121,945 research outputs found
Development of a freehand three-dimensional radial endoscopic ultrasonography system
No full textOesophageal cancer is an aggressive malignancy with an overall five-year survival of 5-10% and
two-thirds of patients have irresectable disease at diagnosis. Accurate staging of oesophageal cancer is
important as survival closely correlates with the stage of the tumour, nodal involvement and presence
of metastases (TNM staging). Endoscopic ultrasonography (EUS) is currently the most reliable
modality for providing accurate T and N staging. Depending on findings of the staging, various
treatment options including endoscopic, oncological, and surgical treatments may be performed.
It was theorised that the development of three-dimensional radial endoscopic ultrasonography would
reduce the operator dependence of EUS and provide accurate dimensional and volume measurements
to aid planning and monitoring of treatment. This thesis investigates the development of a three
dimensional endoscopic ultrasound technique that can be used with the radial echoendoscopes.
Various agar-based tissue mimicking material (TMM) recipes were characterised using a scanning
acoustic macroscope to obtain the acoustic properties of attenuation, backscatter and speed of sound.
Using these results, a number of endoscopic ultrasound phantoms were developed for the in-vitro
investigation and evaluation of 3D-EUS techniques.
To increase my understanding of EUS equipment, the imaging and acoustic properties of the EUS
endoscopes were characterised using a pipe phantom and a hydrophone. The dual ‘single element’
mechanical and ‘multi-element’ electronic echoendoscopes were investigated. Measured imaging
properties included dead space, low contrast penetration, and pipe length. The measured acoustic
properties included transmitted beam plots, active working frequency and peak pressures.
Three-dimensional ultrasound techniques were developed for specific application to EUS. This
included the study of positional monitoring systems, reconstruction algorithms and measurement
techniques. A 3D-EUS system was developed using a Microscribe positional arm and frame grabber
card, to acquire the 3D dataset. A Matlab 3D-EUS toolbox was written to reconstruct and analyse the
volumes. The 3D-EUS systems were evaluated on the EUS phantom and in clinical cases.
The usefulness of the 3D-EUS systems was evaluated in a cohort of patients, who were routinely
investigated by conventional EUS for a variety of upper gastrointestinal pathology. 3D-EUS
accurately staged early tumours and provided the necessary anatomical information to facilitate
treatment. With regards to more advanced tumours, 3D-EUS was more accurate than EUS in T and N
staging. 3D-EUS gave useful anatomical details in a variety of benign conditions such as varicies and
GISTs
Treatment targets, real-world outcomes and optimisation of biologic therapies for the treatment of inflammatory bowel disease
No full textBACKGROUND:
Treatment targets in inflammatory bowel disease (IBD) have evolved from treating
symptoms to mucosal healing (MH), with the goal of altering the natural history of the
disease. The biomarker faecal calprotectin (FC) correlates well with MH and has been
established as a treatment target in IBD. However, whether aiming for, early,
normalisation of FC, results in improved long-term outcomes remains unknown. The
anti-tumour necrosis factor alpha (anti-TNF) drugs, infliximab (IFX) and adalimumab
(ADA), have revolutionised the treatment of IBD and allowed patients to achieve the
objective end-points of normalisation of FC and MH. However, anti-TNF therapy is
expensive. Now biosimilar versions of these drugs are available with significant cost
reductions. Therefore, it is important to assess the suitability of switching patients on
to biosimilar versions to allow for cost savings to be incurred. Furthermore, in the
advent of new biologic therapies for IBD, like vedolizumab (VDZ) and ustekinumab
(UST), which have different mechanisms of action, it is important to establish how
these therapies perform in the real-world setting, especially at achieving objective endpoints.
Although, many respond to these biologic therapies, a significant portion do not
or lose response with time. This is partly mediated by low drug levels in the presence
or absence of antibodies. The concept of performing therapeutic drug monitoring
(TDM) to help optimise therapy is evolving. Establishing therapeutic thresholds for
biologic drugs is therefore important to help guide therapy and improve outcomes.
AIMS:
This thesis aims to use prospective, cross-sectional, and retrospective cohorts of
patients with IBD to investigate the following:
1. The prognostic ability of FC as an early treatment target in CD
2. The real-world outcomes of switching CD patients from originator to biosimilar
CT-P13.
