bluuebunny/crossref_metadata_2025_split huggingface dataset:
LIPUS far-field exposimetry system for uniform stimulation of tissues in-vitro: development and validation with bovine intervertebral disc cells
Authors: Horne Devante A , Jones Peter D , Adams Matthew S , Lotz Jeffrey C , Diederich Chris J 
Published: April 2020

Abstract
Therapeutic Low-intensity Pulsed Ultrasound (LIPUS) has been applied clinically for bone fracture healing and has been shown to stimulate extracellular matrix (ECM) metabolism in numerous soft tissues including intervertebral disc (IVD). In-vitro LIPUS testing systems have been developed and typically include polystyrene cell culture plates (CCP) placed directly on top of the ultrasound transducer in the acoustic near-field (NF). This configuration introduces several undesirable acoustic artifacts, making the establishment of dose-response relationships difficult, and is not relevant for targeting deep tissues such as the IVD, which may require far-field (FF) exposure from low frequency sources. The objective of this study was to design and validate an in-vitro LIPUS system for stimulating ECM synthesis in IVD-cells while mimicking attributes of a deep delivery system by delivering uniform, FF acoustic energy while minimizing reflections and standing waves within target wells, and unwanted temperature elevation within target samples. Acoustic field simulations and hydrophone measurements demonstrated that by directing LIPUS energy at 0.5, 1.0, or 1.5 MHz operating frequency, with an acoustic standoff in the FF (125–350 mm), at 6-well CCP targets including an alginate ring spacer, uniform intensity distributions can be delivered. A custom FF LIPUS system was fabricated and demonstrated reduced acoustic intensity field heterogeneity within CCP-wells by up to 93% compared to common NF configurations. When bovine IVD cells were exposed to LIPUS (1.5 MHz, 200 μs pulse, 1 kHz pulse frequency, and ISPTA = 120 mW cm−2) using the FF system, sample heating was minimal (+0.81 °C) and collagen content was increased by 2.6-fold compared to the control and was equivalent to BMP-7 growth factor treatment. The results of this study demonstrate that FF LIPUS exposure increases collagen content in IVD cells and suggest that LIPUS is a potential noninvasive therapeutic for stimulating repair of tissues deep within the body such as the IVD.
A Gaussian Process Model of Human Electrocorticographic Data
Authors: Owen Lucy L W , Muntianu Tudor A , Heusser Andrew C , Daly Patrick M , Scangos Katherine W , Manning Jeremy R 
Published: April 2020

Abstract
We present a model-based method for inferring full-brain neural activity at millimeter-scale spatial resolutions and millisecond-scale temporal resolutions using standard human intracranial recordings. Our approach makes the simplifying assumptions that different people’s brains exhibit similar correlational structure, and that activity and correlation patterns vary smoothly over space. One can then ask, for an arbitrary individual’s brain: given recordings from a limited set of locations in that individual’s brain, along with the observed spatial correlations learned from other people’s recordings, how much can be inferred about ongoing activity at other locations throughout that individual’s brain? We show that our approach generalizes across people and tasks, thereby providing a person- and task-general means of inferring high spatiotemporal resolution full-brain neural dynamics from standard low-density intracranial recordings.
Wi-ESP—A tool for CSI-based Device-Free Wi-Fi Sensing (DFWS)
Authors: Atif Muhammad , Muralidharan Shapna , Ko Heedong , Yoo Byounghyun 
Published: April 2020

