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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.

Aim: To evaluate how transportability methods are currently used for real-world evidence (RWE) generation to inform good practices and support adoption and acceptance of these methods in the RWE context. Methods: We conducted a targeted literature review to identify studies that transported an effect estimate of the clinical effectiveness or safety of a biomedical exposure to a target real-world population. Records were identified from PubMed-indexed articles published any time before 25 July 2023 (inclusive). Two reviewers screened abstracts/titles and reviewed the full text of candidate studies to identify the final set of articles. Data on the therapeutic area, exposure(s), outcome(s), original and target populations and details of the transportability analysis (e.g., analytic method used, estimate transported, stated assumptions) were abstracted from each article. Results: Of 458 unique records identified, six were retained in the final review. Articles were published during 2021–2023, focused on the US/Canada context, and covered a range of therapeutic areas. Four studies transported an RCT effect estimate, while two transported effect estimates derived from real-world data. Almost all articles used weighting methods to transport estimates. Two studies discussed all transportability assumptions, and one evaluated the likelihood of meeting all assumptions and the impact of potential violations. Conclusion: The use of transportability methods for RWE generation is an emerging and promising area of research to address evidence gaps in settings with limited data and infrastructure. More transparent and rigorous reporting of methods, assumptions and limitations may increase the use and acceptability of transportability for producing robust evidence on treatment effectiveness and safety.

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.

Acutely decompensated heart failure is one of the leading causes of hospitalisation worldwide, with a significant majority of these cases attributed to congestion. Although congestion is commonly mistaken for volume overload, evidence suggests that decompensation can occur without significant water accumulation, being attributed to volume redistribution. Yet, the distinction between intravascular and extravascular congestion in heart failure often blurs, as patients frequently exhibit overlapping features of both, and as patients may transition between phenotypes over time. Considering that differentiation between intravascular and extravascular congestion can lead to different management strategies, the aim of this review was to delineate the pathophysiological nuances between the two, as well as their correlation with clinical, biochemical and imaging indices.

Major depressive disorder (MDD) is associated with substantial morbidity and mortality, yet its diagnosis and treatment rates remain low due to its diverse and often overlapping clinical manifestations. In this context, electroencephalography (EEG) has gained attention as a potential objective tool for diagnosing depression. This study aimed to evaluate the effectiveness of EEG in identifying MDD by analyzing 140 EEG recordings from patients diagnosed with depression and healthy volunteers. Using various machine learning (ML) classification models, we achieved up to 80% accuracy in distinguishing individuals with MDD from healthy controls. Despite its promise, this approach has limitations. The variability in the clinical and biological presentations of depression, as well as patient-specific confounding factors, must be carefully considered when integrating ML technologies into clinical practice. Nevertheless, our findings suggest that an EEG-based ML model holds potential as a diagnostic aid for MDD, paving the way for further refinement and clinical application.

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.

Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn’s disease (CD). In our cross-sectional study, patients with CD were enrolled and blood and fecal samples were collected. Clinical and endoscopic disease activity and body composition were assessed and laboratory tests were made. Fecal bacterial composition was analyzed using the shotgun method. Microbiota alterations based on obesity, lipid parameters, and disease characteristics were analyzed. In this study, 27 patients with CD were analyzed, of which 37.0% were obese based on visceral fat area (VFA). Beta diversities were higher in non-obese patients (p < 0.001), but relative abundances did not differ. C. innocuum had a higher abundance at a high cholesterol level than Bacillota (p = 0.001, p = 0.0034). Adlercreutzia, B. longum, and Blautia alterations were correlated with triglyceride levels. Higher Clostridia (p = 0.009) and B. schinkii (p = 0.032) and lower Lactobacillus (p = 0.035) were connected to high VFA. Disease activity was coupled with dysbiotic elements. Microbiota alterations in obesity highlight the importance of gut microbiota in diseases with a similar inflammatory background and project therapeutic options.

Recently, there has been increased consideration of real-world data (RWD) and real-world evidence (RWE) in regulatory and health technology assessment (HTA) decision-making. Due to challenges in identifying high-quality and relevant RWD sources, researchers and regulatory/HTA bodies may turn to RWD generated in locales outside of the locale of interest (referred to as "transferring RWD"). We therefore performed a review of stakeholder guidance as well as selected case studies to identify themes for researchers to consider when transferring RWD from one jurisdiction to another. Our review highlighted that there is limited consensus on defining decision-grade, transferred RWD; certain stakeholders have issued relevant guidance, but the recommendations are high-level and additional effort is needed to generate comprehensive guidance. Additionally, the case studies revealed that RWD transferability has not been a consistent concern for regulatory/HTA bodies and that more focus has been put on the evaluation of internal validity. To help develop transferability best practices (alongside internal validity best practices), we suggest that researchers address the following considerations in their justification for transferring RWD: treatment pathways, nature of the healthcare system, incidence/prevalence of indication, and patient demographics. We also recommend that RWD transferability should garner more attention as the use of imported RWD could open doors to high-quality data sources and potentially reduce methodological issues that often arise in the use of local RWD; we thus hope this review provides a foundation for further dialogue around the suitability and utility of transferred RWD in the regulatory/HTA decision-making space.

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.

Rolling dynamic compaction (RDC) technology utilises a heavy non-circular module (impact roller) to compact the underlying soil dynamically. The stresses imparted to the soil through this technique and the resulting vibrations, have been the subject of investigation in the field. A finite element (FE) model predicting the settlement and densification of a coarse-grained fill material subject to RDC with a BH-1300 4-sided 8 tonne impact roller has been shown to provide good agreement with that observed in the field. This paper presents estimates using the developed FE model for the peak particle velocity and acceleration, and the maximum stresses applied through each impact upon a coarse-grained soil. Distributions of the results and their empirical formulae are presented herein.

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.

Aim: To evaluate the availability of published comparative real-world evidence (RWE) studies in Medicare patients for the ten drugs set to undergo Centers for Medicare and Medicaid Services (CMS) price negotiations in 2026. Materials & methods: A scoping review was completed in MEDLINE/PubMed to evaluate the availability of comparative RWE investigations conducted among Medicare-eligible patient populations in the US for the following drugs: apixaban, rivaroxaban, sitagliptin, ibrutinib, empagliflozin, etanercept, dapagliflozin, sacubitril/valsartan, ustekinumab and insulin aspart. Results: Of the 170 realworld comparative studies identified, 55 (32.4%) used Medicare real-world data (RWD) while 34 (20.0%) used commercial claims data in conjunction with either Medicare Advantage or Medicare Supplementary databases. The number of studies varied considerably by drug with apixaban and rivaroxaban studies accounting for the majority (i.e., 67.1%) of comparative RWE studies. Approximately a third or less of the comparative RWE studies were conducted in CMS RWD per drug. Conclusion: Our results demonstrate there is a considerable amount of comparative RWE for apixaban, rivaroxaban, and etanercept but limited comparative RWE for the other drugs set to undergo CMS price negotiations in 2026; additionally, our findings set up a number of next steps (e.g., risk of bias assessments) for further exploration of the available evidence base. Overall, CMS and manufacturers should consider proactively generating highquality comparative RWE studies in the Medicare population to ensure that future price negotiations are based on robust evidence.

To develop specific preventive strategies, it is necessary to investigate in detail the occurrence of injuries in young football players. This study aimed to provide details about the type, location, severity, and contact nature of muscle injuries in elite U15 Croatian football players. A total number of 130 muscle injuries occurred during the six competitive seasons, of which 88 were DOMS injuries and 42 were rupture injuries. Specifically, 87% of all muscle injuries belonged to the four major groups, with only 15 injuries to the other muscle groups: hamstrings (43), quadriceps (41), adductors (25), calves (6). The muscle injury incidence was stable during the observed period as the injury incidence rate ratio (IRR) was 1.01 (95%CI: 0.99–1.03), with 3.13 (95%CI: 3.09–3.17) muscle injuries per 1000 h of exposure in the first season and 3.06 (95%CI: 3.02–3.1) in the sixth season. A significantly higher risk for muscle injuries was discovered in the competition as the incidence for the whole observed period was 7.38 (95%CI: 7.29–7.47) compared to 2.25 (95%CI: 2.24–2.26) in the training period. Despite the relatively stable number of sustained muscle injuries, the relative proportion of muscular injuries increased over the years due to a severe decrease in the total number of injuries. Regarding the proportion of players who had sustained a muscle injury, our results suggest that approximately two out of five players can expect a muscular injury over the one-season period. Relatively high injury expectancy rates, as well as reinjury rates, require specific preventive interventions that will reduce the number and severity of new and recurred injuries. Future studies should include a wide set of predictor variables in order to establish the most important injury risk factors.

