Visual scanning behavior and pilot workload

Sophisticated man machine interaction often requires the human operator to perform a stereotyped scan of various instruments in order to monitor and/or control a system. For situations in which this type of stereotyped behavior exists, such as certain phases of instrument flight, scan pattern was shown to be altered by the imposition of simultaneous verbal tasks. A study designed to examine the relationship between pilot visual scan of instruments and mental workload is described. It was found that a verbal loading task of varying difficulty causes pilots to stare at the primary instrument as the difficulty increases and to shed looks at instruments of less importance. The verbal loading task also affected the rank ordering of scanning sequences. By examining the behavior of pilots with widely varying skill levels, it was suggested that these effects occur most strongly at lower skill levels and are less apparent at high skill levels. A graphical interpretation of the hypothetical relationship between skill, workload, and performance is introduced and modelling results are presented to support this interpretation

Entropy, instrument scan and pilot workload

Correlation and information theory which analyze the relationships between mental loading and visual scanpath of aircraft pilots are described. The relationship between skill, performance, mental workload, and visual scanning behavior are investigated. The experimental method required pilots to maintain a general aviation flight simulator on a straight and level, constant sensitivity, Instrument Landing System (ILS) course with a low level of turbulence. An additional periodic verbal task whose difficulty increased with frequency was used to increment the subject's mental workload. The subject's looppoint on the instrument panel during each ten minute run was computed via a TV oculometer and stored. Several pilots ranging in skill from novices to test pilots took part in the experiment. Analysis of the periodicity of the subject's instrument scan was accomplished by means of correlation techniques. For skilled pilots, the autocorrelation of instrument/dwell times sequences showed the same periodicity as the verbal task. The ability to multiplex simultaneous tasks increases with skill. Thus autocorrelation provides a way of evaluating the operator's skill level

Comparison of the prevalence and characteristics of inpatient adverse events using medical records review and incident reporting

Background. Information on adverse events (AEs) in hospitalised patients in developing countries is scanty.Objective. To compare the magnitude and characteristics of inpatient AEs in a tertiary, not-for-profit healthcare facility in Kenya, using medical records review and incident reporting.Methods. Estimation of prevalence was done using incidents reported in 2010 from a random sample of medical records for hospital admissions. Nurse reviewers used 18 screening criteria, followed by physician reviewers to confirm occurrence. An AE was defined as an unexpected clinical event (UE) associated with death, disability or prolonged hospitalisation not explained by the disease condition. The kappa statistic was used to estimate inter-rater agreement, and analysis was done using logistic regression.Results. The study identified 53 UEs from 2 000 randomly selected medical records and 33 reported UEs from 23 026 admissions in the index year. The prevalences of AEs from medical records review and incident reports were 1.4% (95% confidence interval (CI) 0.9 - 2.0) and 0.03% (95% CI 0.012 - 0.063), respectively. Compared with incident reporting, review of medical records identified more disability (13.2% v. 0%; p=0.03) and prolonged hospital stays (43.4% v. 18.2%; p=0.02).Conclusions. Review of medical records is preferable to incident reporting in determining the prevalence of AEs in health facilities with limited inpatient quality improvement experience. Further research is needed to determine whether staff education and a positive culture change through promotion of non-punitive UE reporting or a combination of approaches would improve the comprehensiveness of AE reporting

Specific glial populations regulate hippocampal morphogenesis

The hippocampus plays an integral role in spatial navigation, learning and memory, and is a major site for adult neurogenesis. Critical to these functions is the proper organization of the hippocampus during development. Radial glia are known to regulate hippocampal formation, but their precise function in this process is yet to be defined. We find that in Nuclear Factor I b (Nfib)-deficient mice, a subpopulation of glia from the ammonic neuroepithelium of the hippocampus fail to develop. This results in severe morphological defects, including a failure of the hippocampal fissure, and subsequently the dentate gyrus, to form. As in wild-type mice, immature nestin-positive glia, which encompass all types of radial glia, populate the hippocampus in Nfib-deficient mice at embryonic day 15. However, these fail to mature into GLAST- and GFAP-positive glia, and the supragranular glial bundle is absent. In contrast, the fimbrial glial bundle forms, but alone is insufficient for proper hippocampal morphogenesis. Dentate granule neurons are present in the mutant hippocampus but their migration is aberrant, likely resulting from the lack of the complete radial glial scaffold usually provided by both glial bundles. These data demonstrate a role for Nfib in hippocampal fissure and dentate gyrus formation, and that distinct glial bundles are critical for correct hippocampal morphogenesis

Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults with Focal Epilepsy A Phase 2b Randomized Clinical Trial

