Randomized Phase III Trial of Pegfilgrastim versus Filgrastim after Autologus Peripheral Blood Stem Cell Transplantation

Nonrandomized trials suggest that pegfilgrastim, a pegylated granulocyte colony-stimulating factor, could be used in lieu of filgrastim after autologus peripheral blood stem cell transplantation. This phase III, randomized, double-blinded, placebo-controlled trial compared the efficacy, costs, and safety of single-dose pegfilgrastim (single 6mg dose) versus daily filgrastim (5μg/kg/day) for this indication. Seventy-eight patients, matched for age, sex, underlying disease, stage, and CD34/kg transplant dose were enrolled. Cytokines were started on day +1 posttransplant and continued to an absolute neutrophil count (ANC) of 5×109/L for 3 days or 10×109/L for 1 day. The median time to neutrophil engraftment (ANC >1.5×109/L for 3 days or 5×109/L for 1 day) was the same in both groups (12 days). No differences in platelet engraftment (11 versus 13 days), number of platelet transfusions (5 versus 4), percent with positive cultures for bacterial pathogens (23% versus 15%), days of fever (1 versus 2), deaths prior to engraftment (1 versus 1), or duration of hospital stay (19 versus 19 days) were seen between the pegfilgrastim and filgrastim groups, respectively. Using the average wholesale price for doses used in this trial, there was a per-patient savings of $961 for the pegfilgrastim group (P < .001). This phase III study failed to demonstrate a difference in time to neutrophil engraftment or any clinical sequelae between pegfilgrastim and filgrastim when given post-APBSCT, with pegfilgrastim achieving a cost savings over filgrastim

Epidermal growth factor potentiates renal cell death in hydronephrotic neonatal mice, but cell survival in rats

BACKGROUND: Epidermal growth factor (EGF) markedly attenuates tubular apoptosis induced by unilateral ureteral obstruction (UUO) in the neonatal rat, and reduces apoptosis induced by mechanical stretch of cultured rat tubular cells. METHODS: To investigate the role of EGF in modulating apoptosis resulting from UUO, neonatal wild type and mutant mice lacking EGF (knockout), or with diminished EGF receptor activity (waved-2 mutant) were compared to control mice for tubular apoptosis and atrophy. Rat and mouse kidneys were compared for localization of the EGF receptor. Apoptosis was also measured in cultured mouse tubular cells subjected to stretch and exposed to EGF. RESULTS: UUO reduced endogenous renal EGF expression in wild-type mice. Unlike the rat, exogenous EGF did not decrease tubular apoptosis or atrophy in the obstructed kidney, and significantly increased stretch-induced apoptosis of cultured mouse tubular cells. Tubular apoptosis was 50% lower in the obstructed kidney of EGF knockout and waved-2 mice relative to wild type and heterozygous animals. Exogenous EGF increased tubular apoptosis and doubled atrophy in the obstructed kidney of waved-2 mice. Species differences in EGF receptor localization were detected in 3-day-old kidneys. CONCLUSION: EGF acts as a survival factor in the neonatal rat, but potentiates tubular cell death in the neonatal mouse. Species differences are maintained in cultured cells, suggesting that differences in EGF receptor signaling underlie these opposing effects

Developmental and computational perspectives on infant social cognition

Adults effortlessly and automatically infer complex pat- terns of goals, beliefs, and other mental states as the causes of others’ actions. Yet before the last decade little was known about the developmental origins of these abilities in early infancy. Our understanding of infant social cognition has now improved dramatically: even preverbal infants appear to perceive goals, preferences (Kushnir, Xu, & Wellman, in press), and even beliefs from sparse observations of inten- tional agents’ behavior. Furthermore, they use these infer- ences to predict others’ behavior in novel contexts and to make social evaluations (Hamlin, Wynn, & Bloom, 2007). Keywords: Social cognition; Cognitive Development; Computational Modeling; Theory of Min

