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.

Corneal changes following short-term miniscleral contact lens wear

Purpose To examine the influence of short-term miniscleral contact lens wear on corneal shape, thickness and anterior surface aberrations. Methods Scheimpflug imaging was captured before, immediately following and 3 hours after a short period (3 hours) of miniscleral contact lens wear for 10 young (mean 27 ± 5 years), healthy participants. Natural diurnal variations were considered by measuring baseline diurnal changes obtained on a separate control day without contact lens wear. Results Small but significant anterior corneal flattening was observed immediately following lens removal (overall mean 0.02 ± 0.03 mm, p < 0.001) which returned to baseline levels three hours after lens removal. During the three hour recovery period significant corneal thinning (-13.4 ± 10.5 μm) and posterior surface flattening (0.03 ± 0.02 mm) were also observed (both p < 0.01). The magnitude of posterior corneal flattening during recovery correlated with the amount of corneal thinning (r = 0.69, p = 0.03). Central corneal clearance (maximum tear reservoir depth) was not associated with corneal swelling following lens removal (r = -0.24, p > 0.05). An increase in lower-order corneal astigmatism Z(2,2) was also observed following lens wear (mean -0.144 ± 0.075 μm, p = 0.02). Conclusions Flattening of the anterior corneal surface was observed immediately following lens wear, while ‘rebound’ thinning and flattening of the posterior surface was evident following the recovery period. Modern miniscleral contact lenses that vault the cornea may slightly influence corneal shape and power but do not induce clinically significant corneal oedema during short-term wear.

Sensorineural hearing loss after treatment for head and neck cancer : a review of the literature

Background Definitive cisplatin-based is increasingly delivered as the treatment of choice for patients with head and neck cancer. Sensorineural hearing loss is a significant long term side effect of cisplatin-based chemoradiation and is associated with potential major quality of life issues for patients. Purpose The purpose of this manuscript was to review the mechanism behind sensorineural hearing loss in patients treated with cisplatin-based chemoradiation, including incidence, the contributions of radiotherapy and cisplatin to sensorineural hearing loss and the impact of the toxicity on patient quality of life. Methods Database searches were conducted through PubMed (National Centre for Biotechnology Information) and OvidSP Medline via the Queensland University of Technology Library website. General article searches were conducted through the online search engine Google Scholar. Articles were excluded if the full-text was unavailable, they were not in English or if they were published prior to 1990. Keywords included hearing loss, ototoxicity, cancer, quality of life, cisplatin and radiotherapy. Results/Discussion The total number of journal articles accessed was 290. Due to exclusion criteria, 129 articles were deemed appropriated for review. Findings indicated that sensorineural hearing loss is a significant, long term complication for patients treated with cisplatin-based chemoradiation. Current literature recognises the ototoxic effects of cisplatin and cranial irradiation as separate entities, however the impact of combined modality therapy on sensorineural hearing loss is seldom reported. Multiple risk factors for hearing loss are described, however there are contradictory opinions on incidence and severity and the exact radiation dose threshold responsible for inducing hearing loss in patients receiving combined modality therapy. Sensorineural hearing loss creates a subset of complexities for patients with head and neck cancer and that these patients face significant quality of life impairment. Conclusion The literature review identified that sensorineural hearing loss is a major quality of life issue for patients treated with cisplatin-based chemoradiation for head and neck cancer. Further investigation evaluating the contribution of cisplatin-based chemoradiation to sensorineural hearing loss and the subsequent effect on patient quality of life is warranted.

Art and the anxious city: Public art, public interest and the public good

While public art is often considered a key hallmark of a creative city, artworks in the public realm also have the capacity to act as lightening rods for social anxiety at times of perceived crisis. This paper considers recent debates about government-sponsored public art projects in Queensland in light of three international case studies: Rodin’s Thinker in Paris, Tilted Arc in New York and Vault in Melbourne. It considers whether consensus positions on public art are possible or desirable in light of issues of spatial control, and proposes that well-negotiated anxieties about public art may be an indicator of creative vibrancy and dynamism that will assist in the future understanding of Queensland’s experiment with government-mandated public art.

