Equivalence Point Research Articles

Investigation on the time/frequency domain prediction model of radiation noise based on the source map

The main exterior noise sources of the high-speed train CRH380AM, such as pantograph and bogie, are studied by using the field test sound imaging data, and the equivalent point source spectrums are obtained here. Then, the prediction model of the exterior train noise is presented by using the moving point sound source radiation model in the time/frequency domain. The correctness and effectiveness of the model are verified by the field test data. The radiation contribution of local noise sources is analyzed by using this model, and the following conclusions are obtained: The largest noise sources are in the bogie areas, which provide the radiation contribution rate of about 80% when the train speed is above 300 km/h. The variation of the maximum radiation noise level can be ignored when the train formation or the pantograph lifting position is changed. The model can evaluate the radiated noise of similar vehicles quickly and accurately, which provides technical reference for acoustic optimization design of high-speed train.

An Analysis of the Accuracy of the Transformation of the Coordinators of Mining Maps by Distinct Method

The article presents the results of an analysis of the accuracy of the transformation of the coordinates of the boundary points of neighbouring mining areas in Silesia. The transformations were carried out independently for each mining area caused the equivalent boundary points of neighbouring mining areas in the local coordinate system to have different coordinates in the national PL-2000 system. In addition, analyses were carried out taking into account measurement accuracy confirming the sensitivity of the first order conformal transformation to measurement errors. The differences that occur indicate the need to look for a method that will reduce or eliminate them.

An Analysis of the Accuracy of the Transformation of the Coordinators of Mining Maps by Distinct Method

The article presents the results of an analysis of the accuracy of the transformation of the coordinates of the boundary points of neighbouring mining areas in Silesia. The transformations were carried out independently for each mining area caused the equivalent boundary points of neighbouring mining areas in the local coordinate system to have different coordinates in the national PL-2000 system. In addition, analyses were carried out taking into account measurement accuracy confirming the sensitivity of the first order conformal transformation to measurement errors. The differences that occur indicate the need to look for a method that will reduce or eliminate them.

Time for Dementia: innovation in dementia education

Background:The future healthcare workforce needs the skills, attitudes, and empathy to better meet the needs of those with dementia. Time for Dementia is an educational programme in which healthcare students from a range of professional groups visit a person with dementia and their family carer over a two-year period. The first phase of research demonstrated positive outcomes for students (Banerjee et al., 2021; Daley et al., 2020). Here we discuss the most recent findings from the second phase.Objectives:to evaluate the impact of Time for Dementia on student attitudes, knowledge and empathy towards dementia, and satisfaction of students and families.Methods:A mixed methods longitudinal cohort study was conducted between 2014- 2021. Measures of dementia knowledge, attitudes and empathy were administered to healthcare students at five universities in the south of England before and after (24 months) they completed the Time for Dementia programme. Data were also collected at equivalent time points for a control group of students who had not taken part in the programme. Outcomes were modelled using multilevel linear regression models. Satisfaction surveys were completed by students and families at the end of the programme.Results:2,700 intervention group students, 562 control group students and 803 families consented to participate in the research. Students undertaking the Time for Dementia programme had higher levels of knowledge and positive attitudes at follow-up compared to equivalent students who did not undertake the programme. Satisfaction was high for both students and families, with both perceiving benefits of taking part.Conclusions:The results suggest the Time for Dementia programme is effective in improving the knowledge and attitudes of healthcare students across different professional groups and universities. It also demonstrates that dementia education that meaningfully involves people with dementia and their carers can be delivered at scale for healthcare professionals.

Improved DV-Hop model based on the application of variable scenarios

This work proposes an improved DV-Hop model based on function analysis and simulation parameter determination (named FuncDV-Hop) to address the problems of low positioning accuracy and strong scene dependence of the DV-Hop localization model. The undetermined coefficient optimization, step function segmentation experiment, weight function strategy with equivalent points, and maximum likelihood estimation correction are introduced to reduce the positioning error by analyzing the error reasons in the average hop distance, distance estimation, and least square calculation of the DV-Hop model. The experiment is designed using the control variable method. The total number of nodes, the ratio of beacon nodes, the communication radius, the number of beacon nodes, and the number of unknown nodes are designed as variables to control the experiment. Finally, the experiments of two stages of simulation parameter determination and integration optimization are carried out. The simulation positioning error of all scenarios is reduced by 0.0630–0.2472, and the positioning accuracy is increased by 23.81%–75.85%. Experimental results show that the FuncDV-Hop model has the highest optimization rate of more than 50% in all experimental scenarios compared with the other models, the localization error is reduced by more than 0.1, and the optimization rate is increased by more than 10% in the record parameters of the existing wireless sensor network system.

