Sensitivity of an Elekta iView GT a-Si EPID model to delivery errors for pre-treatment verification of IMRT fields

A Monte Carlo model of an Elekta iViewGT amorphous silicon electronic portal imaging device (a-Si EPID) has been validated for pre-treatment verification of clinical IMRT treatment plans. The simulations involved the use of the BEAMnrc and DOSXYZnrc Monte Carlo codes to predict the response of the iViewGT a-Si EPID model. The predicted EPID images were compared to the measured images obtained from the experiment. The measured EPID images were obtained by delivering a photon beam from an Elekta Synergy linac to the Elekta iViewGT a-Si EPID. The a-Si EPID was used with no additional build-up material. Frame averaged EPID images were acquired and processed using in-house software. The agreement between the predicted and measured images was analyzed using the gamma analysis technique with acceptance criteria of 3% / 3 mm. The results show that the predicted EPID images for four clinical IMRT treatment plans have a good agreement with the measured EPID signal. Three prostate IMRT plans were found to have an average gamma pass rate of more than 95.0 % and a spinal IMRT plan has the average gamma pass rate of 94.3 %. During the period of performing this work a routine MLC calibration was performed and one of the IMRT treatments re-measured with the EPID. A change in the gamma pass rate for one field was observed. This was the motivation for a series of experiments to investigate the sensitivity of the method by introducing delivery errors, MLC position and dosimetric overshoot, into the simulated EPID images. The method was found to be sensitive to 1 mm leaf position errors and 10% overshoot errors.

Integrin-linked kinase as a target for ERG-mediated invasive properties in prostate cancer models

Approximately half of prostate cancers (PCa) carry TMPRSS2-ERG translocations; however, the clinical impact of this genomic alteration remains enigmatic. Expression of v-ets erythroblastosis virus E26 oncogene like (avian) gene (ERG) promotes prostatic epithelial dysplasia in transgenic mice and acquisition of epithelial-to-mesenchymal transition (EMT) characteristics in human prostatic epithelial cells (PrECs). To explore whether ERG-induced EMT in PrECs was associated with therapeutically targetable transformation characteristics, we established stable populations of BPH-1, PNT1B and RWPE-1 immortalized human PrEC lines that constitutively express flag-tagged ERG3 (fERG). All fERG-expressing populations exhibited characteristics of in vitro and in vivo transformation. Microarray analysis revealed >2000 commonly dysregulated genes in the fERG-PrEC lines. Functional analysis revealed evidence that fERG cells underwent EMT and acquired invasive characteristics. The fERG-induced EMT transcript signature was exemplified by suppressed expression of E-cadherin and keratins 5, 8, 14 and 18; elevated expression of N-cadherin, N-cadherin 2 and vimentin, and of the EMT transcriptional regulators Snail, Zeb1 and Zeb2, and lymphoid enhancer-binding factor-1 (LEF-1). In BPH-1 and RWPE-1-fERG cells, fERG expression is correlated with increased expression of integrin-linked kinase (ILK) and its downstream effectors Snail and LEF-1. Interfering RNA suppression of ERG decreased expression of ILK, Snail and LEF-1, whereas small interfering RNA suppression of ILK did not alter fERG expression. Interfering RNA suppression of ERG or ILK impaired fERG-PrEC Matrigel invasion. Treating fERG-BPH-1 cells with the small molecule ILK inhibitor, QLT-0267, resulted in dose-dependent suppression of Snail and LEF-1 expression, Matrigel invasion and reversion of anchorage-independent growth. These results suggest that ILK is a therapeutically targetable mediator of ERG-induced EMT and transformation in PCa.

