From protest to development : the dynamics of change at the Western Province Council of Churches

Bibliography: pages 179-183.The Western Province Council of Churches (WPCC) is an ecumenical organisation based in Cape Town which promotes ideals of justice. From 1971 to 1995 it was a branch of the South African Council of Churches. The WPCC regards itself as a non-governmental organisation (NGO), and it is part of the NGO sector. It is funded by foreign donor agencies. This thesis studies the transformation of the WPCC as an organisation. This occurred as a direct result of the political transition in South Africa between 1990 and 1994. The main forces pressing change upon the WPCC during this period were: (i) its commitment to retain relevance in a changing political and social environment according to the principles of contextual theology; (ii) its need to adapt its mode of operation following considerable changes in the context of its work; and, (iii) the most powerful force, the influence of foreign funding agencies upon the nature of its activities

The amino-acid stress sensing eIF2α kinase GCN2 is a survival biomarker for malignant mesothelioma

BackgroundMalignant mesothelioma is a tumour that is strongly associated with a history of asbestos exposure, and which derives from mesothelial cells that line the serous cavities of the body. The tumour most commonly arises in the pleural cavity, but can also arise in the pericardium, peritoneum, and tunica vaginalis. At present the lesion has a very poor prognosis and is an incurable form of cancer with median survival times of up to 19 months being quoted for some histological subtypes. A large proportion of mesotheliomas have been shown to be arginine auxotrophic, leading to new research for therapeutics which might exploit this potential vulnerability.MethodsWe measured the levels of General Control Non-derepressible 2 (GCN2) protein in malignant mesothelioma tumour samples and determined whether these levels correlate with clinical outcomes.ResultsWe observed that the expression levels of GCN2 correlated with patient survival and was an independent prognostic variable in pairwise comparisons with all available clinical data.ConclusionThese findings suggest that GCN2 levels provides prognostic information and may allow for stratification of care pathways. It may suggest that targeting GCN2 is a viable strategy for mesothelioma therapy development

Structure of the hexameric HerA ATPase reveals a mechanism of translocation-coupled DNA-end processing in archaea.

The HerA ATPase cooperates with the NurA nuclease and the Mre11-Rad50 complex for the repair of double-strand DNA breaks in thermophilic archaea. Here we extend our structural knowledge of this minimal end-resection apparatus by presenting the first crystal structure of hexameric HerA. The full-length structure visualizes at atomic resolution the N-terminal HerA-ATP synthase domain and a conserved C-terminal extension, which acts as a physical brace between adjacent protomers. The brace also interacts in trans with nucleotide-binding residues of the neighbouring subunit. Our observations support a model in which the coaxial interaction of the HerA ring with the toroidal NurA dimer generates a continuous channel traversing the complex. HerA-driven translocation would propel the DNA towards the narrow annulus of NurA, leading to duplex melting and nucleolytic digestion. This system differs substantially from the bacterial end-resection paradigms. Our findings suggest a novel mode of DNA-end processing by this integrated archaeal helicase-nuclease machine.The SAXS data collection was supported by funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (grant agreement N°283570). Research in the N.P.R. laboratory is funded by the Medical Research Council [Career Development Award G0701443]. Research in the L.P. laboratory is funded by a Wellcome Trust Senior Fellowship Award in Basic Biomedical Sciences [grant number 08279/Z/07/Z]. Work in the L.P. and N.P.R. laboratories is also supported by an Isaac Newton Trust Research Grant, and S.M.B. is supported by a BBSRC Doctoral Training Grant.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncomms650

Multimodality Characterization of Cancer-Associated Fibroblasts in Tumor Microenvironment and Its Correlation With Ultrasound Shear Wave-Measured Tissue Stiffness in Localized Prostate Cancer

INTRODUCTION: Growing evidence suggests that the tumor microenvironment (TME) represented by cellular and acellular components plays a key role in the multistep process of metastases and response to therapies. However, imaging and molecular characterization of the TME in prostate cancer (PCa) and its role in predicting aggressive tumor behavior and disease progression is largely unexplored. The study explores the PCa TME through the characterization of cancer-associated fibroblasts (CAFs) using both immunohistochemistry (IHC) and genomics approaches. This is then correlated with transrectal ultrasound shear wave elastography (USWE)-measured tissue stiffness. PATIENTS AND METHODS: Thirty patients with clinically localized PCa undergoing radical prostatectomy for different risk categories of tumor (low, intermediate, and high) defined by Gleason score (GS) were prospectively recruited into this study. Prostatic tissue stiffness was measured using USWE prior to surgery. The CAFs within the TME were identified by IHC using a panel of six antibodies (FAP, SMAα, FSP1, CD36, PDGFRα, and PDGFRβ) as well as gene expression profiling using TempO-sequence analysis. Whether the pattern and degree of immunohistochemical positivity (measured by Quick score method) and expression of genes characterizing CAFs were correlated with USWE- and GS-measured tissue stiffnesses were tested using Spearman’s rank correlation and Pearson correlation. RESULTS: There was a statistically significant correlation between GS of cancers, the pattern of staining for CAFs by immunohistochemical staining, and tissue stiffness measured in kPa using USWE (p < 0.001). Significant differences were also observed in immunohistochemical staining patterns between normal prostate and prostatic cancerous tissue. PDGFRβ and SMAα immunostaining scores increased linearly with increasing the USWE stiffness and the GS of PCa. There was a significant positive correlation between increasing tissue stiffness in tumor stroma and SMAα and PDGFRβ gene expression in the fibromuscular stroma (p < 0.001). CONCLUSION: USWE-measured tissue stiffness correlates with increased SMAα and PDGFRβ expressing CAFs and PCa GSs. This mechanistic correlation could be used for predicting the upgrading of GS from biopsies to radical surgery and response to novel treatments

Resting pastures to improve land condition in northern Australia: guidelines based on the literature and simulation modelling

Pasture rest is a possible strategy for improving land condition in the extensive grazing lands of northern Australia. If pastures currently in poor condition could be improved, then overall animal productivity and the sustainability of grazing could be increased. The scientific literature is examined to assess the strength of the experimental information to support and guide the use of pasture rest, and simulation modelling is undertaken to extend this information to a broader range of resting practices, growing conditions and initial pasture condition. From this, guidelines are developed that can be applied in the management of northern Australia’s grazing lands and also serve as hypotheses for further field experiments. The literature on pasture rest is diverse but there is a paucity of data from much of northern Australia as most experiments have been conducted in southern and central parts of Queensland. Despite this, the limited experimental information and the results from modelling were used to formulate the following guidelines. Rest during the growing season gives the most rapid improvement in the proportion of perennial grasses in pastures; rest during the dormant winter period is ineffective in increasing perennial grasses in a pasture but may have other benefits. Appropriate stocking rates are essential to gain the greatest benefit from rest: if stocking rates are too high, then pasture rest will not lead to improvement; if stocking rates are low, pastures will tend to improve without rest. The lower the initial percentage of perennial grasses, the more frequent the rests should be to give a major improvement within a reasonable management timeframe. Conditions during the growing season also have an impact on responses with the greatest improvement likely to be in years of good growing conditions. The duration and frequency of rest periods can be combined into a single value expressed as the proportion of time during which resting occurs; when this is done the modelling suggests the greater the proportion of time that a pasture is rested, the greater is the improvement but this needs to be tested experimentally. These guidelines should assist land managers to use pasture resting but the challenge remains to integrate pasture rest with other pasture and animal management practices at the whole-property scale

Resting pastures to improve land condition in northern Australia: guidelines based on the literature and simulation modelling

Pasture rest is a possible strategy for improving land condition in the extensive grazing lands of northern Australia. If pastures currently in poor condition could be improved, then overall animal productivity and the sustainability of grazing could be increased. The scientific literature is examined to assess the strength of the experimental information to support and guide the use of pasture rest, and simulation modelling is undertaken to extend this information to a broader range of resting practices, growing conditions and initial pasture condition. From this, guidelines are developed that can be applied in the management of northern Australia’s grazing lands and also serve as hypotheses for further field experiments. The literature on pasture rest is diverse but there is a paucity of data from much of northern Australia as most experiments have been conducted in southern and central parts of Queensland. Despite this, the limited experimental information and the results from modelling were used to formulate the following guidelines. Rest during the growing season gives the most rapid improvement in the proportion of perennial grasses in pastures; rest during the dormant winter period is ineffective in increasing perennial grasses in a pasture but may have other benefits. Appropriate stocking rates are essential to gain the greatest benefit from rest: if stocking rates are too high, then pasture rest will not lead to improvement; if stocking rates are low, pastures will tend to improve without rest. The lower the initial percentage of perennial grasses, the more frequent the rests should be to give a major improvement within a reasonable management timeframe. Conditions during the growing season also have an impact on responses with the greatest improvement likely to be in years of good growing conditions. The duration and frequency of rest periods can be combined into a single value expressed as the proportion of time during which resting occurs; when this is done the modelling suggests the greater the proportion of time that a pasture is rested, the greater is the improvement but this needs to be tested experimentally. These guidelines should assist land managers to use pasture resting but the challenge remains to integrate pasture rest with other pasture and animal management practices at the whole-property scale