IMPORTANCE Many patients with focal epilepsy experience seizures despite treatment with currently available antiseizure medications (ASMs) and may benefit from novel therapeutics. OBJECTIVE To evaluate the efficacy and safety of XEN1101, a novel small-molecule selective Kv7.2/Kv7.3 potassium channel opener, in the treatment of focal-onset seizures (FOSs). DESIGN, SETTING, AND PARTICIPANTS This phase 2b, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging adjunctive trial investigated XEN1101 over an 8-week treatment period from January 30, 2019, to September 2, 2021, and included a 6-week safety follow-up. Adults experiencing 4 or more monthly FOSs while receiving stable treatment (1-3 ASMs) were enrolled at 97 sites in North America and Europe. INTERVENTIONS Patients were randomized 2:1:1:2 to receive XEN1101, 25, 20, or 10mg, or placebo with food once daily for 8 weeks. Dosage titration was not used. On completion of the double-blind phase, patients were offered the option of entering an open-label extension (OLE). Patients not participating in the OLE had follow-up safety visits (1 and 6 weeks after the final dose). MAIN OUTCOMES AND MEASURES The primary efficacy end pointwas the median percent change from baseline in monthly FOS frequency. Treatment-emergent adverse events (TEAEs) were recorded and comprehensive laboratory assessments were made. Modified intention-to-treat analysis was conducted. RESULTS A total of 325 patients who were randomized and treated were included in the safety analysis; 285 completed the 8-week double-blind phase. In the 325 patients included, mean (SD) age was 40.8 (13.3) years, 168 (51.7%) were female, and 298 (91.7%) identified their race as White. Treatment with XEN1101 was associated with seizure reduction in a robust dose-response manner. The median (IQR) percent reduction from baseline in monthly FOS frequency was 52.8%(P < .001 vs placebo; IQR, -80.4%to -16.9%) for 25mg, 46.4% (P < .001 vs placebo; IQR, -76.7%to -14.0%) for 20mg, and 33.2%(P = .04 vs placebo; IQR, -61.8%to 0.0%) for 10mg, compared with 18.2%(IQR, -37.3%to 7.0%) for placebo. XEN1101 was generally well tolerated and TEAEs were similar to those of commonly prescribed ASMs, and no TEAEs leading to death were reported. CONCLUSIONS AND RELEVANCE The efficacy and safety findings of this clinical trial support the further clinical development of XEN1101 for the treatment of FOSs

BAF(mSWI/SNF) complex regulates mediolateral cortical patterning in the developing forebrain

Early forebrain patterning entails the correct regional designation of the neuroepithelium, and appropriate specification, generation, and distribution of neural cells during brain development. Specific signaling and transcription factors are known to tightly regulate patterning of the dorsal telencephalon to afford proper structural/functional cortical arealization and morphogenesis. Nevertheless, whether and how changes of the chromatin structure link to the transcriptional program(s) that control cortical patterning remains elusive. Here, we report that the BAF chromatin remodeling complex regulates the spatiotemporal patterning of the mouse dorsal telencephalon. To determine whether and how the BAF complex regulates cortical patterning, we conditionally deleted the BAF complex scaffolding subunits BAF155 and BAF170 in the mouse dorsal telencephalic neuroepithelium. Morphological and cellular changes in the BAF mutant forebrain were examined using immunohistochemistry and in situ hybridization. RNA sequencing, Co-immunoprecipitation, and mass spectrometry were used to investigate the molecular basis of BAF complex involvement in forebrain patterning. We found that conditional ablation of BAF complex in the dorsal telencephalon neuroepithelium caused expansion of the cortical hem and medial cortex beyond their developmental boundaries. Consequently, the hippocampal primordium is not specified, the mediolateral cortical patterning is compromised, and the cortical identity is disturbed in the absence of BAF complex. The BAF complex was found to interact with the cortical hem suppressor LHX2. The BAF complex suppresses cortical hem fate to permit proper forebrain patterning. We provide evidence that BAF complex modulates mediolateral cortical patterning possibly by interacting with the transcription factor LHX2 to drive the LHX2-dependent transcriptional program essential for dorsal telencephalon patterning. Our data suggest a putative mechanistic synergy between BAF chromatin remodeling complex and LHX2 in regulating forebrain patterning and ontogeny

NFIA controls telencephalic progenitor cell differentiation through repression of the Notch effector Hes1

The balance between self-renewal and differentiation of neural progenitor cells is an absolute requirement for the correct formation of the nervous system. Much is known about both the pathways involved in progenitor cell self-renewal, such as Notch signaling, and the expression of genes that initiate progenitor differentiation. However, whether these fundamental processes are mechanistically linked, and specifically how repression of progenitor self-renewal pathways occurs, is poorly understood. Nuclear factor I A (Nfia), a gene known to regulate spinal cord and neocortical development, has recently been implicated as acting downstream of Notch to initiate the expression of astrocyte-specific genes within the cortex. Here we demonstrate that, in addition to activating the expression of astrocyte-specific genes, Nfia also downregulates the activity of the Notch signaling pathway via repression of the key Notch effector Hes1. These data provide a significant conceptual advance in our understanding of neural progenitor differentiation, revealing that a single transcription factor can control both the activation of differentiation genes and the repression of the self-renewal genes, thereby acting as a pivotal regulator of the balance between progenitor and differentiated cell states