Feasibility of transit photometry of nearby debris discs

Dust in debris discs is constantly replenished by collisions between larger objects. In this paper, we investigate a method to detect these collisions. We generate models based on recent results on the Fomalhaut debris disc, where we simulate a background star transiting behind the disc, due to the proper motion of Fomalhaut. By simulating the expanding dust clouds caused by the collisions in the debris disc, we investigate whether it is possible to observe changes in the brightness of the background star. We conclude that in the case of the Fomalhaut debris disc, changes in the optical depth can be observed, with values of the optical depth ranging from $10^{-0.5}$ for the densest dust clouds to $10^{-8}$ for the most diffuse clouds with respect to the background optical depth of $\sim1.2\times10^{-3}$.Comment: 19 pages, 15 figures, accepted for publication in MNRA

Dust absorption and scattering in the silicon K-edge

The composition and properties of interstellar silicate dust are not well understood. In X-rays, interstellar dust can be studied in detail by making use of the fine structure features in the Si K-edge. The features in the Si K-edge offer a range of possibilities to study silicon-bearing dust, such as investigating the crystallinity, abundance, and the chemical composition along a given line of sight. We present newly acquired laboratory measurements of the silicon K-edge of several silicate-compounds that complement our measurements from our earlier pilot study. The resulting dust extinction profiles serve as templates for the interstellar extinction that we observe. The extinction profiles were used to model the interstellar dust in the dense environments of the Galaxy. The laboratory measurements, taken at the Soleil synchrotron facility in Paris, were adapted for astrophysical data analysis and implemented in the SPEX spectral fitting program. The models were used to fit the spectra of nine low-mass X-ray binaries located in the Galactic center neighborhood in order to determine the dust properties along those lines of sight. Most lines of sight can be fit well by amorphous olivine. We also established upper limits on the amount of crystalline material that the modeling allows. We obtained values of the total silicon abundance, silicon dust abundance, and depletion along each of the sightlines. We find a possible gradient of $0.06\pm0.02$ dex/kpc for the total silicon abundance versus the Galactocentric distance. We do not find a relation between the depletion and the extinction along the line of sight.Comment: 18 pages, 16 figures. Accepted for publication in Astronomy and Astrophysic

Investigating the interstellar dust through the Fe K-edge

The chemical and physical properties of interstellar dust in the densest regions of the Galaxy are still not well understood. X-rays provide a powerful probe since they can penetrate gas and dust over a wide range of column densities (up to $10^{24}\ \rm{cm}^{-2}$). The interaction (scattering and absorption) with the medium imprints spectral signatures that reflect the individual atoms which constitute the gas, molecule, or solid. In this work we investigate the ability of high resolution X-ray spectroscopy to probe the properties of cosmic grains containing iron. Although iron is heavily depleted into interstellar dust, the nature of the Fe-bearing grains is still largely uncertain. In our analysis we use iron K-edge synchrotron data of minerals likely present in the ISM dust taken at the European Synchrotron Radiation Facility. We explore the prospects of determining the chemical composition and the size of astrophysical dust in the Galactic centre and in molecular clouds with future X-ray missions. The energy resolution and the effective area of the present X-ray telescopes are not sufficient to detect and study the Fe K-edge, even for bright X-ray sources. From the analysis of the extinction cross sections of our dust models implemented in the spectral fitting program SPEX, the Fe K-edge is promising for investigating both the chemistry and the size distribution of the interstellar dust. We find that the chemical composition regulates the X-ray absorption fine structures in the post edge region, whereas the scattering feature in the pre-edge is sensitive to the mean grain size. Finally, we note that the Fe K-edge is insensitive to other dust properties, such as the porosity and the geometry of the dust.Comment: 11 pages, 10 figures. Accepted for publication in Astronomy and Astrophysic

Predicting university performance in psychology: the role of previous performance and discipline-specific knowledge

Recent initiatives to enhance retention and widen participation ensure it is crucial to understand the factors that predict students' performance during their undergraduate degree. The present research used Structural Equation Modeling (SEM) to test three separate models that examined the extent to which British Psychology students' A-level entry qualifications predicted: (1) their performance in years 1-3 of their Psychology degree, and (2) their overall degree performance. Students' overall A-level entry qualifications positively predicted performance during their first year and overall degree performance, but negatively predicted their performance during their third year. Additionally, and more specifically, students' A-level entry qualifications in Psychology positively predicted performance in the first year only. Such findings have implications for admissions tutors, as well as for students who have not studied Psychology before but who are considering applying to do so at university

Exploring the roles of urinary HAI-1, EpCAM and EGFR in bladder cancer prognosis and risk stratification

