bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase structure of co-orbital motion with Jupiter
Authors: Qi Yi , de Ruiter Anton
Published: April 2020

In this paper, we investigate the dynamics of the inclined co-orbital motion with Jupiter through a torus phase structure in the Sun–Jupiter circular restricted three-body problem. A semi-analytical method to establish the Hamiltonian approximation for the inclined co-orbital motion is proposed. Phase structures of different kinds of co-orbital behaviours are shown in the torus space clearly. Based on numerical computation, we analyse the evolution and the connection of different co-orbital dynamics. Summarizing results and conclusions in this paper, we find two main principles throughout the investigation of the co-orbital motion: (i) the libration amplitude of the resonant angle for the co-orbital motion is bounded by the corresponding Hamiltonian isosurface in the torus space and (ii) the co-orbital behaviour is influenced by collision curves, and with the decrease of the Hamiltonian value, the influence is more significant.
Hydrogen spin oscillations in a background of axions and the 21-cm brightness temperature
Authors: Lambiase G , Mohanty S
Published: April 2020

The 21-cm line signal arising from the hyperfine interaction in hydrogen has an important role in cosmology and provides a unique method for probing of the universe prior to the star formation era. We propose that the spin flip of Hydrogen by the coherent emission/absorption of axions causes a lowering of their spin temperature and can explain the stronger than expected absorption of 21-cm light reported by the EDGES collaboration. We find the analogy of axion interaction with the two level HI with the Jaynes-Cummings model of a two level atom in a cavity and we derive the spin flip frequency in this formalism and show that the coherent oscillations frequency Ω∝1/fa in contrast with the incoherent transitions between the HI hyperfine levels where the transition rates $\propto 1/f_a^2$. The axion emission and absorption rates are equal but the spin temperature is still lowered due to different selection rules for the spin flip transitions compared to the photon process. We show that the axion process goes in the right direction for explaining the EDGES observation. For this mechanism to work we require a coherent field of relativistic axions with energy Eν peaked at the 21-cm spin-flip energy. Such a coherent background of relativistic axions can arise from the decay of cosmic strings if the decay takes place in the electroweak era.
Open clusters as tracers on radial migration of the galactic disc
Authors: Chen Y Q , Zhao G
Published: April 2020

Radial migration is an important process in the Galactic disc. A few open clusters show some evidence on this mechanism but there is no systematic study. In this work, we investigate the role of radial migration on the Galactic disc based on a large sample of 146 open clusters with homogeneous metallicity and age from Netopil et al. and kinematics calculated from Gaia DR2. The birth site Rb, guiding radius Rg, and other orbital parameters are calculated, and the migration distance |Rg − Rb| is obtained, which is a combination of metallicity, kinematics, and age information. It is found that 44 per cent open clusters have |Rg − Rb| < 1 kpc, for which radial migration (churning) is not significant. Among the remaining 56 per cent open clusters with |Rg − Rb| > 1 kpc, young ones with t < 1.0 Gyr tend to migrate inward, while older clusters usually migrate outward. Different mechanisms of radial migration between young and old clusters are suggested based on their different migration rates, Galactic locations, and orbital parameters. For the old group, we propose a plausible way to estimate migration rate and obtain a reasonable value of $1.5 \pm 0.5 \,\rm {kpc\,Gyr}^{ -1}$ based on 10 intermediate-age clusters at the outer disc, where the existence of several special clusters implies its complicate formation history.
Secular dynamics of hierarchical multiple systems composed of nested binaries, with an arbitrary number of bodies and arbitrary hierarchical structure – III. Suborbital effects: hybrid integration techniques and orbit-averaging corrections
Authors: Hamers Adrian S
Published: April 2020

The secularmultiple code, presented in two previous papers of this series, integrates the long-term dynamical evolution of multiple systems with any number of bodies and hierarchical structure, provided that the system is composed of nested binaries. In the formalism underlying secularmultiple, we previously averaged over all orbits in the system. This approximation significantly speeds up numerical integration of the equations of motion, making large population synthesis studies possible. However, the orbit averaging approximation can break down when the secular evolution time-scale of the system is comparable to or shorter than any of the orbital periods in the system. Here, we present an update to secularmultiple in which we incorporate hybrid integration techniques, and orbit-averaging corrections. With this update, the user can specify which orbits should be integrated directly (without averaging), or assuming averaged orbits. For orbits that are integrated directly, we implemented two integration techniques, one which is based on the regularized Kustaanheimo–Stiefel equations of motion in element form. We also implemented analytical orbit-averaging corrections for pairwise interactions to quadrupole order. The updates presented here provide more flexibility for integrating the long-term dynamical evolution of hierarchical multiple systems. By effectively combining direct integration and orbit averaging the long-term evolution can be accurately computed, but with significantly lower computational cost compared to existing direct N-body codes. We give a number of examples in which the new features are beneficial. Our updated code, which is written in c++ supplemented with a user-friendly interface in python, is freely available.
Rotational de-excitations of C3H+ (1Σ+) by collision with He: new ab initio potential energy surface and scattering calculations
Authors: Kumar Sanchit , Dhilip Kumar T J
Published: April 2020

