Spline Functions Research Articles

Deep learning reconstruction of pressure fluctuations in supersonic shock–boundary layer interaction

The long short-term memory deep-learning model is applied to supersonic shock–boundary layer interaction flow. The study aims to show how near-wall pressure fluctuations can be reconstructed from reduced (under-sampled) datasets of pressure signals. Predicting pressure fluctuations from reduced datasets could allow predictions using less expensive simulations and experiments. The training of the deep learning model is based on direct numerical simulations of supersonic ramp flows, focusing on the regions upstream of and around the shock–boundary layer interaction region. During the pre-processing stage, cubic spline functions increase the fidelity of the sparse signals and feed them to the long-short memory model for an accurate reconstruction. Comparisons are also carried out for different sparsity factors and assess the model's accuracy both qualitatively through the pressure signals and quantitatively using the root mean square error and the power spectra. The deep learning predictions are promising and can be extended to include other aerodynamic or aeroelastic parameters of interest.

Optimizing the utilization of structural resources of flight simulator motion systems

The object of the study is a six degrees-of-freedom motion system of the synergistic type of a flight simulator. The latter is the main technical means for training pilots and means of research and development of aircraft. The task of optimal utilization of its structural resources was solved, which provides an opportunity to improve the quality of motion cueing. The result is the developed method, which ensures optimal use of structural resources of motion systems of flight simulators. This is explained, first of all, by the use of the developed simplified operator for converting the movements of jacks into the movement of a motion system along individual degrees of freedom on the basis of quadratic approximation. Given this, it became possible to describe the coordinates of the centers of the axes of rotation of the motion system by cubic spline functions. Secondly, the solution of the task of estimating the structural resources of the motion system along linear degrees of freedom on the basis of the developed criterion was carried out by an effective modified method of the deformed polyhedron. This method combines the random search method in the first steps of the search and the gradient method in determining the global extremum. Thirdly, the problem of determining the dependence of the coordinates of the pitch and yaw axes along the pitch angle was stated and solved. Owing to the optimal utilization of the structural resources of motion systems, the coordinates of the axis of their rotation along pitch are as close as possible to the coordinate of the axis of the aircraft. Thus, the quality of motion cueing on the flight simulator is significantly increased and it is possible to use motion systems with shorter lengths of jacks, and therefore, to reduce the cost of their manufacture and operation

Промышленная система Российской Федерации: факторы роста и развития

The institutes for implementing industrial policy in the Russian Federation at the present time are considered. The main activities of industrial policy, which are provided for by the Federal Law on Industrial Policy, are stated. The problems that arise in the process of carrying out industrial policy at different levels of government are analysed in detail. The paper shows that local governments do not have a budgetary interest and legally stipulated powers to fulfil industrial policy, the federal level of authority can mainly exercise universal managerial influences. Thus, it is established that at present only regional government bodies have the opportunity to carry out industrial policy measures, taking into account the characteristic features and the region problems. The paper suggests using the cubic spline function to assess the industrialization level and the factors influencing it, as well as the sensitivity coefficient to evaluate the managerial impact effectiveness on the industrial system. The presented criteria were tested in the process of assessing both the industrialization level and the state support activities for industry. The main factors of growing and developing the country’s industrial system are identified. Conclusions are drawn on the impact degree of the state programme of supporting industry and federal special-purpose programmes on target indicators for developing the country’s industry; prospects for further research are outlined.

Bending of a plate from a functionally heterogeneous material in the presence of large deformations

