Analytical Treatment Research Articles

Early antiretroviral therapy favors post-treatment SIV control associated with the expansion of enhanced memory CD8+ T-cells

HIV remission can be achieved in some people, called post-treatment HIV controllers, after antiretroviral treatment discontinuation. Treatment initiation close to the time of infection was suggested to favor post-treatment control, but the circumstances and mechanisms leading to this outcome remain unclear. Here we evaluate the impact of early (week 4) vs. late (week 24 post-infection) treatment initiation in SIVmac251-infected male cynomolgus macaques receiving 2 years of therapy before analytical treatment interruption. We show that early treatment strongly promotes post-treatment control, which is not related to a lower frequency of infected cells at treatment interruption. Rather, early treatment favors the development of long-term memory CD8+ T cells with enhanced proliferative and SIV suppressive capacity that are able to mediate a robust secondary-like response upon viral rebound. Our model allows us to formally demonstrate a link between treatment initiation during primary infection and the promotion of post-treatment control and provides results that may guide the development of new immunotherapies for HIV remission.

Telenursing with elderly people in home care service during the COVID-19 pandemic: quasi-experimental study.

to evaluate telenursing as a support technology in the transition of care for elderly people and their caregivers in the context of home care during the COVID-19 pandemic. quasi-experimental before-after, non-randomized study, with 219 elderly people and caregivers from the home care service, divided into 131 in the intervention groups and 88 in the control group. Analytical treatment, descriptive and inferential statistics were carried out. 1691 calls were made, 1515 to the intervention group and 176 to the control group. It was observed that in the first call there is a greater need for interventions to promote health and this quantity decreases throughout the calls with a significant result (p-value < 0.001). The outcomes analyzed were hospitalization, death, discharge or continuation of the home care service and it was observed that the chance of discharge from the service was nine times greater in the intervention group. Continuity of care from the home care service and discharge after the end of the calls were also significant (p-value < 0.001). telenursing was a technology to support care, mainly for health promotion and discharge from home care services.

Criteria for assessing evidence for biomarker-targeted therapies in rare cancers-an extrapolation framework.

Advances in targeted therapy development and tumor sequencing technology are reclassifying cancers into smaller biomarker-defined diseases. Randomized controlled trials (RCTs) are often impractical in rare diseases, leading to calls for single-arm studies to be sufficient to inform clinical practice based on a strong biological rationale. However, without RCTs, favorable outcomes are often attributed to therapy but may be due to a more indolent disease course or other biases. When the clinical benefit of targeted therapy in a common cancer is established in RCTs, this benefit may extend to rarer cancers sharing the same biomarker. However, careful consideration of the appropriateness of extending the existing trial evidence beyond specific cancer types is required. A framework for extrapolating evidence for biomarker-targeted therapies to rare cancers is needed to support transparent decision-making. To construct a framework outlining the breadth of criteria essential for extrapolating evidence for a biomarker-targeted therapy generated from RCTs in common cancers to different rare cancers sharing the same biomarker. A series of questions articulating essential criteria for extrapolation. The framework was developed from the core topics for extrapolation identified from a previous scoping review of methodological guidance. Principles for extrapolation outlined in guidance documents from the European Medicines Agency, the US Food and Drug Administration, and Australia's Medical Services Advisory Committee were incorporated. We propose a framework for assessing key assumptions of similarity of the disease and treatment outcomes between the common and rare cancer for five essential components: prognosis of the biomarker-defined cancer, biomarker test analytical validity, biomarker actionability, treatment efficacy, and safety. Knowledge gaps identified can be used to prioritize future studies. This framework will allow systematic assessment, standardize regulatory, reimbursement and clinical decision-making, and facilitate transparent discussions between key stakeholders in drug assessment for rare biomarker-defined cancers.

