Detection of Hostile Intent by Spatial Movements.

OBJECTIVE: The ability of people to infer intentions from movement of other vessels was investigated. Across three levels of variability in movements in the path of computer-controlled ships, participants attempted to determine which entity was hostile. BACKGROUND: Detection of hostile intentions through spatial movements of vessels is important in an array of real-world scenarios. This experiment sought to determine baseline abilities of humans to do so. METHODS: Participants selected a discrete movement direction of their ship. Six other ships' locations then updated. A single entity displayed one of two hostile behaviors: shadowing, which involved mirroring the participant's vessel's movements; and hunting, which involved closing in on the participant's vessel. Trials allowed up to 35 moves before identifying the hostile ship and its behavior. Uncertainty was introduced through adding variability to ships' movements such that their path was 0%, 25%, or 50% random. RESULTS: Even with no variability in the ships' movements, accurate detection was low, identifying the hostile entity about 60% of the time. Variability in the paths decreased detection. Detection of hunting was strongly degraded by distance between ownship and the hostile ship, but shadowing was not. Strategies employing different directions of movement across the trial, but also featuring some runs of consecutive movements, facilitated detection. CONCLUSIONS: Early identification of threats based on movement characteristics alone is likely to be difficult, but particularly so when adversaries employ some level of uncertainty to mask their intentions. These findings highlight the need to develop decision aids to support human performance.

Rendezvous Under Temporal Uncertainty.

OBJECTIVE: Three experiments sought to understand performance limitations in controlling a ship attempting to meet another moving ship that approached from various trajectories. The influence of uncertainty, resulting from occasional unpredictable delays in one's own movement, was examined. BACKGROUND: Cognitive elements of rendezvous have been little studied. Related work such as the planning fallacy and bias toward underestimating time-to-contact imply a tendency toward late arrival at a rendezvous. METHODS: In a simplified simulation, participants controlled the speed and/or heading of their own ship once per scenario to try to rendezvous with another ship. Forty-five scenarios of approximately 30 s were conducted with different starting geometries and, in two of three experiments, with different frequencies and lengths of the unexpected delays. RESULTS: Perfect rendezvous were hard to obtain, with a general tendency to arrive late and pass behind the target vessel, although this was dependent on the angle of approach and relative speed. When occasional delays were introduced, less frequent but longer delays disrupted performance more than shorter but more frequent delays. Where delays were possible, but no delay occurred, there was no longer evidence of a general tendency to more frequently pass behind the target ship. Additionally, people did not wait to see if the unpredictable delays would occur before executing a course of action. Different control strategies were deployed and dual axis control was preferred. CONCLUSIONS: The tendency to arrive late and the influence of the possibility of uncertain delays are discussed in relationship to control strategies.

Nautical Collision Avoidance : The Cognitive Challenges of Balancing Safety, Efficiency, and Procedures.

OBJECTIVE: Experimentally investigate maneuver decision preferences in navigating ships to avoid a collision. How is safety (collision avoidance) balanced against efficiency (deviation from path and delay) and rules of the road under conditions of both trajectory certainty and uncertainty. BACKGROUND: Human decision error is a prominent factor in nautical collisions, but the multiple factors of geometry of collisions and role of uncertainty have been little studied in empirical human factors literature. APPROACH: Eighty-seven Mechanical Turk participants performed in a lower fidelity ship control simulation, depicting ownship and a cargo ship hazard on collision or near-collision trajectories of various conflict geometries, while controlling heading and speed with the sluggish relative dynamics. Experiment 1 involved the hazard on a straight trajectory. In Experiment 2, the hazard could turn on unpredictable trials. Participants were rewarded for efficiency and penalized for collisions or close passes. RESULTS: Participants made few collisions, but did so more often when on a collision path. They sometimes violated the instructed rules of the road by maneuvering in front of the hazard ship's path. They preferred speed control to heading control. Performance degraded in conditions of uncertainty. CONCLUSION: Data reveal an understanding of maneuver decisions and conditions that affect the balance between safety and efficiency. APPLICATION: The simulation and data highlight the degrading role of uncertainty and provide a foundation upon which more complex questions can be asked, asked of more trained navigators, and decision support tools examined.

