Development and validation of 'AutoRIF': Software for the automated analysis of radiation-induced foci

Copyright @ 2012 McVean et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: The quantification of radiation-induced foci (RIF) to investigate the induction and subsequent repair of DNA double strands breaks is now commonplace. Over the last decade systems specific for the automatic quantification of RIF have been developed for this purpose, however to ask more mechanistic questions on the spatio-temporal aspects of RIF, an automated RIF analysis platform that also quantifies RIF size/volume and relative three-dimensional (3D) distribution of RIF within individual nuclei, is required. Results: A java-based image analysis system has been developed (AutoRIF) that quantifies the number, size/volume and relative nuclear locations of RIF within 3D nuclear volumes. Our approach identifies nuclei using the dynamic Otsu threshold and RIF by enhanced Laplacian filtering and maximum entropy thresholding steps and, has an application ‘batch optimisation’ process to ensure reproducible quantification of RIF. AutoRIF was validated by comparing output against manual quantification of the same 2D and 3D image stacks with results showing excellent concordance over a whole range of sample time points (and therefore range of total RIF/nucleus) after low-LET radiation exposure. Conclusions: This high-throughput automated RIF analysis system generates data with greater depth of information and reproducibility than that which can be achieved manually and may contribute toward the standardisation of RIF analysis. In particular, AutoRIF is a powerful tool for studying spatio-temporal relationships of RIF using a range of DNA damage response markers and can be run independently of other software, enabling most personal computers to perform image analysis. Future considerations for AutoRIF will likely include more complex algorithms that enable multiplex analysis for increasing combinations of cellular markers.This article is made available through the Brunel Open Access Publishing Fund

A Bayesian parameter estimation approach to pulsar time-of-arrival analysis

The increasing sensitivities of pulsar timing arrays to ultra-low frequency (nHz) gravitational waves promises to achieve direct gravitational wave detection within the next 5-10 years. While there are many parallel efforts being made in the improvement of telescope sensitivity, the detection of stable millisecond pulsars and the improvement of the timing software, there are reasons to believe that the methods used to accurately determine the time-of-arrival (TOA) of pulses from radio pulsars can be improved upon. More specifically, the determination of the uncertainties on these TOAs, which strongly affect the ability to detect GWs through pulsar timing, may be unreliable. We propose two Bayesian methods for the generation of pulsar TOAs starting from pulsar "search-mode" data and pre-folded data. These methods are applied to simulated toy-model examples and in this initial work we focus on the issue of uncertainties in the folding period. The final results of our analysis are expressed in the form of posterior probability distributions on the signal parameters (including the TOA) from a single observation.Comment: 16 pages, 4 figure

Evidence for alignment of the rotation and velocity vectors in pulsars. II. Further data and emission heights

We have conducted observations of 22 pulsars at frequencies of 0.7, 1.4 and 3.1 GHz and present their polarization profiles. The observations were carried out for two main purposes. First we compare the orientation of the spin and velocity vectors to verify the proposed alignment of these vectors by Johnston et al. (2005). We find, for the 14 pulsars for which we were able to determine both vectors, that 7 are plausibly aligned, a fraction which is lower than, but consistent with, earlier measurements. Secondly, we use profiles obtained simultaneously at widely spaced frequencies to compute the radio emission heights. We find, similar to other workers in the field, that radiation from the centre of the profile originates from lower in the magnetosphere than the radiation from the outer parts of the profile.Comment: Accepted by MNRAS. 14 page

Detecting Pulsars with Interstellar Scintillation in Variance Images

Pulsars are the only cosmic radio sources known to be sufficiently compact to show diffractive interstellar scintillations. Images of the variance of radio signals in both time and frequency can be used to detect pulsars in large-scale continuum surveys using the next generation of synthesis radio telescopes. This technique allows a search over the full field of view while avoiding the need for expensive pixel-by-pixel high time resolution searches. We investigate the sensitivity of detecting pulsars in variance images. We show that variance images are most sensitive to pulsars whose scintillation time-scales and bandwidths are close to the subintegration time and channel bandwidth. Therefore, in order to maximise the detection of pulsars for a given radio continuum survey, it is essential to retain a high time and frequency resolution, allowing us to make variance images sensitive to pulsars with different scintillation properties. We demonstrate the technique with Murchision Widefield Array data and show that variance images can indeed lead to the detection of pulsars by distinguishing them from other radio sources.Comment: 8 papes, 9 figures, accepted for publication in MNRA

Targets and self monitoring in hypertension: randomised controlled trial and cost effectiveness analysis

