Concentration Ratio Research Articles

Optimization of Vancomycin Initial Dosing Regimen in Neonates Using an Externally Evaluated Population Pharmacokinetic Model

Background: Vancomycin therapeutic monitoring guidelines were revised in March 2020, and a population pharmacokinetics-guided Bayesian approach to estimate the 24-hour area under the concentration–time curve to the minimum inhibitory concentration ratio has since been recommended instead of trough concentrations. To comply with these latest guidelines, we evaluated published population pharmacokinetic models of vancomycin using an external dataset of neonatal patients and selected the most predictive model to develop a new initial dosing regimen. Methods: The models were identified from the literature and tested using a retrospective dataset of Canadian neonates. Their predictive performance was assessed using prediction- and simulation-based diagnostics. Monte Carlo simulations were performed to develop the initial dosing regimen with the highest probability of therapeutic target attainment. Results: A total of 144 vancomycin concentrations were derived from 63 neonates in the external population. Five of the 28 models retained for evaluation were found predictive with a bias of 15% and an imprecision of 30%. Overall, the Grimsley and Thomson model performed best, with a bias of −0.8% and an imprecision of 20.9%; therefore, it was applied in the simulations. A novel initial dosing regimen of 15 mg/kg, followed by 11 mg/kg every 8 hours should favor therapeutic target attainment. Conclusions: A predictive population pharmacokinetic model of vancomycin was identified after an external evaluation and used to recommend a novel initial dosing regimen. The implementation of these model-based tools may guide physicians in selecting the most appropriate initial vancomycin dose, leading to improved clinical outcomes.

Relative Bioavailability of Omaveloxolone When Capsules Are Sprinkled Over and Mixed in Applesauce Compared With Administration as Intact Omaveloxolone Capsules: A Phase 1, Randomized, Open-Label, Single-Dose, Crossover Study in Healthy Adults.

Omaveloxolone (SKYCLARYS®) is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥16 years in the United States and European Union (EU). The recommended dosage is 150 mg administered orally once daily as three 50-mg capsules. However, some patients with FA may have oropharyngeal dysphagia or difficulty swallowing whole capsules; therefore, alternate method(s) of administration are needed. A Phase 1 clinical study in 32 healthy volunteers evaluated the relative bioavailability, safety, and tolerability of a single dose of omaveloxolone when capsule contents were sprinkled on and mixed in applesauce compared to when taken as intact capsules. Palatability when sprinkled on and mixed in applesauce was assessed with a questionnaire. After a single 150-mg dose, the peak and overall exposures of omaveloxolone were similar irrespective of administration method, with the 90% CIs of the geometric least squares mean ratio (%) for maximum plasma concentration (Cmax), AUC0-t, and AUC0-∞ within the 80% to 125% reference intervals. Omaveloxolone was absorbed more slowly as intact capsules (median tmax, 10 h) compared with sprinkled capsule contents over applesauce (median tmax, 6 h). With chronic daily administration of omaveloxolone to treat FA, the 4-h difference in tmax is not considered clinically relevant. Sprinkled omaveloxolone capsule contents on applesauce were well tolerated, with acceptable palatability and no serious adverse events. Given the similar systemic exposure when capsules were swallowed whole, sprinkling omaveloxolone capsule contents on and mixing in applesauce is a feasible alternative method of administering omaveloxolone and has been included in both the United States and EU prescribing information.

Low temperature offers better foam stability.