Pent-up demand for care among dual-eligible victims of elder financial exploitation in Maine.

Elder financial exploitation (EFE), the misuse of a vulnerable adult's property or resources for personal gain, is a form of elder abuse. This study addresses whether dual-eligible EFE victims were experiencing pent-up demand for health services alleviated through investigation by Adult Protective Services (APS). A quasi-experimental design addressed health service utilization and costs for 131 dual-eligible Maine APS clients over age 60 with substantiated allegations of EFE relative to comparable non-APS controls. APS case files spanning 2007-2012 were linked to 2006-2014 Medicare and Medicaid claims data. Service utilization and costs were analyzed 1 year prior, during, and 2 years after the initial APS investigation. Difference in differences logistic regression and generalized linear models addressed the likelihood of incurring costs and expenditure levels relative to matched controls, respectively. Victims of EFE had higher overall odds of using inpatient and long-term services and supports (LTSS) and higher odds of using LTSS post-investigation than controls. Higher overall levels of outpatient and prescriptions expenditures and higher inpatient expenditures during the APS event year contributed toward APS clients incurring $1,142 higher PMPM total costs than controls. Victims of EFE were experiencing significant pent-up demand for health services post-APS involvement.

Post-pandemic influenza A/H1N1pdm09 is associated with more severe outcomes than A/H3N2 and other respiratory viruses in adult hospitalisations.

This study compares the frequency and severity of influenza A/H1N1pdm09 (A/H1), influenza A/H3N2 (A/H3) and other respiratory virus infections in hospitalised patients. Data from 17 332 adult hospitalised patients admitted to Sir Charles Gairdner Hospital, Perth, Western Australia, with a respiratory illness between 2012 and 2015 were linked with data containing reverse transcription polymerase chain reaction results for respiratory viruses including A/H1, A/H3, influenza B, human metapneumovirus, respiratory syncytial virus and parainfluenza. Of these, 1753 (10.1%) had test results. Multivariable regression analyses were conducted to compare the viruses for clinical outcomes including ICU admission, ventilation, pneumonia, length of stay and death. Patients with A/H1 were more likely to experience severe outcomes such as ICU admission (OR 2.5, 95% CI 1.2-5.5, P = 0.016), pneumonia (OR 3.0, 95% CI 1.6-5.7, P < 0.001) and lower risk of discharge from hospital (indicating longer lengths of hospitalisation; HR 0.64 95% CI 0.47-0.88, P = 0.005), than patients with A/H3. Patients with a non-influenza respiratory virus were less likely to experience severe clinical outcomes than patients with A/H1, however, had similar likelihood when compared to patients with A/H3. Patients hospitalised with A/H1 had higher odds of severe outcomes than patients with A/H3 or other respiratory viruses. Knowledge of circulating influenza strains is important for healthcare preparedness.

Anchoring and Adjustment in Uncertain Spatial Trajectory Prediction.

OBJECTIVE: The aim of this study was to explore the impact of prior information on spatial prediction and understanding of variability. BACKGROUND: In uncertain spatial prediction tasks, such as hurricane forecasting or planning search-and-rescue operations, decision makers must consider the most likely case and the distribution of possible outcomes. Base performance on these tasks is varied (and in the case of understanding the distribution, often poor). Humans must update mental models and predictions with new information, sometimes under cognitive workload. METHOD: In a spatial-trajectory prediction task, participants were anchored on accurate or inaccurate information, or not anchored, regarding the future behavior of an object (both average behavior and the variability). Subsequently, they predicted an object's future location and estimated its likelihood at multiple locations. In a second experiment, participants repeated the process under varying levels of external cognitive workload. RESULTS: Anchoring influenced understanding of most likely predicted location, with fairly rapid adjustment following inaccurate anchors. Increasing workload resulted in decreased overall performance and an impact on the adjustment component of the task. Overconfidence was present in all conditions. CONCLUSION: Prior information exerted short-term influence on spatial predictions. Cognitive load impaired users' ability to effectively adjust to new information. Accurate graphical anchors did not improve user understanding of variability. APPLICATION: Prior briefings or forecasts about spatiotemporal trajectories affect decisions even in the face of initial contradictory information. To best support spatial prediction tasks, efforts also need to be made to separate extraneous load-causing tasks from the process of integrating new information. Implications are discussed.

