Temporal structure in haptic signaling under a cooperative task

Haptic communication between humans plays an important role in society. Although this form of communication is ubiquitous at all levels of society and of human development, little is known about how synchronized coordination of motion between two persons leads to higher-order cognitive functions used in communication. In this study, we developed a novel experimental paradigm of a coin-collecting task in which participants used their hands to control a rod to jointly collect the coins on the screen. We characterized the haptic interactions between paired participants while they were taking part in a cooperative task. The individual participants first completed this task on their own and then with a randomly assigned partner for the cooperative task. Single participant experiments were used as a baseline to compare results of the paired participants. Forces applied to the rod were translated to four possible haptic states which encode the combination of the haptic interactions. As a next step, pairs of consecutive haptic states were then combined into 16 possible haptic signals which were classified in terms of their temporal patterns using a Tsallis q-exponential function. For paired participants, 80% of the haptic signals could be fit by the Tsallis q-exponential. On the other hand, only 30% of the signals found in the single-participant trials could be fit by the Tsallis q-exponential. This shows a clear difference in the temporal structures of haptic signals when participants are interacting with each other and when they are not. We also found 94 a large difference in the number of haptic signals used by paired participants and singles. Single participants only used 1/4 of the possible haptic signals. Paired participants, on the other hand, used more than half of the possible signals. These results suggest that temporal structures present in haptic communication could be linked to the emergence of language at an evolutionary level

Keeping in time with social and non-social stimuli: synchronisation with auditory, visual, and audio-visual cues

Everyday social interactions require us to closely monitor, predict, and synchronise our movements with those of an interacting partner. Experimental studies of social synchrony typically examine the social-cognitive outcomes associated with synchrony, such as affiliation. On the other hand, research on the sensorimotor aspects of synchronisation generally uses non-social stimuli (e.g. a moving dot). To date, the differences in sensorimotor aspects of synchronisation to social compared to non-social stimuli remain largely unknown. The present study aims to address this gap using a verbal response paradigm where participants were asked to synchronise a ‘ba’ response in time with social and non-social stimuli, which were presented auditorily, visually, or audio-visually combined. For social stimuli a video/audio recording of an actor performing the same verbal ‘ba’ response was presented, whereas for non-social stimuli a moving dot, an auditory metronome or both combined were presented. The impact of autistic traits on participants’ synchronisation performance was examined using the Autism Spectrum Quotient (AQ). Our results revealed more accurate synchronisation for social compared to non-social stimuli, suggesting that greater familiarity with and motivation in attending to social stimuli may enhance our ability to better predict and synchronise with them. Individuals with fewer autistic traits demonstrated greater social learning, as indexed through an improvement in synchronisation performance to social vs non-social stimuli across the experiment

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

Relative information content of gestural features of non-verbal communication related to object-transfer interactions

In order to implement reliable, safe and smooth human-robot object handover it will be necessary for service robots to identify non-verbal communication gestures in real-time. This study presents an analysis of the relative information content in the gestural features that together constitute a communication gesture. Based on this information theoretic analysis we propose that the computational complexity of gesture classification, for object handover, can be greatly reduced by applying attention filters focused on static hand shape and orientation

Selecting object pairs for action: is the active object always first?

Perception is linked to action via two routes: a direct route based on affordance information in the environment and an indirect route based on semantic knowledge about objects. The present study explored the factors modulating the recruitment of the two routes, in particular which factors affecting the selection of paired objects. In Experiment 1, we presented real objects among semantically related or unrelated distracters. Participants had to select two objects that can interact. The presence of distracters affected selection times, but not the semantic relations of the objects with the distracters. Furthermore, participants first selected the active object (e.g. teaspoon) with their right hand, followed by the passive object (e.g. mug), often with their left hand. In Experiment 2, we presented pictures of the same objects with no hand grip, congruent or incongruent hand grip. Participants had to decide whether the two objects can interact. Action decisions were faster when the presentation of the active object preceded the presentation of the passive object, and when the grip was congruent. Interestingly, participants were slower when the objects were semantically but not functionally related; this effect increased with congruently gripped objects. Our data showed that action decisions in the presence of strong affordance cues (real objects, pictures of congruently gripped objects) relied on sensory-motor representation, supporting the direct route from perception-to-action that bypasses semantic knowledge. However, in the case of weak affordance cues (pictures), semantic information interfered with action decisions, indicating that semantic knowledge impacts action decisions. The data support the dual-route account from perception-to-action

Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene

Germline mutations in a number of genes involved in the recombinational repair of DNA double-strand breaks are associated with predisposition to breast and ovarian cancer. RAD51C is essential for homologous recombination repair, and a biallelic missense mutation can cause a Fanconi anemia-like phenotype. In index cases from 1,100 German families with gynecological malignancies, we identified six monoallelic pathogenic mutations in RAD51C that confer an increased risk for breast and ovarian cancer. These include two frameshift-causing insertions, two splice-site mutations and two nonfunctional missense mutations. The mutations were found exclusively within 480 pedigrees with the occurrence of both breast and ovarian tumors (BC/OC; 1.3%) and not in 620 pedigrees with breast cancer only or in 2,912 healthy German controls. These results provide the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog and support the 'common disease, rare allele' hypothesis

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Abstract Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer