Sheep mandibular animal models for dental implantology research

Hardcopy of thesis in two volumes; digitized version in one PdfThis inquiry investigated the suitability of the jaw of domestic sheep as an animal model for dental implantology research. Initially, parameters for osseous healing of critical size defects (CSD) in the sheep mandible were established. Pilot studies were conducted using machined-surface implants and a surgical protocol established for dental implant placement in ovine mandibular sites. Subsequent experiments considered the utility of this animal model for examination of techniques designed to enhance osseointegration. Hydroxyapatite-coated implants were compared with titanium plasma-sprayed (TPS) implants, either alone or combined with autogenous bone grafts or a bone graft/collagen vehicle loaded with transforming growth factor-beta (TGF-B). Immunofluorescent bone labelling gave information on the mineral apposition rate (MAR). Implant survival and "acceptability" (likelihood of clinical success) were major output variables, along with histomorphometric analysis of percent bone-implant contact (%BIC) and percent peri-implant bone density (%density). Naturally-occurring "broken-mouth" periodontitis in sheep was identified as a potential confounder. Subsequent experiments considered implants with different surfaces. The model was also extended from a two-stage surgical protocol to include single-stage implants. The effect of pre-existing ovine peridontitis was also examined. A systematic review and meta-analysis of published animal implant experiments was conducted in order to validate the candidate sheep model. Major findings were as follows. The size of non-healing sheep mandibular unicortical CSD is > 12mm. Attempts to establish a chronic non-healing CSD were unsuccessful. The sheep diastema proved unsuitable for implant placement. The model was modified to a postextraction protocol. Implant "acceptability" rates after 3 months integration in the sheep mandible (defined as implant survival with %BIC >10%) ranged from 50% - 100% for different implant surface treatments and placement protocols. Histomorphometric analyses revealed that %BIC ranged from 11 ± 17% to 81 ± 29 % for different titanium surfaces and up to 85 ± 11 % for hydroxyapatite surfaces. Implants with TGF-B plus autogenous bone grafts had %BIC of 36 ± 30% compared with 43 ± 30% for implants with grafts alone. Bone per unit area (%density) adjacent to, but outside of the implant threads, ranged from 63 ± 16% to 86 ± 3% and was markedly lower for titanium plasma-sprayed surfaces and for one-stage implants. Within the implant threads, %density varied from 31 ± 33% to 73.4 ± 8.3%, and was markedly lower for machined titanium surfaces. Sheep periodontitis had little effect on the protocols investigated. The sheep mandibular model was found to be comparable to similar models in other species and merits further development

Biphasic calcium phosphate and polymer-coated bovine bone matrix for sinus grafting in an animal model

Autogenous bone grafting requires a donor site and may lose substantial volume during remodeling. Several bone replacement materials (BRMs) are under development to overcome these limitations, especially for indications for minimally intervention surgeries. The objective of our study was to assess the potential of an equine collagen cone reinforced with biphasic calcium phosphate (CC-BCP) particles and deproteinized bovine bone matrix (BBM) coated with polylactic acid, and poly-ε-caprolactone copolymer (BBM-PCC) and then to compare the outcomes with a deproteinized BBM and an equine CC without a filler in a sheep sinus grafting model in the Elleven female sheep were selected. Two experimental sites on each side of the animals were prepared using an extraoral approach for maxillary sinus wall. The four treatments were performed in each animal through a standardized 10-mm access window. While the BBM access was covered with a collagen membrane, all other sites were closed with an equine collagen membrane. All animals were euthanized after 16 weeks. New bone (NB), residual graft particles, and connective tissue were measured in undemineralized resin-embedded sections. As a result, one sheep did not survive the surgery. All sites in the remaining 10 sheep healed uneventfully. All CC and BBM-PCC grafts resorbed and failed to augment the sinuses. BBM and CC-BCP, in contrast, showed some histologic evidence of NB and surgical site augmentation. The NB fraction in the latter two groups accounted for 10 ± 9 and 4 ± 5%, respectively (p > 0.05). In conclusion, BBM-PCC and collagen cone performed poorly for sinus floor augmentation, while deproteinised BBM and reinforced collagen cone demonstrated comparable outcomes