Use of Ipomoea involucrata B. flower as metallochromic indicator for complexometric titrations

The present work highlights the use of Ipomoea involucrate B. flower extract as a complexometric indicator in complex formation between the EDTA and the following metal solutions (Cu2,+ Ba2,+ Hg2+, Fe3+, and Bi3+). Ipomoea involucrate is a species of the Ipomoea genus, belonging to the family Convolvulaceae. This natural indicator was extracted in 2M HCl at 100 0C for 30-40 minutes, cooled and the extract filtered and extracted with ethyl acetate and the pigment extracted with amyl alcohol which was separated and concentrated over a water bath. The flower extract was screened for its use as an metallochromic indicator at different pHs in metal solutions of Cu2,+ Ba2,+ Hg2+, Fe3+, and Bi3+.This natural indicator from the results obtained gave sharp intense color change at the equivalence point of complex formation between the metals and the EDTA at both acidic and alkaline pHs in the metal solution of Cu2+ and Fe3+ and that with different amount of EDTA used in the titration, which increased as the pH value increased, while the ipomoea indicator gave sharp intense color change at the equivalence point of complex formation between the metals and the EDTA at alkaline pHs in the metal solution of Ba2+, Hg2+ and Bi3+ at pH > 10. Natural flower indicators could take the place of the synthetic metallochromic indicators currently used in conventional laboratories because these flower extracts have excellent performance with sharp and intense color change in end points during the complexometric titrations and simple, cost-effective and environmentally friendly extraction methods.

Resultant Normal Contact Force-Based Contact Friction Model for the Combined Finite-Discrete Element Method and Its Validation

In the conventional FDEM (Combined Finite and Discrete Element Method), each contact pair might have multiple contact points where friction forces are applied, leading to non-unique friction force assignments and potentially introducing computational errors. This study introduces a new contact friction algorithm for FDEM based on the resultant normal contact force. This method necessitates determining the friction force at a unique equivalent contact point, thereby significantly simplifying the computational flow and reducing memory usage. A series of numerical tests are performed to validate the effectiveness of the proposed contact model. Using collision and block sliding tests, the proposed contact friction model is verified to be able to accurately capture the frictional effect between discrete bodies and circumvent the problematic kinetic energy dissipation issue associated with the original contact friction algorithm. For the Brazilian splitting and uniaxial compression tests, the simulated results closely align with those generated using the original contact friction algorithm and match the experimental measurements well, demonstrating the applicability of the proposed algorithm in fracturing analysis. Furthermore, by using the proposed contact friction algorithm, a computational efficiency enhancement of 8% in contact force evaluation can be achieved.

Neural correlates of cognitive control deficits in pediatric mild traumatic brain injury.