Objectives: To assess whether blood pressure control in primary care could be improved with the use of patient held targets and self monitoring in a practice setting, and to assess the impact of these on health behaviours, anxiety, prescribed antihypertensive drugs, patients’ preferences, and costs. \ud Design: Randomised controlled trial. \ud Setting: Eight general practices in south Birmingham. \ud Participants: 441 people receiving treatment in primary care for hypertension but not controlled below the target of < 140/85 mm Hg. \ud Interventions: Patients in the intervention group received treatment targets along with facilities to measure their own blood pressure at their general practice; they were also asked to visit their general practitioner or practice nurse if their blood pressure was repeatedly above the target level. Patients in the control group received usual care (blood pressure monitoring by their practice). \ud Main outcome measures: Primary outcome: change in systolic blood pressure at six months and one year in both intervention and control groups. Secondary outcomes: change in health behaviours, anxiety, prescribed antihypertensive drugs, patients’ preferences of method of blood pressure monitoring, and costs. \ud Results: 400 (91%) patients attended follow up at one year. Systolic blood pressure in the intervention group had significantly reduced after six months (mean difference 4.3 mm Hg (95% confidence interval 0.8 mm Hg to 7.9 mm Hg)) but not after one year (mean difference 2.7 mm Hg (-1.2 mm Hg to 6.6 mm Hg)). No overall difference was found in diastolic blood pressure, anxiety, health behaviours, or number of prescribed drugs. Patients who self monitored lost more weight than controls (as evidenced by a drop in body mass index), rated self monitoring above monitoring by a doctor or nurse, and consulted less often. Overall, self monitoring did not cost significantly more than usual care (£251 ($437; 364 euros) (95% confidence interval £233 to £275) versus £240 (£217 to £263). \ud Conclusions: Practice based self monitoring resulted in small but significant improvements of blood pressure at six months, which were not sustained after a year. Self monitoring was well received by patients, anxiety did not increase, and there was no appreciable additional cost. Practice based self monitoring is feasible and results in blood pressure control that is similar to that in usual care. \u

Shotguns vs Lasers: Identifying barriers and facilitators to scaling-up plant molecular farming for high-value health products.

Plant molecular farming (PMF) is a convenient and cost-effective way to produce high-value recombinant proteins that can be used in the production of a range of health products, from pharmaceutical therapeutics to cosmetic products. New plant breeding techniques (NPBTs) provide a means to enhance PMF systems more quickly and with greater precision than ever before. However, the feasibility, regulatory standing and social acceptability of both PMF and NPBTs are in question. This paper explores the perceptions of key stakeholders on two European Union (EU) Horizon 2020 programmes-Pharma-Factory and Newcotiana-towards the barriers and facilitators of PMF and NPBTs in Europe. One-on-one qualitative interviews were undertaken with N = 20 individuals involved in one or both of the two projects at 16 institutions in seven countries (Belgium, France, Germany, Italy, Israel, Spain and the UK). The findings indicate that the current EU regulatory environment and the perception of the public towards biotechnology are seen as the main barriers to scaling-up PMF and NPBTs. Competition from existing systems and the lack of plant-specific regulations likewise present challenges for PMF developing beyond its current niche. However, respondents felt that the communication of the benefits and purpose of NPBT PMF could provide a platform for improving the social acceptance of genetic modification. The importance of the media in this process was highlighted. This article also uses the multi-level perspective to explore the ways in which NPBTs are being legitimated by interested parties and the systemic factors that have shaped and are continuing to shape the development of PMF in Europe

On-Farm Food Safety and Environmental Farm Plans: A Conceptual Framework for Identifying and Classifying Benefits and Costs

This series of six reports entitled: "On-Farm Food Safety and Environmental Farm Plans: Identifying and Classifying Benefits and Costs" was initiated soon after the launch of the Agricultural Policy Framework (APF) in 2002. The APF recognized the importance of food safety and environmental concerns for the future growth of the agriculture and Agri-food sector. For this reason, Agriculture and Agri-Food Canada (AAFC) commissioned this series of reports to develop a conceptual framework to strengthen our understanding of the potential benefit and cost implications of On-farm Food Safety (OFFS) and Environmental Farm Plans (EFP) that were key components of the APF. The reports were prepared by a group of academics with extensive knowledge of the agriculture and Agri-food sector and issues related to food safety, traceability and the environment. The first report presents a summary of the findings in the five main reports in the series. The second report presents the conceptual framework that was developed to help identify qualitatively the potential benefits and costs that the various players in the agriculture and agri-food supply chain would face in implementing OFFS and EFP programs. The third report applies this framework to pork, the fourth, to beef, the fifth, to grains and the sixth, to dairy. In general, benefits and costs are divided into both demand and supply side effects. In addition, both public and private costs and benefits are considered, especially since they help indicate where a role for government might be required and where markets are not working as well as they might. Based on these preliminary qualitative assessments, the beef and pork sector have more to gain from HACCP-based OFFS and EFP initiatives, due to their ability to gain market share from marketing their products internationally, while the grains sector already benefits internationally from its high quality reputation and the dairy sector is restricted to produce only for the domestic market. However, more work is required in these areas to validate and quantify costs and benefits.Agribusiness, Agricultural and Food Policy, Environmental Economics and Policy, Food Consumption/Nutrition/Food Safety, Production Economics, Resource /Energy Economics and Policy,

