Vancomycin toxicity in neonates: a review of the evidence.

PURPOSE OF REVIEW: Vancomycin is a first-line agent in the treatment of serious Gram-positive infections in the neonatal population. The published evidence on vancomycin toxicity in neonates is limited. This review summarizes preclinical studies and clinical trials describing vancomycin toxicity. We discuss proposed pathophysiology and summarize evidence supporting dose-response relationships, genetic and environmental determinants, and consider future research required to further define vancomycin toxicity. RECENT FINDINGS: Current dosing regimens for vancomycin result in subtherapeutic levels in a large proportion of patients. Higher daily doses have been proposed, which have led to concerns regarding increased toxicity. Nephrotoxicity occurs in 1-9% of neonates receiving currently recommended doses. The incidence is highest in those receiving concomitant nephrotoxic drugs. Vancomycin-associated ototoxicity is rare in patients of all ages. Exposure-toxicity relationships in relation to nephrotoxicity and ototoxicity have not been clearly defined in neonates receiving vancomycin. SUMMARY: Current evidence supports the favourable safety profile of vancomycin in neonates. Further studies that address safety concerns relating to high-dose intermittent dosing regimens are needed. Such studies must include robust and standardized definitions of renal and hearing impairment, and include follow-up of sufficient length to establish the long-term implications of experimental findings

Level of Agreement of 36-Month ASQ-3 between Parents, Child Care Providers, and Health Care Professionals

Introduction Developmental delay is present in approximately 15 percent of children in the United States. 1 Less than one fifth of those children receive early intervention before age 3. Screening processes in pediatric settings are insufficient to identify all children with developmental delay. Objective Investigate the level of agreement in typical methods of administration of the 36 month Ages and Stages Questionnaire 3rd ed. (ASQ 3) between parents, CCPs, and student physical therapists (SPTs). Participants 11 children and parents from 2 childcare centers 5 childcare providers (CCPs) 7 student physical therapists (SPTs) Methods Outcome Measure: 36-Month ASQ-3 Standardized developmental screening tool designed to test a wide age range and be administered by various parties Rapid, simple, and cost effective way to monitor a child’s development Developmental screening was conducted across two testing sessions for each child based on common practices of ASQ-3 administration (Fig. 1). Session 1: Parent scored child’s performance from memory, unless confronted with novel items in which scoring was inferred or administered. SPT was present for questions. Session 2: CCP administered every item and scored the child based on their elicited performance while another SPT scored as an observer. Results Inter-rater Agreement: CCPs and SPTs significantly agreed in 4/5 domains No significant agreement between parents/CCPs or parents/SPTs for any domain (Table 1). Trends in specific domains (Fig. 2): Highly variable across the 5 domains Gross Motor: 73% of parents scored their child’s ability higher than at least one rater from the standardized session by as much as 25 points. Problem Solving: 64% of the parents scored their child as much as 30 points lower than at least one other rater. Conclusion Inter rater agreement between parents and CCPs or healthcare professionals was limited. Clinical Relevance Testing condition for parents was not parallel to the condition for other groups Recommend future exploration into interpretation of this screening tool and best use of the ASQ 3 by parents and CCPs to promote their participation

Vestibulo-oculomotor Function Following a Competitive Season Versus a Non-competitive Season in Collegiate Football Players

Introduction Background Football athletes experience a high number of head impacts during competitive play that do not cause immediate observable signs or symptoms. Research shows that exposure to repeated subconcussive impacts has a negative effect on the vestibulo-oculomotor (V-O) system and can result in long term neurologic dysfunction. Little is known about the ability of the V-O system to recover if an athlete is given an extended time away from subconcussive impacts. Purpose To investigate the difference in V-O function following a non-competitive (due to COVID-19) vs. a competitive season in cleared-to-play football players. Methods Participants 32 Division II football players from Concordia University, St. Paul ages 19-23. Data was collected in 2021 following a non-competitive season and in 2022 following a competitive season. V-O Tests Dynamic Visual Acuity (DVA) Near-Point Convergence (NPC) Results No statistically significant differences in V-O test results were found between the non-competitive and competitive season. Nearly 60% of the athletes had at least one positive V-O test after the competitive season. Conclusion Time away from subconcussive impacts due to a non-competitive season does not appear to have significantly influenced V-O function in collegiate football players. However, of concern is the large number of cleared-to-play athletes testing positive in at least one assessment tool. Clinical Relevance The vestibular system has the opportunity to recover, yet we are still unable to draw firm conclusions about the amount of time away from head impacts that is necessary for full recovery For many of our participants, a single season away from head impacts was not enough time to recover It is recommended that there be further investigation into time away from contact sports and return-to-play protocols in season

