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In this study, effective index birefringence and group index birefringence are investigated for 3 μm-thick silicon-on-insulator (SOI) strip waveguides, and experimental results are compared with simulations. We confirm zero group index birefringence at 1550 nm for a waveguide width of 2.6 μm; the absolute value of the same waveguide's group index birefringence is less than 2 × 10−4 over the measured 150 nm wavelength range. We further verify zero effective index birefringence at 1550 nm for a waveguide width of 3.2 μm, and the absolute value of its effective index birefringence is less than 6 × 10−5 over the same 150 nm wavelength range. Group and effective index birefringence dispersion are calculated based on the birefringence wavelength dependence, and the waveguide width needed to attain zero dispersion for either group or effective index birefringence is identified, at 3.1 μm and 2.7 μm, respectively. As a complement to our experimental findings, COMSOL simulations are conducted to analyze both the geometric- and stress-induced birefringence effects within the waveguides. The simulated birefringence values closely align with our experimental data, thereby validating the experimental results. We thus demonstrate the feasibility of achieving zero birefringence and zero birefringence dispersion through tuning the waveguide width in 3 μm SOI strip waveguides and validate these results via the agreement of a range of measurement methods and simulation.

IMPORTANCE: Despite its relevance for pediatric blood pressure (BP) screening, the long-term predictive utility and natural progression of pediatric BP classification remain understudied. OBJECTIVE: To evaluate BP tracking from childhood to midadulthood using the American Academy of Pediatrics (AAP) thresholds and estimate transition probabilities among BP classifications over time considering multiple time points. DESIGN, SETTING, AND PARTICIPANTS: The analyses were performed in 2023 using data gathered from September 1980 to August 2018 within the longitudinal Cardiovascular Risk in Young Finns Study. Participants had BP examined 9 times over 38 years, from childhood (aged 6-12 years) or adolescence (15-18 years) to young adulthood (21-27 years), late young adulthood (30-37 years), and midadulthood (39-56 years). EXPOSURES: BP classifications (normal, elevated, hypertension) were based on AAP guidelines for children and adolescents and the 2017 American College of Cardiology/American Heart Association guidelines for adults. MAIN OUTCOMES AND MEASURES: Outcomes were BP classifications at follow-up visits. Tracking coefficients were calculated using generalized estimated equations. Transition probabilities among BP classifications were estimated using multistate Markov models. RESULTS: This study included 2918 participants (mean [SD] baseline age, 10.7 [5.0] years; 1553 female [53.2%]). Over 38 years, the tracking coefficient (odds ratio [OR]) for maintaining elevated BP/hypertension was 2.16 (95% CI, 1.95-2.39). Males had a higher probability than females of progressing to and maintaining hypertension and a lower probability of reverting to normal BP from childhood to midadulthood (transition probability: from normal BP to stage 2 hypertension, 0.20; 95% CI, 0.17-0.22 vs 0.08; 95% CI, 0.07-0.10; maintaining stage 2 BP, 0.32; 95% CI, 0.27-0.39 vs 0.14; 95% CI, 0.09-0.21; from stage 2 hypertension to normal BP, 0.23; 95% CI, 0.19-0.26 vs 0.58; 95% CI, 0.52-0.62. For both sexes, the probability of transitioning from adolescent hypertension to normal BP in midadulthood was lower (transition probability, ranging from 0.16; 95% CI, 0.14-0.19 to 0.44; 95% CI, 0.39-0.48) compared with childhood hypertension (transition probability, ranging from 0.23; 95% CI, 0.19-0.26 to 0.63; 95% CI, 0.61-0.66). The probability of maintaining normal BP sharply decreased in the first 5 to 10 years, stabilizing thereafter. Children with normal BP generally maintained this status into adolescence (male: transition probability, 0.64; 95% CI, 0.60-0.67; female: transition probability, 0.81; 95% CI, 0.79-0.84) but decreased by young adulthood (male: transition probability, 0.41; 95% CI, 0.39-0.44; female: transition probability, 0.69; 95% CI, 0.67-0.71). CONCLUSION AND RELEVANCE: Results of this cohort study reveal an enduring association of childhood and adolescent BP (AAP thresholds) with later BP. Although childhood normal BP tends to be maintained into adolescence, the probability of reverting to and sustaining normal BP decreases notably from adolescence to young adulthood. The findings of this study underscore the importance of prevention to maintain normal BP starting in childhood, suggesting adolescence as a potential critical period. The results suggest the potential for less frequent screenings for children with initially normal BP.