There is a growing body of research showing that cerebral pathophysiological processes triggered by pediatric mild traumatic brain injury (pmTBI) may extend beyond the usual clinical recovery timeline. It is paramount to further unravel these processes, because the possible long-term cognitive effects resulting from ongoing secondary injury in the developing brain are not known. In the current fMRI study, neural processes related to cognitive control were studied in 181 patients with pmTBI at sub-acute (SA; ~1 week) and early chronic (EC; ~4 months) stages post-injury. Additionally, a group of 162 age- and sex-matched healthy controls (HC) were recruited at equivalent time points. Proactive (post-cue) and reactive (post-probe) cognitive control were examined using a multimodal attention fMRI paradigm for either congruent or incongruent stimuli. To study brain network function, the triple-network model was used, consisting of the executive and salience networks (collectively known as the cognitive control network), and the default mode network. Additionally, whole-brain voxel-wise analyses were performed. Decreased deactivation was found within the default mode network at the EC stage following pmTBI during both proactive and reactive control. Voxel-wise analyses revealed sub-acute hypoactivation of a frontal area of the cognitive control network (left pre-supplementary motor area) during proactive control, with a reversed effect at the EC stage after pmTBI. Similar effects were observed in areas outside of the triple-network during reactive control. Group differences in activation during proactive control were limited to the visual domain, whereas for reactive control findings were more pronounced during the attendance of auditory stimuli. No significant correlations were present between task-related activations and (persistent) post-concussive symptoms. In aggregate, current results show alterations in neural functioning during cognitive control in pmTBI up to 4 months post-injury, regardless of clinical recovery. We propose that subacute decreases in activity reflect a general state of hypo-excitability due to the injury, while early chronic hyperactivation represents a compensatory mechanism to prevent default mode interference and to retain cognitive control.

Accelerating the prediction of CO2 capture at low partial pressures in metal-organic frameworks using new machine learning descriptors

Metal-Organic frameworks (MOFs) have been considered for various gas storage and separation applications. Theoretically, there are an infinite number of MOFs that can be created; however, a finite amount of resources are available to evaluate each one. Computational methods can be adapted to expedite the process of evaluation. In the context of CO2 capture, this paper investigates the method of screening MOFs using machine learning trained on molecular simulation data. New descriptors are introduced to aid this process. Using all descriptors, it is shown that machine learning can predict the CO2 adsorption, with an R2 of above 0.9. The introduced Effective Point Charge (EPoCh) descriptors, which assign values to frameworks’ partial charges based on the expected CO2 uptake of an equivalent point charge in isolation, are shown to be the second most important group of descriptors, behind the Henry coefficient. Furthermore, the EPoCh descriptors are hundreds of thousands of times faster to obtain compared with the Henry coefficient, and they achieve similar results when identifying top candidates for CO2 capture using pseudo-classification predictions.

An Analytical Method for Determination of Total Iron in Pharmaceuticalgrade Intravenous Iron Colloidal Complexes by Redox-Potentiometry.

Iron carbohydrate complexes are colloidal dispersions made up of polynuclear Fe(III)-oxyhydroxide cores surrounded by a carbohydrate shell that stabilizes the complex in iron colloidal formulations. The current study provides an improved method that is precise, accurate, and linear for quantifying total iron in most Iron Carbohydrate Colloid Drug Products. Redox iodometry with a potentiometric determination is used to evaluate total iron in intravenous formulations. The visual indicator approach is more prone to fluctuations at endpoint calculations. Hence, the voltage potential approach is widely accepted as it is more accurate and sensitive. It tracks the actual change in activity that coincides with the equivalence point that is finally considered an endpoint. The principle is based on the idea that ferric iron in formulation reduces to ferrous iron in the presence of the iodide, which oxidizes to iodine. The released iodine is titrated using sodium thiosulfate. The proposed method was precise, with %RSD (relative standard deviation) not more than 1. The method was linear between 80% and 120%, with a linear regression of 0.999. The percent recovery ranged from 98.20 to 99.98 for the concentration ranges of 80-120. The method's robustness was checked by various analysts using different reagent grades. The proposed potentiometric determination method was precise, accurate, linear, and sensitive. The method was successfully validated, and the total iron content determined for commercial batches agrees with the iron claim on the label. Therefore, this method can be adapted widely for total iron content determination in any Intravenous formulation currently available on the market. The proposed method is more accessible at the Quality Control facilities on an industrial scale.

A new method for instrumental assessment of color stability

The article considers the improvement of methods for testing the color fastness of textile materials with the replacement of the visual method with an objective colorimetric evaluation method. A new method for testing the color fastness of textile materials is proposed. The analysis of domestic and foreign standards that establish the calculation and establishment of color fastness standards for cotton fabrics and their comparison with the norms of international and domestic standards was carried out. It is shown that the development of methods for instrumental determination of color fastness to friction, which is an alternative to the method of visual assessment of the color fastness of any textile material on a gray scale, is currently an urgent and promising scientific and technical task. A new method for testing the color fastness of textile materials is proposed. The overall color difference (ΔE) between the test sample of the color fastness test material and the original sample was measured. For both samples, the over-all color difference was determined in the CIEL*a*b* system, the values of which are converted into equivalent points on a gray scale. The score in terms of the value of ΔE was calculated on a computer using the Ecsel environment and displaying the calculation results on the display screen.

