The successful use of alemtuzumab for treatment of steroid‐refractory acute graft‐versus‐host disease in pediatric patients

SR‐aGVHD remains a significant cause of morbidity and mortality in allogeneic HCT recipients. Alemtuzumab has been used with success in adult patients but has not been studied in the pediatric setting. To estimate the effectiveness of alemtuzumab for the treatment of SR‐aGVHD in pediatric patients, we retrospectively reviewed the charts of 19 patients (median age 4 yr, range 0.5–28 years) with grades II (n = 3), III (n = 10), or IV (n = 6) SR‐aGVHD who received alemtuzumab treatment. Patients received a median dose of 0.9 mg/kg alemtuzumab (range 0.3–2 mg/kg) divided over 2–6 days. Eighty‐nine percent of patients received additional courses. A complete response, defined as GVHD of grade 0 at four wk following the first alemtuzumab course, was observed in nine patients (47%). A partial response, defined as an improvement in grade after four wk, was observed in five patients (26%). There was no response in five patients (26%). The overall response rate at four wk was 73%. Infectious complications included bacteremia (47%), presumed or documented fungal infections (21%), adenovirus viremia (52%), EBV viremia (36%), and CMV viremia (36%). We conclude that alemtuzumab is effective for SR‐aGVHD in pediatric patients with a tolerable spectrum of complications.     

Added noise affects the neural correlates of upright and inverted faces differently

In five experiments, we examine the neural correlates of the interaction between upright faces, inverted faces, and visual noise. In Experiment 1, we examine a component termed the N170 for upright and inverted faces presented with and without noise. Results show a smaller amplitude for inverted faces than upright faces when presented in noise, whereas the reverse is true without noise. In Experiment 2, we show that the amplitude reversal is robust for full faces but not eyes alone across all noise levels. In Experiment 3, we vary contrast to see if this reversal is a result of degrading a face. We observe no reversal effects. Thus, across conditions, adding noise to full faces is a sufficient condition for the N170 reversal. In Experiment 4, we delay the onsets of the faces presented in noise. We replicate the smaller N170 for inverted faces at no delay but observe partial recovery of the N170 for inverted faces at longer delays in static noise. Experiment 5 demonstrates the interaction in low contrast at a behavioral level. We propose a model in which noise interacts with the processing properties of inverted faces more so than upright faces.     

Titanium-Pillared Clay: Preparation Optimization,Characterization, and Artificial Neural Network Modeling

Titanium-pillared clay (Ti-PILC), as one of the most suitable types of porous adsorbents/(photo)catalysts, was prepared from a local type of Iranian clay and titanium isopropoxide. The production process was optimized by changing three operating parameters, including the clay suspension concentration (in the range of 0.5–10% w/v), the H⁺/Ti ratio (2–8 mol/mol), and the calcination temperature (300–700 °C). The largest specific surface area for the Ti-PILC was about 164 m²/g under the clay suspension of 0.5% w/v, H⁺/Ti = 6, with a surface area 273% larger than that of the raw clay. The surface areas obtained from more concentrated clay suspensions were, however, comparable (159 m²/g for 3% w/v clay and H⁺/Ti = 4). An increase in the calcination temperature has a negative effect on the porous texture of Ti-PILC, but based on modeling with artificial neural networks, its contribution was only 7%. Clay suspension and H⁺/Ti ratio play a role of 56 and 37% of the specific surface area. The presence of rutile phase, and in some cases anatase phase of TiO₂ crystals was detected. FTIR and SEM investigations of Ti-PILCs produced under different operating parameters were analyzed.     

Effects of antisense oligonucleotide-mediated depletion of tumor necrosis factor (TNF) receptor 1-associated death domain protein on TNF-induced gene expression

Tumor necrosis factor (TNF) receptor 1-associated death domain protein (TRADD) is an adaptor protein known to be involved in the TNF signaling pathway as well as signaling of other members of the TNF receptor superfamily, including DR3, DR6, p75(NTR), and the Epstein-Barr virus latent membrane protein 1. Current knowledge of the function of the adaptor protein has been derived from studies examining its over-expression in either wild-type or mutated forms. In this study, we analyzed the consequences of antisense oligonucleotide (ASO)-mediated depletion of endogenous TRADD on TNF induction of inflammation-related gene products, such as intercellular adhesion molecule-1, and associated kinase signaling pathways in human umbilical vein endothelial cells. A broader perspective of TRADD's role in TNF signaling was indicated by microarray gene expression analysis, where 20 of 24 genes that showed a 5-fold or greater increase in TNF-induced mRNA expression levels displayed a reduction in TNF-induced expression as a consequence of ASO-mediated knockdown of TRADD. Reduced activation of the nuclear factor-kappaB and c-Jun NH(2)-terminal kinase pathways, as measured by IkappaB-alpha protein levels and the extent of c-Jun phosphorylation, was also observed. These results indicate usage of antisense inhibitors of TRADD expression for modulating diseases associated with TRADD-dependent signal transduction pathways.     

Insights into pediatric rhabdomyosarcoma research: Challenges and goals

Overall survival rates for pediatric patients with high‐risk or relapsed rhabdomyosarcoma (RMS) have not improved significantly since the 1980s. Recent studies have identified a number of targetable vulnerabilities in RMS, but these discoveries have infrequently translated into clinical trials. We propose streamlining the process by which agents are selected for clinical evaluation in RMS. We believe that strong consideration should be given to the development of combination therapies that add biologically targeted agents to conventional cytotoxic drugs. One example of this type of combination is the addition of the WEE1 inhibitor AZD1775 to the conventional cytotoxic chemotherapeutics, vincristine and irinotecan.     

THE FLUORIDATION OF PUBLIC MATER SUPPLIES STATEMENT OF RECOMENDED POLICY

A statement approved "by the Board of Directors on May 29, 1949, and presented on'June 1, 1949, at the annual Conference, Chicago," by, A P. Black, Chairman, Special Committee on A. W. W. A. Policy re Fluoridation of public Water Supplies.