AMI SZ observation of galaxy-cluster merger CIZA J2242+5301: Perpendicular flows of gas and dark matter

© 2018 The Author(s). Arcminute Microkelvin Imager observations towards CIZA J2242+5301, in comparison with observations of weak gravitational lensing and X-ray emission from the literature, are used to investigate the behaviour of non-baryonic dark matter (NBDM) and gas during the merger. Analysis of the Sunyaev-Zel'dovich (SZ) signal indicates the presence of high pressure gas elongated perpendicularly to the X-ray and weak-lensing morphologies, which, given the merger-axis constraints in the literature, implies that high pressure gas is pushed out into a linear structure during core passing. Simulations in the literature closely matching the inferred merger scenario show the formation of gas density and temperature structures perpendicular to the merger axis. These SZ observations are challenging for modified gravity theories in which NBDM is not the dominant contributor to galaxy-cluster gravity.STFC (ST/M001172/1) STFC (ST/K00333X/1) STFC (ST/M007065/1) STFC (ST/H008586/1) STFC (ST/J005673/1

AMI observations of 10 CLASH galaxy clusters: SZ and X-ray data used together to determine cluster dynamical states

© 2016 The Authors. Published by Oxford University Press on behalf of The Royal Astronomical Society.Using Arcminute Microkelvin Imager (AMI) Sunyaev-Zel'dovich (SZ) observations towards 10 CLASH (Cluster Lensing and Supernova Survey with Hubble) clusters, we investigate the influence of cluster mergers on observational galaxy cluster studies. Although selected to be largely relaxed, there is disagreement in the literature on the dynamical states of CLASH sample members. We analyse ourAMIdata in a fully Bayesianway to produce estimated cluster parameters and consider the intrinsic correlations in our Navarro, Frenk and White/generalized Navarro, Frenk and White-based model. Varying pressure profile shape parameters, illustrating an influence of mergers on scaling relations, induces small deviations from the canonical selfsimilar predictions - in agreement with simulations of Poole et al. (2007) who found that merger activity causes only small scatter perpendicular to the relations. We demonstrate this effect observationally using the different dependences of SZ and X-ray signals to ne that cause different sensitivities to the shocking and/or fractionation produced by mergers. Plotting YX-Mgas relations (where YX = MgasT) derived from AMI SZ and from Chandra X-ray gives ratios of AMI and Chandra YX and Mgas estimates that indicate movement of clusters along the scaling relation, as predicted by Poole et al. (2007). Clusters that have moved most along the relation have the most discrepant TSZ and TX estimates: all the other clusters (apart from one) have SZ and X-ray estimates of Mgas, T and YX that agree within r500. We use SZ versus X-ray discrepancies in conjunction with Chandra maps and TX profiles, making comparisons with simulated cluster merger maps in Poole et al. (2006) to identify disturbed members of our sample and estimate merger stages.We thank the staff of the Mullard Radio Astronomy Observatory for their invaluable assistance in the commissioning and operation of AMI, which is supported by Cambridge University. WJH and CR are grateful for the support of STFC Studentships. CR also acknowledges the support of Cambridge University. MO and YCP acknowledge support from Research Fellowships from Sidney Sussex College and Trinity College, Cambridge, respectively. We thank Arif Babul for his assistance in accessing the Poole et al. online materials. Much of this work was undertaken on the COSMOS Shared Memory system at DAMTP, Cambridge University, operated on behalf of the STFC DiRAC HPC Facility. This equipment is funded by BIS National E-infrastructure capital grant ST/J005673/1 and STFC grants ST/H008586/1, ST/K00333X/1

CXD101 and nivolumab in patients with metastatic microsatellite-stable colorectal cancer (CAROSELL): a multicentre, open-label, single-arm, phase II trial.

