Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study

BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.

Impact of Pollutant Concentration and Particle Deposition on the Radiative Flow of Casson-Micropolar Fluid between Parallel Plates

Assessing the behaviour and concentration of waste pollutants deposited between two parallel plates is essential for effective environmental management.Determining the effectiveness of treatment methods in reducing pollution scales is made easier by analysing waste discharge concentrations.The waste discharge concentration analysis is useful for assessing how effectively wastewater treatment techniques reduce pollution levels.This study aims to explore the Casson micropolar fluid flow through two parallel plates with the influence of pollutant concentration and thermophoretic particle deposition.To explore the mass and heat transport features,thermophoretic particle deposition and thermal radiation are considered.The governing equations are transformed into ordinary differential equations with the help of suitable similarity transformations.The Runge-Kutta-Fehlberg’s fourthfifth order technique and shooting procedure are used to solve the reduced set of equations and boundary conditions.The integration of a neural network model based on the Levenberg-Marquardt algorithm serves to improve the accuracy of predictions and optimize the analysis of parameters.Graphical outcomes are displayed to analyze the characteristics of the relevant dimensionless parameters in the current problem.Results reveal that concentration upsurges as the micropolar parameter increases.The concentration reduces with an upsurge in the thermophoretic parameter.An upsurge in the external pollutant source variation and the local pollutant external source parameters enhances mass transport.The surface drag force declines for improved values of porosity and micropolar parameters.

Strength of circular concrete columns under concentric compression

An experimental study, in which six columns were loaded concentrically toinvestigate the behavior of reinforced normal strength and high strength circular columns underconcentric compression, is described. The concrete strengths of the columns were 30 MPa and 60 MPa.The primary variables considered were the concrete strength and the amount of transversereinforcement. Test results indicate that smaller hoop spacing provides higher column capacity andgreater strength enhancement in a confined concrete core of columns. For the same lateralconfinement, high strength concrete columns develop lower strength enhancement than normal strengthconcrete columns. Both the strength enhancement ratio (f'_(cc) /f'_(co)) and the column capacityratio (P_(test)/P_o) were observed to show linear increase variations with rho_s f_(yt)/f'_c incircular columns.

Shaking table test and numerical analysis of a 1:12 scale model of a special concentrically braced steel frame with pinned connections

This paper describes shaking table tests of a 1：12 scale model of a special concentrically braced steel frame with pinned connections, which was fabricated according to a one-bay braced frame selected from a typical main factory building of a large thermal power plant. In order to investigate the seismic performance of this type of structure, several ground motion accelerations with different levels for seismic intensity Ⅷ, based on the Chinese Code for Seismic Design of Buildings, were selected to excite the model. The results show that the design methods of the members and the connections are adequate and that the structural system will perform well in regions of high seismicity. In addition to the tests, numerical simulations were also conducted and the results showed good agreement with the test results. Thus, the numerical model is shown to be accurate and the beam element can be used to model this structural system.

Wave Loading on Concentric Porous Cylinders with Varying Porosity

Wave diffraction of two concentric porous cylinders with varying porosity was studied by using an analytical method based on eigenfunction matching.The fluid domain around the cylinders is divided into three sub-domains and in each sub-domain an eigenfunction expansion of the velocity potential is obtained by satisfying the Laplace equation,the boundary conditions on the free surface and on the sea bed.The unknown coefficients of eigenfunction expansions are determined by boundary conditions on the porous hulls.In the paper,the boundary conditions are based upon the assumption that the flow in the porous medium is governed by Darcy's law.Two porous-effect parameters applied on two porous cylinders are functions of the vertical coordinate instead of the constant.Wave loading on the outer and inner cylinder is presented in the numerical results.

