Error and uncertainty of adult age estimation of the pubic symphysis in an Australian sub-population using computed tomography

After attending this presentation, attendees will gain awareness of: (1) the error and uncertainty associated with the application of the Suchey-Brooks (S-B) method of age estimation of the pubic symphysis to a contemporary Australian population; (2) the implications of sexual dimorphism and bilateral asymmetry of the pubic symphysis through preliminary geometric morphometric assessment; and (3) the value of three-dimensional (3D) autopsy data acquisition for creating forensic anthropological standards. This presentation will impact the forensic science community by demonstrating that, in the absence of demographically sound skeletal collections, post-mortem autopsy data provides an exciting platform for the construction of large contemporary ‘virtual osteological libraries’ for which forensic anthropological research can be conducted on Australian individuals. More specifically, this study assesses the applicability and accuracy of the S-B method to a contemporary adult population in Queensland, Australia, and using a geometric morphometric approach, provides an insight to the age-related degeneration of the pubic symphysis. Despite the prominent use of the Suchey-Brooks (1990) method of age estimation in forensic anthropological practice, it is subject to intrinsic limitations, with reports of differential inter-population error rates between geographical locations1-4. Australian forensic anthropology is constrained by a paucity of population specific standards due to a lack of repositories of documented skeletons. Consequently, in Australian casework proceedings, standards constructed from predominately American reference samples are applied to establish a biological profile. In the global era of terrorism and natural disasters, more specific population standards are required to improve the efficiency of medico-legal death investigation in Queensland. The sample comprises multi-slice computed tomography (MSCT) scans of the pubic symphysis (slice thickness: 0.5mm, overlap: 0.1mm) on 195 individuals of caucasian ethnicity aged 15-70 years. Volume rendering reconstruction of the symphyseal surface was conducted in Amira® (v.4.1) and quantitative analyses in Rapidform® XOS. The sample was divided into ten-year age sub-sets (eg. 15-24) with a final sub-set of 65-70 years. Error with respect to the method’s assigned means were analysed on the basis of bias (directionality of error), inaccuracy (magnitude of error) and percentage correct classification of left and right symphyseal surfaces. Morphometric variables including surface area, circumference, maximum height and width of the symphyseal surface and micro-architectural assessment of cortical and trabecular bone composition were quantified using novel automated engineering software capabilities. The results of this study demonstrated correct age classification utilizing the mean and standard deviations of each phase of the S-B method of 80.02% and 86.18% in Australian males and females, respectively. Application of the S-B method resulted in positive biases and mean inaccuracies of 7.24 (±6.56) years for individuals less than 55 years of age, compared to negative biases and mean inaccuracies of 5.89 (±3.90) years for individuals greater than 55 years of age. Statistically significant differences between chronological and S-B mean age were demonstrated in 83.33% and 50% of the six age subsets in males and females, respectively. Asymmetry of the pubic symphysis was a frequent phenomenon with 53.33% of the Queensland population exhibiting statistically significant (χ2 - p<0.01) differential phase classification of left and right surfaces of the same individual. Directionality was found in bilateral asymmetry, with the right symphyseal faces being slightly older on average and providing more accurate estimates using the S-B method5. Morphometric analysis verified these findings, with the left surface exhibiting significantly greater circumference and surface area than the right (p<0.05). Morphometric analysis demonstrated an increase in maximum height and width of the surface with age, with most significant changes (p<0.05) occurring between the 25-34 and 55-64 year age subsets. These differences may be attributed to hormonal components linked to menopause in females and a reduction in testosterone in males. Micro-architectural analysis demonstrated degradation of cortical composition with age, with differential bone resorption between the medial, ventral and dorsal surfaces of the pubic symphysis. This study recommends that the S-B method be applied with caution in medico-legal death investigations of unknown skeletal remains in Queensland. Age estimation will always be accompanied by error; therefore this study demonstrates the potential for quantitative morphometric modelling of age related changes of the pubic symphysis as a tool for methodological refinement, providing a rigor and robust assessment to remove the subjectivity associated with current pelvic aging methods.

Prevalence and predictors of refractive error in a genetically isolated population : the Norfolk Island Eye Study

BACKGROUND: We aimed to determine the prevalence and associations of refractive error on Norfolk Island. DESIGN: Population-based study on Norfolk Island, South Pacific. PARTICIPANTS: All permanent residents on Norfolk Island aged ≥ 15 years were invited to participate. METHODS: Patients underwent non-cycloplegic autorefraction, slit-lamp biomicroscope examination and biometry assessment. Only phakic eyes were analysed. MAIN OUTCOME MEASURES: Prevalence and multivariate associations of refractive error and myopia. RESULTS: There were 677 people (645 right phakic eyes, 648 left phakic eyes) aged ≥ 15 years were included in this study. Mean age of participants was 51.1 (standard deviation 15.7; range 15-81). Three hundred and seventy-six people (55.5%) were female. Adjusted to the 2006 Norfolk Island population, prevalence estimates of refractive error were as follows: myopia (mean spherical equivalent ≥ -1.0 D) 10.1%, hypermetropia (mean spherical equivalent ≥ 1.0 D) 36.6%, and astigmatism 17.7%. Significant independent predictors of myopia in the multivariate model were lower age (P < 0.001), longer axial length (P < 0.001), shallower anterior chamber depth (P = 0.031) and increased corneal curvature (P < 0.001). Significant independent predictors of refractive error were increasing age (P < 0.001), male gender (P = 0.009), Pitcairn ancestry (P = 0.041), cataract (P < 0.001), longer axial length (P < 0.001) and decreased corneal curvature (P < 0.001). CONCLUSIONS: The prevalence of myopia on Norfolk Island is lower than on mainland Australia, and the Norfolk Island population demonstrates ethnic differences in the prevalence estimates. Given the significant associations between refractive error and several ocular biometry characteristics, Norfolk Island may be a useful population in which to find the genetic basis of refractive error.

Patient error : a preliminary taxonomy

PURPOSE Current research on errors in health care focuses almost exclusively on system and clinician error. It tends to exclude how patients may create errors that influence their health. We aimed to identify the types of errors that patients can contribute and help manage, especially in primary care. METHODS Eleven nominal group interviews of patients and primary health care professionals were held in Auckland, New Zealand, during late 2007. Group members reported and helped to classify types of potential error by patients. We synthesized the ideas that emerged from the nominal groups into a taxonomy of patient error. RESULTS Our taxonomy is a 3-level system encompassing 70 potential types of patient error. The first level classifies 8 categories of error into 2 main groups: action errors and mental errors. The action errors, which result in part or whole from patient behavior, are attendance errors, assertion errors, and adherence errors. The mental errors, which are errors in patient thought processes, comprise memory errors, mindfulness errors, misjudgments, and—more distally—knowledge deficits and attitudes not conducive to health. CONCLUSION The taxonomy is an early attempt to understand and recognize how patients may err and what clinicians should aim to influence so they can help patients act safely. This approach begins to balance perspectives on error but requires further research. There is a need to move beyond seeing patient, clinician, and system errors as separate categories of error. An important next step may be research that attempts to understand how patients, clinicians, and systems interact to cocreate and reduce errors.

