Genetics of callous-unemotional behavior in children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU

The Near-Infrared Spectrograph (NIRSpec) on the James Webb Space Telescope: IV. Capabilities and predicted performance for exoplanet characterization

The Near-Inrared Spectrograph (NIRSpec) on the James Webb Space Telescope (JWST) is a very versatile instrument, offering multiobject and integral field spectroscopy with varying spectral resolution ($\sim$30 to $\sim$3000) over a wide wavelength range from 0.6 to 5.3 micron, enabling scientists to study many science themes ranging from the first galaxies to bodies in our own Solar System. In addition to its integral field unit and support for multiobject spectroscopy, NIRSpec features several fixed slits and a wide aperture specifically designed to enable high precision time-series and transit as well as eclipse observations of exoplanets. In this paper we present its capabilities regarding time-series observations, in general, and transit and eclipse spectroscopy of exoplanets in particular. Due to JWST's large collecting area and NIRSpec's excellent throughput, spectral coverage, and detector performance, this mode will allow scientists to characterize the atmosphere of exoplanets with unprecedented sensitivity

A longitudinal twin study of the association between childhood autistic traits and psychotic experiences in adolescence

- Background: This twin study investigated whether autistic traits during childhood were associated with adolescent psychotic experiences. - Methods: Data were collected from a community sample of approximately 5000 twin pairs, which included 32 individuals with diagnosed autism spectrum conditions (ASC). Parents rated autistic traits in the twins at four points between ages 8–16 years. Positive, negative, and cognitive psychotic experiences were assessed at age 16 years using self- and parent-report scales. Longitudinal twin analyses tested the associations between these measures. - Results: Autistic traits correlated weakly or nonsignificantly with positive psychotic experiences (paranoia, hallucinations, and grandiosity), and modestly with cognitive psychotic experiences (cognitive disorganisation). Higher correlations were observed for parent-rated negative symptoms and self-reported anhedonia, although the proportion of variance in both accounted for by autistic traits was low (10 and 31 %, respectively). The majority of the genetic influences on negative symptoms and anhedonia were independent of autistic traits. Additionally, individuals with ASC displayed significantly more negative symptoms, anhedonia, and cognitive disorganisation than controls. - Conclusions: Autistic traits do not appear to be strongly associated with psychotic experiences in adolescence; associations were also largely restricted to negative symptoms. Of note, the degree to which the genetic and environmental causes of autistic traits influenced psychotic experiences was limited. These findings thus support a phenotypic and etiological distinction between autistic traits and psychotic experiences

Sports teams as complex adaptive systems: manipulating player numbers shapes behaviours during football small-sided games

Small-sided and conditioned games (SSCGs) in sport have been modelled as complex adaptive systems. Research has shown that the relative space per player (RSP) formulated in SSCGs can impact on emergent tactical behaviours. In this study we adopted a systems orientation to analyse how different RSP values, obtained through manipulations of player numbers, influenced four measures of interpersonal coordination observed during performance in SSCGs. For this purpose we calculated positional data (GPS 15 Hz) from ten U-15 football players performing in three SSCGs varying in player numbers (3v3, 4v4 and 5v5). Key measures of SSCG system behaviours included values of (1) players’ dispersion, (2) teams’ separateness, (3) coupling strength and time delays between participants’ emerging movements, respectively. Results showed that values of participants’ dispersion increased, but the teams’ separateness remained identical across treatments. Coupling strength and time delay also showed consistent values across SSCGs. These results exemplified how complex adaptive systems, like football teams, can harness inherent degeneracy to maintain similar team spatial–temporal relations with opponents through changes in inter-individual coordination modes (i.e., players’ dispersion). The results imply that different team behaviours might emerge at different ratios of field dimension/player numbers. Therefore, sport pedagogists should carefully evaluate the effects of changing RSP in SSCGs as a way of promoting increased or decreased pressure on players

Childhood behaviour problems show the greatest gap between DNA-based and twin heritability

For most complex traits, DNA-based heritability (‘SNP heritability’) is roughly half that of twin-based heritability. A previous report from the Twins Early Development Study suggested that this heritability gap is much greater for childhood behaviour problems than for other domains. If true, this finding is important because SNP heritability, not twin heritability, is the ceiling for genome-wide association studies. With twice the sample size as the previous report, we estimated SNP heritabilities (N up to 4653 unrelated individuals) and compared them with twin heritabilities from the same sample (N up to 4724 twin pairs) for diverse domains of childhood behaviour problems as rated by parents, teachers, and children themselves at ages 12 and 16. For 37 behaviour problem measures, the average twin heritability was 0.52, whereas the average SNP heritability was just 0.06. In contrast, results for cognitive and anthropometric traits were more typical (average twin and SNP heritabilities were 0.58 and 0.28, respectively). Future research should continue to investigate the reasons why SNP heritabilities for childhood behaviour problems are so low compared with twin estimates, and find ways to maximise SNP heritability for genome-wide association studies

