Behavioural characteristics of the cells which form epiretinal membranes

Epiretinal membranes are contractile cellular proliferations that form on the surfaces of the retina after trauma or insult to the posterior segment of the eye. Key cell types involved in membrane formation are retinal glia, retinal pigment epithelia and fibroblastic cells. A bovine tissue culture test system comprising bovine retinal glia, bovine retinal pigment epithelia and bovine scleral fibroblasts was employed in a series of behavioural studies to investigate the effect of soluble mediators and cell contact on migration, settlement and proliferation of the three key cell types in membrane formation. Migration was assessed in vitro in a modified 48-well Boyden chamber, employing a standard chemoattraction assay. The migration of all three test cell types was stimulated by a glycoprotein found abundantly in epiretinal membranes (fibronectin), samples of subretinal fluid and a retinal crude extract. Cells grown from epiretinal membranes removed during surgery for retinal detachment also migrated to fibronectin. Retinal pigment epithelial cells showed less aptitude for migration to soluble stimuli in a Boyden chamber than the other two cell types and when the cell types were labelled and migrated together, the retinal pigment epithelium still migrated less than the other two cell types. Retinal pigment epithelium were also less responsive to platelet derived growth factor. Static cell settlement studies demonstrated that retinal pigment epithelial cells showed more affinity for settlement onto plastic and in the presence of soluble fibronectin, than the other two cell types but the surface of a retinal glial monolayer appeared to be a less attractive substrate than serum coated plastic for the settlement of all three cell types. Video time-lapse microscopy was employed to monitor the settlement of retinal pigment epithelium onto glial and mixed cell layers. It revealed that the settlement process, in which distinct and reproducible stages could be identified, to be one of invasion and incorporation of the test cell types into the underlying cell layer. The fibroblasts entered a glial monolayer more rapidly than the pigment epithelia but the latter after entry, provoked a wave of glial mitotic activity. The results indicated that within the confines of the test system there was interaction between the cell types, both through cell contact and remotely via soluble mediators and these affected the behavioural responses of migration, settlement and proliferation. The findings when extrapolated to epiretinal membrane formation indicated that: the glia were not a particularly good substrate for either fibroblasts or retinal pigment epithelium. The glia secreted substances attractive for the settlement of the retinal pigment epithelium and for the migration of all three cell types and media collected from cultures of retinal pigment epithelial cells was stimulatory for a whole range of activities and provoked a powerful migratory response from the fibroblasts. So that the retinal pigment epithelium though possibly not the most important cell type in epiretinal membranes have an important role in membrane formation by releasing bioactive substances which attract and modify the behaviour of other cell types

Palliative care needs in patients hospitalized with heart failure (PCHF) study: rationale and design

Abstract Aims The primary aim of this study is to provide data to inform the design of a randomized controlled clinical trial (RCT) of a palliative care (PC) intervention in heart failure (HF). We will identify an appropriate study population with a high prevalence of PC needs defined using quantifiable measures. We will also identify which components a specific and targeted PC intervention in HF should include and attempt to define the most relevant trial outcomes. Methods An unselected, prospective, near-consecutive, cohort of patients admitted to hospital with acute decompensated HF will be enrolled over a 2-year period. All potential participants will be screened using B-type natriuretic peptide and echocardiography, and all those enrolled will be extensively characterized in terms of their HF status, comorbidity, and PC needs. Quantitative assessment of PC needs will include evaluation of general and disease-specific quality of life, mood, symptom burden, caregiver burden, and end of life care. Inpatient assessments will be performed and after discharge outpatient assessments will be carried out every 4 months for up to 2.5 years. Participants will be followed up for a minimum of 1 year for hospital admissions, and place and cause of death. Methods for identifying patients with HF with PC needs will be evaluated, and estimates of healthcare utilisation performed. Conclusion By assessing the prevalence of these needs, describing how these needs change over time, and evaluating how best PC needs can be identified, we will provide the foundation for designing an RCT of a PC intervention in HF