Mathematical modelling of soft callus formation in early murine bone repair

Fracture healing is a complicated coupling of many processes. Yet despite the apparent complexity, fracture repair is usually effective. There is, however, no comprehensive mathematical model addressing the multiple interactions of cells, cytokines and oxygen that includes extra-cellular matrix production and that results in the formation of the early stage soft callus. This thesis develops a one dimensional continuum transport model in the context of early fracture healing. Although fracture healing is a complex interplay of many local factors, critical components are identified and used to construct an hypothesis about regulation of the evolution of early callus formation. Multiple cell lines, cellular differentiation, oxygen levels and cytokine concentrations are examined as factors affecting this model of early bone repair. The model presumes diffusive and chemotactic cell migration mechanisms. It is proposed that the initial signalling regime and oxygen availability arising as consequences of bone fracture, are sufficient to determine the quantity and quality of early soft callus formation. Readily available software and purpose written algorithms have been used to obtain numerical solutions representative of various initial conditions. These numerical distributions of cellular populations reflect available histology obtained from murine osteotomies. The behaviour of the numerical system in response to differing initial conditions can be described by alternative in vivo healing pathways. An experimental basis, as illustrated in murine fracture histology, has been utilised to validate the mathematical model outcomes. The model developed in this thesis has potential for future extension, to incorporate processes leading to woven bone deposition, while maintaining the characteristics that regulate early callus formation.

Characterisation of microvasulature changes after closed soft tissue trauma by contrast enhanced micro-CT imaging

INTRODUCTION It is known that the vascular morphology and functionality are changed following closed soft tissue trauma (CSTT) [1], and bone fractures [2]. The disruption of blood vessels may lead to hypoxia and necrosis. Currently, most clinical methods for the diagnosis and monitoring of CSTT with or without bone fractures are primarily based on qualitative measures or practical experience, making the diagnosis subjective and inaccurate. There is evidence that CSTT and early vascular changes following the injury delay the soft tissue tissue and bone healing [3]. However, a precise qualitative and quantitative morphological assessment of vasculature changes after trauma is currently missing. In this research, we aim to establish a diagnostic framework to assess the 3D vascular morphological changes after standardized CSTT in a rat model qualitatively and quantitatively using contrast-enhanced micro-CT imaging. METHODS An impact device was used for the application of a controlled reproducible CSTT to the left thigh (Biceps Femoris) of anaesthetized male Wistar rats. After euthanizing the animals at 6 hours, 24 hours, 3 days, 7 days, or 14 days after trauma, CSTT was qualitatively evaluated by macroscopic visual observation of the skin and muscles. For visualization of the vasculature, the blood vessels of sacrificed rats were flushed with heparinised saline and then perfused with a radio-opaque contrast agent (Microfil, MV 122, Flowtech, USA) using an infusion pump. After allowing the contrast agent to polymerize overnight, both hind-limbs were dissected, and then the whole injured and contra-lateral control limbs were imaged using a micro-CT scanner (µCT 40, Scanco Medical, Switzerland) to evaluate the vascular morphological changes. Correlated biopsy samples were also taken from the CSTT region of both injured and control legs. The morphological parameters such as the vessel volume ratio (VV/TV), vessel diameter (V.D), spacing (V.Sp), number (V.N), connectivity (V.Conn) and the degree of anisotropy (DA) were then quantified by evaluating the scans of biopsy samples using the micro-CT imaging system. RESULTS AND DISCUSSION A qualitative evaluation of the CSTT has shown that the developed impact protocols were capable of producing a defined and reproducible injury within the region of interest (ROI), resulting in a large hematoma and moderate swelling in both lateral and medial sides of the injured legs. Also, the visualization of the vascular network using 3D images confirmed the ability to perfuse the large vessels and a majority of the microvasculature consistently (Figure 1). Quantification of the vascular morphology obtained from correlated biopsy samples has demonstrated that V.D and V.N and V.Sp were significantly higher in the injured legs 24 hours after impact in comparison with the control legs (p<0.05). The evaluation of the other time points is currently progressing. CONCLUSIONS The findings of this research will contribute to a better understanding of the changes to the vascular network architecture following traumatic injuries and during healing process. When interpreted in context of functional changes, such as tissue oxygenation, this will allow for objective diagnosis and monitoring of CSTT and serve as validation for future non-invasive clinical assessment modalities.