AbstractRecent progress in Device-Free Wi-Fi Sensing (DFWS) has established the use of wireless signals like Wi-Fi not only to communicate but also as a tool to enable device-free sensing. As an emerging technique, DFWS has many capable applications such as sensing activity and gesture and fall detection, monitoring elderly, surveillance, and many more applications while waiving out the necessity to mount devices on the object. A wide range of applications can use the channel state information (CSI) from commercial Wi-Fi devices pervasively for ubiquitous sensing. Existing CSI tools, such as the Intel 5300 network interface controller tool or the Atheros 9390 tool, have limitations when deployed in large-scale systems due to their high deployment costs and limitations in the resolution of CSI measurements. Due to these shortcomings, DFWS applications need an alternative CSI tool in order to perform efficiently. In this paper, we present ESP32-based Wi-ESP as a CSI gathering tool that can report detailed CSI measurements based on 802.11n standards. The proposed Wi-ESP tool works as a complete device by collecting the CSI measurements as well as processing further for DFWS applications. Wi-ESP can work as standalone device, unlike other CSI tools, and can offer large-scale deployment to many DFWS applications. In this paper, we have explored the options of Wi-ESP as a tool for CSI measurements and processing and propose it as a tool for DFWS.
From Monetary to Fiscal to Political Union: A Progression to Integration or a Recipe for Failure?
Authors: D’Antoni Massimo 
Published: April 2020

Abstract
In this paper, we discuss the limits of the architecture of the euro from an economic point of view. We first highlight how the choice to create a monetary union was not supported by the accepted theory of optimal currency areas, and how its institutional set-up responded to a special and questionable view of the functioning of the economy, which recognized only a limited role to active macroeconomic policies. We continue by reconstructing the reasons for the emergence of the 2010–2011 debt crisis that can be traced back to the dynamics triggered by the single currency itself, and we highlight the role played by structural differences between various models of capitalism. Finally, we argue that the proposals currently on the table are by no means sufficient to correct the flaws in the European monetary architecture. The prospects are therefore pessimistic about the possibility of monetary union evolving towards a fiscal and political union.
The Term Structures of Expected Loss and Gain Uncertainty*
Authors: Feunou Bruno , Aliouchkin Ricardo Lopez , Tédongap Roméo , Xu Lai 
Published: April 2020

Abstract
We document that the term structures of risk-neutral expected loss and gain uncertainty on S&P 500 returns are upward sloping on average. These shapes mainly reflect the higher premium required by investors to hedge downside risk and the belief that potential gains will increase in the long run. The term structures exhibit substantial time-series variation with large negative slopes during crisis periods. Through the lens of a flexible Jump-Diffusion framework, we evaluate the ability of existing reduced-form option pricing models to replicate these term structures. We stress that three ingredients are particularly important: (i) the inclusion of jumps; (ii) disentangling the price of negative jump risk from its positive analog in the stochastic discount factor specification; and (iii) specifying three latent factors.
Functional networks of co-expressed genes to explore iron homeostasis processes in the pathogenic yeast Candida glabrata
Authors: Denecker Thomas , Zhou Li Youfang , Fairhead Cécile , Budin Karine , Camadro Jean-Michel , Bolotin-Fukuhara Monique , Angoulvant Adela , Lelandais Gaëlle 
Published: April 2020

Abstract
Candida glabrata is a cause of life-threatening invasive infections especially in elderly and immunocompromised patients. Part of human digestive and urogenital microbiota, C. glabrata faces varying iron availability, low during infection or high in digestive and urogenital tracts. To maintain its homeostasis, C. glabrata must get enough iron for essential cellular processes and resist toxic iron excess. The response of this pathogen to both depletion and lethal excess of iron at 30°C have been described in the literature using different strains and iron sources. However, adaptation to iron variations at 37°C, the human body temperature and to gentle overload, is poorly known. In this study, we performed transcriptomic experiments at 30°C and 37°C with low and high but sub-lethal ferrous concentrations. We identified iron responsive genes and clarified the potential effect of temperature on iron homeostasis. Our exploration of the datasets was facilitated by the inference of functional networks of co-expressed genes, which can be accessed through a web interface. Relying on stringent selection and independently of existing knowledge, we characterized a list of 214 genes as key elements of C. glabrata iron homeostasis and interesting candidates for medical applications.
EP06 Successful treatment of alopecia universalis with rituximab therapy
Authors: Oke Anuoluwapo R , Young-Min Steven 
Published: April 2020

Abstract

Background
Alopecia universalis (AU) is a severe subtype of alopecia areata (AA), in which there is non-scarring hair loss affecting the whole body. The pathogenesis involves, increased MHC class I expression in hair follicles, loss of hair follicle immune privilege and autoimmune-mediated damage to pigmented hair. There is no cure for alopecia areata, and though mild cases may have a good chance of either spontaneous or treatment-induced recovery, the prognosis of complete hair loss is poor with less than 10% recovery. Treatment remains a challenge with no reliably effective therapy and in the absence of well-evaluated trials, isolated case reports can influence practice. Here, we present the first report of AU being successfully treated with rituximab with remarkably sustained improvement at 6 years follow up. This case is also the first report of AU developing in adult dermatomyositis (DM) and we speculate upon the implications for the aetiopathogenesis of both conditions.

Methods
A 55-year-old lady, presented with proximal limb weakness, lethargy, a non-itchy rash, pleurisy and breathlessness. The serum creatinine kinase (3369 u/L) and anti-Jo-1 antibodies were elevated consistent with antisynthetase syndrome and a diagnosis of dermatomyositis was made. There was an initial response to corticosteroids and cyclophosphamide. She then relapsed and was treated with IV rituximab. Seventeen months after her initial presentation, she developed widespread hair loss sparing only white hairs (making Telogen Effluvium unlikely), combined with a concurrent relapse of her dermatomyositis. A diagnosis of alopecia universalis (AU) was made. A further course of IV rituximab therapy administered at this stage led to an excellent response in both her dermatomyositis and AU. At three months review, both the AU and the dermatomyositis had entered remission and this has been sustained 6 years on.

Results
Please refer to the conclusion section.

Conclusion
Disease activity in dermatomyositis has been linked with the expression of type I Interferon IFN and this may induce MHC class I expression that is identified on muscle biopsy. It may be that similar type I IFN action on hair follicles may have triggered the development of AU in our case. Whilst this is the first report of AU occurring with adult dermatomyositis, there has been a report of AU occurring in juvenile dermatomyositis. There are also other reports of other combinations of autoimmune conditions occurring with both DM & AU. This case also demonstrates that rituximab, an anti-CD 20 B cell therapy, maybe a useful treatment option in alopecia areata and universalis. This has not been reported elsewhere. Despite postulation that AU is a mainly T cell-driven disease, this case demonstrates that B cells may play a role, in much the same way that we now recognise the importance of B cell involvement in RA.

Disclosures
A.R. Oke None. S. Young-Min None.
EP09 Bamboo nodes in a patient with mixed connective tissue disease
Authors: Christidis Dimitrios C , Lloyd Mark 
Published: April 2020

Abstract

Background
Vocal cord lesions related to autoimmune diseases have been described as early as 1959, when Scarpelli et.al described a case of a woman with systemic lupus erythematosus (SLE) presented with laryngeal oedema. Pathological examination of the tissue revealed inflammatory cells and the lesions were labeled as “inflammatory nodules”. Since then numerous case reports were published describing patients with rheumatic diseases and abnormal vocal cords with Hosako et al. in 1993 proposing the term “bamboo nodes”.

Methods
A 27 year old female, lifelong nonsmoker, developed a husky voice which persisted through the day. She had no odynophagia or dysphagia and occasionally suffered from heartburn.She reported feeling fatigue and described a non-blanching purpuric rash affecting her lower limbs. She was referred to rheumatology and also to ear, nose and throat (ENT) specialist for further assessments including laryngeal endoscopy and autoimmune screen.

Results
The video laryngeal endoscopy revealed an area of linear thickening of the left mid-vocal fold. There was no evidence of reflux or muscle tension. Immunological test's revealed positive antinuclear, ribonuclear and Sm antibodies, with normal serum complement. The erythrocyte sedimentation rate was raised with normal C-reactive protein and there was a polyclonal increase of immunoglobulins. A diagnosis of mixed connective tissue disease with bamboo nodes was made. Her treatment consisted of local corticosteroid injections into the vocal cords with prednisolone 5mg (Solu-DecortinR) and systemic corticosteroids followed by hydroxychoroquine 5mg/kg and azathioprine 2mg/kg. Patient improved clinically but still requires speech therapy as adjunctive to the pharmacological treatment.