The foam's structural longevity, linked to the effectiveness of sclerotherapy, depends on preparation conditions. The factors enhancing the treatment's effectiveness and efficacy are still under discussion. We conducted an invitro preclinical research, which included 144 independent trials. A total of 8 combinations involving 18 trials were designed according to settings of +4°C and room temperature (20-22°C), liquid-to-air ratios of 1/1 and 1/4, and polidocanol concentrations of 0.5% and 1% using the modified Tessari method. Our study aimed to examine the effect of air ratio, agent temperature, and polidocanol concentration on stability by assessing the foam half-time (FHT) and defining the optimal preparation conditions. The mean FHT was 117 ± 30.4 s. The longest FHT was in a 1:4 air-to-sclerosant ratio at +4°C, regardless of the sclerosant concentration (for %0.5 mean FHT: 146.2 ± 13.9 s, for % 1 mean FHT: 146.9 ± 18 s). There was a significant interaction among the three variables on FHT (p = 0.001). Temperature emerged as the primary factor (F(1, 136) = 124, p < 0.001, ηp2 = 0.477), with lower temperatures markedly enhancing the longevity (p < 0.001). Preparation at a temperature of 4°C resulted in an extended FHT of 32.5 s compared to 22°C (95% CI: 24.06-41.04 s). The temperature, agent concentration, and gas ratio significantly influence the stability of the physician-compounded foam. The low temperature at +4°C may offer better FHT for sclerotherapy.

Experimental study on solar wall by considering parametric sensitivity analysis to enhance heat transfer and energy grade using compound parabolic concentrator and pulsating heat pipe

Enhancing high-grade and rapid thermal storage for solar energy utilization is of paramount importance in reducing building energy consumption. Therefore, this study combines the Compound Parabolic Concentrator (CPC) and Pulsating Heat Pipe (PHP) to propose an integrated CPC-PHP solar wall (CPC-PHP-SW) that can enhance solar energy grade and rapid thermal storage. The mixed working fluid for CPC-PHP-SW is developed to reduce the dependence on solar radiation intensity and facilitate PHP startup. Furthermore, the operating characteristics and heat transfer performances of the CPC-PHP-SW are studied experimentally under various factors, including solar radiation intensity, working fluid, and cooling temperature. Sensitivity analyses of these three factors on heat transfer performances are conducted using Multi-factor analysis of variance. Results highlight that solar radiation intensity is the most influential factor on heat transfer performance, followed by cooling temperature, and working fluid. Moreover, employing a CPC with a concentration ratio of 2 reduces thermal resistance by up to 56.46 %, while the maximum effective thermal conductivity increases by up to 129.65 %. A recommended methanol to water ratio is 1:3, which effectively copes with a wide range of solar radiation intensity. These findings provide valuable references for the design and application of CPC-PHP-SW in building envelopes.

Predictive Pattern of Undrained Shear Strength in Stabilized Sulfur Rich Silty Soil Based on Binder and Initial Mixing Water Content

A laboratory investigation was conducted to identify principal variables-initial mixing water content, porosity, and binder content- impacting undrained shear strength (qu) of stabilized sulfur-rich silty soil. An equation for predicting qu of stabilized soil was established based on the experimental data. Initially, samples were prepared with soils sample with different initial water and binder contents. Multicem, a binder consisting of a mix of cement and cement kiln dust, was added to the samples. Three different percentages of Multicem were mixed at five different soil water contents to measure qu of stabilized mixtures to understand how water content and porosity levels in the samples affect the performance of the binder and their combined impact on the strength of the samples. The soil-binder mixtures were compacted and subsequently cured in laboratory-controlled environment. The prepared samples were tested in uniaxial compression test apparatus. The results evidenced that binder content and corresponding porosity affect the strength of specimens at an equal water content. The results showed that at equal initial mixing water content, the qu of a sample increased by increasing binder content. Furthermore, it was observed that increase of binder content has a reverse effect on porosity. It was appeared lowering the soil water content, initially increased the strength until an optimum water content. Further lowering water content increased the porosity and consequently decreased qu of samples. Moreover, a ratio of porosity/volumetric binder content was chosen to evaluate the impact of these two variables on strength of samples. This study showed that qu is an exponential function of porosity/binder volumetric content ratio which depends on initial mixing water content of mixtures. It was shown at water content lower than the optimum, results of stabilization are more effective than in soil at higher water contents. Therefore, reducing the water content and thereby porosity has more significant effect on improving qu than increasing the binder content.

