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Genital psoriasis can be stigmatizing, is highly prevalent among patients with psoriasis, and has limited treatment options. Apremilast is a unique oral immunomodulating phosphodiesterase 4 inhibitor approved for psoriasis treatment. To assess the efficacy and safety of apremilast 30 mg twice daily in patients with genital psoriasis. DISCREET, a phase 3, placebo-controlled trial (NCT03777436), randomized patients with moderate-to-severe genital psoriasis (stratified by affected body surface area <10% or ≥10%) to apremilast or placebo for a 16-week period, followed by an apremilast extension period. Week 16 results are presented. Patients were randomized to apremilast (n = 143) or placebo (n = 146). At Week 16, 39.6% and 19.5% of apremilast and placebo patients, respectively, achieved a modified static Physician Global Assessment of Genitalia response (primary endpoint; score of 0/1, ≥2-point reduction); treatment difference was significant (20.1%, P =.0003). Improvements in genital signs and symptoms, skin involvement, and quality of life were observed. Common treatment-emergent adverse events were diarrhea, headache, nausea, and nasopharyngitis. Lack of active-comparator. Apremilast demonstrated statistically and clinically meaningful genital Physician Global Assessment responses and improvement of signs, symptoms, severity, and quality of life in this first randomized, controlled study of an oral systemic treatment in patients with genital psoriasis. [ABSTRACT FROM AUTHOR]

Identical in situ dust detectors are flown on board the Galileo and Ulysses spacecraft. They record impacts of micrometeoroids in the ecliptic plane at heliocentric distances from 0.7 to 5.4 AU and in a plane almost perpendicular to the ecliptic from -79 [degrees] to +79 [degrees] ecliptic latitude. The combination of both Ulysses and Galileo measurements yields information about the radial and latitudinal distributions of micron- and submicron-sized dust in the Solar System. Two types of dust particles were found to dominate the dust flux in interplanetary space. Interplanetary micrometeoroids covering a wide mass range from [10.sup.-16] to [10.sup.-6] g are recorded mostly inside 3 AU and at latitudes below 30 [degrees]. Interstellar grains with masses between [10.sup.-14] and [10.sup.-12] g have been positively identified outside 3 AU near the ecliptic plane and outside 1.8 AU at high ecliptic latitudes (>50 [degrees]). Interstellar grains move on hyperbolic trajectories through the planetary system and constitute the dominant dust flux (1.5 x [10.sup.-4] [m.sup.-2] [sec.sup.-1]) in the outer Solar System and at high ecliptic latitudes. To compare and analyze the Galileo and Ulysses data sets, a new model is developed based on J. Geophys. Res. 98, 17029-17048, Divine's (1993, 'five populations of interplanetary meteoroids' model. Both models describe the interplanetary meteoroid environment in terms of dust populations on distinct orbits. Taking into account the measured velocities and the effect of radiation pressure on small particles (described by the ratio of radiation pressure force to gravity, [Beta]), we define four populations of meteoroids on elliptical orbits and one population on hyperbolic orbit that can fit the micrometeoroid flux observed by Galileo and Ulysses. Micrometeoroids with masses greater than [10.sup.-10] g and negligible radiation pressure ([Beta] = 0) orbit the Sun on low to moderately eccentric orbits and with low inclinations ([less than or equal to] 30 [degrees]). Populations of smaller particles with mean masses of [10.sup.-11] g ([Beta] = 0.3), [10.sup.-13] g ([Beta] = 0.8), and 5 x [10.sup.-15] g ([Beta] = 0.3), respectively, have components with high eccentricities and have increasingly wider inclination distributions with decreasing mass. Similarities among the orbit distributions of the small particle populations on bound orbits suggest that all are genetically related and are part of an overall micrometeoroid complex that prevails in the inner Solar System. The high-eccentricity component of the small particle populations may actually be [Beta]-meteoroids which are not well characterized by our measurements. Our modeling suggests further that the interstellar dust flux is not reduced at Ulysses' perihelion distance (1.3 AU) and that it contributes about 30% of the total dust flux observed there.

