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.

Transition analysis transforms skeletal traits with an invariant, unidirectional series of stages into a likelihood function with a maximum likelihood value and a 95% confidence interval. Boldsen et al. used transition analysis to develop an adult age estimation method employing components of the cranial sutures, pubic symphysis and ilial portion of the sacroiliac joint, used either in combination or individually. This validation study aimed to use the 36 transition analysis numerical, categorical scores for the anatomical features in conjunction with the ADBOU computer program to assess the accuracy and precision of the age estimates for 149 black individuals from the Pretoria Bone Collection. In addition, the effect of observer variability in scoring of these traits was assessed. Six age estimations were generated by the ADBOU computer program using 1) the cranial sutures only, 2) the pubic symphysis only, 3) the auricular surface of the ilium only, 4) all three features combined, 5) all three features combined and modified by a forensic prior distribution and 6) all three features combined and modified by an archaeological prior distribution. The six point estimate categories, calculated from the maximum likelihood values, were evaluated for accuracy using mean absolute values. The 95% confidence intervals were evaluated for range width and accuracy. Cohen’s Kappa statistics were used to analyse repeatability of the scoring procedure through inter- and intra-observer agreement and Kruskal-Wallis ANOVA statistics to determine the effect of observer differences on the final age estimates. The usefulness of the age ranges were diminished by large widths encompassing up to 95 years. The accuracy for the point estimates fared better for the combined skeletal indicators and overall accuracy was improved by using the archaeological prior distribution. The archaeological prior distribution was also responsible for narrowing the age ranges, especially in the older ages (over 70 years). Age estimates did not differ significantly when using inter- and intra-observer scores, but experience with the method did seem to improve results. Overall, age ranges were too wide, but accuracy could potentially be improved by adding more skeletal components to the method and using a population-specific prior distribution. The method would need considerable adjustments to make it usable in a South African setting. / Dissertation (MSc)--University of Pretoria, 2014. / tm2015 / Anatomy / MSc / Unrestricted

The use of the Daubert Standard in court proceedings has highlighted the need to substantiate scientific findings or claims beyond simply accepting the word of a respected expert. The concept of postmenopausal masculinization of the skull in female crania falls into this category. Dr. Walker references this concept in several articles but there is no research to support this hypothesis. This project examines the theory of postmenopausal masculinization of female crania from several perspectives, using the visual sex estimation method set forth in Standards for Data Collection from Human Skeletal Remains edited by Jane E. Buikstra and Douglas H Ubelaker, photographic seriation of these sex estimation traits, and metric measurements in conjunction with Fordisc 3.1. A sample of 395 crania from the Hamann-Todd Collection at the Cleveland Museum of Natural History was analyzed using all three of these methods to determine if there was a pattern of masculinization in the postmenopausal female sample. The average age for the onset of menopause in the United States is 50, thus there should be an increase in "masculinization" observable through more rugged sex estimation traits, a higher number of females 50 or over being found below the midpoint in photographic seriations of sex estimation traits, and an increase in Fordisc 3.1 sex identification misclassifications in females in this age category. The results of the analyses revealed that there were statistically significant differences between ancestry groups, the sexes, and in some cases, age-groups. The results of this research indicate that though there are some differences between comparison groups, there does not appear to be a cohesive pattern of masculinization in female crania at or after the average age of onset of menopause. Human variation is endless, and even in areas of the skeleton for which it has been established that there is a significant degree of sexual dimorphism, there will be individuals who do not fit neatly into a binary conception of sexual divergence. Though these individuals may be misidentified as the opposite sex using one or all of the methods utilized in this project, this falls short of being classified as a part of the menopausal process in females.

Zoologists classify the savannah buffalo under the Bovini Tribe. Osteologically, the skull differs from that of the water buffalo of Asia, inter alia, in that the vomer does not articulate with the palatine part of the osseus palate. This gross anatomical study gives a detailed description of all the bones of the skull, mandible and hyoid apparatus of the savannah buffalo Syncerus caffer caffer (Sparrman, 1779). These bones are similar in many respects to that of the domestic bovine. However, due to the robustness of the buffalo skull, many aspects pertaining to bones or parts of bones that are different or more pronounced, are of anatomical importance. The sum-total effect of all these features, gives the skull its typical macro-morphology that differentiates it clearly from the other genera in the Bovini Tribe. The more important characteristics that were found, are the following: 1. The skull of young animals retains basic embryonic reshaping potential till quite late in life. It can be seen as a remnant of Meckel's cartilage in the mandible as well as in prolonged remodelling in the regions of the orbit, dorsum of the nose, and most markedly, also in the lateral walls of the cranium. A subsequent temporary atypical fontanel can even leave an osseus scar in the temporal region. 2. Temporary canals, associated with the developing permanent premolars, appear in the maxilla and mandible. 3. A well defined biomechanical supporting pillar forms internally in the skull of the buffalo. It conveys pressure from the lingual side of the caudal molar alveoli, to the ipsilateral external lamina of the frontal bone in the region of the frontal fossa. 4. Apart from one small external segment, fusion of the perpendicular and basal plates of the ethmoid bone to the presphenoid bone, in the region of the orbital plate, makes ethmoid-related sutures the least visible sutures to see in all post-natal stages. 5. The retro-orbital position of the cornual process, and the presence of a nasoincisive suture, are some of the osteological features that are shared with the domestic goat. 6. Pneumatization of the nasal bone and dorsal concha may occur, as well as of the tympanic part of the temporal bone. 7. The detail of the sutures other than those of the ethmoid bone, may allow "fingerprint" identification of specific bones or complete skulls. Other applied aspects of the skull may be of importance to hunters and clinicians. / Thesis (PhD)--University of Pretoria, 2002. / Anatomy and Physiology / unrestricted

