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Background
Hip fractures are a common and costly health problem, resulting in significant morbidity and mortality, as well as high costs for healthcare systems, especially for the elderly. Implementing surgical preventive strategies has the potential to improve the quality of life and reduce the burden on healthcare resources, particularly in the long term. However, there are currently limited guidelines for standardizing hip fracture prophylaxis practices.
Methods
This study used a cost-effectiveness analysis with a finite-state Markov model and cohort simulation to evaluate the primary and secondary surgical prevention of hip fractures in the elderly. Patients aged 60 to 90 years were simulated in two different models (A and B) to assess prevention at different levels. Model A assumed prophylaxis was performed during the fracture operation on the contralateral side, while Model B included individuals with high fracture risk factors. Costs were obtained from the Centers for Medicare & Medicaid Services, and transition probabilities and health state utilities were derived from available literature. The baseline assumption was a 10% reduction in fracture risk after prophylaxis. A sensitivity analysis was also conducted to assess the reliability and variability of the results.
Results
With a 10% fracture risk reduction, model A costs between $8,850 and $46,940 per quality-adjusted life-year ($/QALY). Additionally, it proved most cost-effective in the age range between 61 and 81 years. The sensitivity analysis established that a reduction of ≥ 2.8% is needed for prophylaxis to be definitely cost-effective. The cost-effectiveness at the secondary prevention level was most sensitive to the cost of the contralateral side’s prophylaxis, the patient’s age, and fracture treatment cost. For high-risk patients with no fracture history, the cost-effectiveness of a preventive strategy depends on their risk profile. In the baseline analysis, the incremental cost-effectiveness ratio at the primary prevention level varied between $11,000/QALY and $74,000/QALY, which is below the defined willingness to pay threshold.
Conclusion
Due to the high cost of hip fracture treatment and its increased morbidity, surgical prophylaxis strategies have demonstrated that they can significantly relieve the healthcare system. Various key assumptions facilitated the modeling, allowing for adequate room for uncertainty. Further research is needed to evaluate health-state-associated risks.
In this work, the bioabsorbable materials, namely fibroin, polylactide acid (PLA), magnesium and magnesium oxide are investigated for their application as transient, resistive temperature detectors (RTD). For this purpose, a thin-film magnesium-based meander-like electrode is deposited onto a flexible, bioabsorbable substrate (fibroin or PLA) and encapsulated (passivated) by additional magnesium oxide layers on top and below the magnesium-based electrode. The morphology of different layered RTDs is analyzed by scanning electron microscopy. The sensor performance and lifetime of the RTD is characterized both under ambient atmospheric conditions between 30°C and 43°C, and wet tissue-like conditions with a constant temperature regime of 37°C. The latter triggers the degradation process of the magnesium-based layers. The 3-layers RTDs on a PLA substrate could achieve a lifetime of 8.5 h. These sensors also show the best sensor performance under ambient atmospheric conditions with a mean sensitivity of 0.48 Ω/°C ± 0.01 Ω/°C.
In comparison to single-analyte devices, multiplexed systems for a multianalyte detection offer a reduced assay time and sample volume, low cost, and high throughput. Herein, a multiplexing platform for an automated quasi-simultaneous characterization of multiple (up to 16) capacitive field-effect sensors by the capacitive–voltage (C–V) and the constant-capacitance (ConCap) mode is presented. The sensors are mounted in a newly designed multicell arrangement with one common reference electrode and are electrically connected to the impedance analyzer via the base station. A Python script for the automated characterization of the sensors executes the user-defined measurement protocol. The developed multiplexing system is tested for pH measurements and the label-free detection of ligand-stabilized, charged gold nanoparticles.
Amino acid-based surfactants are valuable compounds for cosmetic formulations. The chemical synthesis of acyl-amino acids is conventionally performed by the Schotten-Baumann reaction using fatty acyl chlorides, but aminoacylases have also been investigated for use in biocatalytic synthesis with free fatty acids. Aminoacylases and their properties are diverse; they belong to different peptidase families and show differences in substrate specificity and biocatalytic potential. Bacterial aminoacylases capable of synthesis have been isolated from Burkholderia, Mycolicibacterium, and Streptomyces. Although several proteases and peptidases from S. griseus have been described, no aminoacylases from this species have been identified yet. In this study, we investigated two novel enzymes produced by S. griseus DSM 40236ᵀ . We identified and cloned the respective genes and recombinantly expressed an α-aminoacylase (EC 3.5.1.14), designated SgAA, and an ε-lysine acylase (EC 3.5.1.17), designated SgELA, in S. lividans TK23. The purified aminoacylase SgAA was biochemically characterized, focusing on its hydrolytic activity to determine temperature- and pH optima and stabilities. The aminoacylase could hydrolyze various acetyl-amino acids at the Nα -position with a broad specificity regarding the sidechain. Substrates with longer acyl chains, like lauroyl-amino acids, were hydrolyzed to a lesser extent. Purified aminoacylase SgELA specific for the hydrolysis of Nε -acetyl-L-lysine was unstable and lost its enzymatic activity upon storage for a longer period but could initially be characterized. The pH optimum of SgELA was pH 8.0. While synthesis of acyl-amino acids was not observed with SgELA, SgAA catalyzed the synthesis of lauroyl-methionine.