Molecular ions play an important role in the astrochemistry of interstellar and circumstellar media. C3H+ has been identified in the interstellar medium recently. A new potential energy surface of the C3H+–He van der Waals complex is computed using the ab initio explicitly correlated coupled cluster with the single, double and perturbative triple excitation [CCSD(T)-F12] method and the augmented correlation consistent polarized valence triple zeta (aug-cc-pVTZ) basis set. The potential presents a well of 174.6 cm−1 in linear geometry towards the H end. Calculations of pure rotational excitation cross-sections of C3H+ by He are carried out using the exact quantum mechanical close-coupling approach. Cross-sections for transitions among the rotational levels of C3H+ are computed for energies up to 600 cm−1. The cross-sections are used to obtain the collisional rate coefficients for temperatures T ≤ 100 K. Along with laboratory experiments, the results obtained in this work may be very useful for astrophysical applications to understand hydrocarbon chemistry.
Shock propagation in accretion discs around merging black holes: self-similar solution
Authors: Bisikalo D V , Zhilkin A G
Published: April 2020

To date, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and the Virgo gravitational wave detectors have registered several events due to merging binary black holes. It is considered that black holes are surrounded by the circumbinary accretion disc therefore such events must be followed by perturbation of the disc and an increase in the flux of electromagnetic radiation from these objects. Our recent numerical investigations have shown that the heating of matter caused by a shock wave leads to an increase in luminosity. This shock wave arises in the accretion disc due to the central object mass loss as a result of the radiation of gravitational waves. In this paper, a self-similar solution is considered. In this solution the accretion disc perturbation is described in a region, dominated by gas pressure, and the matter opacity is determined by Thomson electron scattering processes. Such an analytical model allows us to approximately estimate the magnitude of the electromagnetic response of the gravitational wave event without time-consuming numerical calculations.
Cosmological insights into the assembly of the radial and compact stellar halo of the Milky Way
Authors: Elias Lydia M , Sales Laura V , Helmi Amina , Hernquist Lars
Published: April 2020

Recent studies using Gaia DR2 have identified a massive merger in the early history of the Milky Way (MW) whose debris is dominated by radial and counterrotating orbits. This event, dubbed the Gaia-Enceladus/Gaia-Sausage (GE/GS), is also hypothesized to have built the majority of the inner stellar halo. We use the cosmological hydrodynamic simulation Illustris to place this merger in the context of galaxy assembly within lambda cold dark matter. From ∼150 MW analogues, $\sim \!80 {{ \rm {per\ cent}}}$ have experienced at least one merger of similar mass and infall time as the GE/GS. Within this sample, 37 have debris as radial as the GE/GS, which we dub the ancient radial mergers (ARMs). Counterrotation is not rare among ARMs, with $43 {{ \rm {per\ cent}}}$ having $\gt 40 {{ \rm {per\ cent}}}$ of their debris in counterrotating orbits. However, the compactness inferred for the GE/GS debris given its large radial orbital anisotropy, β, and its substantial contribution to the stellar halo are difficult to reproduce. The median radius of ARM debris is r*,deb ≃ 45 kpc, while GE/GS is thought to be mostly contained within r ∼ 30 kpc. For most MW analogues, few mergers are required to build the inner stellar halo, and ARM debris only accounts for (median) $\sim \!12 {{ \rm {per\ cent}}}$ of inner accreted stars. Encouragingly, we find one ARM that is both compact and dominates the inner halo of its central, making it our best GE/GS analogue. Interestingly, this merger deposits a significant number of stars (M* ≃ 1.5 × 109 M⊙) in the outer halo, suggesting that an undiscovered section of GE/GS may await detection.
Collisional excitation of H2S by molecular hydrogen
Authors: Dagdigian Paul J
Published: April 2020

Accurate estimates of the abundance of H2S, and inferences about the unmeasured H2 density, require accurate knowledge of radiative and collisional rate coefficients. Time-independent close-coupling quantum scattering calculations have been employed to compute rate coefficients for (de-)excitation of para- and ortho-H2S in collisions with para- and ortho-H2. These calculations utilized a potential energy surface for the interaction of H2S with H2 recently computed by the explicitly correlated CCSD(T)-F12a coupled-cluster method. Rate coefficients for temperatures ranging from 5 to 500 K were calculated for all transitions among the first 19 rotational levels of H2S, whose energies are less than or equal to 405 K. These rate coefficients are compared with previous estimates of these quantities.
Polymorphisms in human immunoglobulin heavy chain variable genes and their upstream regions
Authors: Mikocziova Ivana , Gidoni Moriah , Lindeman Ida , Peres Ayelet , Snir Omri , Yaari Gur , Sollid Ludvig M
Published: April 2020

Germline variations in immunoglobulin genes influence the repertoire of B cell receptors and antibodies, and such polymorphisms may impact disease susceptibility. However, the knowledge of the genomic variation of the immunoglobulin loci is scarce. Here, we report 25 potential novel germline IGHV alleles as inferred from rearranged naïve B cell cDNA repertoires of 98 individuals. Thirteen novel alleles were selected for validation, out of which ten were successfully confirmed by targeted amplification and Sanger sequencing of non-B cell DNA. Moreover, we detected a high degree of variability upstream of the V-REGION in the 5′UTR, L-PART1 and L-PART2 sequences, and found that identical V-REGION alleles can differ in upstream sequences. Thus, we have identified a large genetic variation not only in the V-REGION but also in the upstream sequences of IGHV genes. Our findings provide a new perspective for annotating immunoglobulin repertoire sequencing data.
dotdotdot: an automated approach to quantify multiplex single molecule fluorescent in situ hybridization (smFISH) images in complex tissues
Authors: Maynard Kristen R , Tippani Madhavi , Takahashi Yoichiro , Phan BaDoi N , Hyde Thomas M , Jaffe Andrew E , Martinowich Keri
Published: April 2020

