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Process robustness in twin-screw wet granulation:The role of formulation, screw configurations and liquid-to-solid ratios on milled granules and tablets
No full textThis study aimed to examine the effects of formulation, screw configuration, and liquid-to-solid (L/S) ratio on granule and tablet characteristics. Milling was also examined using different screen sizes and types. Two formulations were tested, with filler combinations of mannitol-microcrystalline cellulose (MCC) or MCC-anhydrous dibasic calcium phosphate (DCPA) in a 70:30 ratio, along with 25% allopurinol as the active pharmaceutical ingredient. Three different screw configurations and three L/S ratios were evaluated. A mixer torque rheometer (MTR) was used to determine suitable L/S ratios. The higher excipient solubility resulted in a lower predicted L/S ratio for the mannitol-MCC based formulation compared with the insoluble MCC-DCPA formulation. At the predicted L/S ratio, all granules demonstrated excellent flow properties (>10 g/s), and all tablets had high tensile strengths (>2 MPa). All tablets but the MCC-DCPA formulation at the 110% L/S level had satisfactory dissolution. Formulation and screw configuration had only minor effects on tablet tensile strength (<0.1 MPa). Particle size distribution (PSD) differences were observed in unmilled granules, but these differences were largely evened out after milling. Both mill screen sizes and types impacted residence time but had only a moderate impact on the PSD. The results confirm that twin-screw wet granulation is a robust granulation method, where multiple screw configurations and formulations can yield high-quality drug products. Since twin-screw granules are larger than those from high-shear granulation, milling plays a key role in controlling PSD and optimizing final product quality
Urban vitality versus urban livability: Does vibrancy matter for neighborhood satisfaction and neighborhood happiness?
No full textUrban vitality is often considered a key factor for a successful city, yet its contribution to urban livability remains underexplored. In this paper, we conceptualize and test models linking the built environment, urban vitality, neighborhood satisfaction, and neighborhood happiness. Neighborhood satisfaction and neighborhood happiness are key indicators of urban livability and predictors of subjective well-being. Data come from analyses with geographic information systems and a survey carried out in Oslo, Norway. Results show that three built environment characteristics – proximity to the main city center, higher population density, and accessibility to amenities such as shops, cafes, and restaurants – contribute to increased urban vitality. In turn, urban vitality is positively linked to neighborhood satisfaction and neighborhood happiness. Among all environmental attributes analyzed, urban vitality emerged as the strongest predictor of neighborhood satisfaction. This relationship is strong and positive for all age groups but is more pronounced among younger adults than among middle-aged and older adults. The study's findings suggest that urban vitality plays a critical role not only in fostering vibrant street life, social interaction, and active transport but also in improving overall urban livability, highlighting its importance in urban planning and policy
Dissecting environmental effects with eccentric gravitational wave sources
No full textWe model the effect of resonances between time-varying perturbative forces and the epicyclical motion of eccentric binaries in the gravitational wave (GW) driven regime. These induce secular drifts in the orbital elements, which are reflected in a dephasing of the binary's GW signal, derived here systematically. The resulting dephasing prescriptions showcase a much richer phenomenology with respect to typically adopted models and are better able to model realistic environmental effects. The most important consequences are for gas embedded binaries, which we analyze in detail with a series of analytical calculations, numerical experiments, and a curated set of hydrodynamical simulations for equal masses. Even in these simplified tests, we find the surprising result that dephasing caused by epicyclical resonances dominate over expectations based on smoothed or orbit averaged gas drag models in GW signals that retain mild eccentricity in the detector band (e > 0.05). We discuss how dissecting GW dephasing in its component Fourier modes can be used to probe the coupling of binaries with their surrounding environment in unprecedented detail
Tree-crop combinations and their variable effects on agroecosystem services:A systematic review and meta-analysis of temperate silvoarable agroforestry in the Northern Hemisphere
No full textSilvoarable agroforestry can increase yields and enhance agroecosystem services while enabling efficient field operations through adjustable alley widths. Although several meta-analyses reviewed agricultural diversification and agroforestry, most focused on general systems or individual services at a global scale or within Europe. To date, there has been no study that combines systematic review and meta-analysis to synthesize the effects of temperate silvoarable agroforestry across multiple agroecosystem services. This study analysed 37 empirical studies, covering 87 experiments and 1127 data records. Poplar–cereal combinations were most studied (35 %), followed by walnut–cereal (13 %) and mixed tree–cereal systems (10 %). Results show that temperate silvoarable agroforestry increased biodiversity by 20 % compared to monocropping, with greater gains in systems less than six years old, during spring to early summer, and where leguminous crops were included. For crop yield and soil quality, results were not significant and showed high variability depending on context. Yield declined by 15 % in systems with tree heights over 10 m and alley widths up to 96 m, likely due to shading and belowground competition. Results on carbon sequestration, pest and disease regulation, product quality, and water quality remain inconclusive due to limited data. The findings suggest that silvoarable agroforestry can enhance agroecosystem services. To realize this, genetic diversity (through suitable species selection), spatial design (matching tree height with alley width), and temporal diversity need to be carefully integrated and tailored to farmer's goals, site conditions, and management. More long-term, geographically diverse studies are needed to better guide system design and policy
Lensing and wave optics in the strong field of a black hole
No full textGravitational waves (GWs) are lensed by matter, offering a unique probe of both the large-scale structure of the Universe and the fundamental properties of GW propagation. GWs can also be affected by wave optics effects when their wavelength is comparable to the size of the lens. While this regime has been well studied in the Newtonian approximation, the role of strong gravitational fields remains largely unexplored. This is particularly relevant for lensing by intermediate and supermassive black holes (BHs), which can occur near active galactic nuclei or in compact triple systems. In this work, we analyze the lensing of GWs by a non-rotating BH and compare our results to the Newtonian point-mass approximation. We construct frequency-dependent amplification factors that incorporate strong-field effects, revealing explicit polarization mixing and absorption by the event horizon. Using a fiducial GW event, we explore key phenomenological signatures of BH lensing, highlighting new observational opportunities to probe strong gravitational fields through GW lensing
Small angle X-ray scattering reveals phase transition in sodium oleate-cysteine systems for optimized selenium nanoparticles synthesis
No full textSelenium nanoparticles (SeNPs) can be synthesised via physical, chemical, or biological methods. While physical and chemical approaches offer benefits, they often involve high costs, toxic reagents, and reduced biocompatibility due to stabilizers. Biological synthesis provides a greener, more biocompatible alternative, but faces challenges such as variability in biological sources, slow synthesis, low yields, and scalability issues due to pH sensitivity, toxic precursors, and costly equipment. To address these limitations, we propose a sustainable workflow for SeNPs production using the selenite (SeO32-)-reducing amino acid L-cysteine (Cys) and the eco- and bio-compatible surfactant sodium oleate (NaOl). We report that Cys not only reduces selenite but also induces phase transitions in NaOl, forming a confined environment of vesicles and lamellar structures that facilitate controlled SeNPs nucleation and growth. Through a detailed phase diagram analysis, we elucidate the critical Cys and NaOl concentration regimes and pH conditions thresholds that drive surfactant self-assembly, providing valuable insights into the optimized colloidal environment for SeNPs synthesis. We also report that these confined structures support SeNPs isotropic growth and long-term stability. This method provides a scalable and eco-friendly approach for producing biocompatible SeNPs, addressing some of the challenges of conventional methods
Self-consistent layer-projected scissors operator for band structures of two-dimensional van der Waals materials with large unit cells