A numerical study of relativistic oblique shock reflection

Shocks are ubiquitous in astrophysical sources, many of which involve relativistic bulk motions, leading to the formation of relativistic shocks. Such relativistic shocks have so far been studied mainly in one dimension, for simplicity, but the complex nature of the relevant astrophysical flows often requires higher-dimensional studies. Here, we study the two-dimensional problem of the reflection of a planer shock off of a wall for a general incidence angle and a cold unshocked medium. We use primarily relativistic hydrodynamic numerical simulations and elaborately compare the results to an analytic treatment. The simulations are performed both in the rest frame S of the unshocked fluid, where the dimensionless proper speed of the singly shocked fluid is u1=Γ1β1 and the shock incidence angle is α1, and in the rest frame S′ of the point P of intersection of the incident shock and the wall for regular reflection (RR). Good agreement is obtained between the simulations in these two frames and with the analytic solution. The establishment of a steady flow in frame S′ is explored, along with the transition between the strong and weak shock RR solutions. The transition line between RR and Mach reflection is studied numerically in the u1 − α1 plane and found to coincide with the analytic detachment/sonic line. The flow properties along the sonic line are investigated in detail focusing on how they vary between the Newtonian and relativistic limits.

Non-linear black hole ringdowns: An analytical approach

Due to the nature of gravity, non-linear effects are left imprinted in the quasi-normal modes generated in the ringdown phase of the merger of two black holes. We offer an analytical treatment of the quasi-normal modes at second-order in black hole perturbation theory which takes advantage from the fact that the non-linear sources are peaked around the light ring. As a byproduct, we describe why the amplitude of the second-order mode relative to the square of the first-order amplitude depends only weakly on the initial condition of the problem.

The chaotic four-body problem in Newtonian gravity – II. An ansatz-based approach to analytical solutions

ABSTRACT In this paper, we continue our analysis of the chaotic four-body problem and our study of binary–binary interactions in star clusters. We present a general ansatz-based analytical treatment using statistical mechanics, where each outcome of the four-body problem is regarded as some variation of the three-body problem. For example, when two single stars are produced (the 2 + 1 + 1 outcome), each ejection event is modelled as its own three-body interaction by assuming that the ejections are well separated in time. This is a generalization of the approach adopted in Paper I, based on the density-of-states formalism. There are three possible outcomes for the four-body problem with negative total energies: 2 + 2, 2 + 1 + 1, and 3 + 1. For each outcome, we apply an ansatz-based approach to deriving analytical distribution functions that describe the properties of the products of chaotic four-body interactions involving point particles. To test our theoretical distributions, we perform a set of scattering simulations in the equal-mass point-particle limit using FEWBODY, where we vary the initial ratio of binary semimajor axes. We compare our final theoretical distributions to the simulations for each particular scenario, finding consistently good agreement between the two. The highlights of our results include that binary–binary scatterings act to systematically destroy binaries producing instead a binary and two ejected stars (when the initial binary semimajor axes are similar) or a stable triple (when the initial semimajor axes are very different). The 2 + 2 outcome produces the widest binaries, and the 2 + 1 + 1 outcome produces the most compact binaries.

Capillary-lubrication force exerted on a two-dimensional particle moving towards a thin fluid film

A rigid object moving in a viscous fluid and in close proximity to an elastic wall experiences self-generated elastohydrodynamic interactions. This has been the subject of intense research activity, with recent and growing attention given to the particular case of elastomeric and gel-like substrates. Here, we address the situation where the elastic wall is replaced by a capillary surface. Specifically, we analyse the lubrication flow generated by the prescribed normal motion of a rigid infinite cylinder near the deformable interface separating two immiscible and incompressible viscous fluids. Using a combination of analytical and numerical treatments, we compute the emergent capillary-lubrication force at leading order in capillary compliance, and characterize its dependencies with the interfacial tension, viscosities of the fluids, and length scales of the problem. Interestingly, we identify two main contributions: (i) a velocity-dependent adhesive-like force; (ii) an acceleration-dependant inertia-like force. Our results may have implications for the mobility of colloids near complex interfaces and for the motility of confined microbiological entities.