ObjectivesHospital pharmacies provide centralised intravenous additive services (CIVAS), such as antibiotic reconstitution. The aim of this study was to demonstrate the physicochemical stability of high-concentration cefuroxime sodium in aqueous injections, which is mandatory for the centralised preparation of products with automation.MethodsThe physicochemical stability of three high-concentration injections (1.5 g of cefuroxime sodium in 15 mL, 16 mL and 18 mL of water for injection (WFI)) were studied in two primary packing materials (glass vials and polypropylene syringes). The samples were reconstituted with automation in three mid-sized hospital pharmacies in a good manufacturing practice (GMP) grade A/B cleanroom. During the study, the samples were stored in refrigerated conditions (4°C) and 1.5 g/15 mL solution in ambient temperature (22°C). Cefuroxime and descarbamoyl cefuroxime were analysed by high-performance liquid chromatography with UV detection. In addition, the appearance, pH and uniformity of dosage units were investigated.ResultsThe freshly prepared cefuroxime injections fulfilled the criteria of content uniformity (acceptance value (AV) <15). A significant decrease in concentration of cefuroxime and increase in content of descarbamoyl cefuroxime was observed in all injections. Cefuroxime aqueous injections were physiochemically stable for up to 14 days under refrigeration storage. The relative content of descarbamoyl cefuroxime remained under 3% at 4°C. The solution of 1.5 g/15 mL was stable for only 20 hours in formulations stored for the first 14 days at 4°C and then transferred to 22°C. The colour of the solution changed from light yellow to a darker yellow, and the pH value of the solutions increased during storage. Neither primary packing materials, commercial source of cefuroxime sodium nor exposure to light had any significant effect on the stability of formulations.ConclusionsAlthough limited, we found the shelf life of high-concentration cefuroxime injections in refrigerated conditions sufficient for centralised antibiotic preparation in hospital pharmacy with automation. The limited shelf life of high-concentration cefuroxime injections must be considered when using these formulations.

OVERVIEWTraditionally idea screening has been understood as a selection process, but recent studies have shown that idea evaluators engage in creative activities during screening. This approach has been conceptualized as generative idea screening. In this study, we analyzed how expert evaluators perform generative screening. By analyzing idea screening situations, we found that experts rely primarily on three types of generative activities that focus on adapting, concretizing, or changing an idea. Innovation managers can use this information to organize and direct generative activities during idea screening. We also discovered four idea screening processes: simple evaluation, simple modification, cyclical modification, and cyclical exploration. Adapting and concretizing an idea are prevalent activities in these four processes, which suggests that generative idea screening is best used for identifying and solving issues related to how an idea is presented and implemented.PRACTITIONER TAKEAWAYSGenerative screening is a creative process companies can use to improve upon initial ideas for innovation.Instead of asking experts to merely improve upon ideas, innovation managers can ask them to adaptthe ideas to make them easier to implement; to concretizeideas to make them easier to understand; and/or to changethe idea to encourage divergent thinking.Innovation managers can use generative idea screening as input for further ideation and harvest the experts’ creative potential more effectively, rather than solely focusing on identifying the most promising ideas during screening.

The main protease (Mpro) of SARS-CoV-2 is a key drug target for the development of antiviral therapeutics. Here, we designed and synthesized a series of small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent SARS-CoV-2 Mproinhibitors, including compounds 8n(IC50= 0.0752 μM), 8p(IC50= 0.0887 μM), 8r(IC50= 0.0199 μM), 10a(IC50= 0.0376 μM), 10c(IC50= 0.0177 μM), and 10f(IC50= 0.0130 μM). Most of them additionally inhibited cathepsin L and were also active against SARS-CoV-1 and MERS-CoV Mpro. In Calu-3 cells, several inhibitors, including 8r, 10a, and 10c, displayed high antiviral activity in the nanomolar range without showing cellular toxicity. The cocrystal structure of SARS-CoV-2 Mproin complex with 8prevealed covalent binding to the enzyme’s catalytic residue Cys145 and showed specific, unprecedented interactions within the substrate binding pocket. Compounds 10cand especially 8nwere effective against a panel of naturally occurring nirmatrelvir-resistant mutants, particularly E166V, and showed metabolic stability and additional favorable pharmacokinetic properties, making it a suitable candidate for further preclinical development.

Magnetic refrigeration leads the current commercialization efforts of ambient caloric cooling technologies, is considered among its peers most promising in terms of anticipated energy efficiency gain, and allows for complete elimination of harmful coolants. By now, functional magnetocaloric components (so-called regenerators) based on Mn-substituted and hydrogenated LaFeSi alloys are commercially available. However, this alloy system exhibits magnetostriction, is susceptible to fracture, oxidation, and does not passivate well, rendering it prone to failure and corrosion, particularly when using water as favorable heat exchange medium. Demonstrating stable and extended operation of LaFeSi-based regenerators under realistic conditions with cost-sensitive measures thus constitutes a key milestone for derisking the materials system, paving a path toward reliable and maintenance-friendly magnetic cooling devices. Building upon a fundamental analysis of materials properties, process, and target specifications, we outline a 2-fold protection strategy, encompassing a highly conformal copper coating working in tandem with a tailored inhibitor system. The former is applied using an optimized electroless plating procedure, allowing us to evenly envelop complex regenerator architectures in a dense, nondefective, homogeneous, and ductile copper film of excellent interfacial quality. The latter addresses the corrosion characteristics of both coating and substrate in the application environment. In-device aging experiments prove the effectiveness of our multifaceted approach in maintaining the chemical, mechanical, and functional integrity of LaFeSi regenerators under continuous use.