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

Does early intervention improve outcomes in physiotherapy management of lumbar radicular syndrome? A mixed-methods study protocol.

INTRODUCTION: Lumbar radicular syndrome (LRS) can be a painful and debilitating condition. The optimum management strategies and their timing remain elusive despite extensive research. Surgery provides good short-term outcomes but has concomitant risks and costs. Physiotherapy is commonly practised for patients with LRS but its effects remain equivocal and there is a lack of consensus on the type, duration and timing of physiotherapy intervention. There is a lack of high-quality evidence into new and innovative management strategies and the timings of those strategies for LRS. This pilot trial is an essential preliminary to a definitive randomised controlled trial (RCT) assessing the effectiveness and cost-effectiveness of early physiotherapy intervention for patients with LRS. The study will test the protocol, the intervention, the use of outcome measures and the ability to set-up and run the trial to enable refinement of a future definitive RCT. METHODS AND ANALYSIS: This is a mixed-methods study encompassing an external pilot RCT with integrated qualitative interviews with patients, clinicians and other key stakeholders. 80 patients will be recruited from primary care and randomised, after consent into 1 of 2 groups. Both groups will receive individually tailored, goal orientated physiotherapy. The usual care group will begin their physiotherapy 6 weeks after randomisation and the intervention group at 2 weeks after randomisation. Outcome measures will primarily be feasibility parameters including the ability to recruit and retain patients and to deliver the intervention. Data will be collected at baseline, and 6, 12 and 26 weeks following randomisation. ETHICS AND DISSEMINATION: The study has received favourable ethical review from the East of Scotland Research Ethics Service (EoSRES) on the 20 August 2015 (15/ES/0130). Recruitment began on the 1 March 2016 and is expected to close in January 2017. Data collection is anticipated to be complete in July 2017. The study results will be made available to participants, clinicians involved in the study and the wider clinical community through publication in a peer reviewed journal and at conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN: 25018352, Pre-results; Clinical Trials.Gov: NCT02618278 Document version V1.1 23.9.2016

Molecular basis for functional switching of GFP by two disparate non-native post-translational modifications of a phenyl azide reaction handle

Through the genetic incorporation of a single phenyl azide group into superfolder GFP (sfGFP) at residue 148 we provide a molecular description of how this highly versatile chemical handle can be used to positively switch protein function in vitro and in vivo via either photochemistry or bioconjugation. Replacement of H148 with p-azido-L-phenylalanine (azF) blue shifts the major excitation peak ∼90 nm by disrupting the H-bond and proton transfer network that defines the chromophore charged state. Bioorthogonal click modification with a simple dibenzylcyclooctyne or UV irradiation shifts the neutral-anionic chromophore equilibrium, switching fluorescence to the optimal ∼490 nm excitation. Click modification also improved quantum yield over both the unmodified and original protein. Crystal structures of both the click modified and photochemically converted forms show that functional switching is due to local conformational changes that optimise the interaction networks surrounding the chromophore. Crystal structure and mass spectrometry studies of the irradiated protein suggest that the phenyl azide converts to a dehydroazepine and/or an azepinone. Thus, protein embedded phenyl azides can be used beyond simple photocrosslinkers and passive conjugation handles, and mimic many natural post-translational modifications: modulation though changes in interaction networks

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

Library Design in Combinatorial Chemistry by Monte Carlo Methods

Strategies for searching the space of variables in combinatorial chemistry experiments are presented, and a random energy model of combinatorial chemistry experiments is introduced. The search strategies, derived by analogy with the computer modeling technique of Monte Carlo, effectively search the variable space even in combinatorial chemistry experiments of modest size. Efficient implementations of the library design and redesign strategies are feasible with current experimental capabilities.Comment: 5 pages, 3 figure

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

Development and validation of two clinical prediction models to inform clinical decision-making for lumbar spinal fusion surgery for degenerative disorders and rehabilitation following surgery: protocol for a prospective observational study

