Atypical MEG inter-subject correlation during listening to continuous natural speech in dyslexia

Listening to speech elicits brain activity time-locked to the speech sounds. This so-called neural entrainment to speech was found to be atypical in dyslexia, a reading impairment associated with neural speech processing deficits. We hypothesized that the brain responses of dyslexic vs. normal readers to real-life speech would be different, and thus the strength of inter-subject correlation (ISC) would differ from that of typical readers and be reflected in reading-related measures. We recorded magnetoencephalograms (MEG) of 23 dyslexic and 21 typically-reading adults during listening to ∼10 min of natural Finnish speech consisting of excerpts from radio news, a podcast, a self-recorded audiobook chapter and small talk. The amplitude envelopes of band-pass-filtered MEG source signals were correlated between subjects in a cortically-constrained source space in six frequency bands. The resulting ISCs of dyslexic and typical readers were compared with a permutation-based t-test. Neuropsychological measures of phonological processing, technical reading, and working memory were correlated with the ISCs utilizing the Mantel test. During listening to speech, ISCs were mainly reduced in dyslexic compared to typical readers in delta (0.5–4 Hz) and high gamma (55–90 Hz) frequency bands. In the theta (4−8 Hz), beta (12–25 Hz), and low gamma (25−45 Hz) bands, dyslexics had enhanced ISC to speech compared to controls. Furthermore, we found that ISCs across both groups were associated with phonological processing, technical reading, and working memory. The atypical ISC to natural speech in dyslexics supports the temporal sampling deficit theory of dyslexia. It also suggests over-synchronization to phoneme-rate information in speech, which could indicate more effort-demanding sampling of phonemes from speech in dyslexia. These irregularities in parsing speech are likely some of the complex neural factors contributing to dyslexia. The associations between neural coupling and reading-related skills further support this notion.Peer reviewe

Working poverty is a widespread but under-analyzed and poorly-measured problem in the US

Data and statistics are integral to policymakers in government trying to tackle problems such as working poverty. And yet, estimates of the proportion of working poor in the US vary from 2 to 19 percent. In new research, Brian C. Thiede, Daniel T. Lichter, and Scott R. Sanders seek to explain the variation in statistics around those in working poverty. They write that estimates about the magnitude of working poverty, and on its incidence among racial and ethnic groups can be sensitive to the often technical choices, often based on assumptions about how people get into poverty, made by those who are doing the estimating

Infancy and early childhood maturation of neural auditory change detection and its associations to familial dyslexia risk

Objective: We investigated early maturation of the infant mismatch response MMR, including mismatch negativity (MMN), positive MMR (P-MMR), and late discriminative negativity (LDN), indexing auditory discrimination abilities, and the influence of familial developmental dyslexia risk. Methods: We recorded MMRs to vowel, duration, and frequency deviants in pseudo-words at 0, 6, and 28 months and compared MMRs in subgroups with vs. without dyslexia risk, in a sample overrepresented by risk infants. Results: Neonatal MMN to the duration deviant became larger and earlier by 28 months; MMN was elicited by more deviants only at 28 months. The P-MMR was predominant in infancy; its amplitude increased by 6 and decreased by 28 months; latency decreased with increasing age. An LDN emerged by 6 months and became larger and later by 28 months. Dyslexia risk affected MMRs and their maturation. Conclusions: MMRs demonstrate an expected maturational pattern with 2-3 peaks by 28 months. The effects of dyslexia risk are prominent but not always as expected. Significance: This large-scale longitudinal study shows MMR maturation with three age groups and three deviants. Results illuminate MMR's relation to the adult responses, and hence their cognitive underpinnings, and help in identifying typical/atypical auditory development in early childhood. (c) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Anisotropic Electronic Structure of the Kondo Semiconductor CeFe2Al10 Studied by Optical Conductivity