Objectives: To investigate whether elevated urinary HAI-1, EpCAM and EGFR are independent prognostic biomarkers within non-muscle-invasive bladder cancer (NMIBC) patients, and have utility for risk stratification to facilitate treatment decisions. Results: After accounting for EAU risk group in NMIBC patients, the risk of BC-specific death was 2.14 times higher (95% CI: 1.08 to 4.24) if HAI-1 was elevated and 2.04 times higher (95% CI: 1.02 to 4.07) if EpCAM was elevated. The majority of events occurred in the high-risk NMIBC group and this is where the biggest difference is seen in the survival curves when plotted for EAU risk groups separately. In MIBC patients, being elevated for any of the three biomarkers was significantly associated with BC-specific mortality after accounting for other risk factors, HR = 4.30 (95% CI: 1.85 to 10.03). Patients and Methods: Urinary levels of HAI-1, EpCAM and EGFR were measured by ELISA in 683 and 175 patients with newly-diagnosed NMIBC and MIBC, respectively, recruited to the Bladder Cancer Prognosis Programme. Associations between biomarkers and progression, BC-specific mortality and all-cause mortality were evaluated using univariable and multivariable Cox regression models, adjusted for European Association of Urology (EAU) NMIBC risk groups. The upper 25% of values for each biomarker within NMIBC patients were considered as elevated. Exploratory analyses in urine from MIBC patients were also undertaken. Conclusion: Urinary HAI-1 and EpCAM are prognostic biomarkers for NMIBC patients. These biomarkers have potential to guide treatment decisions for high-risk NMIBC patients. Further analyses are required to define the roles of HAI-1, EpCAM and EGFR in MIBC patients

HumanMethylation450K array–identified biomarkers predict tumour recurrence/progression at initial diagnosis of high-risk non-muscle Invasive bladder cancer

Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/ or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HRNMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable diseas

Host and environmental predictors of exhaled breath temperature in the elderly

BACKGROUND: Exhaled breath temperature has been suggested as a new method to detect and monitor pathological processes in the respiratory system. The putative mechanism of this approach is based upon changes in the blood flow. So far potential factors that influence breath temperature have not been studied in the general population. METHODS: The exhaled breath temperature was measured in 151 healthy non-smoking elderly (aged: 60–80 years) at room temperature with the X-halo device with an accuracy of 0.03°C. We related exhaled breath temperature by use of regression models with potential predictors including: host factors (sex, age) and environmental factors (BMI, physical activity, and traffic indicators). RESULTS: Exhaled breath temperature was lower in women than in men and was inversely associated with age, physical activity. BMI and daily average ambient temperature were positively associated with exhaled breath temperature. Independent of the aforementioned covariates, exhaled breath temperature was significantly associated with several traffic indicators. Residential proximity to major road was inversely associated with exhaled breath temperature: doubling the distance to the nearest major intense road was observed a decrease of 0.17°C (95% CI: -0.33 to -0.01; p = 0.036). CONCLUSIONS: Exhaled breath temperature has been suggested as a noninvasive method for the evaluation of airway inflammation. We provide evidence that several factors known to be involved in proinflammatory conditions including BMI, physical activity and residential proximity to traffic affect exhaled breath temperature. In addition, we identified potential confounders that should be taken into account in clinical and epidemiological studies on exhaled breath temperature including sex, age, and ambient temperature

Methylation of HOXA9 and ISL1 predicts patient outcome in high-grade non-invasive bladder cancer

Introduction Inappropriate DNA methylation is frequently associated with human tumour development, and in specific cases, is associated with clinical outcomes. Previous reports of DNA methylation in low/intermediate grade non-muscle invasive bladder cancer (NMIBC) have suggested that specific patterns of DNA methylation may have a role as diagnostic or prognostic biomarkers. In view of the aggressive and clinically unpredictable nature of high-grade (HG) NMIBC, and the current shortage of the preferred treatment option (Bacillus:Calmette-Guerin), novel methylation analyses may similarly reveal biomarkers of disease outcome that could risk-stratify patients and guide clinical management at initial diagnosis. Methods Promoter-associated CpG island methylation was determined in primary tumour tissue of 36 initial presentation high-grade NMIBCs, 12 low/intermediate-grade NMIBCs and 3 normal bladder controls. The genes HOXA9, ISL1, NKX6-2, SPAG6, ZIC1 and ZNF154 were selected for investigation on the basis of previous reports and/or prognostic utility in low/intermediate-grade NMIBC. Methylation was determined by Pyrosequencing of sodium-bisulphite converted DNA, and then correlated with gene expression using RT-qPCR. Methylation was additionally correlated with tumour behaviour, including tumour recurrence and progression to muscle invasive bladder cancer or metastases. Results The ISL1 genes’ promoter-associated island was more frequently methylated in recurrent and progressive high-grade tumours than their non-recurrent counterparts (60.0% vs. 18.2%, p = 0.008). ISL1 and HOXA9 showed significantly higher mean methylation in recurrent and progressive tumours compared to non-recurrent tumours (43.3% vs. 20.9%, p = 0.016 and 34.5% vs 17.6%, p = 0.017, respectively). Concurrent ISL1/HOXA9 methylation in HG-NMIBC reliably predicted tumour recurrence and progression within one year (Positive Predictive Value 91.7%), and was associated with disease-specific mortality (DSM). Conclusions In this study we report methylation differences and similarities between clinical sub-types of high-grade NMIBC. We report the potential ability of methylation biomarkers, at initial diagnosis, to predict tumour recurrence and progression within one year of diagnosis. We found that specific biomarkers reliably predict disease outcome and therefore may help guide patient treatment despite the unpredictable clinical course and heterogeneity of high-grade NMIBC. Further investigation is required, including validation in a larger patient cohort, to confirm the clinical utility of methylation biomarkers in high-grade NMIBC

Urinary EpCAM in urothelial bladder cancer patients: characterisation and evaluation of biomarker potential

Background: Epithelial cell adhesion molecule is overexpressed in bladder tumours and released from bladder cancer cells in vitro. We test the hypotheses that urinary EpCAM could act as a biomarker for primary bladder cancer detection and risk stratification. Methods: Epithelial cell adhesion molecule was measured by ELISA in urine from 607 patients with primary bladder tumours and in urine from 53 non-cancer controls. Mann–Whitney tests and ROC analyses were used to determine statistical significance and discrimination between non-cancer controls and different stages and grades of disease. Multivariable modelling and Kaplan–Meier analyses were used to determine prognostic significance. The structure of urinary EpCAM was investigated by western blotting and mass spectrometry. Results: Urinary EpCAM levels increase with stage and grade of bladder cancer. Alongside grade and stage, elevated urinary EpCAM is an independent indicator of poor prognosis with a hazard ratio of 1.76 for bladder cancer-specific mortality. The soluble form of EpCAM in urine is the extracellular domain generated by cleavage between ala243 and gly244. Further studies are required to define the influence of other urinary tract malignancies and benign urological conditions on urinary EpCAM. Conclusion: The extracellular domain of EpCAM is shed into urine by bladder tumours. Urinary EpCAM is a strong indicator of bladder cancer-specific survival, and may be useful within a multi-marker panel for disease detection or as a stand-alone marker to prioritise the investigation and treatment of patients. The mechanisms and effects of EpCAM cleavage in bladder cancer are worthy of further investigation, and may identify novel therapeutic targets

The use of the SF-36 questionnaire in adult survivors of childhood cancer: evaluation of data quality, score reliability, and scaling assumptions

BACKGROUND: The SF-36 has been used in a number of previous studies that have investigated the health status of childhood cancer survivors, but it never has been evaluated regarding data quality, scaling assumptions, and reliability in this population. As health status among childhood cancer survivors is being increasingly investigated, it is important that the measurement instruments are reliable, validated and appropriate for use in this population. The aim of this paper was to determine whether the SF-36 questionnaire is a valid and reliable instrument in assessing self-perceived health status of adult survivors of childhood cancer. METHODS: We examined the SF-36 to see how it performed with respect to (1) data completeness, (2) distribution of the scale scores, (3) item-internal consistency, (4) item-discriminant validity, (5) internal consistency, and (6) scaling assumptions. For this investigation we used SF-36 data from a population-based study of 10,189 adult survivors of childhood cancer. RESULTS: Overall, missing values ranged per item from 0.5 to 2.9 percent. Ceiling effects were found to be highest in the role limitation-physical (76.7%) and role limitation-emotional (76.5%) scales. All correlations between items and their hypothesised scales exceeded the suggested standard of 0.40 for satisfactory item-consistency. Across all scales, the Cronbach's alpha coefficient of reliability was found to be higher than the suggested value of 0.70. Consistent across all cancer groups, the physical health related scale scores correlated strongly with the Physical Component Summary (PCS) scale scores and weakly with the Mental Component Summary (MCS) scale scores. Also, the mental health and role limitation-emotional scales correlated strongly with the MCS scale score and weakly with the PCS scale score. Moderate to strong correlations with both summary scores were found for the general health perception, energy/vitality, and social functioning scales. CONCLUSION: The findings presented in this paper provide support for the validity and reliability of the SF-36 when used in long-term survivors of childhood cancer. These findings should encourage other researchers and health care practitioners to use the SF-36 when assessing health status in this population, although it should be recognised that ceiling effects can occur