The racist bodily imaginary: the image of the body-in-pieces in (post)apartheid culture

This paper outlines a reoccurring motif within the racist imaginary of (post)apartheid culture: the black body-in-pieces. This disturbing visual idiom is approached from three conceptual perspectives. By linking ideas prevalent in Frantz Fanon’s description of colonial racism with psychoanalytic concepts such as Lacan’s notion of the corps morcelé, the paper offers, firstly, an account of the black body-in-pieces as fantasmatic preoccupation of the (post)apartheid imaginary. The role of such images is approached, secondly, through the lens of affect theory which eschews a representational ‘reading’ of such images in favour of attention to their asignifying intensities and the role they play in effectively constituting such bodies. Lastly, Judith Butler’s discussion of war photography and the conditions of grievability introduces an ethical dimension to the discussion and helps draw attention to the unsavory relations of enjoyment occasioned by such images

Context Specificity in Causal Signaling Networks Revealed by Phosphoprotein Profiling.

Signaling networks downstream of receptor tyrosine kinases are among the most extensively studied biological networks, but new approaches are needed to elucidate causal relationships between network components and understand how such relationships are influenced by biological context and disease. Here, we investigate the context specificity of signaling networks within a causal conceptual framework using reverse-phase protein array time-course assays and network analysis approaches. We focus on a well-defined set of signaling proteins profiled under inhibition with five kinase inhibitors in 32 contexts: four breast cancer cell lines (MCF7, UACC812, BT20, and BT549) under eight stimulus conditions. The data, spanning multiple pathways and comprising ∼70,000 phosphoprotein and ∼260,000 protein measurements, provide a wealth of testable, context-specific hypotheses, several of which we experimentally validate. Furthermore, the data provide a unique resource for computational methods development, permitting empirical assessment of causal network learning in a complex, mammalian setting.This work was supported by the National Institutes of Health National Cancer Institute (grant U54 CA112970 to J.W.G., G.B.M., S.M., and P.T.S.). S.M.H. and S.M. were supported by the UK Medical Research Council (unit program numbers MC_UP_1302/1 and MC_UP_1302/3). S.M. was a recipient of a Royal Society Wolfson Research Merit Award. The MD Anderson Cancer Center RPPA Core Facility is funded by the National Institutes of Health National Cancer Institute (Cancer Center Core Grant CA16672)

P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (<i>Xiphophorus helleri</i>) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

Dose-response associations between cycling activity and risk of hypertension in regular cyclists: The UK Cycling for Health Study

Most population studies on physical activity and health have involved largely inactive men and women, thus making it difficult to infer if health benefits occur at exercise levels above the current minimum guidelines. The aim was to examine associations between cycling volume and classical cardiovascular risk markers, including hypertension and hypercholesterolemia, in a population sample of habitual cyclists. A nationwide sample comprising 6,949 men and women (aged 47.6 yrs on average) completed questions about their cycling levels, demographics and health. Nearly the entire sample (96.3%) achieved the current minimum physical activity recommendation through cycling alone. There was a dose-response association between cycling volume and risk of diagnosed hypertension (p-trend =0.001), with odds ratios of 0.98 (95% CI, 0.80 – 1.21), 0.86 (0.70, 1.06), 0.67 (95% CI, 0.53 – 0.83) across categories of 23 – 40, 40 – 61, and >61 MET-hr/wk compared with <23 MET-hr/wk. These associations persisted in models adjusted for age, sex, smoking, alcohol, BMI, and other moderate to vigorous physical activities. We also observed inverse associations between cycling volume and other risk factors including BMI and hypercholesterolemia. In summary, results from a population sample of cyclists suggest that additional cardiovascular health benefits can be achieved beyond the current minimum physical activity recommendation

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio