Phase I trial of procarbazine as a 5-day continuous infusion in children with central nervous system tumors.

Seven children with previously treated brain tumors were enrolled in a phase I trial of 5-day continuous-infusion procarbazine at 360, 480, and 638 mg/m2/day. Vitamin B6 levels were monitored. Myelosuppression was moderate though occasionally delayed, and nausea and vomiting were mild. At the highest dose level, a patient experienced severe psychosis that persisted for several weeks. From that dose-limiting toxicity and the degree of myelosuppression, the recommended dose for phase II trials in children is the same as for adults, 450 mg/m2/day

Salvage chemotherapy for recurrent primary brain tumors in children.

Sixty consecutive evaluable children with recurrent primary tumors of the central nervous system were treated with a regimen of vincristine, nitrogen mustard, procarbazine, and prednisone over a 12-year period. Tumor types included medulloblastoma (19), brain-stem glioma (16), astrocytoma (13), and a miscellaneous glioma (12). Responses and sustained survivals were achieved. Responses were highly dependent on tumor type. Disease progression was halted in 73% of the children with medulloblastoma, and three have survived in complete remission for more than 10 years from the start of therapy with vincristine, nitrogen mustard, procarbazine, and prednisone. Two of four patients with anaplastic glioma, are long-term survivors. In contrast, less than one third of children with brain-stem gliomas responded. Toxicity consisted mainly of neutropenia, thrombocytopenia, infections, and rarely a procarbazine rash

Epidemiology and Clinical Features of Patients with Visceral Leishmaniasis Treated by an MSF Clinic in Bakool Region, Somalia, 2004–2006

Our paper describes the epidemiological features of visceral leishmaniasis in the Bakool region, South Central Somalia, over the years 2004 to 2006. Since 2000, Médecins Sans Frontières has been providing care for patients suffering from visceral leishmaniasis in Huddur, located in a region endemic for visceral leishmaniasis. By the end of 2005, we witnessed a dramatic increase in the number of patients admitted to the Huddur centre with visceral leishmaniasis. In our paper, we provide a description of the profile of patients admitted, thus giving an insight into the epidemiology of visceral leishmaniasis in a part of the world where relatively little has been documented and where the true magnitude of this neglected disease remains unknown

Shear Stress Modulation of Smooth Muscle Cell Marker Genes in 2-D and 3-D Depends on Mechanotransduction by Heparan Sulfate Proteoglycans and ERK1/2

During vascular injury, vascular smooth muscle cells (SMCs) and fibroblasts/myofibroblasts (FBs/MFBs) are exposed to altered luminal blood flow or transmural interstitial flow. We investigate the effects of these two types of fluid flows on the phenotypes of SMCs and MFBs and the underlying mechanotransduction mechanisms.Exposure to 8 dyn/cm(2) laminar flow shear stress (2-dimensional, 2-D) for 15 h significantly reduced expression of alpha-smooth muscle actin (alpha-SMA), smooth muscle protein 22 (SM22), SM myosin heavy chain (SM-MHC), smoothelin, and calponin. Cells suspended in collagen gels were exposed to interstitial flow (1 cmH(2)O, approximately 0.05 dyn/cm(2), 3-D), and after 6 h of exposure, expression of SM-MHC, smoothelin, and calponin were significantly reduced, while expression of alpha-SMA and SM22 were markedly enhanced. PD98059 (an ERK1/2 inhibitor) and heparinase III (an enzyme to cleave heparan sulfate) significantly blocked the effects of laminar flow on gene expression, and also reversed the effects of interstitial flow on SM-MHC, smoothelin, and calponin, but enhanced interstitial flow-induced expression of alpha-SMA and SM22. SMCs and MFBs have similar responses to fluid flow. Silencing ERK1/2 completely blocked the effects of both laminar flow and interstitial flow on SMC marker gene expression. Western blotting showed that both types of flows induced ERK1/2 activation that was inhibited by disruption of heparan sulfate proteoglycans (HSPGs).The results suggest that HSPG-mediated ERK1/2 activation is an important mechanotransduction pathway modulating SMC marker gene expression when SMCs and MFBs are exposed to flow. Fluid flow may be involved in vascular remodeling and lesion formation by affecting phenotypes of vascular wall cells. This study has implications in understanding the flow-related mechanobiology in vascular lesion formation, tumor cell invasion, and stem cell differentiation

Observation of electroweak production of two jets and a Z-boson pair

Electroweak symmetry breaking explains the origin of the masses of elementary particles through their interactions with the Higgs field. Besides the measurements of the Higgs boson properties, the study of the scattering of massive vector bosons with spin 1 allows the nature of electroweak symmetry breaking to be probed. Among all processes related to vector-boson scattering, the electroweak production of two jets and a Z-boson pair is a rare and important one. Here we report the observation of this process from proton–proton collision data corresponding to an integrated luminosity of 139 fb−1 recorded at a centre-of-mass energy of 13 TeV with the ATLAS detector at the Large Hadron Collider. We consider two different final states originating from the decays of the Z-boson pair: one containing four charged leptons and another containing two charged leptons and two neutrinos. The hypothesis of no electroweak production is rejected with a statistical significance of 5.7σ, and the measured cross-section for electroweak production is consistent with the Standard Model prediction. In addition, we report cross-sections for inclusive production of a Z-boson pair and two jets for the two final states

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion