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The paper discusses solutions used for estimating fatigue life under variable amplitude multiaxial loading in the high-cycle fatigue domain. Various concurring effects are treated, and their proposed solutions are commented upon. The focus is on the categories of the phase shift effect and of cycle counting. It is concluded that the available experimental data are not sufficient to substantiate a clear decision to follow a definite algorithm. An example of own new experimental data is provided, and the fatigue life estimation run to highlight some more points open for discussion.

Ecological context – the particular environment, and how it shapes mixing dynamics and individual susceptibility surrounding infectious disease events – can have major bearing on epidemic outcomes, yet directly comparable disease events with contrasting ecological contexts are relatively rare in wildlife systems due to concurrent differences in host genetics or pathogen strain. Here, we present a case study of one such event: a spillover of a “goat-clade” Mycoplasma ovipneumoniae strain into one bighorn sheep population that played out against two very different ecological backdrops. One event occurred on the herd’s home range near the Rio Grande Gorge in New Mexico, while the other progressed in a captive facility at Hardware Ranch in Utah. We collected data on antibody and pathogen load patterns through time at the individual level, and examined demographic responses to pathogen invasion to compare the intensity of, and in-host responses to, infection in both settings. While data collection regimens varied between the two sites, general patterns of antibody expansion and gross timing of symptoms were consistent. Symptoms emerged in the captive setting 12.9 days post-exposure, and we estimated an average time to seroconversion among the captive animals of 24.9 days. Clinical signs peaked among the captive animals at approximately 36 days post-infection, consistent with subsequent declines in symptom intensity in the free-ranging herd. At the captive site, older animals exhibited more severe declines in body condition as determined through declines in loin thickness, higher symptom burdens, and a decelerated antibody response to the pathogen. Younger animals were more likely than older animals to clear infection at or before the time of sampling at both sites. This study presents one of the richest datasets on immune responses in bighorn sheep over the course of a newly introduced M. ovipneumoniae strain available to-date.

Landslide susceptibility mapping has proved to be crucial tool for effective disaster management and planning strategies in mountainous regions. The present study is perused to investigate the changes in the landslide susceptibility of the Mandi district of Himachal Pradesh due to road construction. For this purpose, an inventory of 1723 landslides was generated from various sources. Out of these, 1199 (70%) landslides were taken in the training dataset to be used for modelling and prediction purposes, while 524 (30%) landslides were taken in the testing dataset to be used for validation purposes. Eleven landslide causative factors were selected from numerous hydrological, geological and topographical factors and were analyzed for landslide susceptibility mapping using three bivariate statistical models, namely; Frequency Ratio (FR), Certainty Factor (CF) and Shanon Entropy (SE). Two sets of LSM maps i.e. landslide susceptibility map natural (LSMN) and landslide susceptibility map road (LSMR), were generated using the above mentioned bivariate models and were divided into five landslide susceptibility classes namely; very low, low, medium, high and very high. These maps were analyzed for accuracy of prediction and validation using receiver operating characteristic (ROC) curves and area under curve (AUC) technique which indicated that all three bivariate statistical models performed satisfactorily with the SE model had the highest prediction and validation accuracy of 83-86%. Further analysis LSM maps confirmed that the percentage area in high and very high classes of land-slide susceptibility increased by 2.67-4.17% due to road construction activities in the study area.

Objective To examine the association between maternal education level and live birth after in vitro fertilization (IVF). Design Retrospective cohort study. Setting Public fertility center in China. Population 41546 women who underwent the first cycle of fresh or frozen-thawed embryo transfer between 2014 and 2019. Methods The women were divided into four educational categories according to the level of education received (elementary school graduate or less, middle school graduate, high school graduate, college graduate or higher). Main outcome measures Live birth rates. Results Patients were grouped by maternal educational level: elementary school graduate or less (n=1590), middle school graduate (n=10996), high school graduate (n=8354), and college graduate or higher (n=20606). The live birth rate, miscarriage rate, and clinical pregnancy rate in elementary school graduate or less were lower compared to other groups. In multivariate logistic regression analysis, we fail to demonstrate a statistically significant relationship between educational level and live birth in middle school graduate (adjusted odds ratio [AOR] 0.96; 95% confidence interval [CI], 0.84-1.09), high school graduate (AOR 1.01; 95% CI, 0.87-1.14) or college graduate or higher (AOR 1.01; 95% CI, 0.88-1.14) patients compared with the elementary school graduate or less reference group after adjusting for female age, infertility duration, BMI, EM thickness, no. of oocyte retrieved, infertility type, protocol in the fresh cycle, fertilization type, time of transfer and no. of embryo transferred. Conclusion No statistically significant relationship was identified between educational level and live birth in patients undergoing fresh or frozen embryo transfer.

