Variations in pre-analytical FFPE sample processing and bioinformatics: challenges for next generation molecular diagnostic testing in clinical pathology

Advances in cellular pathology techniques will improve diagnostic medicine. However, such improvements have to overcome many challenges including variations in pre-analytical sample processing, bioinformatics data analysis and clinical interpretation of data. In order to resolve such challenges, bioinformatics needs to become more tightly coupled to the experimental methodology development

‘Our voice started off as a whisper and now it is a great big roar’ : The Salford Dementia Associate Panel as a model of involvement in research activities

This paper presents the work of the ‘Salford Dementia Associate Panel’, based at the Salford Institute for Dementia, Salford University (UK). We discuss the roles of the Dementia Associates, in particular around the areas of engagement and research. The panel is made up of people living with dementia, and current and former care partners. It highlights the development of this group over a four-year period and demonstrates over time how the role of a Dementia Associate member has evolved. The panel is involved in research, education and public engagement activities conducted by staff and students within the Institute. The motivations for becoming involved are clearly articulated and demonstrate how the personal backgrounds of individuals have driven the collective involvement and desire to bring about change. The benefits and challenges associated with working as part of a panel are discussed. We conclude by bringing together our experiences as a set of suggestions for others who may wish to create a similar forum to promote the involvement of people living with dementia and former and current care partners

Investigation of the use of inertial sensing equipment for the measurement of hip flexion and pelvic rotation in horse riders

Equestrian sports report three to five times higher incidence rates for lower back pain than that of the general population, with hip flexion angles of 50-60° suggested as a causal factor. Inertial motion capture technology enables dynamic measurement of rider kinematics but data extraction is time-consuming. The aim of this study was to develop a software tool to automate the process of extracting biomechanical data from the XsensTM MVN (MoCap) system to investigate postural changes in riders, comparing static position at halt with dynamic position during the sit phase of rising trot. The software was found to be efficient, reducing data extraction time by 97% when used with a sample of 16 riders. Good correlation was found between hip flexion and pelvic anterior-posterior rotation and between halt and trot but with significantly greater values of hip flexion and pelvic anterior rotation in trot. No riders showed hip flexion >50° at halt but 11 riders (69%) showed hip flexion >50° during the sit phase of rising trot, indicating that dynamic assessment is important when considering rider postural faults that may put them at risk of back injury. Keywords: Hip flexion, Horse rider, Inertial sensor, Motion capture, Pelvic rotatio

The precautions of clinical waste: disposable medical sharps in the United Kingdom

This article deals with recent changes in UK guidance on clinical waste, in particular a shift to disposable, single-use instruments and sharps. I use interviews conducted with nurses from a GP practice and two clinical waste managers at alternative treatment and incineration sites as a springboard for reflection on the relationship between the legislation on clinical waste management and its implementation. Scrutinizing the UK guidance, European legislation and World Health Organization principles, I draw out interviewees’ concerns that the changed practices lead to an expansion of the hazardous waste category, with an increased volume going to incineration. This raises questions regarding the regulations’ environmental and health effects, and regarding the precautionary approach embedded in the regulations. Tracing the diverse reverberations of the term ‘waste’ in different points along the journeys made by sharps in particular, and locating these questions in relation to existing literature on waste, I emphasize that public health rationales for the new practices are not made clear in the guidance. I suggest that this relative silence on the subject conceals both the uncertainties regarding the necessity for these means of managing the risks of infectious waste, and the tensions between policies of precautionary public health and environmental sustainability

Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function:a randomised controlled trial

Background: Allopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance. Methods: We conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo. We recruited community-dwelling participants aged 65 and over with baseline 6-min walk distance of &lt;400 m and no contraindications to magnetic resonance imaging scanning. Outcomes were measured at baseline and 20 weeks. The primary outcome was post-exercise phosphocreatine (PCr) recovery rate measured using 31P magnetic resonance spectroscopy of the calf. Secondary outcomes included 6-min walk distance, short physical performance battery (SPPB), lean body mass measured by bioimpedance, endothelial function and quality of life. Results: In total, 124 participants were randomised, mean age 80 (SD 6) years. A total of 59 (48%) were female, baseline 6-min walk distance was 293 m (SD 80 m) and baseline SPPB was 8.5 (SD 2.0). Allopurinol did not significantly improve PCr recovery rate (treatment effect 0.10 units [95% CI, −0.07 to 0.27], P = 0.25). No significant changes were seen in endothelial function, quality of life, lean body mass or SPPB. Allopurinol improved 6-min walk distance (treatment effect 25 m [95% 4–46, P = 0.02]). This was more pronounced in those with high baseline oxidative stress and urate. Conclusion: Allopurinol improved 6-min walk distance but not PCr recovery rate in older people with impaired physical function. Antioxidant strategies to improve muscle function for older people may need to be targeted at subgroups with high baseline oxidative stress. </p

Effective Quantum Observables

Thought experiments about the physical nature of set theoretical counterexamples to the axiom of choice motivate the investigation of peculiar constructions, e.g. an infinite dimensional Hilbert space with a modular quantum logic. Applying a concept due to BENIOFF, we identify the intrinsically effective Hamiltonians with those observables of quantum theory which may coexist with a failure of the axiom of choice. Here a self adjoint operator is intrinsically effective, iff the Schroedinger equation of its generated semigroup is soluble by means of eigenfunction series expansions.Comment: TeX-file, 32 page

A Variational Level Set Approach for Surface Area Minimization of Triply Periodic Surfaces

In this paper, we study triply periodic surfaces with minimal surface area under a constraint in the volume fraction of the regions (phases) that the surface separates. Using a variational level set method formulation, we present a theoretical characterization of and a numerical algorithm for computing these surfaces. We use our theoretical and computational formulation to study the optimality of the Schwartz P, Schwartz D, and Schoen G surfaces when the volume fractions of the two phases are equal and explore the properties of optimal structures when the volume fractions of the two phases not equal. Due to the computational cost of the fully, three-dimensional shape optimization problem, we implement our numerical simulations using a parallel level set method software package.Comment: 28 pages, 16 figures, 3 table

Advocacy in the tail: Exploring the implications of ‘climategate’ for science journalism and public debate in the digital age

This paper explores the evolving practices of science journalism and public debate in the digital age. The vehicle for this study is the release of digitally stored email correspondence, data and documents from the Climatic Research Unit at the University of East Anglia in the weeks immediately prior to the United Nations Copenhagen Summit (COP-15) in December 2009. Described using the journalistic shorthand of ‘climategate’, and initially promoted through socio-technical networks of bloggers, this episode became a global news story and the subject of several formal reviews. ‘Climategate’ illustrates that media literate critics of anthropogenic explanations of climate change used digital tools to support their cause, making visible selected, newsworthy aspects of scientific information and the practices of scientists. In conclusion, I argue that ‘climategate’ may have profound implications for the production and distribution of science news, and how climate science is represented and debated in the digitally-mediated public sphere

Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections.

Background: A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects.&lt;p&gt;&lt;/p&gt; Methods: Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression.&lt;p&gt;&lt;/p&gt; Results: CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm.&lt;p&gt;&lt;/p&gt; Conclusions: Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.&lt;p&gt;&lt;/p&gt