Introduction of DNA fragments, hundreds of kilobases in size, into mouse embryonic stem (ES) cells would greatly advance the ability to manipulate the mouse genome. Mice generated from such modified cells would permit investigation of the function and expression of very large or crudely mapped genes. Large DNA molecules cloned into yeast artificial chromosomes (YACs) are stable and genetically manipulable within yeast, suggesting yeast-cell fusion as an ideal method for transferring large DNA segments into mammalian cells. Introduction of YACs into different cell types by this technique has been reported; however, the incorporation of yeast DNA along with the YAC has raised doubts as to whether ES cells, modified in this way, would be able to recolonize the mouse germ line. Here we provide, to our knowledge, the first demonstration of germ-line transmission and expression of a large human DNA fragment, introduced into ES cells by fusion with yeast spheroplasts. Proper development was not impaired by the cointegration of a large portion of the yeast genome with the YAC.

SummaryIn a randomized controlled study, we examined the effects of a one‐on‐one cognitive training program on memory, visual and auditory processing, processing speed, reasoning, attention, and General Intellectual Ability (GIA) score for students ages 8–14. Participants were randomly assigned to either an experimental group to complete 60 h of cognitive training or to a wait‐list control group. The purpose of the study was to examine changes in multiple cognitive skills after completing cognitive training with ThinkRx, a LearningRx program. Results showed statistically significant differences between groups on all outcome measures except for attention. Implications, limitations, and suggestions for future research are examined. © 2016 The Authors Applied Cognitive Psychology Published by John Wiley & Sons Ltd.

Objective This paper examines the prevalence and severity of co-morbid pain, insomnia, and depression in a population sample of older adults with osteoarthritis (OA), and assesses characteristics distinguishing participants from non-participants in a randomized clinical trial to improve pain and sleep. Methods Potential subjects were Group Health Cooperative members, age 60+, who had an electronic medical record OA diagnosis in the prior three years. Participants were recruited using a low-cost mailed survey. Fifty-five percent of surveys were completed and returned (n=3321). Persons with Grade II–IV arthritis pain on the Graded Chronic Pain Scale AND reporting sleep difficulties 3+ nights/week during the past month with daytime dysfunction (n=834) were invited to participate in one of three group-format behavioral self-management interventions. A total of 367 participants attended the first group class. Results One-third (36.4%) of survey respondents had clinically elevated levels of OA pain and insomnia. Group participants and non-participants did not differ in ratings of pain severity, sleep disturbance, depression, or receipt of prescription medications for pain or sleep. Participants were significantly older (p<.001) and more likely to be retired (p<.001) than subjects who were eligible to participate but did not. Conclusion Participation in a group-format behavioral intervention for pain and insomnia was not related to participant clinical characteristics, but only to factors associated with ability to attend a daytime class (age and retirement status). We conclude that population-based recruitment yielded randomized trial participants who are clinically generalizable to the population of OA patients with significant pain and insomnia.

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PurposeThe impact of attention problems on academic and social functioning coupled with the large number of children failing to respond to stimulant medication or behavioral therapy makes adjunctive therapies such as cognitive training appealing for families and clinicians of children with attention difficulties or childhood attention deficit hyperactivity disorder. However, the results of cognitive training studies have failed to find far transfer effects with this population. This study examined the quantitative cognitive effects and parent-reported behavioral effects of a clinician-delivered cognitive training program with children who have attention problems.Patients and methodsUsing a randomized controlled study design, we examined the impact of a clinician-delivered cognitive training program on processing speed, fluid reasoning, memory, visual processing, auditory processing, attention, overall intelligence quotient score, and behavior of students (n=13) aged 8–14 years with attention problems. Participants were randomly assigned to either a waitlist control group or a treatment group for 60 hours of cognitive training with ThinkRx, a clinician-delivered intervention that targets multiple cognitive skills with game-like, but rigorous mental tasks in 60–90-minute training sessions at least 3 days per week.ResultsResults included greater mean pretest to posttest change scores on all variables for the treatment group versus the control group with statistically significant differences noted in working memory, long-term memory, logic and reasoning, auditory processing, and intelligence quotient score. Qualitative outcomes included parent-reported changes in confidence, cooperation, and self-discipline.ConclusionChildren with attention problems who completed 60 hours of clinician-delivered ThinkRx cognitive training realized both cognitive and behavioral improvements.

