Accurately simulating the production of radiotherapy portal images using non-zero beam angles

In this study, the delivery and portal imaging of one square-field and one conformal radiotherapy treatment was simulated using the Monte Carlo codes BEAMnrc and DOSXYZnrc. The treatment fields were delivered to a humanoid phantom from different angles by a 6 MV photon beam linear accelerator, with an amorphous-silicon electronic portal imaging device (a-Si EPID) used to provide images of the phantom generated by each field. The virtual phantom preparation code CTCombine was used to combine a computed-tomography-derived model of the irradiated phantom with a simple, rectilinear model of the a-Si EPID, at each beam angle used in the treatment. Comparison of the resulting experimental and simulated a-Si EPID images showed good agreement, within \[gamma](3%, 3 mm), indicating that this method may be useful in providing accurate Monte Carlo predictions of clinical a-Si EPID images, for use in the verification of complex radiotherapy treatments.

Setting a new agenda: Developing an Aboriginal and Torres Strait Islander women's health strategy

The Australian National Aboriginal and Torres Strait Islander Women’s Health Strategy was developed to reflect the health priorities of Aboriginal and Torres Strait Islander women, as identified by Aboriginal and Torres Strait Islander women themselves. This article describes the process used by the Australian Women’s Health Network to develop the strategy. The women involved in the research used the talking circle method and engaged with Aboriginal and Torres Strait Islander women through a process referred to as ‘talkin’ up’, where women ‘talk back’ to one another about issues that matter to them. In this article, we describe the power of the talkin’ up process, as a way for Aboriginal and Torres Strait Islander women to identify their own issues, discuss them in context and talk in a culturally safe environment. The strategy which emerged from this process is an accurate reflection of the issues that are important to Australian Indigenous women and highlights the improvements needed in Aboriginal and Torres Strait Islander women’s health to strengthen and underpin women’s health, Indigeneity and their sense of well-being as Aboriginal and Torres Strait Islander women.

Application of Geographic Modeling Techniques to Quantify Spatial Access to Health Services Before and After an Acute Cardiac Event: The Cardiac ARIA Project

Background: Access to cardiac services is essential for appropriate implementation of evidence-based therapies to improve outcomes. The Cardiac Accessibility and Remoteness Index for Australia (Cardiac ARIA) aimed to derive an objective, geographic measure reflecting access to cardiac services. Methods: An expert panel defined an evidence-based clinical pathway. Using Geographic Information Systems (GIS), a numeric/alpha index was developed at two points along the continuum of care. The acute category (numeric) measured the time from the emergency call to arrival at an appropriate medical facility via road ambulance. The aftercare category (alpha) measured access to four basic services (family doctor, pharmacy, cardiac rehabilitation, and pathology services) when a patient returned to their community. Results: The numeric index ranged from 1 (access to principle referral center with cardiac catheterization service ≤ 1 hour) to 8 (no ambulance service, > 3 hours to medical facility, air transport required). The alphabetic index ranged from A (all 4 services available within 1 hour drive-time) to E (no services available within 1 hour). 13.9 million (71%) Australians resided within Cardiac ARIA 1A locations (hospital with cardiac catheterization laboratory and all aftercare within 1 hour). Those outside Cardiac 1A were over-represented by people aged over 65 years (32%) and Indigenous people (60%). Conclusion: The Cardiac ARIA index demonstrated substantial inequity in access to cardiac services in Australia. This methodology can be used to inform cardiology health service planning and the methodology could be applied to other common disease states within other regions of the world.

MRI study of the changes in crystalline lens shape with accommodation and ageing in humans

Magnetic Resonance Imaging was used to study changes in the crystalline lens and ciliary body with accommodation and aging. Monocular images were obtained in 15 young (19-29 years) and 15 older (60-70 years) emmetropes when viewing at far (6m) and at individual near points (14.5 to 20.9 cm) in the younger group. With accommodation, lens thickness increased (mean±95% CI: 0.33±0.06mm) by a similar magnitude to the decrease in anterior chamber depth (0.31±0.07mm) and equatorial diameter (0.32±0.04mm) with a decrease in the radius of curvature of the posterior lens surface (0.58±0.30mm). Anterior lens surface shape could not be determined due to the overlapping region with the iris. Ciliary ring diameter decreased (0.44±0.17mm) with no decrease in circumlental space or forward ciliary body movement. With aging, lens thickness increased (mean±95% CI: 0.97±0.24mm) similar in magnitude to the sum of the decrease in anterior chamber depth (0.45±0.21mm) and increase in anterior segment depth (0.52±0.23mm). Equatorial lens diameter increased (0.28±0.23mm) with no change in the posterior lens surface radius of curvature. Ciliary ring diameter decreased (0.57±0.41mm) with reduced circumlental space (0.43±0.15mm) and no forward ciliary body movement. Accommodative changes support the Helmholtz theory of accommodation including an increase in posterior lens surface curvature. Certain aspects of aging changes mimic accommodation.

