D presented in a frequency histogram. Results The majority of physiotherapists in this sample were younger than 30 years of age (n = 25, 56.8%) consistent with the presence of a high attrition rate. Almost all respondents exceeded minimum recommended physical activity guidelines (n = 40, 90.9%). Overall the respondents engaged in more vigorous physical activity (median = 180 minutes) and walking (median = 135 minutes) than moderate exercise (median = 35 minutes) each week. Thirty-seven (84.1%) participants reported no pain or discomfort impacting their health-related quality of life, with most (n = 35,79.5%) being in full health. Conclusions Physical-conditioning based interventions for the prevention of musculoskeletal disorders among practicing physiotherapists may be better targeted to role or task specific conditioning rather than general physical conditioning among this physically active population. It is plausible that an inherent attrition of physiotherapists may occur among those not as active or healthy as therapists who cope with the physical demands of clinical practice. Extrapolation of findings from this study may be limited due to the sample characteristics. However, this investigation addressed the study objectives and has provided a foundation for larger scale longitudinal investigations in this field.

Strategies for developing and delivering a parental physical activity intervention : answers to the what and how

Background Parents are at risk for physical inactivity; however, few studies have designed physical activity (PA) interventions specifically applied to individuals with young children. To ensure the effectiveness of interventions, it may be useful to first elicit the needs from the target population and incorporate salient strategies identified to the design and delivery of a resultant intervention. We aimed to explore strategies for what to include in and how to best deliver a program designed to increase parental PA. Methods Twelve parents (6 mothers, 6 fathers) of children younger than 5 years participated in focus group discussions exploring strategies for an intervention program designed to increase parental PA. Results A range of themes such as Focus on the Children and Flexible Life/Family Plans imbedded in strategies such as persuasion and information, problem-solving, skill building, and environmental approaches were identified. In addition, a range of strategies for how to best deliver a parental PA intervention evidenced in emerging themes such as Diverse and Brief and Individualized Approach was discussed. Conclusions Future research should continue to adopt a ground up, community-based approach to the development and implementation of interventions for this at-risk group to ensure sustained involvement in regular PA.

Urinary biomarkers of physical activity : candidates and clinical utility

Chronic physical inactivity is a major risk factor for a number of important lifestyle diseases, while inappropriate exposure to high physical demands is a risk factor for musculoskeletal injury and fatigue. Proteomic and metabolomic investigations of the physical activity continuum - extreme sedentariness to extremes in physical performance - offer increasing insight into the biological impacts of physical activity. Moreover, biomarkers, revealed in such studies, may have utility in the monitoring of metabolic and musculoskeletal health or recovery following injury. As a diagnostic matrix, urine is non-invasive to collect and it contains many biomolecules, which reflect both positive and negative adaptations to physical activity exposure. This review examines the utility and landscape of biomarkers of physical activity with particular reference to those found in urine.

Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice

Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer patients.

Semi-binary based video features for activity representation

Efficient and effective feature detection and representation is an important consideration when processing videos, and a large number of applications such as motion analysis, 3D scene understanding, tracking etc. depend on this. Amongst several feature description methods, local features are becoming increasingly popular for representing videos because of their simplicity and efficiency. While they achieve state-of-the-art performance with low computational complexity, their performance is still too limited for real world applications. Furthermore, rapid increases in the uptake of mobile devices has increased the demand for algorithms that can run with reduced memory and computational requirements. In this paper we propose a semi binary based feature detectordescriptor based on the BRISK detector, which can detect and represent videos with significantly reduced computational requirements, while achieving comparable performance to the state of the art spatio-temporal feature descriptors. First, the BRISK feature detector is applied on a frame by frame basis to detect interest points, then the detected key points are compared against consecutive frames for significant motion. Key points with significant motion are encoded with the BRISK descriptor in the spatial domain and Motion Boundary Histogram in the temporal domain. This descriptor is not only lightweight but also has lower memory requirements because of the binary nature of the BRISK descriptor, allowing the possibility of applications using hand held devices.We evaluate the combination of detectordescriptor performance in the context of action classification with a standard, popular bag-of-features with SVM framework. Experiments are carried out on two popular datasets with varying complexity and we demonstrate comparable performance with other descriptors with reduced computational complexity.