Multiplex single-molecule fluorescent in situ hybridization (smFISH) is a powerful method for validating RNA sequencing and emerging spatial transcriptomic data, but quantification remains a computational challenge. We present a framework for generating and analyzing smFISH data in complex tissues while overcoming autofluorescence and increasing multiplexing capacity. We developed dotdotdot (https://github.com/LieberInstitute/dotdotdot) as a corresponding software package to quantify RNA transcripts in single nuclei and perform differential expression analysis. We first demonstrate robustness of our platform in single mouse neurons by quantifying differential expression of activity-regulated genes. We then quantify spatial gene expression in human dorsolateral prefrontal cortex (DLPFC) using spectral imaging and dotdotdot to mask lipofuscin autofluorescence. We lastly apply machine learning to predict cell types and perform downstream cell type-specific expression analysis. In summary, we provide experimental workflows, imaging acquisition and analytic strategies for quantification and biological interpretation of smFISH data in complex tissues.
Recurrent tumor and treatment-induced effects have different MR signatures in contrast enhancing and non-enhancing lesions of high-grade gliomas
Authors: Cluceru Julia , Nelson Sarah J , Wen Qiuting , Phillips Joanna J , Shai Anny , Molinaro Annette M , Alcaide-Leon Paula , Olson Marram P , Nair Devika , LaFontaine Marisa , Chunduru Pranathi , Villanueva-Meyer Javier E , Cha Soonmee , Chang Susan M , Berger Mitchel S , Lupo Janine M
Published: April 2020

Background

Differentiating treatment-induced injury from recurrent high-grade glioma is an ongoing challenge in neuro-oncology, in part due to lesion heterogeneity. This study aimed to determine whether different MR features were relevant for distinguishing recurrent tumor from the effects of treatment in contrast-enhancing lesions (CEL) and non-enhancing lesions (NEL).

Methods

This prospective study analyzed 291 tissue samples (222 recurrent tumor, 69 treatment-effect) with known coordinates on imaging from 139 patients who underwent preoperative 3T MRI and surgery for a suspected recurrence. 8 MR parameter values were tested from perfusion-weighted, diffusion-weighted, and MR spectroscopic imaging at each tissue sample location for association with histopathological outcome using generalized estimating equation models for CEL and NEL tissue samples. Individual cutoff values were evaluated using receiver operating characteristic curve analysis with 5-fold cross-validation.

Results

In tissue samples obtained from CEL, elevated relative cerebral blood volume (rCBV) was associated with the presence of recurrent tumor pathology (P < 0.03), while increases in normalized choline (nCho) and choline-to-NAA index (CNI) were associated with the presence of recurrent tumor pathology in NEL tissue samples (P < 0.008). A mean CNI cutoff value of 2.7 had the highest performance, resulting in mean sensitivity and specificity of 0.61 and 0.81 for distinguishing treatment-effect from recurrent tumor within the NEL.

Conclusion

Although our results support prior work that underscores the utility of rCBV in distinguishing the effects of treatment from recurrent tumor within the contrast enhancing lesion, we found that metabolic parameters may be better at differentiating recurrent tumor from treatment-related changes in the NEL of high-grade gliomas.
Increased activation of HDAC1/2/6 and Sp1 underlies therapeutic resistance and tumor growth in glioblastoma
Authors: Yang Wen-Bin , Hsu Che-Chia , Hsu Tsung-I , Liou Jing-Ping , Chang Kwang-Yu , Chen Pin-Yuan , Liu Jr-Jiun , Yang Shung-Tai , Wang Jia-Yi , Yeh Shiu-Hwa , Chen Ruei-Ming , Chang Wen-Chang , Chuang Jian-Ying
Published: April 2020

Background

Glioblastoma is associated with poor prognosis and high mortality. Although the use of first-line temozolomide can reduce tumor growth, therapy-induced stress drives stem cells out of quiescence, leading to chemoresistance and glioblastoma recurrence. The specificity protein 1 (Sp1) transcription factor is known to protect glioblastoma cells against temozolomide; however, how tumor cells hijack this factor to gain resistance to therapy is not known.

Methods

Sp1 acetylation in temozolomide-resistant cells and stemlike tumorspheres was analyzed by immunoprecipitation and immunoblotting experiments. Effects of the histone deacetylase (HDAC)/Sp1 axis on malignant growth were examined using cell proliferation–related assays and in vivo experiments. Furthermore, integrative analysis of gene expression with chromatin immunoprecipitation sequencing and the recurrent glioblastoma omics data were also used to further determine the target genes of the HDAC/Sp1 axis.

Results

We identified Sp1 as a novel substrate of HDAC6, and observed that the HDAC1/2/6/Sp1 pathway promotes self-renewal of malignancy by upregulating B cell-specific Mo-MLV integration site 1 (BMI1) and human telomerase reverse transcriptase (hTERT), as well as by regulating G2/M progression and DNA repair via alteration of the transcription of various genes. Importantly, HDAC1/2/6/Sp1 activation is associated with poor clinical outcome in both glioblastoma and low-grade gliomas. However, treatment with azaindolyl sulfonamide, a potent HDAC6 inhibitor with partial efficacy against HDAC1/2, induced G2/M arrest and senescence in both temozolomide-resistant cells and stemlike tumorspheres.

