Drivers and implications of alternative routes to fuels decarbonization in net-zero energy systems.

Energy transition scenarios are characterized by increasing electrification and improving efficiency of energy end uses, rapid decarbonization of the electric power sector, and deployment of carbon dioxide removal (CDR) technologies to offset remaining emissions. Although hydrocarbon fuels typically decline in such scenarios, significant volumes remain in many scenarios even at the time of net-zero emissions. While scenarios rely on different approaches for decarbonizing remaining fuels, the underlying drivers for these differences are unclear. Here we develop several illustrative net-zero systems in a simple structural energy model and show that, for a given set of final energy demands, assumptions about the use of biomass and CO2 sequestration drive key differences in how emissions from remaining fuels are mitigated. Limiting one resource may increase reliance on another, implying that decisions about using or restricting resources in pursuit of net-zero objectives could have significant tradeoffs that will need to be evaluated and managed.

Evolution of phenotypic disparity in the plant kingdom.

The plant kingdom exhibits diverse bodyplans, from single-celled algae to complex multicellular land plants, but it is unclear how this phenotypic disparity was achieved. Here we show that the living divisions comprise discrete clusters within morphospace, separated largely by reproductive innovations, the extinction of evolutionary intermediates and lineage-specific evolution. Phenotypic complexity correlates not with disparity but with ploidy history, reflecting the role of genome duplication in plant macroevolution. Overall, the plant kingdom exhibits a pattern of episodically increasing disparity throughout its evolutionary history that mirrors the evolutionary floras and reflects ecological expansion facilitated by reproductive innovations. This pattern also parallels that seen in the animal and fungal kingdoms, suggesting a general pattern for the evolution of multicellular bodyplans.

SKF96365 modulates activity of CatSper channels in human sperm.

Exposure of human sperm to progesterone (P4) activates cation channel of sperm (CatSper) channels, inducing an intracellular Ca2+ concentration ([Ca2+]i) transient followed by repetitive [Ca2+]i activity (oscillations), which are believed to be functionally important. We investigated the potential significance of store-operated Ca2+-entry in these oscillations using the inhibitor SKF96365 (30 µM; SKF). Following pre-treatment of human sperm with 3 µM P4, exposure to SKF doubled the proportion of oscillating cells (P = 0.00004). In non-pre-treated cells, SKF had an effect similar to P4, inducing a [Ca2+]i transient in >80% of cells which was followed by oscillations in ≈50% of cells. The CatSper blocker RU1968 (11 µM) inhibited the SKF-induced [Ca2+]i increase and reversibly arrested [Ca2+]i oscillations. Using whole-cell patch clamp, we observed that SKF enhanced CatSper currents by 100% within 30 s, but amplitude then decayed to levels below control over the next minute. When cells were stimulated with P4, CatSper currents were stably increased (by 200%). Application of SKF then returned current amplitude to control level or less. When sperm were prepared in medium lacking bovine serum albumin (BSA), both P4 and SKF induced a [Ca2+]i transient in >95% of cells but the ability of SKF to induce oscillations was greatly reduced (P = 0.0009). We conclude that SKF, similar to a range of small organic molecules, activates CatSper channels, but that a secondary blocking action also occurs, which was detected only during patch-clamp recording. The failure of SKF to induce oscillations when cells were prepared without BSA emphasizes that the drug does not fully mimic the actions of P4.

Predictors of Adherence to Continuous Positive Airway Pressure in Older Adults With Apnea and Amnestic Mild Cognitive Impairment.

BACKGROUND: Almost 60% of adults with amnestic mild cognitive impairment (aMCI) have obstructive sleep apnea (OSA). Treatment with continuous positive airway pressure (CPAP) may delay cognitive decline, but CPAP adherence is often suboptimal. In this study, we report predictors of CPAP adherence in older adults with aMCI who have increased odds of progressing to dementia, particularly due to Alzheimer's disease. METHODS: The data are from Memories 2, "Changing the Trajectory of Mild Cognitive Impairment with CPAP Treatment of Obstructive Sleep Apnea." Participants had moderate to severe OSA, were CPAP naïve, and received a telehealth CPAP adherence intervention. Linear and logistic regression models examined predictors. RESULTS: The 174 participants (mean age 67.08 years, 80 female, 38 Black persons) had a mean apnea-hypopnea index of 34.78, and 73.6% were adherent, defined as an average of ≥4 hours of CPAP use per night. Only 18 (47.4%) Black persons were CPAP adherent. In linear models, White race, moderate OSA, and participation in the tailored CPAP adherence intervention were significantly associated with higher CPAP use at 3 months. In logistic models, White persons had 9.94 times the odds of adhering to CPAP compared to Black persons. Age, sex, ethnicity, education, body mass index, nighttime sleep duration, daytime sleepiness, and cognitive status were not significant predictors. CONCLUSIONS: Older patients with aMCI have high CPAP adherence, suggesting that age and cognitive impairment should not be a barrier to prescribing CPAP. Research is needed to improve adherence in Black patients, perhaps through culturally tailored interventions.

Safe handling of hazardous drugs.

Background: This evidence-based practice guideline was developed to update and address new issues in the handling of hazardous drugs including being compliant with NAPRA (National Association of Pharmacy Regulatory Authorities) and USP 800 (United States Pharmacopeia) standards, the use of personal protective equipment and treatment in diverse settings including in the home setting. Methods: This guideline was developed from an adaptation and endorsement of existing guidelines and from three systematic reviews. Prior to publication, this guideline underwent a series of peer, patient, methodological and external reviews to gather feedback. All comments were addressed and the guideline was amended when required. This guideline applies to and is intended for all health care workers who may come into contact with hazardous drugs at any point in the medication circuit. Results: The recommendations represent a reasonable and practical set of procedures that the intended users of this guideline should implement to minimize the opportunity for accidental exposure. These recommendations are not limited to just the point of care, but cover the entire chain of handling of cytotoxics from the time they enter the institution until they leave in the patient or as waste. Conclusions: Decreasing the likelihood of accidental exposure to cytotoxic agents within the medication circuit is the main objective of this evidenced-based guideline. The recommendations differ slightly from previous guidelines due to new evidence.

Pain After Preoperative Ultrasound Guided Hip Injections for Total Hip Arthroplasty: A Pilot Randomized Controlled Trial.

Introduction. Hip replacement is a frequently performed and highly successful treatment for patients with end stage osteoarthritis. Advances in technique and pain management have allowed for rapid mobilization and early discharge after surgery. We hypothesize that pre-incision intra-articular injection of local anesthetic with epinephrine under image guidance combined with post incision peri-articular injection (PAI) may be more effective than PAI alone. Methods. A prospective, randomized, controlled, comparative investigation at a single institution of 41 patients undergoing THA who received standard 30 mL post-arthrotomy, PAI of ropivacaine with epinephrine under direct visualization after prosthesis implantation before closure or an equivalent dose divided into a 10 mL pre-incision, ultrasound guided intra-articular injection and a 20 mL post-arthrotomy PAI. Results. 42 patients were included in this study before its early conclusion with 22 patients in the treatment group and 20 in the control group. There were no significant differences in age, BMI or ASA scores. Additionally, there were no significant differences noted when comparing groups by postoperative outcome measures including OMME, EBL, OR time, PACU minutes, and first and last PACU pain score. Furthermore, there were no significant differences in the PROMs evaluated. Discussion. The addition of ultrasound guided pre-incision intra-articular injection to the standard PAI had no benefit when compared with standard PAI during a THA. Portable mobile phone based ultrasound devices provide a cost effective way to perform musculoskeletal blocks, and further studies on their use and comparative accuracy is warranted. A novel technique for confirmation of injection location is described.

Evaluating Food Intake Outcomes Among Sexual Minority Women: A Systematic Review.

Purpose: Sexual minority women (SMW) have a higher prevalence of obesity and weight-related health disparities when compared with heterosexual women that may be explained by differences in food intake. This systematic review had two primary aims: (1) synthesize the results for food intake outcomes among SMW, organized primarily according to the dietary risk assessment; and (2) identify possible theoretically informed moderators and mediators of the association between women's sexual identity and differences in food intake. Methods: The literature search was conducted using the PubMed and PsycInfo databases to identify articles published until March 23, 2021. Inclusion criteria were: (1) included a sample of adult SMW, (2) quantitatively assessed a food intake outcome, and (3) published in an English language peer-reviewed journal in the past 10 years. Thirteen articles were eligible and included in the review. Results: Overall, there were inconsistent findings comparing food intake between SMW and heterosexual women. There was some evidence to suggest that identity characteristics beyond sexual orientation (e.g., race and gender presentation) and place of residence (e.g., urban vs. rural settings) were plausible moderators. Only one variable pertaining to SMW's developmental history, mother's diet quality, was identified as a possible mediator. The main critiques of the literature include the predominance of convenience sampling, cross-sectional data, and inconsistencies in the measurement of sexual orientation and diet. Conclusion: This review highlights that further work is needed to consider additional hypotheses to explain disparities in obesity and weight-related health disparities among SMW to inform comprehensive behavioral intervention strategies.

Discrimination experiences, resilience, and cardiovascular disease risk factors among sexual minority women.

Resilience, or the process of adapting to adversity, may protect against the harmful effects of minority-related stressors on the cardiovascular health of sexual minority women (SMW). An online survey was conducted in a sample of cisgender, non-heterosexual women to evaluate resilience as a moderator of the association between discrimination experiences and key cardiovascular disease (CVD) risk factors: stress, tobacco-smoking, hazardous alcohol consumption, poor diet quality, physical inactivity, and sedentary behaviors. Overall, 191 women (mean age = 29.34, SD = 6.92; 84.5% White) completed the survey and met eligibility to be included in the data analysis. White race (b = - 6.71, SE = 2.49) and education (b = - 3.36, SE = 0.56) were each independently associated with fewer discrimination experiences. Latinx ethnicity was associated with more discrimination experiences (b = 9.34, SE = 2.61). Education was associated with greater resilience (b = 4.57, SE = 0.83). Multivariable regression models were adjusted for race, ethnicity, and education. Discrimination was associated with a higher likelihood of smoking in the past month (b = 0.04, SE = 0.02) and drinking at hazardous levels (b = 0.09, SE = 0.02). Resilience was associated with less stress (b = - 0.15, SE = 0.02), a lower likelihood of hazardous alcohol consumption (b = - 0.02, SE = 0.01) and less time spent engaging in sedentary behaviors (b = - 0.02, SE = 0.01). One moderation emerged, such that discrimination was negatively associated with stress for those low in resilience (b = - 1.75, SE = 0.58), and not associated with stress for those high in resilience. These findings may inform the development of CVD-risk reduction interventions for SMW, which could include both strategies to mitigate the effects of discrimination on substance use and coping skills to promote resilience.

Piecing together the eophytes - a new group of ancient plants containing cryptospores.

The earliest evidence for land plants comes from dispersed cryptospores from the Ordovician, which dominated assemblages for 60 million years. Direct evidence of their parent plants comes from minute fossils in Welsh Borderland Upper Silurian to Lower Devonian rocks. We recognize a group that had forking, striated axes with rare stomata terminating in valvate sporangia containing permanent cryptospores, but their anatomy was unknown especially regarding conducting tissues. Charcoalified fossils extracted from the rock using HF were selected from macerates and observed using scanning electron microscopy. Promising examples were split for further examination and compared with electron micrographs of the anatomy of extant bryophytes. Fertile fossil axes possess central elongate cells with thick walls bearing globules, occasional strands and plasmodesmata-sized pores. The anatomy of these cells best matches desiccation-tolerant food-conducting cells (leptoids) of bryophytes. Together with thick-walled epidermal cells and extremely small size, these features suggest that these plants were poikilohydric. Our new data on conducting cells confirms a combination of characters that distinguish the permanent cryptospore-producers from bryophytes and tracheophytes. We therefore propose the erection of a new group, here named the Eophytidae (eophytes).