The aerodynamic performance of propellers strongly depends on their geometry and, consequently, on aeroelastic deformations. Knowledge of the extent of the impact is crucial for overall aircraft performance. An integrated simulation environment for steady aeroelastic propeller simulations is presented. The simulation environment is applied to determine the impact of elastic deformations on the aerodynamic propeller performance. The aerodynamic module includes a blade element momentum approach to calculate aerodynamic loads. The structural module is based on finite beam elements, according to Timoshenko theory, including moderate deflections. Several fixed-pitch propellers with thin-walled cross sections made of both isotropic and non-isotropic materials are investigated. The essential parameters are varied: diameter, disc loading, sweep, material, rotational, and flight velocity. The relative change of thrust between rigid and elastic blades quantifies the impact of propeller elasticity. Swept propellers of large diameters or low disc loadings can decrease the thrust significantly. High flight velocities and low material stiffness amplify this tendency. Performance calculations without consideration of propeller elasticity can lead to decreased efficiency. To avoid cost- and time-intense redesigns, propeller elasticity should be considered for swept planforms and low disc loadings.
The growing body of political texts opens up new opportunities for rich insights into political dynamics and ideologies but also increases the workload for manual analysis. Automated speaker attribution, which detects who said what to whom in a speech event and is closely related to semantic role labeling, is an important processing step for computational text analysis. We study the potential of the large language model family Llama 2 to automate speaker attribution in German parliamentary debates from 2017-2021. We fine-tune Llama 2 with QLoRA, an efficient training strategy, and observe our approach to achieve competitive performance in the GermEval 2023 Shared Task On Speaker Attribution in German News Articles and Parliamentary Debates. Our results shed light on the capabilities of large language models in automating speaker attribution, revealing a promising avenue for computational analysis of political discourse and the development of semantic role labeling systems.
The “1. Stokes’ problem”, the “suddenly accelerated flat wall”, is the oldest application of the Navier-Stokes equations. Stokes’ solution of the “problem” does not comply with the mathematical theorem of Cauchy and Kowalewskaya on the “Uniqueness and Existence” of solutions of partial differential equations and violates the physical theorem of minimum entropy production/dissipation of the Thermodynamics of Irreversible Processes. The result includes very high local shear stresses and dissipation rates. That is of special interest for the theory of turbulent and mixed turbulent/laminar flow. A textbook solution of the “1. Stokes Problem” is the Couette flow, which has a constant sheer stress along a linear profile. A consequence is that the Navier-Stokes equations do not describe any S-shaped part of a turbulent profile found in any turbulent Couette experiment. The paper surveys arguments referring to that statement, concerning the history of >150 years. Contrary to this there is always a Navier-Stokes solution near the wall, observed by a linear part of the Couette profile. There a turbulent description (e.g. by the logarithmic law-of-the-wall) fails completely. That is explained by the minimum dissipation requirement together with the Couette feature τ = const. The local co-existence of a turbulent zone and a laminar zone near the wall is stable and observed also at high Reynolds-Numbers.
N-Acyl-amino acids can act as mild biobased surfactants, which are used, e.g., in baby shampoos. However, their chemical synthesis needs acyl chlorides and does not meet sustainability criteria. Thus, the identification of biocatalysts to develop greener synthesis routes is desirable. We describe a novel aminoacylase from Paraburkholderia monticola DSM 100849 (PmAcy) which was identified, cloned, and evaluated for its N-acyl-amino acid synthesis potential. Soluble protein was obtained by expression in lactose autoinduction medium and co-expression of molecular chaperones GroEL/S. Strep-tag affinity purification enriched the enzyme 16-fold and yielded 15 mg pure enzyme from 100 mL of culture. Biochemical characterization revealed that PmAcy possesses beneficial traits for industrial application like high temperature and pH-stability. A heat activation of PmAcy was observed upon incubation at temperatures up to 80 °C. Hydrolytic activity of PmAcy was detected with several N-acyl-amino acids as substrates and exhibited the highest conversion rate of 773 U/mg with N-lauroyl-L-alanine at 75 °C. The enzyme preferred long-chain acyl-amino-acids and displayed hardly any activity with acetyl-amino acids. PmAcy was also capable of N-acyl-amino acid synthesis with good conversion rates. The best synthesis results were obtained with the cationic L-amino acids L-arginine and L-lysine as well as with L-leucine and L-phenylalanine. Exemplarily, L-phenylalanine was acylated with fatty acids of chain lengths from C8 to C18 with conversion rates of up to 75%. N-lauroyl-L-phenylalanine was purified by precipitation, and the structure of the reaction product was verified by LC–MS and NMR.