Search

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.

We present a case of a 14-year-old girl born without the left hemisphere due to prenatal left internal carotid occlusion. We combined longitudinal language and cognitive assessments with functional and structural neuroimaging data to situate the case within age-matched, typically developing children. Despite having had a delay in getting language off the ground during the preschool years, our case performed within the normal range on a variety of standardized language tests, and exceptionally well on phonology and word reading, during the elementary and middle school years. Moreover, her spatial, number, and reasoning skills also fell in the average to above-average range based on assessments during these time periods. Functional MRI data revealed activation in right fronto-temporal areas when listening to short stories, resembling the bilateral activation patterns in age-matched typically developing children. Diffusion MRI data showed significantly larger dorsal white matter association tracts (the direct and anterior segments of the arcuate fasciculus) connecting areas active during language processing in her remaining right hemisphere, compared to either hemisphere in control children. We hypothesize that these changes in functional and structural brain organization are the result of compensatory brain plasticity, manifesting in unusually large right dorsal tracts, and exceptional performance in phonology, speech repetition, and decoding. More specifically, we posit that our case's large white matter connections might have played a compensatory role by providing fast and reliable transfer of information between cortical areas for language in the right hemisphere.

Although substantial work investigates childrens understanding of ordinal and magnitude-based relations, little work hasinvestigated childrens understanding of the vocabulary used for these relations and how relational language knowledgemay be constrained by symbolic number knowledge. In the current study, children were asked which of two numbers wasbigger/smaller than or before/after five. On close trials, the correct answer was 4 or 6 (one away from 5) and on far trials,the correct answer was 3 or 7 (two away from 5). We hypothesized that 4- to 6-year-olds understanding of ordinal relations(before/after) are initially constrained to refer to numbers immediately before/after (i.e., close values), but that this is notthe case for bigger/smaller comparisons. Preliminary results suggest this to be the case, with children performing betteron close trials than far trials for ordinal relations, but not magnitude relations.

The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood. We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.

Shape puzzles can elicit parent-child math talk, which is critical for early math learning. However, little is known abouthow the features of the puzzles impact parent-child interactions through parents math talk. Two- to four-year-old chil-dren and their parents (current N=30; target N=128) completed two shape puzzles. The control puzzle was typical ofcommercial puzzles, including nine distinct shapes. The experimental puzzle included multiple exemplars of shapes (e.g.,three different triangles, three different quadrilaterals). We hypothesized that parents would use richer math talk with theexperimental puzzle. We coded quantity and quality of parent math talk during the interactions. Preliminary results indi-cate that parents mostly used low-level math talk (naming shapes) for both puzzles, but they used more high-level mathtalk (comparing shapes, providing shape definitions) for the experimental than the control puzzle (p=0.054). We discussparticular puzzle features that can stimulate high-quality math talk during parent-child interactions.

We conducted a study of 400 preschool children to determine whether spatial and numerical skills rely on commonprocesses. Children completed a battery of mathematical tasks as part of an ongoing preschool formative assessment develop-ment project. We created theoretically meaningful skills from these tasks and carried out item response theoretic analyses oneach skill. We extracted Rasch scores for each of the skills and carried out multiple factor analyses to determine whether oneor more factors best characterized spatial and numerical skills. Finally, we regressed factor scores on demographic variables,including age, gender, socioeconomic status, and verbal ability. We discuss how our results add to our understanding of theconnection between spatial and numerical processes and their implications for closing the achievement gap in early education.

We explored preschool’s children’s understanding of the correspondence of 3-D objects and 2-D faces in a noveltask. In the “footprints” task children were shown a geometric solid, such as a pyramid or a prism, and asked to select whichshape the solid would make if it were dipped in ink and stamped on a piece of paper. Through a latent class analysis of children’serrors we found children differed significantly in their misconceptions about object structure. Three distinct classes of childrenemerged: children who could only match visible faces, children who believed solids have an ‘essential’ face irrespective ofrotation, and children who differentiated faces based on a solid’s rotation. We examined the characteristics of children in eachof these classes using a battery of spatial tasks and numeric tasks. Our results suggest errors found in older children’s andadults’ reasoning about geometric concepts develop prior to formal schooling.

We review findings from a four-year longitudinal study of language learning conducted on two samples: a sample of typically developing children whose parents vary substantially in socioeconomic status, and a sample of children with pre- or perinatal brain injury. This design enables us to study language development across a wide range of language learning environments and a wide range of language learners. We videotaped samples of children's and parents' speech and gestures during spontaneous interactions at home every four months, and then we transcribed and coded the tapes. We focused on two behaviors known to vary across individuals and environments-child gesture and parent speech-behaviors that have the potential to index, and perhaps even play a role in creating, differences across children in linguistic and other cognitive skills. Our observations have led to four hypotheses that have promise for the development of diagnostic tools and interventions to enhance language and cognitive development and brain plasticity after neonatal injury. One kind of hypothesis involves tools that could identify children who may be at risk for later language deficits. The other involves interventions that have the potential to promote language development. We present our four hypotheses as a summary of the findings from our study because there is scientific evidence behind them and because this evidence has the potential to be put to practical use in improving education.

[No abstract]