The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

The diagnostic utility of executive function assessments in the identification of ADHD in children

Background: Deficits in executive functions have been widely reported to characterise individuals with ADHD. The aim of this study was to evaluate the utility of a range of executive function measures for identifying children with ADHD. Method: Eighty-three children with ADHD and 50 normally-developing children without ADHD were assessed on measures of inhibition, set-shifting, planning, problem-solving, response inhibition, sustained attention and working memory. Measures of sensitivity, specificity, likelihood ratios and diagnostic odds ratios were calculated. Results: Executive function tasks effectively discriminated between children with and without ADHD. Measures of response inhibition and working memory contributed the most to the discriminant function. Conclusions: Cognitive measures of executive function can be used to help identify children with ADHD and could be useful as additional diagnostic tools for clinical practitioners

Working memory deficits can be overcome: Impacts of training and medication on working memory in children with ADHD

This study evaluated the impact of two interventions—a training program and stimulant medication—on working memory (WM) function in children with attention deficit hyperactivity disorder (ADHD). Twenty-five children aged between 8 and 11 years participated in training that taxed WM skills to the limit for a minimum of 20 days, and completed other assessments of WM and IQ before and after training, and with and without prescribed drug treatment. While medication significantly improved visuo-spatial memory performance, training led to substantial gains in all components of WM across untrained tasks. Training gains associated with the central executive persisted over a 6-month period. IQ scores were unaffected by either intervention. These findings indicate that the WM impairments in children with ADHD can be differentially ameliorated by training and by stimulant medication

Children with low working memory and children with ADHD: same or different?

The purpose of this study was to compare working memory (WM), executive function, academic ability, and problem classroom behaviors in children aged 8–11 years who were either identified via routine screening as having low WM, or had been diagnosed with ADHD. Standardized assessments of WM, executive function and reading and mathematics were administered to 83 children with ADHD, 50 children with low WM and 50 typically developing children. Teachers rated problem behaviors on checklists measuring attention, hyperactivity/impulsivity, oppositional behavior, and difficulties associated with executive function in the classroom. The ADHD and low WM groups had highly similar WM and executive function profiles, but were distinguished in two key respects: children with ADHD had higher levels of rated and observed impulsive behavior, and children with low WM had slower response times. Possible mechanisms for these common and distinct deficits are discussed

Effects of beef cattle temperament on feed and water intake

Temperament scoring systems encompass a variety of subjective and objective methods. Chute scoring may be the most common subjective method, and is often used by breed associations in their docility genetic evaluations. The most commonly used objective method is exit velocity, which is calculated from the amount of time it takes for an animal to cross 1.83 meters when exiting the working chute. Measurements of temperament collected using both objective and subjective methodologies have been shown to be heritable, and are associated with differences in cortisol levels and average daily gain in the scientific literature. Thus, the objective of this study was to characterize individual animal variation in feed and water intake and evaluate the relationship between beef cattle temperament and feed and water intake. Five objective (exit velocity; EV) and subjective (chute scores; CS) temperament measures were collected on 106 beef steers every 2 weeks over a 70 d feed and water intake test, CS were ordinal, and reflected the temperament of the animal in the chute (1=calm, 4= continuous resistance). EV was calculated using times recorded by electronic eyes (FarmTek). Entry scores were also collected as a control variable and reflected the mechanisms used to encourage the steers to enter the chute. Daily feed and water intakes on each individual animal were recorded using an Insentec system. All data were averaged over the 70 d test period and included length of each feeding/watering event, number of daily intake events, and mean intake. A general linear model was utilized to evaluate the relationships between temperament measures and intake. CS (averaged over the 5 timepoints) and EV (averaged over the 5 timepoints) did not have a significant impact on feed or water intake (P > 0.05). It is possible that this result is due to the fact that most animals in the study were calm, and thus did not include a lot of variation in these traits. Variation in feed and water intake as described by the standard deviation of all daily intake measures was related to overall feed and water intake, and animals that tend to have higher intakes also have higher variability in their daily feed and water intakes (P, 0.05). In addition, the number of daily feed events and the length spent at the bunk are both significant predictors of feed and water intake (P < 0.05)

The role of ecotourism in conservation: panacea or Pandora's box?

Krüger O. The role of ecotourism in conservation: panacea or Pandora's box? Biodivers. Conserv. 2005;14(3):579-600