Details and elements of structures, which are made of functionally heterogeneous materials and have the property of shape memory and behave pseudo-elastically, may be under the influence of complex loads in the process of manufacturing and operation. Uneven heating of bodies in combination with force factors can lead to large deformations of the material and complex deformation processes. The existing models of the behavior of such elements do not take into account the nonlinearity of geometric relationships and are unsuitable for use with large deformations.
 The article deals with the bending of a plate of finite dimensions from a functionally heterogeneous material in the presence of large plastic deformations. The simulation of plate behavior is based on a nonlinear phenomenological model that describes the properties of shape memory alloys and the thermos-pseudo-plastic behavior of the material at a point. A diagram of a pseudo-elastic material consisting of three curved sections is used.
 The first feature of the formulation of the problem of specifying the area of geometric nonlinearity is the formulation of the boundary conditions around the support. If for a linear problem they are set only along the support line, then to refine the geometrically nonlinear solution, the zero vertical displacements of the plate points and, accordingly, the speed of movement were set in the vicinity of the area of contact with the support. The second feature of the refinement is a significant reduction in the number of coordinate integration steps (up to 5%). At the same time, in order to fulfill the condition of stability, a proportional reduction of the integration step over time is necessary. For a reliable comparison of results, it is necessary to increase the number of time integration steps while decreasing the integration steps by coordinates. This problem was solved using a sequence of numerical experiments. The third feature consists in solving the additional problem of interpolation of the required values in the nodes of the new finer grid by the corresponding value in the nodes of the main grid. This problem is solved using a two-dimensional spline function.

Interval-based reasoning over continuous variables using independent component analysis and Bayesian networks

Bayesian networks (BNs) can be used for probabilistic reasoning over discrete variables. Their extension to the continuous domain, however, remains an open research issue. In this work, we address the Bayesian inference problem for continuous variables when negative evidence is available. This situation is faced when, because of unreliable or imperfect sensors, some variables are observed to be at specific intervals. We propose two solutions to this issue. The first one, dubbed dynamic discrete BN (DD-BN), is simply an adaptation of the dynamic discretization method; the second, referred to as SICA, is based on spline functions and the independent component analysis (ICA) method. SICA can represent a wide range of general multivariate distributions and possesses some integration characteristics that facilitate the inference process. Empirical trials on public datasets and simulated data yielded promising results regarding inference time and accuracy. Indeed, SICA achieved the highest accuracy at the expense of increased inference time with increasing dimensions.

A spline function method for modelling and generating a nonhomogeneous poisson process

ABSTRACT This paper presents a spline-based input modelling method for inferring the rate function of a nonhomogeneous Poisson process (NHPP) given arrival-time observations and a simple method for generating arrivals from the resulting rate function. Splines are a natural choice for modelling rate functions as they are smooth by construction, and highly flexible. Although flexibility is an advantage in terms of reducing the bias with respect to the true rate function, it can lead to overfitting. Our method is therefore based on maximising the penalised NHPP log-likelihood, where the penalty is a measure of rapid changes in the spline-based representation. A controlled empirical comparison of the spline-based method against two recently developed input modelling techniques is presented considering the recovery of the rate function, the propagation of input modelling error, and the performance of methods given data that are under or over-dispersed in comparison to a Poisson process.

Application of two variable hermite splines in digital image processing

During the research, the use of piece-polynomial methods in digital processing of images was considered. The Hermite spline function is chosen from piece-polynomials as a mathematical model in digital processing of signals, and the construction of a two-variable third-order Hermite spline function is presented. An image restoration algorithm was developed based on the constructed mathematical model.

#4404 KIDNEY FUNCTION TRAJECTORY BEFORE AND AFTER ARTERIOVENOUS ACCESS CREATION IN PATIENTS WITH PREDIALYSIS CKD

Abstract Background and Aims Timely arteriovenous (AV) access creation in view of starting hemodialysis is challenged by non-linear kidney function decline and the prospect of competing mortality. In addition, some studies have shown slower CKD progression following AV access creation in patients not on dialysis. While pathophysiological mechanisms, such as ischemic preconditioning and improved kidney perfusion, have been put forward to explain the apparent influence of AV access creation on estimated glomerular filtration rate (eGFR) trajectory, it cannot be ruled out that this finding resulted from an artefact induced by the use of models assuming linear (eGFR) decline before and after AV access creation. Our aim was to describe the kinetics of eGFR decline around the period of AV access creation and to identify different trajectory profiles using models relaxing this hypothesis. Method From 2013 through 2016, the CKD-REIN cohort included 3033 patients with CKD stages 3 to 5 from 40 nationally representative outpatient nephrology clinics in France. Participants were followed for 5 years or until initiation of kidney replacement therapy (KRT), death, or loss to follow-up, whichever came first. This study focused on patients who underwent their first AV access creation during follow-up. Linear mixed models with restricted cubic spline functions (two internal knots, one at AV access creation date, the other, one year before) were used to model a potential non-linear eGFR trajectory over time, based on routine labs. Random effects for the intercept and the spline function components allowed us to deal with individual variations in eGFR trajectory. Instantaneous rates of eGFR decline around AV access creation were then extracted. In addition, we performed latent class mixed models (LCMM) to identify distinct eGFR trajectories. Results During a median follow-up of 5.0 years (interquartile range [IQR], 4.6 to 5.2), 415 (14% of the total population) patients underwent a first AV access creation (32% women, 51% with diabetes). The median age at AV access creation was 69 years (IQR, 61 to 76), and the median eGFR, 13 ml/min/1.73 m² (IQR, 11 to 16). The median numbers of eGFR measurements before and after creation were 12 (IQR, 8 to 19) and 3 (IQR, 2 to 6) respectively. The average eGFR decline in the year before and after AV access creation, assuming constant slopes in each period, was 5.2 ml/min/1.73m² (95% confidence interval [CI], 4.8 to 5.5) and 3.4 ml/min/1.73 m² (95% CI, 3.1 to 3.7), respectively, with a mean difference of −1.8 ml/min/1.73m2 (95% CI, −1.4 to −2.1). Analysis of instantaneous rates showed that the slowdown of eGFR decline began 8.3 months on average (95% CI, 7.8 to 8.6) before AV access creation. The LCMM identified two profiles of eGFR trajectories which mostly differed in the rate of eGFR decline (Figure). In both trajectories, the mean time to the slowdown of eGFR decline preceded time of AV access creation, by 9.1 and 7.2 months in the fastest and slowest eGFR decline trajectories, respectively. Conclusion In nondialysis patients, slowdown of kidney function decline appears to occur several months before AV access creation. Our findings do not support a causal biological effect of AV access creation on CKD progression, but favor alternative hypotheses including optimal management before AV access creation, greater inaccuracy in eGFR estimation in advanced CKD due to muscle mass loss, or simply regression to the mean.

#3256 LONGITUDINAL ASSOCIATION BETWEEN IRON STORES BIOMARKERS AND MAJOR ADVERSE CARDIOVASCULAR EVENTS IN CHRONIC KIDNEY DISEASE

Abstract Background and Aims Iron deficiency is a frequent condition in moderate to severe chronic kidney disease (CKD), often left under-screened, and infrequently supplemented. Iron deficiency is a major contributor to anemia, which is known to negatively impact outcomes and quality of life in CKD. However, evidence of an anemia-independent effect of iron deficiency on cardiovascular morbidity and all-cause mortality has emerged. Current challenges of studying the association between iron deficiency and the risk of events in CKD are the definition of critical thresholds for these biomarkers, the potential interaction between them, and their evolution over time. Previous observational cohort studies have only focused on baseline values of transferrin saturation and ferritin, the two traditional biomarkers of iron deficiency. Our aim was to study the longitudinal association between iron stores biomarkers and cardiovascular risk in CKD by evaluating the total effect of these biomarkers on major adverse cardiovascular events (MACE). Method We used data from the CKD-REIN cohort, which included 3033 patients with moderate to severe CKD from 40 nationally representative nephrology clinics in France between 2013 and 2016. All patients with at least one measurement of TSAT and ferritin were included in the present study. Our primary endpoint was MACE, defined as the first event among cardiovascular death, myocardial infarction, stroke or hospitalization for acute heart failure. Repeated measures of TSAT and ferritin were included as time-dependent variables in cause-specific Cox proportional hazard models for risk of MACE, with initiation of kidney replacement therapy (KRT) and death as competitive events. Models were adjusted for time-varying estimated glomerular filtration rate (eGFR), white cells and baseline age, sex, iron supplementation, and erythropoietin stimulating agents. Analyses were not adjusted for hemoglobin level because the aim of the study was to investigate the total effect of iron deficiency on MACE. Non-linear effects of TSAT and ferritin and their interaction were modeled using natural splines functions. Results A total of 2670 patients were included in the analysis: 65% were men, median age was 68 years (interquartile range IQR 60-76). Median baseline eGFR was 34 ml/min/1.73 m2 (IQR 25-44), TSAT was 24% (IQR 18-30) and ferritin was 127 ng/ml (IQR 72-230). Over a median follow-up period of 4.4 years, participants had a median of 5 (IQR 2-8) and 4 (IQR 2-6) measurements of ferritin and TSAT, respectively; 396 MACE before KRT were recorded. The negative nonlinear association of iron deficiency with MACE was essentially captured by TSAT, and the interaction terms between TSAT and ferritin were not statistically significant (p = 0.94). Compared with patients with TSAT of 20% and ferritin of 100 ng/ml, those with TSAT values < 20% had a higher adjusted hazard of MACE independently of ferritin values (See Figure 1); for example, for TSAT = 10% and ferritin = 100 ng/ml, the hazard ratio (HR) was 1.96, 95% CI (1.60-2.39). Conclusion In CKD patients under nephrology care, current value of TSAT below 20% was associated with higher risk of MACE regardless of ferritin current value. Before investigating strategies of treatment in clinical trials as PIVOTAL in dialysis patients, further studies clarifying critical thresholds of TSAT and ferritin in non-dialysis CKD patients, in presence or absence of anemia and among specific CKD subpopulations are highly desirable.

Associations of air pollutant concentrations with longitudinal kidney function changes in patients with chronic kidney disease

This longitudinal cohort study investigated the associations of air pollutant exposures, including CO, NO, NO2, NOx, O3, PM10, PM2.5, and SO2, with long-term kidney function changes in patients with chronic kidney disease (CKD). We enrolled 447 CKD patients who took part in a universal hospital pre-ESRD care program during 2011–2015. The daily average air pollutant exposures and temperature were estimated for each patient, with different levels of air pollutant concentrations defined by 5-knot and restricted cubic spline function. Predicted annual estimated glomerular filtration (eGFR) slope values by one mixed model were considered as the study outcome. The average age of the study population was 77.1 ± 12.6 years, and the median annual eGFR decreased by 2.1 ml/min/1.73 m2 per year from 30 ml/min/1.73 m2 at baseline during a mean follow-up time of 3.4 years. The univariable and multivariable analyses revealed no significant linear and non-linear associations between 5-knot air pollutant concentrations and annual eGFR slope. In addition, the visualized spline effect plots show insignificant variation patterns in annual eGFR slope values with increased air pollutant concentrations. These results encourage more extensive studies to clarify the causal relationships and mechanisms of long-term specific air pollutant exposures and longitudinal kidney function change, especially in CKD populations.

THE FEATURES OF SPORTS COMPLEX 'SUNKAR' MONITORING BY TERRESTRIAL LASER SCANNING

Abstract. The paper is aimed at the study of monitoring workflow in adverse observation conditions for sports structures. The application of terrestrial laser scanning for monitoring various objects is well-studied. However, the deployment of TLS for large sports structures is challenging. Such structures have huge sizes, complex geometry and need the control of particular elements. The monitoring gets complicated in the case when the structure is placed on a very steep slope, e.g., ski jumps or bobsleigh tracks. The subject of the presented study is the complex of ski jumps 'Sunkar' emplaced in Almaty, Republic of Kazakhstan. The monitoring network for the complex was created using a robotic total station. Due to the extreme sizes of the object (height 70 m, width 8 m, length over 100 m), TLS was accomplished from all points of the network to ensure the necessary density of point clouds and reliable georeferencing. The main observation parameters were the displacements of the ski jumps regarding the longitudinal axis. To retrieve the axis coordinates, the point cloud was sliced along the ski jump surface. The geometry of the longitudinal axis was simulated using spline functions. As an output, the suggested monitoring workflow is provided that ensures the quality of the necessary results.

Early assessment of cardiomyopathy in Duchenne patients by means of longitudinal strain echocardiography.

The diagnosis of Duchenne-linked cardiomyopathy may be challenging. Conventional echocardiographic measurements typically show deterioration beyond the second decade. Global longitudinal strain has been proposed as an earlier marker than left ventricular ejection fraction. A prospective, observational, cross-sectional, case-control study was carried out. Both Duchenne patients and control subjects underwent transthoracic echocardiogram in order to assess left ventricle function. Bayesian linear regression was the main tool for inference. Age effects were parameterised by means of a spline function because of its simplicity to characterise continuous variables and smooth contributions. The posterior distribution of the marginal age effects was used to assess the earliest age of deterioration of each marker. Sixteen Duchenne patients and twenty-two healthy male subjects were enrolled. On overage, cardiac function measures were found for ejection fraction and longitudinal strain among different groups. Age effects on global longitudinal strain are more reliably found at ages of 6 and above, while ejection fraction starts to deteriorate at an older age. Progressive left ventricular dysfunction in Duchenne patients is one of the key issues and starts at an early age with subtle symptoms. This cross-sectional study provides supporting evidence that global longitudinal strain is an earlier marker of disease progression than ejection fraction in Duchenne patients.

Phytochemicals and Glioma: Results from Dietary Mixed Exposure

The information about phytochemicals’ potential to prevent cancer is encouraging, including for glioma. However, most studies on phytochemicals and glioma mainly focused on preclinical studies. Their epidemiological studies were not sufficient, and the evidence on the dose–response relationship is usually limited. Therefore, this investigation examined the association between dietary phytochemical intake and glioma in Chinese adults. This case–control study was carried out in a hospital in China. Based on the dietary information obtained from the food frequency questionnaire, the researchers estimated the phytochemical intake of 506 patients with glioma and 506 controls. Compared with participants in the lowest tertile, the highest intakes of carotene, flavonoids, soy isoflavones, anthocyanin, and resveratrol were associated with a reduced risk of glioma. The WQS and BKMR models suggested that anthocyanin and carotene have a greater influence on glioma. The significant nonlinear dose–response associations between dietary phytochemicals and glioma were suggested using the restricted cubic spline function. According to this study on phytochemicals and glioma, higher intakes of carotene, flavonoids, soy isoflavones, anthocyanins, and resveratrol are linked to a lower risk of glioma. So, we might not be able to ignore how phytochemicals affect gliomas.

Sex-specific effect of perfluoroalkyl substances exposure on liver and thyroid function biomarkers: A mixture approach.

Although studies have investigated the effects of perfluoroalkyl substances (PFASs) on liver and thyroid function, little is known about its combined and sex-specific effect. A total of 688 participants were interviewed and serum PFASs concentration was measured using liquid chromatography/mass spectrometry. Five biomarkers of liver and thyroid function (ALT, GGT, TSH, FT3 and FT4) were chosen as outcomes. A restriction cubic spline function was applied to capture the dose-response relationship between PFASs and liver enzymes and thyroid hormones. Multivariable regression and Bayesian kernel machine regression (BKMR) models were performed to assess the single and overall associations of PFASs with targeted biomarkers. Single-pollutant analyses indicated that increased PFASs concentrations were associated with elevated ALT and GGT levels. BKMR models suggested positive dose-response relationships between PFASs mixtures and ALT and GGT levels. Significant associations were only detected between several PFASs and thyroid hormones, and joint effect of PFASs mixtures on FT3 levels was found at higher concentrations. Meanwhile, sex differences were found in the associations of PFASs with ALT and GGT levels, with significant results only in males. Our findings provide epidemiological evidence for combined and sex-specific effects of PFASs on ALT and GGT levels.

Dynamic Evolution of Cracks in Slag-Modified Soil under Uniaxial Loading Using Real-Time X-Ray Computed Tomography

The cracking behavior of subgrade filling is crucial for the stability of road embankments. Slag-modified soil (SMS), which is commonly used as a reinforcing material for construction in highway and railway engineering, has special mechanical and microstructural characteristics that are easily altered under external disturbances. Although the macroscopic deformation of SMS has been widely examined, research on its cracking behavior at the mesoscale under an external load has received insufficient attention thus far. This study uses real-time X-ray computed tomography (X-CT) as a nondestructive tool for characterizing the microstructure of a SMS specimen subjected to uniaxial compression. Rules for the dynamic propagation of cracks in the specimen during deformation are identified based on two-dimensional (2D) and three-dimensional (3D) visualization and quantitative characterization. The results showed that the SMS can be divided into three components—cracks, soil, and steel slag—based on the density gradients from X-ray CT images. The preprocessed X-ray CT images and reconstructed crack models dynamically demonstrated the expanding and connecting patterns of internal cracks during the entire process of deformation. Values of the crack ratio and the degree of connectivity were positively correlated with the axial strain as expressed by a cubic spline function and a linear function, respectively. Curves of the distribution of the volumes of the cracks suggest that cracks in SMS can be divided into four groups: minicracks, mesocracks, medium cracks, and macroscopic cracks. From quantitative and visual perspectives, a large number of original cracks with small volume and low connectivity were gradually transformed into a main fracture under uniaxial loading. The localized shear band, which existed in the zone adjacent to the main fracture, was generated and obliquely distributed in an irregular, flat strip shape in the middle of the SMS specimen. This study suggests that the real-time X-ray CT scanning technique has broad application prospects for detecting the mesostructure in subgrade filling.

Convergence Analysis of Cubic Spline Function with Fractional Degree and Applications

Convergence Analysis of Cubic Spline Function with Fractional Degree and Applications

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Background: Total metabolic tumor volume (TMTV) and maximum standardized uptake value (SUVmax) may improve upon standard 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)-based assessment during treatment. We report the association of TMTV and SUVmax response by interim PET (PET2) on survival outcomes in patients with primary refractory DLBCL (prDLBCL) and early relapsing DLBCL (erDLBCL). Methods: Adult patients with prDLBCL (less than a complete response at EOT or progression during treatment) or erDLBCL (CR at EOT with a relapse within 12 months) between 2005 and 2019 and seen at Mayo Clinic Rochester were included. The % change (Δ) from baseline to PET2 (after 2 cycles of 1L immunochemotherapy) of TMTV and maximum SUV uptake (SUVmax) were measured. A PET segmentation threshold of 1.5 liver mean SUV + two standard deviations with a minimum volume constraint of 0.5 mL was utilized (MIM Software, Inc., Cleveland OH, USA) with manual input as needed. Functional spline analysis showed a ΔSUVmax decline ≥65% and a ΔTMTV decline ≥75% at PET2 were associated with improved OS and determined threshold for further analysis. Results: 131 patients with prDLBCL or erDLBCL, 131 had complete PET-CT data available (N = 79 prDLBCL, N = 52 erDLBCL). Median baseline TMTV was 939.5 cm3 (range 13.1–6840.4) in prDLBCL and 670.4 cm3 (0.9–5464.5) in erDLBCL (p = 0.01). Baseline median SUVmax was 22.2 (3.1–52.6) in prDLBCL and 19.1 (2.0–49.7) in erDLBCL (p = 0.02). The 2-year estimated OS rate was 21% (95% CI: 13–34) for prDLBCL and 58% (95% CI: 45–75) for erDLBCL. At a median follow up of 77.6 months, 81 patients had died. Among all patients, Two-year OS rate was 53% (95% CI: 42–67) for patients with a PET2 ΔSUVmax decline ≥65% compared to 15% (95% CI: 7–29) for patients with a PET2 ΔSUVmax decline <65% (p < 0.001) (Figure A). PrDLBCL had a 2-year OS rate of 48% (95% CI: 31–74) for a ΔSUVmax ≥65% compared to 7% (95% CI: 2–21) for patients with a ΔSUVmax <65% (p < 0.001)(Figure B), which captured 58% of prDLBCL patients (N = 46). Among all patients, 2-year OS rate was 43% (95% CI: 34–54) for patients with a ΔTMTV ≥75% compared to 5% (95% CI: 1–35) for patients with a ΔTMTV <75% (p < 0.001) (Figure C). All patients with a ΔTMTV <75% had prDLBCL. PrDLBCL had a 2-year OS rate of 28% (95% CI: 18–44) for a ΔTMTV ≥ 75% (Figure D). The outcomes for ΔSUVmax <65% and ΔTMTV <75% at PET2 remained significant in a cox regression model when adjusted for IPI and bulky disease (>10 cm). Encore Abstract - previously submitted to ASCO 2023 Keywords: Aggressive B-cell non-Hodgkin lymphoma, PET-CT Conflicts of interests pertinent to the abstract. M. J. Maurer Employment or leadership position: Exact Sciences - immediate family member Consultant or advisory role: Genmab; Adaptive Biotechnologies Stock ownership: Exact Sciences Research funding: Morphosys; Bristol-Myers-Squibb; Roche/Genentech; Genmab J. Paludo Consultant or advisory role: Abbvie Research funding: Karyopharm; Biofourmis J. R. Cerhan Consultant or advisory role: Bristol-Myers Squibb/Celgene; Protagonist Therapeutics Research funding: NanoString Technologies; Celgene; Genentech; Genmab Other remuneration: Uncompensated relationship: Regeneron T. E. Witzig Consultant or advisory role: Tornado Therapeutics; Salarius Pharmaceuticals Honoraria: Curio Science Research funding: Celgene; Acerta Pharma; Kura Oncology; Acrotech Biopharma; Karyopharm Therapeutics T. M. Habermann Consultant or advisory role: Celgene; Kite/Gilead; MorphoSys; BeiGene; Loxo Oncology Research funding: Genentech; Sorrento; Celgene Other remuneration: Data Monitoring Committee: Tess Therapeutics; SeaGen, Eli Lilly and Co Y. Wang Employment or leadership position: Merck - immediate family member Consultant or advisory role: Loxo; Incyte; Innocare; TG Therapeutics; Kite, A gilead company; Lilly; Janssen; BeiGene Stock ownership: Merck - immediate family member Honoraria: Kite, A Gilead Company Research funding: InnoCare; Incyte; Novartis; Genentech; Loxo; MorphoSys; Genmab G. S. Nowakowski Consultant or advisory role: Celgene; MorphoSys; Genentech; Selvita; Debiopharm Group; Kite/Gilead; TG Therapeutics; Kymera; Karyopharm Therapeutics; Ryvu Therapeutics; Bantham Research funding: Celgene; NanoString Technologies; MorphoSys

