Community land: Proposals for a local authority land scheme, based on a financial study of the Community Land Act, 1975

From an analysis of the financial arrangements of the Community Land Act, this dissertation proposes an alternative framework for a local authority land scheme. The Community Land Act, which enabled local authorities to take development land into public ownership in order to ensure that its development was in the best interests of "the community", was passed by a Labour Government in 1975 and vigorously opposed throughout its existence by the Conservative Party. Chapter 1 outlines the political controversy that surrounded the Act's operation. Its dismantling and imminent repeal by the new Conservative Government comes as no surprise; but the Government stresses that this is on the grounds of its impracticality and not of political opposition. The retention of a high level of Development Land Tax (introduced a year later than the Community Land Act and designed to return a proportion of increases in land values to the community), and of the Land Authority for Wales (an executive body set up to implement the Land Act in the Principality), together with the establishment of Urban Development Corporations (redevelopment bodies to be equipped with broad powers of land acquisition and management), seem to indicate that the Conservative Party is not opposed in principle to public ownership of development land or at least a part of development value. The Government cites the Community Land Act's poor financial performance with respect to the amount of land it provided for development as the reason for its unacceptability. Thus perhaps a practical land scheme would enjoy acceptability and, unlike the Central Land Board of 1947 and the Land Commission of 1967, whose histories are outlined in chapter 2, would survive the short terms of party political power. This is felt to be particularly important to Planning as access to the ownership rights over development land gives the Planner the opportunity to see his proposals implemented in a positive way rather than negatively through existing development control mechanisms. The criteria for practicality and acceptability of a local authority land scheme are thought to be administrative efficiency and effectiveness of implementation and it is believed that both can be fulfilled through the provision of an adequate financial framework. The financial discipline introduced by the Community Land Act is classified in chapter 3 and examined in terms of three "Key Areas". The first of these deals with the administration of Central Government loan sanctions for the commencement of programmes; the second, with the operation of the Community Land Accounts for the continuation of programmes; and the three, with the division of surpluses and financing of deficits on the completion of programmes. For their analysis in chapter according to the experience of six local authorities in a variety of circumstances, another "Key Area"; of land dealing practices before and during the operation of the Community Land Act; is added. The study is carried out principally by means of Questionnaire sur*vey of Council Financial Officials. On the basis of the analysis, conclusions are drawn in chapter 5 as to the suitability of the Land Act's financial arrangements to local authority land dealing, and recommendations are made in chapter 6 for the efficient administration and effective implementation of a future land scheme. If the financial framework of any such scheme is sound, it is thought that survival at the least will be assured and the Planning Profession will be given the opportunity of a fair trial in that which may have been its intended form of operation

Biocompatibility of Silicon Nitride Nanoparticles and Cobalt Chromium Wear Debris from THR

Introduction: Silicon nitride (SiN) is a recently introduced bearing material for THR that has shown potential in its bulk form and as a coating material on cobalt-chromium (CoCr) substrates. Previous studies have shown that SiN has low friction characteristics, low wear rates and high mechanical strength. Moreover, it has been shown to have osseointegration properties. However, there is limited evidence to support its biocompatibility as an implant material. The aim of this study was to investigate the responses of peripheral blood mononuclear cells (PBMNCs) isolated from healthy human volunteers and U937 human histiocytes (U937s) to SiN nanoparticles and CoCr wear particles. Methods: SiN nanopowder (<50nm, Sigma UK) and CoCr wear particles (nanoscale, generated in a multidirectional pin-on-plate reciprocator) were heat-treated for 4 h at 180°C and dispersed by sonication for 10 min prior to their use in cell culture experiments. Whole peripheral blood was collected from healthy donors (ethics approval BIOSCI 10–108, University of Leeds). The PBMNCs were isolated using Lymphoprep® as a density gradient medium and incubated for 24 h in 5% (v/v) CO2at 37°C to allow attachment of mononuclear phagocytes. SiN and CoCr particles were then added to the phagocytes at a volume concentration of 50 µm3 particles per cell and cultured for 24 h in RPMI-1640 culture medium in 5% (v/v) CO2 at 37°C. Cells alone were used as a negative control and lipopolysaccharide (LPS; 200ng/ml) was used as a positive control. Cell viability was measured after 24 h by ATPLite assay and tumour necrosis factor alpha (TNF-α) release was measured by sandwich ELISA. U937s were co-cultured with SiN and CoCr particles at doses of 0.05, 0.5, 5 and 50 µm3 particles per cell for 24h in 5% (v/v) CO2 at 37 C. Cells alone were used as a negative control and camptothecin (2 µg/ml) was used as a positive control. Cell viability was measured after 0, 1, 3, 6 and 9 days. Results from cell viability assays and TNF-α response were expressed as mean ±95% confidence limits and the data was analysed using one-way ANOVA and Tukey-Kramer post-hoc analysis. Results and Discussion: At a high volume concentration of particles (50µm3 per cell), SiN did not affect the viability of PBMNCs, while CoCr significantly reduced the viability over a 24 h period [Figure 1A]. Similarly, SiN particles had no effect on the viability of U937s up to 9 days with a range of particle doses (0.05–50 µm3 per cell) [Figure 2A]. In contrast, CoCr particles significantly reduced the viability of U937s after 6 days [Figure 2B]. Additionally, CoCr particles caused significantly elevated levels of pro-inflammatory cytokine TNF-α, whereas no inflammation was associated with SiN particles [Figure 1B]. Conclusion: This study has demonstrated the in-vitro biocompatibility of SiN nanoparticles. Therefore, SiN is a promising orthopaedic bearing material not only due to its suitable mechanical and tribological properties, but also due to its biocompatibility