A Spectroscopic Study of the Environments of Gravitational Lens Galaxies

(Abridged) We present the first results from our spectroscopic survey of the environments of strong gravitational lenses. The lens galaxy belongs to a poor group of galaxies in six of the eight systems in our sample. We discover three new groups associated with the lens galaxies of BRI 0952-0115 (five members), MG 1654+1346 (seven members), and B2114+022 (five members). We more than double the number of members for another three previously known groups around the lenses MG 0751+2716 (13 total members), PG 1115+080 (13 total members), and B1422+231 (16 total members). We determine the kinematics of the six groups, including their mean velocities, velocity dispersions, and projected spatial centroids. The velocity dispersions of the groups range from 110 +170, -80 to 470 +100, -90 km/s. In at least three of the lenses -- MG0751, PG1115, and B1422 -- the group environment significantly affects the lens potential. These lenses happen to be the quadruply-imaged ones in our sample, which suggests a connection between image configuration and environment. The lens galaxy is the brightest member in fewer than half of the groups. Our survey also allows us to assess for the first time whether mass structures along the line of sight are important for lensing. We first show that, in principle, the lens potential may be affected by line-of-sight structures over a wide range of spatial and redshift offsets from the lens. We then quantify real line-of-sight effects using our survey and find that at least four of the eight lens fields have substantial interloping structures close in projection to the lens, and at least one of those structures (in the field of MG0751) significantly affects the lens potential.Comment: Accepted for publication in the Astrophysical Journal. Figure 6 posted as a JPEG image. Requires emulateapj.st

Mid-Infrared Evidence for Accelerated Evolution in Compact Group Galaxies

We find evidence for accelerated evolution in compact group galaxies from the distribution in mid-infrared colorspace of 42 galaxies from 12 Hickson Compact Groups (HCGs) compared to the the distributions of several other samples including the LVL+SINGS galaxies, interacting galaxies, and galaxies from the Coma Cluster. We find that the HCG galaxies are not uniformly distributed in colorspace, as well as quantitative evidence for a gap. Galaxies in the infall region of the Coma cluster also exhibit a non-uniform distribution and a less well defined gap, which may reflect a similarity with the compact group environment. Neither the Coma Center or interacting samples show evidence of a gap, leading us to speculate that the gap is unique to the environment of high galaxy density where gas has not been fully processed or stripped.Comment: To appear in the Proceedings of the Galaxy Wars: Stellar Populations and Star Formation in Interacting Galaxies Conferenc

Comparison of various characteristics of women who do and do not attend for breast cancer screening

BACKGROUND: Information regarding the characteristics and health of women who do and do not attend for breast cancer screening is limited and representative data are difficult to obtain. METHODS: Information on age, deprivation and prescriptions for various medications was obtained for all women at two UK general practices who were invited to breast cancer screening through the National Health Service Breast Screening Programme. The characteristics of women who attended and did not attend screening were compared. RESULTS: Of the 1064 women invited to screening from the two practices, 882 (83%) attended screening. Screening attenders were of a similar age to non-attenders but came from significantly less deprived areas (30% of attenders versus 50% of non-attenders came from the most deprived areas, P < 0.0001) and were more likely to have a current prescription for hormone replacement therapy (32% versus 19%, P < 0.0001). No significant differences in recent prescriptions of medication for hypertension, heart disease, hypercholesterolaemia, diabetes mellitus, asthma, thyroid disease or depression/anxiety were observed between attenders and non-attenders. CONCLUSION: Women who attend the National Health Service Breast Screening Programme come from less deprived areas and are more likely to have a current prescription for hormone replacement therapy than non-attenders, but do not differ in terms of age or recent prescriptions for various other medications

Epidemiological study of E. coli O157:H7 isolated in Northern Ireland using pulsed-field gel electrophoresis (PFGE)

In Northern Ireland over the last 7 years, there is a mean of 41.9 laboratory reports per annum of human gastrointestinal infection (range 19-54) caused by Escherichia coli O157:H7. In the preceding years 1992-1996, reports were 5.4 per annum, whereas in 1997-2000, reports increased from 30 to 54 per annum. This high level has continued on an annual basis to date. The aim of this study was therefore to retrospectively examine this period of exponential increase in reports to help ascertain the genetic relatedness of strains employing pulsed-field gel electrophoresis (PFGE), as no data on the molecular epidemiology of E. coli O157:H7 in Northern Ireland has yet been published. Clinical isolates (n=84) were PFGE typed employing Xba I digestion and resulting band profiles demonstrated the presence of 13, 9 and 16 clonal types, for 1997, 1998 and 1999, respectively. In 1998, five clonal types remained from 1997 with the introduction of 4 new clonal types, whereas in 1999, 10 new clonal types were observed, accounting for over half (58%) of the E. coli O157 isolates for that year. These data suggest that, unlike gastrointestinal infections due to thermophilic campylobacters, there was considerable genetic evolution of PFGE clonal types of E. coli O157, through the displacement and emergence of genotypes. Further studies are now required to find the environmental reservoirs of these common clonal types of clinical E. coli O157:H7 in Northern Ireland to help define sources and routes of transmission of this infection locally