Partition Dimention of Amalgamation-Side in Cycle Graph

The graph is a pair of sets , where is a finite set whose elements are called vertices, and is the set of pairs of members of . which is called the edge. Let be a simple graph where . The distance between points and is denoted by is the length of the shortest path between and . Given and there is a vertex on the connected graph , then the distance between and is denoted . If is -partition of , then the representation of with respect to is -ordered pairs, . If the -ordered pairs for are all different, then the partition is called a dimension partition. The minimal -number which is the -differentiating partition of is called the partition dimension of and is denoted by . In this study, the partition dimensions of the sided amalgamation result will be determined on an even-order cycle graph. In determining the dimensions of the partition, characterization of the partition dimensions is used in the path graph, the lemma about the distinguishing set and the equivalence point, especially in the even-order cycle graph. The results of this study are pd(Amal(Cn,e,k)) = 3 for n≥4 , pd(Amal(C4,e,k))=4 for k=4 , pd(Amal(C4,e,k))=3+m for k=2m+3 and k=2m+4 where m=1,2,3,...

Synthesis of ruthenium carbonyl cluster complexes containing bis(2′-pyridylethynyl)benzene derivatives: Construction of an extended Zero-valent ruthenium chain

The reactions of Ru3(CO)12 in a refluxing acetonitrile-toluene solution with a half equivalent of the ligand 1,3-bis(pyridin-2-ylethynyl)benzene afforded Ru3(CO)7(μ-CO)[μ-(2-PyCCH)(1,3-C6H3)(2-PyCC)]Ru4(CO)12 (compound 1) and Ru3(CO)7(μ-CO)[μ-(2-PyCCH)(1,3-C6H2)(2-PyCCH)]Ru3(CO)8 (compound 2). Separately, Ru3(CO)12 was treated with a half equivalent of 1,4-bis(pyridin-2-ylethynyl)benzene in a refluxing acetonitrile-toluene solution to generate Ru3(CO)7(μ-CO)[μ-(2-PyCCH)(1,4-C6H3)(2-PyCC)]Ru4(CO)12 (compound 3) and Ru3(CO)8Ru(CO)2[μ-(2-PyCCH)(1,4-C6H2)(2-PyCCH)]Ru3(CO)8 (compound 4). Compounds 1–4 were characterized by FT-IR, NMR, ESI-HRMS and single-crystal X-ray diffraction. The structure of compound 2 was found to contain two triruthenium triangular frameworks, and compound 1 was found to be an intermediate of compound 2. Compounds 1 and 3 were shown to consist of triruthenium and tetraruthenium frameworks. Both compounds 1 and 3 exhibited two types of fluxional behavior in solution due to degenerate rearrangement of the acetylide ligand and restricted rotation. This assumption was confirmed by the variable-temperature 1H NMR, COSY and NOESY spectra. Noticeably, compound 4 possessed a quasilinear pentaruthenium structure, and compound 3 was shown to be an intermediate to compound 4.

Paper chromatography approach for the assessment of interaction between red wine and whole saliva

In-mouth interaction of red wine compounds with salivary proteins is a primary event allegedly responsible for eliciting the mouth-feel sensation of astringency. Those interactions have been currently associated with precipitation of salivary protein/polyphenol complexes. However, such single physicochemical evidence for interaction does not account for the complexity of astringency. This study aimed to develop a paper chromatography method to assess interactions between red wine and the salivary protein fraction using stepwise series of red wine/saliva binary mixtures from 100% wine to 100% saliva (“Alpha and Omega series”). Aliquots of each one of the mixtures were spotted on a cellulose membrane to scrutinize independently the distribution areas of wine components (naturally pink-colored) and salivary protein (stained blue in Coomassie Brilliant R-250). This double target detection revealed interactions between saliva and red wine components along most of the quantitative Alpha and Omega series, a point of equivalence corresponding to maximum interactivity for both complex reactants and a non-diffusible sub-fraction of saliva displaying the highest interactivity. The results indicate a novel way to assess quantitatively physicochemical interactions between red wines and human saliva but also provide new lights to approach the identification of molecular salivary structures involved in triggering astringency.

Integrated proteomics and genomics analysis of paradoxical eczema in psoriasis patients treated with biologics

Few studies have explored the immunology and genetic risk of paradoxical eczema occurring as an adverse event of biologic therapy in patients with psoriasis. We sought to describe the systemic inflammatory signature of paradoxical eczema using proteomics and explore whether this is genetically mediated. This study used the Olink Target 96 Inflammation panel on 256 serum samples from 71 patients with psoriasis and paradoxical eczema, and 75 controls with psoriasis to identify differentially expressed proteins and enriched gene sets. Case samples from 1 or more time points (T1 prebiologic, T2 postbiologic, and T3 postparadoxical eczema) were matched 1:1 with control samples. Genes contributing to enriched gene sets were selected, and functional single nucleotide polymorphisms used to create polygenic risk scores in a genotyped cohort of 88 paradoxical eczema cases and 3124 psoriasis controls. STAMBP expression was lower in cases at T1 than in controls (log-fold change: -0.44; adjusted P= .022); no other proteins reached statistical significance at equivalent time points. Eleven gene sets including cytokine and chemokine pathways were enriched in cases at T2 and 10 at T3. Of the 39 proteins contributing to enriched gene sets, the majority are associated with the atopic dermatitis serum proteome. Apolygenic risk score including 38 functional single nucleotide polymorphisms linked to enriched gene sets was associated with paradoxical eczema (adjusted P= .046). The paradoxical eczema systemic inflammatory proteome trends toward atopic dermatitis at a gene-set level and is detectable before onset of the phenotype. This signature could be genetically determined.

DEVELOPMENT AND VALIDATION OF THE QUANTITATIVE DETERMINATION METHOD FOR A NEW BIOLOGICALLY ACTIVE COMPOUND N-[2-[4-OXO-3(4Н)-QINAZOLINYL]PROPIONYL]-GUANIDINE BY THE METHOD OF TITRATION IN A NON-AQUEOUS MEDIUM

Relevance. Due to the wide spread of diseases of the cardiovascular system, the development and study of drugs aimed at the treatment of diseases of the circulatory system is relevant. A new biologically active compound (BAC) is synthesized at the Department of Pharmaceutical and Toxicological Chemistry of the Volgograd State Medical University – a derivative of quinazoline: N-[2-[4-oxo-3(4H)-quinazolinyl] propionyl]-guanidine (VMA-13-15), which at the stage of preclinical studies confirmed the prospects for use in medical practice as a cardioprotective and neuroprotective drug. The aim of the study is to develop and validate a method for the quantitative determination of N-[2-[4-oxo-3(4H)-quinazolinyl]propionyl]-guanidine (VMA-13-15). Material and methods. The objects of study are laboratory samples of N-[2-[4-oxo-3(4H)-quinazolinyl]propionyl]-guanidine (VMA-13-15, series 2019, 2020 and 2021). A laboratory sample VMA-13-15 twice recrystallized from methanol and dried to constant weight is used as a standard sample (RS). Quantitative determination is carried out by acid-base titration in a non-aqueous medium. The end of the titration is fixed potentiometrically. Results. The ionization constants VMA-13-15 are determined. A procedure is developed for the quantitative determination of N-[2-[4-oxo-3(4H)-quinazolinyl]propionyl]guanidine by acid-base titration in a solvent medium of glacial acetic acid with the establishment of an equivalence point using a potentiometer. The developed method is validated according to the main characteristics: specificity, linearity, correctness, convergence and analytical area. The validation analysis of the developed method confirms that it is suitable for the quantitative determination of the main substance content in the VMA-13-15 substance. Conclusions. A technique for potentiometric titration of N-[2-[4-oxo-3(4H)-quinazolinyl]propionyl]guanidine in a non-aqueous medium is developed and validated.

Eliciting Societal Preferences for Non-health Outcomes: A Person Trade-Off Study in the Context of Genomics

Economic evaluations of health technologies traditionally aim to maximize population health outcomes measured by using quality-adjusted life-years (QALYs). Non-health outcomes, however, may have high social value, and their exclusion has the potential to bias decisions regarding allocation of health care resources. This research positions Australian participants as societal decision-makers to explore their willingness to trade-off health gains in adults for non-health benefits in families with a child affected by a rare disease. To estimate the social value of the different health care interventions, a person trade-off (PTO) method was used. PTOs present participants with groups of beneficiaries that vary in terms of the number of individuals who will benefit, the individuals' characteristics, their expected benefits, or a combination, and ask which group should be prioritized. Each trade-off presented health gains from the treatment of moderate physical and mental health conditions described by the 3-level version of the EuroQol 5-Dimension (EQ-5D-3L) health states. The health gains in these groups were traded-off against non-health gains in families accessing diagnostic genomic testing, and equivalence values were calculated, using median and ratio of means methods, based on the ratio of the group sizes at the point of equivalence. Participants were recruited through Prolific and were stratified according to age, sex, and education.The impact of participant characteristics on equivalence values was assessed using Kruskal-Wallis H tests and ordinary least-squares log-linear regressions. Participants (N=434) positioned as societal decision-makers were generally willing to trade-off adult health gains with the familial non-health benefits of genomic testing, showing a preference for valuing both types of outcomes within public health policy. The aggregation of preferences generated 2 weightings for genomic testing against each health treatment, an unadjusted value and a reweighted value to match target demographic characteristics. Converted into QALY value per test, it was found that participants valued the non-health benefits of genomic testing between 0.730 and 0.756 QALY. A minority of participants always prioritized diagnostic genomic testing over the physical (6.0%) or mental (4.6%) health treatments, with a larger minority always prioritizing the physical (15.4%) or mental (14.8%) health treatments. The findings indicate that participants perceived the non-health parental benefits in children experiencing rare disease to have comparable value to health gains in adults experiencing the moderate physical or mental health conditions described using EQ-5D-3L. These findings suggest that the benefits of genomic tests would be underestimated if only health benefits are included in economic evaluations.

Effects of Oral Sodium Bicarbonate Supplementation on Protein Metabolism and Inflammation in Iraqi Hemodialysis Patients: An Open-Label Randomized Controlled Trial.

The effect of correcting metabolic acidosis on protein metabolism in hemodialysis patients is controversial. To study the effects of oral sodium bicarbonate on protein metabolism and markers of inflammation in acidotic hemodialysis patients. Patients and Methods. An open-label randomized controlled trial was conducted at a single center. Sixty-six clinically stable adult hemodialysis patients were recruited with an average predialysis serum bicarbonate level of <22 mmol/l and a dialysate bicarbonate concentration of 35 mmol/l. Forty-nine participants have completed the study. Oral sodium bicarbonate tablets of 500 mg were given daily in the intervention group (n = 25) for 12 weeks versus the standard of care in the control group (n = 24). Outcomes compared intervention versus nonintervention in both groups at equivalent time points (0 and 3 months). The clinical data, anthropometry, dialysis adequacy, albumin, normalized protein catabolism rate, blood gas analysis, and bicarbonate were recorded at 0 and 3 months. In addition, muscle mass and handgrip strength were measured. Finally, IL-6 as a marker of inflammation was measured at randomization and three months. Serum bicarbonate and pH increased significantly from 17.57 ± 3.34 mmol/L to 20.69 ± 2.54 mmol/L and from 7.26 ± 0.06 to 7.34 ± 0.04, respectively (p < 0.0001). Serum albumin was significantly higher in the intervention group at three months than in the control group, 4.11 ± 0.45 vs. 3.79 ± 0.47 (p value 0.011). Serum potassium significantly decreased in the intervention group at three months compared to the control group, 5.00 ± 0.43 mEq/l vs. 5.33 ± 0.63 mEq/l (p value 0.03). Muscle strength expressed as handgrip has improved significantly in the intervention group at three months compared to the control group, 45.01 ± 19.19 vs. 33.93 ± 15.06 (p value 0.03). The IL-6 values were less in the intervention group at 3 months with a p value of 0.01. The interdialytic weight of the intervention group at three months was 2.42 ± 0.64 compared to the 2.20 ± 1.14 control group, but this did not reach statistical significance (p value of 0.4). The composite of (albumin + nPCR) at three months was achieved in 59.18% of the intervention group compared to 14.28% with a p value of 0.01. Correcting metabolic acidosis in hemodialysis patients improved serum albumin and nPCR without hypokalemia or significant interdialytic weight gain. This was particularly evident in patients with minimal inflammation with low IL-6 values.

Theoretical solutions for 2D mode-I crack-tip stress fields in power-law plastic materials based on the stress factor derived from the developed median-energy–density equivalence method

This study presents the energy density equivalence equation, demonstrating that the strain energy density of an arbitrary representative volume element (RVE) under a complex stress state equals to that under a uniaxial stress state when volume change is neglected. Based on the developed median-energy–density equivalence method, the analytical solution for equivalent stress of the RVE at the energy density equivalence point in power-law plastic materials is derived in a new method and the concept of stress factor is proposed. Additionally, novel special functions are introduced to accurately describe the angular distributions of stresses in this study. By combining the stress factor, integral theoretical solutions for mode-I crack tip stress fields in power-law plastic materials under finite plane conditions are proposed. Finally, parameterized studies are conducted on bending and tension specimens under plane-strain and plane-stress conditions. The results of stress distributions and contour lines predicted by the integral theoretical solutions are compared with the finite element analysis and HRR solutions for five mode-I plane specimens, providing verification of the solutions’ applicability.

P38 Integrating proteomics and genomics to investigate the mechanisms of paradoxical eczema developing in patients with psoriasis treated with biologics: a UK multicentre, longitudinal, cohort study

Abstract Few studies have explored the immunology and genetic risk of paradoxical eczema occurring in patients with psoriasis treated with biologics. This study aims to describe the systemic inflammatory signature of paradoxical eczema using proteomics and explore whether it is genetically mediated. Participants were adults treated with biologics for plaque psoriasis, who were corecruited to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) and Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) studies. To identify differentially expressed proteins and enriched gene sets, we used the Olink Target 96 Inflammation panel on 256 serum samples from BSTOP for 71 cases with paradoxical eczema and 75 controls. Paradoxical eczema was defined as eczema, atopic eczema or atopic dermatitis occurring during biologic exposure. Case samples across three time points [T1: prebiologic (n = 42); T2, postbiologic (n = 45); T3, postparadoxical eczema (n = 41)] were matched 1 : 1 with control samples. Case samples at T2 and T3 were taken during exposure to the same biologic that caused paradoxical eczema. Genes contributing to proteomic signatures were selected, and single-nucleotide polymorphisms (SNPs) that were nonsynonymous or associated with significant expression quantitative trait loci were used to create polygenic risk scores (PRS) in a genotyped cohort of 88 paradoxical eczema cases and 3124 psoriasis controls. Signal transducing adapter molecule 1-binding protein expression was lower in cases at T1 than in controls (log-fold change −0.44, adjusted P = 0.022); no other proteins achieved statistical significance at equivalent time points. Eleven gene sets, including cytokine and chemokine pathways, were enriched in cases at T2 and 10 at T3. Of the 39 proteins contributing to enriched gene sets, 21 are elevated in the sera of patients with atopic dermatitis. A PRS including 38 SNPs linked to enriched gene sets was associated with paradoxical eczema (adjusted P = 0.046). We subdivided the SNPs into those linked to specific gene sets, such as chemokine, cytokine and interleukin (IL)-10 signalling, to generate 10 partitioned PRS. Seven were associated with paradoxical eczema (adjusted P &amp;lt; 0.05). These SNPs do not map to known atopic loci. The paradoxical eczema systemic inflammatory proteome trends toward atopic dermatitis at a gene set level and is detectable before the onset of the phenotype. This signature may be mediated genetically by SNPs associated with these gene sets. Further studies are needed to explore the role of specific pathways (such as IL-10 signalling) in paradoxical eczema and define the inflammatory profile in the skin.