Efficiently capturing large, complex cultural heritage sites with a handheld mobile 3D laser mapping system

Accurate three-dimensional representations of cultural heritage sites are highly valuable for scientific study, conservation, and educational purposes. In addition to their use for archival purposes, 3D models enable efficient and precise measurement of relevant natural and architectural features. Many cultural heritage sites are large and complex, consisting of multiple structures spatially distributed over tens of thousands of square metres. The process of effectively digitising such geometrically complex locations requires measurements to be acquired from a variety of viewpoints. While several technologies exist for capturing the 3D structure of objects and environments, none are ideally suited to complex, large-scale sites, mainly due to their limited coverage or acquisition efficiency. We explore the use of a recently developed handheld mobile mapping system called Zebedee in cultural heritage applications. The Zebedee system is capable of efficiently mapping an environment in three dimensions by continually acquiring data as an operator holding the device traverses through the site. The system was deployed at the former Peel Island Lazaret, a culturally significant site in Queensland, Australia, consisting of dozens of buildings of various sizes spread across an area of approximately 400 × 250 m. With the Zebedee system, the site was scanned in half a day, and a detailed 3D point cloud model (with over 520 million points) was generated from the 3.6 hours of acquired data in 2.6 hours. We present results demonstrating that Zebedee was able to accurately capture both site context and building detail comparable in accuracy to manual measurement techniques, and at a greatly increased level of efficiency and scope. The scan allowed us to record derelict buildings that previously could not be measured because of the scale and complexity of the site. The resulting 3D model captures both interior and exterior features of buildings, including structure, materials, and the contents of rooms.

Submission: Towards a Stronger and More Efficient IP Rights System : Getting the Balance Right

1. In March 2009, the Australian Government, through IP Australia its administrator of Intellectual Property Rights (IPR) acquired by registration or grant, issued two consultation papers for comment by interested stakeholders. 2. The Consultation Papers have invited written submissions directed towards the object of the paper, namely encouraging discussion on certain proposed changes and their impact on business and innovation. 3. I understand the invitation to make written submissions is predominantly in the areas raised by the Consultation Papers and the questions posed. However, I have made a brief reference to several other areas of concern with the current Australian patent law, which in my opinion inhibit innovation and therefore come under the wider agenda of the government to work toward a stronger and more efficient IP rights system. 4. In this regard, the Consultation Papers indicate that if the IPR are less likely to be invalidated and more likely to be enforced, this confidence will reflect in a greater investment in research leading to innovation. 5. This submission relates to the Balance Paper.

Characterisation of a cell wall-anchored protein of Staphylococcus saprophyticus associated with linoleic acid resistance

The Gram-positive bacterium Staphylococcus saprophyticus is the second most frequent causative agent of community-acquired urinary tract infections (UTI), accounting for up to 20% of cases. A common feature of staphylococci is colonisation of the human skin. This involves survival against innate immune defenses including antibacterial unsaturated free fatty acids such as linoleic acid which act by disrupting bacterial cell membranes. Indeed, S. saprophyticus UTI is usually preceded by perineal skin colonisation.

Temporal Characterization of Ossification of the Crania in Australian Subadults: New standards for Age Estimation using Computed Tomography

After attending this presentation, attendees will gain awareness of the ontogeny of cranial maturation, specifically: (1) the fusion timings of primary ossification centers in the basicranium; and (2) the temporal pattern of closure of the anterior fontanelle, to develop new population-specific age standards for medicolegal death investigation of Australian subadults. This presentation will impact the forensic science community by demonstrating the potential of a contemporary forensic subadult Computed Tomography (CT) database of cranial scans and population data, to recalibrate existing standards for age estimation and quantify growth and development of Australian children. This research welcomes a study design applicable to all countries faced with paucity in skeletal repositories. Accurate assessment of age-at-death of skeletal remains represents a key element in forensic anthropology methodology. In Australian casework, age standards derived from American reference samples are applied in light of scarcity in documented Australian skeletal collections. Currently practitioners rely on antiquated standards, such as the Scheuer and Black1 compilation for age estimation, despite implications of secular trends and population variation. Skeletal maturation standards are population specific and should not be extrapolated from one population to another, while secular changes in skeletal dimensions and accelerated maturation underscore the importance of establishing modern standards to estimate age in modern subadults. Despite CT imaging becoming the gold standard for skeletal analysis in Australia, practitioners caution the application of forensic age standards derived from macroscopic inspection to a CT medium, suggesting a need for revised methodologies. Multi-slice CT scans of subadult crania and cervical vertebrae 1 and 2 were acquired from 350 Australian individuals (males: n=193, females: n=157) aged birth to 12 years. The CT database, projected at 920 individuals upon completion (January 2014), comprises thin-slice DICOM data (resolution: 0.5/0.3mm) of patients scanned since 2010 at major Brisbane Childrens Hospitals. DICOM datasets were subject to manual segmentation, followed by the construction of multi-planar and volume rendering cranial models, for subsequent scoring. The union of primary ossification centers of the occipital bone were scored as open, partially closed or completely closed; while the fontanelles, and vertebrae were scored in accordance with two stages. Transition analysis was applied to elucidate age at transition between union states for each center, and robust age parameters established using Bayesian statistics. In comparison to reported literature, closure of the fontanelles and contiguous sutures in Australian infants occur earlier than reported, with the anterior fontanelle transitioning from open to closed at 16.7±1.1 months. The metopic suture is closed prior to 10 weeks post-partum and completely obliterated by 6 months of age, independent of sex. Utilizing reverse engineering capabilities, an alternate method for infant age estimation based on quantification of fontanelle area and non-linear regression with variance component modeling will be presented. Closure models indicate that the greatest rate of change in anterior fontanelle area occurs prior to 5 months of age. This study complements the work of Scheuer and Black1, providing more specific age intervals for union and temporal maturity of each primary ossification center of the occipital bone. For example, dominant fusion of the sutura intra-occipitalis posterior occurs before 9 months of age, followed by persistence of a hyaline cartilage tongue posterior to the foramen magnum until 2.5 years; with obliteration at 2.9±0.1 years. Recalibrated age parameters for the atlas and axis are presented, with the anterior arch of the atlas appearing at 2.9 months in females and 6.3 months in males; while dentoneural, dentocentral and neurocentral junctions of the axis transitioned from non-union to union at 2.1±0.1 years in females and 3.7±0.1 years in males. These results are an exemplar of significant sexual dimorphism in maturation (p<0.05), with girls exhibiting union earlier than boys, justifying the need for segregated sex standards for age estimation. Studies such as this are imperative for providing updated standards for Australian forensic and pediatric practice and provide an insight into skeletal development of this population. During this presentation, the utility of novel regression models for age estimation of infants will be discussed, with emphasis on three-dimensional modeling capabilities of complex structures such as fontanelles, for the development of new age estimation methods.

Multiscale features and information extraction of online strain for long-span bridges

The strain data acquired from structural health monitoring (SHM) systems play an important role in the state monitoring and damage identification of bridges. Due to the environmental complexity of civil structures, a better understanding of the actual strain data will help filling the gap between theoretical/laboratorial results and practical application. In the study, the multi-scale features of strain response are first revealed after abundant investigations on the actual data from two typical long-span bridges. Results show that, strain types at the three typical temporal scales of 10^5, 10^2 and 10^0 sec are caused by temperature change, trains and heavy trucks, and have their respective cut-off frequency in the order of 10^-2, 10^-1 and 10^0 Hz. Multi-resolution analysis and wavelet shrinkage are applied for separating and extracting these strain types. During the above process, two methods for determining thresholds are introduced. The excellent ability of wavelet transform on simultaneously time-frequency analysis leads to an effective information extraction. After extraction, the strain data will be compressed at an attractive ratio. This research may contribute to a further understanding of actual strain data of long-span bridges; also, the proposed extracting methodology is applicable on actual SHM systems.