No full textWe introduce a computationally efficient method to calculate the quasiparticle band structure of general van der Waals (vdW) heterostructures. A layer-projected scissors (LAPS) operator, which depends on the one-body density matrix, is added to the density functional theory Hamiltonian. The LAPS operator corrects the band edges of the individual layers for self-energy effects (both intralayer and interlayer) and unphysical strain fields stemming from the use of model supercells. The LAPS operator is treated self-consistently whereby charge redistribution and interlayer hybridization occurring in response to the band energy corrections are properly accounted for. We present several examples illustrating both the qualitative and quantitative performance of the method, including MoS2 films with up to 20 layers, bilayer MoS2 in an electric field, lattice-matched MoS2/WS2 and MoSe2/WSe2 bilayers, and MoSe2/WS2 moir & eacute; structures. Our work opens the way for predictive modeling of electronic, optical, and topological properties of experimentally relevant vdW materials, including twisted homobilayers and incommensurate heterostructures
A pragmatic individually randomized trial to evaluate bivalent RSV prefusion F protein-based vaccine effectiveness for preventing RSV hospitalizations in adults aged 60 years or above (DAN-RSV):Rationale and trial design
No full textBackground Respiratory syncytial virus (RSV) can cause serious illness in older adults and those with chronic conditions. While the bivalent RSVpreF vaccine has been shown to protect against RSV-related respiratory tract disease, its impact on severe RSV-related and broader cardiorespiratory hospitalizations remains untested in a fully powered randomized trial. This pragmatic, individually randomized, open-label, parallel-group trial aims to evaluate RSVpreF vaccine effectiveness (VE) in reducing the risk of RSV-related and all-cause cardiorespiratory hospitalizations in adults aged 60 and older. Methods DAN-RSV is randomizing Danish adults 1:1 to receive either RSVpreF or no RSV vaccine. The trial uses nationwide registries for recruitment, where eligible citizens are identified and invited via the national electronic messaging system and can provide electronic informed consent remotely. Baseline, safety, and outcome data are collected through the national health registries using the civil registration number provided at consent. Up to 130,000 participants will be enrolled during the 2024/2025 winter season. The primary objective is to assess vaccine effectiveness (VE) against RSV-related respiratory tract disease hospitalization. Secondary endpoints include RSV-related and all-cause lower respiratory tract disease hospitalizations, RSV-related and all-cause cardiorespiratory hospitalizations, and all-cause death. Conclusion DAN-RSV is an innovative trial combining the gold standard of individual randomization with pragmatic data collection via centralized health records and national health registries. This design offers a feasible approach to assess the impact of RSVpreF on clinically meaningful cardio-respiratory outcomes in adults >= 60 years in a real-world setting- while minimizing bias through use of randomization. The results will support cost-effectiveness analyses and inform future vaccination policies. Trial registration NCT06684743, registered November 9, 2024 (https://clinicaltrials.gov/study/NCT06684743) (Am Heart J 2026;291:14-25.
The Effect of Far Infrared Treatment on Changes in Biomarkers in the Arteriovenous Fistula
No full textINTRODUCTION: Far infrared radiation may improve arteriovenous fistula maturation and patency rates in patients on hemodialysis (HD). The mechanism is proposed to involve anti-inflammatory and vasodilatory effects in the arteriovenous fistula. This study examined the impact of far infrared radiation on plasma changes and dialysate excretion of biomarkers of endothelial dysfunction, inflammation, and vasodilation in the arteriovenous fistula during a single HD.METHODS: The study was a randomized, controlled, single-blinded study involving 44 participants on HD with an arteriovenous fistula. Participants were randomized to far infrared radiation or no far infrared radiation (control). Blood samples and dialysate water were drawn before, during, and after 4 h of HD. The change and elimination of biomarkers of endothelial dysfunction, inflammation, and vasodilation was explored in blood and dialysate water, respectively. Changes in plasma levels from the start to the end of HD and the area under the curve for the biomarker concentration were compared between groups by ANCOVA.RESULTS: There was no difference in the change of biomarkers of endothelial dysfunction, inflammation, and vasodilation between the two groups after and during 4 h of HD. There was a minimal excretion of the biomarkers in the dialysate water. Regardless of the treatment group, 4 h of HD caused a significant decrease in tumor necrosis factor-alpha (-1.30 [-1.70; -1.03] pg/mL, p < 0.001), monocyte chemoattractant protein-1 (-32.50 [-50.50; -8.25] pg/mL, p < 0.001), nitrite and nitrate (-20.00 [-27.75; -14.00] µmol/L, p < 0.001) as well as asymmetric dimethylarginine (-0.24 [-0.28; -0.18] µmol/L, p < 0.001).CONCLUSION: Overall, the study is not supportive of a beneficial effect of far infrared radiation on the arteriovenous fistula on biomarkers of endothelial dysfunction, inflammation, or vasodilation during one HD treatment.</p