Background: Peri-device leaks and device thrombi are assumed to lead to ischemic events after percutaneous left atrial appendage occlusion (LAAO). While these device-related complications are well assessed until 12 months after LAAO, no data are available beyond this period.Objective: The purpose of this study was to assess device-related complications beyond 12 months after LAAO.Methods: All patients who underwent successful percutaneous LAAO ≥12 months ago in the 2 participating centers were screened for eligibility. After inclusion, structured transesophageal echocardiography (TEE) was performed to assess peri-device leaks, device thrombus, and other device-related complications.Results: A total of 63 patients were enrolled in the present prospective, 2-center, nonrandomized, single-arm trial. The median time from implantation until long-term TEE was 3.1 years (interquartile range 2.0-5.1 years), ranging from 1.0 to 7.5 years. The number of patients without a detectable leak increased significantly at long-term TEE compared with 6-week follow-up (P = .04). Major peri-device leaks (>5 mm) were detected in 2 patients (3%). Device thrombus was found in 8 patients (13%). Patients with device thrombus at long-term follow-up had larger peri-device leaks at 6-week follow-up than did those without thrombus formation (3.0 [interquartile range 2.7-3.5] vs 1.4 [interquartile range 0.0-2.6]; P = .04). Of those who suffered an ischemic stroke during long-term follow-up (n = 5), 1 patient showed a peri-device leak >5 mm. None of the patients with detected device thrombus had a stroke.Conclusion: Peri-device leaks and device thrombi continue to occur during long-term follow-up after LAAO. The clinical impact of these late occluder complications requires further evaluation in larger prospective trials. [ABSTRACT FROM AUTHOR]

In this work, 1 g model tests on vibratory pile driving in saturated sand are simulated, using different coupled element formulations in conjunction with a hypoplastic constitutive model. Owing to the high frequency of the vibrator in the model tests, the influence of the relative acceleration between the solid and water phases cannot be neglected a priori. The frequently applied u-p formulation assumes the relative acceleration to be zero; hence, two additional element formulations (the u-U and u-p-U approaches) are applied. A general investigation regarding the relative acceleration is first conducted using a semi-analytical approach, based on which the impact of the relative acceleration can be expressed by the wave frequency and hydraulic conductivity alone. Further, a threshold level of applicability of the u-p formulation is established. A comparison of the different element formulations used in the simulation of the vibratory driving model tests reveals that the relative acceleration has little impact, and the frequency threshold level obtained by the analytical solution holds. The simulations exhibit strong accordance with the experimental data in terms of pile penetration and pore pressure development. Different numerical aspects of the element formulations are discussed, including problems regarding volumetric locking and conditioning of the stiffness matrices. [ABSTRACT FROM AUTHOR]

Graphical abstract Health related off-target-phenotypes (OTPs) associated with SNP (single nucleotide polymorphism) markers used in forensic DNA phenotyping (FDP) and biogeographic ancestry inference (BGA). Highlights • 27 of 1766 SNPs used in FDP and BGA reveal health-related information. • Effect sizes for a small subset of the SNPs are considerable. • Off-target phenotypes: disposition to develop cancer, alcohol dependence, asthma. • We provide a list of off-target associations of BGA and FDP SNPs as a resource. Abstract With recent advances in DNA sequencing technologies it has become feasible and cost effective to genotype larger marker sets for forensic purposes. Two technologies that make use of the larger marker sets have come into focus in forensic research and applications; inference of biogeographic ancestry (BGA) and forensic DNA phenotyping (FDP). These methods hold the promise to reveal information about a yet unknown perpetrator from a DNA sample. In contrast, DNA-profiling, that is a standard practice in case work, relies on matching DNA-profiles between crime scene material and suspects on a database of DNA-profiles. Markers for DNA-profiling were developed under the premise to reveal as little additional information about the human source of the profile as possible, the rationale being that personal privacy rights have to be balanced against the public interest in solving a crime. The same argument holds for markers used in BGA and FDP; these markers might also reveal information on off-target phenotypes (OTPs), that go beyond BGA and the phenotypes targeted in FDP. In particular, health related OTPs might shift the balance between privacy protection and public interest. However, to our knowledge, there is currently no convenient resource available to incorporate knowledge on OTPs in BGA and FDP assay design and application. In order to provide such a resource, we performed a systematic search for OTPs associated with a comprehensive set of markers (1766 SNPs) used or suggested to be used for BGA inference and FDP. In this set, we identified a relatively small number of 27 SNPs (1.53%) that convey information on diverse health related OTPs such as cancer risk, induced asthma, or risk of alcoholism. Some of these SNPs are commonly used for FDP and BGA across different marker sets. We conclude that the effects of SNP markers used in FDP and BGA on OTPs are currently limited, with few exceptions that should be considered in a balanced decision on assay design and application. [ABSTRACT FROM AUTHOR]