Upper respiratory symptoms worsen over time and relate to clinical phenotype in COPD.

Copyright © 2015 by the American Thoracic Society.Rationale: How nasal symptoms in patients with chronic obstructive pulmonary disease (COPD) change over time and resolve during naturally occurring exacerbations has not been described previously. Objectives: To evaluate the evolution and impact of upper airway symptoms in a well-defined COPD cohort when stable and at exacerbation. Methods: Patients in the LondonCOPDcohortwere asked about the presence of nasal symptoms (nasal discharge, sneezing, postnasal drip, blocked nose, and anosmia) over an 8-year period (2005-2013) every 3 months at routine clinic visits while in a stable state and daily during exacerbations with the use of diary cards. Data were prospectively collected, and, in a subgroup of patients,COPDAssessment Test scores and human rhinovirus identification by polymerase chain reaction were available. Patients were also defined as having infrequent or frequent exacerbations (<2 or ≥2 exacerbations/yr, respectively). Measurements and Main Results: At an aggregate of 4,368 visits, 209 patients with COPD were asked about their nasal symptoms. At 2,033 visits when the patients were stable, the odds ratio (OR) for nasal discharge increased by 1.32% per year (95% confidence interval [CI], 1.19-1.45; P<0.001); the OR for sneezing increased by 1.16%(95%CI, 1.05-1.29;P = 0.005); theORfor postnasal drip increased by 1.18% (95% CI, 1.03-1.36; P=0.016); and theOR for anosmia increased by 1.19% (95% CI, 1.03-1.37; P = 0.015). At visits when the patients were having exacerbations, nasal discharge was present for 7 days and blocked nose, sneezing, and postnasal drip increased for just 3 days. Anosmia did not change. Nasal dischargewasmore likely inpatientswith frequent exacerbations (OR, 1.96; 95% CI, 1.17-3.28; P= 0.011), and COPD Assessment Test scores were higher by 1.06 units (95% CI, 0.32-1.80; P=0.005) when patients were stable and higher by 1.30 units (95% CI, 0.05-2.57; P= 0.042) during exacerbations. Conclusions: Upper airway symptoms increase over time in patients with COPD and are related to the frequent exacerbation phenotype. These longitudinal changes may be due to increasing airway inflammation or to progression of COPD

Using a multi-lens framework for landscape decisions

1. Landscape decisions are multi-faceted. Framing landscape decision-making as a governance process that requires a collective approach can encourage key stakeholders to come together to co-inform a discussion about their priorities and what constitutes good governance, leading to more holistic landscape decisions. 2. In this paper, we recognise that a suite of complementary and multi-dimensional approaches are in practice used to inform and evaluate land use decisions. We have called these approaches ‘lenses’ because they each provide a different perspective on the same problem. The four lenses are: i) Power and Market Gain, ii) Ecosystem Services, iii), Place-based Identity and iv) Ecocentric. Each brings a different set of evidence and viewpoints (narrative, qualitative and experiential, as well as quantitative metrics such as monetary) to the decision-making process and can potentially reveal problems and solutions that others do not. 3. Considering all lenses together allows dialogue to take place which can reveal the true complexities of landscape decision-making and can facilitate more effective and more holistic decisions. Employing the lenses requires governance structures that give equal weight to all lenses, enable dialogue and coexistence between top down and bottom-up approaches, and permit adaptation to local and granular place-specifics rather than developing “one-size-fits-all” solutions. 4. We propose that formalising the process of balancing all the lenses requires public participation, and that a lens approach should be used to support landscape decisions alongside a checklist that facilitates transparency in the conversation, showing how all evidence has been considered and critically assessed

Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology

Despite the early recognition of the potential of proton imaging to assist proton therapy (Cormack 1963 J. Appl. Phys. 34 2722), the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as computed tomography (CT), the water-equivalent-path-length that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS active pixel sensor technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed

Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma

Aberrant genetic and epigenetic variations drive malignant transformation and are hallmarks of cancer. Using PCR-free sample preparation we achieved the first in-depth whole genome (hydroxyl)-methylcytosine, single-base-resolution maps from a glioblastoma tumour/margin sample of a patient. Our data provide new insights into how genetic and epigenetic variations are interrelated. In the tumour, global hypermethylation with a depletion of 5-hydroxymethylcytosine was observed. The majority of single nucleotide variations were identified as cytosine-to-thymine deamination products within CpG context, where cytosine was preferentially methylated in the margin. Notably, we observe that cells neighbouring tumour cells display epigenetic alterations characteristic of the tumour itself although genetically they appear “normal”. This shows the potential transfer of epigenetic information between cells that contributes to the intratumour heterogeneity of glioblastoma. Together, our reference (epi)-genome provides a human model system for future studies that aim to explore the link between genetic and epigenetic variations in cancer progression.Cancer Research UK 236 (Grant ID: C14303/A17197), Wellcome Trust (Grant ID: 099232/z/12/z

Improving continence in children and young people with neurodisability: a systematic review and survey.

Children and young people with neurodisability often need help to achieve socially acceptable bladder and bowel control. Approaches vary depending on whether or not the impairment results from spinal cord pathology that impairs motor control and sensation of the bladder and bowel. Currently, there is uncertainty about which interventions are effective. The objective was to summarise the available evidence on and current practice for improving continence in children and young people with neurodisability. A systematic review of the effectiveness, cost-effectiveness and factors that modify intervention implementation, alongside a cross-sectional, online survey of current practice with health professionals, parent carers, school and care staff and young people with neurodisability. Twelve databases were searched in the review, resulting in 5756 references; 71 studies (72 papers) were included in the analyses. Most of the evidence was for children with spinal cord pathology, which involved evaluations of pharmacological approaches and surgical techniques, whereas the evidence pertaining to those with non-spinal-cord-related pathology tended to be for behavioural interventions. The methodological quality of studies was rated as being moderate to poor. There were three robust qualitative studies about the experience of continence among children with spinal cord pathology. We found substantial heterogeneity across the interventions that we evaluated in terms of quality, study design and outcomes measured. No economic studies were found. The results were synthesised narratively and reported in text and tables. We did not find any eligible studies evaluating interventions using toilet and clothing adaptations in the review, although the survey highlighted that these types of interventions are frequently used and considered. In total, 949 people responded to the survey: 202 health professionals, 605 parent carers, 122 school and social care staff, and 20 young people. The survey results illustrated the different roles that professionals have in improving continence, highlighting the importance of a multidisciplinary approach to supporting children and young people and their families. Clinicians employ a range of assessments and interventions to improve continence or independent toileting, depending on the needs of the child. Quantitative studies in the review were not methodologically robust. The survey had a risk of response bias. Our research found a dearth of good-quality evidence for many of the interventions currently in use, and no evidence of experiences of implementing interventions for children with non-spinal-cord-related pathology. There was also no evidence of cost-effectiveness of any of the interventions. There is a need to involve young people and families in the design of high-quality evaluative research for interventions that aim to improve continence. This is especially the case for children with autism and learning disability, who have been neglected in previous evaluative and qualitative research. We recommend better training for health, education and care professionals about toileting, informed by evidence and the lived experiences of children and their families. We recommend a joined-up multidisciplinary and holistic approach to improving continence to maximise independence, dignity and comfort. It is vital that children and young people with neurodisability have early access to regular, integrated assessment of their bladder and bowel health, and are fully supported with appropriate personalised treatment. This study is registered as PROSPERO CRD42018100572. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 73. See the NIHR Journals Library website for further project information

OPTIma:a tracking solution for proton computed tomography in high proton flux environments

Currently there is a large discrepancy between the currents that are used for treatments in proton beam therapy facilities and the ultra low beam currents required for many proton CT imaging systems. Here we provide details of the OPTIma silicon strip based tracking system, which has been designed for performing proton CT imaging in conditions closer to the high proton flux environments of modern spot scanning treatment facilities. Details on the physical design, sensor testing, modelling, and track reconstruction are provided along with Monte-Carlo simulation studies of the expected performance for proton beam currents of up to 50 pA at the nozzle when using a σ = ∼10 mm spot scanning cyclotron system. Using a detailed simulation of the proposed OPTIma system, a discrepancy of less than 1% on the Relative Stopping Power is found for various tissues when embedded within a 150 mm diameter Perspex sphere. It is found that by accepting up to 7 protons per bunch it is possible to operate at cyclotron beam currents up to 5 times higher than would be possible with a single proton based readout, significantly reducing the total beam time required to produce an image, while also reducing the discrepancy between the beam currents required for treatment and those used for proton CT