Psychological determinants and outcomes of sedentary and physical activity behaviours

There is now a large body of literature that supports the protective role of physical activity for both physical and psychological health. Sedentary behaviour was previously considered the functional opposite of physical activity, but 10 years ago, Owen and colleagues highlighted the need to study physical activity and sedentary behaviour as two distinct modes of behaviour that can independently influence health [1]. Since then, there has been growing evidence that participation in sedentary behaviours such as television viewing, computer use and sitting at work are associated with higher risk of chronic disease outcomes (type 2 diabetes, obesity), and leisure-time sitting has recently been associated with increased mortality [2]. Growing research points to the possible synergistic effects of physical activity and sedentary behaviours in contributing to health outcomes

Innovations in dietary interventions : Use of a photographic food diary method and telephone linked computerized care in chronic disease

Access to dietetic care is important in chronic disease management and innovative technologies assists in this purpose. Photographic dietary records (PhDR) using mobile phones or cameras are valid and convenient for patients. Innovations in providing dietary interventions via telephone and computer can also inform dietetic practice. Three studies are presented. A mobile phone method was validated by comparing energy intake (EI) to a weighed food record and a measure of energy expenditure (EE) obtained using the doubly labelled water technique in 10 adults with T2 diabetes. The level of agreement between mean (±sd) energy intake mobile phone (8.2±1.7 MJ) and weighed record (8.5±1.6 MJ) was high (p=0.392), however EI/EE for both methods gave similar levels of under-reporting (0.69 and 0.72). All subjects preferred using the mobile phone vs. weighed record. Nineteen individuals with Parkinsons disease kept 3-day PhDRs on three occasions using point-and-shoot digital cameras over a 12 week period. The camera was rated as easy to use by 89%, keeping a PhDR was considered acceptable by 94% and none would rather use a “pen and paper” method. Eighty-three percent felt confident to use the camera again to record intake. An interactive, automated telephone system designed to coach people with T2 diabetes to adopt and maintain diabetes self-care behaviours, including nutrition, showed trends for improvements in total fat, saturated fat and vegetable intake of the intervention group compared to control participants over 6 months. Innovative technologies are acceptable to patients with chronic conditions and can be incorporated into dietetic care.

Effect of cell wall properties of plant tissue on porosity and shrinkage of dried apple

In this study cell wall properties; moisture distribution, stiffness, thickness and cell dimension have been taken into consideration. Cell wall stiffness dependent on complex combination of plant cell microstructures, composition and water holding capacity of the cell. In this work, some preliminary steps taken by investing cell wall properties of apple in order to predict change of porosity and shrinkage during drying. Two different types of apple cell wall characteristic were investigated to correlate with porosity and shrinkage after convective drying. A scanning electron microscope (SEM), 2N Intron, a pyncometer and image J software were used in order to measure and analyze cell characteristics, water dynamics, porosity and shrinkage. Cell stiffness of red delicious apple was found higher than granny smith apples. A significant relationship has found between cell wall characteristics and both heat and mass transfer. Consequently, evolution of porosity and shrinkage noticeably influenced during convective drying by the nature of cell wall. This study has brought better understanding of porosity and shrinkage of dried food stuff in microscopic (cell) level and would provide better insight to attain energy effective drying process and quality food stuff.

Experimental study on the fire performance of superior LSF wall systems

Load bearing Light Gauge Steel Frame (LSF) walls are commonly made of conventional lipped channel sections and gypsum plasterboards. Recently, innovative steel sections such as hollow flange channel sections have been proposed as studs in LSF wall frames with a view to improve their fire resistance ratings. A series of full scale fire tests was then undertaken to investigate the fire performance of the new LSF wall systems under standard fire conditions. Test wall frames made of hollow flange section studs were lined with fire resistant gypsum plasterboards on both sides, and were subjected to increasing temperatures as given by the standard fire curve on one side. Both uninsulated and cavity insulated walls were tested with varying load ratios from 0.2 to 0.6. This paper presents the details of this experimental study on the fire performance of LSF walls and the results. Test results showed that the walls made of the new hollow flange channel section studs have a superior fire performance in comparison to that of lipped channel section stud walls. They also showed that the fire performance of cavity insulated walls was inferior to that of uninsulated walls. The reasons for this fire behaviour are described in this paper.

Activity, motivation and games for young children

The research described in this paper examines the extent to which very young children were able to use the Stomp platform (a floor-based gaming system designed to provide new, active participatory experiences) to engage in game play. We are interested in how children's engagement in different activities within the game world influences their motivation to play games. We map activity to motivational needs of competence, autonomy and relatedness. A detailed examination of two Stomp experiences demonstrates how this type of analysis is useful in identifying the strengths and weaknesses of the games for this audience.