Anatomical modelling of the pregnant radiotherapy patient

This study aimed to take existing anatomical models of pregnant women, currently used for radiation pro-tection and nuclear medicine dose calculations, and adapt them for use in the calculation of fetal dose from external beam radiotherapy (EBRT). The models investigated were ‘KATJA’, which was provided as an MCNPX geometry file, and ‘RPI-P6’, which was provided in a simple, voxelized bina-ry format. In-house code was developed, to convert both mod-els into an `egsphant’ format, suitable for use with DOSXYZnrc. The geometries and densities of the resulting phantoms were evaluated and found to accurately represent the source data. As an example of the use of the phantoms, the delivery of a cranial EBRT treatment was simulated using the BEAMnrc and DOSXYZnrc Monte Carlo codes and the likely out-of-field doses to the fetus in each model was calculated. The results of these calculations showed good agreement (with-in one standard deviation) between the doses calculated in KATJA and PRI-P6, despite substantial anatomical differ-ences between the two models. For a 36 Gy prescription dose to a 233.2 cm3 target in the right brain, the mean doses calcu-lated in a region of interest covering the entire uterus were 1.0 +/- 0.6 mSv for KATJA and 1.3 +/- 0.9 mSv for RPI-P6. This work is expected to lead to more comprehensive studies of EBRT treatment plan design and its effects on fetal dose in the future.

Intellectual property and emerging technologies: The new biology

This unique and comprehensive collection investigates the challenges posed to intellectual property by recent paradigm shifts in biology. It explores the legal ramifications of emerging technologies, such as genomics, synthetic biology, stem cell research, nanotechnology, and biodiscovery. Extensive contributions examine recent controversial court decisions in patent law – such as Bilski v. Kappos, and the litigation over Myriad’s patents in respect of BRCA1 and BRCA2 – while other papers explore sui generis fields, such as access to genetic resources, plant breeders' rights, and traditional knowledge. The collection considers the potential and the risks of the new biology for global challenges – such as access to health-care, the protection of the environment and biodiversity, climate change, and food security. It also considers Big Science projects – such as biobanks, the 1000 Genomes Project, and the Doomsday Vault. The inter-disciplinary research brings together the work of scholars from Australia, Canada, Europe, the UK and the US and involves not only legal analysis of case law and policy developments, but also historical, comparative, sociological, and ethical methodologies. Intellectual Property and Emerging Technologies will appeal to policy-makers, legal practitioners, business managers, inventors, scientists and researchers.

Groucho homologue Grg5 interacts with the transcription factor Runx2-Cbfa1 and modulates its activity during postnatal growth in mice

Runx2-Cbfal, a Runt transcription factor, plays important roles during skeletal development. It is required for differentiation and function of osteoblasts. In its absence, chondrocyte hypertrophy is severely impaired and there is no vascularization of cartilage templates during skeletal development. These tissue-specific functions of Runx2 are likely to be dependent on its interaction with other proteins. We have therefore searched for proteins that may modulate the activity of Runx2. The yeast two-hybrid system was used to identify a groucho homologue, Grg5, as a Runx2-interacting protein. Grg5 enhances Runx2 activity in a cell culture-based assay and by analyses of postnatal growth in mice we demonstrate that Grg5 and Runx2 interact genetically. We also show that Runx2 haploinsufficiency in the absence of Grg5 results in a more severe delay in ossification of cranial sutures and fontanels than occurs with Runx2 haploinsufficiency on a wild-type background. Finally, we find shortening of the proliferative and hypertrophic zones, and expansion of the resting zone in the growth plates of Runx2(+/-)Grg5(-/-) mice that are associated with reduced Ihh expression and Indian hedgehog (Ihh) signaling. We therefore conclude that Grg5 enhances Runx2 activity in vivo.

Miniscleral lens wear influences corneal curvature and optics

Purpose Transient changes in corneal topography associated with soft and conventional or reverse geometry rigid contact lens wear have been well documented; however, only a few studies have examined the influence of scleral contact lens wear upon the cornea. Therefore, in this study, we examined the influence of modern miniscleral contact lenses, which land entirely on the sclera and overlying tissues, upon anterior corneal curvature and optics. Methods Anterior corneal topography and elevation data were acquired using Scheimpflug imaging (Pentacam HR, Oculus) immediately prior to and following 8 hours of miniscleral contact lens wear in 15 young healthy adults (mean age 22 ± 3 years, 8 East Asian, 7 Caucasian) with normal corneae. Corneal diurnal variations were accounted for using data collected on a dedicated measurement day without contact lens wear. Corneal clearance was quantified using an optical coherence tomographer (RS-3000, Nidek) following lens insertion and after 8 hours of lens wear. Results Although corneal clearance was maintained throughout the 8 hour lens wear period, significant corneal flattening (up to 0.08 ± 0.04 mm) was observed, primarily in the superior mid-peripheral cornea, which resulted in a slight increase in against-the-rule corneal astigmatism (mean +0.02/-0.15 x 94 for an 8 mm diameter). Higher order aberration terms of horizontal coma, vertical coma and spherical aberration all underwent significant changes for an 8 mm corneal diameter (p ≤ 0.01), which typically resulted in a decrease in RMS error values (mean change in total higher order RMS -0.035 ± 0.046 µm for an 8 mm diameter). There was no association between the magnitude of change in central or mid-peripheral corneal clearance during lens wear and the observed changes in corneal curvature (p > 0.05). However, Asian participants displayed a significantly greater reduction in corneal clearance (p = 0.04) and greater superior-nasal corneal flattening compared to Caucasians (p = 0.048). Conclusions Miniscleral contact lenses that vault the cornea induce significant changes in anterior corneal surface topography and higher order aberrations following 8 hours of lens wear. The region of greatest corneal flattening was observed in the superior-nasal mid-periphery, more so in Asian participants. Practitioners should be aware that corneal measurements obtained following miniscleral lens removal may mask underlying corneal steepening.

Hypoxic corneal changes following 8 hours of scleral contact lens wear

- Purpose To examine the change in corneal thickness and posterior curvature following 8 hours of miniscleral contact lens wear. - Methods Scheimpflug imaging (Pentacam HR, Oculus) was captured before, and immediately following, 8 hours of miniscleral contact lens wear for 15 young (mean age 22 ± 3 years), healthy participants with normal corneae. Natural diurnal variations were considered by measuring baseline corneal changes obtained on a separate control day without contact lens wear. - Results Over the central 6 mm of the cornea, a small, but highly statistically significant amount of edema was observed following 8 hours of miniscleral lens wear, after accounting for normal diurnal fluctuations (mean ± standard deviation percentage swelling 1.70 ± 0.98%, p < 0.0001). Posterior corneal topography remained stable following lens wear (-0.01 ± 0.07 mm steepening over the central 6 mm, p = 0.60). The magnitude of posterior corneal topographical changes following lens wear did not correlate with the extent of lens-related corneal edema (r = -0.16, p = 0.57). Similarly, the initial central corneal vault (maximum post-lens tear layer depth) was not associated with corneal swelling following lens removal (r = 0.27, p = 0.33). - Conclusions While a small amount of corneal swelling was induced following 8 hours of miniscleral lens wear (on average <2%), modern high Dk miniscleral contact lenses that vault the cornea do not induce clinically significant corneal edema or hypoxic related posterior corneal curvature changes during short-term wear. Longer-term studies of compromised eyes (e.g. corneal ectasia) are still required to inform the optimum lens and fitting characteristics for safe scleral lens wear to minimize corneal hypoxia.