Explorations into Appendicular Ontogeny using a Cross-Sectional, Contemporary U.S. Sample

Investigations into the subadult skeleton have been restricted by sample availability in biological anthropology. Alternatively, the same source of longitudinal data has been repeatedly used, which does not reflect the variability of growth and development (i.e., ontogeny) or the United States (U.S.) population. Small and/or homogenous samples have often resulted in limited or inappropriate modeling choices to investigate the growth and development and variation of the subadult skeleton. Recent technological advancements have made virtual anthropology possible. The use of computed tomography (CT) scans has opened the doors to increasing sample sizes of minority groups and in turn increasing the variation of skeletal information. One repository, the Subadult Virtual Anthropology Database (SVAD), has focused on increasing and diversifying subadult skeletal data to increase the possibilities of subadult research in biological anthropology. The articles in this (non)dissertation collection use the SVAD (M=610, F=416) and the Forensic Anthropology Data Bank (FDB; M=285, F=161) to evaluate three different perspectives of appendicular (i.e., long bone) ontogeny: absolute, relative, and index. First, relative long bone lengths and nonlinear modeling are used as the first-ever evaluation of long bone growth through adult stabilization. Second, the brachial and crural indices are used to explore the chronological ontogenetic trajectories of each index and their ecogeographic patterns. Third, absolute long bone breadth and length measurements are used to create linear and nonlinear equations for estimating subadult stature for forensic application. In doing so, this is the first comprehensive collection of studies that explore three distinct perspectives of long bone ontogeny and variation from the same source of subadult skeletal data, demonstrating the need for additional contemporary subadult samples and novel modeling approaches

Characterisation of disuse-related osteoporosis in an animal model of spinal cord injury

Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.;These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.;Bone quality is assessed using i) ex vivo micro-Computed Tomography (μCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.;Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.;At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.;Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.;The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.;Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected.Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.;These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.;Bone quality is assessed using i) ex vivo micro-Computed Tomography (μCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.;Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.;At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.;Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.;The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.;Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected

A Quantitative Genetic Analysis of Limb Segment Morphology in Humans and Other Primates: Genetic Variance, Morphological Integration, and Linkage Analysis

Limb segment lengths (and, by extension, limb proportions) are widely studied postcranial features in biological anthropology due to the seemingly consistent phenotypic patterning among human and fossil hominin groups. This patterning, widely presumed to be the result of adaptation to thermoregulatory efficiency, has led to the assumption among biological anthropologists that limb proportions in humans are phenotypically stable unless long periods of extreme environmental conditions force adaptive change. Because these traits are considered stable, they have been used to inform multiple areas of anthropological inquiry, including investigations of phylogenetic relationships and fossil species identification, locomotor behavior and the evolution of bipedalism, and migration patterns. The problem with this assumption is that phenotypic patterns may not accurately reflect evolutionary processes, and even if they do, there is no reason to expect phenotype to respond to natural selection solely. Investigations of phenotypic variation need to incorporate genetic variation and covariation to better understand the processes that produced observable patterns, including evolutionary processes. However, the incorporation of genetic parameters is often difficult given that knowledge of familial relationships are required. Therefore, the goal of this project is to use a quantitative genetics approach to estimate the genetic variance and covariance in limb segment lengths and then begin the task of identifying genes which may influence this normal variation. These tasks are accomplished using multiple large, pedigreed samples of primate species, including humans. Linkage analysis on a baboon sample, a well-accepted model organism for humans, is used to identify regions of the genome which may influence limb segment variation. The results presented here suggest that 1) while patterns of genetic and phenotypic variance and covariance across limb segments are broadly similar, there are differences in the details, and 2) while patterns of genetic and phenotypic variance and covariance within and among limb segments generally adhere to expectations set forth by developmental and evolutionary-based hypotheses, there are exceptions. Additionally, several genomic regions are identified which influence limb segment variation. Thus, biological anthropologists must use caution in their assumptions and interpretations regarding limb segment lengths and limb proportions in humans and other primates

Unraveling the population history of the Xiongnu to explain molecular and archaeological models of prehistoric Mongolia

This dissertation explores the prehistory of Mongolia during a time when nomadic tribes created the world\u27s first steppe empire in Inner Asia. These aggregated tribes, known to Chinese historians as Xiongnu, ruled from the 3rd century BCE to the 2nd century CE. They came to define steppe polity construction later used by the Mongol Empire under the reign of Chinggis Khan. These nomads moved extensively over the eastern steppe and interacted, both in trade and intermarriage, with peoples from southern Siberia to Xinjiang. However, the Xiongnu as a people are relatively unknown to scholars since they did not possess a written language of their own. Although analysis on ancient skeletal remains of the Xiongnu have opened new avenues of research into their origins, scholars still do not have a comprehensive understanding of these ancient nomads. This study makes an attempt to elucidate questions of the Xiongnu\u27s history and biological structure by examining craniofacial diversity using a methodology known as geometric morphometrics. Using a suite of multivariate statistical analyses to explain group relationships within and among the Xiongnu to groups in the region, this study explains the origins of the Xiongnu in a biological context and makes inferences about genetic exchanges. A quantitative genetic model is used to test group relationships and infer levels of gene flow between groups. Results indicate the Xiongnu were composed of at least two biologically distinct groups. One sample from an elite cemetery in northern Mongolia shares their ancestry with a Bronze Age population from Mongolia, and possibly, to a later migration of Turks, who came to dominate the eastern steppe between the 6th and 8th centuries CE. The Xiongnu also evidence biological similarity with nomads who composed the Mongol Empire, modern-day Mongolians, and some Siberian groups. These results are similar to genetic studies suggesting a mix of Eastern and Western Eurasian haplogroups while also achieving consensus with models of steppe polity formation proposed by archaeologists, who suggest local ties to extra-local groups through interactive exchange networks. Overall, the Xiongnu nomads are very much a part of Mongolia\u27s past with links to its modern peoples

