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Pilots of aircraft face varying degrees of cognitive workload even during normal flight operations. Periods of low cognitive workload may be followed by periods of high cognitive workload and vice versa. During such changing demands, there exists potential for increased error on behalf of the pilots due to periods of boredom or excessive cognitive task demand. To further understand cognitive workload in aviation, the present study involved collection of electroencephalogram (EEG) data from ten (10) collegiate aviation students in a live-flight environment in a single-engine aircraft. Each pilot possessed a Federal Aviation Administration (FAA) commercial pilot certificate and either FAA class I or class II medical certificate. Each pilot flew a standardized flight profile representing an average instrument flight training sequence. For data analysis, we used four main sub-bands of the recorded EEG signals: delta, theta, alpha, and beta. Power spectral density (PSD) and log energy entropy of each sub-band across 20 electrodes were computed and subjected to two feature selection algorithms (recursive feature elimination (RFE) and lasso cross-validation (LassoCV), and a stacking ensemble machine learning algorithm composed of support vector machine, random forest, and logistic regression. Also, hyperparameter optimization and tenfold cross-validation were used to improve the model performance, reliability, and generalization. The feature selection step resulted in 15 features that can be considered an indicator of pilots' cognitive workload states. Then these features were applied to the stacking ensemble algorithm, and the highest results were achieved using the selected features by the RFE algorithm with an accuracy of 91.67% (± 0.11), a precision of 93.89% (± 0.09), recall of 91.67% (± 0.11), F-score of 91.22% (± 0.12), and the mean ROC-AUC of 0.93 (± 0.06). The achieved results indicated that the combination of PSD and log energy entropy, along with well-designed machine learning algorithms, suggest the potential for the use of EEG to discriminate periods of the low, medium, and high workload to augment aircraft system design, including flight automation features to improve aviation safety. [ABSTRACT FROM AUTHOR]

Tinnitus, a phantom perception of sound in the absence of any external sound source, is a prevalent health condition often accompanied by psychiatric comorbidities. Recent genome-wide association studies (GWAS) highlighted a polygenic nature of tinnitus susceptibility. A shared genetic component between tinnitus and psychiatric conditions remains elusive. Here we present a GWAS using the UK Biobank to investigate the genetic processes linked to tinnitus and tinnitus-related distress, followed by gene-set enrichment analyses. The UK Biobank sample comprised 132,438 individuals with tinnitus and genotype data. Among the study sample, 38,525 individuals reported tinnitus, and 26,889 participants mentioned they experienced tinnitus-related distress in daily living. The genome-wide association analyses were conducted on tinnitus and tinnitus-related distress. We conducted enrichment analyses using FUMA to further understand the genetic processes linked to tinnitus and tinnitus-related distress. A genome-wide significant locus (lead SNP: rs71595470) for tinnitus was obtained in the vicinity of GPM6A. Nineteen independent loci reached suggestive association with tinnitus. Fifteen independent loci reached suggestive association with tinnitus-related distress. The enrichment analysis revealed a shared genetic component between tinnitus and psychiatric traits, such as bipolar disorder, feeling worried, cognitive ability, fast beta electroencephalogram, and sensation seeking. Metabolic, cardiovascular, hematological, and pharmacological gene sets revealed a significant association with tinnitus. Anxiety and stress-related gene sets revealed a significant association with tinnitus-related distress. The GWAS signals for tinnitus were enriched in the hippocampus and cortex, and for tinnitus-related distress were enriched in the brain and spinal cord. This study provides novel insights into genetic processes associated with tinnitus and tinnitus-related distress and demonstrates a shared genetic component underlying tinnitus and psychiatric conditions. Further collaborative attempts are necessary to identify genetic components underlying the phenotypic heterogeneity in tinnitus and provide biological insight into the etiology. [ABSTRACT FROM AUTHOR]

Many Gram-negative bacteria use CdiA effector proteins to inhibit the growth of neighboring competitors. CdiA transfers its toxic CdiA-CT region into the periplasm of target cells, where it is released through proteolytic cleavage. The N-terminal cytoplasm-entry domain of the CdiA-CT then mediates translocation across the inner membrane to deliver the C-terminal toxin domain into the cytosol. Here, we show that proteolysis not only liberates the CdiA-CT for delivery, but is also required to activate the entry domain for membrane translocation. Translocation function depends on precise cleavage after a conserved VENN peptide sequence, and the processed ∆VENN entry domain exhibits distinct biophysical and thermodynamic properties. By contrast, imprecisely processed CdiA-CT fragments do not undergo this transition and fail to translocate to the cytoplasm. These findings suggest that CdiA-CT processing induces a critical structural switch that converts the entry domain into a membrane-translocation competent conformation. Contact-dependent growth inhibition (CDI) is an important mechanism of bacterial competition. Here, Bartelli et al. show that proteolytic processing of a CDI toxin induces a conformational switch required for translocation into target bacteria. [ABSTRACT FROM AUTHOR]

Topobathymetric lidar is becoming an increasingly valuable tool for benthic habitat mapping, enabling safe, efficient data acquisition over coral reefs and other fragile ecosystems. In 2014, a novel topobathymetric lidar system, the Experimental Advanced Airborne Research Lidar-B (EAARL-B), was used to acquire data in priority habitat areas in the U.S. Virgin Islands (USVI), spanning the 0–44-m depth range. In this study, new algorithms and procedures were developed for generating seafloor relative reflectance, along with a suite of shape-based waveform features from EAARL-B. Waveform features were then correlated with percent cover of coral morphologies, domed and branched, and total cover of hard and soft corals. Results show that the EAARL-B can be used to produce useful seafloor relative reflectance mosaics and also that the additional waveform shape-based features contain additional information that may benefit habitat classification—specifically, to aid in distinguishing among hard corals and their coral morphologies, domed and branched. Knowing the spatial extent of changes in coral communities is important to the understanding of resiliency of coral reefs under stress from human impacts. [ABSTRACT FROM AUTHOR]

Stress-induced performance degradation in high-pressure situations has been documented empirically and generated different explanations. The existing theories often assume the distinction between implicit and explicit processing but speculate differently on the impact that high-pressure situations have on their interaction. Although few attempts have been made so far at clarifying these underlying processes mechanistically (e.g., computationally), this paper proposes a detailed, mechanistic, and process-based account based on the Clarion cognitive architecture. This account incorporates facets of existing theories, but explores motivation, metacognition, and their effects on performance degradation. This account has been applied to different tasks that have previously suggested different explanations. These tasks were simulated within the Clarion cognitive architecture and results matched well with human data. Utilizing data from different tasks, we come up with a unified model of stress-induced performance degradation in high-pressure situations, which shows a unified, motivation-based, mechanistic account of these phenomena is possible, thus shedding light on the phenomena and pointing to mechanistic explanations of other related phenomena. [ABSTRACT FROM AUTHOR]

Historical scholars often adopt a solitary ethic, conceiving of their work as the product of a lonely and isolated individual toiling away in a dusty archive. In this article, we assess the validity of this ethic by examining the actual practice of archival research. Drawing on semi-structured interviews with practicing historical sociologists, we reveal that the solitary ethic is largely illusory, and that, instead, the archive is in fact a robustly social world. We identify two core sets of social relationships in the archive—relationships with the archivist and with the archival community—that shape the historical sociologist's experience in the archive. We further show that historical sociologists mobilize these interactions to solve concrete research problems in the archive. We thus argue that the archive's social character should be understood as a methodological opportunity for historical sociologists, allowing them to maximize and extend their research by inspiring creative research strategies. [ABSTRACT FROM AUTHOR]

The well-known benefits of collaborative learning have prompted the development of active learning classrooms that are designed to facilitate peer interaction. Given the expense of designing active learning classrooms, examining student perceptions of these learning spaces is critical. Furthermore, it is not well understood how the type of classroom (active learning or traditional lecture) relates to students' perceptions of collaborative learning. In this study, aviation students (N = 46) were enrolled in the same course taught in the same active-learning manner by the same professor, with one section taught in an active-learning classroom and one taught in a traditional lecture classroom. Relative to the traditional lecture classroom, students perceived the active-learning classroom as being much better suited to collaborative learning and having higher levels of collaborative learning, both in terms of enjoyment and usefulness. Implications for designing learning environments and promoting the value of active learning among students are discussed. [ABSTRACT FROM AUTHOR]

A fundamental question about human behavior is whether fertility responds to disease risk. The standard economic theory of household fertility decision-making generates ambiguous predictions, and the response has large implications for human welfare. We examine the fertility response to the HIV/AIDS pandemic using national household survey data from 14 sub-Saharan African countries. Instrumental variable (IV) estimates using distance to the origin of the pandemic suggest that HIV/AIDS has increased the total fertility rate (TFR) and the number of surviving children. These results rekindle the debate about the fertility response to disease risk, particularly the HIV/AIDS pandemic, and highlight the question of whether the HIV/AIDS pandemic has reduced GDP per capita. [ABSTRACT FROM AUTHOR]

The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the haemopoietic, vascular and immune systems and is overexpressed in acute and chronic myeloid leukaemia progenitor cells. It belongs to the type I cytokine receptor family in which the α-subunits consist of two fibronectin III-like domains that bind cytokine, and a third, evolutionarily unrelated and topologically conserved, N-terminal domain (NTD) with unknown function. Here we show by crystallography that, while the NTD of IL3Rα is highly mobile in the presence of IL-3, it becomes surprisingly rigid in the presence of IL-3 K116W. Mutagenesis, biochemical and functional studies show that the NTD of IL3Rα regulates IL-3 binding and signalling and reveal an unexpected role in preventing spontaneous receptor dimerisation. Our work identifies a dual role for the NTD in this cytokine receptor family, protecting against inappropriate signalling and dynamically regulating cytokine receptor binding and function. [ABSTRACT FROM AUTHOR]

This article examines the effect of introducing a new HIV/AIDS service-prevention of mother-to-child transmission of HIV (PMTCT)-on overall quality of prenatal and postnatal care. My results suggest that local PMTCT introduction in Zambia may have actually increased all-cause child mortality in the short term. There is some evidence that vaccinations may have declined in the short term in association with local PMTCT introduction, suggesting that the new service may have partly crowded out existing pediatric health services. [ABSTRACT FROM AUTHOR]

The endocycle is a variant cell cycle consisting of successive DNA synthesis and gap phases that yield highly polyploid cells. Although essential for metazoan development, relatively little is known about its control or physiologic role in mammals. Using lineage-specific cre mice we identified two opposing arms of the E2F program, one driven by canonical transcription activation (E2F1, E2F2 and E2F3) and the other by atypical repression (E2F7 and E2F8), that converge on the regulation of endocycles in vivo. Ablation of canonical activators in the two endocycling tissues of mammals, trophoblast giant cells in the placenta and hepatocytes in the liver, augmented genome ploidy, whereas ablation of atypical repressors diminished ploidy. These two antagonistic arms coordinate the expression of a unique G2/M transcriptional program that is critical for mitosis, karyokinesis and cytokinesis. These results provide in vivo evidence for a direct role of E2F family members in regulating non-traditional cell cycles in mammals. [ABSTRACT FROM AUTHOR]

