Objectives<p>The geometric configuration of skull is complex and unique to each individual. The main objectives of this study are two fold: 1) to provide a new technique to define the outline of skull profile and 2) to find the common factors defining the ultimate skull configuration in adult population. The secondary objective was to explore the effect of age and sex on skull shape formation.<p>Materials & Methods <p>Ninety-three lateral skull x-ray from the CT scan films were selected and digitized. The lateral skull surface was divided into 3 regions based on the presumed location of coronal and lambdoid sutures. A software program (Canvas 7) was used to match the outer surface of lateral skull with circular curves. Three main curvatures (frontal, parietal, occipital) were consistently identified to overlap the skull periphery. The radius, cord length and inclination of each curvature were measured.. Factor analysis technique was also used to reduce the number of variables explaining the overall shape of skull. Student t-test and regression analysis was also used to explore the effect of sex and age on skull shape. <p>Results <p>There were total of 93 patients in this study (54% male). The average values for three defined curvatures of the skull profile were recorded. Factor analysis produced 3 factors. The first factor explained 32% of total variance and was related to the overall size of the head as represented by total length and the radius of the curvature in vertex and back of the head. The second factor covered 26% of the variance representing the inverse correlation between the angle of the frontal and parietal curves. The third factor revealed the direct correlation of occipital and parietal angle. In all of these factors, the frontal zone variation was independent or opposite of the parieto-occipital zone. A strong direct association between the total length of skull, occipital curve radius and length with the sex was shown. No age related variable was identified.<p>Conclusions <p>There is a large variation in the values of different part of the skull. The skull profile topography can be defined mathematically by two distinct territories: frontal and parieto-occipital zones. These territories hinge on the coronal suture. Therefore, coronal suture may play a dominant role in final skull configuration.

Objectives<p>The geometric configuration of skull is complex and unique to each individual. The main objectives of this study are two fold: 1) to provide a new technique to define the outline of skull profile and 2) to find the common factors defining the ultimate skull configuration in adult population. The secondary objective was to explore the effect of age and sex on skull shape formation.<p>Materials & Methods <p>Ninety-three lateral skull x-ray from the CT scan films were selected and digitized. The lateral skull surface was divided into 3 regions based on the presumed location of coronal and lambdoid sutures. A software program (Canvas 7) was used to match the outer surface of lateral skull with circular curves. Three main curvatures (frontal, parietal, occipital) were consistently identified to overlap the skull periphery. The radius, cord length and inclination of each curvature were measured.. Factor analysis technique was also used to reduce the number of variables explaining the overall shape of skull. Student t-test and regression analysis was also used to explore the effect of sex and age on skull shape. <p>Results <p>There were total of 93 patients in this study (54% male). The average values for three defined curvatures of the skull profile were recorded. Factor analysis produced 3 factors. The first factor explained 32% of total variance and was related to the overall size of the head as represented by total length and the radius of the curvature in vertex and back of the head. The second factor covered 26% of the variance representing the inverse correlation between the angle of the frontal and parietal curves. The third factor revealed the direct correlation of occipital and parietal angle. In all of these factors, the frontal zone variation was independent or opposite of the parieto-occipital zone. A strong direct association between the total length of skull, occipital curve radius and length with the sex was shown. No age related variable was identified.<p>Conclusions <p>There is a large variation in the values of different part of the skull. The skull profile topography can be defined mathematically by two distinct territories: frontal and parieto-occipital zones. These territories hinge on the coronal suture. Therefore, coronal suture may play a dominant role in final skull configuration.

Pigs, mice and human beings are all vertebrate mammals. More than 90% of genomes in pigs and mice are the same as human beings. Experiment pigs and mice are with advantages in purebloods, small size, high reproductive capacity and short life cycle, etc. The tissue structure and metabolism of physiology in pig and mice are similar to human as well. Therefore, laboratory pigs and mice are often used to substitute human beings for biomedical engineering test. The research topics of this thesis are in the area of biomechanical properties of bones in mammal. The objectives of the study are to reveal the biomechanical properties of various types of bones and discuss its implication to human development. The entire thesis is divided into three parts. The first topic used micro-indentation test and FEM analysis for the determination of biomechanical properties of controlled cartilages in pigs. The second topic applied (a) three-point-bend failure test to study the age-related radius strength in mice, (b) tensile test to study the mechanical response of cranial sutures in mice, and (c) optical interferometry for 3D profile determination of mouse cranium. The third topic is for quantitative analysis of patterns in cranial sutures using DFT (Discrete Fourier Transform). The mechanism of diseases (such as osteoporosis, craniosynostosis, etc.) and the complexity of patterns in human cranial sutures in different age groups are discussed.

