Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome

BACKGROUND AND OBJECTIVE: Alemtuzumab (Campath®) is used to prevent graft-versus-host disease and graft failure following pediatric allogeneic hematopoietic cell transplantation. The main toxicity includes delayed immune reconstitution, subsequent viral reactivations, and leukemia relapse. Exposure to alemtuzumab is highly variable upon empirical milligram/kilogram dosing. METHODS: A population pharmacokinetic (PK) model for alemtuzumab was developed based on a total of 1146 concentration samples from 206 patients, aged 0.2-19 years, receiving a cumulative intravenous dose of 0.2-1.5 mg/kg, and treated between 2003 and 2015 in two centers. RESULTS: Alemtuzumab PK were best described using a two-compartment model with a parallel saturable and linear elimination pathway. The linear clearance pathway, central volume of distribution, and intercompartmental distribution increased with body weight. Blood lymphocyte counts, a potential substrate for alemtuzumab, did not impact clearance. CONCLUSION: The current practice with uniform milligram/kilogram doses leads to highly variable exposures in children due to the non-linear relationship between body weight and alemtuzumab PK. This model may be used for individualized dosing of alemtuzumab

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave transient was identified in data recorded by the Advanced LIGO detectors on 2015 September 14. The event candidate, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the gravitational wave data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network Circulars, giving an overview of the participating facilities, the gravitational wave sky localization coverage, the timeline and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the electromagnetic data and results of the electromagnetic follow-up campaign will be disseminated in the papers of the individual teams

An injectable self-healing coordinative hydrogel with antibacterial and angiogenic properties for diabetic skin wound repair

In this work, an injectable, self-healing hydrogel with antibacterial and angiogenic abilities was prepared based on the coordination of multi-arm thiolated polyethylene glycol (SH-PEG) with antibacterial silver ions (Ag+). The injectable and self-healing properties derive from the dynamic nature of the Ag-S coordination bonds. After incorporation of an angiogenic drug desferrioxamine (DFO), we could obtain a multifunctional hydrogel with manageable, resistant to external stress, antibacterial and angiogenic properties. Such unique multifunctional hydrogel thus shows potential to accelerate the healing of some exposed wounds (e.g., diabetic skin wound) under disturbed physiological functions, high risk of bacterial infections, and external mechanical irritation