Force-deformation properties of the human heel pad during barefoot walking

Introduction: The plantar heel pad is a specialized fibroadipose tissue that attenuates and, in part, dissipates the impact energy associated with heel strike. Although near maximal deformation of the heel pad has been shown during running, in vivo measurement of the deformation and structural properties of the heel pad during walking remains largely unexplored. This study employed a fluoroscope, synchronized with a pressure platform, to obtain force–deformation data for the heel pad during walking. Methods: Dynamic lateral foot radiographs were acquired from 6 male and 10 female adults (age, 45 ± 10 yrs; height, 1.66 ± 0.10 m; and weight, 80.7 ± 10.8 kg), while walking barefoot at preferred speeds. The inferior aspect of the calcaneus was digitized and the sagittal thickness and deformation of the heel pad relative to the support surface calculated. Simultaneous measurement of the peak force beneath the heel was used to estimate the principal structural properties of the heel pad. Results: Transient loading profiles associated with walking induced rapidly changing deformation rates in the heel pad and resulted in irregular load–deformation curves. The initial stiffness (32 ± 11 N.mm-1) of the heel pad was an order of magnitude lower than its final stiffness (212 ± 125 N.mm-1) and on average, only 1.0 J of energy was dissipated by the heel pad with each step during walking. Peak deformation (10.3 mm) approached that predicted for the limit of pain tolerance (10.7 mm). Conclusion: These findings suggest the heel pad operates close to its pain threshold even at speeds encountered during barefoot walking and provides insight as to why barefoot runners may adopt ‘forefoot’ strike patterns that minimize heel loading.

Running shoes increase Achilles tendon load in walking : an acoustic propagation study

Background: Footwear remains a prime candidate for the prevention and rehabilitation of Achilles tendinopathy as it is thought to decrease tension in the tendon through elevation of the heel. However, evidence for this effect is equivocal. Purpose: This study used an acoustic transmission technique to investigate the effect of running shoes on Achilles tendon loading during barefoot and shod walking. Methods: Acoustic velocity was measured in the Achilles tendon of twelve recreationally–active males (age, 31±9 years; height, 1.78±0.06 m; weight, 81.0±16.9 kg) during barefoot and shod walking at matched self–selected speed (3.4±0.7 km/h). Standard running shoes incorporating a 10– mm heel offset were used. Vertical ground reaction force and spatiotemporal parameters were determined with an instrumented treadmill. Axial acoustic velocity in the Achilles tendon was measured using a custom built ultrasonic device. All data were acquired at a rate of 100 Hz during 10s of steady–state walking. Statistical comparisons between barefoot and shod conditions were made using paired t–tests and repeated measure ANOVAs. Results: Acoustic velocity in the Achilles tendon was highly reproducible and was typified by two maxima (P1, P2) and minima (M1, M2) during walking. Footwear resulted in a significant increase in step length, stance duration and peak vertical ground reaction force compared to barefoot walking. Peak acoustic velocity in the Achilles tendon (P1, P2) was significantly higher with running shoes. Conclusions: Peak acoustic velocity in the Achilles tendon was higher with footwear, suggesting that standard running shoes with a 10–mm heel offset increase tensile load in the Achilles tendon. Although further research is required, these findings question the therapeutic role of standard running shoes in Achilles tendinopathy.

Near infrared spectroscopy for rapid determination of Mankin score components : a potential tool for quantitative characterization of articular cartilage at surgery