Genetic Analysis Workshop 13: Simulated longitudinal data on families for a system of oligogenic traits

The Genetic Analysis Workshop 13 simulated data aimed to mimic the major features of the real Framingham Heart Study data that formed Problem 1, but under a known inheritance model and with 100 replicates, so as to allow evaluation of the statistical properties of various methods. The pedigrees used were the 330 real pedigree structures (comprising 4692 individuals) with some minor changes to protect confidentiality. Fifty trait genes and 399 microsatellite markers were simulated by gene dropping on 22 autosomal chromosomes. Assuming random ascertainment of families, a system of eight longitudinal quantitative traits (designed to be similar to those in the real data) was generated with a wide range of heritabilities, including some pleiotropic and interactive effects. Genes could affect either the baseline level or the rate of change of the phenotype. Hypertension diagnosis and treatment were simulated with treatment availability, compliance, and efficacy depending on calendar year. Nongenetic traits of smoking and alcohol were generated as covariates for other traits. Death was simulated as a hazard rate depending upon age, sex, smoking, cholesterol, and systolic blood pressure. After the complete data were simulated, missing data indicators were generated based on logistic models fitted to the real data, involving the subject's history of previous missing values, together with that of their spouses, parents, siblings, and offspring, as well as marital status, only-child indicators, current value at certain simulated traits, and the data collection pattern on the cohort into which each subject was ascertained

“Captain of All These Men of Death”: An Integrated Case Study of Tuberculosis in Nineteenth-Century Otago, New Zealand

The South Island of New Zealand saw several major waves of migration in the mid-nineteenth century, predominantly from Europe but also with an ethnically distinct Chinese presence. The rural community of Milton, Otago, was a settler community established primarily by immigrants from the United Kingdom in search of a better quality of life. However, these settlers faced unique challenges related to surviving in an isolated location with very little infrastructure compared to their origin populations. In 2016, excavation was undertaken at St. John’s burial ground, Milton, with the object of using bioarchaeological methods to elucidate the lived experience of the first organized European settlement of this region, particularly in terms of health and disease. Here we present a case study of Burial 21 (B21), a male individual of known identity and a documented cause of death. We use biochemical and paleopathological methods to ground-truth his written history, which includes a period of invalidism due to tuberculosis, and discuss the implications of our findings for the community, provision of care, and quality of life in rural colonial New Zealand. He maha tonu ngā hekenga tāngata ki Te Waka a Māui i ngā tau kei waenga pū o te rau tau 1800, ko te nuinga nō Ūropi, heoi he tokomaha tonu nō Haina. Nā ngā manene nō Peretānia te hapori o Milton i whakatū ki Tokomairaro, i Ōtākou, i tō rātou hiahia ki tētehi oranga kounga ake i tō rātou oranga i Peretānia. Heoi, ko ētehi o ngā wero nui i tau ki ngā manene nei i ahu mai i te noho pūreirei ki tētehi wāhi kāore rawa ngā ratonga i rite ki ngā wāhi i ahu mai ai rātou. I te tau 2016, i hahu kōiwi i te urupā o Hato Hone, i Milton, hei whakamātau i te kaha o te ora me ngā momo mate i pā atu ki ngā tāngata whai i noho i te rohe nei. Nei rā he ripoata mō tētehi kua hahua, kua tapaina ko B21, he tāne ia, ko tōna ingoa kua mōhiotia, ko tōna mate kua āta tuhia. Kua āta whakamātauria ōna kōiwi me ōna toenga kiko mō ngā tohu ora me ngā tohu mate, kia mārama ai mena rānei e hāngai ana ngā tuhinga rongoā mōna, ngā mea i tuhia nōna e takatū ana, tae atu ki te wā i tūroro ia i te mate kohi, ki ngā tohu e puta ana i te mātauranga Rongoā-Koiora ō nāianei. Ka matapakina ngā hīrautanga o ngā kitenga me te māramatanga kua puta i tēnei rangahau e pā ana ki te hapori, ki ngā ratonga hauora, me te kounga o te oranga mō te hunga noho tuawhenua i tērā wā i Aotearoa

