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Thioguanine is an alternative thiopurine for inflammatory bowel disease (IBD) patients.To evaluate the short-term efficacy and safety of low-dose therapeutic drug-monitored (TDM) thioguanine.A retrospective evaluation of IBD patients intolerant to conventional thiopurines started on thioguanine from 2017 to 2019 with dosing guided by TDM was conducted. Clinical response was defined for ulcerative colitis (UC) as a reduction of partial Mayo score ≥3 with reduction in rectal bleeding score of at least 1 and a final rectal bleeding subscore of 0-1 at Week 12 of therapy. Crohn disease (CD) response was defined as a reduction of Harvey-Bradshaw index ≥3 (HBI) at Week 12 of therapy. Remission was defined in UC as partial Mayo score of2 and in CD as HBI score of5.Forty-six patients were included in the study. The median thioguanine dose was 20 mg/day (standard deviation 7.3; range: 10-40 mg/day) with a median 6-thioguanine nucleotide level of 577 pmol/8 × 108 (interquartile range (IQR) IQR 378.5-878.75) for CD and 677.5 pmol/8 × 108 (IQR 523.25-842.25) for UC. The overall clinical response rate was 62% (13/21), intention to treat (ITT). Maintenance of remission was 76% (19/25, ITT). Thirty-seven percent (17/46) of patients experienced an adverse effect. No early cases of nodular regenerative hyperplasia (NRH) were seen.Thioguanine was tolerated well in 63% of patients. A clinical response was seen in 62% of patients, and maintenance of remission was high at 76%. No cases of early NRH were seen. Longer-term follow up is required to ensure safety and to assess durability of response.

Background: Many patients presenting with an acute severe ulcerative colitis to a regional hospital are transferred to a metropolitan hospital for specialised care.Aims: To evaluate the outcomes and characteristics of these patients.Method: A retrospective observational cohort study was conducted to examine the 30-day colectomy rate using prospectively collected data on 69 consecutive index cases of acute severe ulcerative colitis transferred from regional hospitals to our metropolitan hospital meeting Truelove and Witts criteria. Those that avoided colectomy were followed out to 1 year to examine outcomes.Results: The 30-day colectomy rate was 46.4% (32/69) in regional transfer patients. Rescue therapy was administered to 65% (45/69) of patients after transfer to our metropolitan hospital. Colectomy was avoided in 55% of these patients at 30 days. Colectomy free status was maintained in 78%(29/39) of these patients. Mortality was 0% at 30 days and 1 year.Conclusion: Over 50% of the patients failing therapy in a regional centre and requiring transfer avoided short term colectomy with co-ordinated referral for rescue therapy in a tertiary metropolitan inflammatory bowel disease unit. These patients would have ultimately required colectomy in their regional hospital without intervention.

Background: Patients on immunosuppression at the time of acute severe ulcerative colitis have been suggested to be at a higher risk of colectomy than those who are treatment-naïve. The aim of this study was to examine the effect of immunosuppressive therapy on the risk of colectomy. Method: We conducted a retrospective observational cohort study using prospective data examining the 30 day and 1 year colectomy rates of 200 consecutive patients with an index episode of acute severe ulcerative colitis as defined by the Truelove and Witts criteria. Results: Immunosuppression on admission was shown not to increase colectomy rate at 30 days post-admission (immunomodulator: p = 0.422, oral steroids: p = 0.555). A total of 24 patients underwent colectomy between 30 days and 1 year. A three-fold higher risk of colectomy at 1 year was seen in those requiring an immunomodulator prior to the index admission compared with those started de novo during the index admission [41% versus 14% odds ratio (OR): 2.93 (1.19–7.24 p = 0.016)]. Factors most predictive of colectomy at 30 days were abdominal radiographic colonic dilation ⩾5.5 cm, first presentation of ulcerative colitis, C-reactive protein ⩾ 45 mg/l on day 3 of therapy and bowel frequency ⩾8 on day 3. Conclusion: The need for an immunomodulator prior to admission with acute severe ulcerative colitis increases the medium-term colectomy rate by three-fold at 1 year. Prospective studies are needed to confirm these findings and develop strategies to reduce the high risk in this subgroup of patients.

