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

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

Development of the International Spinal Cord Injury Basic Data Set for Informal Caregivers

STUDY DESIGN: Mixed-methods, including expert consensus for initial development and a multi-center repeated measures design for field testing. OBJECTIVES: To develop an International Spinal Cord Injury Basic Data Set for caregivers of individuals with spinal cord injury/disorder (SCI/D) for use in research and clinical care settings. SETTING: International, multi-disciplinary working group with field testing in five North American pediatric rehabilitation hospitals. METHODS: The data set was developed iteratively through meetings and online surveys with a working group of experts in pediatric and adult SCI/D rehabilitation and caregivers of individuals with SCI/D. Initial reliability was examined through repeat administration of a beta form with a sample of caregivers recruited by convenience. The sample was characterized with descriptive statistics. Intra-rater reliability of variables was assessed using Intra-Class Correlations. RESULTS: The beta test form included 27 items, covering 3 domains: (1) demographic information for persons providing care; (2) caregiver\u27s allocation of time and satisfaction; and (3) perceived burden of caregiving. Thirty-nine caregivers completed both administrations. Mean time for completion was 10 min. There was moderate to excellent reliability for the majority of variables, but results indicated necessary revisions to improve reliability and decrease respondent burden. The final version of the data form contains 7 items and is intended for self-administration among informal caregivers of individuals with SCI/D across the lifespan. CONCLUSIONS: The International SCI Basic Data Set for Informal Caregivers can be used to standardize data collection and reporting about informal caregivers for individuals with SCI/D to advance our understanding of this population and the data form has additional utility to screen for caregiver needs in clinical settings

Serial arteriography of the dog: A simplified technique

A new technique for serial arteriography of the infradiaphragmatic arterial system in the experimental animal has been developed. Utilizing this technique 143 arteriograms have been obtained at weekly intervals in 24 dogs for up to 10 weeks. Advantages of the method are reproducible results, inexpensive equipment required, and ease of obtaining high-quality arteriograms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34186/1/0000475.pd

A highly divergent South African geminivirus species illuminates the ancient evolutionary history of this family

Background. We have characterised a new highly divergent geminivirus species, Eragrostis curvula streak virus (ECSV), found infecting a hardy perennial South African wild grass. ECSV represents a new genus-level geminivirus lineage, and has a mixture of features normally associated with other specific geminivirus genera. Results. Whereas the ECSV genome is predicted to express a replication associated protein (Rep) from an unspliced complementary strand transcript that is most similar to those of begomoviruses, curtoviruses and topocuviruses, its Rep also contains what is apparently a canonical retinoblastoma related protein interaction motif such as that found in mastreviruses. Similarly, while ECSV has the same unusual TAAGATTCC virion strand replication origin nonanucleotide found in another recently described divergent geminivirus, Beet curly top Iran virus (BCTIV), the rest of the transcription and replication origin is structurally more similar to those found in begomoviruses and curtoviruses than it is to those found in BCTIV and mastreviruses. ECSV also has what might be a homologue of the begomovirus transcription activator protein gene found in begomoviruses, a mastrevirus-like coat protein gene and two intergenic regions. Conclusion. Although it superficially resembles a chimaera of geminiviruses from different genera, the ECSV genome is not obviously recombinant, implying that the features it shares with other geminiviruses are those that were probably present within the last common ancestor of these viruses. In addition to inferring how the ancestral geminivirus genome may have looked, we use the discovery of ECSV to refine various hypotheses regarding the recombinant origins of the major geminivirus lineages. © 2009 Varsani et al; licensee BioMed Central Ltd

A highly divergent South African geminivirus species illuminates the ancient evolutionary history of this family

Background: We have characterised a new highly divergent geminivirus species, Eragrostis curvula streak virus (ECSV), found infecting a hardy perennial South African wild grass. ECSV represents a new genus-level geminivirus lineage, and has a mixture of features normally associated with other specific geminivirus genera. Results: Whereas the ECSV genome is predicted to express a replication associated protein (Rep) from an unspliced complementary strand transcript that is most similar to those of begomoviruses, curtoviruses and topocuviruses, its Rep also contains what is apparently a canonical retinoblastoma related protein interaction motif such as that found in mastreviruses. Similarly, while ECSV has the same unusual TAAGATTCC virion strand replication origin nonanucleotide found in another recently described divergent geminivirus, Beet curly top Iran virus (BCTIV), the rest of the transcription and replication origin is structurally more similar to those found in begomoviruses and curtoviruses than it is to those found in BCTIV and mastreviruses. ECSV also has what might be a homologue of the begomovirus transcription activator protein gene found in begomoviruses, a mastrevirus-like coat protein gene and two intergenic regions. Conclusion: Although it superficially resembles a chimaera of geminiviruses from different genera, the ECSV genome is not obviously recombinant, implying that the features it shares with other geminiviruses are those that were probably present within the last common ancestor of these viruses. In addition to inferring how the ancestral geminivirus genome may have looked, we use the discovery of ECSV to refine various hypotheses regarding the recombinant origins of the major geminivirus lineages

An 850 micron survey for dust around solar mass stars

We present the results of an 850 micron JCMT/SCUBA survey for dust around 13 nearby solar mass stars. The dust mass sensitivity ranged from 0.005 to 0.16 Earth masses. Three sources were detected in the survey, one of which (HD 107146) has been previously reported. One of the other two submillimeter sources, HD 104860, was not detected by IRAS and is surrounded by a cold, massive dust disk with a dust temperature and mass of Tdust = 33 K and Mdust = 0.16 Mearth. The third source, HD 8907, was detected by IRAS and ISO at 60-87 microns, and has a dust temperature and mass Tdust = 48 K and Mdust = 0.036 Mearth. We find that the deduced masses and radii of the dust disks in our sample are roughly consistent with models for the collisional evolution of planetesimal disks with embedded planets. We also searched for residual gas in two of the three systems with detected submillimeter excesses and place limits on the mass of gas residing in these systems. When the properties measured for the detected excess sources are combined with the larger population of submillimeter excess sources from the literature, we find strong evidence that the mass in small grains declines significantly on a ~200 Myr timescale, approximately inversely with age. However, we also find that the characteristic dust radii of the population, obtained from the dust temperature of the excess and assuming blackbody grains, is uncorrelated with age. This is in contrast to self-stirred collisional models for debris disk evolution which predict a trend of radius increasing with age, t ~ R^3. The lack of agreement suggests that processes beyond self-stirring, such as giant planet formation, play a role in the evolutionary histories of planetesimal disks.Comment: 31 pages, 5 figures. Accepted for publication in the Ap

Corticosteroids in experimental fat embolization

Adult mongrel dogs were given intravenous oleic acid in an experimental model of pulmonary fat embolism. The changes in PaO2, chest roentgenograms, and pulmonary tissues were less marked when high doses of corticosteroids were administered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33929/1/0000196.pd

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

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