The detection of circulating tumour cells in oesophageal adenocarcinoma

MD ThesisThe incidence of oesophageal adenocarcinoma is rising. Overall survival rates remain poor. Traditional methods of staging oesophageal adenocarcinoma fail to identify patients at high risk of early disease recurrence after surgical treatment with curative intent. Circulating tumour cells have been reported to offer prognostic information in patients with certain tumour types including breast, prostate and colorectal. The majority of studies have focused on circulating tumour cell enumeration in patients with metastatic disease. Little is known about the role of circulating tumour cells in oesophageal adenocarcinoma or of the importance of circulating tumour cells in patients without metastatic disease. Cultured oesophageal adenocarcinoma cell lines were used to develop and validate a novel method for detection of tumour cells in whole blood. The method used positive depletion of normal blood cell populations before imaging the cells with an Imagestreamx image flow cytometer. A panel of fluorescently-conjugated antibodies against EpCAM, cytokeratins, survivin, CD45 and DAPI were used to discriminate the tumour cells. A consistent recovery of 48% was achieved across a range of concentrations of cultured oesophageal adenocarcinoma cells added to whole blood. Blood samples from 25 patients undergoing staging for oesophageal adenocarcinoma without known distant metastatic disease were studied. Circulating tumour cells were identified in 5 patients, range 2 – 85 per 5 ml whole blood. Circulating tumour-associated macrophages were identified in a single patient. No difference in overall survival was demonstrated between those patients with circulating tumour cells compared to those without. The developed method produces high quality images allowing for the detection and characterisation of circulating tumour cells. Heterogeneity within the circulating tumour cell population was observed. Circulating tumour cells may be identified in a significant number of patients with oesophageal adenocarcinoma without radiological evidence of distant metastatic disease

Type 2 diabetes in young Indigenous Australians in rural and remote areas: diagnosis screening management and prevention

The burden of type 2 diabetes mellitus (T2DM) among Indigenous children and adolescents is much greater than in non-Indigenous young people and appears to be rising, although data on epidemiology and complications are limited. Young Indigenous people living in remote areas appear to be at excess risk of T2DM.Most young Indigenous people with T2DM are asymptomatic at diagnosis and typically have a family history of T2DM, are overweight or obese and may have signs of hyperinsulinism such as acanthosis nigricans. Onset is usually during early adolescence.Barriers to addressing T2DM in young Indigenous people living in rural and remote settings relate to health service access, demographics, socioeconomic factors, cultural factors, and limited resources at individual and health service levels.We recommend screening for T2DM for any Aboriginal or Torres Strait Islander person aged > 10 years (or past the onset of puberty) who is overweight or obese, has a positive family history of diabetes, has signs of insulin resistance, has dyslipidaemia, has received psychotropic therapy, or has been exposed to diabetes in utero.Individualised management plans should include identification of risk factors, complications, behavioural factors and treatment targets, and should take into account psychosocial factors which may influence health care interaction, treatment success and clinical outcomes.Preventive strategies, including lifestyle modification, need to play a dominant role in tackling T2DM in young Indigenous people

Resolving debris discs in the far-infrared: early highlights from the DEBRIS survey

We present results from the earliest observations of DEBRIS, a Herschel Key Programme to conduct a volume- and flux-limited survey for debris discs in A-type through M-type stars. PACS images (from chop/nod or scan-mode observations) at 100 and 160 micron are presented toward two A-type stars and one F-type star: beta Leo, beta UMa and eta Corvi. All three stars are known disc hosts. Herschel spatially resolves the dust emission around all three stars (marginally, in the case of beta UMa), providing new information about discs as close as 11 pc with sizes comparable to that of the Solar System. We have combined these data with existing flux density measurements of the discs to refine the SEDs and derive estimates of the fractional luminosities, temperatures and radii of the discs.Comment: to be published in A&A, 5 pages, 2 color figure

The Quark-Mass Dependence of Two-Nucleon Systems

We explore the quark-mass dependence of two-nucleon systems. Allowed regions for the scattering lengths in the 1S0 and 3S1 channels as functions of the light-quark masses are determined from the current uncertainty in strong-interaction parameters that appear at next-to-leading order in the effective field theory. Where experimental constraints are absent, as is the case for the quark-mass dependent four-nucleon operators, we use naive dimensional analysis. We find it likely that there is no bound state in the 1S0 channel in the chiral limit. However, given the present uncertainties in strong-interaction parameters it is unclear whether the deuteron is bound or unbound in the chiral limit.Comment: 12 pages LaTeX, 6 ps figs, comments adde

CP Violation beyond the Standard Model

In this talk a number of broad issues are raised about the origins of CP violation and how to test the ideas.Comment: 17 pages, LaTeX, 6 postscript figures. Uses iopart10.clo, iopart12.clo and iopart.cls. Plenary talk given at the BSM Phenomenology Workshop, Durham, UK, 6-11 May 2001. To appear in the proceeding

Observations of Massive Star Forming Regions with Water Masers: Mid-Infrared Imaging

We present here a mid-infrared imaging survey of 26 sites of water maser emission. Observations were obtained at the InfraRed Telescope Facility 3-m telescope with the University of Florida mid-infrared imager/spectrometer OSCIR, and the JPL mid-infrared camera MIRLIN. The main purpose of the survey was to explore the relationship between water masers and the massive star formation process. It is generally believed that water masers predominantly trace outflows and embedded massive stellar objects, but may also exist in circumstellar disks around young stars. We investigate each of these possibilities in light of our mid-infrared imaging. We find that mid-infrared emission seems to be more closely associated with water and OH maser emission than cm radio continuum emission from UC HII regions. We also find from the sample of sources in our survey that, like groups of methanol masers, both water and OH masers have a proclivity for grouping into linear or elongated distributions. We conclude that the vast majority of linearly distributed masers are not tracing circumstellar disks, but outflows and shocks instead.Comment: 49 pages; 23 figures; To appear in February 2005 ApJS; To download a version with better quality figures, go to http://www.ctio.noao.edu/~debuizer