Depth of metabolic response at interim PET and survival outcomes among patients with primary refractory and early relapsing diffuse large B-cell lymphoma (DLBCL).

7543 Background: Total metabolic tumor volume (TMTV) and maximum standardized uptake value (SUVmax) may improve upon standard 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)-based assessment of advanced DLBCL during treatment. We report the association of TMTV and SUVmax changes at interim PET-CT (PET2) on survival outcomes in patients with primary refractory DLBCL (prDLBCL) and early relapsing DLBCL (erDLBCL). Methods: Adult patients with prDLBCL (less than a complete response (CR) or progression by the end of treatment (EOT)) or erDLBCL (CR at EOT with relapse within 12 months) between 2005 and 2019 at Mayo Clinic Rochester were included. The % change (Δ) from baseline to PET2 (after 2 cycles of 1L therapy) of TMTV and SUVmax were measured. A PET segmentation threshold of 1.5 liver mean SUV + two standard deviations with a minimum volume constraint of 0.5 mL was utilized (MIM Software, Inc., Cleveland OH, USA) with manual input as needed. Functional splines analysis determined SUVmax and TMTV threshold for analysis. Results: 131 patients had complete PET-CT data (N=79 prDLBCL, N=52 erDLBCL). Baseline median TMTV and SUVmax were 767.4 cm3 (range 0.9-6840.4) and 20.5 (2.0-52.6), respectively. At a median follow up of 77.6 months, 81 patients had died. 2-year OS rate was 53% (95% CI: 42-67) for patients with a PET2 ΔSUVmax decline ≥65% compared to 15% (95% CI: 7-29) for patients with a PET2 ΔSUVmax decline &lt;65%(p&lt;0.001). PrDLBCL had a 2-year OS rate of 48% (95% CI: 31-74) for a ΔSUVmax ≥65% compared to 7% (95% CI: 2-21) for a ΔSUVmax &lt;65%(p&lt;0.001), which captured 58% of prDLBCL patients (N=46). Two-year OS rate was 43% (95% CI: 34-54) for patients with a ΔTMTV ≥75% compared to 5% (95% CI: 1-35) for patients with ΔTMTV &lt;75% (p&lt;0.001). All patients with a ΔTMTV &lt;75% had prDLBCL. PrDLBCL had a 2-year OS rate of 28% (95% CI: 18-44) for a ΔTMTV ≥75%. The outcomes for ΔSUVmax &lt;65% and ΔTMTV &lt;75% at PET2 remained significant in a cox regression model adjusted for IPI and bulky disease (&gt;10cm)(Table). Conclusions: A ΔTMTV decline &lt;75% or a ΔSUVmax decline &lt;65% at PET2 identified an ultra-high-risk subgroup of DLBCL with particularly poor outcomes, that captured a high percentage of prDLBCL patients, and was significant after adjusting for IPI and bulky baseline disease. These patients may benefit from clinical trials evaluating alternative PET-adapted treatment strategies, but further evaluation among all patients with DLBCL is needed. [Table: see text]

Comprehensive inter-fibre failure analysis and failure criteria comparison for composite materials using micromechanical modelling under biaxial loading

Inter-fibre failure analysis of carbon fibre-reinforced polymer (CFRP) composites, under biaxial loading conditions, has been a longstanding challenge and is addressed in this study. Biaxial failure analysis of IM7/8552 CFRP unidirectional (UD) composites is conducted under various stress states. Two widely accepted failure criteria, the interactive Tsai-Wu and non-interactive Hashin failure criteria, are comprehensively assessed with finite element-based micromechanical analysis. High-fidelity three-dimensional representative volume elements (RVEs) are subjected to biaxial loadings with imposed periodic boundary conditions. Carbon fibres are assumed to be transversely isotropic and linearly elastic. The Drucker-Prager plastic damage constitutive model and cohesive zone model are utilised to simulate the mechanical response of the matrix and fibre-matrix interface, respectively. Coulomb friction is assumed between the fibres and matrix after interface failure. Two sets of biaxial loading scenarios (i.e. transverse stress dominated and shear stress dominated) with the associated failure modes are selected for the failure analysis and assessment of these failure criteria. A data-driven failure envelope for the composites under biaxial loadings is developed using a univariate cubic spline function. Failure mode transition points are determined under biaxial loadings. It is found that the micromechanics-based numerical model is effective in assessing these two existing criteria.

Association between Residential Exposure to Air Pollution and Incident Coronary Heart Disease Is Not Mediated by Leukocyte Telomere Length: A UK Biobank Study.

Higher air pollution exposure and shorter leukocyte telomere length (LTL) are both associated with increased risk of coronary heart disease (CHD), and share plausible mechanisms, including inflammation. LTL may serve as a biomarker of air pollution exposure and may be intervened with to reduce the risk of CHD. To the best of our knowledge, we are the first to test the mediation effect of LTL in the relationship between air pollution exposure and incident CHD. Using the UK Biobank (UKB) data (n = 317,601), we conducted a prospective study linking residential air pollution exposure (PM2.5, PM10, NO2, NOx) and LTL to incident CHD during a mean follow-up of 12.6 years. Cox proportional hazards models and generalized additive models with penalized spline functions were used to model the associations of pollutant concentrations and LTL with incident CHD. We found non-linear associations of air pollution exposure with LTL and CHD. Pollutant concentrations in the lower range were decreasingly associated with longer LTL and reduced risk of CHD. The associations between lower pollutant concentrations and reduced risk of CHD, however, were minimally mediated by LTL (<3%). Our findings suggest that air pollution influences CHD through pathways that do not involve LTL. Replication is needed with improved measurements of air pollution that more accurately assesses personal exposure.