A novel characterisation model for microvasulature changes following closed soft tissue trauma using micro-CT imaging

INTRODUCTION There is evidence that the reduction of blood perfusion caused by closed soft tissue trauma (CSTT) delays the healing of the affected soft tissues and bone [1]. We hypothesise that the characterisation of vascular morphology changes (VMC) following injury allows us to determine the effect of the injury on tissue perfusion and thereby the severity of the injury. This research therefore aims to assess the VMC following CSTT in a rat model using contrast-enhanced micro-CT imaging. METHODOLOGY A reproducible CSTT was created on the left leg of anaesthetized rats (male, 12 weeks) with an impact device. After euthanizing the animals at 6 and 24 hours following trauma, the vasculature was perfused with a contrast agent (Microfil, Flowtech, USA). Both hind-limbs were dissected and imaged using micro-CT for qualitative comparison of the vascular morphology and quantification of the total vascular volume (VV). In addition, biopsy samples were taken from the CSTT region and scanned to compare morphological parameters of the vasculature between the injured and control limbs. RESULTS AND DISCUSSION While the visual observation of the hindlimb scans showed consistent perfusion of the microvasculature with microfil, enabling the identification of all major blood vessels, no clear differences in the vascular architecture were observed between injured and control limbs. However, overall VV within the region of interest (ROI)was  measured to be higher for the injured limbs after 24h. Also, scans of biopsy samples demonstrated that vessel diameter and density were higher in the injured legs 24h after impact. CONCLUSION We believe these results will contribute to the development of objective diagnostic methods for CSTT based on changes to the microvascular morphology as well as aiding in the validation of future non-invasive clinical assessment modalities.

Can vasculature changes be characterised morphologically after closed soft tissue trauma?

INTRODUCTION Closed soft tissue trauma (CSTT) can be the result of a blunt impact, or a prolonged crush injury and involves damage to the skin, muscles and the neurovascular system. It causes a variety of symptoms such as haematoma and in severe cases may result in hypoxia and necrosis. There is evidence that early vasculature changes following the injury delays the tissue healing [1]. However, a precise qualitative and quantitative morphological assessment of vasculature changes after trauma and the effect of this on CSTT healing is currently missing. Research aims: Developing an experimental rat model to characterise the structural changes to the vasculature after trauma qualitatively and quantitatively using micro CT. MATERIAL AND METHODS An impact device was developed to apply a controlled reproducible CSTT to the left thigh (Biceps Femoris) of anaesthetised rats [3]. After euthanizing the animals at 6 hours after trauma, CSTT was qualitatively evaluated by macroscopic observations of the skin and muscles. For vasculature visualisation, the blood vessels of sacrificed rats were flushed with heparinised saline and then perfused with a radio-opaque contrast agent (Microfil) using an infusion pump (Figure 4). The overall changes to the vasculature as a result of impact trauma were characterised qualitatively based on the 3D reconstructed images of the vasculature (Figure 5). For a smaller region of interest, the morphological parameters such as vessel thickness (diameter), spacing, and average number per volume were quantified using the scanner’s software. RESULTS AND DISCUSSION Visual observation of CSTT has revealed a haematoma in some animals (Figure 3). Micro CT images indicate good perfusion of the vasculature with contrast agent, allowing the major vessels to be identified (Figure 5). Qualitatively and quantitatively, no differences between injured and non-injured legs were observed at 6 h after trauma. Further time points of 12h, 24h, 3 days and 14 days after trauma will be characterised for identifying temporal changes of the vasculature during healing. Histomorphometical studies are required for validation of the results derived from the micro CT imaging. CONCLUSION AND FUTURE DIRECTION Findings of this research may contribute towards the establishment of a fundamental basis for the quantitative assessment and monitoring of CSTT based on microvasculature changes after trauma, which will ultimately allow for optimising the clinical treatment and improve patient outcomes.

