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BACKGROUND CONTEXT Complex spinal reconstructions involving corpectomies, or osteotomies, place spinal implants at extremely high stresses that can lead to pseudoarthrosis and ultimately to rod failure, resulting in revision surgery. Current clinical options to increase the biomechanical strength of a construct include increasing rod diameter, changing rod material, or placing an additional satellite/outrigger rod on a standard two rod construct. Fundamentally, all of these constructs still rely on two longitudinal rods across the reconstruction site and are therefore at risk for rod fracture and loss of alignment. Initially described in 2006, the Dual Construct was developed to address this limitation by utilizing four distinct mechanically independent rods, which allowed for the creation of two separate, and distinct, constructs within each patient. Although there is early clinical evidence to support its efficacy, this is the first biomechanical study to compare the Dual Construct to the two-rod and two-rod with satellite configurations in a cadaveric study. PURPOSE To assess the biomechanical impact of the Dual Construct technique to traditional two-rod and two-rod with satellite rod construct in a cadaveric model. STUDY DESIGN/SETTING Biomechanical cadaveric study METHODS Nine fresh-frozen human cadaveric spines (6 males, 3 females, 56 year +/- 9 years) from T9-pelvis were instrumented and tested utilizing all three configurations including two-rod construct, two-rod with satellite construct, and the Dual Construct technique. Biomechanical testing order of the various constructs was randomized to reduce potential effects of order bias. Strain gauges were placed in both the coronal and sagittal planes of the rods to track the strains during flexion-extension and lateral bending while undergoing range of motion testing. Testing was performed using pure-moment flexibility testing protocols. RESULTS In flexion-extension, the resultant strain in the two-rod construct was an average 600±228 microstrain, the two-rod with satellite rod strain averaged 603±237 microstrain, and the Dual Construct averaged 403±149 microstrain. In lateral bending, the resultant strain in the two-rod construct was an average of 266±134 microstrain, the satellite rod strain was an average of 310±158 microstrain, and the Dual Construct averaged 118±51 microstrain. In both flexion extension and lateral bending, a significant reduction in strain was observed between the Dual Construct condition compared to both the two-rod and satellite configurations. No significant difference was found between the two-rod and two-rod with satellite rod configurations. CONCLUSIONS The increase in load sharing significantly decreases the strain experienced across the Dual Construct compared to traditional two-rod and two-rod with satellite constructs. Global rod strains on primary rods cannot be reduced by simply increasing the number of satellite rods, but can only be reduce by increasing the actual number of primary rods.

Adoptive transfer of allogeneic natural killer (NK) cells is becoming a credible immunotherapy for hematological malignancies. In the present work, using an optimized expansion/activation protocol of human NK cells, we generate expanded NK cells (eNK) with increased expression of CD56 and NKp44, while maintaining that of CD16. These eNK cells exerted significant cytotoxicity against cells from 34 B-CLL patients, with only 1 sample exhibiting resistance. This sporadic resistance did not correlate with match between KIR ligands expressed by the eNK cells and the leukemic cells, while cells with match resulted sensitive to eNK cells. This suggests that KIR mismatch is not relevant when expanded NK cells are used as effectors. In addition, we found two examples of de novo resistance to eNK cell cytotoxicity during the clinical course of the disease. Resistance correlated with KIR-ligand match in one of the patients, but not in the other, and was associated with a significant increase in PD-L1 expression in the cells from both patients. Treatment of one of these patients with idelalisib correlated with the loss of PD-L1 expression and with re-sensitization to eNK cytotoxicity. We confirmed the idelalisib-induced decrease in PD-L1 expression in the B-CLL cell line Mec1 and in cultured cells from B-CLL patients. As a main conclusion, our results reinforce the feasibility of using expanded and activated allogeneic NK cells in the treatment of B-CLL.

Author(s): Waibel, Jill S; Holmes, Jon; Rudnick, Ashley; Woods, Daniel; Kelly, Kristen M | Abstract: ObjectivesA current therapeutic challenge of vascular lesions is that they do not always respond effectively to laser treatment. Information on targeted vessels could potentially be used to guide laser treatments. Optical coherence tomography (OCT) is a useful tool for the non-invasive imaging of tissues, including skin hemangiomas and port wine birthmarks. Dynamic OCT is able to rapidly characterize cutaneous blood vessels. The primary goal of this study was to demonstrate the ability of bedside OCT to image (i) overall vessel pattern; (ii) individual vessel morphology, diameter and depth; and (iii) total vessel density as a function of depth in infantile hemangiomas and port wine birthmarks (PWB).Materials and methodsThis IRB approved, observational clinical trial was performed among healthy volunteers ages 3 months-73 years old. All patients presented for laser treatment of either infantile hemangiomas or PWB with skin types ranging from Fitzpatrick I-V. OCT imaging of 49 hemangioma and PWB scans were performed pre- and post-treatment. The diameter and depth of the blood vessels making up the vascular lesions were measured. In addition, normal skin was scanned for comparison. Five datasets for infantile hemangiomas and five for PWB that were without motion artifacts were analyzed.ResultsScanned lesions exhibited variable and highly heterogeneous blood vessel patterns with vessel diameters ranging from 20 to 160 μm, suggesting that the laser treatment with single pulse durations may not be optimal. The largest blood vessel diameter observed (160 μm) may not be adequately treated by commonly used pulsed dye laser pulse durations.ConclusionOCT allowed rapid, non-invasive characterization of the diameter and depth of blood vessels in individual vascular lesions. Imaged lesions consisted of a heterogeneous population of vessel sizes, morphologies, and depth. Future studies could utilize this information to assist development of individualized treatment protocols in an effort to improve vascular birthmark removal. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

The onset of Leber hereditary optic neuropathy is relatively rare in childhood and, interestingly, the rate of spontaneous visual recovery is very high in this group of patients. Here, we report a child harboring a rare pathological mitochondrial DNA mutation, present in heteroplasmy, associated with the disease. A patient follow-up showed a rapid recovery of the vision accompanied by a decrease of the percentage of mutated mtDNA. A retrospective study on the age of recovery of all childhood-onset Leber hereditary optic neuropathy patients reported in the literature suggested that this process was probably related with pubertal changes.

BackgroundDuchenne muscular dystrophy (DMD) is a rare disease that causes the progressive loss of motor abilities such as walking. Standard treatment includes physiotherapy. No trial has evaluated whether or not adding aquatic therapy (AT) to land-based therapy (LBT) exercises helps to keep muscles strong and children independent.ObjectivesTo assess the feasibility of recruiting boys with DMD to a randomised trial evaluating AT (primary objective) and to collect data from them; to assess how, and how well, the intervention and trial procedures work.DesignParallel-group, single-blind, randomised pilot trial with nested qualitative research.SettingSix paediatric neuromuscular units.ParticipantsChildren with DMD aged 7–16 years, established on corticosteroids, with a North Star Ambulatory Assessment (NSAA) score of 8–34 and able to complete a 10-m walk without aids/assistance. Exclusions: > 20% variation between baseline screens 4 weeks apart and contraindications.InterventionsParticipants were allocated on a 1 : 1 ratio to (1) optimised, manualised LBT (prescribed by specialist neuromuscular physiotherapists) or (2) the same plus manualised AT (30 minutes, twice weekly for 6 months: active assisted and/or passive stretching regime; simulated or real functional activities; submaximal exercise). Semistructured interviews with participants, parents (n = 8) and professionals (n = 8) were analysed using Framework analysis. An independent rater reviewed patient records to determine the extent to which treatment was optimised. A cost-impact analysis was performed. Quantitative and qualitative data were mixed using a triangulation exercise.Main outcome measuresFeasibility of recruiting 40 participants in 6 months, participant and therapist views on the acceptability of the intervention and research protocols, clinical outcomes including NSAA, independent assessment of treatment optimisation and intervention costs.ResultsOver 6 months, 348 children were screened – most lived too far from centres or were enrolled in other trials. Twelve (30% of target) were randomised to AT (n = 8) or control (n = 4). People in the AT (n = 8) and control (n = 2: attrition because of parental report) arms contributed outcome data. The mean change in NSAA score at 6 months was –5.5 [standard deviation (SD) 7.8] for LBT and –2.8 (SD 4.1) in the AT arm. One boy suffered pain and fatigue after AT, which resolved the same day. Physiotherapists and parents valued AT and believed that it should be delivered in community settings. The independent rater considered AT optimised for three out of eight children, with other children given programmes that were too extensive and insufficiently focused. The estimated NHS costs of 6-month service were between £1970 and £2734 per patient.LimitationsThe focus on delivery in hospitals limits generalisability.ConclusionsNeither a full-scale frequentist randomised controlled trial (RCT) recruiting in the UK alone nor a twice-weekly open-ended AT course delivered at tertiary centres is feasible. Further intervention development research is needed to identify how community-based pools can be accessed, and how families can link with each other and community physiotherapists to access tailored AT programmes guided by highly specialised physiotherapists. Bayesian RCTs may be feasible; otherwise, time series designs are recommended.Trial registrationCurrent Controlled Trials ISRCTN41002956.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 27. See the NIHR Journals Library website for further project information.