Quantifying the effect of end support restraints on vibration serviceability of mass timber floor systems: Testing

Design of mass timber floor systems is commonly governed by vibration serviceability due to high stiffness-to-weight ratio and low inherent damping of timber. Research and design practice have shown that static deflection under a concentrated load and fundamental natural frequency can be effective and robust indicators for vibration performance of mass timber floors. These design parameters are normally calculated by assuming simply supported conditions in existing design methods. However, such an assumption deviates from actual floor supports, especially in platform-framed buildings, and in-situ end support restraints have been widely recognized as a significant factor affecting the vibration performance. The purpose of the study is to quantify the influence of end support restraints on vibration serviceability of mass timber floors in platform construction through a comprehensive experimental program and analytical treatment. This paper is the first part and focus specifically on the experimental work on cross-laminated timber (CLT) panels. In particular, extensive laboratory tests have been conducted on different CLT floor panels with various end support restraints induced by top loads, self-tapping screws and steel angle brackets. The fundamental natural frequency and mid-span deflection under a concentrated load were measured for each end support configuration. The rotational restraint stiffness was determined by comparing results of restrained supports to those of simple supports and represented as end fixity factors. The analysis of test results shows that the CLT floor-to-wall connection exhibited inherent non-linear behaviour and such characteristic was more significant for higher top loads. Compared with screws and brackets, the top loads dominated the partially restrained effect but such dominance gradually diminished for lower-level top loads. In addition, support wall thickness notably impacts the support restraint. It was then suggested that the clear span could be used to determine deflection and frequency in the design, but further investigation is needed.

Collective radiative interactions in the discrete truncated Wigner approximation

Interfaces of light and matter serve as a platform for exciting many-body physics and photonic quantum technologies. Due to the recent experimental realization of atomic arrays at sub-wavelength spacings, collective interaction effects such as superradiance have regained substantial interest. Their analytical and numerical treatment is however quite challenging. Here we develop a semiclassical approach to this problem that allows to describe the coherent and dissipative many-body dynamics of interacting spins while taking into account lowest-order quantum fluctuations. For this purpose we extend the discrete truncated Wigner approximation, originally developed for unitarily coupled spins, to include collective, dissipative spin processes by means of truncated correspondence rules. This maps the dynamics of the atomic ensemble onto a set of semiclassical, numerically inexpensive stochastic differential equations. We benchmark our method with exact results for the case of Dicke decay, which shows excellent agreement. For small arrays we compare to exact simulations, again showing good agreement at early times and at moderate to strong driving, and to a second order cumulant expansion. We conclude by studying the radiative properties of a spatially extended three-dimensional, coherently driven gas and compare the coherence of the emitted light to experimental results.

Study on the simplified MCH equation and the combined KdV–mKdV equations with solitary wave solutions

This paper is concerned with the traveling wave solutions and analytical treatment of the simplified MCH equation and the combined KdV–mKdV equations. Based on a polynomial about x and t, the rational solutions are investigated. The abundant soliton and periodic wave solutions are obtained by using a direct function. The hyperbolic-type and trigonometric-type solutions are given by utilizing the improved tan(ϕ/2)-expansion method. The dynamic properties of these derived results are shown in some three-dimensional, density and 2D plots. Traveling wave solutions are utilized to depict water waves in the mentioned equations, and that is used in physical science to model quantum field theory, dust-acoustic waves, ion acoustic waves, which is taken into account through the application of the improved tan(ϕ/2)-expansion technique. In addition, the recommended technique allowed us to produce some dynamical wave patterns of kink, kink single soliton, single soliton, compacton, periodic shape and other structures are developed, which are shown using three-dimensional, density and 2D plots to more clearly illustrate the physical layout. The method is one of the proficient and effective approaches which have swiftly developed in order to searching appropriate responses to partial differential equations with nonlinear sciences.

HIV-1 reservoir size after neonatal antiretroviral therapy and the potential to evaluate antiretroviral-therapy-free remission (IMPAACT P1115): a phase 1/2 proof-of-concept study

