"The good guys are doing it anyway": the accommodation of environmental concern among English and Welsh farmers

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.Farmers today are increasingly facing pressure from policy and market forces to improve their environmental performance. Yet – despite widespread recognition of the negative externalities of agriculture on a national and global scale - many farmers would argue that, as ‘custodians of the countryside’ they have always respected and cared for the local environment, and play a central role in creating and maintaining the countryside as we know it today. In this paper, we use evidence emerging from research with farmers across England and Wales to explore farmer accounts of environmental concern and action in the context of both traditional farming values and contemporary imperatives. We draw particularly on scholarly work around constructs of ‘good farming’ to consider the extent to which environmental concern has been accommodated within a wide range of farming contexts across England and Wales. Our findings highlight an intrinsic sense of care towards the environment among farmers and reveal how environmental management has in many ways become an integral part of farming discourse; recognised as synergistic with personal and business goals concerning i) personal respect for the environment and conservation; ii) countryside custodianship; iii) farm legacy and succession; iv) ‘good’ agricultural practice and compliance with regulation; and/or v) financial profitability. We discuss some of the issues arising from our findings and offer our thoughts on implications for efforts to encourage farmers to carry out environmentally beneficial activities. Whilst expressions of environmental concern do not necessarily equate to effective action on the ground, recognising that many farmers believe environmental management to be part of good farming practice provides a more positive foundation for engaging with them on this topic than assuming they need to be cajoled into action.The research on which this paper is based was funded as part of Defra’s Sustainable Intensification Research Platform (Project LM0302)

The Importance of Cerebellar Connectivity on Simulated Brain Dynamics

The brain shows a complex multiscale organization that prevents a direct understanding of how structure, function and dynamics are correlated. To date, advances in neural modeling offer a unique opportunity for simulating global brain dynamics by embedding empirical data on different scales in a mathematical framework. The Virtual Brain (TVB) is an advanced data-driven model allowing to simulate brain dynamics starting from individual subjects’ structural and functional connectivity obtained, for example, from magnetic resonance imaging (MRI). The use of TVB has been limited so far to cerebral connectivity but here, for the first time, we have introduced cerebellar nodes and interconnecting tracts to demonstrate the impact of cerebro-cerebellar loops on brain dynamics. Indeed, the matching between the empirical and simulated functional connectome was significantly improved when including the cerebro-cerebellar loops. This positive result should be considered as a first step, since issues remain open about the best strategy to reconstruct effective structural connectivity and the nature of the neural mass or mean-field models generating local activity in the nodes. For example, signal processing is known to differ remarkably between cortical and cerebellar microcircuits. Tackling these challenges is expected to further improve the predictive power of functional brain activity simulations, using TVB or other similar tools, in explaining not just global brain dynamics but also the role of cerebellum in determining brain states in physiological conditions and in the numerous pathologies affecting the cerebro-cerebellar loop

A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation

BACKGROUND: Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 μl/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. RESULTS: Geltrex™ basement matrix at 5 μl/cm(2) in 24-well (10 μl) or 96-well (2 μl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix. CONCLUSIONS: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-014-0041-5) contains supplementary material, which is available to authorized users

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

Unsuspected Involvement of Spinal Cord in Alzheimer Disease

OBJECTIVE: Brain atrophy is an established biomarker for dementia, yet spinal cord involvement has not been investigated to date. As the spinal cord is relaying sensorimotor control signals from the cortex to the peripheral nervous system and vice-versa, it is indeed a very interesting question to assess whether it is affected by atrophy due to a disease that is known for its involvement of cognitive domains first and foremost, with motor symptoms being clinically assessed too. We, therefore, hypothesize that in Alzheimer’s disease (AD), severe atrophy can affect the spinal cord too and that spinal cord atrophy is indeed an important in vivo imaging biomarker contributing to understanding neurodegeneration associated with dementia. METHODS: 3DT1 images of 31 AD and 35 healthy control (HC) subjects were processed to calculate volume of brain structures and cross-sectional area (CSA) and volume (CSV) of the cervical cord [per vertebra as well as the C2-C3 pair (CSA23 and CSV23)]. Correlated features (ρ > 0.7) were removed, and the best subset identified for patients’ classification with the Random Forest algorithm. General linear model regression was used to find significant differences between groups (p ≤ 0.05). Linear regression was implemented to assess the explained variance of the Mini-Mental State Examination (MMSE) score as a dependent variable with the best features as predictors. RESULTS: Spinal cord features were significantly reduced in AD, independently of brain volumes. Patients classification reached 76% accuracy when including CSA23 together with volumes of hippocampi, left amygdala, white and gray matter, with 74% sensitivity and 78% specificity. CSA23 alone explained 13% of MMSE variance. DISCUSSION: Our findings reveal that C2-C3 spinal cord atrophy contributes to discriminate AD from HC, together with more established features. The results show that CSA23, calculated from the same 3DT1 scan as all other brain volumes (including right and left hippocampi), has a considerable weight in classification tasks warranting further investigations. Together with recent studies revealing that AD atrophy is spread beyond the temporal lobes, our result adds the spinal cord to a number of unsuspected regions involved in the disease. Interestingly, spinal cord atrophy explains also cognitive scores, which could significantly impact how we model sensorimotor control in degenerative diseases with a primary cognitive domain involvement. Prospective studies should be purposely designed to understand the mechanisms of atrophy and the role of the spinal cord in AD