Articular cartilage and bony contact at the distal tibiofibular cartilage contact zone (TFCCZ) is variable. The appropriate placement of syndesmotic hardware would benefit from a more accurate characterization of the proximal extent of the TFCCZ allowing surgeons to place hardware that simultaneously improves biomechanical stability and decreases the risk of iatrogenic cartilage damage. In addition, Ilizarov wire fixation through the distal fibula and tibia can pass through the syndesmosis recess. Anatomically defining the proximal extent of this recess can help decrease the risk of inadvertent capsular penetration. This study anatomically defines the TFCCZ and syndesmosis recess establishing a safe and biomechanically advantageous distance from the plafond for orthopedic fixation. This study measured the height of the TFCCZ and the syndesmotic recess in 3158 anatomical and cadaveric specimens. A TFCCZ was present in 59% of the Robert J. Terry Anatomical Collection specimens. Maximal height of the TFCCZ averaged 5.7±1.7 mm (99% confidence interval [CI], 5.6–5.8 mm) for anatomical specimens and 5.6±1.6 mm (99% CI, 4.6–6.5 mm) for cadaveric dissections. The maximum TFCCZ height was 11.71 mm. Maximal height of the syndesmotic recess averaged 12.8±2.1 mm for anatomical specimens and 13.7±2.7 mm for cadaveric specimens. The “3 cm rule” appears to be appropriate for fine wire fixation accounting for capsular distension that can be associated with injuries but not applicable for syndesmotic fixation. There is a less than 0.1% chance of encountering the TFCCZ cartilage at 10.9 mm above the plafond and a less than 0.01% chance at 12 mm above the plafond. [ Orthopedics. 2017; 40(2):e329–e333.]

In spite of advances in medicine and public health, malaria and other mosquito-borne diseases are on the rise worldwide. Although vaccines, genetically modified mosquitoes and safer insecticides are under development, herein we examine a promising new approach to malaria control through better repellents. Current repellents, usually based on DEET, inhibit host finding by impeding insect olfaction, but have significant drawbacks. We discuss how comparative genomics, using data from the Anopheles genome project, allows the rapid identification of members of three protein classes critical to insect olfaction: odorant-binding proteins, G-protein-coupled receptors, and odorant-degrading enzymes. A rational design approach similar to that used by the pharmaceutical industry for drug development can then be applied to the development of products that interfere with mosquito olfaction. Such products have the potential to provide more complete, safer and longer lasting protection than conventional repellents, preventing disease transmission by interrupting the parasite life cycle. BioEssays 25:1011–1020, 2003. © 2003 Wiley Periodicals, Inc.

Skin involvement is of major prognostic value in systemic sclerosis (SSc) and often the primary outcome in clinical trials. Nevertheless, an objective, validated biomarker of skin fibrosis is lacking. Optical coherence tomography (OCT) is an imaging technology providing high-contrast images with 4 μm resolution, comparable with microscopy ('virtual biopsy'). The present study evaluated OCT to detect and quantify skin fibrosis in SSc.We performed 458 OCT scans of hands and forearms on 21 SSc patients and 22 healthy controls. We compared the findings with histology from three skin biopsies and by correlation with clinical assessment of the skin. We calculated the optical density (OD) of the OCT images employing Matlab software and performed statistical analysis of the results, including intraobserver/interobserver reliability, employing SPSS software.Comparison of OCT images with skin histology indicated a progressive loss of visualisation of the dermal-epidermal junction associated with dermal fibrosis. Furthermore, SSc affected skin showed a consistent decrease of OD in the papillary dermis, progressively worse in patients with worse modified Rodnan skin score (p0.0001). Additionally, clinically unaffected skin was also distinguishable from healthy skin for its specific pattern of OD decrease in the reticular dermis (p0.001). The technique showed an excellent intraobserver and interobserver reliability (intraclass correlation coefficient0.8).OCT of the skin could offer a feasible and reliable quantitative outcome measure in SSc. Studies determining OCT sensitivity to change over time and its role in defining skin vasculopathy may pave the way to defining OCT as a valuable imaging biomarker in SSc.

The initial steps of odorant recognition in the insect olfactory system involve odorant binding proteins (OBPs) and odorant receptors (ORs). While large families of OBPs have been identified in the malaria vector A. gambiae, little is known about their expression pattern in the numerous sensory hairs of the female antenna. We applied whole mount fluorescence in Situ hybridization (WM-FISH) and fluorescence immunohistochemistry (WM-FIHC) to investigate the sensilla co-expression of eight A. gambiae OBPs (AgOBPs), most notably AgOBP1 and AgOBP4, which all have abundant transcripts in female antenna. WM-FISH analysis of female antennae using AgOBP-specific probes revealed marked differences in the number of cells expressing each various AgOBPs. Testing combinations of AgOBP probes in two-color WM-FISH resulted in distinct cellular labeling patterns, indicating a combinatorial expression of AgOBPs and revealing distinct AgOBP requirements for various functional sensilla types. WM-FIHC with antisera to AgOBP1 and AgOBP4 confirmed expression of the respective proteins by support cells and demonstrated a location of OBPs within sensilla trichodea. Based on the finding that AgOBP1 and AgOBP4 as well as the receptor type AgOR2 are involved in the recognition of indole, experiments were performed to explore if the AgOBP-types and AgOR2 are co-expressed in distinct olfactory sensilla. Applying two-color WM-FISH with AgOBP-specific probes and probes specific for AgOR2 revealed a close association of support cells bearing transcripts for AgOBP1 and AgOBP4 and neurons with a transcript for the receptor AgOR2. Moreover, combined WM-FISH/-FIHC approaches using an AgOR2-specific riboprobe and AgOBP-specific antisera revealed the expression of the "ligand-matched" AgOBP1, AgOBP4 and AgOR2 to single trichoid hairs. This result substantiates the notion that a specific response to indole is mediated by an interplay of the proteins.

Summary: Upper extremity reconstruction is most often encountered in trauma patients. Although the rate of complications from elective orthopedic procedures remains relatively low, these complications are oftentimes in the form of open joints or joint infections that can be devastating. Classically, wounds of the shoulder girdle have been treated with large muscles such as the pectoralis major, pectoralis minor, and latissimus dorsi. Flaps more local to the area including the deltoid muscle flap have been overlooked due to their small size. Despite its size, the anterior deltoid can be used for shoulder girdle reconstruction with minimal functional deficit and allows for reconstruction of the glenohumeral joint without sacrifice of the larger muscles of the upper trunk. This study reports a case of a chronic shoulder girdle wound and successful management with the use of an anterior deltoid muscle flap.

Extension of elastographic methods to a microscopic scale is expected to provide invaluable information on soft tissue mechanobiology, by facilitating hitherto impossible experiments to study the relationship between local variations in extracellular matrix stiffness and cellular behaviour. Optical coherence tomography (OCT) is an optical backscatter imaging modality with micron-scale resolution, and ability to measure the sub-micron displacements associated with low-amplitude shear deformation. OCT should therefore be a good imaging modality on which to base a future microelastography system. This work aims to demonstrate the potential of a novel method for quantitative OCT-based microelastography. A vibrating needle was used to generate bursts of 4-10 cycles of 500Hz shear waves within gelatine phantoms of varying stiffness. Shear displacements were measured as a function of time and distance from the needle, using four M-mode images acquired simultaneously using a four-channel swept-source OCT system. Displacement was arranged to be in the OCT-axial direction and the vibrating needle was positioned within the OCT scan plane so that shear waves propagated along the line from one optical channel to another. Shear-wave speed was then calculated from inter-channel differences of shear-wave arrival time and compared with the shear-wave speed determined by a more conventional absolute time-of-arrival (TOA) method. The results confirm that the measured shear-wave speed increases, as expected, in proportion with the gelatine concentration, and the amplitude decreases as gel stiffness rises. The channel-difference (4-channel) method produced results that were equivalent to those from the absolute TOA method. This overall approach shows promise for the eventual provision of microelastography as a research tool in cancer cell biology. Further work is required to optimise the system, to fully characterise and compare the two methods, to automate arrival-time determination and to create elasticity images.