3. The real-world outcomes of the biologics VDZ and UST
4. The association of drug levels with objective outcomes in IBD patients receiving
anti-TNF and VDZ therapy
METHODS:
FC study: A retrospective cohort study was performed utilising medical records from
incident cases of CD (2005-2017). The last FC measurement within 12-months of
diagnosis was used to determine early normalisation (cut-off <250 μg/g). The primary
end-point was time to first disease progression (composite of progression in Montreal
disease behaviour; CD-related surgery; or CD-related hospitalisation).
CT-P13 switch study: A prospective switch study was performed at the Edinburgh
IBD Unit. Clinical and biochemical parameters (Harvey Bradshaw Index [HBI], Creactive
protein [CRP] and FC) plus serum for IFX levels were collected prior to
patients final Remicade infusion and at 6- and 12-months after switching to CT-P13.
All adverse events during follow up were recorded.
Real-world outcome studies for VDZ and UST: Two large retrospective studies were
performed across several NHS health boards in Scotland. Clinical outcomes were
collected from patients receiving VDZ (UC and CD) and UST (CD only) by review of
routine medical records.
TDM studies: Two cross-sectional studies were performed. HBI, CRP, drug levels and
FC were collected on patients receiving ADA (CD only) or VDZ therapy (CD and UC).
Biologic remission was defined as: CRP <5 mg/L and FC <250 μg/g. For perianal CD,
a retrospective review of medical records was performed to find anti-TNF TDM
samples that were matched with assessments of fistula healing / closure.
RESULTS:
FC Study: A total of 375 patients out of 1368 incident cases were included (median
follow up 5.3 years). Patients with normalised levels of FC had a significantly lower
risk of composite disease progression (hazard ratio, 0.36; 95% CI, 0.24–0.53; p<.01).
CT-P13 switch study: No significant difference was observed between HBI (p=0.07),
CRP (p=0.13), FC (p=0.25) and trough IFX levels (p=0.47) comparing before and at
6- and 12-months after the switch to CT-P13 (n=110). Rate of serious adverse events
was 13.5 per 100 patient years of follow-up (PYF).
Real-world outcome studies in VDZ and UST: In UC (n=180), 12-month cumulative
rates of clinical remission, MH, and deep remission on VDZ were 57.4%, 47.3% and
38.5% respectively. In CD (n=260), 12-month cumulative rates of clinical remission,
MH, and deep remission on VDZ were 58.4%, 38.9% and 28.3% respectively. In the
UST CD cohort (n=216 CD), 12-month cumulative rates of clinical remission, MH, and
deep remission were 32.0%, 32.7%, and 19.3%, respectively. The serious adverse
event rate was 15.6 per 100 PYF and 13.6 per 100 PYF for the VDZ and UST cohorts,
respectively.
TDM studies: For ADA (n=152 CD patients), patients in biologic remission had
significantly higher ADA levels compared to others (12.0 vs 8.0 μg/mL, p<0.01). An
optimum ADA level of >8.5 μg/mL was identified for predicting biologic remission. For
VDZ, (n=30 UC; 43 CD), no difference was observed in median VDZ levels between
patients in and not in biologic remission (10.6 vs. 9.8 μg/mL, p=0.35). For the anti-TNF
levels in perianal disease (ADA, n=35; IFX, n=29), patients with fistula healing had
higher levels of anti-TNF versus those without fistula healing (ADA: 12.6 vs 2.7 μg/mL,
p6.8 μg/mL and
>9.8 μg/mL was identified for fistula healing and closure, respectively. For IFX, an
optimum trough level of >7.1 μg/mL was identified for both fistula healing and closure.
