Path-dependence of the Plio-Pleistocene glacial/interglacial cycles.

We find strong path dependence in the evolution of the Plio-Pleistocene glaciations using CLIMBER-2 Earth System Model simulations from the mid-Pliocene to modern preindustrial (3 My-0 My BP) driven by a gradual decrease in volcanic carbon dioxide outgassing and regolith removal from basal ice interaction. Path dependence and hysteresis are investigated by alternatively driving the model forward and backward in time. Initiating the model with preindustrial conditions and driving the model backward using time-reversed forcings, the increase in volcanic outgassing back-in-time (BIT) does not generate the high CO2 levels and relatively ice-free conditions of the late Pliocene seen in forward-in-time (FIT) simulations of the same model. This behavior appears to originate from nonlinearities and initial state dependence in the carbon cycle. A transition from low-amplitude sinusoidal obliquity (~41 ky) and precession (~23 ky) driven glacial/interglacial cycles to high-amplitude ~100 ky likely eccentricity-related sawtooth cycles seen between -1.25 My and -0.75 My BP (the Mid-Pleistocene transition or "MPT") in FIT simulations disappears in BIT integrations depending on the details of how the regolith removal process is treated. A transition toward depleted regolith and lowered atmospheric CO2 levels are both required to reproduce the MPT.

Role of atmospheric resonance and land-atmosphere feedbacks as a precursor to the June 2021 Pacific Northwest Heat Dome event.

We demonstrate an indirect, rather than direct, role of quasi-resonant amplification of planetary waves in a summer weather extreme. We find that there was an interplay between a persistent, amplified large-scale atmospheric circulation state and soil moisture feedbacks as a precursor for the June 2021 Pacific Northwest "Heat Dome" event. An extended resonant planetary wave configuration prior to the event created an antecedent soil moisture deficit that amplified lower atmospheric warming through strong nonlinear soil moisture feedbacks, favoring this unprecedented heat event.

Pharmacokinetics of erlotinib for the treatment of high-grade glioma in a pediatric patient with cystic fibrosis: case report and review of the literature.

A 12-year-old girl with cystic fibrosis was diagnosed with a high-grade glioma after radiographic and biopsy results confirmed the primary intracranial lesion. She was treated with single-agent erlotinib during and after daily localized radiation therapy. Pharmacokinetic studies were conducted to assess the effect of pancreatic enzyme deficiency and intestinal malabsorption secondary to cystic fibrosis on the bioavailability of orally administered erlotinib, a lipophilic drug. Pharmacokinetic analysis of plasma samples from days 1 and 8 demonstrated that absorption of oral erlotinib was not affected by the patient's cystic fibrosis when the drug was given concomitantly with pancreatic enzyme replacement. When pediatric patients with cystic fibrosis are receiving erlotinib or other lipophilic oral drugs, continued supplementation of pancreatic enzymes is recommended, with therapeutic drug monitoring of plasma drug concentrations when feasible, and close observation for therapeutic responses and adverse effects.

Impact of a prescription review program on the accuracy and safety of discharge prescriptions in a pediatric hospital setting.

OBJECTIVE: The purpose of this study was to determine if a prescription review service, at the time of discharge, enhances the accuracy and safety of prescriptions written at an academic pediatric hospital. METHODS: The study took place over a 30-day period and included prescriptions written for patients being discharged from the General Pediatric and Pediatric Intensive Care Services at the University of Maryland Hospital for Children, a 120-bed academic pediatric hospital. Discharge prescriptions were faxed to the Inpatient Pediatric Pharmacy where they were reviewed by a pediatric clinical pharmacist. Specific review criteria were aimed at detecting prescribing errors that included patient identification, medication selection, dosing, and therapy omission. A prescriber was notified via alpha page when errors were identified and advised on corrective measures. Interventions were compiled and analyzed to determine the overall impact of the discharge prescription review program. RESULTS: Over the 30-day period, 74 discharge prescriptions were reviewed by a pediatric clinical pharmacist. At least one prescribing error was detected in 81% of the prescriptions reviewed. Overall, 101 prescribing errors were documented and included patient identification, medication selection and dose calculation errors. The estimated cost-savings attributed to the interventions is approximately $7670. CONCLUSION: Through the discharge prescription review program, the pediatric clinical pharmacists were able to make interventions on the majority of prescriptions reviewed. The types of errors that required interventions have been identified as potential sources for major medication errors in the pediatric population. We concluded that the review of discharge prescriptions by a pediatric clinical pharmacist was an effective method of preventing prescribing errors in the pediatric environment.