Abstract Background/Purpose We initiated a pediatric surgical program including a caregiver for the induction of anesthesia. We measured preoperative midazolam administration, preoperative time, induction time, and program satisfaction. Methods Families with children undergoing surgery during the study period were included. Preoperative midazolam administration, preoperative time, and induction time were compared between participants and controls. Satisfaction surveys were given to participating caregivers and staff. Results The rate of preoperative midazolam use decreased from 41% (392/964) to 13% (16/118) among participants vs controls (p < 0.0001). After linear regression analysis, this difference persisted as an adjusted odds ratio of 0.29 (95% CI = 0.16–0.52). Preoperative and induction times (minutes) were similar between groups (76.2 vs 82.2, 13.8 vs 16.2, p = nonsignificant). Based on 5-point Likert surveys, the program was rated as "beneficial" or "very beneficial" to the patient by caregivers (99.2%) and staff (77.5%). Caregivers stated it "reduced" or "greatly reduced" anxiety for them (87.1%) and their child (93.2%). Conclusions Opponents of similar programs suggest familial presence slows care and is disruptive. Our program decreased utilization of preoperative anxiolytics with no effect on operating room efficiency. Both hospital staff and participants felt the program was beneficial to the patient. Perceived caregiver and child anxiety was reduced. Type of study Treatment study. Level of evidence Level III. [ABSTRACT FROM AUTHOR]

Background Omalizumab, a recombinant anti-IgE antibody, effectively treats chronic spontaneous urticaria. Evidence is lacking in patients with chronic inducible urticarias (CIndUs), which are frequently H 1 -antihistamine resistant. Objective From the current published literature, we aimed to determine the strength of evidence for omalizumab efficacy and safety in the treatment of CIndUs. Methods We performed a PubMed search to identify evidence on omalizumab use in the following 9 CIndU subtypes: symptomatic dermographism, cold urticaria, delayed-pressure urticaria, solar urticaria, heat urticaria, vibratory angioedema, cholinergic urticaria, contact urticaria, and aquagenic urticaria. Results Forty-three trials, case studies, case reports, and analyses were identified. Our review indicates that omalizumab has substantial benefits in patients with various CIndUs. The evidence is strongest for symptomatic dermographism, cold urticaria, and solar urticaria. Little/no evidence was available on vibratory angioedema and aquagenic and contact urticaria. Our review supports rapid onset of action demonstrated through early symptom control in most cases, sometimes within 24 hours. Many patients gained complete/partial symptom relief and substantially improved quality of life. Adverse events were generally low, with omalizumab being well tolerated by most patients, including children. Conclusions A strong body of evidence supports the use of omalizumab in the treatment of patients with therapy-refractory CIndU. More data from randomized controlled studies are warranted. [ABSTRACT FROM AUTHOR]

The seasonality of African swine fever (ASF) outbreaks in domestic pigs differs between temperate and subtropical/tropical regions. We hypothesise that variations in the importance of wild boar-to-farm and farm-to-farm transmission routes shape these contrasting patterns, and we emphasise the implications for effective ASF control. [ABSTRACT FROM AUTHOR]

Chronic urticaria (CU) is a debilitating mast cell–driven disease, often refractory to standard therapy (ie, antihistamines). Lirentelimab, an anti–sialic acid–binding immunoglobulin-like lectin 8 mAb, selectively inhibits mast cells and depletes eosinophils. We sought to determine safety and efficacy of lirentelimab in patients with CU. This phase 2a study enrolled patients with CU refractory to up to 4-fold H1-antihistamine doses. Patients received 6 monthly intravenous doses of lirentelimab (0.3, 1, and up to 3 mg/kg). Primary efficacy end point was change in Urticaria Control Test score at week 22. Urticaria Activity Score weekly average (UAS7) was assessed in patients with chronic spontaneous urticaria (CSU), and Cholinergic UAS7 was used for patients with cholinergic urticaria (CholU). A total of 45 patients were enrolled in 4 cohorts (n = 13 omalizumab-naive CSU, n = 11 omalizumab-refractory CSU, n = 11 CholU, n = 10 symptomatic dermographism). Urticaria Control Test scores increased with lirentelimab across cohorts, with mean changes at week 22 of 11.1 ± 4.1, 4.8 ± 7.0, 6.5 ± 6.2, and 3.4 ± 4.1 and complete response rates (Urticaria Control Test score ≥ 12) of 92%, 36%, 82%, and 40%, respectively. In omalizumab-naive and omalizumab-refractory patients with CSU, disease activity decreased at week 22 (mean UAS7 change, −73% and −47%, respectively), with UAS7 response rates (≥50% reduction) of 77% and 45%, respectively. In patients with symptomatic dermographism, 50% (5 of 10) and 40% (4 of 10) had complete itch and hive resolution by FricTest, respectively, and 100% (7 of 7) evaluable patients with CholU had negative responses to Pulse-Controlled Ergometry exercise test. Most common adverse events included infusion-related reactions (43%; all mild/moderate and transient), nasopharyngitis (21%), and headache (19%). No treatment-related serious adverse events occurred. Lirentelimab demonstrated activity across 3 forms of antihistamine-refractory CU. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1-antihistamines along with 1 or more add-on therapies. Objectives: We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H1-antihistamines at up to 4 times the approved dose plus H2-antihistamines, leukotriene receptor antagonists, or both. Methods: In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary objective of the study was to evaluate the overall safety of omalizumab compared with placebo. Efficacy (itch severity, hive, and urticaria activity scores) was evaluated at weeks 12 and 24. Results: The overall incidence and severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients; the safety profile was consistent with omalizumab in patients with allergic asthma. At week 12, the mean change from baseline in weekly itch severity score was −8.6 (95% CI, −9.3 to −7.8) in the omalizumab group compared with −4.0 (95% CI, −5.3 to −2.7) in the placebo group (P < .001). Significant improvements were seen for additional efficacy end points at week 12; these benefits were sustained to week 24. Conclusion: Omalizumab was well tolerated and reduced the signs and symptoms of CIU/CSU in patients who remained symptomatic despite the use of H1-antihistamines (up to 4 times the approved dose) plus H2-antihistamines, leukotriene receptor antagonists, or both. [Copyright &y& Elsevier]

Objective: Tooth extractions may trigger clinical symptoms of hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH). The aim of this study was to determine how many tooth extractions were followed by symptoms of HAE-C1-INH in patients with and without preoperative short-term prophylaxis with C1 inhibitor concentrate. Study design: Tooth extractions and clinical symptoms of HAE-C1-INH were determined from clinical record files of 171 patients with HAE-C1-INH. Results: Facial swelling or potentially life-threatening laryngeal edema, or both, occurred in 124/577 tooth extractions (21.5%) without prophylaxis. Similar symptoms occurred in a fewer proportion of patients undergoing extractions (16/128; 12.5%) after short-term prophylaxis with C1 inhibitor concentrate. The graded dose-response relationship was significant at P < .05. Conclusions: Short-term prophylaxis with C1 inhibitor concentrate significantly reduces the risk of HAE-C1-INH symptoms after tooth extraction. In some patients, however, facial swellings and laryngeal edema symptoms may occur despite prophylaxis. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to evaluate the safety and effectiveness of the SeptRx patent foramen ovale (PFO) closure device (SeptRx, Inc., Fremont, California). Background: A PFO is a relatively common remnant of the fetal circulation that can be associated with cryptogenic stroke, transient ischemic attack, migraine, or decompression sickness. Percutaneous PFO closure with different devices has been performed for many years. However, most of the common devices leave a relatively large amount of material in the left and right atria. The SeptRx PFO device (SeptRx, Inc.) is the first PFO closure device designed to fit directly into the pocket of the PFO. Methods: From July 2006 to May 2007, 13 patients between 18 and 65 years of age with a history of cryptogenic stroke or transient ischemic attack were included into this first-in-man trial. All patients received 100 mg aspirin and 75 mg clopidogrel for 6 months. Follow-up was done at 1 and 6 months after procedure with transesophageal echocardiography and transcranial Doppler. Results: In 11 of 13 patients, PFO closure with the SeptRx device was successfully performed. In 2 patients, PFO closure with this device was not possible due to the anatomy of the PFO; 1 device was retrieved before release, and the other was recaptured with a snare. After 30 days, 6 of the 11 PFOs were closed; after 6 months, all were closed. No adverse events occurred. Conclusions: The SeptRx PFO closure device appears to be safe and effective. The advantage of this occluder is that there is only minimal foreign material on the left and right sides of the interatrial septum. This is the first such “in-tunnel” PFO closure device. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema caused by mutations in the factor XII gene is a recently described disease entity that occurs mainly in women. It differs from hereditary angioedema caused by C1 inhibitor deficiency. Objective: To assess the clinical symptoms, factors triggering acute attacks, and treatments of this disease. Methods: Thirty-five female patients with hereditary angioedema and the factor XII mutations p.Thr309Lys and p.Thr309Arg who came from 13 unrelated families were studied. The observation period was 8.4 years on average (range, 2-26 years). Results: Patients had on average 12.7 ± 7.9 angioedema attacks per year. Recurrent facial swellings occurred in all patients; skin swellings other than facial, abdominal pain attacks, tongue swellings, and laryngeal edema occurred less frequently. Some factors that triggered angioedema attacks were trauma, physical pressure, and emotional stress. Clinical symptoms started mainly after intake of oral contraceptives (17 women) or pregnancy (3 women). Exacerbation of the symptoms occurred after oral contraceptive use (8 women), pregnancy (7 women), hormone replacement therapy (3 women), intake of angiotensin-converting enzyme inhibitors (2 women), and an angiotensin 1 receptor blocker (1 woman). Effective treatments included C1 inhibitor concentrate for angioedema attacks (6 women) and, for prophylaxis, progesterone (8 women), danazol (2 women), and tranexamic acid (1 woman). No difference between mutation p.Thr309Arg and p.Thr309Lys was found. Conclusions: Facial swelling is a cardinal symptom of this condition. Estrogens may have a great influence, but this influence is highly variable. Various treatment options are available. [Copyright &y& Elsevier]

The inference of biogeographic ancestry (BGA) has become a focus of forensic genetics. Misinference of BGA can have profound unwanted consequences for investigations and society. We show that recent admixture can lead to misclassification and erroneous inference of ancestry proportions, using state of the art analysis tools with (i) simulations, (ii) 1000 genomes project data, and (iii) two individuals analyzed using the ForenSeq DNA Signature Prep Kit. Subsequently, we extend existing tools for estimation of individual ancestry (IA) by allowing for different IA in both parents, leading to estimates of parental individual ancestry (PIA), and a statistical test for recent admixture. Estimation of PIA outperforms IA in most scenarios of recent admixture. Furthermore, additional information about parental ancestry can be acquired with PIA that may guide casework. • We improve statistical methods for Biogeographical Ancestry inference to account for different admixture of both parents. • The resulting recent admixture model has a higher accuracy in estimating individual admixture in most cases. • We give a likelihood ratio test for recent admixture, which is both highly specific and sensitive for recent admixture. • We find evidence of recent admixture in the 1000 genomes dataset. • The self-report on recent admixture of two self-sequenced samples was only confirmed in one case. [ABSTRACT FROM AUTHOR]