We report temperature-dependent polarized optical conductivity [$\sigma(\omega)$] spectra of CeFe$_2$Al$_{10}$, which is a reference material for CeRu$_2$Al$_{10}$ and CeOs$_2$Al$_{10}$ with an anomalous magnetic transition at 28 K. The $\sigma(\omega)$ spectrum along the b-axis differs greatly from that in the $ac$-plane, indicating that this material has an anisotropic electronic structure. At low temperatures, in all axes, a shoulder structure due to the optical transition across the hybridization gap between the conduction band and the localized $4f$ states, namely $c$-$f$ hybridization, appears at 55 meV. However, the gap opening temperature and the temperature of appearance of the quasiparticle Drude weight are strongly anisotropic indicating the anisotropic Kondo temperature. The strong anisotropic nature in both electronic structure and Kondo temperature is considered to be relevant the anomalous magnetic phase transition in CeRu$_2$Al$_{10}$ and CeOs$_2$Al$_{10}$.Comment: 5 pages, 4 figure

Infant event-related potentials to speech are associated with prelinguistic development

Neural auditory processing and prelinguistic communication build the foundation for later language development, but how these two are associated is not well known. The current study investigated how neural speech processing is associated with the level and development of prelinguistic skills in 102 infants. We recorded event-related potentials (ERPs) in 6-months-olds to assess the neural detection of a pseudoword (obligatory responses), as well as the neural discrimination of changes in the pseudoword (mismatch responses, MMRs). Prelinguistic skills were assessed at 6 and 12 months of age with a parental questionnaire (Infant-Toddler Checklist). The association between the ERPs and prelinguistic skills was examined using latent change score models, a method specifically constructed for longitudinal analyses and explicitly modeling intra-individual change. The results show that a large obligatory P1 at 6 months of age predicted strong improvement in prelinguistic skills between 6 and 12 months of age. The MMR to a frequency change was associated with the concurrent level of prelinguistic skills, but not with the improvement of the skills. Overall, our results highlight the strong association between ERPs and prelinguistic skills, possibly offering opportunities for early detection of atypical linguistic and communicative development.Peer reviewe

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML

Settling tubes for size analysis of fine and coarse fractions of oceanic sediments

Instrumentation for rapid, high precision size analysis of silt and sand size particles has been acquired and/or developed by the marine geology group of the School of Oceanography of Oregon State University. A Cahn automatic electrobalance with particle sedimentation accessories is used for size analysis of the silt fraction of pelagic sediment; a large diameter settling tube developed at Oregon State University is used for analysis of the sand size fraction. The data generated with these systems are recorded by a strip chart recorder as well as by a high speed paper tape punch. Computer programs to deal with large volumes of data and to calculate various size parameters for each sample have been developed for this instrumentation and are documented in this report. Instrumentation has also been developed to permit specific size fractions to be separated from the bulk sediment to allow compositional studies of the different size modes. All documentation necessary to understand this instrumentation system is presented in this report, and thus is available to all students interested in textural classifications of pelagic sediments

Rapid Diagnostic Algorithms as a Screening Tool for Tuberculosis: An Assessor Blinded Cross-Sectional Study

Background: A major obstacle to effectively treat and control tuberculosis is the absence of an accurate, rapid, and low-cost diagnostic tool. A new approach for the screening of patients for tuberculosis is the use of rapid diagnostic classification algorithms. Methods: We tested a previously published diagnostic algorithm based on four biomarkers as a screening tool for tuberculosis in a Central European patient population using an assessor-blinded cross-sectional study design. In addition, we developed an improved diagnostic classification algorithm based on a study population at a tertiary hospital in Vienna, Austria, by supervised computational statistics. Results: The diagnostic accuracy of the previously published diagnostic algorithm for our patient population consisting of 206 patients was 54% (CI: 47%–61%). An improved model was constructed using inflammation parameters and clinical information. A diagnostic accuracy of 86% (CI: 80%–90%) was demonstrated by 10-fold cross validation. An alternative model relying solely on clinical parameters exhibited a diagnostic accuracy of 85% (CI: 79%–89%). Conclusion: Here we show that a rapid diagnostic algorithm based on clinical parameters is only slightly improved by inclusion of inflammation markers in our cohort. Our results also emphasize the need for validation of new diagnostic algorithms in different settings and patient populations

Comprehensive Analysis of the 16p11.2 Deletion and Null Cntnap2 Mouse Models of Autism Spectrum Disorder

Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept1)4Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of therapeutics and we anticipate both our positive and negative findings will be utilized as a resource for the broader scientific community