Infants born with HIV-1 require lifelong antiretroviral therapy (ART). We aimed to assess whether very early ART in neonates might restrict HIV-1 reservoirs, an important step towards ART-free remission. IMPAACT P1115 is an ongoing, phase 1/2, proof-of-concept study in which infants were enrolled at 30 research clinics in 11 countries (Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, the USA, Zambia, and Zimbabwe) into two cohorts. Infants at least 34 weeks' gestational age at high risk for in-utero HIV-1 with either untreated maternal HIV-1 (cohort 1) or who were receiving pre-emptive triple antiretroviral prophylaxis outside of the study (maternal ART permissible; cohort 2) were included. All infants initiated treatment within 48 h of life. Cohort 1 initiated three-drug nevirapine-based ART, and cohort 2 initiated three-drug nevirapine-based prophylaxis then three-drug nevirapine-based ART following HIV diagnosis by age 10 days. We added twice-daily coformulated oral ritonavir 75 mg/m2 and lopinavir 300 mg/m2 from 14 days of life and 42 weeks postmenstrual age. We discontinued nevirapine 12 weeks after two consecutive plasma HIV-1 RNA levels below limit of detection. We tracked virological suppression, safety outcomes, and meeting a predetermined biomarker profile at age 2 years (undetectable RNA since week 48, HIV-1 antibody-negative, HIV-1 DNA not detected, and normal CD4 count and CD4 percentage) to assess qualification for analytical treatment interruption. This study is registered with ClinicalTrials.gov, NCT02140255. Between Jan 23, 2015, and Dec 14, 2017, 440 infants were included in cohort 1 and 20 were included in cohort 2. 54 of these infants (34 from cohort 1 and 20 from cohort 2) had confirmed in-utero HIV-1 and were enrolled to receive study ART. 33 (61%) of 54 infants were female and 21 (39%) were male. The estimated probability of maintaining undetectable plasma RNA through to 2 years was 33% (95% CI 17-49) in cohort 1 and 57% (28-78) in cohort 2. Among infants maintaining protocol-defined virological control criteria through to study week 108, seven of 11 (64%, 95% CI 31-89) in cohort 1 and five of seven (71%, 29-96) in cohort 2 had no detected HIV-1 DNA. Ten of 12 (83%, 52-100) in cohort 1 and all seven (100%, 59-100) in cohort 2 tested HIV-1 antibody-negative at week 108. Among 54 infants initiated on very early ART, ten (19%; six in cohort 1 and four in cohort 2) met all criteria for possible analytical treatment interruption. Reversible grade 3 or 4 adverse events occurred in 15 (44%) of 34 infants in cohort 1 and seven (35%) of 20 infants in cohort 2. Very early ART for in-utero HIV-1 can achieve sustained virological suppression in association with biomarkers indicating restricted HIV-1 reservoirs by age 2 years, which might enable potential ART-free remission. National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Lah Number Mediated Analytical Two‐center Two‐electron Integrals of Coulomb Green Function of H‐like Orbitals for 1Σ States

AbstractEnergetics of two‐center two‐electron (2c–2e) systems carry challenges in theoretical understanding of Schrödinger equation (SE) for well‐known divergence of Coulomb interactions and nuclear separation (R) in modified H‐like AOs, Slater type orbitals (STOs), Gaussian type orbitals (GTOs), B‐spline, Sturmian function and etc. employed to VBT and MOT. Certain elegant computational and analytical techniques were developed for STO, GTO and other square integrable basis set within Born‐Oppenheimer (BO) approximation. STOs and GTOs have an essential limitation of absence of radial nodes. Thus, analytical treatment has become an urge for H‐like AOs. We have considered the diatomic molecules only for the sake of simplicity. Employing Sheffer identity in associated Laguerre polynomial/Whittaker‐M function forms of H‐like AOs and transforming integrals into elliptic coordinates with two nuclei on two foci furnishes exact, analytical and simple Coulomb integrals (Js) in terms of R. Lah number originated from for nuclear coordinates only due to Sheffer identity shows that energetics of diatomic molecules can be anticipated as extremum function of R. Therefore, the optimization of potential energy surface (PES) of electrons as gradient of R may lead to σ‐bond formation. In this paper, we have developed diagonal Js for bound states of H2 molecule.

Understanding participant perspectives around HIV cure-related studies involving antiretroviral analytical treatment interruption in the United Kingdom

