Challenges of ultra large scale integration of biomedical computing systems

The NCRI Informatics Initiative is overseeing the implementation of an informatics framework for the UK cancer research community. The framework advocates an integrated multidisciplinary method of working between scientific and medical communities. Key to this process is community adoption of high quality acquisition, storage, sharing and integration of diverse data elements to improve knowledge of the causes, prevention and treatment of cancer. The integration of the complex data and meta-data used by these multiple communities is a significant challenge and there are technical, resource-based and sociological issues to be addressed. In this paper we review progress aimed at establishing the framework and outline key challenges in ultra large scale integration of biomedical computing systems

Physiotherapy for Patients with Sciatica Awaiting Lumbar Micro-discectomy Surgery: A Nested, Qualitative Study of Patients' Views and Experiences

Background and Purpose Sciatica is a common clinical condition that can be extremely painful, disabling and life‐changing. Whether conservative or surgical treatment for sciatica secondary to an intervertebral disc prolapse is most effective is still much debated. An important component of conservative treatment is physiotherapy, which aims to promote physical and psychological health for the patient, whilst resorption of the disc takes place. This paper reports a qualitative study of patients' views and experiences of a bespoke physiotherapy intervention for the treatment of sciatica. Methods A qualitative study nested within a pilot randomized controlled trial of bespoke physiotherapy for the treatment of patients with sciatica awaiting lumbar microdiscectomy surgery. Patients randomized to receive bespoke physiotherapy in the intervention arm of the trial were invited to take part in semi‐structured interviews. Twenty‐one in‐depth, semi‐structured interviews took place. All interviews were recorded, fully transcribed and thematically analysed. Results Most patients in the sample found the physiotherapy valuable, appreciating the individual nature of the approach, the exercises to reduce pain and discomfort, techniques for improving functional spinal movement, walking and dynamic posture, and manual therapy and cardiovascular exercise. A small number did not find the physiotherapy of benefit. Sixteen patients in the sample went on to proceed with surgery, but most of these found value in having had the physiotherapy first. Discussion Many patients with sciatica appreciate the value of physiotherapy prior to surgery. Future research should examine patients' experiences of bespoke physiotherapy delivered within primary care

Patient journey following lumbar spinal fusion surgery (LSFS): protocol for a multicentre qualitative analysis of the patient rehabilitation experience (FuJourn)

INTRODUCTION: There has been a 65% increase in lumbar spinal fusion surgery (LSFS) worldwide over the last 13 years, with costs of £26 million to the UK National Health Service annually. Patient dissatisfaction with outcome and persistent pain and disability incurs further costs. Three trials provide low-quality evidence for the role of physiotherapy. Our UK surveys investigating physiotherapy/surgeon practice concluded rehabilitation should be tailored to the individual patient owing to considerable clinical heterogeneity. This study will explore the perceptions of patients who undergo LSFS to inform precision rehabilitation. METHODS AND ANALYSIS: A qualitative study, using interpretive phenomenological analysis, will recruit a purposive sample (n=40) to ensure patterns of similarity and difference in their journeys can be explored. In-depth semistructured interviews will be undertaken following discharge from hospital and at 12 months postsurgery. Patients' preoperative and postoperative experiences, underlying attitudes and beliefs towards the surgical intervention, facilitators and barriers to recovery, adherence to advice and physiotherapy, experiences of rehabilitation and return to normal function/activity/work will be explored. A 12-month patient diary will provide real time access to patient data, capturing a weekly record of life as lived, including symptoms, medication, experiences of stages of recovery, rehabilitation adherence, healthcare professional appointments, attitudes, their feelings and experiences throughout their journey. Data will be analysed in a number of stages in accordance with interpretive phenomenological analysis, supported using NVivo software. Analysis of the first interviews and patient diaries will afford a rich density of data to build an overall understanding of the patients' lived experiences, informing the 12-month interview. Strategies (eg, reflexivity) will ensure trustworthiness. ETHICS AND DISSEMINATION: The study has ethical approval (IRAS 223283). Findings will ensure that patient-driven data inform precision rehabilitation by understanding the patient journey. Findings will be disseminated through peer-reviewed journals and conferences

The multifunctional poly(A)-binding protein (PABP) 1 is subject to extensive dynamic post-translational modification, which molecular modelling suggests plays an important role in co-ordinating its activities