Sri Lanka in global medical research: a scientific analysis of the Sri Lankan research output during 2000-2009

Background Scientific research is an essential component in guiding improvements in health systems. There are no studies examining the Sri Lankan medical research output at international level. The present study evaluated the Sri Lankan research performance in medicine as reflected by the research publications output between years 2000-2009. Methods This study was based on Sri Lankan medical research publication data, retrieved from the SciVerse Scopus® from January 2000 to December 2009. The process of article selection was as follows: Affiliation - 'Sri Lanka' or 'Ceylon', Publication year - 'January 2000 to December 2009' and Subject area - 'Life and Health Sciences'. The articles identified were classified according to disease, medical speciality, institutions, major international collaborators, authors and journals. Results Sri Lanka's cumulative medical publications output between years 2000-2009 was 1,740 articles published in 160 different journals. The average annual publication growth rate was 9.1%. Majority of the articles were published in 'International' (n = 950, 54.6%) journals. Most articles were descriptive studies (n = 611, 35.1%), letters (n-345, 19.8%) and case reports (n = 311, 17.9%). The articles were authored by 148 different Sri Lankan authors from 146 different institutions. The three most prolific local institutions were Universities of; Colombo (n = 547), Kelaniya (n = 246) and Peradeniya (n = 222). Eighty four countries were found to have published collaborative papers with Sri Lankan authors during the last decade. UK was the largest collaborating partner (n = 263, 15.1%). Malaria (n = 75), Diabetes Mellitus (n = 55), Dengue (n = 53), Accidental injuries (n = 42) and Lymphatic filariasis (n = 40) were the major diseases studied. The 1,740 publications were cited 9,708 times, with an average citation of 5.6 per paper. The most cited paper had 203 citations, while there were 597 publications with no citations. The Sri Lankan authors' contribution to the global medical research output during the last decade was only 0.086%. Conclusion The Sri Lankan medical research output during the last decade is only a small fraction of the global research output. There it is a necessity to setup an enabling environment for research, with a proper vision, support, funds and training. In addition, collaborations across the region need to be strengthened to face common regional health challenges. Keywords: Sri Lanka, Medical research, Publication, Analysis

Occupational therapy students’ contribution to occasions of service during practice placements in health settings

Currently in the Australian higher education sector, the productivity benefits of occupational therapy clinical education placements are a contested issue. This article will report results of a study that developed a methodology for documenting time use during placements and investigated the productivity changes associated with occupational therapy clinical education placements in Queensland, Australia. Supervisors’ and students’ time use during placements and how this changed for supervisors compared to pre- and post-placement is also presented. Methods: Using a cohort survey design, participants were students from two Queensland universities, and their supervisors employed by Queensland Health. Time use was recorded in 30 minute blocks according to particular categories. Results: There was a significant increase in supervisors’ time spent in patient care activities (F = 94.0112,12.37 df, P < 0.001) between pre- and during placement (P < 0.001) and decrease between during and post-placement (P < 0.001). Supervisors’ time spent in all non-patient care activities was also significant (F = 4.5802,16 df, P = 0.027) increasing between pre- and during placement (P = 0.028). There was a significant decrease in supervisors’ time spent in placement activities (F = 5.1332,19.18 df, P = 0.016) from during to post-placement. Students spent more time than supervisors in patient care activities while on placement. Discussion: A novel method for reporting productivity and time-use changes during clinical education programs for occupational therapy has been applied. Supervisors spent considerable time in assessing and managing students and their clinical education role should be seen as core business in standard occupational therapy practice. This paper will contribute to future assessments of the economic.

Health Workforce Governance: Improved Access, Good Regulatory Practice, Safer Patients

With increasing recognition of the international market in health professionals and the impact of globalism on regulation, the governance of the health workforce is moving towards greater public engagement and increased transparency. This book discusses the challenges posed by these processes, such as improved access to health services and how structures can be reformed so that good practice is upheld and quality of service and patient safety are ensured.

Investigating the change in three dimensional deformity for idiopathic scoliosis using axially loaded MRI

Background: Adolescent idiopathic scoliosis is a complex three-dimensional deformity, involving a lateral deformity in the coronal plane and axial rotation of the vertebrae in the transverse plane. Gravitational loading plays an important biomechanical role in governing the coronal deformity, however, less is known about how they influence the axial deformity. This study investigates the change in three-dimensional deformity of a series of scoliosis patients due to compressive axial loading. Methods: Magnetic resonance imaging scans were obtained and coronal deformity (measured using the coronal Cobb angle) and axial rotations measured for a group of 18 scoliosis patients (Mean major Cobb angle was 43.4 o). Each patient was scanned in an unloaded and loaded condition while compressive loads equivalent to 50% body mass were applied using a custom developed compressive device. Findings: The mean increase in major Cobb angle due to compressive loading was 7.4 o (SD 3.5 o). The most axially rotated vertebra was observed at the apex of the structural curve and the largest average intravertebral rotations were observed toward the limits of the coronal deformity. A level-wise comparison showed no significant difference between the average loaded and unloaded vertebral axial rotations (intra-observer error = 2.56 o) or intravertebral rotations at each spinal level. Interpretation: This study suggests that the biomechanical effects of axial loading primarily influence the coronal deformity, with no significant change in vertebral axial rotation or intravertebral rotation observed between the unloaded and loaded condition. However, the magnitude of changes in vertebral rotation with compressive loading may have been too small to detect given the resolution of the current technique.