Earliest record of transfer cells in Lower Devonian plants.

Key sources of information on the nature of early terrestrial ecosystems are the fossilized remains of plants and associated organic encrustations, which are interpreted as either biofilms, biological soil crusts or lichens. The hypothesis that some of these encrustations might be the remains of the thalloid gametophytes of embryophytes provided the stimulus for this investigation. Fossils preserved in charcoal were extracted from Devonian Period (Lochkovian Stage, c. 410-419 Myr old) sediments at a geological site in Shropshire (UK). Scanning electron micrographs (SEMs) of the fossils were compared with new and published SEMs of extant bryophytes and tracheophytes, respectively. One specimen was further prepared and imaged by transmission electron microscopy. Fossils of thalloid morphology were composed almost entirely of cells with labyrinthine ingrowths; these also were present in fossils of axial morphology where they were associated with putative food-conducting cells. Comparison with modern embryophytes demonstrates that these distinctive cells are transfer cells (TCs). Our fossils provide by far the earliest geological evidence of TCs. They also show that some organic encrustations are the remains of thalloid land plants and that these are possibly part of the life cycle of a newly recognized group of plants called the eophytes.

Eyes and Ears on Patient Safety: Sources of Notifications About the Health, Performance, and Conduct of Health Practitioners.

OBJECTIVE: The aim of the study was to describe the sources of notifications of concern ("notifications") regarding the health, performance, and conduct of health practitioners from 14 registered professions in Australia. METHODS: This retrospective cohort study analyzed 43,256 notifications lodged with the Australian Health Practitioner Regulation Agency and the Health Professional Councils Authority between 2011 and 2016. We used descriptive statistical analysis to describe the characteristics of these notifications, including their source, issue and domain, and subject. RESULTS: Patients and their relatives lodged more than three-quarters (78%) of notifications regarding clinical performance, including diagnosis, treatment, and communication. Fellow practitioners were a common source of notifications about advertising and titles. Self-reports commonly related to health impairments, such as mental illness or substance use. Other agencies played a role in reporting concerns about prescribing or supply of medicines. CONCLUSIONS: Various actors in the healthcare system play different roles in sketching the picture of healthcare quality and safety that notifications present to regulators. Improved understanding of which sources are most likely to raise which concerns may enhance regulators' ability to identify and respond to patient safety risks.

The effect of time on packed cell volume following packed red blood cell transfusion in anemic dogs.

OBJECTIVE: To compare the PCV at several timepoints following packed red blood cell (pRBC) administration to anemic dogs and to assess if underlying cause of anemia or regenerative status significantly affects these measurements. DESIGN: Prospective, observational study from November 2016 to October 2017. SETTING: A small animal emergency and specialty hospital. ANIMALS: Forty-six anemic client-owned dogs that received a total of 50 pRBC transfusions for management of anemia. INTERVENTIONS: Blood was collected, and a PCV was obtained prior to pRBC transfusion (T0), immediately after (T1), 30 minutes after (T2), 1 hour after (T3), 2 hours after (T4), and 4 hours after (T5) the transfusion. Underlying causes of anemia were classified as hemorrhage, hemolysis, and ineffective erythropoiesis. Dogs were also categorized in regard to regenerative status of anemia and the presence or absence of expected continued blood loss or destruction. MEASUREMENTS AND MAIN RESULTS: The mean PCV at T0 was 0.15 L/L (15%). After administration of a pRBC transfusion, the mean PCV at T1 was 0.28 L/L (28%). For all other timepoints (T2, T3, T4, and T5), the mean PCV was 0.27 L/L (27%). The PCV did not change significantly over time post-transfusion (P = 0.184), and no pairwise combinations of times differed significantly (paired t-tests; P > 0.05 for all). When dogs were categorized via regeneration status and continued blood loss or hemolysis, results were consistent. CONCLUSIONS: There was no significant change in PCV from the value obtained immediately after pRBC transfusion up to 4 hours post-transfusion in dogs with several different causes of anemia. These results suggest that obtaining a PCV immediately after administering a pRBC transfusion to an anemic dog may be just as reliable as obtaining a measurement 2 hours after the transfusion. This remains true for dogs with expected continued red blood cell loss or destruction.