Title: Notch4, uncovering an immunomodulator in allergic asthmaAuthors: Beatriz Moyaa,b, Manali Mukherjeec and Parameswaran Nairca. Department of Allergy, Hospital Universitario 12 de Octubre, Madrid, Spainb. Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spainc. Division of Respirology, Department of Medicine, McMaster University, Hamilton & Firestone Institute for Respiratory Health, St Joseph’s Healthcare, Hamilton, ON, CanadaCorrespondence to : Beatriz Moya. Allergy Department. Hospital Universitario 12 de Octubre, Madrid, SpainEmail:drbeatrizmoya@gmail.comAcknowledgements : Dr. Mukherjee is supported by investigator award from Canadian Institutes of Health Research and Canadian Allergy, Asthma, and Immunology Foundation. She has received honorarium from AZ, GSK and her university has received grants from Methapharm Speciality Pharmaceuticals. Dr. Nair is supported by the Frederick E. Hargreave Teva Innovation Chair in Airway Diseases. He has received honoraria from AZ, Sanofi, Teva, Merck, Novartis and Equillium and his university has received research grants from AZ, Teva, Sanofi, Novartis, BI and Methapharm. The authors recognize Dr. Anna Globinska for graphical abstract design and Dr. Rodrigo Jiménez-Saiz for critical review of the manuscript.Keywords: Allergic asthma; Airway inflammation; Th2 cell; Th17 cell; Treg cell; Notch4 receptorAbbreviations: Th, T helper; UFPs, pollutant ultrafine particles; AMs, alveolar macrophages; Treg cells, regulatory T cells; ILC2s, type 2 innate lymphoid cells; GDF15, cytokine growth and differentiation factor 15; IL, interleukin; IL-6R, interleukin-6 receptor; IL-4R, interleukin-4 receptorWord count: 918/1000

Accurate chemical kinetics are essential for reactor design and operation. However, despite recent advances in “big data” approaches, availability of kinetic data is often limited in industrial practice. Herein, we present a comparative proof-of-concept study for kinetic parameter estimation from limited data. Cross-validation (CV) is implemented to nonlinear least-squares (LS) fitting and evaluated against Markov chain Monte Carlo (MCMC) and genetic algorithm (GA) routines using synthetic data generated from a simple model reaction. As expected, conventional LS is fastest but least accurate in predicting true kinetics. MCMC and GA are effective for larger data sets but tend to overfit to noise for limited data. Cross-validation least-square (LS-CV) strongly outperforms these methods at much reduced computational cost, especially for significant noise. Our findings suggest that implementation of cross-validation with conventional regression provides an efficient approach to kinetic parameter estimation with high accuracy, robustness against noise, and only minimal increase in complexity.

Aim A robust and user-friendly software tool was developed for the prediction of dopamine D2 receptor occupancy (RO) in patients with schizophrenia treated with either olanzapine or risperidone. This tool can facilitate clinician exploration of the impact of treatment strategies on RO using sparse plasma concentration measurements. Methods Previously developed population pharmacokinetic (PPK) models for olanzapine and risperidone were combined with a PD model for D2 receptor occupancy (RO) and implemented in the R programming language. MAP Bayesian estimation was used to provide predictions of plasma concentration and receptor occupancy and based on sparse PK measurements. Results The average (standard deviation) response times of the tools were 2.8 (3.1) and 5.3 (4.3) seconds for olanzapine and risperidone, respectively. The mean error (95% confidence interval) and root mean squared error (RMSE, 95% CI) of predicted versus observed concentrations were 3.73 ng/mL (-2.42 – 9.87) and 10.816 (6.71 – 14.93) for olanzapine, and 0.46 ng/mL (-4.56 – 5.47) and 6.68 (3.57 – 9.78) for risperidone and its active metabolite (9-OH risperidone). Mean error and RMSE of RO were -1.47% (-4.65 – 1.69) and 5.80 (3.89 – 7.72) for olanzapine and -0.91% (-7.68 – 5.85) and 8.87 (4.56 – 13.17) for risperidone. Conclusion Treatment of schizophrenia with antipsychotics offers unique challenges and requires careful monitoring to establish the optimal dosing regimen. Our monitoring software predicts RO in a reliable and accurate form.