Numerical investigation of laminar heat transfer and nanofluid flow between two porous horizontal concentric cylinders

In this study, the laminar heat transfer and nanofluid flow between two porous horizontal concentric cylinders was investigated. The problem is investigated in two different geometries and the Re=10, 25, 50, 75, 100 and volume fraction 0, 0.2%, 0.5%, 2% and 5% that related to copper nanoparticles, and porous medium porosity of 0.5 and 0.9. Compared to the first geometry, the convective coefficient in the second geometry increases by 8.3%, 7% and 5.5% at Reynolds numbers of 100, 75 and 50, respectively. Comparison of the outlet temperatures for two heat fluxes of 300 and 1200 W/m^2 indicates a 2.5% temperature growth by a fourfold increase in the heat fluxes. Also, the higher Nusselt number is associated with the second geometry occurring at porosities of 0.9 and 0.5, respectively. In both geometries, the Nusselt number values at the porosity of 0.9 are higher, which is due to the increased nanofluid convection at higher porosities. The velocity of the nanofluid experiences a two-fold increase at the outlet compared to its inlet velocity in the first geometry and for both porosities. Similarly, a three-fold increase was achieved in the second geometry and for both porosities.

SATELLITE-BASED ANALYSIS ON THE CONCENTRIC EYEWALL REPLACEMENT CYCLES OF SUPER TYPHOON MUIFA (1109)

Multisatellite data is used to analyze the characteristics of three eyewall replacement cycles(ERCs) during the lifetime of Typhoon Muifa(1109).Spiral rainbands evolutions,concentric eyewall(CE) structure modes,CE durations,and intensity changes are discussed in detail.In addition,an ERC evolution model of Typhoon Muifa is given.There are four main findings.(1) The outer spiral rainband joins end to end to form the outer eyewall after it disconnects from the original(inner) eyewall.The inner eyewall weakens as the outer eyewall becomes axisymmetric and is intensified.The contraction of the outer eyewall causes the inner eyewall to dissipate rapidly.Finally,the ERC ends with an annular eyewall or spiral rainbands.(2) Although the CE duration times of Typhoon Muifa's three ERCs covered a large range,the CE structures were all maintained for approximately 5 h from the formation of the axisymmetric outer eyewall to the end of the cycle.(3) There is no obvious precipitation reflectivity in the eye or moat region for the subsidence flow.The convection within the two eyewalls is organized as a radially outward slope with increasing height.(4) Typhoon intensity estimation results based on ADT may not explain the intensity variations associated with ERC correctly,while the typhoon's warm core data retrieved from AMSU-A works well.

Concept Development and Implementation of Family Care/Caring Theory in Concentric Sphere Family Environment Theory

Caring is directed toward a variety of things. One of them is thought to be the concept of “family caring” aimed at families. This study attempts to clarify family caring and develop Family Care/ Caring Theory (FCCT), with the aim of implementing it in conjunction with an existing family nursing theory, the Concentric Sphere Family Environment Theory (CSFET). In Japan and in Hong Kong, family ethnography (including formal interviews) was conducted. As a result, the item “family health care nurses and their colleagues” was added to the family external environment of the CSFET. In the family environment, evidence was obtained to the effect that the family system unit is cared for by the nursing professional, and conversely the family system unit cares for the nursing professional, in a circular transaction. Observing the two-dimensional plane formed by the structural distance and functional distance, family caring assumes a structure of concentric circles, and according to transactions, the structural distance and functional distance between the nursing professional and family system unit are gradually approached, and through deepening of mutual trust maintain an appropriate distance. Moreover observing the three-dimensional space-time continuum which is created through addition of the temporal distance, family caring forms a helical structure. As transactions are repeated along the temporal axis, the family system unit’s self-actualization of other individuals and the self-actualization of the nursing professional are realized. Through these processes, a family care/caring relationship is reinforced and established. This is the concept of FCCT. Through future utilization in clinical settings this will be empirically substantiated, and it will be necessary to continue making creative corrections and revisions.

Case study on stratospheric and mesospheric concentric gravity waves generated by deep convection

Concentric gravity waves(CGWs)in the middle and upper atmosphere show wave-coupling processes between the lower atmosphere and the middle and upper atmosphere.In this research,we analyzed a case of CGWs detected simultaneously by the AIRS(Atmospheric Infrared Sounder)and the VIIRS/DNB(Day/Night Band of the Visible Infrared Imager Radiometer Suite)in the stratosphere and mesosphere.Results showed that gravity waves(GWs)were generated by the collocated Hurricane Bejisa on the island of Mauritius.The AIRS data showed arc-like phase fronts of GWs with horizontal wavelengths of 190 and 150 km at 21:08 coordinated universal time(UTC)on 1 January 2014 and at 10:00 UTC on 2 January 2014,whereas the DNB observed arced GWs with horizontal wavelengths of 60 and 150 km in the same geographic regions at 22:24 UTC.The characteristics of CGW parameters in the stratosphere(~40 km)and the mesosphere(~87 km),such as the vertical wavelength,intrinsic frequency,and intrinsic horizontal phase speed,were first derived together with the background winds from ERA5 reanalysis data and Horizontal Wind Model data through the dispersion relationship of GWs and the wind-filtering theory.

Walking and Aerobic Capacity in Old Adults after Concentric and Eccentric Endurance Exercise at Self-Selected Intensities

Self-selected exercise intensity can be a useful exercise prescription tool for older adults;however, it is not known if it can elicit improvements in walking and aerobic capacity. In older adults, effects of concentric or eccentric endurance exercise at self-selected walking speed were examined on 1-mile indoor walk performance, predicted maximum oxygen uptake and physiological parameters. Twenty-four older adults (67 ± 4 years) completed 3 × 30 min treadmill walks per week for 12-weeks on level (LTW, n = 11, 0%) or downhill (DTW, n = 13, ﹣10%) treadmill gradient at a self- selected speed, which progressed every 4 weeks. Maximal oxygen uptake was predicted using a 1-mile walk at 4-week intervals with physiological responses recorded using a portable metabolic system. One-mile walking speed increased from baseline following 8- and 12-weeks (12 weeks: LTW: 13% ± 6%, DTW: 14% ± 9%,

The forward and inverse problem of cardiac magnetic fields based on concentric ellipsoid torso-heart model

This paper constructs a concentric ellipsoid torso-heart model by boundary element method and investigates the impacts of model structures on the cardiac magnetic fields generated by both equivalent primary source--a current dipole and volume currents. Then by using the simulated magnetic fields based on torso-heart model as input, the cardiac current sources--an array of current dipoles by optimal constrained linear inverse method are constructed. Next, the current dipole array reconstruction considering boundaries is compared with that in an unbounded homogeneous medium. Furthermore, the influence of random noise on reconstruction is also considered and the reconstructing effect is judged by several reconstructing parameters.

Effect of initial crystallization temperature and surface diffusion on formation of GaAs multiple concentric nanoring structures by droplet epitaxy

GaAs multiple concentric nano-ring structures(CNRs)are prepared with multistep crystallization procedures by droplets epitaxy on GaAs(001)to explore the influence of different initial crystallization temperatures on CNRs morphology.Atomic force microscope(AFM)images show that GaAs nanostructures are more likely to form elliptical rings due to diffusion anisotropy.Meanwhile,with the increase of initial crystallization temperature,the inner ring height and density of CNRs are increased,and outer rings are harder to form.In addition,the mechanism of formation of CNRs is discussed by classical nucleation theory and diffusion theory.The method can be used to calculate the diffusion activation energy of gallium atoms(0.7±0.1 eV)on the GaAs(001)surface conveniently.

Concentric Annular Clearance-Controllable Pressure Characteristics Research of a High Pressure Pneumatic Pressure Assembly

High pressure is an important development orientation in pneumatic field,since it can not only improve dynamic characteristics of pneumatic system but also decrease the size of components and mounting space.Due to the advantages of high energy density and high instant expansibility,high pressure gas has been widely used in many applications.However,systematic researches are lacked especially in pressure characteristics which are very important in pneumatic system at present.In a high pressure pneumatic system,the pressure of a fixed cavity with annular clearance needs to be controlled within a wide range,so a single stage proportional slide valve is proposed to satisfy the requirements of high pressure and low flow rate.First,working principle and structure of the pressure assembly and the slide valve are introduced.Then mathematical model of the high pressure pneumatic system is built up;controllable pressure range is simulated,and influence of uncertain factors,such as fit clearance of the pressure valve and the cavity on controllable pressure,is discussed.Finally,a test bench of the pressure assembly is built up,and the controllable pressure and step response experiments are carried out.Both simulation and experimental results show that the designed slide valve can satisfy the requirements well.The proposed clearance presumption method based on simulation and experimental results is valuable for indirect measurement of processing tolerance.

Geometric shapes of the interface surface of bicomponent flows between two concentric rotating cylinders

In this paper, the shape problem of interface of bicomponent flows between two concentric rotating cylinders is investigated. With tensor analysis, the problem is reduced to an energy functional isoperimetric problem when neglecting the effects of the dissipative energy caused by viscosity. We derive the associated Euler-Lagrangian equation, which is a nonlinear elliptic boundary value problem of the second order. Moreover, by considering the effects of the dissipative energy, we propose another total energy functional to characterize the geometric shape of the interface, and obtain the corresponding Euler-Lagrangian equation, which is also a nonlinear elliptic boundary value problem of the second order. Thus, the problem of the geometric shape is converted into a nonlinear boundary value problem of the second order in both cases.

Rheological properties and concentration evolution of thickened tailings under the coupling effect of compression and shear

Cemented paste backfill(CPB)is a key technology for green mining in metal mines,in which tailings thickening comprises the primary link of CPB technology.However,difficult flocculation and substandard concentrations of thickened tailings often occur.The rheological properties and concentration evolution in the thickened tailings remain unclear.Moreover,traditional indoor thickening experiments have yet to quantitatively characterize their rheological properties.An experiment of flocculation condition optimization based on the Box-Behnken design(BBD)was performed in the study,and the two response values were investigated:concentration and the mean weighted chord length(MWCL)of flocs.Thus,optimal flocculation conditions were obtained.In addition,the rheological properties and concentration evolution of different flocculant dosages and ultrafine tailing contents under shear,compression,and compression-shear coupling experimental conditions were tested and compared.The results show that the shear yield stress under compression and compression-shear coupling increases with the growth of compressive yield stress,while the shear yield stress increases slightly under shear.The order of shear yield stress from low to high under different thickening conditions is shear,compression,and compression-shear coupling.Under compression and compression-shear coupling,the concentration first rapidly increases with the growth of compressive yield stress and then slowly increases,while concentration increases slightly under shear.The order of concentration from low to high under different thickening conditions is shear,compression,and compression-shear coupling.Finally,the evolution mechanism of the flocs and drainage channels during the thickening of the thickened tailings under different experimental conditions was revealed.

Dynamics and genetic regulation of macronutrient concentrations during grain development in maize

Nitrogen(N), phosphorus(P), and potassium(K) are essential macronutrients that are crucial not only for maize growth and development, but also for crop yield and quality. The genetic basis of macronutrient dynamics and accumulation during grain filling in maize remains largely unknown. In this study, we evaluated grain N, P, and K concentrations in 206 recombinant inbred lines generated from a cross of DH1M and T877 at six time points after pollination. We then calculated conditional phenotypic values at different time intervals to explore the dynamic characteristics of the N, P, and K concentrations. Abundant phenotypic variations were observed in the concentrations and net changes of these nutrients. Unconditional quantitative trait locus(QTL) mapping revealed 41 non-redundant QTLs, including 17, 16, and 14 for the N, P, and K concentrations, respectively. Conditional QTL mapping uncovered 39 non-redundant QTLs related to net changes in the N, P, and K concentrations. By combining QTL, gene expression, co-expression analysis, and comparative genomic data, we identified 44, 36, and 44 candidate genes for the N, P, and K concentrations, respectively, including GRMZM2G371058 encoding a Doftype zinc finger DNA-binding family protein, which was associated with the N concentration, and GRMZM2G113967encoding a CBL-interacting protein kinase, which was related to the K concentration. The results deepen our understanding of the genetic factors controlling N, P, and K accumulation during maize grain development and provide valuable genes for the genetic improvement of nutrient concentrations in maize.

Trends of surface ozone based on hourly concentrations in the Beijing–Tianjin–Hebei region during 2017–2021

As a typical secondary air pollutant,surface ozone has been monitored routinely since 2013 in China.Most studies on the spatiotemporal variation of ozone have been centered around the daily maximum 8-h average,with little attention paid to the trends of hourly ozone,especially hourly ozone exceedances.Focusing on hourly ozone exceedances and peak values,the spatiotemporal trends of hourly ozone at 77 sites in 13 cities of the Beijing-Tianjin-Hebei(BTH)region during 2017-2021 were analyzed in this study.The number of hours with exceedances(N_(H200))in 2019 was nearly three times that of 2021.On a five-year average,the percentage of cumulative NH200 in June accounted for up to 40.5%of all hourly exceedances.Cities in central Hebei Province had the highest cumulative annual N_(H200).June had the highest average hourly ozone exceeded multiples of 0.158.The top two cities with the highest average exceeded multiple were Tangshan(0.166)and Beijing(0.158).Tangshan and Xingtai ranked as the top two in terms of the mean of the 10 highest daily maximum ozone concentrations(MTDM),with 286.74 and 285.37μg m^(−3),respectively.The gap between the MTDM and the daily maximum of hourly ozone averaged over all sites had narrowed to 97.88μg m^(−3) in 2021,much lower than that in other years,which indicated that the stability and convergence of ozone pollution in BTH region had been enhanced in 2021 to some extent.

A Facile Li_(2)TiO_(3) Surface Modification to Improve the Structure Stability and Electrochemical Performance of Full Concentration Gradient Li-Rich Oxides

Full concentration gradient lithium-rich layered oxides are catching lots of interest as the next generation cathode for lithium-ion batteries due to their high discharge voltage,reduced voltage decay and enhanced rate performance,whereas the high lithium residues on its surface impairs the structure stability and long-term cycle performance.Herein,a facile multifunctional surface modification method is implemented to eliminate surface lithium residues of full concentration gradient lithium-rich layered oxides by a wet chemistry reaction with tetrabutyl titanate and the post-annealing process.It realizes not only a stable Li_(2)TiO_(3)coating layer with 3D diffusion channels for fast Li^(+)ions transfer,but also dopes partial Ti^(4+)ions into the sub-surface region of full concentration gradient lithium-rich layered oxides to further strengthen its crystal structure.Consequently,the modified full concentration gradient lithium-rich layered oxides exhibit improved structure stability,elevated thermal stability with decomposition temperature from 289.57℃to 321.72℃,and enhanced cycle performance(205.1 mAh g^(-1)after 150 cycles)with slowed voltage drop(1.67 mV per cycle).This work proposes a facile and integrated modification method to enhance the comprehensive performance of full concentration gradient lithium-rich layered oxides,which can facilitate its practical application for developing higher energy density lithium-ion batteries.

An Exact Analytical Method for Magnetic Field Computation and Electromagnetic Torque in a Concentric Magnetic Gear

准确计算磁力齿轮电磁转矩是设计、分析磁力齿轮的关键,采用二维全局解析法计算同心式磁力齿轮气隙磁场。求解场域划分为内外转子永磁体、内外两层气隙和调磁定子的槽形区域,3类子区域的拉普拉斯方程和泊松方程通过边界连续条件建立联系。得到内外两层气隙区域的矢量磁位磁通密度解析表达式,有利于方便、快速、精确地计算任意转子位置的电磁转矩。计算了内外两层气隙磁场和内外转子电磁转矩,将气隙磁场波形和内外转子电磁转矩波形分别与二维有限元法计算波形作比较,结果吻合,证明了方法的正确性和有效性。

Similarity Reductions of Nearly Concentric KdV Equation

Basing on the direct method developed by Clarkson and Kruskal, the nearly concentric Korteweg-de Vries （ncKdV） equation can be reduced to three types of （1＋1）-dimensional variable coefficients partial differential equations （PDEs） and three types of variable coefficients ordinary differential equation. Furthermore, three types of （1＋1）-dimensional variable coefficients PDEs are all reduced to constant coefficients PDEs by some transformations.