Symmetry in Human Evolution, from Biology to Behaviours

Our knowledge of human evolution has made particular progress recently, due to the discovery of new fossils, the use of new methods and multidisciplinary approaches. Moreover, studies on the departure from symmetry, including variations in fluctuating or directional asymmetries, have contributed to the expansion of this knowledge. This Special Issue brings together articles that deal with symmetry and human evolution. The notion of symmetry is addressed, including whether to reconstruct deformed fossil specimens, study biological variations within hominins or compare them with extant primates, address the shape of the brain or seek possible relationships between biological and behavioural data

Multi-scale imaging and modelling of bone

The multi-level organization of bone facilitates the exploitation of in-vivo micro-scale information which is currently lacking for clinical applications. The three sub-projects presented in this thesis investigate the human skeletal system at multiple scales using magnetic resonance imaging (MRI) with the aim of providing new techniques for extracting finer scale information in-vivo. At the whole organ level, human knee joint kinematics was studied using a combined MRI strategy. This new strategy enables the in-vivo investigation of tibiofemoral locomotion under body weight-bearing conditions by modelling the knee flexion angle as a function of the femur and tibia cartilage surfaces in contact. The resultant "contact" trajectory may potentially be used to understand the mechanical cause of cartilage degeneration and as a biomarker to detect abnormalities in the lower limb. At the molecular level, in-vivo MR diffusion tensor imaging (DTI) has been performed for the first time in the human tibia epiphysis. By tracking the water molecules inside the red marrow, the organization of trabecular bone network may be understood as the streamlines formed by anisotropic diffusion trajectories. This sub-project aims to understand the organization of trabecular bone networks non-invasively, which is usually performed ex-vivo through biopsies. The feasibility and reproducibility of DTI is studied. Finally, a new MR imaging protocol named multi-directional sub-pixel enhancement (mSPENT) is proposed and developed to quantify the trabecular bone structural arrangement at the meso-scale. By modulating a dephasing gradient to manipulate the underlying spin system inside each voxel, the resulting mSPENT image contrast varies with gradient at different directions based on the magnetization at the corresponding voxel. A tensor-based method is further developed to model this contrast change, leading to a localized quantification of tissue structural orientation beyond the conventional MR imaging resolution

Virtual Morphology and Evolutionary Morphometrics in the new millenium.

EDITED VOLUME; abstract N/

Diffusion tensor imaging and resting state functional connectivity as advanced imaging biomarkers of outcome in infants with hypoxic-ischaemic encephalopathy treated with hypothermia

Therapeutic hypothermia confers significant benefit in term neonates with hypoxic-ischaemic encephalopathy (HIE). However, despite the treatment nearly half of the infants develop an unfavourable outcome. Intensive bench-based and early phase clinical research is focused on identifying treatments that augment hypothermic neuroprotection. Qualified biomarkers are required to test these promising therapies efficiently. This thesis aims to assess advanced magnetic resonance imaging (MRI) techniques, including diffusion tensor imaging (DTI) and resting state functional MRI (fMRI) as imaging biomarkers of outcome in infants with HIE who underwent hypothermic neuroprotection. FA values in the white matter (WM), obtained in the neonatal period and assessed by tract-based spatial statistics (TBSS), correlated with subsequent developmental quotient (DQ). However, TBSS is not suitable to study grey matter (GM), which is the primary site of injury following an acute hypoxic-ischaemic event. Therefore, a neonatal atlas-based automated tissue labelling approach was applied to segment central and cortical grey and whole brain WM. Mean diffusivity (MD) in GM structures, obtained in the neonatal period correlated with subsequent DQ. Although the central GM is the primary site of injury on conventional MRI following HIE; FA within WM tissue labels also correlated to neurodevelopmental performance scores. As DTI does not provide information on functional consequences of brain injury functional sequel of HIE was studied with resting state fMRI. Diminished functional connectivity was demonstrated in infants who suffered HIE, which associated with an unfavourable outcome. The results of this thesis suggest that MD in GM tissue labels and FA either determined within WM tissue labels or analysed with TBSS correlate to subsequent neurodevelopmental performance scores in infants who suffered HIE treated with hypothermia and may be applied as imaging biomarkers of outcome in this population. Although functional connectivity was diminished in infants with HIE, resting state fMRI needs further study to assess its utility as an imaging biomarker following a hypoxic-ischaemic brain injury.Open Acces