9,796 research outputs found
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
Development of a freehand three-dimensional radial endoscopic ultrasonography system
Get PDFOesophageal 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
Minding Your Business column memorializing the author\u27s father, a partner in t
No full textMinding Your Business column memorializing the author\u27s father, a partner in the John N. Cole entrepreneurial business, and recommending the film The Forgotten Maine by Michael Fiori of Brunswick
Letter from Ois�n Ua Mor�in to Fr. O'Callaghan
No full textHolograph letter from Ois�n Ua Mor�in of The New Leader, 205 New Brunswick Street, Dublin, to Fr. O'Callaghan [Rome]. The author of the article is happy if his name is disclosed to Dr. O'Hagan and will be glad to be in communication with him; he is Fr. E. Carroll in Crayford, Kent
Formulating an improved in vitro hepatic model for drug development and toxicity testing
Get PDFThere is a need in the pharmaceutical industry for more informative and
functional in vitro human models for drug testing as the currently used animal
models have poor correlation to their human counterparts. The liver is the
main organ of metabolism and xenobiotics detoxification. As such, a human
hepatic in vitro model with improved metabolic functions similar to primary
human hepatocytes (PHHs) could reduce the number of animals needed in
pre-clinical testing and enhance the relevance of data obtained for
subsequent in vivo testing.
Most immortalized hepatic cell lines are derived from carcinomas and do not
retain a full range of functional activity in vitro. Here we have compared a
novel hepatic cell line (HepaRG™), an intrinsic co-culture of hepatocyte and
cholangiocyte-like cells, with the commonly used C3A cell line which is a
derivative of HepG2 cells, in terms of metabolic competency. We found that
the HepaRG™ cells out-perform C3As in a number of metabolic functions
that include phase I and II metabolism as well as CYP activity. This makes
the HepaRG™ cell line a strong alternative to PHHs for in vitro pre-clinical
drug testing.
Next, we considered the platform for in vitro modelling. There are currently
many tissue engineering models available with improved cell culture
characteristics such as 3D spheroids, microfluidic models or 3D printing.
However, these methods are costly and time consuming. We have used
nanopatterned culture plates to develop a cheaper and faster platform that
will produce an enhanced human hepatic culture capable of sustaining a
differentiated state for several weeks. Such a model will also allow for multi-experimentation
or repeat dosage and would be a significant step towards
reducing small animal in vivo testing and may correlate better to pre-clinical
human trials.
We have specifically selected a nanopatterned and oxygen plasma treated
culture system that has shown promise in differentiating other stem-like cells
into organ specific cultures without the use of additional chemicals or
hormones. By growing HepaRG™ progenitor (HepaRG-P™ ) cells on these
prototype plates, we showed a much earlier differentiation compared with the
established HepaRG-P™ cell culture protocols. Improved functionality at this
early time point can also be seen in terms of CYP activity and markers of
maturation. There is also some evidence to suggest specific zonation of
mature HepaRG™s within this model.
Finally, a real-time, label–free monitoring of cell culture fitness, that
encompasses a quantitative analysis of cell culture during treatment with a
pharmacological agent, is desirable. An electrical cell impedance substrate
(ECIS) platform that fulfils the above criteria was validated for real-time, non-invasive,
monitoring of the HepaRG™ cell culture. Chlorpromazine (CPZ), a
model cholestatic drug, was used to assess its effect on the HepaRG™ cells
using ECIS. This study also gave us the opportunity for a more in-depth
analysis of CPZ-induced cholestasis by not only analysing tight junctions,
adhesion and cell membrane integrity, but also by studying the bile acid and
xenobiotic transporters and the inflammatory and adaptive responses to
CPZ-induced injury. We have shown disruption of membrane integrity,
changes in bile acid transporters and the regulation of both xenobiotic and
phospholipid transporters as well as inflammatory markers.
In conclusion, in this thesis I have demonstrated that by using a novel cell
line with novel prototype culture plates (nanopatterned) and a label free
technique (ECIS) to measure cellular fitness, a much improved in vitro model
of drug testing can be developed
The Selling of an Author ; Promoting John Irving
No full textCauquil Véronique. The Selling of an Author ; Promoting John Irving. In: Cahiers Charles V, n°10,1988. Le livre aujourd'hui (Grande-Bretagne, Irlande, États-Unis) pp. 91-100
Breathomics in liver disease
Get PDFBACKGROUND:
Non-alcoholic fatty liver disease (NAFLD) may progress to cirrhosis and
end-stage liver disease. The prevalence is increasing in line with the global obesity epidemic. There is a need to develop a non-invasive diagnostic tool that could be used as a point of care. Exhaled breath contains a vast array of volatile organic compounds (VOCs) with potential for diagnostic exploitation.
