Quality of DNA extracted from formalin-fixed, paraffin-embedded canine tissues.

Veterinary pathology tissue banks are valuable resources for genetic studies. However, limited data exist as to whether quality DNA can be extracted from these tissues for use in canine genotyping studies. We extracted DNA from 44 formalin-fixed, paraffin-embedded (FFPE) tissue blocks from dogs; 9 of these dogs had DNA available from whole blood samples that had been banked. We genotyped DNA from 30 of 44 tissue blocks and 9 whole blood samples on the Illumina CanineHD BeadChip; DNA quality was insufficient in 14 of 44 samples from tissue blocks. There was significant correlation between the 260/280 ratio and single-nucleotide variation (SNV) call rate (p = 0.0276; r2 = 0.162); 23 of 30 samples from FFPE were genotyped with > 65% call rates. Median pairwise identical-by-state (IBS) analysis was 0.99 in 8 pairs of dogs with call rates > 65%. Neither age of tissue block nor specific tissue types were associated with significant differences in DNA concentration, 260/280 ratio, or SNV call rate. DNA extracted from tissue blocks can have variable quality, although comparable levels of homozygosity suggest that extracts from FFPE with call rates > 65% might provide similar results to samples from whole blood when analyzed on the Illumina CanineHD BeadChip

Inference in the context of uncertain complex urban environments for climate change conscious planning and design

This thesis looks at the urban environment as the centre of human habitation. It governs the comfort of much of the human population and is essential to life itself. In the modern world, it is governed at many levels and this thesis approaches two of them: modelling a building’s system and elements of urban city design. Urban climate, in the UK, is being increasingly affected by climate change and urban pollution remains a concern. How cities are maintained and designed is being adjusted to consider these interactions. This thesis looks at the impact of roughness of the cities-scape on wind speed, considered a factor capable of improving air quality . This thesis will looks at urban albedo and the impact it has on air temperature at ground level compared with the general degree of urban density. Uncertainty is a part of complex systems such as cities which contain many elements and in order to address this models are used to describe these system. A modeller will not have access to all information or the time to address every element at a high level of detail. The Gaussian processes used in this thesis have inherent uncertainty quantification, and they make estimates that make allowances for inaccuracies. This means conclusions drawn using this method can be considered more robust to uncertainties in the data. This thesis will examine empirical data using different methodologies to draw conclusions about model fitness of the methods used. The case studies that are used are the problem of emulator construction for the building energy models (BEMs) and two example relationships of urban weather from the Birmingham University Climate Laboratory (BUCL) and the urban fabric. Building energy use, through domestic, office and industrial consumption, is a major part of how we as a society consumes electricity/gas and this consumption is metered. Building systems are modelled using physical principles which requires a large amount of information about constructed systems, user behaviour and the ambient environment which is very costly justifying alternatives such as statistical modelling. This thesis will showcase how they can be used to address the issue of climate change for a building energy use, in cooling

Supporting spatial learning in virtual environments

This thesis explores the acquisition of spatial knowledge as a means to support wayfinding in virtual environments. Specifically, the thesis presents an investigation into the potential benefits one might gain through the application of a variety of tools, each of which has been designed to support one of the three stages of cognitive map development - landmark-based representation, route-based representation, and survey-based representation (Siegel & White, 1975). Each tool has been evaluated with respect to improvements in wayfinding, and also in their support for environmental learning. Measures were taken of each tool used in isolation, and also when used together as a complete toolset. The between-subjects evaluation process involved 101 participants, randomly assigned to one of five conditions. Each participant was asked to navigate a virtual environment to locate three specific items. To evaluate wayfinding, participants were asked to perform the same task on six occasions within the same session. After discovering all items, a measure indicating route efficiency was recorded. On completing all six trials participants were asked to produce a map of the virtual environment. It was hypothesised that the presence of tools would improve the acquisition of spatial knowledge, and thus route efficiency and map production. Comparing the 'no-tool' and the 'all tool' conditions, a 2x6 repeated measures ANOVA found that when providing the tools concurrently there was a statistically significant improvement in the efficiency of route taken (F(1,38)=4.63, p<0.05). However, when evaluating the tools in isolation, no significant improvement in route efficiency was found. Also, no significant difference between conditions was identified when comparing the quality of maps produced by participants across conditions. The thesis concludes by arguing that the application of the complete toolset benefits wayfinding, although it is noted that the evidence does not support the hypothesis that this is caused by improved spatial learning.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