Effect of Visualization Training on Uncertain Spatial Trajectory Predictions.

OBJECTIVE: The goal of this study was to explore the ways in which visualizations influence the prediction of uncertain spatial trajectories (e.g., the unknown path of a downed aircraft or future path of a hurricane) and participant overconfidence in such prediction. BACKGROUND: Previous research indicated that spatial predictions of uncertain trajectories are challenging and are often associated with overconfidence. Introducing a visualization aid during training may improve the understanding of uncertainty and reduce overconfidence. METHOD: Two experiments asked participants to predict the location of various trajectories at a future time. Mean and variance estimates were compared for participants who were provided with a visualization and those who were not. RESULTS: In Experiment 1, participants exhibited less error in mean estimations when a linear visualization was present but performed worse than controls once the visualization was removed. Similar results were shown in Experiment 2, with a nonlinear visualization. However, in both experiments, participants who were provided with a visualization did not retain any advantage in their variance estimations once the visualization was removed. CONCLUSIONS: Visualizations may support spatial predictions under uncertainty, but they are associated with benefits and costs for the underlying knowledge being developed. APPLICATION: Visualizations have the potential to influence how people make spatial predictions in the presence of uncertainty. Properly designed and implemented visualizations may help mitigate the cognitive biases related to such predictions.

DMRT1 is required for Müllerian duct formation in the chicken embryo.

DMRT1 is a conserved transcription factor with a central role in gonadal sex differentiation. In all vertebrates studied, DMRT1 plays an essential function in testis development and/or maintenance. No studies have reported a role for DMRT1 outside the gonads. Here, we show that DMRT1 is expressed in the paired Müllerian ducts in the chicken embryo, where it is required for duct formation. DMRT1 mRNA and protein are expressed in the early forming Müllerian ridge, and in cells undergoing an epithelial to mesenchyme transition during duct morphogenesis. RNAi-mediated knockdown of DMRT1 in ovo causes a greatly reduced mesenchymal layer, which blocks caudal extension of the duct luminal epithelium. Critical markers of Müllerian duct formation in mammals, Pax2 in the duct epithelium and Wnt4 in the mesenchyme, are conserved in chicken and their expression disrupted in DMRT1 knockdown ducts. We conclude that DMRT1 is required for the early steps of Müllerian duct development. DMRT1 regulates Müllerian ridge and mesenchyme formation and its loss blocks caudal extension of the duct. While DMRT1 plays an important role during testis development and maintenance in many vertebrate species, this is the first report showing a requirement for DMRT1 in Müllerian duct development.

Vascular smooth muscle desensitization in rabbit epigastric and mesenteric arteries during hemorrhagic shock.

The decompensatory phase of hemorrhage (shock) is caused by a poorly defined phenomenon termed vascular hyporeactivity (VHR). VHR may reflect an acute in vivo imbalance in levels of contractile and relaxant stimuli favoring net vascular smooth muscle (VSM) relaxation. Alternatively, VHR may be caused by intrinsic VSM desensitization of contraction resulting from prior exposure to high levels of stimuli that temporarily adjusts cell signaling systems. Net relaxation, but not desensitization, would be expected to resolve rapidly in an artery segment removed from the in vivo shock environment and examined in vitro in a fresh solution. Our aim was to 1) induce shock in rabbits and apply an in vitro mechanical analysis on muscular arteries isolated pre- and postshock to determine whether VHR involves intrinsic VSM desensitization, and 2) identify whether net VSM relaxation induced by nitric oxide and cyclic nucleotide-dependent protein kinase activation in vitro can be sustained for some time after relaxant stimulus washout. The potencies of phenylephrine- and histamine-induced contractions in in vitro epigastric artery removed from rabbits posthemorrhage were decreased by ∼0.3 log units compared with the control contralateral epigastric artery removed prehemorrhage. Moreover, a decrease in KCl-induced tonic, relative to phasic, tension of in vitro mesenteric artery correlated with the degree of shock severity as assessed by rates of lactate and K(+) accumulation. VSM desensitization was also caused by tyramine in vivo and PE in vitro, but not by relaxant agents in vitro. Together, these results support the hypothesis that VHR during hemorrhagic decompensation involves contractile stimulus-induced long-lasting, intrinsic VSM desensitization.