White root rot of Bletilla striata: the pathogen, biological characterization, and fungicide screening.

Bletilla striata is an endangered traditional medicinal herb in China. In May 2020, the emergence of white root rot severely impacted the quality and yield of B. striata, affecting about 5% of the plants at plant nurseries of the Chengdu Academy of Agricultural and Forestry Sciences. Through a series of experiments and evaluations, the pathogen was identified as Fusarium solani. This is the first report of B. striata white root rot caused by F. solani in Sichuan, China. To better understand this disease and provide data support for its control, a combination of morphological, molecular characterisation and pathogenicity determination was used in this study for assessment. Meanwhile, the effects of different carbon and nitrogen sources, culture medium, temperature, photoperiod and pH on mycelial growth and spore production of F. solani were investigated. In addition, effective fungicides were screened and the concentration ratios of fungicides were optimized using response surface methodology (RSM). The experimental results showed that sucrose was the optimum carbon source for the pathogen, and the optimum temperature and pH were 25°C and pH 7, respectively, while light did no significant effect. Effective fungicides were screened, among which difenoconazole showed the strongest inhibition with EC50 of 142.773 µg/mL. The optimum fungicide concentration scheme (difenoconazole, pyraclostrobin, and thiophanate-methyl at 395.42, 781.03, and 561.11 µg/mL, respectively) was obtained using response surface methodology (RSM) to improve the inhibition rate of 92.24 ± 0.34%. This study provides basic data for the pathogen characterization of B. striata white root rot and its potential fungicides in Sichuan, China. In addition, the optimal fungicide concentration ratios were obtained through response surface methodology (RSM) optimization, which significantly enhanced the fungicidal effect and provided a scientific basis for the future control of B. striata white root rot.

Synergistic antioxidant and antibacterial activities of polyphenol extracts from mangosteen peels in preservation of Pangasius hypophthalmus fish balls

In recent years, natural preservatives have attracted more and more attention in food processing since they can enhance food shelf-life and safety. In this study, the polyphenol extract was obtained from mangosteen peels using enzyme-microwave assisted method, characterized for its antioxidant and antimicrobial activities and subsequently used as a natural additive in fish ball preservation. Results revealed that the mangosteen peel polyphenol powder (MPP) had a high phenolic content of 154 mg gallic acid equivalent/g dry matter, which led to high 2,2-diphenyl-1-picrylhydrazyl free radical scavenging capacity of 95 mg Trolox equivalent/g dry matter. MPP also exhibited effective antimicrobial activity against E. coli and S. aureus, expressed by its large inhibitory zones (11.3 and 12.1 mm, respectively) and small ratios (less than 4) of minimum bactericidal concentration over minimum inhibitory concentration against tested bacteria. The MPP supplementation at the levels of 38 mg/100 g and 53 mg/100 g into fish balls remarkably improved their gel strength, reduced lipid oxidation, limited protein oxidation and structural degradation as compared to those of the control without any addition or with synthetic preservatives. Especially, the addition of 53 mg MPP/100 g could sufficiently retard the microorganism growth. The synergistic effects of MPP in both antioxidant and antimicrobial activities hence could extend the shelf-life of fish balls, more than 40 %, as compared to butylated hydroxytoluene (synthetic antioxidant) or sodium benzoate (synthetic antimicrobial) with their single effects. These findings imply that MPP could be potentially used as a natural additive in preservation of fish and meat products.

Surface plasmon resonance synergistic coupling effects of gold nanoparticulates with silver grating in P3HT: PC61BM-based organic solar cell

A systematic study was carried out to observe possible boosts in the performance of poly-(3-hexyl thiophene):phenyl-C61-butyric acid methyl ester (P3HT:PC61BM) based organic solar cell via synergistic coupling of plasmonic effects. Various volume concentration ratios of gold nanoparticles and nanorods ranging from 2%, 4%, 6%, and 8% were used to determine an optimum condition. An indicative 2% optimum condition led to synergistic tests. The synergistic coupling of gold nanorods with backcontact grating revealed a power conversion efficiency (PCE) of 4.88%. Since post-thermal annealing process results in optimum interfacial surface morphology and structural reorganization, a post-process hypothesis was performed to observe the behavior of the devices at RT with further comparisons at 40 °C. A further increase in the initial performance of the devices was observed with an optimum PCE of 5.43%. The behavior in the performances revealed stable measurements mostly attributed to conditions below the glass transition temperature of P3HT:PC61BM.

