Distortions to Passage of Time Judgements (POTJ) due to virtual threat are predicted by autonomic activation.

Humans' sense of the passage of time is subjective and determined by psychophysiological responses to the environment. The passing of time has been perceived to significantly slow in stressful situations, such as accidents or virtual threats. The current study will explore distortions in the perception of passage of time when threat is simulated using virtual reality (VR).

Trait impulsivity influences behavioural and physiological responses to threat in a virtual environment.

Trait impulsivity represents a tendency to take action without forethought or consideration of consequences. This trait is multifaceted and can be decomposed into attentional, motor and non-planning subtypes of impulsivity. The purpose of the current study was to investigate how subtypes of trait impulsivity responded to different degrees of threat within room-scale virtual reality (VR) with respect to behaviour and level of physiological activation.

Functional connectivity across dorsal and ventral attention networks in response to task difficulty and experimental pain.

The dorsal and ventral attention networks (DAN & VAN) provide a framework for studying attentional modulation of pain. It has been argued that cognitive demand distracts attention from painful stimuli via top-down reinforcement of task goals (DAN), whereas pain exerts an interruptive effect on cognitive performance via bottom-up pathways (VAN). The current study explores this explanatory framework by manipulating pain and task demand in combination with functional near-infrared spectroscopy (fNIRS) and Granger Causal Connectivity Analyses (GCCA).

The psychophysiological mechanisms of real-world time experience.

Our sense of time is fallible, often resulting in the sensation of time flying by quickly or dragging slowly. It has been suggested that changes in sympathetic (SNS) and parasympathetic nervous system (PNS) activity may influence the perceived passage of time, however this proposition has never been tested during real-world temporal experience. The current study directly tested the relationship between the passage of time and SNS-PNS activity in the real-world.

Classification of Game Demand and the Presence of Experimental Pain Using Functional Near-Infrared Spectroscopy.

Pain tolerance can be increased by the introduction of an active distraction, such as a computer game. This effect has been found to be moderated by game demand, i.e.

Effortful listening: Sympathetic activity varies as a function of listening demand but parasympathetic activity does not.

Research on listening effort has used various physiological measures to examine the biological correlates of listening effort but a systematic examination of the impact of listening demand on cardiac autonomic nervous system activity is still lacking. The presented study aimed to close this gap by assessing cardiac sympathetic and parasympathetic responses to variations in listening demand. For this purpose, 45 participants performed four speech-in-noise tasks differing in listening demand-manipulated as signal-to-noise ratio varying between +23 dB and -16 dB-while their pre-ejection period and respiratory sinus arrythmia responses were assessed.

The Role of the Prefrontal Cortex and Functional Connectivity during Maritime Operations: An fNIRS study.

Introduction: Watchkeeping is a significant activity during maritime operations, and failures of sustained attention and decision-making can increase the likelihood of a collision.

Methods: A study was conducted in a ship bridge simulator where 40 participants (20 experienced/20 inexperienced) performed: (1) a 20-min period of sustained attention to locate a target vessel and (2) a 10-min period of decision-making/action selection to perform an evasive maneuver. Half of the participants also performed an additional task of verbally reporting the position of their vessel.

Assessment of threat and negativity bias in virtual reality.

Negativity bias, i.e., tendency to respond strongly to negative stimuli, can be captured via behavioural and psychophysiological responses to potential threat.

A Neuroergonomics Approach to Mental Workload, Engagement and Human Performance.

The assessment and prediction of cognitive performance is a key issue for any discipline concerned with human operators in the context of safety-critical behavior. Most of the research has focused on the measurement of mental workload but this construct remains difficult to operationalize despite decades of research on the topic. Recent advances in Neuroergonomics have expanded our understanding of neurocognitive processes across different operational domains.

Routine Plasma-Based Genotyping to Comprehensively Detect Germline, Somatic, and Reversion Mutations among Patients with Advanced Solid Tumors.

Purpose: PARP inhibitors (PARPi) are efficacious in multiple cancers harboring germline (and possibly somatic) mutations. Acquired reversions can restore function, causing resistance to PARPi and/or platinum-based chemotherapy. The optimal method of identifying patients with germline, somatic, and/or reversion mutations in has not been established.

Molecular Mechanisms of Acquired Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14-Mutant NSCLC.

Purpose: Molecular mechanisms of acquired resistance to MET tyrosine kinase inhibitors (TKI) are poorly understood. We aimed to characterize the genomic mechanisms of resistance to type I and type II MET TKIs and their impact on sequential MET TKI therapy outcomes in patients with metastatic exon 14-mutant NSCLC.

Experimental Design: Genomic alterations occurring at the time of progression on MET TKIs were studied using plasma and tissue next-generation sequencing (NGS).

Identification of osimertinib-resistant L792 mutations by cfDNA sequencing: oncogenic activity assessment and prevalence in large cfDNA cohort.

