Cadherin-5: a biomarker for metastatic breast cancer with optimum efficacy in oestrogen receptor-positive breast cancers with vascular invasion

Background: A glycoproteomic study has previously shown cadherin-5 (CDH5) to be a serological marker of metastatic breast cancer when both protein levels and glycosylation status were assessed. In this study we aimed to further validate the utility of CDH5 as a biomarker for breast cancer progression. Methods: A nested case–control study of serum samples from breast cancer patients, of which n=52 had developed a distant metastatic recurrence within 5 years post-diagnosis and n=60 had remained recurrence-free. ELISAs were used to quantify patient serum CDH5 levels and assess glycosylation by Helix pomatia agglutinin (HPA) binding. Clinicopathological, treatment and lifestyle factors associated with metastasis and elevated biomarker levels were identified. Results: Elevated CDH5 levels (P=0.028) and ratios of CDH5:HPA binding (P=0.007) distinguished patients with metastatic disease from those that remained metastasis-free. Multivariate analysis showed that the association between CDH5:HPA ratio and the formation of distant metastases was driven by patients with oestrogen receptor (ER+) positive cancer with vascular invasion (VI+). Conclusions: CDH5 levels and the CDH5 glycosylation represent biomarker tests that distinguish patients with metastatic breast cancer from those that remain metastasis-free. The test reached optimal sensitivity and specificity in ER-positive cancers with vascular invasion

Chemotherapy relatedcognitive impairment in colorectal cancer patients

The aim of this thesis was to establish the extent of objective and subjective cognitive impairment in patients with resected colorectal cancer who required adjuvant chemotherapy treatment compared to those who did not. Specific objectives were to i) identify the extent and nature of cognitive impairments ii) explore changes in cognitive function over time and iii) identify relationships between cognitive function and psychosocial outcomes. The qualitative study aimed to further evaluate the lived experience of patients diagnosed with colorectal cancer undergoing adjuvant chemotherapy treatment over time. A mixed method longitudinal comparative study was conducted to address these objectives’. A convenience sample of 98 patients with resected colorectal cancer were recruited from 5 London based NHS Trusts. Participants consisted of 63 patients scheduled for 6 months adjuvant chemotherapy treatment and 35 patients who did not require any further systemic treatment. Each participant completed a neuropsychological test battery and psychosocial self-report questionnaires and/or a semi structured interview prior to the start of the treatment, during and 3 months after the end of treatment. The results showed objective cognitive impairment in a statistically significant (p<0.01) proportion (ranging from 42% -60% depending on the definition used) of participants in both patient groups at all assessment time points (from before chemotherapy treatment to 3 months after it finished); with very little change over time (small to medium effect sizes). Verbal memory, motor function and executive function were most affected in both groups. There was no significant association between overall objective cognitive impairment and fatigue, anxiety/depression or quality of life. All psychosocial outcomes were all highly correlated with cognitive symptoms at every time point. Cognitive symptoms (such as memory lapses and word findng problems) were also reported at every time point by participants in the interview study, which corroborated the results of the quantitative analysis. The results of this study address a gap in the literature and highlight the extent of cognitive impairments in patients with colorectal cancer. The clinical implications of the findings are discussed

Determination of the Far-Infrared Cosmic Background Using COBE/DIRBE and WHAM Data

Determination of the cosmic infrared background (CIB) at far infrared wavelengths using COBE/DIRBE data is limited by the accuracy to which foreground interplanetary and Galactic dust emission can be modeled and subtracted. Previous determinations of the far infrared CIB (e.g., Hauser et al. 1998) were based on the detection of residual isotropic emission in skymaps from which the emission from interplanetary dust and the neutral interstellar medium were removed. In this paper we use the Wisconsin H-alpha Mapper (WHAM) Northern Sky Survey as a tracer of the ionized medium to examine the effect of this foreground component on determination of the CIB. We decompose the DIRBE far infrared data for five high Galactic latitude regions into H I and H-alpha correlated components and a residual component. We find the H-alpha correlated component to be consistent with zero for each region, and we find that addition of an H-alpha correlated component in modeling the foreground emission has negligible effect on derived CIB results. Our CIB detections and 2 sigma upper limits are essentially the same as those derived by Hauser et al. and are given by nu I_nu (nW m-2 sr-1) < 75, < 32, 25 +- 8, and 13 +- 3 at 60, 100, 140, and 240 microns, respectively. Our residuals have not been subjected to a detailed anisotropy test, so our CIB results do not supersede those of Hauser et al. We derive upper limits on the 100 micron emissivity of the ionized medium that are typically about 40% of the 100 micron emissivity of the neutral atomic medium. This low value may be caused in part by a lower dust-to-gas mass ratio in the ionized medium than in the neutral medium, and in part by a shortcoming of using H-alpha intensity as a tracer of far infrared emission.Comment: 38 pages, 8 figures. Accepted for publication in Ap