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.

A spontaneous coronary artery dissection (SCAD) during the postpartum period is a serious medical emergency and the most important non-atherosclerotic cause of coronary artery disease (CAD) in this population. While conservative management is recommended in most SCAD scenarios, cases complicated by hemodynamic instability or cardiogenic shock are particularly challenging and might be amenable only with invasive percutaneous or cardiothoracic surgical management. Herein, we present a case of a 35-year-old otherwise healthy woman that suffered an intense emotional stress event and was subsequently admitted with crushing chest pain to the emergency department. The initial electrocardiogram showed dynamic changes suggesting anterolateral ST-elevation myocardial infarction. She gave birth to a healthy child 3 months before the current presentation. Diagnostic angiography found no occlusive CAD but instead an extensive intramural hematoma originating from the left main artery dissection and extending to the whole left coronary circulation was observed. Hemodynamic instability and hypotension soon followed, and the patient went into cardiogenic shock. The heart team opted for conservative and supportive intensive care management without surgical or percutaneous intervention. This decision ultimately led to the successful extubation of the patient and the achievement of hemodynamic stability. The patient was eventually safely discharged home without any permanent disability.

Major depressive disorder (MDD) is associated with substantial morbidity and mortality, yet its diagnosis and treatment rates remain low due to its diverse and often overlapping clinical manifestations. In this context, electroencephalography (EEG) has gained attention as a potential objective tool for diagnosing depression. This study aimed to evaluate the effectiveness of EEG in identifying MDD by analyzing 140 EEG recordings from patients diagnosed with depression and healthy volunteers. Using various machine learning (ML) classification models, we achieved up to 80% accuracy in distinguishing individuals with MDD from healthy controls. Despite its promise, this approach has limitations. The variability in the clinical and biological presentations of depression, as well as patient-specific confounding factors, must be carefully considered when integrating ML technologies into clinical practice. Nevertheless, our findings suggest that an EEG-based ML model holds potential as a diagnostic aid for MDD, paving the way for further refinement and clinical application. [ABSTRACT FROM AUTHOR]

Rolling dynamic compaction (RDC) is a soil compaction technique, which is capable of improving thick layers of soil at a relatively fast operating speed. The paper presents the results of laboratory experiments conducted on 1:13 scale models of the four-sided, 8 and 12 t, Broons BH-1300 and BH-1300 HD impact rollers, respectively, to study the performance of the scale model at four different operating speeds. A series of laboratory tests is undertaken using transparent soils and the particle image velocimetry (PIV) technique to investigate the effectiveness of the models. The transparent soil employed in this study consists of fused quartz and a pore fluid that matched the refractive index of the fused quartz. A one-particle thick layer of coloured fused quartz is embedded in the centre plane of the transparent soil to visualize soil internal displacements and a digital camera is used to capture the speckled pattern during the scale model testing process. The results show that the heavier module induces greater soil displacements at each operating speed. The optimal operating speed is approximately 299 mm/s for both module weights. The most significant soil displacements occur within the first 20 passes and no obvious ground improvement is observed after 35 passes. The results of this study demonstrate the unique capability of transparent soil to study soil displacements induced by the ground improvement scale models. Key words: rolling dynamic compaction, impact roller, ground improvement, transparent soil, particle image velocimetry. Le compactage dynamique par roulement (CDR) est une technique de compactage du sol, capable d'ameliorer des couches epaisses de sol a une vitesse de fonctionnement relativement rapide. L'article presente les resultats d'experiences de laboratoire menees sur des modeles a l'echelle 1:13 des rouleaux d'impact Broons BH-1300 et BH-1300 HD a quatre cotes, de 8 et 121, respectivement, afin d'etudier les performances du modele reduit a quatre vitesses de fonctionnement differentes. Une serie d'essais en laboratoire est realisee a l'aide de sols transparents et de la technique de velocimetrie par images de particules (PIV) afin d'etudier l'efficacite des modeles. Le sol transparent utilise dans cette etude se compose de quartz fondu et d'un fluide interstitiel dont l'indice de refraction correspond a celui du quartz fondu. Une couche de quartz fondu colore d'une epaisseur d'une particule est incorporee dans le plan central du sol transparent pour visualiser les deplacements internes du sol et un appareil photo numerique est utilise pour capturer le motif mouchete pendant le processus d'essai du modele reduit. Les resultats montrent que le module le plus lourd induit des deplacements de sol plus importants a chaque vitesse de fonctionnement. La vitesse optimale de fonctionnement est d'environ 299 mm/s pour les deux poids de modules. Les deplacements du sol les plus importants se produisent au cours des 20 premiers passages et aucune amelioration evidente du sol n'est observee apres 35 passages. Les resultats de cette etude demontrent la capacite unique du sol transparent permettant d'etudier les deplacements du sol induits par les modeles d'amelioration du sol a l'echelle. [Traduit par la Redaction] Mots-cles : compaction dynamique par roulement, rouleau a impact, amelioration du sol, sol transparent, velocimetrie par image de particules., Introduction The stability and serviceability of foundations are highly dependent on the bearing capacity and settlement of the underlying soil. With the global increase in population and the consequent growing [...]

