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1 Extent and rate of absorption of erythromycin were studied in 24 healthy volunteers whose disposition kinetics after i.v. injections had been previously documented. 2 Two clinically attractive oral dosage regimens were administered: erythromycin stearate tablets 1 h before meals (Regimen A), and erythromycin base capsules 30 min after start of meals (Regimen B), each equivalent to erythromycin 250 mg, 6 h apart for 9 doses. 3 Serum concentrations of erythromycin measured during the 1st and 9th (steady-state) dosing intervals resulted in higher maximum serum concentrations for Regimen A (median 1.1, range 0-3.3 and 2.7, 0.6-7.3 mg/l for Doses 1 and 9, respectively) compared with Regimen B (0.4, 0-2.2 and 1.4, 0.2-4.9 mg/l). 4 Absorption occurred earlier with Regimen A with times to maximum concentrations (median, range) being 128, 60-greater than 360 and 118, 75-210 min for doses 1 and 9 respectively, (lag times 75, 15- greater than 360 and 73, 10-110 min) compared with 303, 130-greater than 360 and 173, 45-greater than 360 min (lag times 183, 70-greater than 360 and 190, 20-330 min) for Regimen B. 5 Where it could be assessed, absolute bioavailability for Regimen A was approximately 30% (Dose 1) and 65% (Dose 9) and 40% for both doses of Regimen B. 6 Whereas individual serum concentration-time curves were accurately predicted by the mean for Regimen A, predictability for Regimen B was impossible due to prolonged and variable lag time. 7 The large intersubject variability in erythromycin serum concentration after oral administration, has been shown conclusively to be related to variability in absorption kinetics and absolute bioavailability rather than to variability in disposition kinetics. [ABSTRACT FROM AUTHOR]

1 It is well-known that considerable variability and unpredictability in serum concentrations results from orally administered erythromycin. 2 Disposition kinetics and their variability were studies in 24 healthy subjects after a single dose of erythromycin lactobionate and four doses were studied to evaluate dose-related variability in five other subjects. 3 Erythromycin kinetics were adequately described by a classical two compartment open model with little intersubject variability. 4 Dose-related variability occurred. Clearance was independent of dose but T1/2 beta and Vdss increased with dose. 5 Data are presented to show that non-invasive sampling of urine and saliva are of limited value in studying erythromycin pharmacokinetics. [ABSTRACT FROM AUTHOR]

The Hallmarks Survey is based on the 85 indicators recommended by the National League for Nursing (NLN) for the Hallmarks of Excellence in Nursing Education. With permission from the NLN, graduate students in nursing education developed this survey as a holistic and systematic tool for nurse faculty to use for assessment of program components. Analysis of data from 53 faculty respondents yielded areas of strength and areas for development for each hallmark category. Recommendations based on survey findings were disseminated to diverse audiences in multiple venues. A follow-up evaluation of the survey was also conducted. The Hallmarks Survey provides comprehensive assessment data that faculty may use to promote excellence in nursing education. [ABSTRACT FROM AUTHOR]

Purpose: This Hydrocephalus Clinical Research Network (HCRN) study had two aims: (1) to compare the predictive performance of the original ETV Success Score (ETVSS) using logistic regression modeling with other newer machine learning models and (2) to assess whether inclusion of imaging variables improves prediction performance using machine learning models., Methods: We identified children undergoing first-time ETV for hydrocephalus that were enrolled prospectively at HCRN sites between 200 and 2020. The primary outcome was ETV success 6 months after index surgery. The cohort was randomly divided into training (70%) and testing (30%) datasets. The classic ETVSS variables were used for logistic regression and machine learning models. Predictive performance of each model was evaluated on the testing dataset using area under the receiver operating characteristic curve (AUROC)., Results: There were 752 patients that underwent first time ETV, of which 185 patients (24.6%) experienced ETV failure within 6 months. For aim 1, using the classic ETVSS variables, machine learning models did not outperform logistic regression with AUROC 0.60 (95% CI: 0.52-0.69) for Naïve Bayes (highest machine learning model performance) and 0.68 (95% CI: 0.60-0.76) for logistic regression. After inclusion of imaging features (aim 2), machine learning model prediction improved but remained no better than the above logistic regression with the highest AUROC of 0.67 (95% CI: 0.59-0.75) attained using Naïve Bayes architecture compared to 0.68 (95% CI: 0.59-0.76) for logistic regression., Conclusions: This contemporary multicenter observational cohort study demonstrated that machine learning modeling strategies did not improve performance of the ETVSS model over logistic regression., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Shunt infections are a common complication when treating hydrocephalus by cerebrospinal fluid (CSF) shunt placement. The source of infecting pathogens is not well understood. One hypothesis, which we explored here, is that microorganisms persist chronically in the host long before a symptomatic infection occurs and may be detectable in surgical events preceding infection. A cohort of 13 patients was selected, for which CSF samples were available from an infection episode and from a previous surgery event, which was either an initial shunt placement or a revision. Microbiota were analyzed both directly from CSF and from isolates cultured from CSF on aerobic and anaerobic media. The detection and identification of bacteria was done with high throughput DNA sequencing methods and mass spectrometry. The presence of bacteria was confirmed in 4 infection samples, of which 2 were after initial placement and 2 after revision surgery. Taxonomic identification was consistent with clinical microbiology laboratory results. Bacteria were not detected in any of the CSF samples collected at the time of the previous surgical events. While our findings do not provide direct evidence for long-term persistence of pathogens, they suggest the need for consideration of additional source material, such as biofilm and environmental swabs, and/or the use of more sensitive and specific analytical methods., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hodor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The frog fauna of New Guinea is exceptionally diverse but very poorly known. Here we describe a new species of pelodryadid treefrog that is currently known only from two specimens from a single site in Hela Province in the highlands of Papua New Guinea. Genetic data show that the new species is closely related to the torrent-breeding species Litoria angiana (Boulenger, 1915) from which it can be readily distinguished by its more slender body and limbs, relatively long forelimbs, and aspects of body colouration and tuberculation. The type locality is on Gigira Ridge, a massive limestone spur extending off New Guinea's Central Cordillera and we hypothesise that the distinctive slender limbs and relatively long forelimbs of the species may be adaptations for clambering, either in complex montane forest habitats or potentially within karst. The ongoing discovery of rare and seemingly localised frog species in Melanesia emphasises that recent estimates of a regional anuran fauna in excess of 700 species that were derived from known candidate species are likely conservative.