Cell-free DNA (cfDNA) next-generation sequencing has the potential to capture tumor heterogeneity and genomic evolution under treatment pressure in a non-invasive manner. Here, we report the detection of L792 mutations, a non-covalent mechanism of osimertinib resistance, using Guardant360 cfDNA testing in a patient with metastatic -mutant non-small cell lung cancer (NSCLC) whose disease progressed on osimertinib. We subsequently analyzed a large cohort of over 1800 additional patient samples harboring an T790M mutation and identified a concomitant L792 mutation in a total of 22 (1.

Validation of Microsatellite Instability Detection Using a Comprehensive Plasma-Based Genotyping Panel.

Purpose: To analytically and clinically validate microsatellite instability (MSI) detection using cell-free DNA (cfDNA) sequencing.

Experimental Design: Pan-cancer MSI detection using Guardant360 was analytically validated according to established guidelines and clinically validated using 1,145 cfDNA samples for which tissue MSI status based on standard-of-care tissue testing was available. The landscape of cfDNA-based MSI across solid tumor types was investigated in a cohort of 28,459 clinical plasma samples.

Analysis of Cell-Free DNA from 32,989 Advanced Cancers Reveals Novel Co-occurring Activating Alterations and Oncogenic Signaling Pathway Aberrations.

Purpose: is an emerging oncogenic target showing promise in phase I/II clinical trials. An understudied aspect of -driven cancers is the extent to which co-occurring genomic alterations exist and how they may impact prognosis or therapeutic response.

Experimental Design: Somatic activating alterations were identified among 32,989 consecutive patients with metastatic solid tumors tested with a clinical cell-free circulating tumor DNA (cfDNA) assay.

FNIRS activity in the prefrontal cortex and motivational intensity: impact of working memory load, financial reward, and correlation-based signal improvement.

Previous research has demonstrated changes in neurovascular activation of the prefrontal cortex to increased working memory load. The primary purpose of the current paper was to investigate overload of working memory capacity using functional near-infrared spectroscopy (fNIRS) within the framework of motivational intensity theory. A secondary goal was to explore the influence of the correlation-based signal improvement (CBSI) as a method for correcting the influence of systemic variables.

Radiologic and Genomic Evolution of Individual Metastases during HER2 Blockade in Colorectal Cancer.

Targeting HER2 is effective in 24% of ERBB2 amplified metastatic colorectal cancer; however, secondary resistance occurs in most of the cases. We studied the evolution of individual metastases during treatment to discover spatially resolved determinants of resistance. Circulating tumor DNA (ctDNA) analysis identified alterations associated with resistance in the majority of refractory patients.

The Landscape of Actionable Genomic Alterations in Cell-Free Circulating Tumor DNA from 21,807 Advanced Cancer Patients.

Cell-free DNA (cfDNA) sequencing provides a noninvasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types. To facilitate interpretation of the genomic complexity of circulating tumor DNA in advanced, treated cancer patients, we developed methods to identify cfDNA copy-number driver alterations and cfDNA clonality.

Validation of a Plasma-Based Comprehensive Cancer Genotyping Assay Utilizing Orthogonal Tissue- and Plasma-Based Methodologies.

To analytically and clinically validate a circulating cell-free tumor DNA sequencing test for comprehensive tumor genotyping and demonstrate its clinical feasibility. Analytic validation was conducted according to established principles and guidelines. Blood-to-blood clinical validation comprised blinded external comparison with clinical droplet digital PCR across 222 consecutive biomarker-positive clinical samples.

Publisher correction: Young inversion with multiple linked QTLs under selection in a hybrid zone.

In Fig. 5 of the version of this Article originally published, the final number on the x axes of each panel was incorrectly written as 1.5; it should have read 7.

Discrimination of Germline T790M Mutations in Plasma Cell-Free DNA Allows Study of Prevalence Across 31,414 Cancer Patients.

Plasma cell-free DNA (cfDNA) analysis is increasingly used clinically for cancer genotyping, but may lead to incidental identification of germline-risk alleles. We studied T790M mutations in non-small cell lung cancer (NSCLC) toward the aim of discriminating germline and cancer-derived variants within cfDNA. Patients with -mutant NSCLC, some with known germline T790M, underwent plasma genotyping.

Young inversion with multiple linked QTLs under selection in a hybrid zone.

Fixed chromosomal inversions can reduce gene flow and promote speciation in two ways: by suppressing recombination and by carrying locally favoured alleles at multiple loci. However, it is unknown whether favoured mutations slowly accumulate on older inversions or if young inversions spread because they capture pre-existing adaptive quantitative trait loci (QTLs). By genetic mapping, chromosome painting and genome sequencing, we have identified a major inversion controlling ecologically important traits in Boechera stricta.