Opportunities and Barriers of Telemedicine in Rheumatology: A Participatory, Mixed-Methods Study

Despite all its promises, telemedicine is still not widely implemented in the care of rheumatic and musculoskeletal diseases (RMDs). The aim of this study is to investigate opportunities, barriers, acceptance, and preferences concerning telemedicine among RMD patients and professional stakeholders. From November 2017 to December 2019, a participatory, mixed-methods study was conducted, consisting of (1) expert interviews (n = 27) with RMD patients and professional stakeholders, (2) a national paper-based patient survey (n = 766), and (3) focus groups (n = 2) with patient representatives and rheumatologists. The qualitative findings indicate that patients equate personal contact with physical face-to-face contact, which could be reduced by implementing telemedicine, thus negatively influencing the patient–doctor relationship. Correspondingly “no personal contact with the doctor” is the main reason (64%) why 38% of the surveyed patients refuse to try telemedicine. Professional stakeholders expect telemedicine to contribute to the effective allocation of scarce resources in rheumatology care. The main barriers reported by stakeholders were the scarcity of time resources in RMD care, the absence of physical examinations, and organizational challenges associated with the implementation of telemedicine in RMD care. While the exact integration of telemedicine into routine care has yet to be found, the consequences on the patient-physician relationship must be permanently considered.

Cosmological simulations of number counts

In this paper we present for the first time the angular power spectra C ℓ(z,z') for number counts from relativistic N-body simulations. We use the relativistic N-body code gevolution with its exact integration of lightlike geodesics which include all relativistic scalar contributions to the number counts. We compare our non-perturbative numerical results with the results from class using the hmcode approximation for the non-linear matter power spectrum. We find that this simple description is excellent for both, the density and the convergence. On the other hand, the current implementation of redshift-space distortions in Boltzmann codes is not accurate. We also find that the largest contribution to the unequal-redshift power spectra is the cross-correlation of the density and the lensing contribution to the number counts, especially for redshift bins that are far apart. Correlating the number counts with the convergence map we find that the signal is dominated by the lensing-lensing term when the convergence field redshift is not higher than the number counts one, while it is dominated by the density-lensing term in the opposite case. In the present study, the issue of galaxy bias is deliberately left aside by considering only unbiased samples of matter particles from the simulations.

On Truly Nonlinear Oscillator Equations of Ermakov-Pinney Type

In this paper we present a general class of differential equations of Ermakov-Pinney type which may serve as truly nonlinear oscillators. We show the existence of periodic solutions by exact integration after the phase plane analysis. The related quadratic Lienard type equations are examined to show for the first time that the Jacobi elliptic functions may be solution of second-order autonomous non-polynomial differential equations.

Schrödinger Equations in Electromagnetic Fields: Symmetries and Noncommutative Integration

We study symmetry properties and the possibility of exact integration of the time-independent Schrödinger equation in an external electromagnetic field. We present an algorithm for constructing the first-order symmetry algebra and describe its structure in terms of Lie algebra central extensions. Based on the well-known classification of the subalgebras of the algebra e(3), we classify all electromagnetic fields for which the corresponding time-independent Schrödinger equations admit first-order symmetry algebras. Moreover, we select the integrable cases, and for physically interesting electromagnetic fields, we reduced the original Schrödinger equation to an ordinary differential equation using the noncommutative integration method developed by Shapovalov and Shirokov.

Plitidepsin: Mechanisms and Clinical Profile of a Promising Antiviral Agent against COVID-19

Current standard treatment of COVID-19 lacks in effective antiviral options. Plitidepsin, a cyclic depsipeptide authorized in Australia for patients with refractory multiple myeloma, has recently emerged as a candidate anti-SARS-CoV-2 agent. The aim of this review was to summarize current knowledge on plitidepsin’s clinical profile, anti-tumour and anti-SARS-CoV-2 mechanisms and correlate this with available or anticipated, preclinical or clinical evidence on the drug’s potential for COVID-19 treatment.PubMed, Scopus, CENTRAL, clinicaltrials.gov, medRxiv and bioRxiv databases were searched.Plitidepsinexerts its anti-tumour and antiviral properties primarily through acting on isoforms of the host cell’s eukaryotic-translation-elongation-factor-1-alpha (eEF1A). Through inhibiting eEF1A and therefore translation of necessary viral proteins, it behaves as a “host-directed” anti-SARS-CoV-2 agent. In respect to its potent anti-SARS-CoV-2 properties, the drug has demonstrated superior ex vivo efficacy compared to other host-directed agents and remdesivir, and it might retain its antiviral effect against the more transmittable B.1.1.7 variant. Its well-studied safety profile, also in combination with dexamethasone, may accelerate its repurposing chances for COVID-19 treatment. Preliminary findings in hospitalized COVID-19 patients, have suggested potential safety and efficacy of plitidepsin, in terms of viral load reduction and clinical resolution. However, the still incomplete understanding of its exact integration into host cell–SARS-CoV-2 interactions, its intravenous administration exclusively purposing it for hospital settings the and precocity of clinical data are currently considered its chief deficits. A phase III trial is being planned to compare the plitidepsin–dexamethasone regimen to the current standard of care only in moderately affected hospitalized patients. Despite plitidepsin’s preclinical efficacy, current clinical evidence is inadequate for its registration in COVID-19 patients.Therefore, multicentre trials on the drug’s efficacy, potentially also studying populations of emerging SARS-CoV-2 lineages, are warranted.