The coexistence of granular liquid-like phase (cluster) and gas-like phase (void) in fluidization, a spontaneous symmetry-breaking dissipative state, contributes to excellent mixing behavior in multi-phase reactors. In present study, a universal granular state equation to describe phase coexistence far from critical point is developed, where both the inelastic solid-collision and asymmetrical instability is taken into consideration. Catastrophe theory is applied to find the stable boundary of phase coexistence, and verified by cold-flow experiment with different solid pressure. A phase diagram, based on both theoretical analysis and experimental study, is given as a useful guideline of design and operation of efficient multi-phase reactors.

Background: Resolution of inflammation is now recognized as a tightly regulated and active process. Lipoxins (LX) are lead members of a larger family of specialized pro-resolving mediators with unique anti-inflammatory and pro-resolving properties. Recent studies implicated natural killer (NK) cells in the resolution of allergic airway inflammation, notably in promoting eosinophil apoptosis. The aim of the study was to better understand the pro-resolving actions of NK cells and LXA4 during allergic eosinophilic airway inflammation. Methods: 20 subjects with grass pollen allergic rhinitis were included. A nasal provocation test with either a single grass pollen allergen threshold dose or diluent was used. Nasal lavage fluid and cells were collected at baseline and at different time points after challenge. For in vitro assays, eosinophils were incubated with NK cells. Results: We observed that NK cells were recruited to the nasal mucosa shortly after the initiation of the allergic inflammatory response. This recruitment correlated with eosinophilic inflammation. In vitro assays demonstrated that direct contact and a combined action of CD56bright and CD56dim NK cells were needed to promote autologous eosinophil apoptosis. We furthermore observed that local LXA4 production correlated with the peak of neutrophil nasal mucosal infiltration, suggesting a potential role of neutrophils in LXA4 biosynthesis during the early phase of the allergic inflammatory response. Last, LXA4 appeared as essential to inhibit the in vitro release of eosinophil superoxide triggered by NK cells. Conclusion: Together, these findings indicate a synergistic role for NK cells and LXA4 in the resolution of allergic eosinophilic inflammation.

A document by Gualberto Ruaño M.D., written on Authorea.

This article proposes an analytical model to understand the rod-growth of eutectic in the bulk undercooled melt. Based on the previous derivations of the lamellar eutectic growth models, relaxing the assumptions of small Peclet numbers, the model is derived by considering melt kinetic and thermal undercoolings. The intent of this model is to predict the transitions in eutectic pattern for conditions of the low and high growth velocity. In addition to investigation of the transition between lamellar and rod eutectic pattern, mathematical simplifications of solving Bessel function are presented as well, which is the most important priority to model calculation.

In the development of personalized medicine, the ultrasensitive detection of point mutations that correlate with diseases is important to improve the efficacy of treatment and guide clinical medication. In this study, locked nucleic acid (LNA) was introduced as an amplification suppressor of a massive number of wild-type alleles in an amplification refractory mutation system (ARMS) to achieve the detection of low-abundance mutations with high specificity and sensitivity of at least 0.1%. By integrating the length of clamp, base type, number and position of LNA modifications, we have established a “shortest length with the fewest LNA bases” principle from which each LNA base would play a key role in the affinity and the ability of single base discrimination could be improve. Finally, based on this LNA design guideline, a series of the most important single point mutation sites of epidermal growth factor receptor (EGFR) was verified to achieve the optimal amplification state which as low as 0.1% mutation gene amplification was not affected under the wild gene amplification was completely inhibited, demonstrating that the proposed design principle has good applicability and versatility and is of great significance for the detection of circulating tumor DNA.