Abstract
Clinical practice guidelines support cognitive rehabilitation for people with a history of mild traumatic brain injury (mTBI) and cognitive impairment, but no class I randomized clinical ...trials have evaluated the efficacy of self-administered computerized cognitive training. The goal of this study was to evaluate the efficacy of a self-administered computerized plasticity-based cognitive training programmes in primarily military/veteran participants with a history of mTBI and cognitive impairment. A multisite randomized double-blind clinical trial of a behavioural intervention with an active control was conducted from September 2013 to February 2017 including assessments at baseline, post-training, and after a 3-month follow-up period. Participants self-administered cognitive training (experimental and active control) programmes at home, remotely supervised by a healthcare coach, with an intended training schedule of 5 days per week, 1 h per day, for 13 weeks. Participants (149 contacted, 83 intent-to-treat) were confirmed to have a history of mTBI (mean of 7.2 years post-injury) through medical history/clinician interview and persistent cognitive impairment through neuropsychological testing and/or quantitative participant reported measure. The experimental intervention was a brain plasticity-based computerized cognitive training programme targeting speed/accuracy of information processing, and the active control was composed of computer games. The primary cognitive function measure was a composite of nine standardized neuropsychological assessments, and the primary directly observed functional measure a timed instrumental activities of daily living assessment. Secondary outcome measures included participant-reported assessments of cognitive and mental health. The treatment group showed an improvement in the composite cognitive measure significantly larger than that of the active control group at both the post-training +6.9 points, confidence interval (CI) +1.0 to +12.7, P = 0.025, d = 0.555 and the follow-up visit (+7.4 points, CI +0.6 to +14.3, P = 0.039, d = 0.591). Both large and small cognitive function improvements were seen twice as frequently in the treatment group than in the active control group. No significant between-group effects were seen on other measures, including the directly-observed functional and symptom measures. Statistically equivalent improvements in both groups were seen in depressive and cognitive symptoms.
Advancing our understanding of Earth system dynamics (ESD) depends on the development of models and other analytical tools that apply physical, biological, and chemical data. This ambition to ...increase understanding and develop models of ESD based on site observations was the stimulus for creating the networks of Long-Term Ecological Research (LTER), Critical Zone Observatories (CZOs), and others. We organized a survey, the results of which identified pressing gaps in data availability from these networks, in particular for the future development and evaluation of models that represent ESD processes, and provide insights for improvement in both data collection and model integration.From this survey overview of data applications in the context of LTER and CZO research, we identified three challenges: (1) widen application of terrestrial observation network data in Earth system modelling, (2) develop integrated Earth system models that incorporate process representation and data of multiple disciplines, and (3) identify complementarity in measured variables and spatial extent, and promoting synergies in the existing observational networks. These challenges lead to perspectives and recommendations for an improved dialogue between the observation networks and the ESD modelling community, including co-location of sites in the existing networks and further formalizing these recommendations among these communities. Developing these synergies will enable cross-site and cross-network comparison and synthesis studies, which will help produce insights around organizing principles, classifications, and general rules of coupling processes with environmental conditions.
Conservationists are continually seeking new strategies to reverse population declines and safeguard against species extinctions. Here we evaluate the potential efficacy of a recently proposed ...approach to offset a major anthropogenic threat to many marine vertebrates: incidental bycatch in commercial fisheries operations. This new approach, compensatory mitigation for marine bycatch (CMMB), is conceived as a way to replace or reduce mandated restrictions on fishing activities with compensatory activities (e.g., removal of introduced predators from islands) funded by levies placed on fishers. While efforts are underway to bring CMMB into policy discussions, to date there has not been a detailed evaluation of CMMB's potential as a conservation tool, and in particular, a list of necessary and sufficient criteria that CMMB must meet to be an effective conservation strategy. Here we present a list of criteria to assess CMMB that are tied to critical ecological aspects of the species targeted for conservation, the range of possible mitigation activities, and the multi-species impact of fisheries bycatch. We conclude that, overall, CMMB has little potential for benefit and a substantial potential for harm if implemented to solve most fisheries bycatch problems. In particular, CMMB is likely to be effective only when applied to short-lived and highly-fecund species (not the characteristics of most bycatch-impacted species) and to fisheries that take few non-target species, and especially few non-seabird species (not the characteristics of most fisheries). Thus, CMMB appears to have limited application and should only be implemented after rigorous appraisal on a case-specific basis; otherwise it has the potential to accelerate declines of marine species currently threatened by fisheries bycatch.
Orofacial clefts (OFCs) of the lip and/or palate are among the most common human birth defects. Current treatment strategies focus on functional and cosmetic repair but even when this care is ...available, individuals born with OFCs are at high risk for persistent neurobehavioral problems. In addition to learning disabilities and reduced academic achievement, recent evidence associates OFCs with elevated risk for a constellation of psychiatric outcomes including anxiety disorders, autism spectrum disorder, and schizophrenia. The relationship between these outcomes and OFCs is poorly understood and controversial. Recent neuroimaging studies in humans and mice demonstrate subtle morphological brain abnormalities that co-occur with OFCs but specific molecular and cellular mechanisms have not been investigated. Here, we provide the first evidence directly linking OFC pathogenesis to abnormal development of GABAergic cortical interneurons (cINs). Lineage tracing revealed that the structures that form the upper lip and palate develop in molecular synchrony and spatiotemporal proximity to cINs, suggesting these populations may have shared sensitivity to genetic and/or teratogenic insult. Examination of cIN development in a mouse model of nonsyndromic OFCs revealed significant disruptions in cIN proliferation and migration, culminating in misspecification of the somatostatin-expressing subgroup. These findings reveal a unified developmental basis for orofacial clefting and disrupted cIN development, and may explain the significant overlap in neurobehavioral and psychiatric outcomes associated with OFCs and cIN dysfunction. This emerging mechanistic understanding for increased prevalence of adverse neurobehavioral outcomes in OFC patients is the entry-point for developing evidence-based therapies to improve patient outcomes.
PDF