Social skills of children with 22q11 Deletion Syndrome: A social cognitive neuroscience approach

The 22q11 DS is the most common genetic deletion syndrome. The deletion is believed to result in the dysregulation of the dopamine, GABA, and glutamate systems which, in turn, affects the prefrontal cortex, associated circuitry, and cognitive abilities governed by these brain regions. Research suggests that 22q11 DS children experience attention and executive function deficits; clinical observation also suggests impaired social abilities. This study sought to empirically identify if 22q11 DS children experience social skills, executive function, and/or executive attention impairments, and how these skills may be associated. A social cognitive neuroscience approach was used that attempted to relate these three areas of functioning (neurochemical, neurocognitive, and social). The study was conducted as part of a longitudinal project at Rockefeller University. Fifty-one 22q11 DS children and 30 control participants took part in the study. Parents completed the Social Skills Rating System (SSRS) and Behavior Rating Inventory of Executive Function (BRIEF). The children were administered two computerized tests, the Wisconsin Card Sorting Test: 64 - Computer Version (WCST: 64-CV) and the Attention Network Test for Children (ANT). When compared with control participants, 22q11 DS children were found to: (1) have more impaired social skills, (2) be more likely to score in the clinically impaired range on the BRIEF global and subscale measures, and (3) have more perseverative responses and errors on the WCST: 64-CV. No significant group differences were found on the ANT; however a group x age interaction was detected. Correlational analysis revealed a significant, negative association between the BRIEF and SSRS total scores. A simple regression found that the BRIEF Global Composite score accounted for 42.4% of the variance in affected children\u27s social skills. Secondary analyses revealed significant associations between SSRS and BRIEF subscale scores. A multiple regression revealed that emotional control, planning, and monitoring skills were significant predictors of Total Social Skills Scores in affected children. A significant group x socio-economic status interaction was also found. This study suggests that social and executive function skills are associated in 22q11 DS children. This has direct implications for remediation efforts and supports the validity of utilizing a social cognitive neuroscience approach

Young infants prefer prosocial to antisocial others

Cognitive Development, No. 26, pp. 30–39The current study replicates and extends the finding (Hamlin, Wynn & Bloom, 2007) that infants prefer individuals who act prosocially toward unrelated third parties over those who act antisocially. Using different stimuli from those used by Hamlin et al. (2007), somewhat younger subjects, and 2 additional social scenarios, we replicated the findings that (a) infants prefer those who behave prosocially versus antisocially, and (b) these preferences are based on the social nature of the actions. The generality of infants’ responses across multiple examples of prosocial and antisocial actions supports the claim that social evaluation is fundamental to perceiving the world

Konuşma Öncesi Dönem Çocuklarının Sosyalite Değerlendirmesi

İnsanların diğer insanları değerlendirebilme kapasitesi, sosyal dünya içerisinde yollarını bulabilmek için temel öneme sahiptir. İnsanlar, çevrelerinde bulunan diğer insanların hareketlerini ve niyetlerini yorumlayabilmek ve kimin arkadaş kimin hasım, kimin uygun bir sosyal partner olabileceği, kimin olamayacağı konularında doğru yargılarda bulunabilmek durumundadır. Gerçekte, tüm sosyal hayvanlar kendilerine yardımcı olabilecek bireysel türdeşlerini tanıma ve bu bireyleri kendilerine zarar verebilecek olan diğerlerinden ayırt edebilme kabiliyetinden faydalanmaktadır. Yetişkin insanlar diğer insanları hızla ve otomatik olarak, hem davranış hem de fiziksel özellikler temelinde değerlendirirler, fakat ontogenetik orijin ve bu kabiliyetin gelişimi iyi anlaşılmamaktadır. Burada, 6 ve 10 aylık çocukların diğerlerine karşı davranışlarını, o bireylerin sempatik mi kaçınılması gereken birimi olduğuna karar vermelerinde göz önüne alındığını gösteriyoruz...