The performance of three advanced constitutive models has been evaluated based on element tests and on a comparative study on the simulation of vibratory pile driving tests in saturated sand. The inspected constitutive models are the Sanisand model and Hypoplasticity with Intergranular Strain (Hypo+IGS) as well as with Intergranular Strain Anisotropy (Hypo+ISA) extension. The performance of the constitutive models is first evaluated by the simulation of element tests used for the parameter calibration of the sand used in the model tests. The constitutive models are then applied for the simulation of a vibratory pile driving test. The pile penetration, the driving force, the pore water pressure development and the incremental displacement in the vicinity of the pile tip are compared to the measurements in the model tests. The strengths and weaknesses of the different constitutive models are assessed. Generally, the model predictions showed good agreement with the experimental results. Despite different constitutive formulations (hypoplastic vs. elasto-plastic), all three models were able to reproduce the main mechanisms of the driving process properly. It may be concluded that all three models allow a proper prediction of vibratory pile driving as long as a proper calibration of the material parameters is secured. [ABSTRACT FROM AUTHOR]

The back-analysis of model tests on piles subjected to high-cyclic lateral loading using the high-cycle accumulation (HCA) model is presented. The installation of the pile prior to the lateral loading is taken into account using a Coupled-Eulerian–Lagrangian method. A comparison between the measured pile rotation and the results of simulations with incorporation of the installation-induced soil changes as well as simulations assuming wished-in-place initial conditions is made. A distinct influence of the installation process on the lateral response of the pile is observed. The installed piles exhibit larger resistance and less accumulation of deformation during the cyclic loading. The simulations taking into account the installation process are in better accordance with the measurements in the model tests compared to the wished-in-place simulations. It is concluded that the consideration of the installation process in a back-analysis of driven piles subjected to monotonic or cyclic loading is of great importance. [ABSTRACT FROM AUTHOR]

The installation process changes the state of the soil in the vicinity of a pile and therefore influences its load-displacement behaviour during the operational phase following the installation. The installation process itself and its effect on the pile behaviour under a subsequent high-cyclic loading are numerically investigated in this work. Two different installation techniques, namely impact driving and jacking, are investigated using a coupled Eulerian-Lagrangian approach in combination with a hypoplastic material model. Either ideally drained or partially drained conditions are assumed. Afterwards the pile response to a high-cyclic loading with up to five million load cycles is studied using a high-cycle accumulation (HCA) model. Compared to a wished-in-place (WIP) pile, the simulations accounting for the installation process showed considerable less permanent pile displacements in case of initially medium dense sand. However, the opposite was observed in case of initially dense sand. Current practice assuming a WIP state as the starting point in numerical simulations seems thus to be conservative for initially medium dense sand but leads to an underestimation of permanent deformations for initially dense sand. • Coupled Eulerian-Lagrangian (CEL) method considering partially drained conditions for problems with high accelerations. • Simulation of pile installation considering partially drained conditions using the CEL method. • Influence of the installation on the long-term cyclic behaviour using the high-cycle accumulation (HCA) model. [ABSTRACT FROM AUTHOR]

A parametric study on the long-term deformations of monopile foundations for offshore wind turbines is presented. The finite element calculations of a monopile in fine sand were performed with a high-cycle accumulation (HCA) model. The results are analyzed with respect to the horizontal displacements, the tilting of the pile head, settlement of the ground surface and effective stress changes in the surrounding soil. The dimensions of the pile (diameter, length of embedding, wall thickness), the initial density of the sand and the cyclic loading (average value, amplitude, lever arm) have been varied. The influence of the drainage conditions (either fully drained or partially drained) is also discussed. The validity of Miner's rule is checked for both types of drainage conditions. Furthermore, the effect of changes of the direction of the cycles and of a multidimensional cyclic loading is addressed. The interesting phenomenon of a "self-healing", i.e. a re-erection of the deformed monopile after a storm event, is demonstrated based on simulations with small cycles following a large preloading. Simulations with homogeneous and stochastically fluctuating fields of void ratio are compared. [ABSTRACT FROM AUTHOR]

