Design and fabrication of tubular scaffolds via direct writing in a melt electrospinning mode

Flexible tubular structures fabricated from solution electrospun fibers are finding increasing use in tissue engineering applications. However it is difficult to control the deposition of fibers due to the chaotic nature of the solution electrospinning jet. By using non-conductive polymer melts instead of polymer solutions the path and collection of the fiber becomes predictable. In this work we demonstrate the melt electrospinning of polycaprolactone in a direct writing mode onto a rotating cylinder. This allows the design and fabrication of tubes using 20 μm diameter fibers with controllable micropatterns and mechanical properties. A key design parameter is the fiber winding angle, where it allows control over scaffold pore morphology (e.g. size, shape, number and porosity). Furthermore, the establishment of a finite element model as a predictive design tool is validated against mechanical testing results of melt electrospun tubes to show that a lesser winding angle provides improved mechanical response to uniaxial tension and compression. In addition, we show that melt electrospun tubes support the growth of three different cell types in vitro and are therefore promising scaffolds for tissue engineering applications.

A general method to determine sampling windows for nonlinear mixed effects models with an application to population pharmacokinetic studies

Optimal design methods have been proposed to determine the best sampling times when sparse blood sampling is required in clinical pharmacokinetic studies. However, the optimal blood sampling time points may not be feasible in clinical practice. Sampling windows, a time interval for blood sample collection, have been proposed to provide flexibility in blood sampling times while preserving efficient parameter estimation. Because of the complexity of the population pharmacokinetic models, which are generally nonlinear mixed effects models, there is no analytical solution available to determine sampling windows. We propose a method for determination of sampling windows based on MCMC sampling techniques. The proposed method attains a stationary distribution rapidly and provides time-sensitive windows around the optimal design points. The proposed method is applicable to determine sampling windows for any nonlinear mixed effects model although our work focuses on an application to population pharmacokinetic models.

The hygienic efficacy of different hand-drying methods : a review of the evidence

The transmission of bacteria is more likely to occur from wet skin than from dry skin; therefore, the proper drying of hands after washing should be an integral part of the hand hygiene process in health care. This article systematically reviews the research on the hygienic efficacy of different hand-drying methods. A literature search was conducted in April 2011 using the electronic databases PubMed, Scopus, and Web of Science. Search terms used were hand dryer and hand drying. The search was limited to articles published in English from January 1970 through March 2011. Twelve studies were included in the review. Hand-drying effectiveness includes the speed of drying, degree of dryness, effective removal of bacteria, and prevention of cross-contamination. This review found little agreement regarding the relative effectiveness of electric air dryers. However, most studies suggest that paper towels can dry hands efficiently, remove bacteria effectively, and cause less contamination of the washroom environment. From a hygiene viewpoint, paper towels are superior to electric air dryers. Paper towels should be recommended in locations where hygiene is paramount, such as hospitals and clinics.

Everyday resilience : narratives of single refugee women with children

This article offers a critical exploration of the concept of resilience, which is largely conceptualized in the literature as an extraordinary atypical personal ability to revert or ‘bounce back’ to a point of equilibrium despite significant adversity. While resilience has been explored in a range of contexts, there is little recognition of resilience as a social process arising from mundane practices of everyday life and situated in person -environment interactions. Based on an ethnographic study among single refugee women with children in Brisbane, Australia, the women’s stories on navigating everyday tensions and opportunities revealed how resilience was a process operating inter-subjectively in the social spaces connecting them to their environment. Far beyond the simplistic binaries of resilience versus non-resilient, we concern ourselves here with the everyday processual, person environment nature of the concept. We argue that more attention should be paid to day-to-day pathways through which resilience outcomes are achieved, and that this has important implications for refugee mental health practice frameworks.