The Effect of Low-Processing Temperature on the Physicochemical and Mechanical Properties of Bovine Hydroxyapatite Bone Substitutes

Bovine bone grafts (BBX) require protein removal as part of the manufacturing process to reduce antigenicity and, in consequence, to be safely used in humans. Deproteinisation may have direct effects on the characteristics of the bone material and on in vivo material performance. This research aimed to comprehensively study the physicochemical and mechanical properties of BBX processed at low deproteinisation processing temperatures. Cubes of bovine bone (8 mm3) were treated with temperatures between 100 °C and 220 °C at 30 °C intervals and with pressures ranging from 1.01 to 24.58 Bar. The samples were characterised topographically and mechanically using scanning electron microscopy (SEM), atomic force microscopy (AFM), and uniaxial bending tests. The organic content and the chemical composition were determined using thermogravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FTIR). X-ray diffraction (XRD) and FTIR were also used to quantitatively determine the specimen crystallinity. Increasing temperature/pressure was associated with decreasing protein levels and compressive strength and increasing surface irregularities and crystallinity. The findings suggest that low-temperature processed bone is likely to exhibit a rapid in vivo degradation rate. The deproteinisation temperature can be adjusted to tailor the graft properties for specific applications

The Australia Telescope 20 GHz (AT20G) Survey: The Bright Source Sample

The Australia Telescope 20 GHz (AT20G) Survey is a blind survey of the whole Southern sky at 20 GHz (with follow-up observations at 4.8 and 8.6 GHz) carried out with the Australia Telescope Compact Array (ATCA) from 2004 to 2007. The Bright Source Sample (BSS) is a complete flux-limited subsample of the AT20G Survey catalogue comprising 320 extragalactic (|b|>1.5 deg) radio sources south of dec = -15 deg with S(20 GHz) > 0.50 Jy. Of these, 218 have near simultaneous observations at 8 and 5 GHz. In this paper we present an analysis of radio spectral properties in total intensity and polarisation, size, optical identifications and redshift distribution of the BSS sources. The analysis of the spectral behaviour shows spectral curvature in most sources with spectral steepening that increases at higher frequencies (the median spectral index \alpha, assuming S\propto \nu^\alpha, decreases from \alpha_{4.8}^{8.6}=0.11 between 4.8 and 8.6 GHz to \alpha_{8.6}^{20}=-0.16 between 8.6 and 20 GHz), even if the sample is dominated by flat spectra sources (85 per cent of the sample has \alpha_{8.6}^{20}>-0.5). The almost simultaneous spectra in total intensity and polarisation allowed us a comparison of the polarised and total intensity spectra: polarised fraction slightly increases with frequency, but the shapes of the spectra have little correlation. Optical identifications provided an estimation of redshift for 186 sources with a median value of 1.20 and 0.13 respectively for QSO and galaxies.Comment: 34 pages, 19 figures, tables of data included, replaced with version published in MNRA

Further developments towards a genome-scale metabolic model of yeast

BACKGROUND: To date, several genome-scale network reconstructions have been used to describe the metabolism of the yeast Saccharomyces cerevisiae, each differing in scope and content. The recent community-driven reconstruction, while rigorously evidenced and well annotated, under-represented metabolite transport, lipid metabolism and other pathways, and was not amenable to constraint-based analyses because of lack of pathway connectivity. RESULTS: We have expanded the yeast network reconstruction to incorporate many new reactions from the literature and represented these in a well-annotated and standards-compliant manner. The new reconstruction comprises 1102 unique metabolic reactions involving 924 unique metabolites - significantly larger in scope than any previous reconstruction. The representation of lipid metabolism in particular has improved, with 234 out of 268 enzymes linked to lipid metabolism now present in at least one reaction. Connectivity is emphatically improved, with more than 90% of metabolites now reachable from the growth medium constituents. The present updates allow constraint-based analyses to be performed; viability predictions of single knockouts are comparable to results from in vivo experiments and to those of previous reconstructions. CONCLUSIONS: We report the development of the most complete reconstruction of yeast metabolism to date that is based upon reliable literature evidence and richly annotated according to MIRIAM standards. The reconstruction is available in the Systems Biology Markup Language (SBML) and via a publicly accessible database http://www.comp-sys-bio.org/yeastnet/