PABP1 [poly(A)-binding protein 1] is a central regulator of mRNA translation and stability and is required for miRNA (microRNA)-mediated regulation and nonsense-mediated decay. Numerous protein, as well as RNA, interactions underlie its multi-functional nature; however, it is unclear how its different activities are co-ordinated, since many partners interact via overlapping binding sites. In the present study, we show that human PABP1 is subject to elaborate post-translational modification, identifying 14 modifications located throughout the functional domains, all but one of which are conserved in mouse. Intriguingly, PABP1 contains glutamate and aspartate methylations, modifications of unknown function in eukaryotes, as well as lysine and arginine methylations, and lysine acetylations. The latter dramatically alter the pI of PABP1, an effect also observed during the cell cycle, suggesting that different biological processes/stimuli can regulate its modification status, although PABP1 also probably exists in differentially modified subpopulations within cells. Two lysine residues were differentially acetylated or methylated, revealing that PABP1 may be the first example of a cytoplasmic protein utilizing a ‘methylation/acetylation switch’. Modelling using available structures implicates these modifications in regulating interactions with individual PAM2 (PABP-interacting motif 2)-containing proteins, suggesting a direct link between PABP1 modification status and the formation of distinct mRNP (messenger ribonucleoprotein) complexes that regulate mRNA fate in the cytoplasm

Analysis of particulate emissions from tropical biomass burning using a global aerosol model and long-term surface observations

We use the GLOMAP global aerosol model evaluated against observations of surface particulate matter (PM₂⋅₅) and aerosol optical depth (AOD) to better understand the impacts of biomass burning on tropical aerosol over the period 2003 to 2011. Previous studies report a large underestimation of AOD over regions impacted by tropical biomass burning, scaling particulate emissions from fire by up to a factor of 6 to enable the models to simulate observed AOD. To explore the uncertainty in emissions we use three satellite-derived fire emission datasets (GFED3, GFAS1 and FINN1). In these datasets the tropics account for 66-84% of global particulate emissions from fire. With all emission datasets GLOMAP underestimates dry season PM₂⋅₅ concentrations in regions of high fire activity in South America and underestimates AOD over South America, Africa and Southeast Asia. When we assume an upper estimate of aerosol hygroscopicity, underestimation of AOD over tropical regions impacted by biomass burning is reduced relative to previous studies. Where coincident observations of surface PM₂⋅₅ and AOD are available we find a greater model underestimation of AOD than PM₂⋅₅, even when we assume an upper estimate of aerosol hygroscopicity. Increasing particulate emissions to improve simulation of AOD can therefore lead to overestimation of surface PM₂⋅₅ concentrations. We find that scaling FINN1 emissions by a factor of 1.5 prevents underestimation of AOD and surface PM₂⋅₅ in most tropical locations except Africa. GFAS1 requires emission scaling factor of 3.4 in most locations with the exception of equatorial Asia where a scaling factor of 1.5 is adequate. Scaling GFED3 emissions by a factor of 1.5 is sufficient in active deforestation regions of South America and equatorial Asia, but a larger scaling factor is required elsewhere. The model with GFED3 emissions poorly simulates observed seasonal variability in surface PM₂⋅₅ and AOD in regions where small fires dominate, providing independent evidence that GFED3 underestimates particulate emissions from small fires. Seasonal variability in both PM₂⋅₅ and AOD is better simulated by the model using FINN1 emissions. Detailed observations of aerosol properties over biomass burning regions are required to better constrain particulate emissions from fires

Procedia Computer Science Looking at Clouds from Both Sides: the advantages and disadvantages of placing personal narratives in the Cloud

Abstract This article explores the nature of cloud computing in the context of processing sensitive personal data as part of a personal narrative. In so doing, it identifies general security concerns about cloud computing and presents examples of cloud technologies used to process such data. The use of personal narratives in electronic patient records and in voice output communication aids is compared and contrasted and the implications of the advent of cloud computing for these two scenarios is considered

The climatic importance of uncertainties in regional aerosol-cloud radiative forcings over recent decades