Bicycle safety for children and young people : an analysis of child deaths in Queensland

Bicycle riding can be a positive experience for children and young people that builds confidence, independence and promotes healthy recreation. However, these benefits are dependent upon safe bicycle riding practices. Between 1 January 2004 and 31 December 2011, 12 children and young people under the age of 18 years died in bicycle incidents in Queensland. An additional 1736 bicycle-related injuries requiring emergency department attendance are estimated to have occurred between 2008 and 2009 in Queensland for children and young people under the age of 18 years. Of the twelve bicycle-related deaths between 2004 and 2011 in Queensland, two children were aged between 5-9 years, 5 young people were 10-14 years of age and 5 young people were between 15-17 years. The two children aged 5-9 years were riding their bikes for recreation. Children aged 10-14 years were most likely to have been killed in an incident while riding to school in the morning, with teenagers aged 15-17 years most likely to be killed in incidents occurring after school and in the evening. Bicycle riders are vulnerable road users, particularly children and young people. This is due to several factors that can be grouped into: 1) developmental characteristics such as body size and proportions, perceptional and attentional issues, road safety awareness and risk taking behaviours, and 2) environmental factors such as supervision and shared road use with vehicles. This paper examines safety issues for children and young people who have died in bicycle-related incidents in Queensland, and outlines areas of focus for injury prevention practitioners.

Impact of opening a new emergency department on healthcare service and patient outcomes : analyses based on linking ambulance, emergency and hospital databases

Background Emergency department (ED) crowding caused by access block is an increasing public health issue and has been associated with impaired healthcare delivery, negative patient outcomes and increased staff workload. Aim To investigate the impact of opening a new ED on patient and healthcare service outcomes. Methods A 24-month time series analysis was employed using deterministically linked data from the ambulance service and three ED and hospital admission databases in Queensland, Australia. Results Total volume of ED presentations increased 18%, while local population growth increased by 3%. Healthcare service and patient outcomes at the two pre-existing hospitals did not improve. These outcomes included ambulance offload time: (Hospital A PRE: 10 min, POST: 10 min, P < 0.001; Hospital B PRE: 10 min, POST: 15 min, P < 0.001); ED length of stay: (Hospital A PRE: 242 min, POST: 246 min, P < 0.001; Hospital B PRE: 182 min, POST: 210 min, P < 0.001); and access block: (Hospital A PRE: 41%, POST: 46%, P < 0.001; Hospital B PRE: 23%, POST: 40%, P < 0.001). Time series modelling indicated that the effect was worst at the hospital furthest away from the new ED. Conclusions An additional ED within the region saw an increase in the total volume of presentations at a rate far greater than local population growth, suggesting it either provided an unmet need or a shifting of activity from one sector to another. Future studies should examine patient decision making regarding reasons for presenting to a new or pre-existing ED. There is an inherent need to take a ‘whole of health service area’ approach to solve crowding issues.

Prevalence of breast cancer treatment sequelae over 6 years of follow-up

Background: There is a need to better describe and understand the prevalence of breast cancer treatment-related adverse effects amenable to physical therapy and rehabilitative exercise. Prior studies have been limited to single issues and lacked long term follow-up. The Pulling Through Study provides data on prevalence of adverse effects in breast cancer survivors followed over six years. Methods: A population-based sample of Australian women (n=287) diagnosed with invasive, unilateral breast cancer was followed for a median of 6.6 years and prospectively assessed for treatment-related complications at 6, 12, 18 months, and 6 years post-diagnosis. Assessments included post-surgical complications, skin or tissue reaction to radiation therapy, upper-body symptoms, lymphedema, 10% weight gain, fatigue, and upper-quadrant function. The proportion of women with positive indication for each complication and one or more complication was estimated using all available data at each time point. Women were only considered to have a specific complication if they reported the highest two levels of the Likert scale for self-reported issues. Results: At six years post-diagnosis over 60% of women experienced one or more side effects amenable to rehabilitative intervention. The proportion of women experiencing 3 or more side effects decreased throughout follow-up, while the proportion experiencing no side effects remained stable around 40% from 12 months to six years. Weight gain was the only complication to increase in prevalence over time. Conclusion: These data support the development of a multi-disciplinary prospective surveillance approach for the purposes of managing and treating adverse effects in breast cancer survivors.