METHODOLOGY:
The study was a prospective single-centre cohort study (ClinicalTrials.gov: NCT02950610). In the present study, exhaled breath of 60 well-characterised NAFLD (cirrhotics and non-cirrhotic) patients was compared against that of self-declared healthy individuals. Gas chromatography - mass spectrometry and electronic signature of breath using a metal oxide semi-conductor sensor electronic nose was studied. Data were analysed using R studio (v 2.3.2) and SPSS 21. An unbiased machine learning clustering technique was applied. A 5-year longitudinal data was collected with endpoints of disease progression, liver disease-related complications and all-cause mortality.
RESULTS:
Combined dimethyl sulphide (DMS) and D-limonene led to better discrimination of patients with NAFLD cirrhosis from healthy volunteers (AUROC 0.98; 95% CI 0.93–1.00; p <0.001) and patients with NAFLD cirrhosis from those with non-cirrhotic NAFLD (AUROC 0.91; 95% CI 0.82–1.00; p <0.001). Breath terpinene concentrations discriminated between patients with non-cirrhotic NAFLD and healthy volunteers (AUROC 0.84; 95% CI 0.68–0.99; p = 0.002). The eNose was able to differentiate between healthy from non-cirrhotic NAFLD (p<0.001, CVV 96.8%) and NAFLD cirrhotic (p<0.001, CVV 95.1%). An unbiased clustering technique further classified the patients into three distinct clusters. Cluster 1 consists of 23 patients, cluster 2 consists of 24 patients, and cluster 3 consists of 13 patients. The clusters were comparable in clinical phenotyping. Cluster 2 was identified as a higher risk group with significant differences in serum hyaluronic acid levels (p=0.001), portal hypertension(p=0.003) and dimethyl sulphide (p=0.041) and D-limonene (p=0.015). Cluster 2 was associated with a significant 5-year odds risk of 8.5 [95%CI 1.8 – 39.7] for disease progression. A 25% decompensation rate, 12.5% variceal bleeding and 12.5% all-cause mortality were noted in cluster 2 compared with 4.3% and 0% for decompensation. No variceal bleeding and 1% all-cause mortality was observed in cluster 1 and 3, respectively.
CONCLUSION:
Electronic noses can differentiate between healthy and patient groups with high confidence. In addition, unbiased clustering within the NAFLD spectrum identifies three subtypes: mild, moderate, and severe disease phenotypes. These results warrant prospective studies on the potential of exhaled breath fingerprinting using eNose technology as point-of-care diagnostics and identifying high-risk disease progressors
The construction of Karen Karnak: The multi-author-function
No full textThis thesis is situated within the comparatively recent developments of Web 2.0 and the emergence of interactive WikiMedia, and explores the mode of authorship within a Read/Write culture compared to that of a Read/Only tradition. The hypothesis of this study is that the role of the audience has become merged with the author, and as such, represents new functions and attributes, distinct from a more conventional concept of authorship, in which the roles of audience and author are more separate. Read/Write and participatory culture, as defined by this study, is focused on collaboration, and includes the influences of D.I.Y. culture, Open-Source practices and the production of text by multiple authors. Multi-authorship presents a re-thinking of several concepts which support the notion of the individual author, since the focus of multi-authorship is not on attribution and ownership of a finished text, but on the continued malleability of a text. Modes of multi-authorship, demonstrated in the use of the pseudonyms Alan Smithee and Karen Eliot, represent declarative authors whose names signify multiple origins, whilst concurrently indicating a distinct body of work. The function of these names form an important context to this study, since primary research involves the construction of an experimental mode of multi-authorship utilising WikiMedia technology and the interaction of thirty nine participants, who are invited to create a body of work under the collective pseudonym Karen Karnak. The data generated by this experiment is analysed using aspects of Michel Foucault's author-function to identify and determine power structures inherent in the WikiMedia context. The interplay of power structures, including concepts such as identity, ownership and the body of work, affect the resulting mode of authorship and contribute to the construction of Karen Karnak, suggesting further areas of research into the emerging multi-author
Preclinical Experience of the Mayo Spheroid Reservoir Bioartificial Liver (SRBAL) in Management of Acute Liver Failure
Get PDFThe Spheroid Reservoir Bioartificial Liver (SRBAL) is an innovative treatment option for acute liver failure (ALF). This extracorporeal support device, which provides detoxification and other liver functions using high-density culture of porcine hepatocyte spheroids, has been reported in three randomized large animal studies. A meta-analysis of these three preclinical studies was performed to establish efficacy of SRBAL treatment in terms of survival benefit and neuroprotective effect. The studies included two hepatotoxic drug models of ALF (D-galactosamine, α-amanitin/lipopolysaccharide) or a liver resection model (85% hepatectomy) in pigs or monkeys. The SRBAL treatment was started in three different settings starting at 12 h, 24 h or 48 h after induction of ALF; comparisons were made with two similar control groups in each model. SRBAL therapy was associated with significant survival and neuroprotective benefits in all three animal models of ALF. The benefits of therapy were dose dependent with the most effective configuration of SRBAL being continuous treatment of 24 h duration and dose of 200 g of porcine hepatic spheroids. Future clinical testing of SRBAL in patients with ALF appears warranted
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