X-ray Halos and Large Grains in the Diffuse Interstellar Medium

Recent observations with dust detectors on board the interplanetary spacecraft Ulysses and Galileo have recorded a substantial flux of large interstellar grains with radii between 0.25 and 2.0 mu entering the solar system from the local interstellar cloud. The most commonly used interstellar grain size distribution is characterized by a a^-3.5 power law in grain radii a, and extends to a maximum grain radius of 0.25 mu. The extension of the interstellar grain size distribution to such large radii will have a major effect on the median grain size, and on the amount of mass needed to be tied up in dust for a given visual optical depth. It is therefore important to investigate whether this population of larger dust particles prevails in the general interstellar medium, or if it is merely a local phenomenon. The presence of large interstellar grains can be mainly inferred from their effect on the intensity and radial profiles of scattering halos around X-ray sources. In this paper we examine the grain size distribution that gives rise to the X-ray halo around Nova Cygni 1992. The results of our study confirm the need to extend the interstellar grain size distribution in the direction of this source to and possibly beyond 2.0 mu. The model that gives the best fit to the halo data is characterized by: (1) a grain size distribution that follows an a^-3.5 power law up to 0.50 mu, followed by an a^-4.0 extension from 0.50 mu to 2.0 mu; and (2) silicate and graphite (carbon) dust-to-gas mass ratios of 0.0044 and 0.0022, respectively, consistent with solar abundances constraints. Additional observations of X-ray halos probing other spatial directions are badly needed to test the general validity of this result.Comment: 17 pages, incl. 1 figure, accepted for publ. by ApJ Letter

Strong New Constraints on the Extragalactic Background Light in the Near- to Mid-IR

Direct measurements of the extragalactic background light (EBL) in the near-IR to mid-IR waveband are extremely difficult due to an overwhelming foreground from the zodiacal light that outshines the faint cosmological diffuse radiation field by more than an order of magnitude. Indirect constraints on the EBL are provided by gamma-ray observations of AGN. Using the combination of the Fermi Gamma-Ray Space Telescope together with the current generation of ground-based air Cherenkov telescopes (H.E.S.S., MAGIC, and VERITAS) provides unprecedented sensitivity and spectral coverage for constraining the EBL in the near- to mid-IR. In this paper we present new limits on the EBL based on the analysis of the broad-band spectra of a select set of gamma-ray blazars covering 200 MeV to several TeV. The EBL intensity at 15 microns is constrained to be 1.36 +/- 0.58 nW m^-2 sr^-1. We find that the fast evolution and baseline EBL models of Stecker et al. (2006), as well as the model of Kneiske et al. (2004), predict significantly higher EBL intensities in the mid-IR (15 microns) than is allowed by the constraints derived here. In addition, the model of Franceschini et al. (2008) and the fiducial model of Dominguez et al. (2011) predict near- to mid-IR ratios smaller than that predicted by our analysis. Namely, their intensities in the near-IR are too low while their intensities in the mid-IR are marginally too high. All of the aforementioned models are inconsistent with our analysis at the >3 sigma level.Comment: 37 pages, 13 figures, updated subject headings, accepted by Ap

ALMA Observations of Supernova 1987A

Supernova (SN) 1987A has provided a unique opportunity to study how SN ejecta evolve in 30 years time scale. We report our ALMA spectral observations of SN 1987A, taken in 2014, 2015 and 2016, with detections of CO, 28SiO, HCO+ and SO, with weaker lines of 29SiO. We find a dip in the SiO line profiles, suggesting that the ejecta morphology is likely elongated. The difference of the CO and SiO line profiles is consistent with hydrodynamic simulations, which show that Rayleigh-Taylor instabilities causes mixing of gas, with heavier elements much more disturbed, making more elongated structure. Using 28SiO and its isotopologues, Si isotope ratios were estimated for the first time in SN 1987A. The estimated ratios appear to be consistent with theoretical predictions of inefficient formation of neutron rich atoms at lower metallicity, such as observed in the Large Magellanic Cloud (about half a solar metallicity). The deduced large HCO+ mass and small SiS mass, which are inconsistent to the predictions of chemical model, might be explained by some mixing of elements immediately after the explosion. The mixing might have made some hydrogen from the envelope to sink into carbon and oxygen-rich zone during early days after the explosion, enabling the formation of a substantial mass of HCO+. Oxygen atoms may penetrate into silicon and sulphur zone, suppressing formation of SiS. Our ALMA observations open up a new window to investigate chemistry, dynamics and explosive-nucleosynthesis in supernovae

Submillimeter wavelength survey of the galactic plane from l = -5 deg to l = +62 deg: Structure and energetics of the inner disk