Attunement to haptic information helps skilled performers select implements for striking a ball in cricket

This study examined the perceptual attunement of relatively skilled individuals to physical properties of striking implements in the sport of cricket. We also sought to assess whether utilising bats of different physical properties influenced performance of a specific striking action: the front foot straight drive. Eleven, skilled male cricketers (mean age = 16.6 ± 0.3 years) from an elite school cricket development programme consented to participate in the study. Whist blindfolded, participants wielded six bats exhibiting different mass and moment of inertia (MOI) characteristics and were asked to identify their three most preferred bats for hitting a ball to a maximum distance by performing a front foot straight drive (a common shot in cricket). Next, participants actually attempted to hit balls projected from a ball machine using each of the six bat configurations to enable kinematic analysis of front foot straight drive performance with each implement. Results revealed that, on first choice, the two bats with the smallest mass and MOI values (1 and 2) were most preferred by almost two-thirds (63.7%) of the participants. Kinematic analysis of movement patterns revealed that bat velocity, step length and bat-ball contact position measures significantly differed between bats. Data revealed how skilled youth cricketers were attuned to the different bat characteristics and harnessed movement system degeneracy to perform this complex interceptive action.

Proteomics science & society : the role of knowledge translation in moving towards clinical applications

Background: Outside the mass-spectrometer, proteomics research does not take place in a vacuum. It is affected by policies on funding and research infrastructure. Proteomics research both impacts and is impacted by potential clinical applications. It provides new techniques & clinically relevant findings, but the possibilities for such innovations (and thus the perception of the potential for the field by funders) are also impacted by regulatory practices and the readiness of the health sector to incorporate proteomics-related tools & findings. Key to this process is how knowledge is translated. Methods: We present preliminary results from a multi-year social science project, funded by the Canadian Institutes of Health Research, on the processes and motivations for knowledge translation in the health sciences. The proteomics case within this wider study uses qualitative methods to examine the interplay between proteomics science and regulatory and policy makers regarding clinical applications of proteomics. Results: Adopting an interactive format to encourage conference attendees’ feedback, our poster focuses on deficits in effective knowledge translation strategies from the laboratory to policy, clinical, & regulatory arenas. An analysis of the interviews conducted to date suggests five significant choke points: the changing priorities of funding agencies; the complexity of proteomics research; the organisation of proteomics research; the relationship of proteomics to genomics and other omics sciences; and conflict over the appropriate role of standardisation. Conclusion: We suggest that engagement with aspects of knowledge translation, such as those mentioned above, is crucially important for the eventual clinical application ofproteomics science on any meaningful scale.

A randomised controlled trial of an enhanced interdisciplinary community based group program for people with Parkinson’s disease: study rationale and protocol

Parkinson’s disease (PD) is a progressive, chronic neurodegenerative disorder for which there is no known cure. Physical exercise programs may be used to assist with the physical management of PD. Several studies have demonstrated that community based physical therapy programs are effective in reducing physical aspects of disability among people with PD. While multidisciplinary therapy interventions may have the potential to reduce disability and improve the quality of life of people with PD, there is very limited clinical trial evidence to support or refute the use of a community based multidisciplinary or interdisciplinary programs for people with PD. A two group randomized trial is being undertaken within a community rehabilitation service in Brisbane, Australia. Community dwelling adults with a diagnosis of Idiopathic Parkinson’s disease are being recruited. Eligible participants are randomly allocated to a standard exercise rehabilitation group program or an intervention group which incorporates physical, cognitive and speech activities in a multi-tasking framework. Outcomes will be measured at 6-week intervals for a period of six months. Primary outcome measures are the Montreal Cognitive Assessment (MoCA) and the Timed Up and Go (TUG) cognitive test. Secondary outcomes include changes in health related quality of life, communication, social participation, mobility, strength and balance, and carer burden measures. This study will determine the immediate and long-term effectiveness of a unique multifocal, interdisciplinary, dual-tasking approach to the management of PD as compared to an exercise only program. We anticipate that the results of this study will have implications for the development of cost effective evidence based best practice for the treatment of people with PD living in the community.