A phase (Ph) 0/Ia study of brigimadlin concentration in brain tissue and a non-randomized, open-label, dose escalation study of brigimadlin in combination with radiotherapy (RT) in patients (pts) with newly diagnosed glioblastoma (GBM).

2017 Background: MDM2 inhibits tumor suppressor p53. Brigimadlin, a potent MDM2–p53 antagonist, restores wild-type (wt) p53 function and has shown early efficacy in pts with solid tumors (LoRusso et al Cancer Disc 2023). GBM is an area of unmet need with 5-year survival &lt;10%. In p53 wt GBM pt-derived xenograft models, brigimadlin promotes tumor cell apoptosis and extends survival in combination with RT. Methods: NCT05376800 is a Ph 0/Ia open-label, single-arm trial that aims to measure brigimadlin concentration in brain tumor tissue in pts with histologically or radiologically newly diagnosed GBM eligible for resection (Ph 0) and determine the maximum tolerated dose of brigimadlin plus RT in pts with TP53wt, IDH wt, MGMT promoter unmethylated GBM (Ph Ia). In Ph 0, pts received one brigimadlin dose (30 mg or 45 mg) ~12–24 h before resection. Ph 0 primary endpoints are the measured total concentration and the calculated unbound concentration of brigimadlin in brain tissue homogenate from non-contrast enhancing (NCE) and contrast enhancing (CE) regions. The predefined threshold for trial continuation is 0.5 nmol/L (corresponding to IC50 in GBM cell lines) unbound brigimadlin in CE samples in ≥50% of pts. Brigimadlin concentration was measured using LC/MS and corrected for amount of brigimadlin in residual blood. Unbound concentration was calculated using an in vitro estimate of unbound fraction (fu): 0.654% (rat brain slice). fu in human plasma was 0.22%. Kp,uu (ratio of unbound concentration in brain vs plasma) was calculated. Biomarker testing was performed. Results: Data are available for 11 pts (brigimadlin 30 mg: n=6; 45 mg: n=5). In the 30 mg group, median total brigimadlin concentration in NCE samples was 267 nmol/L (4 samples, range 86–316 nmol/L) and 332 nmol/L (6 samples, range 272–952 nmol/L) in CE samples. In the 45 mg group, median total brigimadlin concentration in NCE samples was 197 nmol/L (5 samples, range 140–347 nmol/L) and 603 nmol/L (5 samples, range 441–905 nmol/L) in CE samples. Unbound concentration exceeded the 0.5 nmol/L threshold in most cases (Table). Post-brigimadlin, an increase in selected p53 target gene expression was observed in CE vs NCE tissue. Conclusions: Unbound brigimadlin concentrations in CE regions in all pts receiving the low dose of 30 mg brigimadlin exceeded the 0.5 nmol/L threshold. Kp,uu in most patients was close to 1 in CE regions. Biomarker data support target engagement in brain tissue. Our findings support continued investigation of brigimadlin in GBM. Recruitment is ongoing. Updated data will be presented. Clinical trial information: NCT05376800 . [Table: see text]

High plasma magnesium and phosphorus levels and their correlation with struvite urolithiasis in buffaloes