Results from a large scale survey of the first quadrant of the Milky Way galactic plane at wavelengths of 150, 250, and 300 microns with a 10x10 arcmin beam are presented. The emission detected in the survey arises from compact sources, most of which are identified with known peaks of 5 GHz and/or CO emission, and from an underlying diffuse background with a typical angular width of approximately 0.9 deg (FWHM) which accounts for most of the emission. A total of 80 prominent discrete sources were identified and characterized, of which about half were not previously reported at far infrared wavelengths. The total infrared luminosity within the solar circle is approximately 1 to 2x10 to the 10th power L sub 0, and is probably emitted by dust that resides in molecular clouds

Examining Chemotherapy-Related Cognitive Changes in Colorectal Cancer Patients: A Feasibility Trial

Introduction: Research suggests that chemotherapy may be related to decline in patients’ cognitive functions. Objectives: To assess the feasibility and acceptability of a multi-site study designed to examine the nature and extent of chemotherapy-related cognitive changes in colorectal cancer patients. Method: Data was collected over 8 months using objective and self-reported measures of cognitive functioning and self-reported quality of life, fatigue and mood questionnaires. The assessment battery was administered pre- and mid-chemotherapy treatment to a consecutive sample of colorectal cancer patients across three Londonbased NHS Trusts. Participants included patients who had undergone colorectal surgery and were scheduled to have adjuvant chemotherapy treatment, or no further cancer treatment. Main outcome measures: Recruitment procedures, rate of recruitment, suitability of exclusion/inclusion criteria, acceptability of data collection procedures and the battery, and attrition rates. Results: From 1 April 2014 to 1 December 2014, 42 eligible participants were invited to take part in the trial. Of the 17 that completed pre-chemotherapy assessments, only 1 withdrew at follow-up due to reasons of ill health from disease recurrence. All participants completed the entire battery and indicated that they found the trial acceptable. Conclusions: What went wrong: Strained researcher resources; loss of eligible participants to competing studies, restrictive upper age limit. Possible solutions: Removal of upper age limit, an increased dedicated research team to increase rate of recruitment. The large multi-site study is feasible with suggested amendments and is acceptable to patients and medical teams. Acceptability of trial to medical teams is further evidenced by requests of collaboration from two additional London based NHS Trusts. Lessons learned: This feasibility trial provides evidence to other researchers designing similar studies in this area of an acceptable design and the need for appropriate funding for resources to recruit large enough consecutive samples of patients with solid tumour cancers

Infrared Emission from Supernova Remnants: Formation and Destruction of Dust

We review the observations of dust emission in supernova rem- nants (SNRs) and supernovae (SNe). Theoretical calculations suggest that SNe, particularly core-collapse, should make significant quantities of dust, perhaps as much as a solar mass. Observations of extragalactic SNe have yet to find anywhere near this amount, but this may be the result of observa- tional limitations. SN 1987A, in the process of transitioning from a SN to an SNR, does show signs of a significant amount of dust forming in its ejecta, but whether this dust will survive the passage of the reverse shock to be injected into the ISM is unknown. IR observations of SNRs have not turned up significant quantities of dust, and the dust that is observed is generally swept-up by the forward shock, rather than created in the ejecta. Because the shock waves also destroy dust in the ISM, we explore the question of whether SNe might be net destroyers, rather than net creators of dust in the universe.Comment: Published in the Springer Handbook of Supernova

The destruction and survival of dust in the shell around SN 2008S

SN 2008S erupted in early 2008 in the grand design spiral galaxy NGC 6946. The progenitor was detected by Prieto et al. in Spitzer Space Telescope images taken over the four years prior to the explosion, but was not detected in deep optical images, from which they inferred a self-obscured object with a mass of about 10 Msun. We obtained Spitzer observations of SN 2008S five days after its discovery, as well as coordinated Gemini and Spitzer optical and infrared observations six months after its outburst. We have constructed radiative transfer dust models for the object before and after the outburst, using the same r^-2 density distribution of pre-existing amorphous carbon grains for all epochs and taking light-travel time effects into account for the early post-outburst epoch. We rule out silicate grains as a significant component of the dust around SN 2008S. The inner radius of the dust shell moved outwards from its pre-outburst value of 85 AU to a post-outburst value of 1250 AU, attributable to grain vaporisation by the light flash from SN 2008S. Although this caused the circumstellar extinction to decrease from Av = 15 before the outburst to 0.8 after the outburst, we estimate that less than 2% of the overall circumstellar dust mass was destroyed. The total mass-loss rate from the progenitor star is estimated to have been (0.5-1.0)x10^-4 Msun yr^-1. The derived dust mass-loss rate of 5x10^-7 Msun yr^-1 implies a total dust injection into the ISM of up to 0.01 Msun over the suggested duration of the self-obscured phase. We consider the potential contribution of objects like SN 2008S to the dust enrichment of galaxies.Comment: 9 pages, 7 figures, 3 tables. rv2. To appear in MNRA