To determine characteristics and prognostic predictors of patients with hepatocellular carcinoma (HCC) in association with non-alcoholic fatty liver disease (NAFLD).We reviewed the records of all patients with NAFLD associated HCC between 2000 and 2012. Data collected included demographics; histology; presence or absence of cirrhosis, size and number of HCC, alpha-fetoprotein, body mass index (BMI), and the presence of diabetes, hypertension, or dyslipidaemia.Fifty-four patients with NAFLD associated HCC were identified. Mean age was 64 years with 87% male. Fifteen percent (8/54) were not cirrhotic. 11%, 24% and 50% had a BMI of25 kg/m2, 25-29 kg/m2 and ≥30 kg/m2 respectively. Fifty-nine percent were diabetic, 44% hypertensive and 26% hyperlipidaemic. Thirty-four percent of the patients had ≤1 of these risk factors. Non-cirrhotics had a significantly larger mean tumour diameter at diagnosis than cirrhotics (P=0.041). Multivariate analysis did not identify any other patient characteristics that predicted the size or number of HCC.HCC can develop in NAFLD without cirrhosis. At diagnosis such tumours are larger than those in cirrhotics, conferring a poorer prognosis.

The advent of u-learning environments requires the development of appropriate u-learning models to inform the use of such environments. As there is no single u-learning model to suit all environments and learning situations, there is a need to develop a methodology for developing models appropriate to various environments and situations. This chapter outlines such a methodology as a useful framework on which to base the derivation of particular models for specific situations. The study then illustrates the use of this methodology to derive a particular model: a task-based u-learning model, incorporating well-bounded learning content. Following this, the study proposes a system architecture to embody this derived u-learning model, and, then describes the implementation of this architecture through the development and deployment of the Walkabout u-Learning Environment.

Protein is the major component of the intra-lysosomal storage material which characteristically accumulates in Batten's disease. In the late-infantile, juvenile and adult forms of the disease, and in a form affecting sheep, this protein is principally composed of a single polypeptide, subunit c of mitochondrial ATP synthase. Subunit c is not stored in the infantile form of Batten's disease, supporting recent genetic data which suggest this is a distinct disease. Nor is subunit c found in storage material within other lysosomal storage diseases or in lipofuscin of old age. Subunit c storage, therefore, is specific for the later-onset forms of Batten's disease and indeed may be central to their aetiology.

A platform independent agent-based virtual educational environment (PIAVEE) is described. PIAVEE is conceptualized as a lightweight, flexible environment that links educational resources through a virtual data base and that is supported by an intelligent delivery system. PIAVEE is implemented through an evolutionary process, whose initial focus is the development of and access to, the virtual data base. The paper describes the initial implementations, which focus on proof of concept and basic level functionality.

Ovine ceroid-lipofuscinosis is an inherited neurodegenerative disorder characterised by the accumulation of storage cytosomes in brain and visceral organs. Phosphorylated dolichol-containing compounds, largely in the form of dolichyl pyrophosphoryl oligosaccharides, have been shown to constitute 1–2% of the dry weight of storage cytosomes isolated from brain and pancreas, and 0.5 and 0.1% respectively of storage cytosomes insolated from liver and kidney. The carbohydrate portion of these glyconjugates in storage cytosomes insolated from brain, pancreas and liver consisted of a series of oligosaccharides of composition Man 2–9 GlcNAc 2 , with Man 5–8 GlcNAc 2 predominating. The concentrations of dolichyl pyrophosphoryl oligosaccharides in storage cytosomes from ovine ceroid-lipofuscinosis are much higher than has been reported for endoplasmic reticulum, their normal functional location.