The ability to study the gross morphological changes occurring during tissue formation is vital to producing tissue-engineered structures of clinically relevant dimensions in vitro. Here, we have used nondestructive methods of digital imaging and optical coherence tomography to monitor the early-stage formation and subsequent maturation of fibrin-based tissue-engineered ligament constructs. In addition, the effect of supplementation with essential promoters of collagen synthesis, ascorbic acid (AA) and proline (P), has been assessed. Contraction of the cell-seeded fibrin gel occurs unevenly within the first 5 days of culture around two fixed anchor points before forming a longitudinal ligament-like construct. AA+P supplementation accelerates gel contraction in the maturation phase of development, producing ligament-like constructs with a higher collagen content and distinct morphology to that of unsupplemented constructs. These studies highlight the importance of being able to control the methods of tissue formation and maturation in vitro to enable the production of tissue-engineered constructs with suitable replacement tissue characteristics for repair of clinical soft-tissue injuries.

The role for beta blockers in advanced heart failure (New York Heart Association class IV) remains undefined because of concerns about tolerability and uncertainty about efficacy. We report the use of a short‐acting intravenous beta blocker in combination with inotropic therapy as a means to bridge five patients with advanced heart failure to chronic oral beta blockade; two of these patients had been chronically managed with intravenous inotrope. At 4 months' follow‐up, all patients remained on beta‐blocker therapy and none was hospitalized for heart failure or had received intravenous diuretics. Given the early separation of survival curves in the randomized clinical trials of beta blockers in heart failure, it is possible that these patients will accrue a survival benefit. We conclude that some patients with advanced heart failure can be offered oral beta‐blocker therapy by bridging with a combination of intravenous inotrope and short‐acting intravenous beta blocker.

We present theoretical and experimental studies on the sensitivity variation versus optical path difference (OPD) in Fourier domain spectral interferometry using configurations which produce Talbot bands. Such configurations require that the two interfering beams use different parts of the diffraction grating in the interrogating spectrometer. We show that by manipulating the power distribution within the two interfering beams, the OPD value where maximum sensitivity is achieved can be conveniently tuned, as well as the sensitivity variation with OPD. Furthermore, creating a gap between the two beams leads to adjustment of the minimum detectable OPD value, while the widths of the beams determine the maximum detectable OPD value. These features cannot be explained by theoretical models involving spectrometer resolution elements only. Improvement in the sensitivity variation with depth is demonstrated experimentally.

Optical coherence tomography (OCT) allows non-invasive imaging of sub-surface structures in vivo, ideally without a need for target preparation. In conventional OCT, the contrast for blood vessels depends on a variety of factors and can be challenging. Speckle variance has been recognized as a method to enhance contrast for blood flow without the application of contrast agents in OCT images. Here, we demonstrate the possibility of extracting blood flow information from a volumetric OCT datasets that was obtained routinely from a human participant. We used a commercially available OCT system with a clinical CE-mark. The light source has a central wavelength of 1310 nm. Using Multi-Beam technology, the system achieves an isometric resolution of better than 7.5 μm in tissue over the entire imaging depth of around 1 mm. At 1 mm image width, 21 frames (B-scans) per second can be imaged. We used the speckle variance in order to enhance the contrast for blood vessels in vivo. This method allowed us determining the presence and depth of blood flow within the 1 mm penetration depth, without dependence on direction or orientation of the blood flow with respect to the scanning beam.

A power-efficient Fourier domain optical coherence tomography fiber system is presented free of mirror terms. The object and reference beams from the interferometer are spatially separated to illuminate different parts of the diffraction grating in the spectrometer according to a method inspired from the use of Talbot bands. In this way, the system is made sensitive to only one sign of the optical path difference in the interferometer.

Background Optical coherence tomography (OCT) has been recently shown to be a novel quantitative reliable tool to assess skin involvement in Systemic Sclerosis (SSc) (1). However the sensitivity to change over-time has not been evaluated. Objectives The present study aimed to compare skin assessment by OCT over-time in patients with SSc. Methods We performed 52 OCT scans of dorsal forearms on 26 sites of analysis from 17 SSc patients (9 with diffuse, 8 with limited subset according to Le Roy et al; F/M =15:2; mean disease duration at baseline ± SD =6±4.5 years) at 0 and 24 months. Clinical skin involvement was assessed using the modified Rodnan skin score (mRss). Minimum and Maximum Optical Density (Min and Max OD) of the mean-A scans were calculated employing Matlab software as previously described (1). Comparison of the mRss at the site of analysis and Min and Max OD at the 2 time-points was performed by two-tailed paired t-test employing GraphPrism software. Results Fourteen sites of analysis with local mRss=0 did not change over 24 months. Accordingly, both Min and Max OD showed only an average +2.98% and -0.05% change, respectively (p>0.05). By contrast, at 6 sites of analysis mRss improved by 2 points (three sites with local score “2” improved to “0”, three sites with local score of “3” improved to “1”). At these sites Min OD showed an average increase of 23.92% (p=0.0084) and Max OD of 25.13% (p=0.008). At 4 sites of analysis mRss improved by 1 point (two sites with local score “3” improved to “2”, one site with local score of “2” improved to “1”, one site with local score of “1” improved to “0”). At these sites Min OD and Max OD showed no significant improvement (Min OD of 1.93% and Max OD of 8.15%; p>0.05 for both). Furthermore, both Min and Max OD showed a trend towards a decrease (-3.54%, -5.41% respectively) at the 2 sites of analysis with worsening mRSS (one point increase). Conclusions Although a low number of observations, this preliminary study provides the first evidence suggesting that OCT of the skin is sensitive to change over time and is consistent with mRss. The lack of improvement of OCT findings at sites with a mRSS of 1 deserves further evaluation to determine whether this is associated with poor accuracy of mRSS or room for improvement in OCT analysis. Studies including a larger number of patients and sites of analysis with different grades of skin involvement and improvement/deterioration of clinical score are needed for more definitive validation. References Abignano G, Aydin SZ, Castillo-Gallego C et al. Virtual Skin biopsy by Optical Coherence Tomography: the first quantitative imaging biomarker for Scleroderma. Ann Rheum Dis 2013;72:1845-51. Disclosure of Interest G. Abignano: None declared, L.-A. Bissell: None declared, J. Britton: None declared, G. Lettieri: None declared, D. Woods Employee of: Michelson Diagnostics, M. Buch: None declared, D. McGonagle: None declared, P. Emery: None declared, F. Del Galdo: None declared DOI 10.1136/annrheumdis-2014-eular.4697

A solid evidence base for appropriate antithrombotic therapy in patients with complex transcatheter aortic valve replacement (TAVR) is not yet established. This is especially important because approximately 40% of patients with TAVR from both the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) registry1 and the Placement of Aortic Transcatheter Valves (PARTNER) trial2 cohorts had baseline diagnosis of atrial fibrillation (AF) and may have had an indication for anticoagulation in addition to the protocol-directed 6 months of dual antiplatelet therapy (clopidogrel and aspirin) after TAVR.

Background Skin involvement in systemic sclerosis (SSc) is often primary outcome in clinical trials but it is still orphan of a quantitative imaging technique. Optical Coherence Tomography (OCT) is an emerging imaging technology for clinical examination employing a low-intensity infra-red laser beam and providing high-contrast 2 mm deep skin images with a 4 micron resolution. Objectives The aim of this study was to evaluate face validity and reliability of OCT in SSc. Methods Dorsal aspect of forearms was assessed employing topical probe “VivoSight” (Michelson Diagnostics) and optics of Swept-source Fourier-Domain type with a laser wavelength of 1305±15 nm. Clinical skin involvement was determined using the mRSS. The study included 8 foreams from 8 healthy controls (HC) and 5 forearms for each group scored from “0” to “3” from 13 SSc patients. Hematoxylin-Eosin (H&E) staining was performed from forearm skin biopsy, within 1 cm of OCT scanned region, in one HC and one SSc patient (mRSS=3 on the site of analysis). Matlab software was employed to calculate mean optical density (OD) of the scans. Signal changes within epidermis (ED), Dermal-Epidermal Junction (DEJ) and dermis of SSc patients and HC were analysed and collated to a unique graph. To investigate the intraobserver and interobserver reproducibility, intraclass correlation coefficient (ICC) and limits of agreement (LoA) were calculated for the minimum value after the first peak and the maximum value of the second peak of the averaged A-scans. Results OCT images collected in HC showed a regular hyper-reflective border of the skin surface and a homogeneous hypo-reflective epidermal layer. The papillary dermis (PD) was visualized as hyper-reflective area compared to the adjacent ED allowing the visualization of the DEJ. Mean OD data showed that DEJ was a OD nadir region between 60 and 70 micron from the surface, the PD a high density region (OD range:0.64-0.72; micron range:60-100) and the reticular dermis (RD) had a OD ranging from 0.72 and 0.4. In contrast SSc affected tissues (mRSS=3) showed no DEJ and no increase in OD in the PD which appeared with a range density of 0.61-0.56. Interestingly in SSc non-affected tissues (mRSS=0), the valley corresponding to DEJ was still visible with an almost normal OD range of the PD (OD=0.64-0.67) and an OD of the second peak lower than healthy subjects. In the remaining cases (mRSS=1 and 2) the valley after the entrance peak was still visible, however with a weaker second peak compared to healthy skin and SSc non-affected skin. Validation with HE LoA=0.94-0.99) in both parameters measured by the same clinician on the two separate occasions. The interobserver reliability was also excellent with ICC>0.89 (LoA=0.61-0.97) in both parameters assessed by two investigators. Conclusions This is a proof of concept validation of face validity of OCT as quantitative imaging technique of scleroderma skin. The potential of this tool is supported by an excellent reliability. Sensitivity to change ability of OCT is under evaluation to determine whether the technique could be used as outcome measure of skin involvement in SSc. Disclosure of Interest None Declared

Background Standard treatment of Duchenne muscular dystrophy (DMD) includes regular physiotherapy. There are no data to show whether adding aquatic therapy (AT) to land-based exercises helps maintain motor function. We assessed the feasibility of recruiting and collecting data from boys with DMD in a parallel-group pilot randomised trial (primary objective), also assessing how intervention and trial procedures work. Methods Ambulant boys with DMD aged 7–16 years established on steroids, with North Star Ambulatory Assessment (NSAA) score ≥8, who were able to complete a 10-m walk test without aids or assistance, were randomly allocated (1:1) to 6 months of either optimised land-based exercises 4 to 6 days/week, defined by local community physiotherapists, or the same 4 days/week plus AT 2 days/week. Those unable to commit to a programme, with >20% variation between NSAA scores 4 weeks apart, or contraindications to AT were excluded. The main outcome measures included feasibility of recruiting 40 participants in 6 months from six UK centres, clinical outcomes including NSAA, independent assessment of treatment optimisation, participant/therapist views on acceptability of intervention and research protocols, value of information (VoI) analysis and cost-impact analysis. Results Over 6 months, 348 boys were screened: most lived too far from centres or were enrolled in other trials; 12 (30% of the targets) were randomised to AT (n = 8) or control (n = 4). The mean change in NSAA at 6 months was −5.5 (SD 7.8) in the control arm and −2.8 (SD 4.1) in the AT arm. Harms included fatigue in two boys, pain in one. Physiotherapists and parents valued AT but believed it should be delivered in community settings. Randomisation was unattractive to families, who had already decided that AT was useful and who often preferred to enrol in drug studies. The AT prescription was considered to be optimised for three boys, with other boys given programmes that were too extensive and insufficiently focused. Recruitment was insufficient for VoI analysis. Conclusions Neither a UK-based RCT of AT nor a twice weekly AT therapy delivered at tertiary centres is feasible. Our study will help in the optimisation of AT service provision and the design of future research. Trial registration ISRCTN41002956 Electronic supplementary material The online version of this article (doi:10.1186/s40814-017-0132-0) contains supplementary material, which is available to authorized users.