Brains swinging in concert: cortical phase synchronization while playing guitar

<p>Abstract</p> <p>Background</p> <p>Brains interact with the world through actions that are implemented by sensory and motor processes. A substantial part of these interactions consists in synchronized goal-directed actions involving two or more individuals. Hyperscanning techniques for assessing fMRI simultaneously from two individuals have been developed. However, EEG recordings that permit the assessment of synchronized neuronal activities at much higher levels of temporal resolution have not yet been simultaneously assessed in multiple individuals and analyzed in the time-frequency domain. In this study, we simultaneously recorded EEG from the brains of each of eight pairs of guitarists playing a short melody together to explore the extent and the functional significance of synchronized cortical activity in the course of interpersonally coordinated actions.</p> <p>Results</p> <p>By applying synchronization algorithms to intra- and interbrain analyses, we found that phase synchronization both within and between brains increased significantly during the periods of (i) preparatory metronome tempo setting and (ii) coordinated play onset. Phase alignment extracted from within-brain dynamics was related to behavioral play onset asynchrony between guitarists.</p> <p>Conclusion</p> <p>Our findings show that interpersonally coordinated actions are preceded and accompanied by between-brain oscillatory couplings. Presumably, these couplings reflect similarities in the temporal properties of the individuals' percepts and actions. Whether between-brain oscillatory couplings play a causal role in initiating and maintaining interpersonal action coordination needs to be clarified by further research.</p

Auditory Deficit as a Consequence Rather than Endophenotype of Specific Language Impairment: Electrophysiological Evidence

Are developmental language disorders caused by poor auditory discrimination? This is a popular theory, but behavioural evidence has been inconclusive. Here we studied children with specific language impairment, measuring the brain's electrophysiological response to sounds in a passive paradigm. We focused on the T-complex, an event-related peak that has different origins and developmental course from the well-known vertex response.We analysed auditory event-related potentials to tones and syllables from 16 children and 16 adolescents with specific language impairment who were compared with 32 typically-developing controls, matched for gender, IQ and age.We replicated prior findings of significant reduction in Ta amplitude for both children and adolescents with specific language impairment, which was particularly marked for syllables. The topography of the T-complex to syllables indicated a less focal response in those with language impairments. To distinguish causal models, we considered correlations between size of the Ta response and measures of language and literacy in parents as well as children. The best-fitting model was one in which auditory deficit was a consequence rather than a cause of difficulties in phonological processing.The T-complex to syllables has abnormal size and topography in children with specific language impairment, but this is more likely to be a consequence rather than a cause of difficulties in phonological processing

Exploring diurnal variation using piecewise linear splines:an example using blood pressure

Background: There are many examples of physiological processes that follow a circadian cycle and researchers are interested in alternative methods to illustrate and quantify this diurnal variation. Circadian blood pressure (BP) deserves additional attention given uncertainty relating to the prognostic significance of BP variability in relation to cardiovascular disease. However, the majority of studies exploring variability in ambulatory blood pressure monitoring (ABPM) collapse the data into single readings ignoring the temporal nature of the data. Advanced statistical techniques are required to explore complete variation over 24 h. Methods: We use piecewise linear splines in a mixed-effects model with a constraint to ensure periodicity as a novel application for modelling daily blood pressure. Data from the Mitchelstown Study, a cross-sectional study of Irish adults aged 47–73 years (n = 2047) was utilized. A subsample (1207) underwent 24-h ABPM. We compared patterns between those with and without evidence of subclinical target organ damage (microalbuminuria). Results: We were able to quantify the steepest rise and fall in SBP, which occurred just after waking (2.23 mmHg/30 min) and immediately after falling asleep (−1.93 mmHg/30 min) respectively. The variation about an individual’s trajectory over 24 h was 12.3 mmHg (standard deviation). On average those with microalbuminuria were found to have significantly higher SBP (7.6 mmHg, 95% CI 5.0–10.1) after adjustment for age, sex and BMI. Including an interaction term between each linear spline and microalbuminuria did not improve model fit. Conclusion: We have introduced a practical method for the analysis of ABPM where we can determine the rate of increase or decrease for different periods of the day. This may be particularly useful in examining chronotherapy effects of antihypertensive medication. It offers new measures of short-term BP variability as we can quantify the variation about an individual’s trajectory but also allows examination of the variation in slopes between individuals (random-effects)

Associating Facial Expressions and Upper-Body Gestures with Learning Tasks for Enhancing Intelligent Tutoring Systems

Learning involves a substantial amount of cognitive, social and emotional states. Therefore, recognizing and understanding these states in the context of learning is key in designing informed interventions and addressing the needs of the individual student to provide personalized education. In this paper, we explore the automatic detection of learner’s nonverbal behaviors involving hand-over-face gestures, head and eye movements and emotions via facial expressions during learning. The proposed computer vision-based behavior monitoring method uses a low-cost webcam and can easily be integrated with modern tutoring technologies. We investigate these behaviors in-depth over time in a classroom session of 40 minutes involving reading and problem-solving exercises. The exercises in the sessions are divided into three categories: an easy, medium and difficult topic within the context of undergraduate computer science. We found that there is a significant increase in head and eye movements as time progresses, as well as with the increase of difficulty level. We demonstrated that there is a considerable occurrence of hand-over-face gestures (on average 21.35%) during the 40 minutes session and is unexplored in the education domain. We propose a novel deep learning approach for automatic detection of hand-over-face gestures in images with a classification accuracy of 86.87%. There is a prominent increase in hand-over-face gestures when the difficulty level of the given exercise increases. The hand-over-face gestures occur more frequently during problem-solving (easy 23.79%, medium 19.84% and difficult 30.46%) exercises in comparison to reading (easy 16.20%, medium 20.06% and difficult 20.18%)

Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study

<p>Abstract</p> <p>Background</p> <p>Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected <it>at </it>or <it>after </it>diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort.</p> <p>Methods</p> <p>In a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS).</p> <p>Results</p> <p>Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3a_desArg), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3a_desArgand ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer.</p> <p>Conclusions</p> <p>We show that serum protein profiles are already altered up to three years before breast cancer detection.</p