INTRODUCTION: Potential predictors of poor outcome will be measured at baseline: (1) preoperatively to develop a clinical prediction model to predict which patients are likely to have favourable outcome following lumbar spinal fusion surgery (LSFS) and (2) postoperatively to predict which patients are likely to have favourable long-term outcomes (to inform rehabilitation). METHODS AND ANALYSIS: Prospective observational study with a defined episode inception of the point of surgery. Electronic data will be collected through the British Spine Registry and will include patient-reported outcome measures (eg, Fear-Avoidance Beliefs Questionnaire) and data items (eg, smoking status). Consecutive patients (≥18 years) undergoing LSFS for back and/or leg pain of degenerative cause will be recruited. EXCLUSION CRITERIA: LSFS for spinal fracture, inflammatory disease, malignancy, infection, deformity and revision surgery. 1000 participants will be recruited (n=600 prediction model development, n=400 internal validation derived model; planning 10 events per candidate prognostic factor). The outcome being predicted is an individual's absolute risk of poor outcome (disability and pain) at 6 weeks (objective 1) and 12 months postsurgery (objective 2). Disability and pain will be measured using the Oswestry Disability Index (ODI), and severity of pain in the previous week with a Numerical Rating Scale (NRS 0-10), respectively. Good outcome is defined as a change of 1.7 on the NRS for pain, and a change of 14.3 on the ODI. Both linear and logistic (to dichotomise outcome into low and high risk) multivariable regression models will be fitted and mean differences or ORs for each candidate predictive factor reported. Internal validation of the derived model will use a further set of British Spine Registry data. External validation will be geographical using two spinal registries in The Netherlands and Switzerland. ETHICS AND DISSEMINATION: Ethical approval (University of Birmingham ERN_17-0446A). Dissemination through peer-reviewed journals and conferences

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

FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation

Identifying the steps involved in striatal development is important both for understanding the striatum in health and disease, and for generating protocols to differentiate striatal neurons for regenerative medicine. The most prominent neuronal subtype in the adult striatum is the medium spiny projection neuron (MSN), which constitutes more than 85% of all striatal neurons and classically expresses DARPP-32. Through a microarray study of genes expressed in the whole ganglionic eminence (WGE: the developing striatum) in the mouse, we identified the gene encoding the transcription factor Forkhead box protein P1 (FoxP1) as the most highly up-regulated gene, thus providing unbiased evidence for the association of FoxP1 with MSN development. We also describe the expression of FoxP1 in the human fetal brain over equivalent gestational stages. FoxP1 expression persisted through into adulthood in the mouse brain, where it co-localised with all striatal DARPP-32 positive projection neurons and a small population of DARPP-32 negative cells. There was no co-localisation of FoxP1 with any interneuron markers. FoxP1 was detectable in primary fetal striatal cells following dissection, culture, and transplantation into the adult lesioned striatum, demonstrating its utility as an MSN marker for transplantation studies. Furthermore, DARPP-32 expression was absent from FoxP1 knock-out mouse WGE differentiated in vitro, suggesting that FoxP1 is important for the development of DARPP-32-positive MSNs. In summary, we show that FoxP1 labels MSN precursors prior to the expression of DARPP-32 during normal development, and in addition suggest that FoxP1 labels a sub-population of MSNs that are not co-labelled by DARPP-32. We demonstrate the utility of FoxP1 to label MSNs in vitro and following neural transplantation, and show that FoxP1 is required for DARPP-32 positive MSN differentiation in vitro

Contribution of vegetation and peat fires to particulate air pollution in Southeast Asia

Smoke haze, caused by vegetation and peat fires in Southeast Asia, is of major concern because of its adverse impact on regional air quality. We apply two different methods (a chemical transport model and a Lagrangian atmospheric transport model) to identify the locations of fires contributing to the increased mass concentration of particulate matter with diameters less than 2.5 μ m (PM 2.5 ) in Singapore over the period 2004–09. We find that fires in southern Sumatra account for the greatest percentage of the total fire enhancement to PM 2.5 concentrations in Singapore (42–62%), with fires in central Sumatra and Kalimantan contributing 21–35% and 14–15%, respectively. Furthermore, we find that fires in these regions also increase PM 2.5 concentrations in other major cities across Southeast Asia. Our results suggest that acting to reduce fires in southern and central Sumatra (specifically in the eastern parts of the provinces of Jambi, South Sumatra, Lampung and Riau) and southwest Kalimantan (the southern extent of the provinces of West, Central and South Kalimantan) would have the greatest benefit to particulate air quality in Singapore and more widely across Southeast Asia