PURPOSE The purpose of this study was to demonstrate the potential of near infrared (NIR) spectroscopy for characterizing the health and degenerative state of articular cartilage based on the components of the Mankin score. METHODS Three models of osteoarthritic degeneration induced in laboratory rats by anterior cruciate ligament (ACL) transection, meniscectomy (MSX), and intra-articular injection of monoiodoacetate (1 mg) (MIA) were used in this study. Degeneration was induced in the right knee joint; each model group consisted of 12 rats (N = 36). After 8 weeks, the animals were euthanized and knee joints were collected. A custom-made diffuse reflectance NIR probe of 5-mm diameter was placed on the tibial and femoral surfaces, and spectral data were acquired from each specimen in the wave number range of 4,000 to 12,500 cm(-1). After spectral data acquisition, the specimens were fixed and safranin O staining (SOS) was performed to assess disease severity based on the Mankin scoring system. Using multivariate statistical analysis, with spectral preprocessing and wavelength selection technique, the spectral data were then correlated to the structural integrity (SI), cellularity (CEL), and matrix staining (SOS) components of the Mankin score for all the samples tested. RESULTS ACL models showed mild cartilage degeneration, MSX models had moderate degeneration, and MIA models showed severe cartilage degenerative changes both morphologically and histologically. Our results reveal significant linear correlations between the NIR absorption spectra and SI (R(2) = 94.78%), CEL (R(2) = 88.03%), and SOS (R(2) = 96.39%) parameters of all samples in the models. In addition, clustering of the samples according to their level of degeneration, with respect to the Mankin components, was also observed. CONCLUSIONS NIR spectroscopic probing of articular cartilage can potentially provide critical information about the health of articular cartilage matrix in early and advanced stages of osteoarthritis (OA). CLINICAL RELEVANCE This rapid nondestructive method can facilitate clinical appraisal of articular cartilage integrity during arthroscopic surgery.

Fuzzy logic to evaluate driving maneuvers: An integrated approach to improve training

Driver training is one of the interventions aimed at mitigating the number of crashes that involve novice drivers. Our failure to understand what is really important for learners, in terms of risky driving, is one of the many drawbacks restraining us to build better training programs. Currently, there is a need to develop and evaluate Advanced Driving Assistance Systems that could comprehensively assess driving competencies. The aim of this paper is to present a novel Intelligent Driver Training System (IDTS) that analyses crash risks for a given driving situation, providing avenues for improvement and personalisation of driver training programs. The analysis takes into account numerous variables acquired synchronously from the Driver, the Vehicle and the Environment (DVE). The system then segments out the manoeuvres within a drive. This paper further presents the usage of fuzzy set theory to develop the safety inference rules for each manoeuvre executed during the drive. This paper presents a framework and its associated prototype that can be used to comprehensively view and assess complex driving manoeuvres and then provide a comprehensive analysis of the drive used to give feedback to novice drivers.

Gray matter deficits, mismatch negativity, and outcomes in schizophrenia

Reduced mismatch negativity (MMN) in response to auditory change is a well-established finding in schizophrenia and has been shown to be correlated with impaired daily functioning, rather than with hallmark signs and symptoms of the disorder. In this study, we investigated (1) whether the relationship between reduced MMN and impaired daily functioning is mediated by cortical volume loss in temporal and frontal brain regions in schizophrenia and (2) whether this relationship varies with the type of auditory deviant generating MMN. MMN in response to duration, frequency, and intensity deviants was recorded from 18 schizophrenia subjects and 18 pairwise age- and gender-matched healthy subjects. Patients’ levels of global functioning were rated on the Social and Occupational Functioning Assessment Scale. High-resolution structural magnetic resonance scans were acquired to generate average cerebral cortex and temporal lobe models using cortical pattern matching. This technique allows accurate statistical comparison and averaging of cortical measures across subjects, despite wide variations in gyral patterns. MMN amplitude was reduced in schizophrenia patients and correlated with their impaired day-to-day function level. Only in patients, bilateral gray matter reduction in Heschl’s gyrus, as well as motor and executive regions of the frontal cortex, correlated with reduced MMN amplitude in response to frequency deviants, while reduced gray matter in right Heschl’s gyrus also correlated with reduced MMN to duration deviants. Our findings further support the importance of MMN reduction in schizophrenia by linking frontotemporal cerebral gray matter pathology to an automatically generated event-related potential index of daily functioning.