The concentrations of phosphorylated dolichol (P-dolichol) and of non-phos-phorylated dolichol were estimated in a number of different tissues from ceroid-lipofuscinosis (CL) and control cases. The P-dolichol contents of four tissues, brain, pancreas, muscle and kidney were significantly greater than control values. Liver and spleen showed little or no increase in P-dolichol content. Though non-phos-phorylated dolichol levels were higher in CL tissues than in control tissues, the differences were significant only for brain and pancreas. In control muscle, a linear age-related increase in non-phosphorylated dolichol content was observed. The relative amounts of the major homologs of P-dolichol and of non-phosphorylated dolichol were estimated. Each tissue has a characteristic homolog size-distribution, and there is close similarity between the size-distribution profiles of P-dolichol and of non-phosphorylated dolichol for each tissue.

Because differences in hexosaminidase isoenzyme profiles of granulocytes and lymphocytes suggested that such profiles might help to distinguish between various types of leukemia, we examined leukocyte extracts from 55 untreated children and 12 controls by automated anion-exchange chromatography. In 23 of 27 cases of the common form of childhood acute lymphoblastic leukemia, the activity of hexosaminidase component I was greatly increased; the activity ratio of hexosaminidase I to hexosaminidase A was greater than 0.5 in 18 of these cases, whereas for other types of leukemia and for all normal cells tested, the ratio was less than 0.2. A raised hexosaminidase I was shown to be associated with leukemic cells by the finding of normal isoenzyme profiles of bone-marrow cells from 17 patients in remission who had such an increase either at diagnosis or in relapse. Hexosaminidase isoenzyme analysis had diagnostic value and may provide a new marker for study of leukocyte differentiation. (N Engl J Med 29...

• In an infant with Wolman disease, confirmation of the diagnosis was made before death or radiological and enzymological criteria. It is the first case reported in a Pakistani infant. (Am J Dis Child130:545-547, 1976)

This thesis deals with the problem of digital communication over noisy dispersive channels. The dispersion causes the overlapping of successive received pulses thus creating intersymbol interference which severely limits the performance of conventional receivers designed to combat only additive interference or noise. In this thesis Bayes estimation theory has been applied to obtain a new, optimum, unrealizable receiver structure for the improved reception of noisy, dispersed, pulse amplitude-modulated (PAM) signals. By making certain approximations, a realization of this structure, known as the estimate feedback receiver or equalizer, is obtained. It consists of the combination of a matched filter and a nonlinear, recursive equalizer having, in the case of binary signals, a hyperbolic tangent nonlinearity in the feedback path. The well known decision feedback equalizer is shown to be a small noise limiting case of the estimate feedback equalizer. A saturating limiter is also considered as an approximation to the hyperbolic tangent nonlinearity. A new adaptive algorithm for the iterative adjustment of the estimate feedback equalizer is derived. It incorporates an extrapolation process which has the purposes of accelerating convergence of the equalizer's parameters to their optimum values and of maintaining the equalizer's frame of reference. It is constrained so that the equalizers parameters always move toward their optimum values. Computer simulations are used to demonstrate the properties of the adaptive estimate feedback equalizer and to compare them to those of presently known equalizers. When the estimate feedback equalizer is used, without a matched filter preceding it, to equalize phase distorted channels, its performance is seen to be superior to that of existing equalizers. The performance of an equalizer using a saturating limiter in place of the optimum hyperbolic tangent nonlinearity is seen to be almost as good as that of the estimate feedback equalizer. Thesis Doctor of Philosophy (PhD)