BackgroundTo test efficacy, HIV cure-related trials often require a period of intensively monitored interruption of antiretroviral therapy (ART) (analytical treatment interruption or ATI). As individuals who started ART during primary HIV infection (PHI) are often recruited, we asked people already enrolled in an observational PHI study about their willingness and concerns around participating in cure-related studies involving ATIs. MethodsPeople who were diagnosed with PHI and started ART, attending two London HIV clinics, provided informed consent to complete a digital survey in clinic between 21/07/21 to October 31, 2023. Questions comprised of sociodemographics, motivations, concerns and practical considerations influencing willingness to participate in studies involving ATI. Hierarchical clustering of responses was performed using the ‘pheatmap’ R statistical package and ranked from most to least concerned. Responses were cross-referenced with enrolment into an ATI study which recruited from this cohort. ResultsOf 352 eligible participants, 75 completed the survey. The majority were white, cisgender men who have sex with men, 34/75 (45 %) were born outside the UK. 29 (39 %) expressed interest in joining ATI studies. Participants who were interested or unsure in joining ATI studies were primarily motivated (53/65, 82 % very or moderately interested) by an altruistic desire to help scientific research. Across all participants, onward HIV transmission was the predominant concern (67/75, 89 % very or moderately concerned), and similar levels of concerns reported if the HIV viral load threshold to restarting ART was increased from 500 to 50 000 copies/mL. Most participants preferred weekly (23/65, 35 %) or fortnightly (11/65, 17 %) viral load monitoring during an ATI. Before taking part in a study involving an ATI, participants stated they would prefer to discuss this with their HIV doctor (55/65, 85 %). ConclusionIn this small survey, 39 % of respondents expressed interest in joining studies involving ATIs, primarily for altruistic reasons. Participants were more interested in joining a potential ATI study if a novel intervention was included than simply an ATI alone. The main concern expressed was risk of viral transmission. To inform practical and study design considerations for future ATI studies, unrestricted access for mitigation of transmission risk should be included, and regular, frequent viral load monitoring is preferred.

Preferential selection of viral escape mutants by CD8+ T cell 'sieving' of SIV reactivation from latency.

HIV rapidly rebounds after interruption of antiretroviral therapy (ART). HIV-specific CD8+ T cells may act to prevent early events in viral reactivation. However, the presence of viral immune escape mutations may limit the effect of CD8+ T cells on viral rebound. Here, we studied the impact of CD8 immune pressure on post-treatment rebound of barcoded SIVmac293M in 14 Mamu-A*01 positive rhesus macaques that initiated ART on day 14, and subsequently underwent two analytic treatment interruptions (ATIs). Rebound following the first ATI (seven months after ART initiation) was dominated by virus that retained the wild-type sequence at the Mamu-A*01 restricted Tat-SL8 epitope. By the end of the two-month treatment interruption, the replicating virus was predominantly escaped at the Tat-SL8 epitope. Animals reinitiated ART for 3 months prior to a second treatment interruption. Time-to-rebound and viral reactivation rate were significantly slower during the second treatment interruption compared to the first. Tat-SL8 escape mutants dominated early rebound during the second treatment interruption, despite the dominance of wild-type virus in the proviral reservoir. Furthermore, the escape mutations detected early in the second treatment interruption were well predicted by those replicating at the end of the first, indicating that escape mutant virus in the second interruption originated from the latent reservoir as opposed to evolving de novo post rebound. SL8-specific CD8+ T cell levels in blood prior to the second interruption were marginally, but significantly, higher (median 0.73% vs 0.60%, p = 0.016). CD8+ T cell depletion approximately 95 days after the second treatment interruption led to the reappearance of wild-type virus. This work suggests that CD8+ T cells can actively suppress the rebound of wild-type virus, leading to the dominance of escape mutant virus after treatment interruption.

A drift‐diffusion based electrothermal model for organic thin‐film devices including electrical and thermal environment

AbstractWe derive and investigate a stationary model for the electrothermal behavior of organic thin‐film devices including their electrical and thermal environment. Whereas the electrodes are modeled by Ohm's law, the electronics of the organic device itself is described by a generalized van Roosbroeck system with temperature‐dependent mobilities and using Gauss–Fermi integrals for the statistical relation. The currents give rise to Joule heat which together with the heat generated by the generation/recombination of electrons and holes in the organic device occur as source terms in the heat flow equation that has to be considered on the whole domain. The crucial task is to establish that the quantities in the transfer conditions at the interfaces between electrodes and the organic semiconductor device have sufficient regularity. Therefore, we restrict the analytical treatment of the system to two spatial dimensions. We consider layered organic structures, where the physical parameters (total densities of transport states, reference energy levels , disorder parameter, basic mobilities, activation energies, relative dielectric permittivity, heat conductivity) are piecewise constant, and we work in a setting for some . We prove the existence of weak solutions using Schauder's fixed point theorem and a regularity result for strongly coupled systems with nonsmooth data and mixed boundary conditions that is verified by Caccioppoli estimates and a Gehring‐type lemma.