Conclusion

Our study uncovers a previously unknown regulatory mechanism in which the HDAC6/Sp1 axis induces cell division and maintains the stem cell population to fuel tumor growth and therapeutic resistance.
Does the Primacy System Work? State versus Federal Implementation of the Clean Water Act
Authors: Fowler Luke , Birdsall Chris
Published: April 2020

In the United States, environmental federalism largely relies on a system for policy implementation that allows the federal government to delegate primary program authority (or primacy) to state agencies. Although it is an ingrained feature of several major federal environmental policies, such as the Clean Water Act (CWA), there is little evidence to indicate what impact delegating authorities has on programs. In order to examine this, the authors use a synthetic control technique to determine how actual CWA program outcomes in five states compare to expected outcomes if EPA retained primary authority. Findings indicate that while there were no significant differences in Texas and Oklahoma, state primacy led to improved program outcomes in Florida, but worse outcomes in Maine and South Dakota. Conclusions suggest that primacy has asymmetrical impacts that largely depend on state implementation systems, which carries important implications for environmental federalism.
EP10 A rare cause of lobular panniculitis
Authors: Mudawi Tareg , Amoasii Constanta , Clewes Adrian
Published: April 2020

Background

Weber-Christian disease is a rare inflammatory disorder of the subcutaneous fatty tissue. It is characterised by painful relapsing, subcutaneous nodules occurring preferentially at the upper arm, thigh and trunk regions. The disease is often accompanied by recurrent temperatures and constitutional symptoms.

Methods

We aimed to increase awareness regarding clinical presentation, diagnosis, and treatment of this rare disorder.

Results

A 65 year old female had been investigated thoroughly within a period of 7 years by a number of dermatology and rheumatology departments of North West hospitals. Symptoms started after mastitis with skin rash in form of macular blanching on upper abdomen and episodes of fever ranging between 38 and 40 degree Celsius, fatigability and arthritis. C-reactive protein was 300 mg/l, Erythrocytes Sedimentation Rate 150 mm/H and haemoglobin 95 g/L, positive lupus anticoagulant and negative anti-nuclear antibodies as well as extractable nuclear antibodies and normal complement levels C3 and C4 . Investigations results showed no evidence of infection, malignancy, vasculitis or connective tissue disease. PET scan revealed subcutaneous fat inflammation with increased uptake in mediastinum fat, initial skin biopsy showed lobular panniculitis with mild dermatitis suggestive of lupus profundus. Symptoms and inflammatory markers responded well to steroids however all tried DMARDs (methotrexate, azathoprime, hydroxychlorquine and mycophenolate) as well as dapsone and colchicine were not successful. In addition, 2 doses of rituximab were also ineffective in controlling her disease. Following a required excessive steroid therapy she developed cataract, osteopenia, and diabetes and became cushingoid. Repeated biopsy from the skin showed mixed inflammatory lobular pannicuilitis with neutrophils, lymphocytes and histiocytic. As per Dermatology Multi-Disciplinary Team the diagnosis of Weber-Christian disease was raised. As her condition continued to be very active she was also referred to London, where treatment with anakinra was organised.

Conclusion

The diagnosis of Weber-Christian disease depends on the presence of relapsing fever, systemic inflammation and panniculitis and prognosis varies depending on the response to steroids or DMARDs. For diagnosis you need to exclude all likely differential diagnoses of lobular panniculitis, like infections, certain malignancies, alpha-1-antitrypsin deficiency, pancreatitis and systemic lupus erythematosus. In conclusion, the patient has symptoms and signs as well as investigation results in keeping with Weber-Christian disease. Due to the rare nature of this disease the patient went through, multiple rheumatology and dermatology reviews and investigations and treatment trials over a period of 7 years prior to the correct diagnosis being reached. We believe reporting this case would raise awareness and improve on future patients journeys and care.

Disclosures

T. mudawi None. C. Amoasii None. A. Clewes None.
EP24 A comparison of the effect of written leaflets, online information and real-time Doppler images: a qualitative study in South Asians
Authors: Kumar Kanta , Bradbury-Jones Caroline , Armitage Christopher J , Peters Sarah , Raizada Sabrina , Wong Peter
Published: April 2020

Background

There is poor medication adherence in patients of South Asian origin with rheumatoid arthritis (RA). There are limited interventions to improve patient engagement. The objective of this study was to explore how patients of South Asian origin make sense of their disease after receiving written leaflets compared to online information or visualising real-time Doppler Ultrasound (DUS) images of their inflamed joints.

Methods

Patients of South Asian origin with RA were recruited from two NHS hospitals in the West Midlands, UK. In-depth semi-structured interviews were undertaken following exposure to vignettes designed to elicit patients’ perspectives on: (1) written leaflets, (2) online information to complement face-to-face interaction with healthcare professionals, and (3) DUS during the early stages of the disease journey. Data were analysed thematically until data saturation was reached in twenty individuals.

Results

The responses to vignette scenarios were described by patients: [1] perspectives on written leaflets at the early stages of the disease journey, [2] perspectives of online information to compliment face-to-face interaction with healthcare professionals, [3] perspective of DUS during the early stages of the disease journey. Overall, patients found real-time DUS more valuable in understanding RA and RA medications compared to other methods. Patients reported DUS reduced anxiety and helped address misconceptions about long-term disease and its ability to be controlled.