A collection of folklore and local history stories from Pádraig Naofa, Droichead Banndan (school) (Bandon, Co. Cork), collected as part of the Schools' Folklore Scheme, 1937-1938 under the supervision of teacher Pádraig Ó Faoláin., Surfeit Well / Mahony, Kevin O' -- Kilbrittain Castle / Ahern, John -- Sore Eye Well / Walsh, Michael -- Christmas Customs -- Tigh Molaige / Ahern, John -- Old Head of Kinsale Lighthouse / Ahern, John -- Haunted House / Rearden, Jeremiah -- Faction Fights / Reardon, Jeremiah -- Áit a' Chóiste -- I once heard of a young boy who lived near the sea so that it was customary for him to cross some fields to take him to the beach. -- Haunted Castle -- Kilbrogan Churchyard / Walsh, Michael -- Seán Dearg Nash / Walsh, Michael -- Ghost-Story / Shannon, Henry -- There is a haunted house not far from Bandon. -- Holy Well / Jennings, Thomas -- Old Cures -- There are many stories told about fairies and their doings. -- Tobar na Súl / Mahony, Kevin O -- Cill Cholmáin / Murphy, Donal -- Gaggan / Murphy, Donal -- Castlebernard -- At the back of my uncle's house there is an old fort. / Scannell, James -- This is a story which is spoken of by the people of Bandon. / Mahony, Jeremiah O -- Leigheasanna Áitiúla -- Ainmneacha Áiteanna Aitiúla -- Caisleán Uí Mhathúna -- Cill Mo Eassan / Hyde, Joe -- Old Fairs and Markets in Bandon -- Tan-Yards -- Distilleries and Breweries -- Bandon River and Bandon / Crowley, Mr Stephen -- Bandon Bridge was the name given to the new town by the English but the Irish would not listen to it. / Crowley, Mr Stephen -- Cromwell in Bandon / Crowley, Mr Stephen -- Seanscéal i dtaobh Tigh Molaige / Leary, Humphrey O' -- Aibítir -- Miss Mary Hickey now Mrs. Sullivan was evicted from her father's house in Kilbeg in her young days by the bailiffs. / Crotty, Thomas -- Poem -- Tannery and weaving were the chief industries in Bandon about 100 years ago. / Burke, Gregory -- In the dealyard near the Dispensary was a stage coach (Bianconi) station. -- Tugtar "Síghle Muinnteardha" ar dhuine a bhíonn go mór le gach aoinne. / Leary, Humphrey O' -- Seanráite -- Scéalta -- Caoineadh -- Father Thomas Shinnick / Crowley, Mr Stephen -- Cotton-Mills of Bandon / Crowley, Mr Stephen -- Castlelack or Caisleán na Leachta / Crowley, Mr Stephen -- Scéal -- Scéal / Leary, Humphrey O' -- Donchadh Dubh - Highwayman / Crowley, Mr Stephen -- Old Preaching House or Unitarian Church, Bandon / Crowley, Mr Stephen -- Charm / Scannell, James -- Story / Scannell, James -- Story / Carthy, Timothy Mc -- In Caisleán na Leachta, Bandon in the lane leading to the house where Sean Dearg nash lived there is a large stone. -- Story / Twomey, Timothy -- Story -- About sixty years ago an old bróg fair was held annually in Ballineen. / Burke, Dermot -- Bleach / Desmond, Patrick -- Factory Lane / Desmond, Patrick -- Story -- Paddy Gaffney was the first Catholic to live in Bandon. / Lucey, Michael -- Bean a chailla céile. / Leary, Humphrey O' -- Paidir i gcomhair an Tromluí -- Seanráite Eile -- Uair amháin do dhein tailliúir clóca do cailín. -- Hanging Holiday in Bandon / Crowley, Mr S.J. -- At Gallows' Hill -- Bandon and its Churches -- St Patrick's Catholic Church, Bandon -- Famous Bishop -- Distinguished Pastor -- Kilbrogan Church -- At Gurteen -- At an election of member of Parliament for the Borough of Bandon Bridge held in Courthouse, Bandon, on December 13th, 1832 the following persons voted. -- Legend of Downdaniel -- Barry Óg -- Biographical Sketches of Persons Remarkable in Local History - Daniel Maclise -- Kinalmeaky -- Bandon -- Pound -- Hatters' Lane -- Burial Scene in Bandon 1829 / Coughlan, John B. -- Scenes at an Election of MP for Bandon Borough -- St Peter's Church Bells -- Street Ballad / Coughlan, John B., Supported by funding from the Department of Arts, Heritage and the Gaeltacht (Ireland), University College Dublin, and the National Folklore Foundation (Fondúireacht Bhéaloideas Éireann), 2014-2016.