Analytical treatment with the Nucci reduction technique on the p-forced nonlinear Klein–Gordon equation

Analytical treatment with the Nucci reduction technique on the p-forced nonlinear Klein–Gordon equation

Static Stability of Planar Contacting Systems: Analytical Treatment in Euclidean Space

Abstract This paper gives an exact theory in Euclidean space for studying the static stability of planar rigid systems held by one or more frictional and frictionless contacts under gravity. Static stability analysis deals with determining the feasible locations of the Centre of gravity (CG) which ensure stability. The analysis is performed here in two steps- finding the equilibrium region and finding the stability region as a subset of the equilibrium region. The stability region is determined through the analytical treatment of an elegant geometric characterization. These results are also verified through elegant geometric reasoning based on curvature theory in-plane kinematics. In the end, stability analyses of some physical systems containing generic contacting curves are il- lustrated and the results are presented with physical interpretations.

Global history, the emergence of chaos and inducing sustainability in networks of socio-ecological systems.

In this study, we propose a simplified model of a socio-environmental system that accounts for population, resources, and wealth, with a quadratic population contribution in the resource extraction term. Given its structure, an analytical treatment of attractors and bifurcations is possible. In particular, a Hopf bifurcation from a stable fixed point to a limit cycle emerges above a critical value of the extraction rate parameter. The stable fixed-point attractor can be interpreted as a sustainable regime, and a large-amplitude limit cycle as an unsustainable regime. The model is generalized to multiple interacting systems, with chaotic dynamics emerging for small non-uniformities in the interaction matrix. In contrast to systems where a specific parameter choice or high dimensionality is necessary for chaos to emerge, chaotic dynamics here appears as a generic feature of the system. In addition, we show that diffusion can stabilize networks of sustainable and unsustainable societies, and thus, interconnection could be a way of increasing resilience in global networked systems. Overall, the multi-systems model provides a timescale of predictability (300-1000 years) for societal dynamics comparable to results from other studies, while indicating that the emergent dynamics of networks of interacting societies over longer time spans is likely chaotic and hence unpredictable.

Deterministic correlations enhance synchronization in oscillator populations with heterogeneous coupling.

Synchronization is a critical phenomenon that displays a pivotal role in a wealth of dynamical processes ranging from natural to artificial systems. Here, we untangle the synchronization optimization in a system of globally coupled phase oscillators incorporating heterogeneous interactions encoded by the deterministic-random coupling. We uncover that, within the given restriction, the added deterministic correlations can profoundly enhance the synchronizability in comparison with the uncorrelated scenario. The critical points manifesting the onset of synchronization and desynchronization transitions, as well as the level of phase coherence, are significantly shaped by the increment of deterministic correlations. In particular, we provide an analytical treatment to properly ground the mechanism underlying synchronization enhancement and substantiate that the analytical predictions are in fair agreement with the numerical simulations. This study is a step forward in highlighting the importance of heterogeneous coupling among dynamical agents, which provides insights for control strategies of synchronization in complex systems.

Application of the Variational Iteration Method for the time-fractional Kaup-Kupershmidt Equation and the Boussinesq-Burger equation

The variational iteration method is used to deal with linear and nonlinear differential equations. The main characteristics of the method lie in its flexibility and ability to accurately and easily solve nonlinear equations. In this work, a general framework is presented for a variational iteration method for the analytical treatment of partial differential equations in fluid mechanics. The Caputo sense is used to describe fractional derivatives. The time-fractional Kaup-Kupershmidt (KK) equation is investigated, as it is the solution of the system of partial differential equations via the Boussinesq-Burger equation. By comparing the results that are obtained by the variational iteration method with those obtained by the two-dimensional Legendre multiwavelet, the optimal homotopy asymptotic method (OHAM), the q-homotopy analysis transform method, the Laplace Adomian Decomposition Method, and the homotopy perturbation method, the first method proved to be very effective and convenient. The main methodology in this work is anticipated to be applied to various fractional calculus, linear, and nonlinear problems.