Conclusion

We have developed new understanding regarding the educational utility of a DUS session in patients of South Asian origin and how these sessions can be optimised to increase patient engagement and medication adherence.

Disclosures

K. Kumar None. C. Bradbury-Jones None. C. Armitage None. S. Peters None. S. Raizada None. P. Wong None.
EP34 Assessing the ability of anti-C1q antibody measurement to predict a flare of lupus nephritis
Authors: Bahal Sameer , Pyne Dev , Rajakariar Ravindra , Lewis Myles , Pakozdi Angela , Cove-Smith Andrea
Published: April 2020

Background

Systemic lupus erythematous (SLE) is a multi-system autoimmune disease which has a relapsing and remitting course. Patients with lupus nephritis (LN) are at risk of relapse and hence long term follow up and disease monitoring are of particular importance. Anti-C1q antibodies (C1Q Ab) are observed in 30-60% of patients with SLE. It has been postulated that the presence of C1Q Ab can predict a flare of LN. Here we undertook a prospective follow up of patients after having a C1Q Ab measurement to determine whether the result predicted a flare of LN.

Methods

SLE patients attending an Inner-City Lupus Center, were involved in the study. All fulfilled the 2012 SLICC criteria for SLE. A point-in-time measurement of C1Q Ab was made using an ELISA kit (Orgentec Diagnostika GmbH). A positive test defined by the manufacturer is a level above 10 U/ml. Medical records of patients were reviewed over the following 1 year to identify LN flares. A renal flare was defined as a doubling of the protein creatinine ratio with a subsequent decision to escalate immunosuppressive therapy. Chi Squared tests were used to assess statistical significance. 9 patients who were being treated for a flare of LN at the time of C1Q Ab were excluded from the analysis.

Results

116 lupus patients were included in the study. Of those, 52 had biopsy proven LN (45%). Positive C1Q ab was more common in patients with a history of biopsy proven LN (n = 17, 32.7%) compared to those with non-renal SLE (n = 10, 15.6%),(p = 0.03). Renal flares tended to be more common in C1q ab positive LN patients (n = 4, 26.7%) compared to those without C1q ab (n = 2, 7.14%). (p = 0.782). Of the 64 patients with non-renal SLE, 1 (10%) C1Q Ab positive patient subsequently developed LN compared with 1 (1.85%) C1Q Ab negative patient (p = 0.173).There was no correlation between the level of C1Q Ab and the rate of LN flares. Having a positive dsDNA antibody level at the time of sampling also did not appear to predict a flare.

Conclusion

C1Q Ab has a known correlation with LN, however its ability to predict flares has been less well characterised. Our prospective analysis shows that although the C1Q Ab positive patients were more likely to have a flare of LN in the following year, there was not a statistically significant difference between the C1Q Ab positive and negative groups. In addition, only a relatively small proportion of C1Q Ab positive patients went on to have a flare (20%). Our data therefore does not support the use of C1Q Ab as a predicting factor for a subsequent flare of LN.

Disclosures

S. Bahal None. D. Pyne None. R. Rajakariar None. M. Lewis None. A. Pakozdi None. A. Cove-Smith None.
O10 Combining clinical and ultrasound assessment to taper biologic therapies in patients with RA in routine clinical practice
Authors: Pillai Harikrishnan , Nolkha Nilesh , Yau Augustus , Matthews Susan , Hall Alison , Hirsch George , Venkatachalam S
Published: April 2020

Background

There is growing evidence for tapering biologic therapies in patients with rheumatoid arthritis in sustained clinical remission to avoid overtreatment and minimise side-effects. Ultrasound assessment for subclinical synovitis adds to clinical assessment of patients with rheumatoid arthritis suitable for tapering biologic therapies. Our primary objective was to combine clinical and ultrasound assessment to select patients with rheumatoid arthritis for tapering biologic therapies in routine clinical practice. The secondary objectives were to identify predictors for successful tapering and assess the cost savings to the local health economy by optimising the use of high cost drugs.

Methods

All patients with rheumatoid arthritis on a biologic therapy for 2 years and in sustained clinical remission (DAS28≤2.6) over the previous year were seen in the remission clinic. They had an Ultrasound scan of the small joints of the hands, wrists and other symptomatic joints. Patients with no activity on Power Doppler were advised to lengthen the interval of their biologic therapy gradually and were followed once every 3 months. Patients were not on oral steroids but continued conventional DMARDs. Patients had a dedicated helpline if they had a flare.

Results

Ninety-three of the 120 patients with rheumatoid arthritis on biologic therapy seen in the biologic remission clinic between January and October 2019 were eligible and all but one agreed to taper. They were 70% female with a mean age of 62.8 years and mean duration of disease 14.6 years. Their mean duration of biologic therapy was 6.3 years; mean baseline DAS28 was 6.3 pre-biologic therapy and 1.7 before tapering. Fifty-seven of the patients were on a TNF inhibitor and 35 were on other biologic therapies. Forty of the ninety-two patients were co-prescribed DMARDs. Screening failure was due to clinical activity in 13 patients, Ultrasound Power Doppler activity in 23 patients, interstitial lung disease in 2 patients and shoulder surgery in one. Only two of the 40 patients who had completed 6 months had a flare and reverted to the baseline frequency. Of the remaining 52 patients, 22 patients had completed 3 months at the tapered dose and 3 patients who were in the initial 3 months had a flare and reverted to the baseline frequency. Initial drug-cost savings at 6 months was approximately £45,000.