Unsuspected Involvement of Spinal Cord in Alzheimer Disease

Objective: Brain atrophy is an established biomarker for dementia, yet spinal cord involvement has not been investigated to date. As the spinal cord is relaying sensorimotor control signals from the cortex to the peripheral nervous system and vice-versa, it is indeed a very interesting question to assess whether it is affected by atrophy due to a disease that is known for its involvement of cognitive domains first and foremost, with motor symptoms being clinically assessed too. We, therefore, hypothesize that in Alzheimer’s disease (AD), severe atrophy can affect the spinal cord too and that spinal cord atrophy is indeed an important in vivo imaging biomarker contributing to understanding neurodegeneration associated with dementia. Methods: 3DT1 images of 31 AD and 35 healthy control (HC) subjects were processed to calculate volume of brain structures and cross-sectional area (CSA) and volume (CSV) of the cervical cord [per vertebra as well as the C2-C3 pair (CSA23 and CSV23)]. Correlated features (ρ > 0.7) were removed, and the best subset identified for patients’ classification with the Random Forest algorithm. General linear model regression was used to find significant differences between groups (p ≤ 0.05). Linear regression was implemented to assess the explained variance of the Mini-Mental State Examination (MMSE) score as a dependent variable with the best features as predictors. Results: Spinal cord features were significantly reduced in AD, independently of brain volumes. Patients classification reached 76% accuracy when including CSA23 together with volumes of hippocampi, left amygdala, white and gray matter, with 74% sensitivity and 78% specificity. CSA23 alone explained 13% of MMSE variance. Discussion: Our findings reveal that C2-C3 spinal cord atrophy contributes to discriminate AD from HC, together with more established features. The results show that CSA23, calculated from the same 3DT1 scan as all other brain volumes (including right and left hippocampi), has a considerable weight in classification tasks warranting further investigations. Together with recent studies revealing that AD atrophy is spread beyond the temporal lobes, our result adds the spinal cord to a number of unsuspected regions involved in the disease. Interestingly, spinal cord atrophy explains also cognitive scores, which could significantly impact how we model sensorimotor control in degenerative diseases with a primary cognitive domain involvement. Prospective studies should be purposely designed to understand the mechanisms of atrophy and the role of the spinal cord in AD

Black Holes in Gravity with Conformal Anomaly and Logarithmic Term in Black Hole Entropy

We present a class of exact analytic and static, spherically symmetric black hole solutions in the semi-classical Einstein equations with Weyl anomaly. The solutions have two branches, one is asymptotically flat and the other asymptotically de Sitter. We study thermodynamic properties of the black hole solutions and find that there exists a logarithmic correction to the well-known Bekenstein-Hawking area entropy. The logarithmic term might come from non-local terms in the effective action of gravity theories. The appearance of the logarithmic term in the gravity side is quite important in the sense that with this term one is able to compare black hole entropy up to the subleading order, in the gravity side and in the microscopic statistical interpretation side.Comment: Revtex, 10 pages. v2: minor changes and to appear in JHE

Acceptability and feasibility of peer assisted supervision and support for intervention practitioners: a Q-methodology evaluation

Evidence-based interventions often include quality improvement methods to support fidelity and improve client outcomes. Clinical supervision is promoted as an effective way of developing practitioner confidence and competence in delivery; however, supervision is often inconsistent and embedded in hierarchical line management structures that may limit the opportunity for reflective learning. The Peer Assisted Supervision and Support (PASS) supervision model uses peer relationships to promote the self-regulatory capacity of practitioners to improve intervention delivery. The aim of the present study was to assess the acceptability and feasibility of PASS amongst parenting intervention practitioners. A Q-methodology approach was used to generate data and 30 practitioners volunteered to participate in the study. Data were analyzed and interpreted using standard Q-methodology procedures and by-person factor analysis yielded three factors. There was consensus that PASS was acceptable. Participants shared the view that PASS facilitated an environment of support where negative aspects of interpersonal relationships that might develop in supervision were not evident. Two factors represented the viewpoint that PASS was also a feasible model of supervision. However, the third factor was comprised of practitioners who reported that PASS could be time consuming and difficult to fit into existing work demands. There were differences across the three factors in the extent to which practitioners considered PASS impacted on their intervention delivery. The findings highlight the importance of organizational mechanisms that support practitioner engagement in supervision

Rotating black holes with equal-magnitude angular momenta in d=5 Einstein-Gauss-Bonnet theory

We construct rotating black hole solutions in Einstein-Gauss-Bonnet theory in five spacetime dimensions. These black holes are asymptotically flat, and possess a regular horizon of spherical topology and two equal-magnitude angular momenta associated with two distinct planes of rotation. The action and global charges of the solutions are obtained by using the quasilocal formalism with boundary counterterms generalized for the case of Einstein-Gauss-Bonnet theory. We discuss the general properties of these black holes and study their dependence on the Gauss-Bonnet coupling constant $\alpha$. We argue that most of the properties of the configurations are not affected by the higher derivative terms. For fixed $\alpha$ the set of black hole solutions terminates at an extremal black hole with a regular horizon, where the Hawking temperature vanishes and the angular momenta attain their extremal values. The domain of existence of regular black hole solutions is studied. The near horizon geometry of the extremal solutions is determined by employing the entropy function formalism.Comment: 25 pages, 7 figure

Perturbations of Gauss-Bonnet Black Strings in Codimension-2 Braneworlds

We derive the Lichnerowicz equation in the presence of the Gauss-Bonnet term. Using the modified Lichnerowicz equation we study the metric perturbations of Gauss-Bonnet black strings in Codimension-2 Braneworlds.Comment: 26 pages, no figures, clarifying comments and one reference added, to be published in JHE