Safety and efficacy of rivastigmine in children with Down syndrome: A double blind placebo controlled trial.

Individuals with Down syndrome (DS) have decreased cholinergic function and an uneven profile of cognitive abilities, with more pronounced deficits in learning, memory, and expressive language. Cholinesterase inhibitors may improve cognitive function in adults and adolescents with DS, but studies in children with DS have been limited. This study aimed to: (i) investigate the safety and efficacy of rivastigmine treatment; (ii) build upon our open-label studies in children with DS in a double-blind, placebo-controlled clinical trial; and (iii) investigate specific cognitive domains that may respond to rivastigmine treatment. We conducted a 20-week double-blind, placebo-controlled trial to investigate the safety and efficacy of rivastigmine in 22 children and adolescents with DS aged 10-17 years. Safety measures included reports of adverse events, laboratory parameters, and electrocardiograms. Efficacy measures included parental assessments of adaptive behavior and executive function, and direct measures of language and memory. No group differences were found on safety measures and 22 of 24 participants that passed study screening completed the study. The results did not demonstrate evidence for significant improvement in aspects of cognition, language, or overall function in the children receiving rivastigmine. Our results suggest that rivastigmine is safe and well-tolerated for children and adolescents with DS, but may not be effective for improving performance on the selected measures in this study. However, larger samples and/or alternate measures could possibly reveal improvements in cognitive function with rivastigmine treatment. Further research is needed to define a battery of cognitive measures that is sensitive to treatment effects in DS. © 2016 Wiley Periodicals, Inc.

Project Baseline: An unprecedented resource to study plant evolution across space and time.

PREMISE OF THE STUDY: Project Baseline is a seed bank that offers an unprecedented opportunity to examine spatial and temporal dimensions of microevolution during an era of rapid environmental change. Over the upcoming 50 years, biologists will withdraw genetically representative samples of past populations from this time capsule of seeds and grow them contemporaneously with modern samples to detect any phenotypic and molecular evolution that has occurred during the intervening time. METHODS: We carefully developed this living genome bank using protocols to enhance its experimental value by collecting from multiple populations and species across a broad geographical range in sites that are likely to be preserved into the future. Seeds are accessioned with site and population data and are stored by maternal line under conditions that maximize seed longevity. This open-access resource will be available to researchers at regular intervals to evaluate contemporary evolution. KEY RESULTS: To date, the Project Baseline collection includes 100-200 maternal lines of each of 61 species collected from over 831 populations on sites that are likely to be preserved into the future across the United States (∼78,000 maternal lines). Our strategically designed collection circumvents some problems that can cloud the results of "resurrection" studies involving naturally preserved or existing seed collections that are available fortuitously. CONCLUSIONS: The resurrection approach can be coupled with long-established and newer techniques over the next five decades to elucidate genetic change and thereby vastly improve our understanding of temporal and spatial changes in phenotype and the evolutionary processes underlying it.

Evolutionary insights from studies of geographic variation: Contemporary variation and looking to the future.

In an age of rapid global change, it is imperative that we continue to improve our understanding of factors that govern genetic differentiation in plants to inform biologically reasonable predictions for the future and enlighten conservation and restoration practices. In this special issue, we have assembled a set of original research and reviews that employ diverse approaches, both classic and contemporary, to illuminate patterns of phenotypic and genetic variation, probe the underlying evolutionary processes that have contributed to these patterns, build predictive models, and test evolutionary hypotheses. Our goal was to underscore the unique insights that can be obtained through the complementary and distinct studies of plant populations across species' geographic ranges.

Geographic variation in climate as a proxy for climate change: Forecasting evolutionary trajectories from species differentiation and genetic correlations.

PREMISE OF THE STUDY: Climate change models for California predict a warmer, drier future, potentially resulting in shorter growing seasons. If phenotypic differences between closely related species currently distributed across a moisture and temperature gradient represent adaptations to their abiotic environment, then as conditions become warmer and drier, populations presently adapted to cooler and wetter conditions may evolve to become more similar to those adapted to warmer and drier conditions. Two sister species, Clarkia unguiculata and C. exilis, are distributed across a moisture and temperature gradient in the southern Sierra Nevada, providing an opportunity to predict how this process may occur. METHODS: In a greenhouse experiment using wild-collected seeds from 11 populations in the southern Sierra Nevada, we examined relationships among elevation, climatic conditions, and population means for each trait, then evaluated bivariate relationships among maternal family means, using raw values and controlling for population and seed mass effects on phenotype. KEY RESULTS: Clarkia exilis occupied warmer, drier conditions, typically at lower elevations, than C. unguiculata did and flowered earlier and faster, producing smaller flowers with lower herkogamy. In C. unguiculata, petal area, herkogamy, and the rate of flower production were positively correlated with days to first flower. CONCLUSIONS: If selection favors earlier flowering, smaller petals, or faster flower production in C. unguiculata, then the genetic correlations among these traits should reinforce their joint evolution. Moreover, the correlations between these traits and herkogamy may promote the evolution of self-fertilization as an indirect response to selection, a previously unrecognized potential outcome of climate change.

Sleep disturbance and neuropsychological function in young children with ADHD.

Sleep disturbance, common among children with ADHD, can contribute to cognitive and behavioral dysfunction. It is therefore challenging to determine whether neurobehavioral dysfunction should be attributed to ADHD symptoms, sleep disturbance, or both. The present study examined parent-reported sleep problems (Children's Sleep Habits Questionnaire) and their relationship to neuropsychological function in 64 children, aged 4-7 years, with and without ADHD. Compared to typically developing controls, children with ADHD were reported by parents to have significantly greater sleep disturbance--including sleep onset delay, sleep anxiety, night awakenings, and daytime sleepiness--(all p ≤ .01), and significantly poorer performance on tasks of attention, executive control, processing speed, and working memory (all p < .01). Within the ADHD group, total parent-reported sleep disturbance was significantly associated with deficits in attention and executive control skills (all p ≤ .01); however, significant group differences (relative to controls) on these measures remained (p < .01) even after controlling for total sleep disturbance. While sleep problems are common among young children with ADHD, these findings suggest that inattention and executive dysfunction appear to be attributable to symptoms of ADHD rather than to sleep disturbance. The relationships among sleep, ADHD symptoms, and neurobehavioral function in older children may show different patterns as a function of the chronicity of disordered sleep.

Utility of the test of memory malingering (TOMM) in children ages 4-7 years with and without ADHD.

There is growing consensus that assessment for non-credible performance is a necessary component of pediatric neuropsychological examination. The current study examined the utility and validity of the Test of Memory Malingering (TOMM) in children ages 4-7 years with and without Attention-deficit/Hyperactivity Disorder (ADHD); 66 children (30 controls, 36 ADHD) completed all three TOMM trials. There were no significant group differences in total score on any trial, or passing rate for Trial 2 or Retention. Four-year-olds with ADHD achieved "passing" score on Trial 1 less often than controls. Across groups, performance on Trial 2 and Retention improved with age, such that 85% of the sample achieved a passing score. Four-year-olds had greater difficulty and achieved a passing score significantly less often than children 5-7 years. Moreover, half of the 4-year-olds performed worse on Retention than Trial 2, calling into question the utility of the Retention trial at this age. Performance was associated with IQ only within the ADHD group on the Retention trial. Results suggest that the TOMM can be used with confidence in clinical groups as young as 5 years. Among 4-year-olds, performance appears dependent on severity of ADHD or disruptive behaviors, and may be associated with factors other than effort.