ATX-101 for reduction of submental fat: A phase III randomized controlled trial

BackgroundATX-101, an injectable form of deoxycholic acid, causes adipocytolysis when injected subcutaneously into fat.ObjectiveWe sought to evaluate the efficacy and safety of ATX-101.MethodsIn this phase III trial (REFINE-2), adults dissatisfied with their moderate or severe submental fat (SMF) were randomized to ATX-101 or placebo. Coprimary end points, evaluated at 12 weeks after last treatment, were composite improvements of 1 or more grades and 2 or more grades in SMF observed on both the validated Clinician- and Patient-Reported SMF Rating Scales. Other end points included magnetic resonance imaging–based assessment of submental volume, assessment of psychological impact of SMF, and additional patient-reported outcomes.ResultsAmong those treated with ATX-101 or placebo (n = 258/treatment group), 66.5% versus 22.2%, respectively, achieved a composite improvement of 1 or more grades (Mantel-Haenszel risk ratio 2.98; 95% confidence interval 2.31-3.85) and 18.6% versus 3.0% achieved a composite improvement of 2 or more grades in SMF (Mantel-Haenszel risk ratio 6.27; 95% confidence interval 2.91-13.52; P < .001 for both). Those treated with ATX-101 were more likely to achieve submental volume reduction confirmed by magnetic resonance imaging, greater reduction in psychological impact of SMF, and satisfaction with treatment (P < .001 for all). Overall, 85.7% of adverse events in the ATX-101 group and 76.9% in the placebo group were localized to the injection site.LimitationsFollow-up was limited to 44 weeks.ConclusionATX-101 is an alternative treatment for SMF reduction

Prostate Stereotactic Ablative Radiation Therapy Using Volumetric Modulated Arc Therapy to Dominant Intraprostatic Lesions

PurposeTo investigate boosting dominant intraprostatic lesions (DILs) in the context of stereotactic ablative radiation therapy (SABR) and to examine the impact on tumor control probability (TCP) and normal tissue complication probability (NTCP).Methods and MaterialsTen prostate datasets were selected. DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Four plans were produced for each dataset: (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3) boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose; and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning target volume (PTV) prescription was 42.7 Gy in 7 fractions. DILs were initially prescribed 115% of the PTVProstate prescription, and PTVDIL prescriptions were increased in 5% increments until organ-at-risk constraints were reached. TCP and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman models respectively.ResultsWhen treating the prostate alone, the median PTVDIL prescription was 125% (range: 110%-140%) of the PTVProstate prescription. Median PTVDIL D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same PTVDIL prescriptions and similar PTVDIL median doses were possible when including the proxSV within the prescription. TCP depended on prostate α/β ratio and was highest with an α/β ratio = 1.5 Gy, where the additional TCP benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and was considered unacceptably high in 5 cases, which, when replanned with an emphasis on reducing maximum dose to 0.5 cm3 of rectum (Dmax0.5cc), as well as meeting existing constraints, resulted in considerable rectal NTCP reductions.ConclusionsBoosting DILs in the context of SABR is technically feasible but should be approached with caution. If this therapy is adopted, strict rectal constraints are required including Dmax0.5cc. If the α/β ratio of prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by prescribing SABR to the whole prostate, without the need for DIL boosting

An Update on the Anatomy of the Forehead Compartments

Background: The forehead is one of the most frequent locations for neuromodulator and soft tissue filler applications;however, the underlying anatomy is still poorly understood. Thus far, the presence of deep forehead compartments has not been confirmed. Methods: Twenty Caucasian cephalic specimens, 15 fresh frozen (six female and nine male) and five with formalin-phenol embalmment (three female and two male) were investigated using contrast-enhanced computed tomographic scans, dye injections, and anatomical dissections. Results: Three superficial (one central and two lateral) and three deep (one central and two lateral) forehead compartments were identified. The superficial fat compartments were found within the subcutaneous fat tissue (layer 2) and measured 2.1 x 4.6 mm for the superficial central forehead compartments and the right superficial lateral forehead compartments and 2.6 x 3.2 cm for the left superficial lateral forehead compartments, with a mean volume of 2.5, 3.1, and 3.4 cc, respectively. The deep fat compartments were identified deep to the frontalis muscle but superficial to the periosteum with an extent of 6.4 x 5.9 cm for the deep central forehead compartments, 2.6 x 5.8 cm for the right deep lateral forehead compartments, and 2.7 x 5.8 cm for the left deep lateral forehead compartments, and a mean volume of 9.1, 1.6, and 1.4 cc, respectively. Conclusions: The results presented in this study increase the understanding of the forehead anatomy. Understanding the presence of the superficial and the deep forehead compartments allows one to change the signs of frontal aging. The deep forehead compartments are in general avascular planes and permit blunt dissection for access to the supraorbital region