The intention with this thesis is to improve the method to assess dental wear as an age indicator by examining its correlation with the closure of cranial suture and the influence diet has on dental wear. This thesis explores this correlation through a comparative study between a collection of skulls with unknown context and a control group with known context. Age assessment of cranial sutures is one of the oldest and most questionable methods of physical anthropology. The studies that were carried out in the beginning of the 21st century have shown a useful correlation between the cranial sutures closure and age assessment. Research on food is essential for understanding a society, and dental health has always been important for wellbeing. A difference between populations today and historical populations is the dental wear that causes infections. All these premises make this research interesting to explore further, to learn more about what the teeth can tell us about historic populations.

BACKGROUND: Pleiotropy is a biological phenomenon of a single gene exhibiting influence over several different seemingly disparate phenotypes. This phenomenon poses significant challenges to fully understanding the etiologies of many different Mendelian diseases. Two such Mendelian diseases are Idiopathic Hypogonadotropic Hypogonadism (IHH) and Craniosynostosis (CS). IHH results from the failure of differentiation, migration, secretion, or action of the GnRH neurons resulting in absent puberty and infertility. CS is characterized by premature fusion of one or more of the cranial sutures resulting in dysmorphic shape of the skull that can lead to life-threatening raised intercranial pressure requiring surgical intervention. Thus far, 77 genes have been implicated in IHH and 128 genes have been implicated CS, both representing ~50% of the cases in their respective diseases. Recent research has suggested a shared molecular landscape in CS and IHH but the full ensemble of this overlap is not known. OBJECTIVE: This study will attempt to utilize human genetics, bioinformatics, statistics, phenotype data of IHH patients, and the prior literature in order to ascertain the full extent of the shared biology of IHH and CS. METHODS: The gene sets of both IHH and CS were used in gene overlap statistical analysis to investigate shared genetics. Whole exome sequencing data from 1,395 patients from the IHH cohort of the Massachusetts General Hospital were used for gene-variant burden analysis to determine genetic overlap with CS. Detailed physician notes from this cohort were used to determine phenotypic presence of CS in IHH. Conversely, evidence of reproductive phenotypes in genetically characterized CS patients was gathered from the reported CS gene literature. The CS and IHH gene sets were also bioinformatically analyzed using both the Metascape and DAVID bioinformatic platforms for pathway annotation, protein-protein interaction (PPI), and functional interactions to provide evidence for the mechanism of shared biology. RESULTS: Of the 128 CS genes and 77 IHH genes, 4 were determined to be causal for both diseases with a further 3 considered as potentially causal candidates for both diseases. The 4 overlapping causal genes were tested using three different methods and this overlap was determined to be of statistical significance (p<0.05). Furthermore, the phenotypic review revealed that while there was not a significant enrichment for CS phenotypes in the IHH cohort, the literature review yielded 49 of 128 CS genes that were reported with phenotypic evidence of failure of the hypothalamic-pituitary portion of the HPG axis. Gene-variant burden analysis yielded nominal (p<0.05) enrichment in the IHH cohort for 17 CS genes, of which 3 were significant after Bonferroni multiple testing correction (p<0.00039). The CS/IHH gene sets were both enriched in 44 shared pathways according to Metascape and 17 shared pathways according to DAVID. PPI analysis yielded 3 shared communities between the two disorders with enrichment in fibroblast signaling, ossification, and cardiac chamber development. CONCLUSIONS: The shared biology between IHH and CS was significantly greater than what was previously appreciated. Shared pathways of the two gene sets point toward the neural crest origin of subpopulations of the GnRH neuron and cranial suture osteoblast as a possible foundation for this shared biology, as well as the migratory nature of these two cells and the role that many genes in both gene sets play in cellular motility. Several CS genes emerge as candidates for IHH and must be individually evaluated. Functional studies should be used to confirm and further unravel the underlying mechanisms for the biological overlap between these two diseases. This study may provide a model for preemptive in silico work prior to more expensive in vitro or in vivo studies of pleiotropy.