Baryon fractions in clusters of galaxies: evidence against a preheating model for entropy generation

The Millennium Gas project aims to undertake smoothed-particle hydrodynamic resimulations of the Millennium Simulation, providing many hundred massive galaxy clusters for comparison with X-ray surveys (170 clusters with kTsl > 3 keV). This paper looks at the hot gas and stellar fractions of clusters in simulations with different physical heating mechanisms. These fail to reproduce cool-core systems but are successful in matching the hot gas profiles of non-cool-core clusters. Although there is immense scatter in the observational data, the simulated clusters broadly match the integrated gas fractions within r500 . In line with previous work, however, they fare much less well when compared to the stellar fractions, having a dependence on cluster mass that is much weaker than is observed. The evolution with redshift of the hot gas fraction is much larger in the simulation with early preheating than in one with continual feedback; observations favour the latter model. The strong dependence of hot gas fraction on cluster physics limits its use as a probe of cosmological parameters.Comment: 16 pages, 18 figures, 4 tables. Accepted for publication in MNRA

Sunyaev-Zel'dovich clusters in millennium gas simulations

Large surveys using the Sunyaev–Zel’dovich (SZ) effect to find clusters of galaxies are now starting to yield large numbers of systems out to high redshift, many of which are new dis- coveries. In order to provide theoretical interpretation for the release of the full SZ cluster samples over the next few years, we have exploited the large-volume Millennium gas cosmo- logical N-body hydrodynamics simulations to study the SZ cluster population at low and high redshift, for three models with varying gas physics. We confirm previous results using smaller samplesthattheintrinsic(spherical)Y500–M500relationhasverylittlescatter(σlog10Y ≃0.04), is insensitive to cluster gas physics and evolves to redshift 1 in accordance with self-similar expectations. Our preheating and feedback models predict scaling relations that are in excel- lent agreement with the recent analysis from combined Planck and XMM–Newton data by the Planck Collaboration. This agreement is largely preserved when r500 and M500 are derived using thehydrostaticmassproxy,YX,500,albeitwithsignificantlyreducedscatter(σlog10Y ≃0.02),a result that is due to the tight correlation between Y500 and YX,500. Interestingly, this assumption also hides any bias in the relation due to dynamical activity. We also assess the importance of projection effects from large-scale structure along the line of sight, by extracting cluster Y500 values from 50 simulated 5 × 5-deg2 sky maps. Once the (model-dependent) mean signal is subtracted from the maps we find that the integrated SZ signal is unbiased with respect to the underlying clusters, although the scatter in the (cylindrical) Y500–M500 relation increases in the preheating case, where a significant amount of energy was injected into the intergalactic medium at high redshift. Finally, we study the hot gas pressure profiles to investigate the origin of the SZ signal and find that the largest contribution comes from radii close to r500 in all cases. The profiles themselves are well described by generalized Navarro, Frenk & White profiles but there is significant cluster-to-cluster scatter. In conclusion, our results support the notion that Y500 is a robust mass proxy for use in cosmological analyses with clusters

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

CCN3 is dynamically regulated by treatment and disease state in multiple sclerosis

Background: Multiple sclerosis (MS) is an immune-mediated disease that damages myelin in the central nervous system (CNS). We investigated the profile of CCN3, a known regulator of immune function and a potential mediator of myelin regeneration, in multiple sclerosis in the context of disease state and disease-modifying treatment. Methods: CCN3 expression was analysed in plasma, immune cells, CSF and brain tissue of MS patient groups and control subjects by ELISA, western blot, qPCR, histology and in situ hybridization. Results: Plasma CCN3 levels were comparable between collective MS cohorts and controls but were significantly higher in progressive versus relapsing-remitting MS and between patients on interferon-β versus natalizumab. Higher body mass index was associated with higher CCN3 levels in controls as reported previously, but this correlation was absent in MS patients. A significant positive correlation was found between CCN3 levels in matched plasma and CSF of MS patients which was absent in a comparator group of idiopathic intracranial hypertension patients. PBMCs and CD4+ T cells significantly upregulated CCN3 mRNA in MS patients versus controls. In the CNS, CCN3 was detected in neurons, astrocytes and blood vessels. Although overall levels of area immunoreactivity were comparable between non-affected, demyelinated and remyelinated tissue, the profile of expression varied dramatically. Conclusions: This investigation provides the first comprehensive profile of CCN3 expression in MS and provides rationale to determine if CCN3 contributes to neuroimmunological functions in the CNS