Objective. To assess the accuracy and precision in measurement of pairwise implant displacement across three methods of cranial base superimposition. Background. Cephalometric superimposition is the principal radiographic method used to evaluate changes within the craniofacial skeleton. Many studies have examined the accuracy of software intended to produce cephalometric superimposition. Such studies have utilized anatomic landmarks, selected by the respective software manufacturers, as registration points for constructing superimpositions and their analysis. As a result, these studies are only as accurate as the stability and validity of anatomic registration landmarks used. To our knowledge, no other study has utilized metallic implants to critically assess digital vs. analog cephalometric cranial base superimposition. Methods. Serial cephalograms from twenty-two patients across three time points containing metallic implants were obtained from the Mathews Acquisition Group. Each of the sixty-six cephalograms was traced by hand and digitally. Cranial base superimpositions were completed according to the analog structural method proposed by Björk and Skieller, and Johnston, and then by Dolphin version 11.5 and Quick Ceph Studio V3.2.8 digital software according to manufactures instructions. Total displacement measurements of selected implants across paired time points were recorded for both digital methods and analog method of superimposition with analog serving as the reference. Results: There were no statistically significant contrasts of mean total displacement of implants by superimposition method (p = 0.999). No significant differences are reported in mean implant displacement when comparing digital to analog superimposition methods for contrasts by time, structure, or implant location. Conclusions: The results show that there are no significant differences in accuracy and precision of digital and analog cranial base superimposition. The results of this study suggest that cranial base superimpositions on S-Na that are registered on S may be a good approximation of the structural method of cranial base superimposition. There are many methodological differences between digital and analog cranial base superimposition and future research examining such differences is recommended.

Introduktion: Skador på främre korsbandet är en av de vanligaste ortopediska skadorna hos hundar. Korsbandets huvudsakliga uppgift är att stabilisera knäleden. En främre korsbandsskada kan behandlas konservativt eller operativt, och i bägge fall är rehabilitering en viktig åtgärd. Syfte: Belysa studier kring postoperativ rehabilitering av främre korsbandsskada hos hund. Frågeställningar var; “Vilka postoperativa rehabiliteringsmetoder för främre korsbandsskada har studerats för hund?” och “Vilka effekter har de olika behandlingarna i studierna visat?” Metod: Denna systematiska litteraturstudie har följt Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) och granskningsmallar för originalstudier från Statens beredning för medicinsk utvärdering (SBU). Sökningen för litteratursammanställningen gjordes på PubMed och Scopus. Resultat: Tio artiklar kvalificerades för inkludering. Några rehabiliteringsmetoder som nämnts är bandage, köldterapi, ROM-träning, gång på vattenband, löpband, promenader, CCT och elektroterapi. Resultatet visar att extensionsvinkeln påverkas i högre grad än flexionsvinkeln. Vattenbandsträning och CCT ökar ledvinkeln postoperativt och ESWT ger snabbare belastning av det opererade benet. MET tillsammans med bandage, kall kompression och kall kompression tillsammans med bandage gav hade bäst effekt på svullnad. Konklusion: Resultatet visar att rehabilitering och fysioterapeutiska åtgärder är en viktig del för att återfå bästa möjliga funktion, minska smärta samt att förebygga försämrad funktion postoperativt efter en CrCL skada. Vidare forskning med fördjupning på rehabiliteringstyp och antal rehabiliteringstillfällen behövs för att kunna fastställa vilken rehabilitering som är mest gynnsam.

This project employs a modified version of the Bioarchaeology of Care (BoC) in an analysis of Burial 1 from the Mississippi State Asylum, Jackson, MS. Burial 1 is a skeletal individual recovered from the historic MSA cemetery. Notably, Burial 1 exhibits recidivistic cranial trauma in the form of cranial depression fractures (CDFs) and significant entheseal changes in the upper extremities. However, because there is no identifying information associated with Burial 1, interpretations of the caretaking they may have received, both prior to and after institutionalization, include short- and long-term outcomes from their community and the MSA. Additionally, Burial 1’s CDFs and subsequent traumatic brain injury likely increased their risk of being institutionalized and created complications for them in the MSA. Despite the limitations of this study, future research applying a modified BoC could lead to otherwise unknown information about the lived experiences of institutionalized patients in historic institutions of care.

Twelve pairs of cadaveric pelvic limbs were harvested from skeletally mature dogs. Tibias were randomly assigned pairwise to two study groups: locking buttress screw fixation (LBS) and bone-screw-fastener fixation (BSF). A tibial plateau leveling osteotomy (TPLO) was performed. Each specimen was positioned in a servohydraulic testing machine to simulate physiological orientation and loading at the mid-point of the stance phase at the walk. Cyclic loading was performed for 30,000 cycles at 4Hz with a peak-load of 1000N. The cyclic test was then continued by stepwise increasing the peak-load at a rate of 75N per 500 cycles until failure of the construct. The findings of this current study suggest that stabilization of the TPLO with BSF in the proximal part of a locking TPLO plate provided similar biomechanical stability under cyclic axial loading conditions as the LBS. BSF may be an acceptable alternative to LBS for TPLO.

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