What kind of dialogue do we need? Gender, deliberation and comprehensive values

Recent branches of political theory, including feminism, communitarianism, identity theory and difference theory, have criticised liberalism and liberal democratic politics for failing to recognise the importance of group diversity and identity. In response, political and democratic theorists have increasingly appealed to public deliberation as a means of resolving political questions. Deliberative democrats, for example, have sought to move beyond traditional understandings of democracy as a merely representative system by recasting it as a regime in which individual citizens determine policy outcomes and political decisions through their active participation in public dialogue with one another. Many liberals, meanwhile, have increasingly sought to ground liberal principles in agreements struck between participants in some form of deliberative process. That is, having taken on board claims about the importance of difference and identity to the ways in which people think and the values they hold, many liberal political theorists have felt the need to retreat from controversial commitments to substantive principles such as autonomy, and have instead grounded their theories in a more general commitment to public dialogue. Where liberalism was generally seen as either a perfectionist theory which stipulated the supremacy of certain values over others or a contractualist theory premised upon some appropriately modelled agreement between individuals bound by common standards of rationality, it is now increasingly seen as a deliberative theory rooted in inclusive dialogue among situated individuals. In making the transition from contractualism to deliberation, many liberals feel that they have developed a more effective way of justifying liberal principles in circumstances of diversity, by foregrounding inclusive, collective dialogue over hypothetical contracts and agreement models which require everyone to act and think in the same way

Ascertaining the nature and timing of mire degradation : using palaeoecology to assist future conservation management in Northern England

This study was initiated under contract VT0419 from English Nature (Natural England) to CECQR. In 2015, additional funding was provided by the Yorkshire Peat Partnership, for 210Pb dating, to refine age–depth estimates. We thank the following for fieldwork co-ordination, logistics or field assistance: Miriam Baynes, Mike Sutcliffe, Martin Furness, Gez Marshall, Paul Duncan, Tim Page, Andrew Windrum, Craig Sandham and Jackie Smith. We thank the Editor and two anonymous reviewers for suggestions for improvements.Peer reviewedPublisher PD

Brief communication: landslide motion from cross correlation of UAV-derived morphological attributes

Unmanned aerial vehicles (UAVs) can provide observations of high spatio-temporal resolution to enable operational landslide monitoring. In this research, the construction of digital elevation models (DEMs) and orthomosaics from UAV imagery is achieved using structure-from-motion (SfM) photogrammetric procedures. The study examines the additional value that the morphological attribute of "openness", amongst others, can provide to surface deformation analysis. Image-cross-correlation functions and DEM subtraction techniques are applied to the SfM outputs. Through the proposed integrated analysis, the automated quantification of a landslide's motion over time is demonstrated, with implications for the wider interpretation of landslide kinematics via UAV surveys

Pre-trial inter-laboratory analytical validation of the FOCUS4 personalised therapy trial.

INTRODUCTION: Molecular characterisation of tumours is increasing personalisation of cancer therapy, tailored to an individual and their cancer. FOCUS4 is a molecularly stratified clinical trial for patients with advanced colorectal cancer. During an initial 16-week period of standard first-line chemotherapy, tumour tissue will undergo several molecular assays, with the results used for cohort allocation, then randomisation. Laboratories in Leeds and Cardiff will perform the molecular testing. The results of a rigorous pre-trial inter-laboratory analytical validation are presented and discussed. METHODS: Wales Cancer Bank supplied FFPE tumour blocks from 97 mCRC patients with consent for use in further research. Both laboratories processed each sample according to an agreed definitive FOCUS4 laboratory protocol, reporting results directly to the MRC Trial Management Group for independent cross-referencing. RESULTS: Pyrosequencing analysis of mutation status at KRAS codons12/13/61/146, NRAS codons12/13/61, BRAF codon600 and PIK3CA codons542/545/546/1047, generated highly concordant results. Two samples gave discrepant results; in one a PIK3CA mutation was detected only in Leeds, and in the other, a PIK3CA mutation was only detected in Cardiff. pTEN and mismatch repair (MMR) protein expression was assessed by immunohistochemistry (IHC) resulting in 6/97 discordant results for pTEN and 5/388 for MMR, resolved upon joint review. Tumour heterogeneity was likely responsible for pyrosequencing discrepancies. The presence of signet-ring cells, necrosis, mucin, edge-effects and over-counterstaining influenced IHC discrepancies. CONCLUSIONS: Pre-trial assay analytical validation is essential to ensure appropriate selection of patients for targeted therapies. This is feasible for both mutation testing and immunohistochemical assays and must be built into the workup of such trials. TRIAL REGISTRATION NUMBER: ISRCTN90061564