A Qualitative Assessment of the Benefits and Costs of On-Farm Food Safety and Environmental Farm Plans in the Dairy Sector

This series of six reports entitled: "On-Farm Food Safety and Environmental Farm Plans: Identifying and Classifying Benefits and Costs" was initiated soon after the launch of the Agricultural Policy Framework (APF) in 2002. The APF recognized the importance of food safety and environmental concerns for the future growth of the agriculture and Agri-food sector. For this reason, Agriculture and Agri-Food Canada (AAFC) commissioned this series of reports to develop a conceptual framework to strengthen our understanding of the potential benefit and cost implications of On-farm Food Safety (OFFS) and Environmental Farm Plans (EFP) that were key components of the APF. The reports were prepared by a group of academics with extensive knowledge of the agriculture and Agri-food sector and issues related to food safety, traceability and the environment. The first report presents a summary of the findings in the five main reports in the series. The second report presents the conceptual framework that was developed to help identify qualitatively the potential benefits and costs that the various players in the agriculture and agri-food supply chain would face in implementing OFFS and EFP programs. The third report applies this framework to pork, the fourth, to beef, the fifth, to grains and the sixth, to dairy. In general, benefits and costs are divided into both demand and supply side effects. In addition, both public and private costs and benefits are considered, especially since they help indicate where a role for government might be required and where markets are not working as well as they might. Based on these preliminary qualitative assessments, the beef and pork sector have more to gain from HACCP-based OFFS and EFP initiatives, due to their ability to gain market share from marketing their products internationally, while the grains sector already benefits internationally from its high quality reputation and the dairy sector is restricted to produce only for the domestic market. However, more work is required in these areas to validate and quantify costs and benefits.Agribusiness, Agricultural and Food Policy, Environmental Economics and Policy, Food Consumption/Nutrition/Food Safety, Marketing, Production Economics, Resource /Energy Economics and Policy,

Gender differences in the kinetics and kinematics of distance running: implications for footwear design

Interest in distance running amongst females has expanded rapidly. Although there are numerous health benefits associated with running, the occurrence of injury is well documented. Given the relative susceptibility of females to overuse running injuries, a key issue within the discipline of footwear biomechanics that has yet to be appropriately addressed is the specific demands of athletic footwear for females. The aim of this study was therefore to provide both a kinetic and 3-D kinematic comparison of male and female runners in order to determine the relative susceptibility of females to the proposed mechanisms of overuse injuries and whether based on this information, females require more specific footwear designs to meet their needs. Twelve male participants and twelve female participants completed five successful trials running at 4.0ms-1+5%. 3-D angular joint kinematics from the hip, knee and ankle were collected using an eight camera motion analysis system. In addition simultaneous tibial acceleration and ground reaction forces were obtained. Differences in impact parameters and joint kinematics were subsequently compared using independent samples t-tests. Females were found to be associated with significantly greater knee abduction, knee internal rotation and ankle eversion, whilst males were associated with significantly greater hip flexion. Based on these findings it is recommended that females select running footwear with design characteristics aimed towards the reduction of coronal plane ankle eversion in order to reduce the incidence of injury

Gravitational wave detection using pulsars: status of the Parkes Pulsar Timing Array project

The first direct detection of gravitational waves may be made through observations of pulsars. The principal aim of pulsar timing array projects being carried out worldwide is to detect ultra-low frequency gravitational waves (f ~ 10^-9 to 10^-8 Hz). Such waves are expected to be caused by coalescing supermassive binary black holes in the cores of merged galaxies. It is also possible that a detectable signal could have been produced in the inflationary era or by cosmic strings. In this paper we review the current status of the Parkes Pulsar Timing Array project (the only such project in the Southern hemisphere) and compare the pulsar timing technique with other forms of gravitational-wave detection such as ground- and space-based interferometer systems.Comment: Accepted for publication in PAS