Visually assessed breast density, breast cancer risk and the importance of the craniocaudal view

Contains fulltext : 69403.pdf (publisher's version ) (Open Access)INTRODUCTION: Mammographic density is known to be a strong risk factor for breast cancer. A particularly strong association with risk has been observed when density is measured using interactive threshold software. This, however, is a labour-intensive process for large-scale studies. METHODS: Our aim was to determine the performance of visually assessed percent breast density as an indicator of breast cancer risk. We compared the effect on risk of density as measured with the mediolateral oblique view only versus that estimated as the average density from the mediolateral oblique view and the craniocaudal view. Density was assessed using a visual analogue scale in 10,048 screening mammograms, including 311 breast cancer cases diagnosed at that screening episode or within the following 6 years. RESULTS: Where only the mediolateral oblique view was available, there was a modest effect of breast density on risk with an odds ratio for the 76% to 100% density relative to 0% to 25% of 1.51 (95% confidence interval 0.71 to 3.18). When two views were available, there was a considerably stronger association, with the corresponding odds ratio being 6.77 (95% confidence interval 2.75 to 16.67). CONCLUSION: This indicates that a substantial amount of information on risk from percentage breast density is contained in the second view. It also suggests that visually assessed breast density has predictive potential for breast cancer risk comparable to that of density measured using the interactive threshold software when two views are available. This observation needs to be confirmed by studies applying the different measurement methods to the same individuals

Genetic Analysis Workshop 15: gene expression analysis and approaches to detecting multiple functional loci

National Institutes of Health (AR44422, N01-AR-7-2232, 5R01-HL049609-14, IR01-AG021917-01A1); Genome Canada and Associations AFP; Polyarctique-Groupe Taitbout; Rhumatisme et Travail; Arthritis Research Campaign; Unversity of Minnesota; Minnesota Supercomputing Institute; National Institute of General Medical Sciences (R01 GM31575

Supporting international medical graduates’ transition to their host-country: realist synthesis

Context Many health services and systems rely on the contribution of international medical graduates (IMGs) to the workforce. However, concern has grown around their regulation and professional practice. There is a need, in the absence of strong evidence and a robust theoretical base, for a deeper understanding of the efficacy of interventions used to support IMGs’ transition to their host countries. This study seeks to explore and synthesise evidence relating to interventions developed for IMGs. It aims to provide educators and policy makers with an understanding of how interventions should be developed to support IMGs in their transition to the workplace, particularly looking to identify how and why they are effective. Methods The realist synthesis involved an initial systematic search of the literature for the period January 1990 to April 2015. Secondary searches were conducted throughout the review in order to inform and test the developing programme theory. The context, mechanism and outcome data were extracted from all sources meeting the inclusion criteria. Fourteen case studies were included to further aid theory refinement. Results Sixty-two articles were identified, describing diverse interventions of varying intensity. A further 26 articles were identified through a secondary search. The findings illustrate that, alongside a developed programme, ongoing support and cultural awareness at organisational and training levels are crucial. Individual differences must also be taken into consideration. This will ensure that IMGs engage in transformative learning, increase their levels of self-efficacy and cultural health capital, and reduce feelings of stress and anxiety. These factors will have an impact on work, interactions and cultural adjustment. Conclusions Organisational, training and individual contexts all play a role in IMGs’ adjustment during the transition process. Establishing ongoing support is critical. A list of recommendations for implementation is given