Understanding the proximate and ultimate causes of phenotypic variation is fundamental in evolutionary research, as such variation provides the substrate for selection to act upon. Although trait variation can arise due to selection, the importance of neutral processes is sometimes understudied. We presented the first reference-quality genome of the Red Diamond Rattlesnake (Crotalus ruber) and used range-wide 'omic data to estimate the degree to which neutral and adaptive evolutionary processes shaped venom evolution. We characterized population structure and found substantial genetic differentiation across two populations, each with distinct demographic histories. We identified significant differentiation in venom expression across age classes with substantially reduced but discernible differentiation across populations. We then used conditional redundancy analysis to test whether venom expression variation was best predicted by neutral divergence patterns or geographically variable (a)biotic factors. Snake size was the most significant predictor of venom variation, with environment, prey availability, and neutral sequence variation also identified as significant factors, though to a lesser degree. By directly including neutrality in the model, our results confidently highlight the predominant, yet not singular, role of life history in shaping venom evolution., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Objective: When the peritoneal cavity cannot serve as the distal shunt terminus, nonperitoneal shunts, typically terminating in the atrium or pleural space, are used. The comparative effectiveness of these two terminus options has not been evaluated. The authors directly compared shunt survival and complication rates for ventriculoatrial (VA) and ventriculopleural (VPl) shunts in a pediatric cohort., Methods: The Hydrocephalus Clinical Research Network Core Data Project was used to identify children ≤ 18 years of age who underwent either VA or VPl shunt insertion. The primary outcome was time to shunt failure. Secondary outcomes included distal site complications and frequency of shunt failure at 6, 12, and 24 months., Results: The search criteria yielded 416 children from 14 centers with either a VA (n = 318) or VPl (n = 98) shunt, including those converted from ventriculoperitoneal shunts. Children with VA shunts had a lower median age at insertion (6.1 years vs 12.4 years, p < 0.001). Among those children with VA shunts, a hydrocephalus etiology of intraventricular hemorrhage (IVH) secondary to prematurity comprised a higher proportion (47.0% vs 31.2%) and myelomeningocele comprised a lower proportion (17.8% vs 27.3%) (p = 0.024) compared with those with VPl shunts. At 24 months, there was a higher cumulative number of revisions for VA shunts (48.6% vs 38.9%, p = 0.038). When stratified by patient age at shunt insertion, VA shunts in children < 6 years had the lowest shunt survival rate (p < 0.001, log-rank test). After controlling for age and etiology, multivariable analysis did not find that shunt type (VA vs VPl) was predictive of time to shunt failure. No differences were found in the cumulative frequency of complications (VA 6.0% vs VPl 9.2%, p = 0.257), but there was a higher rate of pneumothorax in the VPl cohort (3.1% vs 0%, p = 0.013)., Conclusions: Shunt survival was similar between VA and VPl shunts, although VA shunts are used more often, particularly in younger patients. Children < 6 years with VA shunts appeared to have the shortest shunt survival, which may be a result of the VA group having more cases of IVH secondary to prematurity; however, when age and etiology were included in a multivariable model, shunt location (atrium vs pleural space) was not associated with time to failure. The baseline differences between children treated with a VA versus a VPl shunt likely explain current practice patterns.