Signatures of adaptation to a monocot host in the plant-parasitic cyst nematode Heterodera sacchari.

Interactions between plant-parasitic nematodes and their hosts are mediated by effectors, i.e. secreted proteins that manipulate the plant to the benefit of the pathogen. To understand the role of effectors in host adaptation in nematodes, we analysed the transcriptome of Heterodera sacchari, a cyst nematode parasite of rice (Oryza sativa) and sugarcane (Saccharum officinarum). A multi-gene phylogenetic analysis showed that H. sacchari and the cereal cyst nematode Heterodera avenae share a common evolutionary origin and that they evolved to parasitise monocot plants from a common dicot-parasitic ancestor. We compared the effector repertoires of H. sacchari with those of the dicot parasites Heterodera glycines and Globodera rostochiensis to understand the consequences of this transition. While, in general, effector repertoires are similar between the species, comparing effectors and non-effectors of H. sacchari and G. rostochiensis shows that effectors have accumulated more mutations than non-effectors. Although most effectors show conserved spatiotemporal expression profiles and likely function, some H. sacchari effectors are adapted to monocots. This is exemplified by the plant-peptide hormone mimics, the CLAVATA3/EMBRYO SURROUNDING REGION-like (CLE) effectors. Peptide hormones encoded by H. sacchari CLE effectors are more similar to those from rice than those from other plants, or those from other plant-parasitic nematodes. We experimentally validated the functional significance of these observations by demonstrating that CLE peptides encoded by H. sacchari induce a short root phenotype in rice, whereas those from a related dicot parasite do not. These data provide a functional example of effector evolution that co-occurred with the transition from a dicot-parasitic to a monocot-parasitic lifestyle.

TERMINAL FLOWER-1/CENTRORADIALIS inhibits tuberisation via protein interaction with the tuberigen activation complex.

Potato tuber formation is a secondary developmental programme by which cells in the subapical stolon region divide and radially expand to further differentiate into starch-accumulating parenchyma. Although some details of the molecular pathway that signals tuberisation are known, important gaps in our knowledge persist. Here, the role of a member of the TERMINAL FLOWER 1/CENTRORADIALIS gene family (termed StCEN) in the negative control of tuberisation is demonstrated for what is thought to be the first time. It is shown that reduced expression of StCEN accelerates tuber formation whereas transgenic lines overexpressing this gene display delayed tuberisation and reduced tuber yield. Protein-protein interaction studies (yeast two-hybrid and bimolecular fluorescence complementation) demonstrate that StCEN binds components of the recently described tuberigen activation complex. Using transient transactivation assays, we show that the StSP6A tuberisation signal is an activation target of the tuberigen activation complex, and that co-expression of StCEN blocks activation of the StSP6A gene by StFD-Like-1. Transcriptomic analysis of transgenic lines misexpressing StCEN identifies early transcriptional events in tuber formation. These results demonstrate that StCEN suppresses tuberisation by directly antagonising the function of StSP6A in stolons, identifying StCEN as a breeding marker to improve tuber initiation and yield through the selection of genotypes with reduced StCEN expression.

Mid-Devonian Archaeopteris Roots Signal Revolutionary Change in Earliest Fossil Forests.