Factors Associated With the Frequency of Monitoring of Liver Enzymes, Renal Function and Lipid Laboratory Markers Among Individuals Initiating Combination Antiretroviral Therapy: A Cohort Study

Background As the average age of the HIV-positive population increases, there is increasing need to monitor patients for the development of comorbidities as well as for drug toxicities. Methods We examined factors associated with the frequency of measurement of liver enzymes, renal function tests, and lipid levels among participants of the Canadian Observational Cohort (CANOC) collaboration which follows people who initiated HIV antiretroviral therapy in 2000 or later. We used zero-inflated negative binomial regression models to examine the associations of demographic and clinical characteristics with the rates of measurement during follow-up. Generalized estimating equations with a logit link were used to examine factors associated with gaps of 12&nbsp;months or more between measurements. Results Electronic laboratory data were available for 3940 of 7718 CANOC participants. The median duration of electronic follow-up was 3.5&nbsp;years. The median (interquartile) rates of tests per year were 2.76 (1.60, 3.73), 2.55 (1.44, 3.38) and 1.42 (0.50, 2.52) for liver, renal and lipid parameters, respectively. In multivariable zero-inflated negative binomial regression models, individuals infected through injection drug use (IDU) were significantly less likely to have any measurements. Among participants with at least one measurement, rates of measurement of liver, renal and lipid tests were significantly lower for younger individuals and Aboriginal Peoples. Hepatitis C co-infected individuals with a history of IDU had lower rates of measurement and were at greater risk of having 12&nbsp;month gaps between measurements. Conclusions Hepatitis C co-infected participants infected through IDU were at increased risk of gaps in testing, despite publicly funded health care and increased risk of comorbid conditions. This should be taken into consideration in analyses examining factors associated with outcomes based on laboratory parameters

Association Between Myopia, Ultraviolet B Radiation Exposure, Serum Vitamin D Concentrations, and Genetic Polymorphisms in Vitamin D Metabolic Pathways in a Multicountry European Study.

IMPORTANCE: Myopia is becoming increasingly common globally and is associated with potentially sight-threatening complications. Spending time outdoors is protective, but the mechanism underlying this association is poorly understood. OBJECTIVE: To examine the association of myopia with ultraviolet B radiation (UVB; directly associated with time outdoors and sunlight exposure), serum vitamin D concentrations, and vitamin D pathway genetic variants, adjusting for years in education. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional, population-based random sample of participants 65 years and older was chosen from 6 study centers from the European Eye Study between November 6, 2000, to November 15, 2002. Of 4187 participants, 4166 attended an eye examination including refraction, gave a blood sample, and were interviewed by trained fieldworkers using a structured questionnaire. Myopia was defined as a mean spherical equivalent of -0.75 diopters or less. Exclusion criteria included aphakia, pseudophakia, late age-related macular degeneration, and vision impairment due to cataract, resulting in 371 participants with myopia and 2797 without. EXPOSURES: Exposure to UVB estimated by combining meteorological and questionnaire data at different ages, single-nucleotide polymorphisms in vitamin D metabolic pathway genes, serum vitamin D3 concentrations, and years of education. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) of UVB, serum vitamin D3 concentrations, vitamin D single-nucleotide polymorphisms, and myopia estimated from logistic regression. RESULT: Of the included 3168 participants, the mean (SD) age was 72.4 (5) years, and 1456 (46.0%) were male. An SD increase in UVB exposure at age 14 to 19 years (OR, 0.81; 95% CI, 0.71-0.92) and 20 to 39 years (OR, 0.7; 95% CI, 0.62-0.93) was associated with a reduced adjusted OR of myopia; those in the highest tertile of years of education had twice the OR of myopia (OR, 2.08; 95% CI, 1.41-3.06). No independent associations between myopia and serum vitamin D3 concentrations nor variants in genes associated with vitamin D metabolism were found. An unexpected finding was that the highest quintile of plasma lutein concentrations was associated with a reduced OR of myopia (OR, 0.57; 95% CI, 0.46-0.72). CONCLUSIONS AND RELEVANCE: Increased UVB exposure was associated with reduced myopia, particularly in adolescence and young adulthood. The association was not altered by adjusting for education. We found no convincing evidence for a direct role of vitamin D in myopia risk. The relationship between high plasma lutein concentrations and a lower risk of myopia requires replication