An evolving perspective on physical activity counselling by medical professionals

Background Physical inactivity is a modifiable risk factor for many chronic conditions and a leading cause of premature mortality. An increasing proportion of adults worldwide are not engaging in a level of physical activity sufficient to prevent or alleviate these adverse effects. Medical professionals have been identified as potentially powerful sources of influence for those who do not meet minimum physical activity guidelines. Health professionals are respected and expected sources of advice and they reach a large and relevant proportion of the population. Despite this potential, health professionals are not routinely practicing physical activity promotion. Discussion Medical professionals experience several known barriers to physical activity promotion including lack of time and lack of perceived efficacy in changing physical activity behaviour in patients. Furthermore, evidence for effective physical activity promotion by medical professionals is inconclusive. To address these problems, new approaches to physical activity promotion are being proposed. These include collaborating with community based physical activity behaviour change interventions, preparing patients for effective brief counselling during a consultation with the medical professional, and use of interactive behaviour change technology. Summary It is important that we recognise the latent risk of physical inactivity among patients presenting in clinical settings. Preparation for improving patient physical activity behaviours should commence before the consultation and may include physical activity screening. Medical professionals should also identify suitable community interventions to which they can refer physically inactive patients. Outsourcing the majority of a comprehensive physical activity intervention to community based interventions will reduce the required clinical consultation time for addressing the issue with each patient. Priorities for future research include investigating ways to promote successful referrals and subsequent engagement in comprehensive community support programs to increase physical activity levels of inactive patients. Additionally, future clinical trials of physical activity interventions should be evaluated in the context of a broader framework of outcomes to inform a systematic consideration of broad strengths and weaknesses regarding not only efficacy but cost-effectiveness and likelihood of successful translation of interventions to clinical contexts.

An analytical tool that quantifies cellular morphology changes from three-dimensional fluorescence images

The most common software analysis tools available for measuring fluorescence images are for two-dimensional (2D) data that rely on manual settings for inclusion and exclusion of data points, and computer-aided pattern recognition to support the interpretation and findings of the analysis. It has become increasingly important to be able to measure fluorescence images constructed from three-dimensional (3D) datasets in order to be able to capture the complexity of cellular dynamics and understand the basis of cellular plasticity within biological systems. Sophisticated microscopy instruments have permitted the visualization of 3D fluorescence images through the acquisition of multispectral fluorescence images and powerful analytical software that reconstructs the images from confocal stacks that then provide a 3D representation of the collected 2D images. Advanced design-based stereology methods have progressed from the approximation and assumptions of the original model-based stereology(1) even in complex tissue sections(2). Despite these scientific advances in microscopy, a need remains for an automated analytic method that fully exploits the intrinsic 3D data to allow for the analysis and quantification of the complex changes in cell morphology, protein localization and receptor trafficking. Current techniques available to quantify fluorescence images include Meta-Morph (Molecular Devices, Sunnyvale, CA) and Image J (NIH) which provide manual analysis. Imaris (Andor Technology, Belfast, Northern Ireland) software provides the feature MeasurementPro, which allows the manual creation of measurement points that can be placed in a volume image or drawn on a series of 2D slices to create a 3D object. This method is useful for single-click point measurements to measure a line distance between two objects or to create a polygon that encloses a region of interest, but it is difficult to apply to complex cellular network structures. Filament Tracer (Andor) allows automatic detection of the 3D neuronal filament-like however, this module has been developed to measure defined structures such as neurons, which are comprised of dendrites, axons and spines (tree-like structure). This module has been ingeniously utilized to make morphological measurements to non-neuronal cells(3), however, the output data provide information of an extended cellular network by using a software that depends on a defined cell shape rather than being an amorphous-shaped cellular model. To overcome the issue of analyzing amorphous-shaped cells and making the software more suitable to a biological application, Imaris developed Imaris Cell. This was a scientific project with the Eidgenössische Technische Hochschule, which has been developed to calculate the relationship between cells and organelles. While the software enables the detection of biological constraints, by forcing one nucleus per cell and using cell membranes to segment cells, it cannot be utilized to analyze fluorescence data that are not continuous because ideally it builds cell surface without void spaces. To our knowledge, at present no user-modifiable automated approach that provides morphometric information from 3D fluorescence images has been developed that achieves cellular spatial information of an undefined shape (Figure 1). We have developed an analytical platform using the Imaris core software module and Imaris XT interfaced to MATLAB (Mat Works, Inc.). These tools allow the 3D measurement of cells without a pre-defined shape and with inconsistent fluorescence network components. Furthermore, this method will allow researchers who have extended expertise in biological systems, but not familiarity to computer applications, to perform quantification of morphological changes in cell dynamics.

Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine : involvement of adenosine and dopamine receptors

Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A₁ agonist, N⁶-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D₁ and D₂ receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D₁R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D₂R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor sensitization or tolerance after chronic exposure. Taken together, these findings demonstrate that theacrine significantly enhances activity; an effect which is mediated by both the adenosinergic and dopaminergic systems.

Delta opioid-receptor function in the dorsal striatum plays a role in high levels of ethanol consumption in rats

Binge-like patterns of excessive drinking during young adulthood increase the propensity for alcohol use disorders (AUDs) later in adult life; however, the mechanisms that drive this are not completely understood. Previous studies showed that the δ-opioid peptide receptor (DOP-R) is dynamically regulated by exposure to ethanol and that the DOP-R plays a role in ethanol-mediated behaviors. The aim of this study was to determine the role of the DOP-R in high ethanol consumption from young adulthood through to late adulthood by measuring DOP-R-mediated [(35)S]GTPγS binding in brain membranes and DOP-R-mediated analgesia using a rat model of high ethanol consumption in Long Evans rats. We show that DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia changes during development, being highest during early adulthood and reduced in late adulthood. Intermittent access to ethanol but not continuous ethanol or water from young adulthood leads to an increase in DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia into late adulthood. Multiple microinfusions of naltrindole into the dorsal striatum or multiple systemic administration of naltrindole reduces ethanol consumption, and following termination of treatment, DOP-R activity in the dorsal striatum is attenuated. These findings suggest that DOP-R activity in the dorsal striatum plays a role in high levels of ethanol consumption and suggest that targeting the DOP-R is an alternative strategy for the treatment of AUDs.

The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking

A major problem in treating alcohol use disorders (AUDs) is the high rate of relapse due to stress and re-exposure to cues or an environment previously associated with alcohol use. Stressors can induce relapse to alcohol-seeking in humans or reinstatement in rodents. Delta opioid peptide receptors (DOP-Rs) play a role in cue-induced reinstatement of ethanol-seeking; however, their role in stress-induced reinstatement of ethanol-seeking is not known. The objective of this study was to determine the role of DOP-Rs in yohimbine-stress-induced reinstatement of ethanol-seeking. Male, Long-Evans rats were trained to self-administer 10% ethanol in daily 30-minute operant self-administration sessions using a FR3 schedule of reinforcement, followed by extinction training. Once extinction criteria were met, we examined the effects of the DOP-R antagonist, SoRI-9409 (0–5 mg/kg, i.p.) on yohimbine (2 mg/kg, i.p.) stress-induced reinstatement. Additionally, DOP-R-stimulated [35S]GTPS binding was measured in brain membranes and plasma levels of corticosterone (CORT) were determined. Pre-treatment with SoRI-9409 decreased yohimbine stress-induced reinstatement of ethanol-seeking but did not affect yohimbine-induced increases in plasma CORT levels. Additionally, yohimbine increased DOP-R-stimulated 35[S]GTPS binding in brain membranes of ethanol-trained rats, an effect that was inhibited by SoRI-9409. This suggests that the DOP-R plays an important role in yohimbine-stress-induced reinstatement of ethanol-seeking behavior, and DOP-R antagonists may be promising candidates for further development as a treatment for AUDs.