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This study investigates the efficacy of sodium alginate (SA), xanthan gum (XG), guar gum (GG) and chitosan (CS) — each applied at five different solid biopolymer-to-water mass ratios (or dosages) and cured for 7 d and 28 d — on the unconfined compressive strength (UCS) performance of a high plasticity clayey soil. Moreover, on identifying the optimum biopolymer-treatment scenarios, their performance was compared against conventional stabilization using hydrated lime. For a given curing time, the UCS for all biopolymers followed a rise–fall trend with increasing biopolymer dosage, peaking at an optimum dosage and then subsequently decreasing, such that all biopolymer-stabilized samples mobilized higher UCS values compared to the unamended soil. The optimum dosage was found to be 1.5% for SA, XG and CS, while a notably lower dosage of 0.5% was deemed optimum for GG. Similarly, for a given biopolymer type and dosage, increasing the curing time from 7 d to 28 d further enhanced the UCS, with the achieved improvements being generally more pronounced for XG- and CS-treated cases. None of the investigated biopolymers was able to produce UCS improvements equivalent to those obtained by the 28-d soil–lime samples; however, the optimum XG, GG and CS dosages, particularly after 28 d of curing, were easily able to replicate 7-d lime stabilization outcomes achieved with as high as twice the soil's lime demand. Finally, the fundamental principles of clay chemistry, in conjunction with the soil mechanics framework, were employed to identify and discuss the clay–biopolymer stabilization mechanisms.

3D printing is developing rapidly and enables the production of parts manufactured using different materials. These includes zirconium dioxide (ZrO2), which can be of particular interest for bone tissue engineering and implantology. However, highly accurate part-dimensions are a must for these applications, which is why this study addresses geometrical deviations which occur during the printing process and thermal post-processing.Six sets of test geometries with 50 individual features were 3D printed with two different ZrO2 slurries (3 mol% yttria-stabilized ZrO2) and scanned with a profilometer. After debinding and sintering, the profilometer scan was repeated and the deviations and shrinkage factors were determined.A notable difference is observed when the same ceramic is processed using two different slurries. For instance, one used ceramic slurry, LithaCon 210, exhibits shrinkage factors of shrXY=21.2±3.4% (n=78) and shrZ=23.6±0.54% (n=24) for protruding structures, while the other ceramic slurry, LithaCon 280, shows shrinkage factors of shrXY=21.7±3.3% (n=78) and shrZ=24.5±0.55% (n=24).Geometric deviations differed for intruding (like holes and slots) and protruding (like pillars) geometries, being more pronounced in case of intruding geometries, especially where printing overhangs occur.Although the shrinkage during sintering needs further investigation, these experimental findings are a good starting point to validate and refine simulation models for shrinkage and improve production processes of 3D printed ceramics.

A representative sub-surface shear wave velocity model is crucial for seismic hazard studies, as seismic waves are affected by sub-surface characteristics. The offered data in this article were mainly developed based on a quasi-static cone penetration test (q-CPT) collected at the west coast town of Aceh, Indonesia. Microtremor datasets measured at the same locations were employed to extend the depth of the sub-surface models and to validate the models. The in-situ q-CPT data were collected using a locally manufactured Begemann's type cone penetration test apparatus. Twenty seven (27) q-CPT soundings were performed to typical depths of 20 m or measuring cone tip resistances of at least 150 kg/cm2. Several empirical approaches were employed to deduce the sub-surface parameters, including shear wave velocity. To enhance the sub-surface model depth, 23 in-situ microtremor data were recorded using 3 components (3C) of Geobit S100 and RaspberrySHAKE (RS-3D) seismometers at the same locations where the q-CPTs were sounded. At the same time, these microtremor datasets were also utilized to validate the developed sub-surface shear wave velocity models using the forward modeling method. Therefore, all the proposed sub-surface shear wave models presented in this article have been validated. These sub-surface shear wave velocity models can be used for site characterization, i.e., site response analysis, seismic microzonation, or spatial urban planning.

DNA transposon-based gene delivery vectors represent a promising new branch of randomly integrating vector development for gene therapy. For the side-by-side evaluation of the piggyBac and Sleeping Beauty systems—the only DNA transposons currently employed in clinical trials—during therapeutic intervention, we treated the mouse model of tyrosinemia type I with liver-targeted gene delivery using both transposon vectors. For genome-wide mapping of transposon insertion sites we developed a new next-generation sequencing procedure called streptavidin-based enrichment sequencing, which allowed us to identify approximately one million integration sites for both systems. We revealed that a high proportion of piggyBac integrations are clustered in hot regions and found that they are frequently recurring at the same genomic positions among treated animals, indicating that the genome-wide distribution of Sleeping Beauty-generated integrations is closer to random. We also revealed that the piggyBac transposase protein exhibits prolonged activity, which predicts the risk of oncogenesis by generating chromosomal double-strand breaks. Safety concerns associated with prolonged transpositional activity draw attention to the importance of squeezing the active state of the transposase enzymes into a narrower time window.

Objectives: To develop and validate a simple approach for building cost-effective imaging phantoms for Cone Beam Computed Tomography (CBCT) using a modified Polyjet additive manufacturing technology where a single material can mimic a range of human soft-tissue radiation attenuation. Materials and Methods: Single material test phantoms using a cubic lattice were designed in 3-Matic 15.0 software . Keeping the individual cubic lattice volume constant, eight different percentage ratio (R) of air: material from 0% to 70% with a 10% increment were assigned to each sample. The phantoms were printed in three materials, namely Vero PureWhite, VeroClear and TangoPlus using Polyjet technology. The CT value analysis, non-contact profile measurement and microCT-based volumetric analysis was performed for all the samples. Results: The printed test phantoms produced a grey value spectrum equivalent to the radiation attenuation of human soft tissues in the range of −757 to +286 HU on CT. The results from dimensional comparison analysis of the printed phantoms with the digital test phantoms using non-contact profile measurement showed a mean accuracy of 99.07 % and that of micro-CT volumetric analysis showed mean volumetric accuracy of 84.80–94.91%. The material and printing costs of developing 24 test phantoms was 83.00 Euro. Conclusions: The study shows that additive manufacturing-guided macrostructure manipulation modifies successfully the radiographic visibility of a material in CBCT imaging with 1 mm3 resolution, helping customization of imaging phantoms.

Current medical imaging phantoms are usually limited by simplified geometry and radiographic skeletal homogeneity, which confines their usage for image quality assessment. In order to fabricate realistic imaging phantoms, replication of the entire tissue morphology and the associated CT numbers, defined as Hounsfield Unit (HU) is required. 3D printing is a promising technology for the production of medical imaging phantoms with accurate anatomical replication. So far, the majority of the imaging phantoms using 3D printing technologies tried to mimic the average HU of soft tissue human organs. One important aspect of the anthropomorphic imaging phantoms is also the replication of realistic radiodensities for bone tissues. In this study, we used filament printing technology to develop a CT-derived 3D printed thorax phantom with realistic bone-equivalent radiodensity using only one single commercially available filament. The generated thorax phantom geometry closely resembles a patient and includes direct manufacturing of bone structures while creating life-like heterogeneity within bone tissues. A HU analysis as well as a physical dimensional comparison were performed in order to evaluate the density and geometry agreement between the proposed phantom and the corresponding CT data. With the achieved density range (-482 to 968 HU) we could successfully mimic the realistic radiodensity of the bone marrow as well as the cortical bone for the ribs, vertebral body and dorsal vertebral column in the thorax skeleton. In addition, considering the large radiodensity range achieved a full thorax imaging phantom mimicking also soft tissues can become feasible. The physical dimensional comparison using both Extrema Analysis and Collision Detection methods confirmed a mean surface overlap of 90% and a mean volumetric overlap of 84,56% between the patient and phantom model. Furthermore, the reproducibility analyses revealed a good geometry and radiodensity duplicability in 24 printed cylinder replicas. Thus, according to our results, the proposed additively manufactured anthropomorphic thorax phantom has the potential to be efficiently used for validation of imaging- and radiation-based procedures in precision medicine.

Micaceous soils are common in many tropical countries and regions, and in some locations with moderate climate. The soils are spongy and unstable when loaded and are not considered suitable as construction material in earth structures. To resolve the issue, this work examined performance of micaceous soil reinforced with a combination of jute fibers, hydrated lime or slag-lime. A total of 28 sample sets were prepared at various dosages. Unconfined compression tests were conducted on the samples cured for 7 d and 28 d, respectively. The test results suggested that the unconfined compressive strength (UCS) and material stiffness were increased with the inclusion of up to 1% fiber and decreased if additional fibers were used. The ductility was improved consistently with up to 1.5% fiber content. The inclusions of fibers combined with hydrated lime or slag-lime further enhanced strength and stiffness of micaceous soil, and the improvement depended on the dosages used. For the dosages examined, jute fibers outweighed lime and slag in gaining ductility, and the optimal fiber content was 1% where strength and ductility were considered.