Recently, there has been increased consideration of real-world data (RWD) and real-world evidence (RWE) in regulatory and health technology assessment (HTA) decision-making. Due to challenges in identifying high-quality and relevant RWD sources, researchers and regulatory/HTA bodies may turn to RWD generated in locales outside of the locale of interest (referred to as “transferring RWD”). We therefore performed a review of stakeholder guidance as well as selected case studies to identify themes for researchers to consider when transferring RWD from one jurisdiction to another. Our review highlighted that there is limited consensus on defining decision-grade, transferred RWD; certain stakeholders have issued relevant guidance, but the recommendations are high-level and additional effort is needed to generate comprehensive guidance. Additionally, the case studies revealed that RWD transferability has not been a consistent concern for regulatory/HTA bodies and that more focus has been put on the evaluation of internal validity. To help develop transferability best practices (alongside internal validity best practices), we suggest that researchers address the following considerations in their justification for transferring RWD: treatment pathways, nature of the healthcare system, incidence/prevalence of indication, and patient demographics. We also recommend that RWD transferability should garner more attention as the use of imported RWD could open doors to high-quality data sources and potentially reduce methodological issues that often arise in the use of local RWD; we thus hope this review provides a foundation for further dialogue around the suitability and utility of transferred RWD in the regulatory/HTA decision-making space.

Objective To compare real-world effectiveness and safety of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AFib) for prevention of stroke.Study design and setting A comparative cohort study in UK general practice data from The Health Improvement Network database.Participants and interventions Before matching, 5655 patients ≥18 years with nonvalvular AFib who initiated at least one DOAC between 1 July 2014 and 31 December 2020 were included. DOACs of interest included apixaban, rivaroxaban, edoxaban and dabigatran, with the primary comparison between apixaban and rivaroxaban. Initiators of DOACs were defined as new users with no record of prescription for any DOAC during 12 months before index date.Primary and secondary outcome measures The primary outcome was stroke (ischaemic or haemorrhagic). Secondary outcomes included the occurrence of all-cause mortality, myocardial infarction (MI), transient ischaemic attacks (TIA), major bleeding events and a composite angina/MI/stroke (AMS) endpoint.Results Compared with rivaroxaban, patients initiating apixaban showed similar rates of stroke (HR: 0.93; 95% CI 0.64 to 1.34), all-cause mortality (HR: 1.03; 95% CI 0.87 to 1.22), MI (HR: 0.95; 95% CI 0.54 to 1.68), TIA (HR: 1.03; 95% CI 0.61 to 1.72) and AMS (HR: 0.96; 95% CI 0.72 to 1.27). Apixaban initiators showed lower rates of major bleeding events (HR: 0.60; 95% CI 0.47 to 0.75).Conclusions Among patients with nonvalvular AFib, apixaban was as effective as rivaroxaban in reducing rate of stroke and safer in terms of major bleeding episodes. This head-to-head comparison supports conclusions drawn from indirect comparisons of DOAC trials against warfarin and demonstrates the potential for real-world evidence to fill evidence gaps and reduce uncertainty in both health technology assessment decision-making and clinical guideline development.