A pooled subgroup analysis of glucarpidase treatment in 86 pediatric, adolescent, and young adult patients receiving high-dose methotrexate therapy in open-label trials

Acute kidney injury; Glucarpidase; MethotrexateLesió renal aguda; Glucarpidasa; MetotrexatLesión renal aguda; Glucarpidasa; MetotrexatoBackground Delayed methotrexate elimination can occur in patients undergoing high-dose methotrexate cancer treatment. Effectiveness of glucarpidase for rapidly reducing methotrexate concentrations was shown in compassionate-use trials in patients aged 0–84 years. Methods We performed post hoc analyses of infants (≥28 days to <2 years), children (≥2 to <12 years), adolescents (≥12 to <15 years), and young adults (≥15 to <25 years) from four multicenter, open-label, single-arm, glucarpidase compassionate-use trials. Patients had toxic methotrexate levels due to delayed methotrexate elimination and/or renal dysfunction, and received glucarpidase (50 U/kg). The primary endpoint was clinically important reduction (CIR) in plasma methotrexate (methotrexate ≤1 μmol/L at all post-glucarpidase measurements) based on high-performance liquid chromatography. Results Among 86 patients included in efficacy analyses, CIR was achieved by zero of one infant (0.0%), five of 16 children (31.3%), seven of 24 adolescents (29.2%), and 26/45 young adults (57.8%). Median methotrexate reduction was 98.7% or higher in each group 15 minutes post-glucarpidase. Patients with pre-glucarpidase methotrexate less than 50 μmol/L (35/42, 83.3%) were more likely to achieve CIR than those with methotrexate 50 μmol/L or higher (1/37, 2.7%). The most common treatment-related adverse event was paresthesia, occurring in three adolescents (4.5%) and six young adults (5.2%). No other treatment-related adverse event occurred in 5% or higher of any age group. Conclusion After accounting for pre-glucarpidase methotrexate levels, glucarpidase efficacy at inducing CIR in pediatric/young adult patients was consistent, with efficacy observed in the overall study population (i.e., patients aged 0–84), and no unexpected safety findings were observed. These findings demonstrate glucarpidase (50 U/kg) is an effective and well-tolerated dose for pediatric, adolescent, and young adult patients

Plasma sheet and (nonstorm) ring current formation from solar and polar wind sources

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95352/1/jgra17511.pd

MESSENGER and Mariner 10 flyby observations of magnetotail structure and dynamics at Mercury

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94896/1/jgra21525.pd

A systematic review of parental involvement in cognitive behavioural therapy for adolescent anxiety disorders

Anxiety disorders are common among adolescents and lead to poor long-term outcomes. Cognitive Behavioural Therapy (CBT) is an evidenced-based intervention for adolescent anxiety disorders, but little is known about whether and how parents should be involved. This systematic review evaluated how parents have been involved and associated treatment outcomes in studies of CBT for adolescent anxiety disorders. Electronic systematic searches were conducted in PsycINFO, Embase, CINAHL, Medline, AMED databases, to identify studies investigating CBT for adolescent anxiety disorder(s) that included parents in treatment. Twenty-three studies were identified. Parents were involved in treatment in a number of different ways: by attending separate parent sessions, joint parent-adolescent sessions, or both, or through provision of a workbook while attending some adolescent sessions. Content varied but was most typically aimed at the parent developing an understanding of core CBT components and skills to help them manage their adolescent’s anxiety and avoidance. Treatment outcomes indicate that CBT with parental involvement is an effective intervention for adolescent anxiety disorders, however it is not possible to draw conclusions regarding whether parental involvement (generally or in any particular form) enhances treatment outcomes. Poor reporting and methodological issues also limit the conclusions. Further research is required to identify whether there are particular types of parental involvement in CBT that bring clinical benefits to adolescents with anxiety disorders generally, as well as in particular circumstances

The Energetic Particle Detector (EPD) Investigation and the Energetic Ion Spectrometer (EIS) for the Magnetospheric Multiscale (MMS) Mission

Abstract The Energetic Particle Detector (EPD) Investigation is one of 5 fields-and-particles investigations on the Magnetospheric Multiscale (MMS) mission. MMS comprises 4 spacecraft flying in close formation in highly elliptical, near-Earth-equatorial orbits targeting understanding of the fundamental physics of the important physical process called magnetic reconnection using Earth’s magnetosphere as a plasma laboratory. EPD comprises two sensor types, the Energetic Ion Spectrometer (EIS) with one instrument on each of the 4 spacecraft, and the Fly’s Eye Energetic Particle Spectrometer (FEEPS) with 2 instruments on each of the 4 spacecraft. EIS measures energetic ion energy, angle and elemental compositional distributions from a required low energy limit of 20 keV for protons and 45 keV for oxygen ions, up to \u3e0.5 MeV (with capabilities to measure up to \u3e1 MeV). FEEPS measures instantaneous all sky images of energetic electrons from 25 keV to \u3e0.5 MeV, and also measures total ion energy distributions from 45 keV to \u3e0.5 MeV to be used in conjunction with EIS to measure all sky ion distributions. In this report we describe the EPD investigation and the details of the EIS sensor. Specifically we describe EPD-level science objectives, the science and measurement requirements, and the challenges that the EPD team had in meeting these requirements. Here we also describe the design and operation of the EIS instruments, their calibrated performances, and the EIS in-flight and ground operations. Blake et al. (The Flys Eye Energetic Particle Spectrometer (FEEPS) contribution to the Energetic Particle Detector (EPD) investigation of the Magnetospheric Magnetoscale (MMS) Mission, this issue) describe the design and operation of the FEEPS instruments, their calibrated performances, and the FEEPS in-flight and ground operations. The MMS spacecraft will launch in early 2015, and over its 2-year mission will provide comprehensive measurements of magnetic reconnection at Earth’s magnetopause during the 18 months that comprise orbital phase 1, and magnetic reconnection within Earth’s magnetotail during the about 6 months that comprise orbital phase 2