Abstract Earthquake stability assessment of large opencast mine slopes are complex and non-linear problems, often addressed using pseudo-static approaches neglecting material-induced failures and the role of pore-fluids. In this study, a numerical approach is used to understand the dynamic response of saturated and partially saturated soils. For this purpose user-defined elements have been implemented in Abaqus/Standard including user-defined material models. The governing equations involving coupled fluid flow and finite deformation processes in partially saturated soils are derived within the framework of the Theory of Porous Media. The stress-strain behavior of granular soils is represented by a hypoplastic constitutive model and for clayey soils the ISA-Clay model is used. The saturation-suction behavior is modeled using the van Genuchten model. To account for the large scale of the finite element model, a scaling procedure of the system of equations is proposed to purge the influence of initial stress. The performance of the user-defined elements is tested by back analysis of a centrifuge test available in the literature. Finally, large-scale fully coupled finite element simulations are performed to study the response of a flooded opencast mine under earthquake loading. The paper illustrates the importance of accounting the pore-fluids as independent phases in the context of seismic analysis of slopes and the influence of simplifications on which the calculation is based are highlighted. The simulations show strong wave diffraction effects for inhomogeneous dump structures, resulting in smaller displacements in near-surface areas of the slope. Further it was found that large areas of the dump show a temporary decrease of effective stress. The initial strong differences in stiffness between the different materials may decrease with time after several seismic events due stress redistributions caused by earthquakes. Highlights • Large-scale FE simulation of an opencast mine with inhomogeneous internal geometry. • Influence of additional compaction measures on the earthquake resistance. • Influence of initial stress on the numerical stability of large-scale FE simulations. • Modification of the System of Equations for large-scale geotechnical simulations. [ABSTRACT FROM AUTHOR]

Background: Chronic urticaria is a frequent and debilitating skin disease. Its symptoms commonly fluctuate considerably from day to day. As of yet, the only reliable tool to assess disease activity is the Urticaria Activity Score, which prospectively documents the signs and symptoms of urticaria for several days. Objective: We sought to develop and validate a novel patient-reported outcome instrument to retrospectively assess urticaria control, the Urticaria Control Test (UCT). Methods: Potential UCT items were developed by using established methods (literature research and expert and patient involvement). Subsequently, item reduction was performed by using a combined approach, applying impact and regression analysis. The resulting UCT instrument was then tested for its validity, reliability, and screening accuracy. Results: A 4-item UCT with a recall period of 4 weeks was developed based on 25 potential UCT items tested in 508 patients with chronic urticaria. A subsequent validation study with the 4-item UCT in 120 patients with chronic urticaria demonstrated that this new tool exhibits good convergent and known-groups validity, as well as excellent test-retest reliability. In addition, the screening accuracy to identify patients with urticaria with insufficiently controlled disease was found to be high. Conclusions: The UCT is the first valid and reliable tool to assess disease control in patients with chronic urticaria (spontaneous and inducible). Its retrospective approach and simple scoring system make it an ideal instrument for the management of patients with chronic urticaria in clinical practice. [Copyright &y& Elsevier]

The Theory of Porous Media (TPM) has served as a reliable theory to deduce governing equations for unsaturated soils. In most works, the unsaturated soil is considered as a three-phase medium composed of air, water and solid. This neglects effects caused by the presence of residual water and/or entrapped (immobile) air attached to the particles. In this work, a set of governing equations for unsaturated soils with residual water and entrapped air is deduced. A mass transfer mechanism between the free air and the entrapped air is considered. The present work focuses only on the entrapped air attached to the particles (immobile air), and therefore it is assumed to have the same intrinsic velocity as the solid. This assumption allows to keep the same number of independent kinematic variables as in conventional three-phase theories. The performance of the theory is examined in simulations of water retention curves subjected to suction cycles, as well as in the dynamic analysis of a centrifuge test on a dam subjected to earthquake loading. [ABSTRACT FROM AUTHOR]