Overconfidence in Projecting Uncertain Spatial Trajectories.

OBJECTIVE: The aim of this study was to understand factors that influence the prediction of uncertain spatial trajectories (e.g., the future path of a hurricane or ship) and the role of human overconfidence in such prediction. BACKGROUND: Research has indicated that human prediction of uncertain trajectories is difficult and may well be subject to overconfidence in the accuracy of forecasts as is found in event prediction, a finding that indicates that humans insufficiently appreciate the contributions of variance in nature to their predictions. METHOD: In two experiments, our paradigm required participants to observe a starting point, a position at time T, and then make a prediction of the location of the trajectory at time NT. They experienced several trajectories from the same underlying model but perturbed by random variance in heading and speed. RESULTS: In Experiment 1A, people predicted linear paths well and were better in heading predictions than in speed predictions. However, participants greatly underestimated the variance in predicted location, indicating overconfidence. In Experiment 1B, the effect was replicated with frequencies rather than probabilities used in variance estimates. In Experiment 2, people predicted nonlinear trajectories poorly, and overconfidence was again observed. Overconfidence was reduced on the more difficult predictions. In both main experiments, those better at predicting the mean were not better at predicting the variance. CONCLUSIONS: Predicting the level of uncertainty in spatial trajectories is not well done and may involve qualitatively different abilities than prediction of the mean. APPLICATION: Improving real-world performance at prediction demands developing better understanding of variability, not just the average case. Biases in prediction of uncertainty may be addressed through debiasing training and/or visualization tools that could assist in more calibrated action planning.

Spatiotemporal expression patterns of doublesex and mab-3 related transcription factor 1 in the chicken developing gonads and Mullerian ducts.

Sex of birds is genetically determined by the inheritance of sex chromosomes (ZZ for male and ZW for female), and the Z-linked gene named doublesex and mab-3 related transcription factor 1 (DMRT1) is a candidate sex-determining gene in avian species. However, the mechanisms underlying sex determination in birds are not yet understood, and the expression patterns of the DMRT1 protein in urogenital tissues have not been identified. In the current study, we used immunohistochemistry to investigate the detailed expression patterns of the DMRT1 protein in the urogenital systems (including Müllerian ducts) in male and female chicken embryos throughout embryonic development. Gonadal somatic cells in the male indifferent gonads showed stronger expressions of DMRT1 compared with those in the female indifferent gonads well before the presumptive period of the sex determination, and Sertoli cells forming testicular cords expressed DMRT1 in the testes after sex determination. Germ cells expressed DMRT1 equally in males and females after sex determination. The expression was continuous in males, but in females it gradually disappeared from the germ cells in the central part of the cortex of the left ovary toward both edges. The DMRT1 was also detected in the tubal ridge, which is a precursor of the Müllerian duct, and at the mesenchyme and outermost coelomic epithelium of the Müllerian duct in both sexes. Strong expression was observed in the males, but it was restricted to coelomic epithelium after the regression of the duct started. Thus, we observed the detailed spatiotemporal expression patterns of DMRT1 in the developing chicken urogenital systems throughout embryonic development, suggesting its various roles in the development of urogenital tissues in the chicken embryo.

Supporting detection of hostile intentions: automated assistance in a dynamic decision-making context.

In a dynamic decision-making task simulating basic ship movements, participants attempted, through a series of actions, to elicit and identify which one of six other ships was exhibiting either of two hostile behaviors. A high-performing, although imperfect, automated attention aid was introduced. It visually highlighted the ship categorized by an algorithm as the most likely to be hostile. Half of participants also received automation transparency in the form of a statement about why the hostile ship was highlighted. Results indicated that while the aid's advice was often complied with and hence led to higher accuracy with a shorter response time, detection was still suboptimal. Additionally, transparency had limited impacts on all aspects of performance. Implications for detection of hostile intentions and the challenges of supporting dynamic decision making are discussed.

How history trails and set size influence detection of hostile intentions.

Previous research suggests people struggle to detect a series of movements that might imply hostile intentions of a vessel, yet this ability is crucial in many real world Naval scenarios. To investigate possible mechanisms for improving performance, participants engaged in a simple, simulated ship movement task. One of two hostile behaviors were present in one of the vessels: Shadowing-mirroring the participant's vessel's movements; and Hunting-closing in on the participant's vessel. In the first experiment, history trails, showing the previous nine positions of each ship connected by a line, were introduced as a potential diagnostic aid. In a second experiment, the number of computer-controlled ships on the screen also varied. Smaller set size improved detection performance. History trails also consistently improved detection performance for both behaviors, although still falling well short of optimal, even with the smaller set size. These findings suggest that working memory plays a critical role in performance on this dynamic decision making task, and the constraints of working memory capacity can be decreased through a simple visual aid and an overall reduction in the number of objects being tracked. The implications for the detection of hostile intentions are discussed.

Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes.

Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) offers safe and effective therapy for certain viral infections and could prove useful in the eradication of tumor cells. Whether or not the infused T cells persist for extended periods, retaining their ability to expand in response to antigenic stimulation, is not known. We now report long-term detection of gene-marked Epstein-Barr virus (EBV)-specific CTLs in immunocompromised patients at risk for the development of EBV lymphoproliferative disease. Infusions of CTLs not only restored cellular immune responses against EBV, but also established populations of CTL precursors that could respond to in vivo or ex vivo challenge with the virus for as long as 18 months. Our findings support wider use of antigen-specific CTLs in adoptive immunotherapy.

Matched controlled study to evaluate the effect of endometrial polyps on pregnancy and implantation rates following in vitro fertilization-embryo transfer (IVF-ET).

PURPOSE: To determine if endometrial polyps negatively effect outcome following in vitro fertilization-embryo transfer (IVF-ET) and whether hysteroscopic resection improves pregnancy and implantation rates and/or decreases miscarriage rates. METHODS: Retrospective study with two matched controlled groups (polyps vs no polyps) based on age and previous number of IVF failures. The polyp group was further stratified by whether polypectomy was performed or not. RESULTS: There was no difference or even trend for lower pregnancy rates or higher miscarriage rates with the presence of endometrial polyps. CONCLUSIONS: These data do not support the recommendation for hysteroscopic resection of endometrial polyps to aid conception rates.

Evaluation of reproducible and transparent research practices in pulmonology.

BACKGROUND: Study reproducibility is valuable for validating or refuting results. Provision of reproducibility indicators, such as materials, protocols, and raw data in a study improve its potential for reproduction. Efforts to reproduce noteworthy studies in the biomedical sciences have resulted in an overwhelming majority of them being found to be unreplicable, causing concern for the integrity of research in other fields, including medical specialties. Here, we analyzed the reproducibility of studies in the field of pulmonology. METHODS: 500 pulmonology articles were randomly selected from an initial PubMed search for data extraction. Two authors scoured these articles for reproducibility indicators including materials, protocols, raw data, analysis scripts, inclusion in systematic reviews, and citations by replication studies as well as other factors of research transparency including open accessibility, funding source and competing interest disclosures, and study preregistration. FINDINGS: Few publications included statements regarding materials (10%), protocols (1%), data (15%), and analysis script (0%) availability. Less than 10% indicated preregistration. More than half of the publications analyzed failed to provide a funding statement. Conversely, 63% of the publications were open access and 73% included a conflict of interest statement. INTERPRETATION: Overall, our study indicates pulmonology research is currently lacking in efforts to increase replicability. Future studies should focus on providing sufficient information regarding materials, protocols, raw data, and analysis scripts, among other indicators, for the sake of clinical decisions that depend on replicable or refutable results from the primary literature.

Properties of synovial cells in culture.

Derangements of synovial membranes and cartilage occur early in the course of rheumatoid arthritis. These important alterations of the joint tissues are probably the in vivo reflections of complicated inflammatory and immunological events. In our laboratory we have been interested in studying alterations of synovial lining cells in rheumatoid arthritis, most recently by the use of serially propagated cultures of these cells. The cellular traits described in such cultures serve to distinguish these synovial cells from other types of human fibroblasts, and several cellular alterations have been found in cultures derived from membranes of rheumatoid arthritic patients. One important finding is increased resistance of cultured rheumatoid cells to infection with rubella and NDV; this and other cellular changes suggest the possibility of an occult virus infection in the rheumatoid cells. Such viral persistence could be theoretically linked with the immunologic aberrations in rheumatoid arthritis, discussed in this symposium.

Interleukin 4 (B cell stimulatory factor 1) can mediate the induction of lymphokine-activated killer cell activity directed against fresh tumor cells.

Interleukin 4 (IL-4) expresses multiple biologic activities, including B cell, mast cell, and T cell stimulation. We showed that the incubation of resting splenocytes from C57BL/6 mice solely in purified native or recombinant mouse IL-4 results in the generation of lymphokine-activated killer (LAK) activity directed against fresh, syngeneic sarcoma cells. The precursor activated by IL-4 expresses surface asialo-GM1. In addition, IL-4 is capable of amplifying the splenic LAK activity induced by recombinant IL-2. The generation, by IL-4, of killer cells with broad antitumor reactivity raises the possibility of using IL-4 alone or in combination with IL-2 in the immunotherapy of cancer in animal models.

MHC Class III products: an electron microscopic study of the C3 convertases of human complement.

We have reported a transmission electron microscopic study of the two C3 convertases of human complement and their precursors. The corresponding proteins and complexes of the classical and alternative pathway appear very similar. Cofactors C3b and C4b are nearly indistinguishable and display a characteristic but highly irregular substructure. C2 and Factor B are globular with diameters of 85 +/- 8 A and 80 +/- 8 A and both consist of three discrete globular domains each approximately 40 A in diameter. Bb and C2a each contain two domains connected by a short linker segment. Both domains of Bb and one domain of C2a are 42 A in diameter (28 kd), while the second domain of C2 is 47 A in diameter (39 kd). Attachment of the enzymatic subunits to cofactors occurs through one domain only.

Fas antigen stimulation induces marked apoptosis of T lymphocytes in human immunodeficiency virus-infected individuals.

Apoptosis (programmed cell death) of T lymphocytes has been proposed as a mechanism which plays an important role in the pathogenesis of human immunodeficiency virus (HIV) disease. Activation of Fas (CD95) can either result in costimulation of proliferation and cytokine production or in the induction of apoptosis of T lymphocytes. This raises the possibility that Fas is involved in the observed T cell apoptosis during HIV disease. In this report we show that peripheral blood CD4+ and CD8+ T lymphocytes from HIV-infected individuals undergo apoptosis in vitro in response to antibody stimulation (cross-linking) of Fas at a much higher frequency than from uninfected controls. This anti-Fas-induced T cell apoptosis is markedly higher than spontaneous T cell apoptosis in HIV-infected individuals. Antibodies against other members of the tumor necrosis factor (TNF)/nerve growth factor receptor family such as CD27, CD30, CD40, 4-1BB, p55 TNF receptor, p75 TNF receptor, and TNF receptor-related protein did not result in any increase of T cell apoptosis above that spontaneously observed in HIV+ individuals. Anti-Fas-induced apoptosis was much higher in symptomatic HIV-infected individuals; and the magnitude of anti-Fas-induced CD4+ T cell apoptosis correlated inversely with peripheral blood CD4+ T cell absolute counts. Surface expression of Fas on T cells was also found to be higher in HIV-infected individuals. Resting and activated CD4+ and CD8+ T cells both underwent apoptosis in response to anti-Fas antibody. L-Selectin positive memory CD4+ T cells were especially susceptible to anti-Fas-induced apoptosis. These findings show that CD4+ and CD8+ T lymphocytes in HIV-infected individuals are primed in vivo to undergo apoptosis in response to Fas stimulation, suggesting that Fas signaling may be responsible for the T lymphocyte functional defects and depletion observed in HIV disease.