The origin of trees and forests in the Mid Devonian (393-383 Ma) was a turning point in Earth history, marking permanent changes to terrestrial ecology, geochemical cycles, atmospheric CO2 levels, and climate. However, how all these factors interrelate remains largely unknown. From a fossil soil (palaeosol) in the Catskill region near Cairo NY, USA, we report evidence of the oldest forest (mid Givetian) yet identified worldwide. Similar to the famous site at Gilboa, NY, we find treefern-like Eospermatopteris (Cladoxylopsida). However, the environment at Cairo appears to have been periodically drier. Along with a single enigmatic root system potentially belonging to a very early rhizomorphic lycopsid, we see spectacularly extensive root systems here assigned to the lignophyte group containing the genus Archaeopteris. This group appears pivotal to the subsequent evolutionary history of forests due to possession of multiple advanced features and likely relationship to subsequently dominant seed plants. Here we show that Archaeopteris had a highly advanced root system essentially comparable to modern seed plants. This suggests a unique ecological role for the group involving greatly expanded energy and resource utilization, with consequent influence on global processes much greater than expected from tree size or rooting depth alone.

Complaint risk among mental health practitioners compared with physical health practitioners: a retrospective cohort study of complaints to health regulators in Australia.

OBJECTIVES: To understand complaint risk among mental health practitioners compared with physical health practitioners. DESIGN: Retrospective cohort study, using incidence rate ratios (IRRs) to analyse complaint risk and a multivariate regression model to identify predictors of complaints. SETTING: National study using complaints data from health regulators in Australia. PARTICIPANTS: All psychiatrists and psychologists ('mental health practitioners') and all physicians, optometrists, physiotherapists, osteopaths and chiropractors ('physical health practitioners') registered to practice in Australia between 2011 and 2016. OUTCOME MEASURES: Incidence rates, source and nature of complaints to regulators. RESULTS: In total, 7903 complaints were lodged with regulators over the 6-year period. Most complaints were lodged by patients and their families. Mental health practitioners had a complaint rate that was more than twice that of physical health practitioners (complaints per 1000 practice years: psychiatrists 119.1 vs physicians 48.0, p<0.001; psychologists 21.9 vs other allied health 7.5, p<0.001). Their risk of complaints was especially high in relation to reports, records, confidentiality, interpersonal behaviour, sexual boundary breaches and the mental health of the practitioner. Among mental health practitioners, male practitioners (psychiatrists IRR: 1.61, 95% CI 1.39 to 1.85; psychologists IRR: 1.85, 95% CI 1.65 to 2.07) and older practitioners (≥65 years compared with 36-45 years: psychiatrists IRR 2.37, 95% CI 1.95 to 2.89; psychologists IRR 1.78, 95% CI 1.47 to 2.14) were at increased risk of complaints. CONCLUSIONS: Mental health practitioners were more likely to be the subject of complaints than physical health practitioners. Areas of increased risk are related to professional ethics, communication skills and the health of mental health practitioners themselves. Further research could usefully explore whether addressing these risk factors through training, professional development and practitioner health initiatives may reduce the risk of complaints about mental health practitioners.

Identification of TIMING OF CAB EXPRESSION 1 as a temperature-sensitive negative regulator of tuberization in potato.

For many potato cultivars, tuber yield is optimal at average daytime temperatures in the range 14-22 °C. Above this range, tuber yield is reduced for most cultivars. We previously reported that moderately elevated temperature increases steady-state expression of the core circadian clock gene TIMING OF CAB EXPRESSION 1 (StTOC1) in developing tubers, whereas expression of the StSP6A tuberization signal is reduced, along with tuber yield. In this study we provide evidence that StTOC1 links environmental signalling with potato tuberization by suppressing StSP6A autoactivation in the stolons. We show that transgenic lines silenced in StTOC1 expression exhibit enhanced StSP6A transcript levels and changes in gene expression in developing tubers that are indicative of an elevated sink strength. Nodal cuttings of StTOC1 antisense lines displayed increased tuber yields at moderately elevated temperatures, whereas tuber yield and StSP6A expression were reduced in StTOC1 overexpressor lines. Here we identify a number of StTOC1 binding partners and demonstrate that suppression of StSP6A expression is independent of StTOC1 complex formation with the potato homolog StPIF3. Down-regulation of StTOC1 thus provides a strategy to mitigate the effects of elevated temperature on tuber yield.

