GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

ManyBabies4: Infants' Social Evaluations

In this project we investigate a fundamental aspect of human nature: evaluating others’ actions as praiseworthy or blameworthy. We do so in a closely coordinated, multi-laboratory, standardized study aimed at replicating the helping/hindering finding reported by (Hamlin, Wynn, & Bloom, 2007). Using a video-taped version of the original puppet show, labs from around the world will collect data from infants between the ages of 5.5 and 10.5 months

Using infrared eye-tracking to explore ordinal numerical processing in toddlers with Fragile X Syndrome

Abstract Background Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and non-idiopathic autism. Individuals with FXS present with a behavioral phenotype of specific and selective deficits in an array of cognitive skills. Disruption of number processing and arithmetic abilities in higher-functioning adults and female adolescents with FXS has been well established. Still, both numerical skills and developmentally antecedent cognitive processes have just begun to be investigated in toddlers with FXS. The goal of the current study was to assess how very young children with FXS respond to ordinal relationships among numerical magnitudes. Methods Infrared eye-tracking was used to explore infants’ novelty recognition during passive viewing of ordinal numerical sequences; t-tests were used to analyze group differences in looking time. Results Ordinal recognition of numerical magnitudes is significantly impaired in young toddlers with FXS. Conclusions This study is the first to experimentally evaluate early number sense and ordinal recognition in toddlers with FXS, and our findings reveal that ordinal recognition of numerical magnitudes is significantly impaired in young toddlers with FXS, suggesting that later arithmetic impairments associated with FXS may have their origins in a developmental impairment of this more basic aspect of numerical cognition

An eye tracking investigation of color-location binding in infants' visual short-term memory.

Two experiments examined 8- and 10-month-old infants' (N = 71) binding of object identity (color) and location information in visual short-term memory (VSTM) using a one-shot change detection task. Building on previous work using the simultaneous streams change detection task, we confirmed that 8- and 10-month-old infants are sensitive to changes in binding between identity and location in VSTM. Further, we demonstrated that infants recognize specifically what changed in these events. Thus, infants' VSTM for binding is robust and can be observed in different procedures and with different stimuli

'Big team' science challenges us to reconsider authorship

Big team science challenges researchers to revisit three issues around authorship: (1) What is an authorship-worthy contribution, (2) How should contributions be documented, and (3) How should disagreements among large teams of co-authors be handled? We propose steps that the community can take to resolve these issues

‘Big team’ science challenges us to reconsider authorship

No abstract available

Developmental changes in visual short-term memory in infancy: evidence from eye-tracking.

We assessed visual short-term memory (VSTM) for color in 6- and 8-month-old infants (n = 76) using a one-shot change detection task. In this task, a sample array of two colored squares was visible for 517 ms, followed by a 317-ms retention period and then a 3000-ms test array consisting of one unchanged item and one item in a new color. We tracked gaze at 60 Hz while infants looked at the changed and unchanged items during test. When the two sample items were different colors (Experiment 1), 8-month-old infants exhibited a preference for the changed item, indicating memory for the colors, but 6-month-olds exhibited no evidence of memory. When the two sample items were the same color and did not need to be encoded as separate objects (Experiment 2), 6-month-old infants demonstrated memory. These results show that infants can encode information in VSTM in a single, brief exposure that simulates the timing of a single fixation period in natural scene viewing, and they reveal rapid developmental changes between 6 and 8 months in the ability to store individuated items in VSTM

Developmental changes in visual short-term memory in infancy: evidence from eye-tracking.

We assessed visual short-term memory (VSTM) for color in 6- and 8-month-old infants (n = 76) using a one-shot change detection task. In this task, a sample array of two colored squares was visible for 517 ms, followed by a 317-ms retention period and then a 3000-ms test array consisting of one unchanged item and one item in a new color. We tracked gaze at 60 Hz while infants looked at the changed and unchanged items during test. When the two sample items were different colors (Experiment 1), 8-month-old infants exhibited a preference for the changed item, indicating memory for the colors, but 6-month-olds exhibited no evidence of memory. When the two sample items were the same color and did not need to be encoded as separate objects (Experiment 2), 6-month-old infants demonstrated memory. These results show that infants can encode information in VSTM in a single, brief exposure that simulates the timing of a single fixation period in natural scene viewing, and they reveal rapid developmental changes between 6 and 8 months in the ability to store individuated items in VSTM

Rapid and highly specific screening for NPM1 mutations in acute myeloid leukemia

NPM1 mutations, the most frequent molecular alterations in acute myeloid leukemia (AML), have become important for risk stratification and treatment decisions for patients with normal karyotype AML. Rapid screening for NPM1 mutations should be available shortly after diagnosis. Several methods for detecting NPM1 mutations have been described, most of which are technically challenging and require additional laboratory equipment. We developed and validated an assay that allows specific, rapid, and simple screening for NPM1 mutations. FAST PCR spanning exons 8 to 12 of the NPM1 gene was performed on 284 diagnostic AML samples. PCR products were visualized on a 2 % agarose E-gel and verified by direct sequencing. The FAST PCR screening method showed a specificity and sensitivity of 100 %, i.e., all mutated cases were detected, and none of negative cases carried mutations. The limit of detection was at 5-10 % of mutant alleles. We conclude that the FAST PCR assay is a highly specific, rapid (less than 2 h), and sensitive screening method for the detection of NPM1 mutations. Moreover, this method is inexpensive and can easily be integrated in the routine molecular diagnostic work-up of established risk factors in AML using standard laboratory equipment