Interocular corneal symmetry in refractive error groups

Purpose: To examine between eye differences in corneal higher order aberrations and topographical characteristics in a range of refractive error groups. Methods: One hundred and seventy subjects were recruited including; 50 emmetropic isometropes, 48 myopic isometropes (spherical equivalent anisometropia ≤ 0.75 D), 50 myopic anisometropes (spherical equivalent anisometropia ≥ 1.00 D) and 22 keratoconics. The corneal topography of each eye was captured using the E300 videokeratoscope (Medmont, Victoria, Australia) and analyzed using custom written software. All left eye data were rotated about the vertical midline to account for enantiomorphism. Corneal height data were used to calculate the corneal wavefront error using a ray tracing procedure and fit with Zernike polynomials (up to and including the eighth radial order). The wavefront was centred on the line of sight by using the pupil offset value from the pupil detection function in the videokeratoscope. Refractive power maps were analysed to assess corneal sphero-cylindrical power vectors. Differences between the more myopic (or more advanced eye for keratoconics) and the less myopic (advanced) eye were examined. Results: Over a 6 mm diameter, the cornea of the more myopic eye was significantly steeper (refractive power vector M) compared to the fellow eye in both anisometropes (0.10 ± 0.27 D steeper, p = 0.01) and keratoconics (2.54 ± 2.32 D steeper, p < 0.001) while no significant interocular difference was observed for isometropic emmetropes (-0.03 ± 0.32 D) or isometropic myopes (0.02 ± 0.30 D) (both p > 0.05). In keratoconic eyes, the between eye difference in corneal refractive power was greatest inferiorly (associated with cone location). Similarly, in myopic anisometropes, the more myopic eye displayed a central region of significant inferior corneal steepening (0.15 ± 0.42 D steeper) relative to the fellow eye (p = 0.01). Significant interocular differences in higher order aberrations were only observed in the keratoconic group for; vertical trefoil C(3,-3), horizontal coma C(3,1) secondary astigmatism along 45 C(4, -2) (p < 0.05) and vertical coma C(3,-1) (p < 0.001). The interocular difference in vertical pupil decentration (relative to the corneal vertex normal) increased with between eye asymmetry in refraction (isometropia 0.00 ± 0.09, anisometropia 0.03 ± 0.15 and keratoconus 0.08 ± 0.16 mm) as did the interocular difference in corneal vertical coma C (3,-1) (isometropia -0.006 ± 0.142, anisometropia -0.037 ± 0.195 and keratoconus -1.243 ± 0.936 μm) but only reached statistical significance for pair-wise comparisons between the isometropic and keratoconic groups. Conclusions: There is a high degree of corneal symmetry between the fellow eyes of myopic and emmetropic isometropes. Interocular differences in corneal topography and higher order aberrations are more apparent in myopic anisometropes and keratoconics due to regional (primarily inferior) differences in topography and between eye differences in vertical pupil decentration relative to the corneal vertex normal. Interocular asymmetries in corneal optics appear to be associated with anisometropic refractive development.

The role of chemotherapy in the treatment of adult soft tissue sarcomas

Adult soft tissue sarcomas are relatively rare tumours which are curable with radical surgery. Approximately 50% of patients will develop inoperable disease or metastases for which chemotherapy may be inappropriate. Only two cytotoxic agents - doxorubicin and ifosfamide - have activity in > 20% of patients. For both these agents there is evidence of a dose-response relationship. There is currently no good evidence that combination chemotherapy confers a clinical benefit compared with single agents. Outside a clinical trial, standard first-line therapy should be with single agent doxorubicin at a dose intensity ≥ 70 mg2 every 3 weeks. Approximately 25% of patients may be expected to respond to this regimen. There is the suggestion that responses may occur to ifosfamide in patients who progress on doxorubicin. The role of chemotherapy in the adjuvant setting remains uncertain. Several trials have suggested a modest relapse-free and overall survival benefit for the use of post-operative chemotherapy and a recent overview of 14 randomised trials confirms a small though significant benefit. These benefits have to be weighed against the toxicity of chemotherapy. The importance of treating all patients with soft tissue sarcomas in clinical trials is stressed. There is an urgent need to define new active agents to treat this disease.

Identification and elimination of a matrix-induced systematic error in LA–ICP–MS 206Pb/238U dating of zircon

Black et al. (2004) identified a systematic difference between LA–ICP–MS and TIMS measurements of 206Pb/238U in zircons, which they correlated with the incompatible trace element content of the zircon. We show that the offset between the LA–ICP–MS and TIMS measured 206Pb/238U correlates more strongly with the total radiogenic Pb than with any incompatible trace element. This suggests that the cause of the 206Pb/238U offset is related to differences in the radiation damage (alpha dose) between the reference and unknowns. We test this hypothesis in two ways. First, we show that there is a strong correlation between the difference in the LA–ICP–MS and TIMS measured 206Pb/238U and the difference in the alpha dose received by unknown and reference zircons. The LA–ICP–MS ages for the zircons we have dated can be as much as 5.1% younger than their TIMS age to 2.1% older, depending on whether the unknown or reference received the higher alpha dose. Second, we show that by annealing both reference and unknown zircons at 850 °C for 48 h in air we can eliminate the alpha-dose-induced differences in measured 206Pb/238U. This was achieved by analyzing six reference zircons a minimum of 16 times in two round robin experiments: the first consisting of unannealed zircons and the second of annealed grains. The maximum offset between the LA–ICP–MS and TIMS measured 206Pb/238U for the unannealed zircons was 2.3%, which reduced to 0.5% for the annealed grains, as predicted by within-session precision based on counting statistics. Annealing unknown zircons and references to the same state prior to analysis holds the promise of reducing the 3% external error for the measurement of 206Pb/238U of zircon by LA–ICP–MS, indicated by Klötzli et al. (2009), to better than 1%, but more analyses of annealed zircons by other laboratories are required to evaluate the true potential of the annealing method.

A stochastic thermostat algorithm for coarse-grained thermomechanical modeling of large-scale soft matters : theory and application to microfilaments

As all-atom molecular dynamics method is limited by its enormous computational cost, various coarse-grained strategies have been developed to extend the length scale of soft matters in the modeling of mechanical behaviors. However, the classical thermostat algorithm in highly coarse-grained molecular dynamics method would underestimate the thermodynamic behaviors of soft matters (e.g. microfilaments in cells), which can weaken the ability of materials to overcome local energy traps in granular modeling. Based on all-atom molecular dynamics modeling of microfilament fragments (G-actin clusters), a new stochastic thermostat algorithm is developed to retain the representation of thermodynamic properties of microfilaments at extra coarse-grained level. The accuracy of this stochastic thermostat algorithm is validated by all-atom MD simulation. This new stochastic thermostat algorithm provides an efficient way to investigate the thermomechanical properties of large-scale soft matters.

Error modeling and calibration of exteroceptive sensors for accurate mapping applications

Reliable robotic perception and planning are critical to performing autonomous actions in uncertain, unstructured environments. In field robotic systems, automation is achieved by interpreting exteroceptive sensor information to infer something about the world. This is then mapped to provide a consistent spatial context, so that actions can be planned around the predicted future interaction of the robot and the world. The whole system is as reliable as the weakest link in this chain. In this paper, the term mapping is used broadly to describe the transformation of range-based exteroceptive sensor data (such as LIDAR or stereo vision) to a fixed navigation frame, so that it can be used to form an internal representation of the environment. The coordinate transformation from the sensor frame to the navigation frame is analyzed to produce a spatial error model that captures the dominant geometric and temporal sources of mapping error. This allows the mapping accuracy to be calculated at run time. A generic extrinsic calibration method for exteroceptive range-based sensors is then presented to determine the sensor location and orientation. This allows systematic errors in individual sensors to be minimized, and when multiple sensors are used, it minimizes the systematic contradiction between them to enable reliable multisensor data fusion. The mathematical derivations at the core of this model are not particularly novel or complicated, but the rigorous analysis and application to field robotics seems to be largely absent from the literature to date. The techniques in this paper are simple to implement, and they offer a significant improvement to the accuracy, precision, and integrity of mapped information. Consequently, they should be employed whenever maps are formed from range-based exteroceptive sensor data. © 2009 Wiley Periodicals, Inc.