BackgroundUrolithiasis is a common urinary tract disease in buffaloes, almost exclusively affects young males, and has significant economic and production impacts. We have investigated hemato-biochemical and urinary changes in an attempt to deduce their correlation with struvite urolithiasis in buffaloes. MethodsTen male buffalo calves with obstructive urolithiasis were used. Blood samples were used for hematology and elemental analysis. Urine samples were used for physico-chemical examination, microscopy, and elemental analysis. Uroliths were subjected to chemical functional group determination using the FTIR spectroscopy. ResultsThe mean neutrophil, leukocyte, and neutrophil-to-lymphocyte ratio was significantly (p < 0.05) higher in urolithic buffaloes than in healthy controls. The mean blood calcium and magnesium concentrations were significantly (p < 0.05) lower and higher in urolithic buffaloes than in healthy controls, respectively. Mean blood phosphorus concentration and calcium-phosphorus ratio were found to be non-significantly (p > 0.05) higher and lower in urolithic buffaloes than in healthy controls, respectively. The urine pH was highly alkaline. Multiple prismatic lid-shaped crystals, along with erythrocytes, leukocytes, and epithelial cells, were found in urine. The mean urinary magnesium and phosphorus concentrations were non-significantly (p < 0.05) higher in urolithic buffaloes than in healthy controls. A positive correlation of magnesium (r = 0.864, p = 0.001) and phosphorus (r = 0.849, p = 0.002) concentrations between the blood and urine was observed in urolithic buffaloes. The FTIR spectra of uroliths were similar to those of magnesium ammonium phosphate hexahydrate, MgNH4PO4·6H2O or struvite. ConclusionThe findings suggest that high plasma magnesium and phosphorus concentrations have a positive correlation with struvite urolithiasis in buffaloes.

Synergistic effect of selected carboxylic acids and phenolic compounds detected by the FRAP method

Antioxidants in nutrition are a widely discussed topic. In this study, a synergistic effect was observed for 13 selected substances – antioxidants and potential synergists, whereby two substances were mixed in the same concentration ratio of 1:1. The antioxidant capacity (AC) of the mixtures was determined using the FRAP method. The AC measured was compared with a theoretical AC value (as only additive effect) to calculate the synergistic or antagonistic effect. Out of 78 possible combinations, a synergistic effect (SE) was detected in 72. For the 10 combinations, the SE was more than twice that of the pure substances. The largest synergistic effect was exhibited by vanillin and 4-hydroxybenzoic acid with increases even above 200% compared to the pure substances. Some of the phenolic substances that were subject to measurement can be used for the fortification of fruit juices.

Association between adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations, the Netherlands, May 2021 to November 2022: a population-based prospective cohort study.

BackgroundNon-severe adverse events (AE) including pain at injection site or fever are common after COVID-19 vaccination.AimTo describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations.MethodsParticipants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within 2 months after vaccination and provided 6 monthly serum samples during May 2021-November 2022. Logistic regression analyses were performed to investigate AE determinants after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the SARS-CoV-2 spike protein receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2-naive participants to assess the association between AE and log-transformed antibody concentrations 3-8 weeks after mRNA vaccination.ResultsWe received 47,947 completed AE questionnaires by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention. AE were reported more frequently by women, younger participants (< 60 years), participants with medical risk conditions and Spikevax recipients (vs Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38; 95% CI: 1.23-1.54).ConclusionsOur study suggests that high pre-vaccination antibody levels are associated with AE, and experiencing AE may be a marker for higher antibody response to vaccination.

Mathematical Models of Natural Rubber Sheets Drying: Difference Acid Coagulation Cases

The mathematical model for drying process is a useful tool in process optimization and drying chamber design. The research purposes of this study were to investigate the influence of drying temperature on drying time and the modelling the drying kinetics of the natural rubber (NR) sheets. The NR sheets which produce from commercial formic acid, commercial acetic acids, and ammonia plus commercial formic acid were studied at drying temperature of 40, 50, and 60oC and air speed of 0.5 m/s. The results indicated that the drying time was substantially reduced with an increase in temperature. The moisture content ratio of rubber sheets produce from commercial formic acid coagulation was similar to the sheets produce from commercial acetic acids coagulation. However, the drying time of them were longer than the drying time of the sheets produce from ammonia plus commercial formic acid coagulation. Finally, the logarithmic model was the best model which suitable to predict the moisture content ratio of the sheets drying with all experimental condition.