Lunar-solar rhythmpatterns: Towards the material cultures of tides

The movements of the oceans, and the liminal margins of sea, land and fresh water have profound implications for human / non-human life. Those movements and margins are rhythmically affected by tides which are thus a key means by which the forceful materiality of water is animated. Where salt water meets land and river mouths, ceaseless, varying, daily, monthly and seasonal rhythms of sea level rise and fall occur. Complex patterns and rhythms of inter-tidal areas, currents, mixing of salt and fresh water, erosion, transportation and deposition and many impacts on human systems are created. Due to location, orientation and sea/land topography, coastal areas around the world are subject to either microtides, mesotides, or macrotides (4 metres and higher). Particularly in the case of the latter, the rhythms of the tides extend out into a range of intersecting eco-social assemblages. This paper discusses tides and their rhythms, sets them in debates about temporality/nature, and introduces the idea of rhythmpattern which is timespace animated. It also considers dissonance and consonance within and between tidal rhythmpatterns and their overwriting by development

"Who Milks the Cows at Maesgwyn?" The Animality of UK Rural Landscapes in Affective Registers

Landscapes are complex outplays of intersecting flows of agency in which humans and non-humans combine in a series of registers, and in cycles of comings and goings to make meshworks of life in place. The presence of animals in some landscapes can be particularly culturally, politically, ecologically, and economically significant but are often overlooked or only partially acknowledged. Here I focus on UK rural landscapes which are rich in animal presences both historically and today. I show how animal presences, and human engagements with them, form key elements of individual and collective practices and imaginings of identity. These presences come in many interrelating, messy, and contesting forms, such as companion animals, wildlife, agricultural livestock, and animals bound up with conservation and field sports. In the shifting meshworks of social, cultural, economic, political and ecological forces at work in rural landscapes, the composition of these animal presences, and the natures of these encounters, will be ever-changing but also retain familiar themes and iconographies. I argue that the animality of rurality is far more strongly represented in popular culture (television, film, literature) than it has been in academic readings of the rural. I also suggest that much of the exchange that makes up animality-rurality meshworks is articulated in affective/emotional registers. Landscape and rural studies need to develop awareness of these registers, and means by which they can be more sensitively investigated. This will be an important step in developing our understandings of all landscapes and the practices of relational, affective, everyday life, both of humans and non-humans, within them. © 2013 Copyright Landscape Research Group Ltd

The XMM Cluster Survey: optical analysis methodology and the first data release

The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMM–Newton Science Archive. Its main aims are to measure cosmological parameters and trace the evolution of X-ray scaling relations. In this paper we present the first data release from the XMM Cluster Survey (XCS-DR1). This consists of 503 optically confirmed, serendipitously detected, X-ray clusters. Of these clusters, 256 are new to the literature and 357 are new X-ray discoveries. We present 463 clusters with a redshift estimate (0.06 1.0, including a new spectroscopically confirmed cluster at z= 1.01); (ii) 66 clusters with high TX (>5 keV); (iii) 130 clusters/groups with low TX (<2 keV); (iv) 27 clusters with measured TX values in the Sloan Digital Sky Survey (SDSS) ‘Stripe 82’ co-add region; (v) 77 clusters with measured TX values in the Dark Energy Survey region; (vi) 40 clusters detected with sufficient counts to permit mass measurements (under the assumption of hydrostatic equilibrium); (vii) 104 clusters that can be used for applications such as the derivation of cosmological parameters and the measurement of cluster scaling relations. The X-ray analysis methodology used to construct and analyse the XCS-DR1 cluster sample has been presented in a companion paper, Lloyd-Davies et al

HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage

Histone deacetylase 1 (HDAC1) is a nuclear enzyme involved in transcriptional repression. We detected cytosolic HDAC1 in damaged axons in brains of humans with multiple sclerosis and of mice with cuprizone-induced demyelination, in ex vivo models of demyelination and in cultured neurons exposed to glutamate and tumor necrosis factor-α. Nuclear export of HDAC1 was mediated by the interaction with the nuclear receptor CRM-1 and led to impaired mitochondrial transport. The formation of complexes between exported HDAC1 and members of the kinesin family of motor proteins hindered the interaction with cargo molecules, thereby inhibiting mitochondrial movement and inducing localized beading. This effect was prevented by inhibiting HDAC1 nuclear export with leptomycin B, treating neurons with pharmacological inhibitors of HDAC activity or silencing HDAC1 but not other HDAC isoforms. Together these data identify nuclear export of HDAC1 as a critical event for impaired mitochondrial transport in damaged neurons