Tetrahedra of varying density and their applications

We propose concepts to utilize basic mathematical principles for computing the exact mass properties of objects with varying densities. For objects given as 3D triangle meshes, the method is analytically accurate and at the same time faster than any established approximation method. Our concept is based on tetrahedra as underlying primitives, which allows for the object’s actual mesh surface to be incorporated in the computation. The density within a tetrahedron is allowed to vary linearly, i.e., arbitrary density fields can be approximated by specifying the density at all vertices of a tetrahedral mesh. Involved integrals are formulated in closed form and can be evaluated by simple, easily parallelized, vector-matrix multiplications. The ability to compute exact masses and centroids for objects of varying density enables novel or more exact solutions to several interesting problems: besides the accurate analysis of objects under given density fields, this includes the synthesis of parameterized density functions for the make-it-stand challenge or manufacturing of objects with controlled rotational inertia. In addition, based on the tetrahedralization of Voronoi cells we introduce a precise method to solve $$L_{2|\infty }$$ L 2 | ∞ Lloyd relaxations by exact integration of the Chebyshev norm. In the context of additive manufacturing research, objects of varying density are a prominent topic. However, current state-of-the-art algorithms are still based on voxelizations, which produce rather crude approximations of masses and mass centers of 3D objects. Many existing frameworks will benefit by replacing approximations with fast and exact calculations. Graphic abstract

Stability of a Point Charge for the Vlasov–Poisson System: The Radial Case

We consider the Vlasov–Poisson system with repulsive interactions. For initial data a small, radial, absolutely continuous perturbation of a point charge, we show that the solution is global and disperses to infinity via a modified scattering along trajectories of the linearized flow. This is done by an exact integration of the linearized equation, followed by the analysis of the perturbed Hamiltonian equation in action-angle coordinates.

Mechanical Proof of the Maxwell-Boltzmann Speed Distribution With Analytical Integration

The Maxwell-Boltzmann speed distribution is the probability distribution that describes the speeds of the particles of ideal gases. The Maxwell-Boltzmann speed distribution is valid for both un-mixed particles (one type of particle) and mixed particles (two types of particles). For mixed particles, both types of particles follow the Maxwell-Boltzmann speed distribution. Also, the most probable speed is inversely proportional to the square root of the mass. The Maxwell-Boltzmann speed distribution of mixed particles is based on kinetic theory; however, it has never been derived from a mechanical point of view. This paper proves the Maxwell-Boltzmann speed distribution and the speed ratio of mixed particles based on probability analysis and Newton’s law of motion. This paper requires the probability density function (PDF) ψ^ab(u_a; v_a, v_b) of the speed u_a  of the particle with mass M_a  after the collision of two particles with mass M_a  in speed v_a  and mass M_b  in speed v_b . The PDF ψ^ab(u_a; v_a, v_b)  in integral form has been obtained before. This paper further performs the exact integration from the integral form to obtain the PDF ψ^ab(u_a; v_a, v_b)  in an evaluated form, which is used in the following equation to get new distribution P_new^a(u_a)  from old distributions P_old^a(v_a) and P_old^b(v_b). When P_old^a(v_a) and P_old^b(v_b)  are the Maxwell-Boltzmann speed distributions, the integration P_new^a(u_a)  obtained analytically is exactly the Maxwell-Boltzmann speed distribution. P_new^a(u_a)=∫_0^∞ ∫_0^∞ ψ^ab(u_a;v_a,v_b) P_old^a(v_a) P_old^b(v_b) dv_a dv_b,    a,b = 1 or 2 The mechanical proof of the Maxwell-Boltzmann speed distribution presented in this paper reveals the unsolved mechanical mystery of the Maxwell-Boltzmann speed distribution since it was proposed by Maxwell in 1860. Also, since the validation is carried out in an analytical approach, it proves that there is no theoretical limitation of mass ratio to the Maxwell-Boltzmann speed distribution. This provides a foundation and methodology for analyzing the interaction between particles with an extreme mass ratio, such as gases and neutrinos.