Conclusion

Tapering of biologic therapies in patients with rheumatoid arthritis is feasible in routine clinical practice. Ultrasound is helpful to stratify patients for biologic tapering and has enabled a higher proportion of patients to remain in remission after tapering.

Disclosures

H. Pillai: None. N. Nolkha: None. A. Yau: None. S. Matthews: None. A. Hall: None. G. Hirsch: None. S. Venkatachalam: None.
O16 Incidence, prevalence and associated comorbidity of axSpA within the UK: a retrospective database analysis
Authors: Morgan Christopher L. I , White Abigail , Tomlinson Mark , Scott Amie , Tian Haijun
Published: April 2020

Background

This study reports the incidence and prevalence of axial spondyloarthritis (axSpA) in the UK, and describes the baseline characteristics and comorbidities associated with the condition.

Methods

This study was conducted using the Clinical Practice Research Datalink, a large routine primary care database in the UK. Approximately 60% of contributing English primary care practices are linked to Hospital Episode Statistics (HES) secondary care data. AxSpA and relevant comorbidities were identified from Read or International Statistical Classification of Diseases and Related Health Problems-10 codes in primary care or HES datasets, respectively. The date of first axSpA diagnosis defined the index date. Patients with ≥90 days between practice registration and first axSpA diagnosis were classified as incident cases. The incidence and prevalence of axSpA were calculated annually from 2003-2017 for the UK as a whole, each constituent nation and English practices linked to HES data, to maximise case ascertainment. Comorbidities occurring prior to the index date (inclusive) were reported and compared with non-axSpA patients matched for age, sex, primary care practice and concurrent practice registration.

Results

Overall, 20,199 axSpA patients were identified, of whom 8,387 (41.5%) were classified as incident cases. Of the incident cases, 2,600 (31.0%) were female. Mean age at first diagnosis was 45.5 years (standard deviation [SD]: 17.2), mean body mass index was 27.2 kg/m2 (SD: 5.9) and 2,481 (29.6%) patients were current smokers. In 2017, the incidence of axSpA was 8.0 per 100,000 person-years and the prevalence was 15.8 per 10,000 population, an increase from 12.7 per 10,000 population in 2003. For patients from English practices linked to HES data, the incidence was 10.8 per 100,000 person-years and the prevalence was 17.5 per 10,000 population. 8,385 (∼100.0%) axSpA patients could be matched to non-axSpA controls. At baseline, all selected comorbidities were significantly increased in axSpA cases vs controls (Table).

Conclusion

This study reports an increasing prevalence of axSpA over the study period and higher rates of specific comorbidities in patients with axSpA vs matched controls. Caveats related to routine database studies, including secular changes in case ascertainment and observation bias, should be considered when interpreting these results.

Disclosures

C.L.I. Morgan: Other; Employee of: Pharmatelligence. A. White: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. M. Tomlinson: Consultancies; Novartis. A. Scott: Consultancies; Novartis. H. Tian: Other; Employee of: Novartis.
O37 Utility of RA classification criteria in early inflammatory arthritis referral prioritisation
Authors: Imaduddin Syed M , O'Biern Patrick
Published: April 2020

Background

Early arthritis clinics are increasingly utilised as a method of ensuring patients suspected of disease are assessed promptly to enable suitable treatment. Early recognition with treat to target has been demonstrated in systematic reviews to significantly improve mortality and morbidity outcomes. The United Kingdom’s National Institute for Health and Care Excellence (NICE) recommend potentially affected patients are referred from primary care within 3 days and seen in secondary care within 3 weeks. We hypothesised that utilising the ACR/EULAR 2010 rheumatoid arthritis classification criteria we could identify variables within the primary care referral which make an early arthritis more or less likely.

Methods

A retrospective study of all the patients seen in early inflammatory arthritis (EIA) Clinic from September 2017 to August 2018 in Aneurin Bevan University Health Board. EULAR scores of 145 patients were calculated based on the data provided in the primary care referral. These scores and their components were then compared to the eventual diagnosis.

Results

EULAR score of ≥ 5 had specificity of > 78% and sensitivity of < 30% in predicting EIA. EULAR score of 8 or more was 100% specific for EIA with positive likelihood ratio of infinity. Whereas EULAR score < 3 had a specificity of > 70% and sensitivity of < 45% for Non EIA with a positive likelihood ratio of 1.59. Considering individual EULAR components a high positive Rheumatoid Factor (RF) or Anti-citrullinated peptide antibody (ACPA) and involvement of greater than 10 joints had a positive likelihood ratio of ≥ 3.00 for EIA. A low positive RF or ACPA had a specificity of 66.67% and sensitivity of 27.59% for EIA with a positive likelihood ratio of 0.83. Surprisingly involvement of 4-10 small joints or 2-10 large joints or just 1 large joint had a specificity of ≥ 75% for EIA and a positive likelihood ratio of greater than 1.00. A positive ESR or CRP had a specificity of 36.84% and sensitivity of 67.92% with a positive likelihood ratio for EIA of 1.08. A negative ESR and CRP had a specificity of 67.92% and a sensitivity of 35.00% for Non EIA with a positive likelihood ratio of 1.09. The duration of symptoms of < 6 weeks had a specificity of 77.55% and sensitivity of 24.39% with positive likelihood ratio for Non EIA of 1.08, however duration of > 6 weeks had a positive likelihood ratio of 0.97 for EIA with a lower specificity of 22.45% .