Influence of feeding a soft diet on proteoglycan expression in rat temporomandibular joint discs

ObjectivesExtracellular matrix components play a significant role in maintaining tissue integrity and pathological processes of the temporomandibular joint (TMJ). This study aimed to evaluate the influence of a soft diet on the mRNA expression of proteoglycans and glycosaminoglycans (GAGs) linked to proteoglycan core proteins in rat TMJ discs. MethodsThirty 4-week-old male Wistar rats were assigned to one of two groups: a control group fed a regular pellet diet and a soft diet group fed a powdered diet for 4 weeks. The mRNA expression levels of 12 proteoglycans in TMJ discs were evaluated using real-time polymerase chain reaction (PCR). In addition, histomorphometric and biochemical analyses were performed to evaluate the thickness and deoxyribonucleic acid (DNA), GAG, and water content of the TMJ discs. ResultsThe TMJ disc thickness in the anterior, intermediate, and posterior bands decreased significantly in the soft diet group. The GAG content decreased significantly in the soft-diet group, whereas no significant differences in DNA content or water content ratio were observed between the groups. Real-time PCR indicated that the expression levels of aggrecan, versican, biglycan, decorin, fibromodulin, lumican, and chondroadherin decreased in the soft diet group. The expression levels of all versican isoforms decreased in the soft diet group. ConclusionsThese results indicate that the biomechanical environment of the TMJ caused by a soft diet is closely related to the expression of proteoglycans in TMJ discs, which may eventually increase the fragility of the TMJ discs.

Encapsulation of Lactobacillus plantarum in W1/O/W2 double emulsions stabilized with the high-intensity ultrasound-treated pea protein and pectin

This study focuses on developing a water-in-oil-in-water (W1/O/W2) double emulsion system using high-intensity ultrasound (HIU)-treated pea protein isolate (HIU-PPI) and pectin to encapsulate Lactobacillus plantarum (L. plantarum). The effects of ultrasound treatment on pea protein isolate (PPI) characteristics such as solubility, particle size, emulsification, surface hydrophobicity, and surface free sulfhydryl group were examined, determining optimal HIU processing conditions was 400 W for 10 min. The developed W1/O/W2 double emulsion system based on HIU-PPI demonstrated effective encapsulation and protection of L. plantarum, especially at the HIU-PPI concentration of 4 %, achieving an encapsulation efficiency of 52.65 %. Incorporating both HIU-PPI and pectin as emulsifiers increased the particle size and significantly enhanced the emulsion’s viscosity. The highest bacterial encapsulation efficiency of the emulsion, 59.94 %, was attained at a HIU to pectin concentration ratio of 3:1. These emulsions effectively encapsulate and protect L. plantarum, with the concentration of HIU-PPI being a critical factor in enhancing probiotic survival under simulated gastrointestinal digestion. However, the concurrent utilization of pectin and HIU-PPI as emulsifiers did not provide a notable advantage compared to the exclusive use of HIU-PPI in enhancing probiotic viability during in vitro simulated digestion. This research offers valuable perspectives for the food industry on harnessing environmentally friendly, plant-based proteins as emulsifiers in probiotic delivery systems. It underscores the potential of HIU-modified pea protein and pectin in developing functional food products that promote the health benefits of probiotics.

Effects of Tryptophan and Tyrosine on the Transformation of Monophenols in Chromophoric Dissolved Organic Matter Solutions: Enhance the Forward Transformation and Reduce the Reverse Transformation.