Micaceous soil is a problematic soil due to its low strength and poor ductility. In this context, the performances of micaceous soils were improved by applying a combination of granulated blast furnace slag, fiber and polymer additive. The dosages examined included 0%–30% mica, 3%–15% slag and 0.25%–1.25% fiber by weight, and 0.1–0.5 g/L polymer additive. Most of the combinations were found to increase the material strength and ductility, yet to be optimized. To refine the dosage, response surface method was used to conduct experimental design and develop predictive models for material strength. The developed models formulate the material strength as a nonlinear function of dosages and, by interrogating it, can optimize additive contents in terms of target requirements. The models were verified through trials and can be used to determine dosages to upscale micaceous soils to field conditions.

Summary: In 2019, Germany passed the Digital Healthcare Act, which, among other things, created a “Fast-Track” regulatory and reimbursement pathway for digital health applications in the German market. The pathway explicitly provides for flexibility in how researchers can present evidence for new digital products, including the use of real-world data and real-world evidence. Against this backdrop, the Digital Medicine Society and the Health Innovation Hub of the German Federal Ministry of Health convened a set of roundtable discussions to bring together international experts in evidence generation for digital medicine products. This Viewpoint highlights findings from these discussions with the aims of (1) accelerating and stimulating innovative approaches to digital medical product evaluation, and (2) promoting international harmonisation of best evidentiary practices. Advancing these topics and fostering international agreement on evaluation approaches will be vital to the safe, effective, and evidence-based deployment and acceptance of digital health applications globally.

The influence of towing speed on the effectiveness of the 4-sided impact roller using earth pressure cells (EPCs) is investigated. Two field trials were undertaken; the first trial used three EPCs placed at varying depths between 0.5 m and 1.5 m with towing speeds of 9–12 km/h. The second used three EPCs placed at a uniform depth of 0.8 m, with towing speeds of 5–15 km/h. The findings from the two trials confirmed that towing speed influences the pressure imparted to the ground and hence compactive effort. This paper proposes that the energy imparted to the ground is best described in terms of work done, which is the sum of the change in both potential and kinetic energies. Current practice of using either kinetic energy or gravitational potential energy should be avoided as neither can accurately quantify rolling dynamic compaction (RDC) when towing speed is varied. Keywords: Rolling dynamic compaction (RDC), Optimum towing speed, Ground improvement

This study aims to investigate the effect of mica content on the mechanical properties of clays. Commercially available ground mica was blended with a locally available clayey soil, at varying mica contents by mass of 5%, 10%, 15%, 20%, 25% and 30%, to artificially prepare various micaceous clay blends. The preliminary testing phase included consistency limits and standard Proctor compaction tests. The primary testing program consisted of unconfined compression (UC), direct shear (DS) and scanning electron microscopy (SEM) tests. The test results showed that the liquid and plastic limits exhibited a linear, monotonically increasing trend with increase in mica content. The rate of increase in the plastic limit, however, was found to be greater than that of the liquid limit, thereby leading to a gradual transition towards a non-plastic, cohesionless character. The soft, spongy fabric and high water demand of the mica mineral led to higher optimum water contents and lower maximum dry unit weights with increasing mica content. Under low confinement conditions, i.e. the UC test and the DS test at low normal stresses, the shear strength was adversely affected by mica. However, the closer packing of the clay and mica components in the matrix under high confinement conditions offsets the adverse effects of mica by inducing frictional resistance at the shearing interface, thus leading to improved strength resistance. Keywords: Micaceous clay, Mica content, Consistency limits, Compaction, Shear strength, Confinement, Frictional resistance

Rolling dynamic compaction (RDC), which employs non-circular module towed behind a tractor, is an innovative soil compaction method that has proven to be successful in many ground improvement applications. RDC involves repeatedly delivering high-energy impact blows onto the ground surface, which improves soil density and thus soil strength and stiffness. However, there exists a lack of methods to predict the effectiveness of RDC in different ground conditions, which has become a major obstacle to its adoption. For this, in this context, a prediction model is developed based on linear genetic programming (LGP), which is one of the common approaches in application of artificial intelligence for nonlinear forecasting. The model is based on in situ density-related data in terms of dynamic cone penetrometer (DCP) results obtained from several projects that have employed the 4-sided, 8-t impact roller (BH-1300). It is shown that the model is accurate and reliable over a range of soil types. Furthermore, a series of parametric studies confirms its robustness in generalizing data. In addition, the results of the comparative study indicate that the optimal LGP model has a better predictive performance than the existing artificial neural network (ANN) model developed earlier by the authors. Keywords: Ground improvement, Rolling dynamic compaction (RDC), Linear genetic programming (LGP), Dynamic cone penetrometer (DCP) test