Opportunities and Barriers of Telemedicine in Rheumatology: A Participatory Mixed-Methods-Study (Preprint)

BACKGROUND The global burden of rheumatic and musculoskeletal diseases (RMDs) is rising. Professional ressources in rheumatology are scarce. The use of telemedicine could improve access to RMD care. Despite all its promises, telemedicine is still not widely implemented in RMD care. OBJECTIVE To investigate opportunities, barriers, acceptance, and preferences concerning telemedicine among RMD patients and professional stakeholders involved in RMD patient management. METHODS From November 2017 to December 2019 a participatory mixed-methods-study was conducted based on three parts: (1) qualitative expert interviews with RMD patients and professional stakeholders that were used to participatively design (2) a national paper-based patient survey. The survey results were hence discussed in (3) focus groups with patient representatives and rheumatologists. RESULTS Fifteen patients and 26 professional stakeholders participated in the qualitative and further 766 patients took part in the quantitative research. The qualitative interview data reveals opportunities and barriers from the patients' (n=5) and professional stakeholders’(n=23) perspectives: Patients appreciate the potentials of telemedicine to overcome space and time in health care. In contrast, the loss of personal patient-doctor contact is the main concern of patients regarding telemedicine use. Personal contact is equated with physical face-to-face contact, which could be reduced by implementing telemedicine, thus negatively influencing the patient-doctor relationship. Professional stakeholders expect telemedicine to contribute to effective allocation of scarce resources in rheumatology care. This is countered by the absence of physical examinations and organizational challenges as barriers of the use of telemedicine. Both, patients and professional stakeholders describe telemedicine as something broad and complex to define. These qualitative findings align with the survey results: 38% (264/690) of the surveyed patients refuse to try telemedicine, 32% (216/690) are not sure, and 30% (210/690) would like to try telemedicine. ‘No personal contact with the doctor’ (64%, 220/346) was most frequently chosen as a reason against telemedicine, followed by ‘Data security’ (28%, 96/346). Patients prefer to use the telephone (60%, 206/341) over video-consultations (35%, 118/341) as telemedicine use cases. Only 2 (0.3%, 2/714) survey participants indicated that they already had a video consultation with their physician. The focus groups revealed a homogeneous spectrum of opinions with participants confirming the survey results. Patients (n=10) emphasize the high relevance of physical doctor-patient contact. Rheumatologists (n=4) highlight the potential of telemedicine, as a support of existing care structures. However, the exact integration of telemedicine into medical routines remains unclear, especially in view of scarce time resources in rheumatology care. CONCLUSIONS As digital transformation of rheumatology care progresses, the desire for a close patient-doctor relationship persists. Many study participants fear that the use of telemedicine will have negative effects on patient-doctor relationship and therefore oppose the use of telemedicine. We identified further barriers and opportunities, such as information needs, digital infrastructure and equipment requirements, and patient preferences on the composition of digital services, to guide the design and implementation of telemedicine in rheumatology care.

Discrete adjoint aerodynamic shape optimization using symbolic analysis with OpenFEMflow

The combination of gradient-based optimization with the adjoint method for sensitivity analysis is a very powerful and popular approach for aerodynamic shape optimization. However, differentiating CFD codes is a time consuming and sometimes a challenging task. Although there are a few open-source adjoint CFD codes available, due to the complexity of the code, they might not be very suitable to be used for educational purposes. An adjoint CFD code is developed to support students for learning adjoint aerodynamic shape optimization as well as developing differentiated CFD codes. To achieve this goal, we used symbolic analysis to develop a discrete adjoint CFD code. The least-squares finite element method is used to solve the compressible Euler equations around airfoils in the transonic regime. The symbolic analysis method is used for exact integration to generate the element stiffness and force matrices. The symbolic analysis is also used to compute the exact derivatives of the residuals with respect to both design variables (e.g., the airfoil geometry) and the state variables (e.g., the flow velocity). Besides, the symbolic analysis allows us to compute the exact Jacobian of the governing equations in a computationally efficient way, which is used for Newton iteration. The code includes a build-in gradient-based optimization algorithm and is released as open-source to be available freely for educational purposes.