BACKGROUND: Patients with microsatellite stable (MSS) colorectal carcinoma (CRC) do not respond to immune checkpoint inhibitors. Preclinical models suggested synergistic anti-tumour activity combining CXD101 and anti-programmed cell death protein 1 treatment; therefore, we assessed the clinical combination of CXD101 and nivolumab in heavily pre-treated patients with MSS metastatic CRC (mCRC). PATIENTS AND METHODS: This single-arm, open-label study enrolled patients aged 18 years or older with biopsy-confirmed MSS CRC; at least two lines of systemic anticancer therapies (including oxaliplatin and irinotecan); at least one measurable lesion; Eastern Cooperative Oncology Group performance status of 0, 1 or 2; predicted life expectancy above 3 months; and adequate organ and bone marrow function. Nine patients were enrolled in a safety run-in study to define a tolerable combination schedule of CXD101 and nivolumab, followed by 46 patients in the efficacy assessment phase. Patients in the efficacy assessment cohort were treated orally with 20 mg CXD101 twice daily for 5 consecutive days every 3 weeks, and intravenously with 240 mg nivolumab every 2 weeks. The primary endpoint was immune disease control rate (iDCR). RESULTS: Between 2018 and 2020, 55 patients were treated with CXD101 and nivolumab. The combination therapy was well tolerated with the most frequent grade 3 or 4 adverse events being neutropenia (18%) and anaemia (7%). Immune-related adverse reactions commonly ascribed to checkpoint inhibitors were surprisingly rare although we did see single cases of pneumonitis, hypothyroidism and hypopituitarism. There were no treatment-related deaths. Of 46 patients assessable for efficacy, 4 (9%) achieved partial response and 18 (39%) achieved stable disease, translating to an immune disease control rate of 48%. The median overall survival (OS) was 7.0 months (95% confidence interval 5.13-10.22 months). CONCLUSIONS: The primary endpoint was met in this phase II study, which showed that the combination of CXD101 and nivolumab, at full individual doses in the treatment of advanced or metastatic MSS CRC, was both well tolerated and efficacious

AMI-CL J0300+2613: A Galactic anomalous-microwave-emission ring masquerading as a galaxy cluster

The Arcminute Microkelvin Imager (AMI) carried out a blind survey for galaxy clusters via their Sunyaev-Zel'dovich effect decrements between 2008 and 2011. The first detection, known as AMI-CL J0300+2613, has been reobserved with AMI equipped with a new digital correlator with high dynamic range. The combination of the new AMI data and more recent high-resolution sub-mm and infra-red maps now shows the feature in fact to be a ring of positive dust-correlated Galactic emission, which is likely to be anomalous microwave emission (AME). If so, this is the first completely blind detection of AME at arcminute scales

Reciprocal relationship between expression of hypoxia inducible factor 1α (HIF-1α) and the pro-apoptotic protein Bid in ex vivo colorectal cancer

Hypoxia inducible factor 1 (HIF-1) represses the transcription of pro-apoptotic bid in colorectal cancer cells in vitro. To assess the clinical relevance of this observation, HIF-1α and Bid were assessed in serial sections of 39 human colorectal adenocarcinomas by immunohistochemistry. In high HIF-1α nuclear-positive cell subpopulations, there was a significant reduction in Bid expression (ANOVA, P=0.04). Given the role of Bid in drug-induced apoptosis, these data add impetus to strategies targeting HIF-1 for therapeutic gain

Free-form modelling of galaxy clusters: A Bayesian and data-driven approach

A new method is presented for modelling the physical properties of galaxy clusters. Our technique moves away from the traditional approach of assuming specific parameterized functional forms for the variation of physical quantities within the cluster, and instead allows for a 'freeform' reconstruction, but one for which the level of complexity is determined automatically by the observational data and may depend on position within the cluster. This is achieved by representing each independent cluster property as some interpolating or approximating function that is specified by a set of control points, or 'nodes', for which the number of nodes, together with their positions and amplitudes, are allowed to vary and are inferred in a Bayesian manner from the data. We illustrate our nodal approach in the case of a spherical cluster by modelling the electron pressure profile P e (r) in analyses both of simulated Sunyaev-Zel'dovich (SZ) data from the Arcminute MicroKelvin Imager (AMI) and of real AMI observations of the cluster MACS J0744+3927 in the CLASH sample. We demonstrate that one may indeed determine the complexity supported by the data in the reconstructed P e (r), and that one may constrain two very important quantities in such an analysis: the cluster total volume integrated Comptonization parameter (Y tot ) and the extent of the gas distribution in the cluster (r max ). The approach is also well-suited to detecting clusters in blind SZ surveys, in the case where the population of radio sources is known in advance.This work was performed using both the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), and COSMOS Shared Memory system at DAMTP, University of Cambridge operated on behalf of the STFC DiRAC HPC Facility. Darwin Supercomputer is provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council. COSMOS Shared Memory system is funded by BIS National E-infrastructure capital grant ST/J005673/1 and STFC grants ST/H008586/1, ST/K00333X/1 ... YCP acknowledges support from a Trinity College Junior Research Fellowship

Enhanced fluorescence from X-Ray line coincidence pumping

Many resonant photo-pumped X-ray laser schemes that use a strong pump line such as Ly-α or He-α to populate the upper laser state of a separate lasing material have been proposed over the last four decades but none have been demonstrated. As a first step to creating a photo-pumped X-ray laser we have decided to reinvestigate some of these schemes at the Orion laser facility with the goal to show enhanced fluorescence. In particular we look at using the Ly-α or He-α K lines to pump the 1s–3p and 4p transitions in H-like Cl and see fluorescence on the 4f–3d line at 65 Å and the 3d–2p line at 23 Å. Preliminary experiments are presented that show a modest enhancement. As an alternative we also look at enhancing the 2p–2s line in Ne-like Ge at 65 Å using the Ly-α Mg line to photo-pump the 2s–3p line of Ne-like Ge. Calculations are presented that suggest modest enhancements of 2.5

The first legal mortgagor: a consumer without adequate protection?

This article contends that the UK government’s attempt to create a well-functioning consumer credit market will be undermined if it fails to reform the private law framework relating to the first legal mortgage. Such agreements are governed by two distinct regulatory regimes that are founded upon very different conceptions of the mortgagor. The first, the regulation of financial services overseen by the Financial Conduct Authority, derives from public law and is founded upon a conception of the mortgagor as “consumer”. The other is land law, private law regulation implemented by the judiciary and underpinned by a conception of the mortgagor as “landowner”. Evidence suggests that the operation of these two regimes prevents mortgagors from receiving fair and consistent treatment. The current reform of financial services regulation therefore will change only one part of this governance regime and will leave mortgagors heavily reliant upon a regulator that still has to prove itself. What this article argues is that reform of the rules of private law must also be undertaken with the aim of initiating a paradigm shift in the conception of the mortgagor from “landowner” to “consumer”. Cultural shifts of this kind take time but the hope is that this conceptual transformation will occur in time to deter the predicted rise in mortgage possessions

Oestrogen receptor β and neoadjuvant therapy with tamoxifen: prediction of response and effects of treatment

In order to elucidate the relative importance of oestrogen receptor (ER)α, ERβ and an ERβ variant (ERβ2/βcx) in the response of breast cancers to tamoxifen, tumour levels of each receptor were assessed in 36 patients before and after 3 months of neoadjuvant treatment with tamoxifen (20 mg daily). All patients were postmenopausal women presenting with large ERα-positive breast cancers. Clinical response to treatment was assessed by tumour volume changes as determined from sequential ultrasounds and pathological response by comparison of the tumour morphology before and after treatment. Of 33 cases, 23 (70%) were classified as having a clinical response and 16 (48%) as having a response pathologically. All tumours stained positively for ERα and ERβ and 15 out of 33 (45%) for ERβ2/βcx. There were no significant differences in quantitative expression of any receptor between tumours that subsequently responded and that did not, whether response was assessed clinically or pathologically. Tamoxifen treatment was associated with a decrease in ERα, but an increase was the most frequent change (17 out of 33) in ERβ, and no consistent change was evident in staining of the ERβ2/βcx variant. In summary, ERβ1 and ERβ2/βcx variant protein are detected in ERα-positive breast tumours but their expression is not associated with a response to tamoxifen. Differential changes in ERα and ERβ were seen with treatment