‘It’s my back…’; developing the coming to spinal clinic resource to improve the health literacy of young people with adolescent idiopathic scoliosis and their parents

This study focussed on identifying the key concerns and information needs of young people with Adolescent Idiopathic Scoliosis (AIS) and their parents and examined what resources might help improve young people’s ‘participativeness’ and health literacy during clinic consultations. A qualitative participatory design underpinned the study. Workshops involving multiple methods were used to engage with young people with AIS and their parents, who were recruited through a regional children’s hospital. The study design was informed by patient and public consultation with eight young people and two parents. 10 young people (aged 14–16 years) and 11 of their parents participated in the study. Young people and their parents reported uncertainty and anxiety before coming to clinic and faced issues participating in the consultation, being involved in decision-making and understanding the information and language. These challenges resulted in unmet information needs. Young people’s health literacy relating to an AIS diagnosis and treatment is facilitated by them being prepared and informed before coming to clinic and be actively supported to be involved during the consultation. We collaboratively developed the ‘Coming to Spinal Clinic’ resource to help young people with AIS and parents prepare for and get the most out of their visit

High-Precision Photothermal Ablation using Biocompatible Palladium Nanoparticles and Laser Scanning Microscopy

Herein, we report a straightforward method for the scalable preparation of Pd nanoparticles (Pd-NPs) with reduced inherent cytotoxicity and high photothermal conversion capacity. These Pd-NPs are rapidly taken up by cells and able to kill labeled cancer cells upon short exposure to near-infrared (NIR) light. Following cell treatment with Pd-NPs, ablated areas were patterned with high precision by laser scanning microscopy, allowing one to perform cell migration assays with unprecedented accuracy. Using coherent Raman microscopy, cells containing Pd-NPs were simultaneously ablated and imaged. This novel methodology was combined with intravital imaging to mediate microablation of cancerous tissue in tumor xenografts in mice

The effects of graded motor imagery and its components on chronic pain: A systematic review and meta-analysis

This is the post-print version of the final paper published in The Journal of Pain. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 The American Pain Society.Graded motor imagery (GMI) is becoming increasingly used in the treatment of chronic pain conditions. The objective of this systematic review was to synthesize all evidence concerning the effects of GMI and its constituent components on chronic pain. Systematic searches were conducted in 10 electronic databases. All randomized controlled trials (RCTs) of GMI, left/right judgment training, motor imagery, and mirror therapy used as a treatment for chronic pain were included. Methodological quality was assessed using the Cochrane risk of bias tool. Six RCTs met our inclusion criteria, and the methodological quality was generally low. No effect was seen for left/right judgment training, and conflicting results were found for motor imagery used as stand-alone techniques, but positive effects were observed for both mirror therapy and GMI. A meta-analysis of GMI versus usual physiotherapy care favored GMI in reducing pain (2 studies, n = 63; effect size, 1.06 [95% confidence interval, .41, 1.71]; heterogeneity, I2 = 15%). Our results suggest that GMI and mirror therapy alone may be effective, although this conclusion is based on limited evidence. Further rigorous studies are needed to investigate the effects of GMI and its components on a wider chronic pain population.NHMR

The Role of Domestic Integrated Battery Energy Storage Systems for Electricity Network Performance Enhancement

Low carbon technologies are necessary to address global warming issues through electricity decabonisation, but their large-scale integration challenges the stability and security of electricity supply. Energy storage can support this transition by bringing flexibility to the grid but since it represents high capital investments, the right choices must be made in terms of the technology and the location point in the network. Most of the potential for storage is achieved when connected further from the load, and Battery Energy Storage Systems (BESS) are a strong candidate for behind-the-meter integration. This work reviews and evaluates the state-of-the-art development of BESS, analysing the benefits and barriers to a wider range of applications in the domestic sector. Existing modelling tools that are key for a better assessment of the impacts of BESS to the grid are also reviewed. It is shown that the technology exists and has potential for including Electric Vehicle battery reuse, however it is still mostly applied to optimise domestic photovoltaic electricity utilisation. The barriers to a wider integration are financial, economic, technical, as well as market and regulation. Increased field trials and robust numerical modelling should be the next step to gain investment confidence and allow BESS to reach their potential