Tryptophan (Trp) and tyrosine (Tyr) are the primary precursors of protein-like components in dissolved organic matter. Phenolic compounds are ubiquitous in aquatic environments and are considered the main electron donor in chromophoric dissolved organic matter (CDOM). Our results showed that Trp and Tyr (50 μM) enhanced the transformation of six monophenols (20 μM) with varying numbers of -CH3 and -OCH3 substituent groups by a factor of 1.0-1.8. The enhancement factor increased with the ratio of Trp (Tyr) to monophenols. In four different CDOM solutions (5 mg C/L, pH 8.0), a maximum enhancement factor of 3.2-6.7 was observed at a Trp/monophenol concentration ratio of 50. Conversely, monophenols greatly inhibited the transformation of Trp or Tyr. The enhancement factor decreased as the initial pH increased from 3.0 to 10.0. Additionally, the enhancement factor was not directly proportional to the oxidation potential of monophenol. We propose that the promotion effects are generated through the direct oxidation of monophenols by Trp (Tyr) radicals as well as through the reaction between Trp (Tyr) radicals and the one-electron reductant of CDOM.

Eccentrically compressed behavior of UHPC columns considering the P-delta effect

Eccentric compression is a critical behavior observed in arches and columns, particularly in structures constructed with ultra-high performance concrete (UHPC). Compared to normal concrete structures, those made with UHPC exhibit distinct behaviors that need to be clearly investigated. This study comprehensively investigates UHPC columns under eccentric compression load through experimental study and theoretical analysis. Various experimental parameters, including slenderness ratio, eccentricity distance, fiber content, and stirrup ratio, were examined across 26 UHPC columns. Failure modes were evaluated using digital image correlation (DIC) methods. The load-displacement responses indicated that slender columns subjected to significant eccentricity exhibited load decreases during yielding stages, whereas short columns experienced load increases. This discrepancy in yielding stages was attributed to P-delta effects. In addition, theoretical models were developed to determine the ultimate bearing capacity of columns experiencing compression-controlled and tension-controlled failures, considering the P-delta effect caused by the different slenderness ratios. The moment magnifying coefficients for UHPC were calibrated based on theoretical analyses of the limit curvature of eccentric compression members. The proposed theoretical models agreed well with the experimental results, with an average ratio of 1.02. The second-order effect for the case of UHPC short column with a slenderness ratio of 5 can be ignored as per Eurocode 2, which is less than 10 % of the corresponding first-order effect.

Characterization of the surface-active exopolysaccharide produced by Halomonas sp TGOS-10: Understanding its role in the formation of marine oil snow.

In this study, we characterize the exopolymer produced by Halomonas sp. strain TGOS-10 -one of the organisms found enriched in sea surface oil slicks during the Deepwater Horizon oil spill. The polymer was produced during the early stationary phase of growth in Zobell's 2216 marine medium amended with glucose. Chemical and proton NMR analysis showed it to be a relatively monodisperse, high-molecular-mass (6,440,000 g/mol) glycoprotein composed largely of protein (46.6% of total dry weight of polymer). The monosaccharide composition of the polymer is typical to that of other marine bacterial exopolymers which are generally rich in hexoses, with the notable exception that it contained mannose (commonly found in yeast) as a major monosaccharide. The polymer was found to act as an oil dispersant based on its ability to effectively emulsify pure and complex oils into stable oil emulsions-a function we suspect to be conferred by the high protein content and high ratio of total hydrophobic nonpolar to polar amino acids (52.7:11.2) of the polymer. The polymer's chemical composition, which is akin to that of other marine exopolymers also having a high protein-to-carbohydrate (P/C) content, and which have been shown to effect the rapid and non-ionic aggregation of marine gels, appears indicative of effecting marine oil snow (MOS) formation. We previously reported the strain capable of utilising aromatic hydrocarbons when supplied as single carbon sources. However, here we did not detect biodegradation of these chemicals within a complex (surrogate Macondo) oil, suggesting that the observed enrichment of this organism during the Deepwater Horizon spill may be explained by factors related to substrate availability and competition within the complex and dynamic microbial communities that were continuously evolving during that spill.

