Resonant tunneling in a Luttinger liquid for arbitrary barrier transmission

A numerically exact dynamical quantum Monte Carlo approach has been developed and applied to transport through a double barrier in a Luttinger liquid with arbitrary transmission. For strong transmission, we find broad Fabry-Perot Coulomb blockade peaks, with a lineshape parametrized by a single parameter, but at sufficiently low temperatures, non-Lorentzian universal lineshapes characteristic of coherent resonant tunneling emerge, even for strong interactions. For weak transmission, our data supports the recently proposed correlated sequential tunneling picture and is consistent with experimental results on intrinsic nanotube dots.Comment: 4 pages, 4 figure

Stem cell transplantation for rheumatic autoimmune diseases

Immunoablative therapy and hematopoietic stem cell transplantation (HSCT) is an intensive treatment modality aimed at 'resetting' the dysregulated immune system of a patient with immunoablative therapy and allow outgrowth of a nonautogressive immune system from reinfused hematopoietic stem cells, either from the patient (autologous HSCT) or a healthy donor (allogeneic HSCT). HSCT has been shown to induce profound alterations of the immune system affecting B and T cells, monocytes, and natural killer and dendritic cells, resulting in elimination of autoantibody-producing plasma cells and in induction of regulatory T cells. Most of the available data have been collected through retrospective cohort analyses of autologous HSCT, case series, and translational studies in patients with refractory autoimmune diseases. Long-term and marked improvements of disease activity have been observed, notably in systemic sclerosis, systemic lupus erythematosus, and juvenile idiopathic arthritis, and treatment-related morbidity and mortality have improved due to better patient selection and modifications of transplant regimens. Treatment-related mortality has decreased to approximately 7%. Prospective, randomised, controlled clinical trials are ongoing or planned in systemic sclerosis, systemic lupus erythematosus, and several nonrheumatological conditions

Allogeneic stem cell transplantation for rheumatic autoimmune diseases

Haematopoietic stem cell transplantation (HSCT) has evolved from an experimental concept to an effective treatment option for severe autoimmune diseases and has a unique ability to restore immune regulation. It is a complex multistep procedure involving the administration of high doses of immunosuppressive medication and transplantation of stem cells. Most HSCT procedures in autoimmune disease have involved autologous stem cells. In the case of allogeneic transplantation, stem cells are derived from peripheral blood or bone marrow of a healthy HLA-matched donor. Allogeneic HSCT has curative potential based on studies in experimental models of autoimmune disease, case reports, and a registry analysis but carries significant risks of rejection and graft-versus-host disease. Unless these risks become manageable, allogeneic HSCT should be offered only if all alternative treatment options have failed, if a patient has a suitable donor, and if a patient still has a chance to benefit significantly from the procedure

Applied machine learning and artificial intelligence in rheumatology

Machine learning as a field of artificial intelligence is increasingly applied in medicine to assist patients and physicians. Growing datasets provide a sound basis with which to apply machine learning methods that learn from previous experiences. This review explains the basics of machine learning and its subfields of supervised learning, unsupervised learning, reinforcement learning and deep learning. We provide an overview of current machine learning applications in rheumatology, mainly supervised learning methods for e-diagnosis, disease detection and medical image analysis. In the future, machine learning will be likely to assist rheumatologists in predicting the course of the disease and identifying important disease factors. Even more interestingly, machine learning will probably be able to make treatment propositions and estimate their expected benefit (e.g. by reinforcement learning). Thus, in future, shared decision-making will not only include the patient's opinion and the rheumatologist's empirical and evidence-based experience, but it will also be influenced by machine-learned evidence

Prospective clinical evaluation of a novel anatomic cuff for forearm crutches in patients with osteoarthritis.

The use of forearm crutches has been associated with pain and neuropraxia along the ulnar bone. Whilst anatomic grips have improved comfort of crutch walking, to date anatomic forearm cuffs have not been clinically evaluated. The aim of this clinical pilot study was to determine if the use of forearm crutches with anatomic cuffs reduces pain and increases comfort and function in long-term users of forearm crutches during a 4-week period. Prospective study in ten patients suffering from end-stage osteoarthritis of the lower extremity. All participants were long-term users of conventional forearm crutches. Participants used forearm crutches with an anatomically shaped cuff for 4-weeks. General health was assessed using the SF-36, and the crutches were evaluated using a newly developed questionnaire focusing on symptoms along the forearm. Pain and paresthesia along the forearms decreased by 3.3 points (95% confidence interval difference (CI): [-5.0; -1.6], p = .004) and 3.5 points (95%CI: [-5.1; -1.9], p = .002), respectively, after using the crutches with the new anatomic cuff for 4 weeks. Comfort and sense of security of crutch use increased by 3.0 points (95%CI: [1.3; 4.7], p = .007) and 2.4 points (95%CI: [0.7; 4.1], p = .024). Cross-correlation analysis revealed correlations among items in the same item category and no correlations between items of different item categories of the new questionnaires. An anatomically shaped cuff increases comfort of forearm crutches. Further research should confirm long-term clinical improvement. This study was registered retrospectively in ISRCTN (TRN: ISRCTN 11135150 ) on 14/02/2017

Imaging of ανβ3 integrin expression in rheumatoid arthritis with [68Ga]Ga-NODAGA-RGDyk PET/CT in comparison to [18F]FDG PET/CT

[Ga-68] Ga-NODAGA-RGDyk PET/CT and [F-18] FDG PET/CT were performed in a 65-year-old woman during the work-up of a squamous cell carcinoma of the tongue within a clinical study protocol. Images revealed both tracers' uptake in the primary tumor and cervical lymph nodes, but also bilaterally in the shoulders, elbows, wrists, metacarpophalangeal, interphalangeal, and hip joints. The patient had been diagnosed with rheumatoid arthritis 8 years prior to the examination. Images showed a significantly higher [F-18] FDG than [Ga-68] Ga-NODAGA-RGDyk uptake in primary tumor and cervical lymph nodes. However, the patient with moderately active rheumatoid arthritis had similar levels of [Ga-68]Ga-NODAGA-RGDyk and [F-18] FDG uptake in the involved joints, but with no [Ga-68] Ga-NODAGA-RGDyk uptake in the surrounding muscles, unlike with [F-18]FDG. Our case suggests that [Ga-68]Ga-NODAGA-RGDyk PET/CT allows imaging of integrins expression in rheumatoid arthritis, including integrins expressed in synovial angiogenesis, with potentially a better signal-to-noise ratio than on [F-18]FDG PET/CT. (C) 2021 The Author(s). Published by Elsevier Masson SAS

Differentiation Potential of CD14+ Monocytes into Myofibroblasts in Patients with Systemic Sclerosis

BACKGROUND: Circulating monocytes are a highly plastic and functionally heterogeneic cell type with an activated phenotype in patients with systemic sclerosis (SSc). CD14(+) monocytes have the potential to differentiate into extra-cellular matrix (ECM) producing cells, possibly participating in fibrogenesis. AIM: To study the effect of GM-CSF, IL-4 and endothelin -1 (ET-1) alone or in combination on monocyte differentiation into myofibroblasts. METHODS: CD14(+) cells were isolated from peripheral blood from 14 SSc patients and healthy controls by positive selection and incubated with different combinations of GM-CSF, IL-4 and ET-1 for 14 days. Type-1 collagen and α-SMA were detected by Western blot, qPCR and confocal microscopy. HLA-DR, CD11c and CD14 expression was analysed by flow cytometry. A collagen gel contraction assay was performed for functional myofibroblast assessment. RESULTS: GM-CSF both induced collagen and α-SMA expression after 14 days. ET-1 further increased GM-CSF-induced collagen expression in a dose dependent manner up to 30-fold. IL-4/GM-CSF combination leads to a more DC-like phenotype of monocytes associated with reduced collagen and α-SMA expression compared to GM-CSF alone. Collagen and α-SMA expression was higher in monocytes from SSc patients and monocytes were more prone to obtain a spindle form. In contrast to controls, ET-1 and IL-4 alone were sufficient to induce α-SMA expression in monocytes from SSc patients. Despite the induction of α-SMA expression, monocyte-derived myofibroblasts only had a moderate capability of contraction in functional analyses. CONCLUSION: SSc monocytes display increased maturation towards myofibroblasts demonstrated by their phenotype and α-SMA expression when compared to monocytes from healthy controls, however only with minor functional contraction properties

A next-generation inverse-geometry spallation-driven ultracold neutron source

The physics model of a next-generation spallation-driven high-current ultracold neutron (UCN) source capable of delivering an extracted UCN rate of around an-order-of-magnitude higher than the strongest proposed sources, and around three-orders-of-magnitude higher than existing sources, is presented. This UCN-current-optimized source would dramatically improve cutting-edge UCN measurements that are currently statistically limited. A novel "Inverse Geometry" design is used with 40 L of superfluid $^4$He (He-II), which acts as a converter of cold neutrons (CNs) to UCNs, cooled with state-of-the-art sub-cooled cryogenic technology to $\sim$1.6 K. Our design is optimized for a 100 W maximum heat load constraint on the He-II and its vessel. In our geometry, the spallation target is wrapped symmetrically around the UCN converter to permit raster scanning the proton beam over a relatively large volume of tungsten spallation target to reduce the demand on the cooling requirements, which makes it reasonable to assume that water edge-cooling only is sufficient. Our design is refined in several steps to reach $P_{UCN}=2.1\times10^9\,/$s under our other restriction of 1 MW maximum available proton beam power. We then study effects of the He-II scattering kernel as well as reductions in $P_{UCN}$ due to pressurization to reach $P_{UCN}=1.8\times10^9\,/$s. Finally, we provide a design for the UCN extraction system that takes into account the required He-II heat transport properties and implementation of a He-II containment foil that allows UCN transmission. We estimate a total useful UCN current from our source of $R_{use}=5\times10^8\,/$s from a 18 cm diameter guide 5 m from the source. Under a conservative "no return" approximation, this rate can produce an extracted density of $>1\times10^4\,/$cm$^3$ in $<$1000~L external experimental volumes with a $^{58}$Ni (335 neV) cut-off potential.Comment: Submitted to Journal of Applied Physic

Late-onset systemic sclerosis—a systematic survey of the EULAR scleroderma trials and research group database

Objective. The clinical course of SSc depends on subtype, organ involvement and age. Few data are reported on patients suffering from late-onset SSc. Methods. We analysed data from 8554 patients prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) group database. Late-onset SSc was defined as onset of non-RP disease features at or beyond 75 years of age. Disease characteristics, clinical features, disease course and mortality were evaluated. Results. A total of 123 patients with SSc onset at or beyond 75 years of age were identified. Compared with patients <75 years they had more frequently limited than diffuse SSc and a higher prevalence of anti-centromere autoantibodies. Fewer old patients had digital ulcers. The modified Rodnan's skin score, the prevalence of lung fibrosis and renal crisis did not differ significantly between groups. Pulmonary hypertension (PH) measured by echocardiography was more prevalent in the late-onset group, as well as arterial hypertension and diastolic dysfunction. Late-onset SSc remained a positive predictor for PH in multivariate analyses. No significant difference of the two groups in skin score or diffusion capacity was observed during follow-up. Mortality due to SSc was higher in the late-onset group, but the survival time from diagnosis was longer compared with the younger patients. Conclusion. Late-onset SSc shows a distinct clinical presentation and outcome. Patients with late-onset SSc suffer more frequently from the limited subtype and PH, but fewer patients have digital ulcers. PH may in part be determined by underlying cardiovascular diseas