Pesticides coated to the seed surface potentially pose an ecological risk to granivorous birds that consume incompletely buried or spilled seeds. To assess the toxicokinetics of seeds treated with ...current-use fungicides, Japanese quail (Coturnix japonica) were orally dosed with commercially coated wheat seeds. Quail were exposed to metalaxyl, tebuconazole, and fludioxonil at either a low dose (0.0655, 0.0308, and 0.0328 mg/kg of body weight, respectively) or a high dose (0.196, 0.0925, and 0.0985 mg/kg of body weight, respectively). Fungicides were rapidly absorbed and distributed to tissues. Tebuconazole was metabolized into tert-butylhydroxy-tebuconazole. All compounds were eliminated to below detection limits within 24 h. The high detection frequencies observed in fecal samples potentially offer a non-invasive matrix to monitor pesticide exposure. With the summation of total body burden across plasma, tissue, and fecal samples, less than 9% of the administered dose was identified as the parent fungicide, demonstrating the importance to monitor both active ingredients and their metabolites in biological samples.
The Children's Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multi-agent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly ...diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients.
The trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≥ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≥ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible.
At end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups (
= .29) or by treatment regimen (
= .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients.
COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.
Large B‐cell lymphoma with IRF4 rearrangement is a provisional entity in the 2017 World Health Organization classification. In order to characterize these lymphomas in children from the United ...States, IRF4 FISH and immunohistochemical stains were performed on 32 follicular lymphoma and diffuse large B‐cell lymphoma (DLBCL) from Children's Oncology Group studies. Two DLBCLs (6%) had IRF4 rearrangements, one involving the ileocecal valve and another involving the tonsil and cerebrospinal fluid. Both cases had strong, diffuse IRF4/MUM1 immunohistochemical staining, which may be a pathologic clue to the diagnosis. Reclassification of these cases may have prognostic and therapeutic implications.
Post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients has become one of the most common forms of lymphoproliferation in childhood and is a serious complication ...of SOT. More than 90% of cases are of B-cell origin, Epstein Barr virus (EBV) positive and are mostly occurring in the early post-transplant period. Pathologically and clinically it is a heterogenous disease ranging from being responsive to reduced immunosuppression without further intervention to rapidly progressive fulminant PTLD requiring prompt initiation of therapy. Prognosis overall is favorable. Current treatment strategies as well new promising targeted immune-based therapies such as rituximab and EBV-specific cytotoxic T-lymphocytes are being discussed.
We present a multiwavelength examination of the supernova remnant (SNR) S26 in the nearby galaxy NGC 300 using data from Chandra X-ray Observatory, XMM-Newton X-ray Observatory, Hubble Space ...Telescope (HST), the Very Large Array, and the Australia Telescope Compact Array. We simultaneously fit all of the available X-ray data with a thermal plasma model and find a temperature of 0.77 0.13 keV with a hydrogen column density of ( ) × 1020 cm−2. HST imaging allows us to measure a semimajor axis of 0.78 0.10 arcsec ( ) and a semiminor axis of arcsec ( ). This precise size helps to constrain the age and velocity of the shock to be ( ) × 103 yr and km s−1. We also fit photometry of the surrounding stars to infer the age and mass of the progenitor star to be 8 1 Myr and M . Based on measured radio properties of the source and assuming equipartition, the estimated radio luminosity of ∼1.7 × 1034 erg s−1 over the 108-1011 Hz frequency range results in a minimum magnetic field associated with this SNR of 0.067 mG and the minimum energy needed to power the observed synchrotron emission of 1.5 × 1049 erg. The size and temperature of N300-S26 appear to be similar to the Galactic SNR G311.5-0.3 except that G311.5-0.3 has a significantly lower X-ray luminosity, is older, and has a slower shock velocity.
Summary
The Children's Oncology Group's A5971 trial examined central nervous system (CNS) prophylaxis and early intensification in paediatric patients diagnosed with CNS‐negative Stage III and IV ...lymphoblastic lymphoma. Using a 2 × 2 factorial design, the study randomized patients to Children's Cancer Group (CCG) modified Berlin‐Frankfurt‐Muenster (BFM) acute lymphoblastic leukaemia (ALL) regimen with intensified intrathecal (IT) methotrexate (MTX) (Arm A1) or an adapted non‐Hodgkin lymphoma/BFM‐95 therapy with high dose MTX in interim maintenance but no IT‐MTX in maintenance (Arm B1). Each cohort was randomized ± intensification (cyclophosphamide/anthracycline) (Arms A2/B2). For the 254 randomized patients, there was no difference in 5‐year event‐free survival (EFS) for the four arms: Arm A1, 80% 95% confidence interval (CI) 67–89% and Arm A2, 81% (95% CI 69–89%); Arm B1, 80% (95% CI 68–88%) and Arm B2, 84% (95% CI 72–91%). The cumulative incidence of CNS relapse was 1·2%. Age <10 years and institutional imaging response at 2 weeks was associated with improved outcomes (P < 0·001 and P = 0·014 for overall survival). CNS positive patients (n = 12) did poorly 5‐year EFS of 63% (95% CI 29–85%). For CNS‐negative patients, there was no difference in outcome based on CNS prophylaxis (IT‐MTX versus HD‐MTX) or with intensification.
Abstract
We have carried out a study of the X-ray properties of the supernova remnant (SNR) population in M33 with XMM–Newton, comprising deep observations of eight fields in M33 covering all of the ...area within the D25 contours, and with a typical luminosity of 7.1 × 1034 erg s−1 (0.2–2.0 keV). Here, we report our work to characterize the X-ray properties of the previously identified SNRs in M33, as well as our search for new X-ray detected SNRs. With our deep observations and large field of view we have detected 105 SNRs at the 3σ level, of which 54 SNRs are newly detected in X-rays, and three are newly discovered SNRs. Combining XMM–Newton data with deep Chandra survey data allows detailed spectral fitting of 15 SNRs, for which we have measured temperatures, ionization time-scales and individual abundances. This large sample of SNRs allows us to construct an X-ray luminosity function, and compare its shape to luminosity functions from host galaxies of differing metallicities and star formation rates to look for environmental effects on SNR properties. We conclude that while metallicity may play a role in SNR population characteristics, differing star formation histories on short time-scales, and small-scale environmental effects appear to cause more significant differences between X-ray luminosity distributions. In addition, we analyse the X-ray detectability of SNRs, and find that in M33 SNRs with higher S ii/H α ratios, as well as those with smaller galactocentric distances, are more detectable in X-rays.
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