Development of a low-cost air sensor package and indoor air quality monitoring in a California middle school: Detection of a distant wildfire.

A low-cost air sensor package was used to monitor indoor air quality (IAQ) in a classroom at the Albany Middle School in the San Francisco Bay Area of California. A rapid increase in carbon dioxide (CO2) was observed in the classroom as soon as it is occupied. When the classroom is unoccupied, the CO2 levels decay slowly toward the outdoor background level. All high CO2 concentrations observed inside the classroom, above the outdoor background, was due to exhaling of the occupants. The CO2 concentrations generally exceed the recommended level of 1000 ppb towards the end of the school day. The exceedances and slow decay may suggest that the ventilation rate in this school is not sufficient. The particulate level in the classroom was low until a distant wildfire advected large amount of particulate matter to the San Francisco Bay Area. Very high (10-15 times compared to the background) particle numbers (per m3 of particles with diameter >0.3 µm) were observed in the classroom during the wildfire. These particles were relatively small (0.3-1.0 µm) and the filters (MERV 8) of the ventilation system were unable to filter them out. Therefore, the measurements made by low-cost particle counters can inform the school administrators of adverse IAQ during future wildfire (or other combustion) events. The particle number was independent of the occupation before and during the wildfire suggesting that all observed particles were infiltrated into the classroom from outside. Consistent with previous studies, no appreciable increase in the local ambient CO2 background was observed during this distant wildfire event. Implications: Low-cost air sensors are effective in monitoring indoor air quality in classrooms. The CO2 levels in classrooms are mainly generated indoors due to exhalation of occupants. Concentration of CO2 generally exceed the recommended level of 1000 ppb towards the end of the school day. In contrast, the particulate matter mostly comes from outdoors and small particles penetrate though the filters normally used at schools. Distant wildfires do not increase the local CO2 background appreciably, but significantly increase the particulate matter concentrations both indoors and outdoors. Further investigations are needed to assure that ventilation rates in classrooms are sufficiently health protective.

Population Pharmacokinetics of Vancomycin in the Pediatric Cardiac Surgical Population.

OBJECTIVE: Vancomycin is often used in the pediatric cardiac surgical population, but few pharmacokinetic data are available to guide dosing. METHODS: A retrospective, population pharmacokinetic study was performed for patients <19 years of age initiated on vancomycin after cardiac surgery in the cardiac intensive care unit from 2011-2016 in our institution. Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM. Simulation was performed to determine a dosing strategy that most frequently obtained an AUC0-24:MIC (minimum inhibitory concentration) ratio of >400. RESULTS: A total of 261 patients (281 cardiac surgical procedures, cardiopulmonary bypass 82.3%) met inclusion criteria (60.1% male, median age 0.31 [IQR, 0.07-0.77] years). Vancomycin (14.5 ± 1.7 mg/kg/dose) was administered at median postoperative day 9 (IQR, 4-14), with a mean serum concentration of 11.5 ± 5.5 mg/L at 8.9 ± 3.8 hours after a dose. Population pharmacokinetic analysis demonstrated that a 1-compartment proportional error model with allometrically scaled weight best fit the data, with creatinine clearance and postmenstrual age as significant covariates. Simulation identified that a dosing regimen of 20 mg/kg/dose every 8 hours was most likely to achieve an AUC0-24:MIC ratio > 400 at a mean trough serum concentration of 12.9 ± 3.2 mg/L. CONCLUSIONS: Vancomycin dosing in the postoperative pediatric cardiac surgical population should incorporate postmenstrual age and creatinine clearance. A vancomycin dose of 20 mg/kg every 8 hours is a reasonable empiric strategy.