Conclusion

The total EULAR score and individual components can be used to prioritize primary care referrals. A EULAR score of less than 3, duration of symptoms of < 6 weeks, a negative ESR and CRP, a low positive RF or ACPA makes EIA less likely.

Disclosures

S.M. Imaduddin None. P. O'Biern None.
P15 An audit of the management of Behçet's disease in a tertiary referral centre against guidelines from EULAR and the National Centres of Excellence
Authors: Weightman Jessica , Griffiths Bridget , Pandit Ranjeet , Stroud Catherine , Price Ashleigh D , Lorenzi Alice R
Published: April 2020

Background

BD patients are managed equivalently by multiple medical specialties in our trust. Failure to switch from IV to s/c antiTNFalpha therapies was noted and our use of methotrexate, hydroxychloroquine and cyclophosphamide deviates from guidelines. Whether this effects outcome is unknown it but seems likely to be considered clinically useful. A national audit would determine if our management is an anomaly or in keeping with standard practice in the UK prompting review of our treatment algorithm.

Methods

Involved specialities provided details of BD patients in their care. Electronic case records from January 2009 to July 2019 were reviewed. Data were extracted using standard pro-forma classifying patients into 3 groups determined by their most severe manifestation: less severe (predominant musculoskeletal, mucocutaneous); ophthalmic (all eye disease) and severe disease (predominant CNS and vascular disease). Medication was assessed against guidelines for escalation and de-escalation protocols.

Results

50 patients (representing approximately 7% of the national BD population) were identified from 4 specialties (Table 1). 23 were female; 45 identified as White British. 26 were regularly reviewed by 2 or more specialties, 4 had discontinued follow up. 26/50 had used antiTNFalpha therapies and 9/50 had received IV cyclophosphamide. Adherence to guidelines was determined by specialty and disease severity (Table 1). The EULAR guideline was followed least well by Rheumatology; low rates of adherence to the national guideline reflected frequent use of methotrexate and hydroxychloroquine in the less severe group and failure to switch to from IV to sub-cutaneous antiTNFalpha therapies. Deviations from national and EULAR guidelines in the ‘severe’ category related to the first line use of IV cyclophosphamide for acute organ/sight threatening disease.

Conclusion

BD patients are managed equivalently by multiple medical specialties in our Trust. Failure to switch from IV to s/c antiTNFalpha therapies was noted and our use of methotrexate, hydroxychloroquine and cyclophosphamide deviates from guidelines. Whether this effects outcome is unknown it but seems likely to be considered clinically useful. A national audit would determine if our management is an anomaly or in keeping with standard practice in the UK prompting review of our treatment algorithm.

Disclosures

J. Weightman None. B. Griffiths None. R. Pandit None. C. Stroud None. A.D. Price None. A.R. Lorenzi None.
P46 Takotsubo cardiomyopathy in a GPA patient receiving rituximab therapy
Authors: Jayanti Santhosh P , Nair Sulfi , Makkuni Damodar
Published: April 2020

Background

Cardiac involvement in GPA is quite rare. Patients with GPA are two times more likely to die of cardiovascular complications as compared to the general population due to accelerated atherosclerosis. Cardiac involvement in GPA is secondary to necrotising vasculitis with granulomatous infiltrates, usually resulting in coronary artery thrombosis. We present a case of Takotsubo cardiomyopathy in a patient of GPA treated with rituximab. There has previously only been one case report of a patient on rituximab therapy developing Takotsubo cardiomyopathy.

Methods

This 67-year-old woman was diagnosed with GPA in January 2018 when she presented with a necrotic lung lesion along with nasal crusting and leg ulcers. Her ANCA was 102 i.u./ml at the time. We treated with cyclophosphamide and azathioprine to good effect. Then she had a relapse six months later and presented to the hospital with stridor due to subglottic stenosis. At this point we switched to rituximab and methotrexate to induce remission, her ANCA titres settled to 3.4 i.u./ml at this point. After her second cycle of rituximab, she presented to the hospital with shortness of breath, chest pain and stridor in November 2018.

Results

At her presentation with chest pain in November 2018, an ECG was performed, which showed an incomplete LBBB with ST elevation in anterior leads with a troponin level of 550ng/ml. A repeat ECG after 2 hours, showed ST elevations in anterolateral leads with a troponin level of 1259ng/ml. We treated this as an acute myocardial infarction. An echocardiogram was obtained, which was remarkable in that it showed no new regional wall motion abnormalities. A subsequent coronary angiogram confirmed that there was no coronary artery disease raising the possibility of Takotsubo cardiomyopathy.

Conclusion

Rituximab is implicated in cardiac arrhythmia and coronary vasospasm during the infusion, reduction in LVEF, non-ischaemic cardiomyopathy, cardiogenic shock after. Our patient had a myocardial infarction with normal coronaries, and she was going through a very emotionally stressful period with her husband’s illness at the time of her presentation, which makes Takatsubo cardiomyopathy a very likely diagnosis. There are few case reports in the literature and, clinicians should be aware of this rare complication.

Disclosures

S.P. Jayanti None. S. Nair None. D. Makkuni None.
P65 Exploring ethnic disparities in early arthritis care
Authors: James Lija , Clarke Benjamin D , Salerno Rosaria , Audu Aderonke , Steer Sophia , Galloway James B
Published: April 2020

Background

The National Health Service caters to a variety of rheumatology patients from increasingly diverse multi-ethnic backgrounds. Despite this, societal, organisational and personal barriers remain across the UK. These are known to directly and indirectly influence access to care although no inference can be generalised at a local level. Our south London trust has one of the highest non-white patient bases in the UK, hence our interest in wanting to explore the cultural differences around delivery of care. We set out to use the national inflammatory arthritis audit (NEIAA) data from our department to ensure equitable service provision and delivery using quality improvement methodology.

Methods

The NEIAA data for our trust observes performance across the seven NICE quality indicators for rheumatoid arthritis. Of interest was evaluation of standards 1 to 6, as too few data existed for standard 7. Ethnicity was coded according to the NEIAA categories as white or non-white. Differences by disease severity indicators were analysed. A descriptive analysis was performed with an understanding that no assumptions or statistical interpretations could be made to these observed differences.

Results

A total of 471 patients had data available. Of these, 124 (26%) had a diagnosis of early inflammatory arthritis, of whom 34 (27%) were non-white and 80 (73%) were white. Non-white patients were younger, more were seropositive, had a higher baseline DAS28, worse MSK-HQ scores, worse mental health scores and worse HAQ scores. Non-white patients were less likely to have a patient reported outcome recorded. Attainment of quality standards 1, 2, 3 and 6 had equiproportionate representation of non-white and white patients. Standards 4 (provision of education) and 5 (agreement of treatment target) demonstrated fewer non-white patients meeting the target. Standard 5 demonstrated the most disparity. 83% of white patients had an agreed target compared to 47% of non-white (Odds ratio 5.6 (CI 2.2-14.1)). To describe this, our non-white patients were more than 5 times less likely to have an agreed treatment target.

Conclusion

Cultural differences exist in health-seeking behaviour, verbal language, written comprehension and in unconscious bias. The NEIAA results within our trust suggest differences exist by ethnic groupings in early arthritis care. Although challenges and taboos remain in discussing these variations, more work needs to be undertaken to explore healthcare disparities and why these occur. Research within this field is limited to date. We plan to adopt a quality improvement approach using stakeholder engagement meetings, process-mapping and driver diagrams to evaluate how best to achieve change.

Disclosures

L. James None. B.D. Clarke None. R. Salerno None. A. Audu None. S. Steer None. J.B. Galloway None.
P67 Risk factors for musculoskeletal pain amongst health and social care workers in the UK: results from the Health and Employment After Fifty (HEAF) study
Authors: D'Angelo Stefania , Ntani Georgia , Syddall Holly , Harris E C , Linaker Cathy , Stevens Martin , Walker-Bone Karen
Published: April 2020

Background

Musculoskeletal disorders are one of the main causes of sickness absence in the UK and their prevalence is likely to increase in workers, with the rise of state pension age. Previous research has shown that these conditions are common among health and social care workers. Therefore, we aimed to describe the prevalence of musculoskeletal pain among health and social care workers and to explore personal and occupational risk factors for pain at specific anatomical sites and for multi-site pain.

Methods

We used data from the second year of follow up of the Health and Employment After Fifty (HEAF) study, a cohort study of 8,134 adults aged 50-64, recruited through 24 English general practices. Health and social care workers, identified through the Standard Occupational Classification 2010, were the focus of this cross-sectional analysis.

The outcome under investigation was self-reported pain lasting more than a day in the past month, at one or more of eight anatomical sites: neck, low back, mid-back, shoulder, elbow, wrist/hand, knee, foot/ankle. Socio-demographic variables, self-reported health measures, psychosocial work factors (job dissatisfaction, lack of appreciation, lack of support) and occupational activities (kneeling or squatting for more than 1 hr/day, standing for most of the day) were ascertained through postal questionnaire, and associations with pain at specific anatomical sites and multi-site (≥2 anatomical sites) pain were explored with logistic regression, firstly adjusted for age and sex and then adjusted for additional confounders.

Results

A total of 282 participants were working in health and social care at second year follow up. Mean age was 59 years and 90% of them were women. Of these workers, n = 199 (71%) reported pain in at least one site, while n = 147 (52%) reported multi-site pain. The most reported anatomical sites with pain were knee and low back, with a prevalence of 39% and 34% respectively. Significant risk factors for knee pain were poor self-rated health (OR = 4.2; 95%CI 2.1 to 8.2) and being exposed to kneeling for longer than an hour/day at work (OR = 2.0; 95%CI 1.2 to 3.4). Similar results were found for low back pain, while for multi-site pain mental exhaustion also appeared to have an effect. None of the socio-demographic variables or psychosocial work factors influenced the outcomes.

Conclusion

In a sample of health and social care workers in the UK, the prevalence of low back, neck and multi-site pain is high. The common risk factors were being exposed to kneeling at work and reporting poor/fair health.

Disclosures

S. D'Angelo: None. G. Ntani: None. H. Syddall: None. E.C. Harris: None. C. Linaker: None. M. Stevens: None. K. Walker-Bone: None.