A biphasic scaffold design combined with cell sheet technology for simultaneous regeneration of alveolar bone/periodontal ligament complex

This study describes the design of a biphasic scaffold composed of a Fused Deposition Modeling scaffold (bone compartment) and an electrospun membrane (periodontal compartment) for periodontal regeneration. In order to achieve simultaneous alveolar bone and periodontal ligament regeneration a cell-based strategy was carried out by combining osteoblast culture in the bone compartment and placement of multiple periodontal ligament (PDL) cell sheets on the electrospun membrane. In vitro data showed that the osteoblasts formed mineralized matrix in the bone compartment after 21 days in culture and that the PDL cell sheet harvesting did not induce significant cell death. The cell-seeded biphasic scaffolds were placed onto a dentin block and implanted for 8 weeks in an athymic rat subcutaneous model. The scaffolds were analyzed by μCT, immunohistochemistry and histology. In the bone compartment, a more intense ALP staining was obtained following seeding with osteoblasts, confirming the μCT results which showed higher mineralization density for these scaffolds. A thin mineralized cementum-like tissue was deposited on the dentin surface for the scaffolds incorporating the multiple PDL cell sheets, as observed by H&E and Azan staining. These scaffolds also demonstrated better attachment onto the dentin surface compared to no attachment when no cell sheets were used. In addition, immunohistochemistry revealed the presence of CEMP1 protein at the interface with the dentine. These results demonstrated that the combination of multiple PDL cell sheets and a biphasic scaffold allows the simultaneous delivery of the cells necessary for in vivo regeneration of alveolar bone, periodontal ligament and cementum. © 2012 Elsevier Ltd.

ATF5, a possible regulator of osteogenic differentiation in human adipose-derived stem cells

The regulatory pathways involved in maintaining the pluripotency of embryonic stem cells are partially known, whereas the regulatory pathways governing adult stem cells and their "stem-ness" are characterized to an even lesser extent. We, therefore, screened the transcriptome profiles of 20 osteogenically induced adult human adipose-derived stem cell (ADSC) populations and investigated for putative transcription factors that could regulate the osteogenic differentiation of these ADSC. We studied a subgroup of donors' samples that had a disparate osteogenic response transcriptome from that of induced human fetal osteoblasts and the rest of the induced human ADSC samples. From our statistical analysis, we found activating transcription factor 5 (ATF5) to be significantly and consistently down-regulated in a randomized time-course study of osteogenically differentiated adipose-derived stem cells from human donor samples. Knockdown of ATF5 with siRNA showed an increased sensitivity to osteogenic induction. This evidence suggests a role for ATF5 in the regulation of osteogenic differentiation in adipose-derived stem cells. To our knowledge, this is the first report that indicates a novel role of transcription factors in regulating osteogenic differentiation in adult or tissue specific stem cells. © 2012 Wiley Periodicals, Inc.

Non-combinatorial library screening reveals subsite cooperativity and identifies new high-efficiency substrates for kallikrein-related peptidase 14

An array of substrates link the tryptic serine protease, kallikrein-related peptidase 14 (KLK14), to physiological functions including desquamation and activation of signaling molecules associated with inflammation and cancer. Recognition of protease cleavage sequences is driven by complementarity between exposed substrate motifs and the physicochemical signature of an enzyme's active site cleft. However, conventional substrate screening methods have generated conflicting subsite profiles for KLK14. This study utilizes a recently developed screening technique, the sparse matrix library, to identify five novel high-efficiency sequences for KLK14. The optimal sequence, YASR, was cleaved with higher efficiency (k(cat)/K(m)=3.81 ± 0.4 × 10(6) M(-1) s(-1)) than favored substrates from positional scanning and phage display by 2- and 10-fold, respectively. Binding site cooperativity was prominent among preferred sequences, which enabled optimal interaction at all subsites as indicated by predictive modeling of KLK14/substrate complexes. These simulations constitute the first molecular dynamics analysis of KLK14 and offer a structural rationale for the divergent subsite preferences evident between KLK14 and closely related KLKs, KLK4 and KLK5. Collectively, these findings highlight the importance of binding site cooperativity in protease substrate recognition, which has implications for discovery of optimal substrates and engineering highly effective protease inhibitors.