CONCLUSIONS:
Normalisation of FC within 12-months of diagnosis is associated with a reduced risk
of progression in CD, supporting its use as an early treatment target. Transition to CTP13
from originator for the treatment of CD has no negative effect on outcomes at 12-
months. Furthermore, the newer biologics VDZ and UST are effective treatments for
achieving both clinical remission and MH in IBD. Finally, TDM can be utilised to
optimise anti-TNF therapy, whilst the role of TDM in the context of VDZ therapy is likely
limited
A Multi-Language Comparison of Influences on Author Verification using Character N-Grams
No full textWe create a new multi-language corpus for author verification based on Wikipedia talkpages, and evaluate the influence that differences in topic and time have on character n-gram author profiles. Topic alignment between two texts is found to increase author verification precision, and an authors writing style is found to change over time, but not more significantly after 3 years than after 1 year.Information ArchitectureWISElectrical Engineering, Mathematics and Computer Scienc
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The vanishing author in computer-generated works: a critical analysis of recent Australian case law
No full textAbstract
The use of software is ubiquitous in the creation of many copyright works, yet the requirement in copyright law that every work have a human author who engages in independent intellectual effort means that its use may prevent copyright subsistence. Several recent Australian cases have refocused attention on authorship as an essential criterion of copyright subsistence, and these cases suggest that much computer-produced output may be authorless and thus lack copyright protection. This article, the first in a two-part series, analyses how each case deals with the question of authorship of computer-produced works and why the use of software diminishes copyright protection for a significant number of computer-generated works. The article critiques the application of conventional notions of human authorship developed in the pre-computer age to modern productions and suggests alternative approaches to authorship that satisfy both the major objectives of copyright policy and the need to adapt to the computer age. The article argues that, without a broader judicial approach to authorship of computer-generated works, Parliament must remedy the lacuna in protection for these ‘authorless’ works. Possible solutions for reform are suggested. In a forthcoming article, the author comprehensively examines those reform proposals
Diffusive author(s), cohesive author: Analysis of S/N (1994)
No full textThis study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)
Dissipative Range Scaling of Higher Order Structure Functions for Velocity and Passive Scalars
No full textDifferently to Kolmogorov's second similarity hypothesis, we find that the 2n-th order velocity and scalar structure functions scale with n-th order moment of the energy dissipation and the scalar dissipation, respectively. The origins of this scaling are analyzed by the transport equations of the fourth order velocity and scalar increment moments and by direct numerical simulations
Fast implementation of iterative adaptive approach for wideband unambiguous radar detection
No full textAccepted author manuscriptMicrowave Sensing, Signals & System
Ratio of n-6/n-3 in the diets of beef cattle
No full textEffects of feeding heat-treated canola (C), soybean (S) and flax (F) or mixtures on growth and slaughter characteristics, taste and fatty acid (FA) composition of beef tissue were investigated using 128 crossbred steers to determine the potential of improving the nutritional quality of beef for humans. For Trial 1 (48 steers), dietary treatments were: roasted C, extruded C, roasted S, extruded S, roasted F and extruded F. For Trial 2 (80 steers), the dietary treatments were: S:F (1:1), S:C (1:1), C:F (1:1) and S:F:C (1:1:1), and the oilseeds were processed either by roasting or extruding before mixing. Soybean meal and soybean oil were used to give equivalent lipid and protein contents to each experimental diet. The basal diet consisted of grass silage, barley grain, vitamins and minerals. Steers were fed for a minimum of 100d then slaughtered at a uniform degree of finish. Growth and slaughter characteristics of the steers were only slightly affected by dietary treatment in that the soybean-fed steers consumed more feed and had a higher average daily gain than the canola or flax-fed animals in Trial 1. There was no difference in taste panel parameters for any of the treatments. Inclusion of flax in the diet increased the total n-3 content of meat. Similar results were found for canola and C18:1n-9 although this was not the case for soybean and the n-6 FA. For the n-6 FA in the PL and neutral lipid fractions of the meat samples, levels were correlated with high dietary levels of n-6 or n-9 with low levels of n-3 while for the n-3 FA, levels were correlated with high dietary n-3 levels and low n-6 levels. Oilseed processing method did not have an effect on any fatty acid levels. It is possible to modify the FA composition of beef meat toward a healthier profile by including heat-treated oilseeds in the diet to influence the degree of lipid metabolism in the rumen.ID: S0377840111004007; M3: Article; Accession Number: S0377840111004007; Author: M.A. McNiven (a, ⁎); Author: J.L. Duynisveld (b); Author: T. Turner (a); Author: A.W. Mitchell (a); Affiliation: Department of Health Management, Atlantic Veterinary College, University of PEI, Charlottetown, PEI, Canada C1A 4P3; Affiliation: Agriculture and Agri-Food Canada, Nappan, NS, Canada B0L 1C0; Keyword: Oilseeds; Keyword: Roasted; Keyword: Extruded; Keyword: Fatty acids; Keyword: Healthy fat; Number of Pages: 11; Language: English
After seven years in Key West, Florida, author John N. Cole learned to appreciat
No full textAfter seven years in Key West, Florida, author John N. Cole learned to appreciate Maine winters for their beauty and power
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