Androgen receptor phosphorylation status at serine 578 predicts poor outcome in prostate cancer patients

Purpose: Prostate cancer growth is dependent upon androgen receptor (AR) activation, regulated via phosphorylation. Protein kinase C (PKC) is one kinase that can mediate AR phosphorylation. This study aimed to establish if AR phosphorylation by PKC is of prognostic significance. Methods: Immunohistochemistry for AR, AR phosphorylated at Ser-81 (pARS81), AR phosphorylated at Ser-578 (pARS578), PKC and phosphorylated PKC (pPKC) was performed on 90 hormone-naïve prostate cancer specimens. Protein expression was quantified using the weighted histoscore method and examined with regard to clinico-pathological factors and outcome measures; time to biochemical relapse, survival from biochemical relapse and disease-specific survival. Results: Nuclear PKC expression strongly correlated with nuclear pARS578 (c.c. 0.469, p=0.001) and cytoplasmic pARS578 (c.c. 0.426 p=0.002). High cytoplasmic and nuclear pARS578 were associated with disease-specific survival (p<0.001 and p=0.036 respectively). High nuclear PKC was associated with lower disease-specific survival when combined with high pARS578 in the cytoplasm (p=0.001) and nucleus (p=0.038). Combined high total pARS81 and total pARS578 was associated with decreased disease-specific survival (p=0.005) Conclusions: pARS578 expression is associated with poor outcome and is a potential independent prognostic marker in hormone-naïve prostate cancer. Furthermore, PKC driven AR phosphorylation may promote prostate cancer progression and provide a novel therapeutic target

Generalized Korn's inequality and conformal Killing vectors

Korn's inequality plays an important role in linear elasticity theory. This inequality bounds the norm of the derivatives of the displacement vector by the norm of the linearized strain tensor. The kernel of the linearized strain tensor are the infinitesimal rigid-body translations and rotations (Killing vectors). We generalize this inequality by replacing the linearized strain tensor by its trace free part. That is, we obtain a stronger inequality in which the kernel of the relevant operator are the conformal Killing vectors. The new inequality has applications in General Relativity.Comment: 8 page

Treating reading difficulties with colour [Editorial]

yesAround 3-6% of children in the United Kingdom have substantial difficulties learning to read, a condition often referred to as dyslexia. They are at high risk of educational underachievement. In a 1996 editorial in The BMJ, Margaret Snowling argued that dyslexia is a verbal (not a visual) disorder.1 An accumulation of evidence supports this position and shows that reading difficulties are best dealt with by interventions that target underlying weaknesses in phonological language skills and letter knowledge.2 The 2009 Rose report, which provides guidance for professionals in schools on identifying and teaching young people with dyslexia and reading difficulties, stresses the importance of early, phonological interventions.3 Despite this evidence, dyslexia is often associated with subjective experiences of visual distortions that lead to discomfort during reading (sometimes termed visual stress). It has been argued that these symptoms can be alleviated by using coloured overlays and lenses.4 Symptoms of visual stress are not unique to dyslexia, and proponents do not claim that the use of colour directly addresses the underlying cause of the reading difficulty. However, they argue that the reduction in visual distortion brought about by a change in colour can improve reading accuracy and fluency.

Treating reading difficulties with colour: Authors’ reply to Evans and Allen

yesWe thank Professors Evans and Allen for their interest in our article.1 2 The charity websites we reviewed refer to colour as though it offers a scientific, evidence based treatment; none referred to feedback from the membership. For example, one charity website makes the claim that “Research in the UK and in Australia shows that people who need coloured filters, who are said to have visual stress, need to have exactly the right colour.” This is incorrect. The research overwhelmingly shows little advantage, or at best conflicting results.3 4

Factors driving the decarbonisation of industrial clusters: A rapid evidence assessment of international experience

Reducing industrial emissions to achieve net-zero targets by the middle of the century will require profound and sustained changes to how energy intensive industries operate. Preliminary activity is now underway, with governments of several developed economies starting to implement policy and providing funding to support the deployment of low carbon infrastructure into high emitting industrial clusters. While clusters appear to offer the economies of scale and institutional capacity needed to kick-start the industrial transition, to date there has been little systematic assessment of the factors that may influence the success of these initiatives. Drawing from academic and grey literature, this paper presents a rapid evidence assessment of the approaches being used to drive the development of low carbon industrial clusters internationally. Many projects are still at the scoping stage, but it is apparent that current initiatives focus on the deployment of carbon capture technologies, alongside hydrogen as a future secondary revenue stream. This model of decarbonisation funnels investment into large coastal clusters with access to low carbon electricity and tends to obscure questions about the integration of these technologies with other decarbonisation interventions, such as material efficiency and electrification. The technology focus also omits the importance that a favourable location and shared history and culture appears to have played in helping progress the most advanced initiatives; factors that cannot be easily replicated elsewhere. If clusters are to kick-start the low-carbon industrial transition, then greater attention is needed to the social and political dimensions of this process and to a broader range of decarbonisation interventions and cluster types than represented by current projects

The factors determining uptake of energy crop cultivation and woodland creation in England: Insights from farmers and landowners

Perennial energy crops (PECs) and trees have key roles to play in delivering the negative emissions needed for the UK to reduce greenhouse gas emissions to net zero by 2050. Significant changes to land use are needed and the decision to make changes will lie with individual landowners. Using in-depth, semi-structured interviews, this research explores the attitudes of farmers and landowners in England to replacing traditional arable and livestock farming with growing annual or perennial energy crops or planting trees. It was concluded that considerable government policy intervention will be needed to overcome the many economic and social barriers in place including lack of markets and attractive contracts for growers, high establishment costs, loss of annual income, high prices available for cereal crops and the cultural division between farming and forestry. Although energy crops and woodland creation are generally researched and regulated separately, this research suggests that annual energy crops, PECs and woodland creation form a spectrum of land use options for a landowner, with the propensity to adopt these crops being determined predominantly by crop attributes including the risk of planting and the term of commitment