Global models of planetary system formation in radiatively-inefficient protoplanetary discs

(Abridged) We present the results of N-body simulations of planetary systems formation in radiatively-inefficient disc models, where positive corotation torques may counter the rapid inward migration of low mass planets driven by Lindblad torques. The aim of this work is to examine the nature of planetary systems that arise from oligarchic growth in such discs. We adapt the commonly-used Mercury-6 symplectic integrator by including simple prescriptions for planetary migration (types I and II), planetary atmospheres that enhance the probability of planetesimal accretion by protoplanets, gas accretion onto forming planetary cores, and gas disc dispersal. We perform a suite of simulations for a variety of disc models with power-law surface density and tempera- ture profiles, with a focus on models in which unsaturated corotation torques can drive outward migration of protoplanets. In some models we account for the quenching of corotation torques that arises when planetary orbits become eccentric. Approximately half of our simulations lead to the successful formation of gas giant planets with a broad range of masses and semimajor axes. We conclude that convergent migration induced by corotation torques operating during planet formation can enhance the growth rate of planetary cores, but these often migrate into the central star because corotation torques saturate. Outward migration of planetary cores of modest mass can lead to the formation of gas giant planets at large distances from the central star, similar to those observed recently through direct imaging surveys. The excitation of planetary eccentricities through planet-planet scat- tering during oligarchic growth may quench the effects of corotation torques, however, such that inward migration is driven by Lindblad torques.Comment: To be published in MNRA

Molecular differences between two Jeryl Lynn mumps virus vaccine component strains, JL5 and JL2

The Jeryl Lynn (JL) vaccine against mumps virus (MuV) contains two components, MuVJL5 and MuVJL2, which differ by over 400 nt. Due to the occurrence of bias in the direction of mutation, these differences and those found in nucleotide sequences of different isolates of the minor component in the vaccine (MuVJL2) might be due to the effect of ADAR-like deaminases on MuV grown in tissue-cultured cells. A molecular clone of MuVJL2 (pMuVJL2) and MuVJL2-specific helper plasmids were constructed in order to investigate molecular interactions between MuVJL5 and MuVJL2, to augment the existing molecular clone of MuVJL5 (pMuVJL5) and MuVJL5-specific helper plasmids. Genome and mRNA termini of MuVJL2 were characterized, and an unusual oligo-G insertion transcriptional editing event was detected near the F mRNA polyadenylation site of MuVJL2, but not of MuVJL5. Genes encoding glycoproteins of rMuVJL2 and rMuVJL5 have been exchanged to characterize the oligo-G insertion, which associated with the specific sequence of the F gene of MuVJL2 and not with any other genes or the RNA-dependent RNA polymerase of strain MuVJL2. The results indicate that a single G-to-A sequence change obliterates the co-transcriptional editing of the F mRNA and that this oligo-G insertion does not affect the growth of the virus

The Herschel–ATLAS data release 2, Paper I. Submillimeter and far-infrared images of the South and North Galactic Poles: the largest Herschel survey of the extragalactic sky