This is the final version of the article. Available from American Meteorological Society via the DOI in this record.Regional patterns of aerosol radiative forcing are important for understanding climate change on decadal time scales. Uncertainty in aerosol forcing is likely to vary regionally and seasonally because of the short aerosol lifetime and heterogeneous emissions. Here the sensitivity of regional aerosol cloud albedo effect (CAE) forcing to 31 aerosol process parameters and emission fluxes is quantified between 1978 and 2008. The effects of parametric uncertainties on calculations of the balance of incoming and outgoing radiation are found to be spatially and temporally dependent. Regional uncertainty contributions of opposite sign cancel in global-mean forcing calculations, masking the regional importance of some parameters. Parameters that contribute little to uncertainty in Earth's global energy balance during recent decades make significant contributions to regional forcing variance. Aerosol forcing sensitivities are quantified within 11 climatically important regions, where surface temperatures are thought to influence large-scale climate effects. Substantial simulated uncertainty in CAE forcing in the eastern Pacific leaves open the possibility that apparent shifts in the mean ENSO state may result from a forced aerosol signal on multidecadal time scales. A likely negative aerosol CAE forcing in the tropical North Atlantic calls into question the relationship between Northern Hemisphere aerosol emission reductions and CAE forcing of sea surface temperatures in the main Atlantic hurricane development region on decadal time scales. Simulated CAE forcing uncertainty is large in the North Pacific, suggesting that the role of the CAE in altering Pacific tropical storm frequency and intensity is also highly uncertain.Data can be made available upon request from the corresponding author. L. A. Regayre is funded by a Doctoral Training Grant from the Natural Environment Research Council (NERC) and a CASE studentship with the Met Office Hadley Centre. B. B. B. Booth was supported by the Joint UK DECC/Defra Met Office Hadley Centre Climate Programme (GA01101). K. S. Carslaw acknowledges funding from the Royal Society Wolfson Award. We acknowledge funding from NERC under AEROS and GASSP Grants NE/G006172/1 and NE/J024252/1. This work made use of the facilities of N8 HPC provided and funded by the N8 consortium and EPSRC (EP/K000225/1). The Met Office Hadley Centre is coordinated by the University of Leeds and the University of Manchester. The authors thank three anonymous reviewers for their constructive comments on this article

Does early intervention improve outcomes in the physiotherapy management of lumbar radicular syndrome? Results of the POLAR pilot randomised controlled trial

OBJECTIVE: To investigate the feasibility of undertaking a definitive randomised controlled trial (RCT). SETTING: This was a pilot, pragmatic superiority RCT with a qualitative element, recruiting from 14 general practitioner (GP) practices in England. PARTICIPANTS: Patients over 18 years of age presenting to their GP with unilateral lumbar radicular syndrome (LRS), defined as radicular pain and/or neurological symptoms originating from lumbar nerve roots, were eligible to participate in the study, those who did not have a clear understanding of the English language or had comorbidities preventing rehabilitation were ineligible. INTERVENTIONS: Participants were randomised into early intervention physiotherapy or usual care with the former receiving their treatment within 2 weeks after randomisation and the latter 6 weeks postrandomisation. Both groups received a patient-centred, goal-orientated physiotherapy programme specific to their needs. Participants received up to six treatment sessions over an 8-week period. OUTCOME MEASURES: Process outcomes to determine the feasibility of the study and an exploratory analysis of patient-reported outcomes, including self-rated disability, pain and general health, these were collected at baseline, 6, 12 and 26 weeks postrandomisation. RESULTS: 80 participants were recruited in 10 GP practices over 34 weeks and randomised to (early intervention physiotherapy n=42, usual care n=38). Follow-up rates at 26 weeks were 32 (84%) in the usual care and 36 (86%) in the early intervention physiotherapy group. The mean area under the curve (larger values indicating more disability) for the Oswestry Disability Index over the 26 weeks was 16.6 (SD 11.4) in the usual care group and 16.0 (SD 14.0) in the intervention group. A difference of -0.6 (95% CI -0.68 to 5.6) in favour of the intervention group. CONCLUSIONS: The results of the study suggest a full RCT is feasible and will provide evidence as to the optimal timing of physiotherapy for patients with LRS. TRIAL REGISTRATION NUMBER: NCT02618278, ISRCTN25018352

Subseafloor microbial communities in hydrogen-rich vent fluids from hydrothermal systems along the Mid-Cayman Rise

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Environmental Microbiology 18 (2016): 1970–1987, doi:10.1111/1462-2920.13173.Warm fluids emanating from hydrothermal vents can be used as windows into the rocky subseafloor habitat and its resident microbial community. Two new vent systems on the Mid-Cayman Rise each exhibits novel geologic settings and distinctively hydrogen-rich vent fluid compositions. We have determined and compared the chemistry, potential energy yielding reactions, abundance, community composition, diversity, and function of microbes in venting fluids from both sites: Piccard, the world's deepest vent site, hosted in mafic rocks; and Von Damm, an adjacent, ultramafic-influenced system. Von Damm hosted a wider diversity of lineages and metabolisms in comparison to Piccard, consistent with thermodynamic models that predict more numerous energy sources at ultramafic systems. There was little overlap in the phylotypes found at each site, although similar and dominant hydrogen-utilizing genera were present at both. Despite the differences in community structure, depth, geology, and fluid chemistry, energetic modelling and metagenomic analysis indicate near functional equivalence between Von Damm and Piccard, likely driven by the high hydrogen concentrations and elevated temperatures at both sites. Results are compared with hydrothermal sites worldwide to provide a global perspective on the distinctiveness of these newly discovered sites and the interplay among rocks, fluid composition and life in the subseafloor.National Aeronautics and Space Administration Grant Number: NNX09AB756; Alfred P. Sloan Foundation; NSF Grant Number: OCE10618