Transforming the core business of teaching and learning in classrooms through ICT

Information and Communication Technology (ICT) has become an integral part of societies across the globe. This study demonstrates how successful technology integration by 10 experienced teachers in an Australian high school was dependent on teacher-driven change and innovation that influenced the core business of teaching and learning. The teachers were subject specialists across a range of disciplines, engaging their Year Eight students (aged 12–14 years) in the Technology Rich Classrooms programme. Two classrooms were renovated to accommodate the newly acquired computer hardware. The first classroom adopted a one-to-one desktop model with all the computers with Internet access arranged in a front-facing pattern. The second classroom had computers arranged in small groups. The students also used Blackboard to access learning materials after school hours. Qualitative data were gathered from teachers mainly through structured and unstructured interviews and a range of other approaches to ascertain their perceptions of the new initiative. This investigation showed that ICT was impacting positively on the core business of teaching and learning. Through the support of the school leadership team, the built environment was enabling teachers to use ICT. This influenced their pedagogical approaches and the types of learning activities they designed and implemented. As a consequence, teachers felt that students were motivated and benefited through this experience.

Interventions to control nosocomial infections : study designs and statistical issues

There is a wide range of potential study designs for intervention studies to decrease nosocomial infections in hospitals. The analysis is complex due to competing events, clustering, multiple timescales and time-dependent period and intervention variables. This review considers the popular pre-post quasi-experimental design and compares it with randomized designs. Randomization can be done in several ways: randomization of the cluster [intensive care unit (ICU) or hospital] in a parallel design; randomization of the sequence in a cross-over design; and randomization of the time of intervention in a stepped-wedge design. We introduce each design in the context of nosocomial infections and discuss the designs with respect to the following key points: bias, control for nonintervention factors, and generalizability. Statistical issues are discussed. A pre-post-intervention design is often the only choice that will be informative for a retrospective analysis of an outbreak setting. It can be seen as a pilot study with further, more rigorous designs needed to establish causality. To yield internally valid results, randomization is needed. Generally, the first choice in terms of the internal validity should be a parallel cluster randomized trial. However, generalizability might be stronger in a stepped-wedge design because a wider range of ICU clinicians may be convinced to participate, especially if there are pilot studies with promising results. For analysis, the use of extended competing risk models is recommended.

Multilevel competing risk models to evaluate the risk of nosocomial infection

Introduction Risk factor analyses for nosocomial infections (NIs) are complex. First, due to competing events for NI, the association between risk factors of NI as measured using hazard rates may not coincide with the association using cumulative probability (risk). Second, patients from the same intensive care unit (ICU) who share the same environmental exposure are likely to be more similar with regard to risk factors predisposing to a NI than patients from different ICUs. We aimed to develop an analytical approach to account for both features and to use it to evaluate associations between patient- and ICU-level characteristics with both rates of NI and competing risks and with the cumulative probability of infection. Methods We considered a multicenter database of 159 intensive care units containing 109,216 admissions (813,739 admission-days) from the Spanish HELICS-ENVIN ICU network. We analyzed the data using two models: an etiologic model (rate based) and a predictive model (risk based). In both models, random effects (shared frailties) were introduced to assess heterogeneity. Death and discharge without NI are treated as competing events for NI. Results There was a large heterogeneity across ICUs in NI hazard rates, which remained after accounting for multilevel risk factors, meaning that there are remaining unobserved ICU-specific factors that influence NI occurrence. Heterogeneity across ICUs in terms of cumulative probability of NI was even more pronounced. Several risk factors had markedly different associations in the rate-based and risk-based models. For some, the associations differed in magnitude. For example, high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with modest increases in the rate of nosocomial bacteremia, but large increases in the risk. Others differed in sign, for example respiratory vs cardiovascular diagnostic categories were associated with a reduced rate of nosocomial bacteremia, but an increased risk. Conclusions A combination of competing risks and multilevel models is required to understand direct and indirect risk factors for NI and distinguish patient-level from ICU-level factors.