The data presented in this article contain datasets of passive noise measurements at regolith sites in Adelaide, South Australia. The data were acquired using three component (3C) LE-3Dlite Lennartz seismometers with an eigenfrequency of 1 Hz. The data were acquired at eight sites across Adelaide׳s regolith in a hexagonal array layout. Four tests, each with a duration of 30 min, were conducted at different times. The ambient noise data can be used for both horizontal to vertical spectral ratio (HVSR) analysis and array analyses, which are essential to obtain the site fundamental frequency and the ellipticity of the fundamental mode Rayleigh waves at the measured site. The array analyses are useful to obtain the dispersion curves, which are needed to estimate the shear wave velocity profile. Keywords: Passive noise, Array, HVSR, SPAC, Regolith

Rolling dynamic compaction (RDC), which involves the towing of a noncircular module, is now widespread and accepted among many other soil compaction methods. However, to date, there is no accurate method for reliable prediction of the densification of soil and the extent of ground improvement by means of RDC. This study presents the application of artificial neural networks (ANNs) for a priori prediction of the effectiveness of RDC. The models are trained with in situ dynamic cone penetration (DCP) test data obtained from previous civil projects associated with the 4-sided impact roller. The predictions from the ANN models are in good agreement with the measured field data, as indicated by the model correlation coefficient of approximately 0.8. It is concluded that the ANN models developed in this study can be successfully employed to provide more accurate prediction of the performance of the RDC on a range of soil types.

Seven or fourteen days or twelve months after suturing one tube into the pyloric sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged esophagitis with a constantly lowered pressure not only in the pyloric, but also in the lower esophageal sphincter and a failure of both sphincters. Throughout the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given intraperitoneally once a day (10 µg/kg, 10 ng/kg, last application 24 h before assessment), or continuously in drinking water at 0.16 µg/ml, 0.16 ng/ml (12 ml/rat per day), or directly into the stomach 5 min before pressure assessment (a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through an esophageal or duodenal incision). This treatment alleviates i) the esophagitis (macroscopically and microscopically, at either region or interval), ii) the pressure in the pyloric sphincter, and iii) the pressure in the lower esophageal sphincter (cmH2O). In the normal rats it increases lower esophageal sphincter pressure, but decreases the pyloric sphincter pressure. Ranitidine, given using the same protocol (50 mg/kg, intraperitoneally, once daily; 0.83 mg/ml in drinking water; 50 mg/kg directly into the stomach) does not have an effect in either rats with esophagitis or in normal rats. Keywords:: stable gastric pentadecapeptide BPC 157, ranitidine, pyloric sphincter dysfunction, sphincter pressure, rat esophagitis

Objectives: The development of accelerated approval programs for high morbidity and unmet need conditions has driven the use of single-arm studies in drug development. Regulatory and health technology assessment (HTA) agencies are recognizing that high-quality external control arms (ECAs), built using real-world data, can reduce uncertainties arising from single-arm studies. This review compared 7 case studies of regulatory and HTA agencies' evaluations of oncology ECAs., Methods: Food and Drug Administration multidisciplinary reviews for oncology submissions from 2014 to 2021 were screened to identify 7 cases (2 blinatumomab indications, avelumab, and erdafitinib, entrectinib, trastuzumab deruxtecan, and idecabtagene vicleucel) with ECAs to support efficacy claims. Regulatory (Food and Drug Administration, European Medicines Agency, Health Canada) and HTA (pan-Canadian Oncology Drug Review, National Institute for Health and Care Excellence, Federal Joint Committee, Haute Autorité de Santé, and Pharmaceutical Benefits Advisory Committee) submissions for these cases were reviewed. The decision makers' ECA critiques and the level of influence on the decision were analyzed and categorized., Results: Across case studies, selection bias and confounding were the most common ECA critiques. Nevertheless, agreement in critiques between and among regulators and HTA bodies was low. ECA influence on agencies' decisions also varied., Conclusions: Evaluating the same ECA evidence, agencies focused on methodologic issues (ie, selection bias and confounding), but were often not aligned on their critiques. Further research is needed to fully characterize how agencies evaluate ECAs. This study is a first step in critically evaluating agencies' critiques of ECAs and highlights the need for future guidance development around ECA design and generation., (Copyright © 2022. Published by Elsevier Inc.)