The Effectiveness of Alcohol Screening and Brief Intervention in Emergency Departments: A Multicentre Pragmatic Cluster Randomized Controlled Trial

BACKGROUND: Alcohol misuse is common in people attending emergency departments (EDs) and there is some evidence of efficacy of alcohol screening and brief interventions (SBI). This study investigated the effectiveness of SBI approaches of different intensities delivered by ED staff in nine typical EDs in England: the SIPS ED trial. METHODS AND FINDINGS: Pragmatic multicentre cluster randomized controlled trial of SBI for hazardous and harmful drinkers presenting to ED. Nine EDs were randomized to three conditions: a patient information leaflet (PIL), 5 minutes of brief advice (BA), and referral to an alcohol health worker who provided 20 minutes of brief lifestyle counseling (BLC). The primary outcome measure was the Alcohol Use Disorders Identification Test (AUDIT) status at 6 months. Of 5899 patients aged 18 or more presenting to EDs, 3737 (63·3%) were eligible to participate and 1497 (40·1%) screened positive for hazardous or harmful drinking, of whom 1204 (80·4%) gave consent to participate in the trial. Follow up rates were 72% (n?=?863) at six, and 67% (n?=?810) at 12 months. There was no evidence of any differences between intervention conditions for AUDIT status or any other outcome measures at months 6 or 12 in an intention to treat analysis. At month 6, compared to the PIL group, the odds ratio of being AUDIT negative for brief advice was 1·103 (95% CI 0·328 to 3·715). The odds ratio comparing BLC to PIL was 1·247 (95% CI 0·315 to 4·939). A per protocol analysis confirmed these findings. CONCLUSIONS: SBI is difficult to implement in typical EDs. The results do not support widespread implementation of alcohol SBI in ED beyond screening followed by simple clinical feedback and alcohol information, which is likely to be easier and less expensive to implement than more complex interventions

Employing Dietary Comparators to Perform Risk Assessments for Anti-Androgens Without Using Animal Data

This study investigated the use of androgen receptor (AR) reporter gene assay data in a non-animal exposure-led risk assessment in which in vitro anti-androgenic activity and exposure data were put into context using a naturally occurring comparator substance with a history of dietary consumption. First, several dietary components were screened to identify which selectively interfered with AR signaling in vitro, using the AR CALUX® test. The IC50 values from these dose-response data together with measured or predicted human exposure levels were used to calculate exposure:activity ratios (EARs) for the dietary components and a number of other well-known anti-androgenic substances. Both diindolylmethane (DIM) and resveratrol are specifically-acting dietary anti-androgens. The EARs for several anti-androgens were therefore expressed relative to the EAR of DIM, and how this ‘dietary comparator ratio’ (DCR) approach may be used to make safety decisions was assessed using an exposure-led case study for an anti-androgenic botanical ingredient. This highlights a pragmatic approach which allows novel chemical exposures to be put into context against dietary exposures to natural anti-androgenic substances. The DCR approach may have utility for other modes of action where appropriate comparators can be identified

Observational diagnostics of gas in protoplanetary disks

Protoplanetary disks are composed primarily of gas (99% of the mass). Nevertheless, relatively few observational constraints exist for the gas in disks. In this review, I discuss several observational diagnostics in the UV, optical, near-IR, mid-IR, and (sub)-mm wavelengths that have been employed to study the gas in the disks of young stellar objects. I concentrate in diagnostics that probe the inner 20 AU of the disk, the region where planets are expected to form. I discuss the potential and limitations of each gas tracer and present prospects for future research.Comment: Review written for the proceedings of the conference "Origin and Evolution of Planets 2008", Ascona, Switzerland, June 29 - July 4, 2008. Date manuscript: October 2008. 17 Pages, 6 graphics, 134 reference

Conflicting logics of public relations in the English NHS: a qualitative study of communications and engagement

Since the formation of the NHS, all UK citizens have been entitled to access a universal health service, but radical changes to the NHS are now occurring. Although recent NHS policy claims that ‘the NHS belongs to us all’ and ‘the NHS is a social movement’, these collectivist rhetorical claims appear when such communitarian discourse is under threat, as NHS England’s (2014) Five Year Forward View tries to square the circle of efficiency, quality and equity. Historically, patients and user-groups have formed support networks and social movements, and collectively campaigned for their voices to be heard by policy makers, clinicians and managers. In contrast to the discourse of user movements, the field of marketing and public relations generally relies on the idea of the public as consumers rather than citizens. As complex governance arrangements blur the lines between public and private, concerns have been raised about how ‘spin’ associated with public relations might contravene accountability, communicative rationality and deliberative or participatory democracy. Using qualitative methods, we conducted empirical research in two localities to explore the role of communications and engagement staff as they worked to ‘transform’ the NHS in line with the vision of the Five Year Forward View. We gathered documentary data and interview data from people whose roles required them to ‘do engagement’. These staff came from a range of backgrounds, including professional marketing backgrounds, and many were unaware of emancipatory goals or user-led involvement and activism. Our analysis examines the competing logics of marketing and patient empowerment within a key stakeholder matrix document and that surfaced in participants’ accounts of their engagement practices.NIH