Observation-constrained kinetic modeling of isoprene SOA formation in the atmosphere

Abstract. Isoprene has the largest global non-methane hydrocarbon emission, and the oxidation of isoprene plays a crucial role in the formation of secondary organic aerosol (SOA). Two primary processes are known to contribute to SOA formation from isoprene oxidation: (1) the reactive uptake of isoprene-derived epoxides on acidic or aqueous particle surfaces and (2) the absorptive gas–particle partitioning of low-volatility oxidation products. In this study, we developed a new multiphase condensed isoprene oxidation mechanism that includes these processes with key molecular intermediates and products. The new mechanism was applied to simulate isoprene gas-phase oxidation products and SOA formation from previously published chamber experiments under a variety of conditions and atmospheric observations during the Southern Oxidant and Aerosol Studies (SOAS) field campaign. Our results show that SOA formation from most of the chamber experiments is reasonably reproduced using our mechanism, except when the concentration ratios of initial nitric oxide to isoprene exceed ∼ 2, the formed SOA is significantly underpredicted. The SOAS simulations also reasonably agree with the measurements regarding the diurnal pattern and concentrations of different product categories, while the total isoprene SOA remains underestimated. The molecular compositions of the modeled SOA indicate that multifunctional low-volatility products contribute to isoprene SOA more significantly than previously thought, with a median mass contribution of ∼ 57 % to the total modeled isoprene SOA. However, this contribution is intricately intertwined with IEPOX-derived SOA (IEPOX: isoprene-derived epoxydiols), posing challenges for their differentiation using bulk aerosol composition analysis (e.g., the aerosol mass spectrometer with positive matrix factorization). Furthermore, the SOA from these pathways may vary greatly, mainly dependent on the volatility estimation and treatment of particle-phase processes (i.e., photolysis and hydrolysis). Our findings emphasize that the various pathways to produce these low-volatility species should be considered in models to more accurately predict isoprene SOA formation. The new condensed isoprene chemical mechanism can be further incorporated into regional-scale air quality models, such as the Community Multiscale Air Quality Modelling System (CMAQ), to assess isoprene SOA formation on a larger scale.

Vancomycin: An analysis and evaluation of eight population pharmacokinetic models for clinical application in general adult population.

Based on the recent guidelines for vancomycin therapeutic drug monitoring (TDM), the area under the curve to minimum inhibitory concentration ratio was to be employed combined with the usage of population pharmacokinetic (popPK) model for dosing adaptation. Yet, deploying these models in a clinical setting requires an external evaluation of their performance. This study aimed to evaluate existing vancomycin popPK models from the literature for the use in TDM within the general patient population in a clinical setting. The models under external evaluation were chosen based on a review of literature covering vancomycin popPK models developed in general adult populations. Patients' data were collected from Charles-Le Moyne Hospital (CLMH). The external evaluation was performed with NONMEM® (v7.5). Additional analyses such as evaluating the impact of number of samples on external evaluation, Bayesian forecasting, and a priori dosing regimen simulations were performed on the best performing model. Eight popPK models were evaluated with an independent dataset that included 40 patients and 252 samples. The model developed by Goti and colleagues demonstrated superior performance in diagnostic plots and population predictive performance, with bias and inaccuracy values of 0.251% and 22.7%, respectively, and for individual predictive performance, bias and inaccuracy were -4.90% and 12.1%, respectively. When limiting the independent dataset to one or two samples per patient, the Goti model exhibited inadequate predictive performance for inaccuracy, with values exceeding 30%. Moreover, the Goti model is suitable for Bayesian forecasting with at least two samples as prior for the prediction of the next trough concentration. Furthermore, the vancomycin dosing regimen that would maximize therapeutic targets of area under the curve to minimum inhibitory concentration ratio (AUC24/MIC) and trough concentrations (Ctrough) for the Goti model was 20 mg/kg/dose twice daily. Considering the superior predictive performance and potential for Bayesian forecasting in the Goti model, future research aims to test its applicability in clinical settings at CLMH, both in a priori and a posteriori scenario.