Background: The Drug Burden Index (DBI), a measure of an individual's exposure to anticholinergic and sedative medications, is associated with functional impairment in community-dwelling, older people. In people from residential aged care facilities (RACFs), DBI score does not appear to be associated with functional impairment, but is associated with an increased risk of falls. Objective: We investigated the associations between increasing DBI score and mortality in older adults living in RACFs. Methods: Study participants (n = 602; 70.9%female), recruited from 51 RACFs in Sydney, Australia, had a mean- standard deviation (SD) age of 85.7- 6.4 years and a mean - SD DBI score of 0.58 - 0.64. Results: Exposure to anticholinergic medication was 33.6% and sedative medications 41.9%. All-cause mortality after a variable follow-up time (774-1269 days) was 36.2% (n = 218), with the leading causes of death classified as stroke (n = 46; 21.1%), ischaemic heart disease/cardiovascular system (n = 44; 20.2%) and pneumonia (n = 31; 14.2%). One-year mortality multivariate models showed that the DBI categories low (n = 260; hazard ratio [HR] 1.13; 95% CI 0.82, 1.57) and high (n = 153; HR 1.19; 95% CI 0.82, 1.74) were not associated with mortality. This lack of a significant association remained after dichotomization into the anticholinergic and sedative components of the DBI. Conclusions: We found that with high exposure to anticholinergic and sedative medications, there was no significant association between increasing DBI score and all-cause mortality in old individuals living in RACFs. Further research into the adverse effects of medication use on the mortality of institutionalized older individuals is needed. [ABSTRACT FROM AUTHOR]

In this paper we report the results of a study which investigated the affordances of multi-user virtual environments (MUVEs) for collaborative learning from a design perspective. Utilizing a mixed methods approach, we conducted a comparative study of the effect of varying representational and interactional design features on a collaborative design activity in three online synchronous environments. We compared environments featuring multiple modes of interaction (MUVEs), shared representations (text chat and 2D still images) and text-only features. Sixty-one students enrolled in an undergraduate course on Child Development participated in the study. Participants were asked to design a theoretically-based, developmentally appropriate, preschool classroom setting. Students were randomly assigned to one of three online learning environments that provided varying levels of representation and interaction. Significant differences in collaborative problem solving interactions were found. Participants in the shared representations + text condition evidenced stronger learning outcomes as regards substantive discussion and integration of child development concepts; while participants in the MUVE condition reported the most enjoyment with the experience. These findings are explained by the concepts of representational guidance, representational bias, educational affordances and interface design metaphors. Suggestions for the design of MUVEs for collaborative learning are provided. [ABSTRACT FROM AUTHOR]

Death receptors (DRs) are members of the tumor necrosis factor receptor superfamily that possess a cytoplasmic death domain (DD). DRs regulate important operational and homeostatic aspects of the immune system. They transmit signals through apical protein complexes, which are nucleated by the DD adaptors FADD and TRADD, to control cellular outcomes that range from apoptosis to gene activation. FADD and TRADD also nucleate several distal signaling complexes, which mediate cross-talk between distinct DR signaling pathways. Moreover, together with other DR signal transducers, FADD and TRADD participate in functional complexes assembled by certain non-DR immune cell receptors, such as pattern-recognition receptors. Thus, DR signal transducers may provide important nodes of coordination in immune signaling networks. [ABSTRACT FROM AUTHOR]

The importance of conventional dendritic cells (cDCs) in the processing and presentation of antigen is well established, but the contribution of plasmacytoid dendritic cells (pDCs) to these processes, and hence to T cell immunity, remains unclear. Here we showed that unlike cDCs, pDCs continued to synthesize major histocompatibility complex (MHC) class II molecules and the MHC class II ubiquitin ligase MARCH1 long after activation. Sustained MHC class II–peptide complex formation, ubiquitination and turnover rendered pDCs inefficient in the presentation of exogenous antigens but enabled pDCs to continuously present endogenous viral antigens in their activated state. As the antigen-presenting abilities of cDCs and pDCs are fundamentally distinct, these two cell types may activate largely nonoverlapping repertoires of CD4+ T cells. [ABSTRACT FROM AUTHOR]

TH-17 cells are a distinct lineage of proinflammatory T helper cells that are essential for autoimmune disease. In mice, commitment to the TH-17 lineage is dependent on transforming growth factor-β and interleukin 6 (IL-6). Here we demonstrate that IL-23 and IL-1β induced the development of human TH-17 cells expressing IL-17A, IL-17F, IL-22, IL-26, interferon-γ, the chemokine CCL20 and transcription factor RORγt. In situ, TH-17 cells were identified by expression of the IL-23 receptor and the memory T cell marker CD45RO. Psoriatic skin lesions contained IL-23-producing dendritic cells and were enriched in the cytokines produced by human TH-17 cells that promote the production of antimicrobial peptides in human keratinocytes. Our data collectively indicate that human and mouse TH-17 cells require distinct factors during differentiation and that human TH-17 cells may regulate innate immunity in epithelial cells. [ABSTRACT FROM AUTHOR]

The mechanisms responsible for the immunosuppression associated with sepsis or some chronic blood infections remain poorly understood. Here we show that infection with a malaria parasite (Plasmodium berghei) or simple systemic exposure to bacterial or viral Toll-like receptor ligands inhibited cross-priming. Reduced cross-priming was a consequence of downregulation of cross-presentation by activated dendritic cells due to systemic activation that did not otherwise globally inhibit T cell proliferation. Although activated dendritic cells retained their capacity to present viral antigens via the endogenous major histocompatibility complex class I processing pathway, antiviral responses were greatly impaired in mice exposed to Toll-like receptor ligands. This is consistent with a key function for cross-presentation in antiviral immunity and helps explain the immunosuppressive effects of systemic infection. Moreover, inhibition of cross-presentation was overcome by injection of dendritic cells bearing antigen, which provides a new strategy for generating immunity during immunosuppressive blood infections. [ABSTRACT FROM AUTHOR]

Several studies have indicated that CD8+ T cells require CD4+ T cell help for memory formation. Evidence suggests that such help can be antigen independent, challenging whether the 'licensing' of dendritic cells (DCs) by CD4+ T cells is ever required for cytotoxic T lymphocyte (CTL) responses. We show here that help is essential for the generation of CTL immunity to herpes simplex virus 1 and that CD4+ T cells mediate help in a cognate, antigen-specific way. We provide direct in vivo evidence for DC licensing by helper T cells and show that licensing is rapid and essential for the formation of effector and memory CTLs. In situations in which DCs are poorly licensed by pathogen-derived signals, our findings suggest that CTL immunity may be heavily dependent on cognate DC licensing. [ABSTRACT FROM AUTHOR]

Investigates whether there are specific characteristics which distinguish small firms which switch banks from those which only consider switching and in particular tests whether there is any evidence of the 'informational capture' of smaller firms in the banking relationship. Data, method and variables; Empirical results and conclusion.

Despite the clear association between myocardial injury, heart failure and depressed myocardial energetics, little is known about upstream signals responsible for remodeling myocardial metabolism after pathological stress. Here, we report increased mitochondrial calmodulin kinase II (CaMKII) activation and left ventricular dilation in mice one week after myocardial infarction (MI) surgery. By contrast, mice with genetic mitochondrial CaMKII inhibition are protected from left ventricular dilation and dysfunction after MI. Mice with myocardial and mitochondrial CaMKII overexpression (mtCaMKII) have severe dilated cardiomyopathy and decreased ATP that causes elevated cytoplasmic resting (diastolic) Ca2+ concentration and reduced mechanical performance. We map a metabolic pathway that rescues disease phenotypes in mtCaMKII mice, providing insights into physiological and pathological metabolic consequences of CaMKII signaling in mitochondria. Our findings suggest myocardial dilation, a disease phenotype lacking specific therapies, can be prevented by targeted replacement of mitochondrial creatine kinase or mitochondrial-targeted CaMKII inhibition. Little is known about how cardiac metabolism remodels following cardiac injury. Here, the authors show that mitochondrial CaMKII plays an important role in remodeling cardiac metabolism after injury and that replacement of mitochondrial creatine kinase improves energetics and protects against adverse remodeling. [ABSTRACT FROM AUTHOR]

A correction to the article "Can Disease Specific Funding Harm Health? Child Mortality in the Shadow of HIV/AIDS Service Expansion" that was published in the previous issue. [ABSTRACT FROM AUTHOR]