We present the largest submillimeter images that have been made of the extragalactic sky. The Herschel Astrophysical Terahertz Large Area Survey (H-ATLAS) is a survey of 660 deg2 with the PACS and SPIRE cameras in five photometric bands: 100, 160, 250, 350, and 500 μm. In this paper we present the images from our two largest fields, which account for ~75% of the survey. The first field is 180.1 deg2 in size, centered on the north Galactic pole (NGP), and the second is 317.6 deg2 in size, centered on the south Galactic pole. The NGP field serendipitously contains the Coma cluster. Over most (~80%) of the images, the pixel noise, including both instrumental noise and confusion noise, is approximately 3.6, and 3.5 mJy pix−1 at 100 and 160 μm, and 11.0, 11.1 and 12.3 mJy beam−1 at 250, 350 and 500 μm, respectively, but reaches lower values in some parts of the images. If a matched filter is applied to optimize point-source detection, our total 1σ map sensitivity is 5.7, 6.0, and 7.3 mJy at 250, 350, and 500 μm, respectively. We describe the results of an investigation of the noise properties of the images. We make the most precise estimate of confusion in SPIRE maps to date, finding values of 3.12 ± 0.07, 4.13 ± 0.02, and 4.45 ± 0.04 mJy beam−1 at 250, 350, and 500 μm in our un-convolved maps. For PACS we find an estimate of the confusion noise in our fast-parallel observations of 4.23 and 4.62 mJy beam−1 at 100 and 160 μm. Finally, we give recipes for using these images to carry out photometry, both for unresolved and extended sources

Preoperative chemoradiation with capecitabine, irinotecan and cetuximab in rectal cancer: significance of pre-treatment and post-resection RAS mutations

Background: The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation (CRT) is uncertain. Methods: In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen. Results: Eighty-two patients were recruited and 76 underwent surgery, with R0 resection in 67 (82%, 90%CI: 73–88%) (four patients with clinical complete response declined surgery). Twenty–four patients (30%) had an excellent clinical or pathological response (ECPR). Using NGS 24 (46%) of 52 matched biopsies/resections were discrepant: ten patients (19%) gained 13 new resection mutations compared to biopsy (12 KRAS, one PIK3CA) and 18 (35%) lost 22 mutations (15 KRAS, 7 PIK3CA). Tumours only ever testing RAS wild-type had significantly greater ECPR than tumours with either biopsy or resection RAS mutations (14/29 [48%] vs 10/51 [20%], P=0.008), with a trend towards increased overall survival (HR 0.23, 95% CI 0.05–1.03, P=0.055). Conclusions: This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss

Incidental nutrient transfers: Assessing critical times in agricultural catchments using high-resolution data

AbstractManaging incidental losses associated with liquid slurry applications during closed periods has significant cost and policy implications and the environmental data required to review such a measure are difficult to capture due to storm dependencies. Over four years (2010–2014) in five intensive agricultural catchments, this study used high-resolution total and total reactive phosphorus (TP and TRP), total oxidised nitrogen (TON) and suspended sediment (SS) concentrations with river discharge data to investigate the magnitude and timing of nutrient losses. A large dataset of storm events (defined as 90th percentile discharges), and associated flow-weighted mean (FWM) nutrient concentrations and TP/SS ratios, was used to indicate when losses were indicative of residual or incidental nutrient transfers. The beginning of the slurry closed period was reflective of incidental and residual transfers with high storm FWM P (TP and TRP) concentrations, with some catchments also showing elevated storm TP:SS ratios. This pattern diminished at the end of the closed period in all catchments. Total oxidised N behaved similarly to P during storms in the poorly drained catchments and revealed a long lag time in other catchments. Low storm FWM P concentrations and TP:SS ratios during the weeks following the closed period suggests that nutrients either weren't applied during this time (best times chosen) or that they were applied to less risky areas (best places chosen). For other periods such as late autumn and during wet summers, where storm FWM P concentrations and TP:SS ratios were high, it is recommended that an augmentation of farmer knowledge of soil drainage characteristics with local and detailed current and forecast soil moisture conditions will help to strengthen existing regulatory frameworks to avoid storm driven incidental nutrient transfers