Cognitive rehabilitation training is a promising technique for remediating the cognitive deficits associated with brain injury. Extant research is dominated by computer-based interventions with varied results. Results from clinician-delivered cognitive rehabilitation are notably lacking in the literature. The current study examined the cognitive outcomes following ThinkRx, a clinician-delivered cognitive rehabilitation training program for soldiers recovering from traumatic brain injury and acquired brain injury. In a retrospective chart review, we examined cognitive outcomes of 11 cases who had completed an average of 80 h of ThinkRx cognitive rehabilitation training delivered by clinicians and supplemented with digital training exercises. Outcome measures included scores from six cognitive skill batteries on the Woodcock Johnson – III Tests of Cognitive Abilities. Participants achieved gains in all cognitive skills tested and achieved statistically significant changes in long-term memory, processing speed, auditory processing, and fluid reasoning with very large effect sizes. Clinically significant changes in multiple cognitive skills were also noted across cases. Results of the study suggest that ThinkRx clinician-delivered cognitive training supplemented with digital exercises may be a viable method for targeting the cognitive deficits associated with brain injury.

Cognitive training is growing in popularity as an intervention for children who struggle to learn. In the current study, we compared the equivalency of two delivery models of the same cognitive training program, ThinkRx, for children ages 8-14. In a randomized controlled trial assessing equivalence, we compared cognitive outcomes between a group who received 60 h of ThinkRx cognitive training delivered one-on-one by a cognitive trainer (n = 20) versus a group of children who received 30 h of ThinkRx delivered by a cognitive trainer and the other 30 h through digital training procedures (n = 18). Results showed no significant differences between groups on tests of working memory, logic and reasoning, auditory processing, visual processing, processing speed, or overall IQ score. Results were significantly different on the test of long-term memory. These results suggest that both delivery models are equivalent cognitive training interventions for children. Keywords Cognitive training. Brain training. Cognition. Learning disabilities. LearningRx Learning struggles are a key characteristic of neurodevelopmental disorders-including specific learning disorder, attention deficit hyperactivity disorder (ADHD), and language disorder (American Psychiatric Association 2013)-but are also found among neurotypical children. Cognitive skill deficits are common among children who struggle to learn, especially deficits in working memory (Alloway et al. 2009), processing speed (Lewandowski et al. 2007), and executive functions (McQuade et al. 2011). Because cognitive skills are

Nearly half of all mild brain injury sufferers experience long-term cognitive impairment, so an important goal in rehabilitation is to address their multiple cognitive deficits to help them return to prior levels of functioning. Cognitive training, or the use of repeated mental exercises to enhance cognition, is one remediation method for brain injury. The primary purpose of this hypothesis-generating pilot study was to explore the statistical and clinical significance of cognitive changes and transfer of training to real-life functioning following 60 h of Brain Booster, a clinician-delivered cognitive training program, for six patients with mild traumatic brain injury (TBI) or non-traumatic acquired brain injury (ABI). The secondary purpose was to explore changes in functional connectivity and neural correlates of cognitive test gains following the training. We used a multiple case study design to document significant changes in cognitive test scores, overall IQ score, and symptom ratings; and we used magnetic resonance imaging (MRI) to explore trends in functional network connectivity and neural correlates of cognitive change. All cognitive test scores showed improvement with statistically significant changes on five of the seven measures (long-term memory, processing speed, reasoning, auditory processing, and overall IQ score). The mean change in IQ score was 20 points, from a mean of 108 to a mean of 128. Five themes emerged from the qualitative data analysis including improvements in cognition, mood, social identity, performance, and Instrumental Activities of Daily Living (IADLs). With MRI, we documented significant region-to-region changes in connectivity following cognitive training including those involving the cerebellum and cerebellar networks. We also found