Conclusion
Bamboo nodes are a rare manifestation of autoimmune diseases and currently there is no gold standard on how to manage them. This case highlights the need of close collaboration between ENT, rheumatology and speech&language therapy.

Disclosures
D.C. Christidis None. M. Lloyd None.
EP14 Association between initial csDMARD strategy and disease activity at 6 months in patients with new onset rheumatoid arthritis
Authors: Wood Sarah , Hyrich Kimme , Verstappen Suzanne , Steinke Douglas 
Published: April 2020

Abstract

Background
Until 2018, NICE guidance recommended the use of a combination of disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate (MTX), in the initial management of people with rheumatoid arthritis (RA). In 2018 the guideline was updated to recommend monotherapy with MTX due to uncertainties in the evidence for combination therapy. However, it remains a requirement for progression onto any biologic that the patient should have persistent high disease activity and/or have intolerance to, a minimum of two DMARDs. The aim of this study was to understand the association between initial treatment strategy and EULAR response at 6 months.

Methods
This analysis included patients recruited to the longitudinal observational Rheumatoid Arthritis Medication Study (RAMS) in the UK who were DMARD naïve and had symptoms for less than 1 year. Patients were defined as either starting MTX monotherapy or MTX in combination with another DMARD (6 weeks either side of MTX start date) and categorised into EULAR non responders or moderate/ good responders after 6 months. A logistic regression model was applied to test the association between initial treatment strategy and EULAR response at 6 months, adjusting for confounders.

Results
A total of 948 participants were included in the analysis. MTX monotherapy was prescribed in 72% (n = 678) of patients and combination therapy was prescribed in 28% (n = 270) of patients, the majority of whom received MTX plus hydroxychloroquine (HCQ) (n = 236, 87%). There was no significant difference between the MTX monotherapy and combination therapy groups in EULAR response at 6-months (adjusted odds ratio [aOR] 0.77, 95% CI 0.53 to 1.14).

Conclusion
In this large UK observational study investigating the effect of treatment strategy within the first 6 weeks of presentation and treatment response at 6 months, there was no significant difference between combination DMARD therapy and MTX monotherapy on EULAR response. Most patients received MTX in combination with HCQ, for which little evidence exists.

Disclosures
S. Wood None. K. Hyrich Consultancies; ABBVIE. Grants/research support; BMS, PFIZER, UCB. S. Verstappen None. D. Steinke None.
EP15 Switching to biosimilar adalimumab: a real world study
Authors: Begum Julie , Nisar Muhammad K 
Published: April 2020

Abstract

Background
Since the introduction of anti-TNF biosimilars in routine clinical practice, there has been a drive to implement the switch program for all biosimilars at the point of availability. Our Trust was aligned to NHS England strategy which required adoption of biosimilar within three months for new patients and one year for switchers. This could help deliver significant savings to the NHS whilst achieving similar clinical outcomes. We report our early experience of introducing adalimumab biosimilar (Imraldi®).

Methods
A list of all patients prescribed adlimumab was extracted through our database. A ‘switch’ letter was drafted and sent to all patients including Imraldi information sheet. Patients were given the opportunity to contact nurse helpline as needed. We reviewed all relevant records and collected data on any adverse events and disease outcome on either side of the switch.

Results
198 patients were identified established on adalimumab. All had switched by October 2019 to Imraldi. Mean age of switchers was 48 (range 16-83 years). Gender distribution was equal (99 each). 35 (17%) were Asian, two Afro-Caribbean, four other and the remaining 157 (80%) were White Caucasian. 54 (27%) had RA, 81 (41%) PsA, 57 (29%) AS and six had JIA. Co-prescribed DMARDs included methotrexate (n = 53, 27%), sulfasalazine (n = 15, 7.5%), hydroxychloroquine (n = 14, 7%) and leflunomide in two individuals. 83 (42%) participants were prescribed adalimumab monotherapy. Prior to switch, median DAS28 for RA group was 2.28 (0.57 - 6.29). Median BASDAI and spinal VAS for AS cohort was 3.3 (0.8 - 8.8) and 3.0 (0 - 9) respectively. Tender and swollen joint components for PsARC were median three (0-8 tender, 0-6 swollen) in PsA group. Only 30% of the patients had been reviewed face-to-face following the switch. Their respective median disease activity indices were not significantly different from pre-switch assessments. Eleven patients had complained of adverse events including injection site reaction (n = 7) and loss of disease control (n = 6). Six of these decided against further biosimilar and requested to return to the originator. No obvious precipitating factors were identified.

Conclusion
Our experience of switching adalimumab patients has been reasonably successful. All were happy to switch after receiving a letter and having the opportunity to contact if necessary. Substantial annual cost savings of over £300,000 have been projected for this financial year. At group level there were no major differences in disease outcomes and 90% reported no issues. However, just under 10% of those reviewed have decided to return to the originator within three months of switch with loss of efficacy and thereby confidence in the drug. We support the routine switching from originator to biosimilar adalimumab however close monitoring is required certainly in the first few weeks of dose administration.

Disclosures
J. Begum None. M.K. Nisar None.
EP42 Delaying diagnosis: inflammatory back pain and the other features of suspected spondyloarthritis have been rarely featured in musculoskeletal health professions literature
Authors: McCrum Carol 
Published: April 2020

Abstract

Background
The diagnostic delays commonly experienced by many people with spondyloarthritis (SpA), particularly axial spondyloarthritis, is a global concern. Early diagnosis is important since earlier intervention supports better outcomes, responses to treatment and reductions in the many personal impacts. Although core knowledge within Rheumatology, research indicates that the key feature of inflammatory back pain and the signs, symptoms and risk factors for axial and peripheral SpA are under-recognised in primary care. This study investigated the prevalence within musculoskeletal health professional literature (physiotherapy, osteopathy, chiropractic) of the terminology, clinical features and risk factors that appear in recommended criteria to support suspicion of axial and peripheral SpA and referral to rheumatology.

Methods
A systematic search and bibliometric analysis was undertaken across databases and musculoskeletal professional literature sources until 30 September 2019 (see Table 1) . The search was applied to all text, without limits except English language where enabled. Occurrences of terms were identified and the literature sources graded as 'core', 'peripheral', 'minimally accessed', or 'beyond scope' of musculoskeletal health professions to reflect likely professional exposure to the sources.

Results
Only 22 journal articles were found with any of the searched terms within core musculoskeletal profession journals. Prevalence included 'inflammatory back pain' (2 articles), 'axial spondyloarthritis' (2 articles), 'spondyloarthropathy ' (12 articles), 'reactive arthritis (3 articles), 'oligoarthritis' (1 article), psoriasis (2 articles). Prevalence was significantly more predominant in peripheral journal specialties; rheumatology (5,967) including 'inflammatory back pain' (424 articles); orthopaedics, sports medicine, spine and pain (257 articles) and medicine/general practice (44).

Conclusion
This review highlights the significant lack of profile in musculoskeletal literature of inflammatory back pain as a clinical presentation, or other features that are key in suspecting axial and peripheral spondyloarthritis. This scarcity may contribute to limited awareness, knowledge and confidence of musculoskeletal health professions with screening for spondyloarthritis and a factor in delayed diagnosis. The findings suggest the importance of raising the profile of the features of suspected spondyloarthritis, inflammatory back pain and the other risk factors for axial and peripheral spondyloarthritis within global core musculoskeletal literature to support screening for SpA to become routine in musculoskeletal clinical practice.
Disclosures: C. McCrum: Honoraria; Novartis.