63 research outputs found

    Investment of Corporate Cash

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    Increasing the Velocity of Corporate Funds

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    Incorporation of Eye-Tracking and Gaze Feedback to Characterize and Improve Radiologist Search Patterns of Chest X-rays: A Randomized Controlled Clinical Trial

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    Diagnostic errors in radiology often occur due to incomplete visual assessments by radiologists, despite their knowledge of predicting disease classes. This insufficiency is possibly linked to the absence of required training in search patterns. Additionally, radiologists lack consistent feedback on their visual search patterns, relying on ad-hoc strategies and peer input to minimize errors and enhance efficiency, leading to suboptimal patterns and potential false negatives. This study aimed to use eye-tracking technology to analyze radiologist search patterns, quantify performance using established metrics, and assess the impact of an automated feedback-driven educational framework on detection accuracy. Ten residents participated in a controlled trial focused on detecting suspicious pulmonary nodules. They were divided into an intervention group (received automated feedback) and a control group. Results showed that the intervention group exhibited a 38.89% absolute improvement in detecting suspicious-for-cancer nodules, surpassing the control group's improvement (5.56%, p-value=0.006). Improvement was more rapid over the four training sessions (p-value=0.0001). However, other metrics such as speed, search pattern heterogeneity, distractions, and coverage did not show significant changes. In conclusion, implementing an automated feedback-driven educational framework improved radiologist accuracy in detecting suspicious nodules. The study underscores the potential of such systems in enhancing diagnostic performance and reducing errors. Further research and broader implementation are needed to consolidate these promising results and develop effective training strategies for radiologists, ultimately benefiting patient outcomes.Comment: Submitted for Review in the Journal of the American College of Radiology (JACR

    Distinct Clinicopathologic Clusters of Persons with TDP-43 Proteinopathy

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    To better understand clinical and neuropathological features of TDP-43 proteinopathies, data were analyzed from autopsied research volunteers who were followed in the National Alzheimer’s Coordinating Center (NACC) data set. All subjects (n = 495) had autopsy-proven TDP-43 proteinopathy as an inclusion criterion. Subjects underwent comprehensive longitudinal clinical evaluations yearly for 6.9 years before death on average. We tested whether an unsupervised clustering algorithm could detect coherent groups of TDP-43 immunopositive cases based on age at death and extensive neuropathologic data. Although many of the brains had mixed pathologies, four discernible clusters were identified. Key differentiating features were age at death and the severity of comorbid Alzheimer’s disease neuropathologic changes (ADNC), particularly neuritic amyloid plaque densities. Cluster 1 contained mostly cases with a pathologic diagnosis of frontotemporal lobar degeneration (FTLD-TDP), consistent with enrichment of frontotemporal dementia clinical phenotypes including appetite/eating problems, disinhibition and primary progressive aphasia (PPA). Cluster 2 consisted of elderly limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) subjects without severe neuritic amyloid plaques. Subjects in Cluster 2 had a relatively slow cognitive decline. Subjects in both Clusters 3 and 4 had severe ADNC + LATE-NC; however, Cluster 4 was distinguished by earlier disease onset, swifter disease course, more Lewy body pathology, less neocortical TDP-43 proteinopathy, and a suggestive trend in a subgroup analysis (n = 114) for increased C9orf72 risk SNP rs3849942 T allele (Fisher’s exact test p value = 0.095). Overall, clusters enriched with neocortical TDP-43 proteinopathy (Clusters 1 and 2) tended to have lower levels of neuritic amyloid plaques, and those dying older (Clusters 2 and 3) had far less PPA or disinhibition, but more apathy. Indeed, 98% of subjects dying past age 85 years lacked clinical features of the frontotemporal dementia syndrome. Our study revealed discernible subtypes of LATE-NC and underscored the importance of age of death for differentiating FTLD-TDP and LATE-NC

    Climatic history of the northeastern United States during the past 3000 years

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    Many ecosystem processes that influence Earth system feedbacks – vegetation growth, water and nutrient cycling, disturbance regimes – are strongly influenced by multidecadal- to millennial-scale climate variations that cannot be directly observed. Paleoclimate records provide information about these variations, forming the basis of our understanding and modeling of them. Fossil pollen records are abundant in the NE US, but cannot simultaneously provide information about paleoclimate and past vegetation in a modeling context because this leads to circular logic. If pollen data are used to constrain past vegetation changes, then the remaining paleoclimate archives in the northeastern US (NE US) are quite limited. Nonetheless, a growing number of diverse reconstructions have been developed but have not yet been examined together. Here we conduct a systematic review, assessment, and comparison of paleotemperature and paleohydrological proxies from the NE US for the last 3000 years. Regional temperature reconstructions (primarily summer) show a long-term cooling trend (1000 BCE–1700 CE) consistent with hemispheric-scale reconstructions, while hydroclimate data show gradually wetter conditions through the present day. Multiple proxies suggest that a prolonged, widespread drought occurred between 550 and 750 CE. Dry conditions are also evident during the Medieval Climate Anomaly, which was warmer and drier than the Little Ice Age and drier than today. There is some evidence for an acceleration of the longer-term wetting trend in the NE US during the past century; coupled with an abrupt shift from decreasing to increasing temperatures in the past century, these changes could have wide-ranging implications for species distributions, ecosystem dynamics, and extreme weather events. More work is needed to gather paleoclimate data in the NE US to make inter-proxy comparisons and to improve estimates of uncertainty in reconstructions

    Under-Reporting of Road Traffic Mortality in Developing Countries: Application of a Capture-Recapture Statistical Model to Refine Mortality Estimates

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    Road traffic injuries are a major cause of preventable death in sub-Saharan Africa. Accurate epidemiologic data are scarce and under-reporting from primary data sources is common. Our objectives were to estimate the incidence of road traffic deaths in Malawi using capture-recapture statistical analysis and determine what future efforts will best improve upon this estimate. Our capture-recapture model combined primary data from both police and hospital-based registries over a one year period (July 2008 to June 2009). The mortality incidences from the primary data sources were 0.075 and 0.051 deaths/1000 person-years, respectively. Using capture-recapture analysis, the combined incidence of road traffic deaths ranged 0.192–0.209 deaths/1000 person-years. Additionally, police data were more likely to include victims who were male, drivers or pedestrians, and victims from incidents with greater than one vehicle involved. We concluded that capture-recapture analysis is a good tool to estimate the incidence of road traffic deaths, and that capture-recapture analysis overcomes limitations of incomplete data sources. The World Health Organization estimated incidence of road traffic deaths for Malawi utilizing a binomial regression model and survey data and found a similar estimate despite strikingly different methods, suggesting both approaches are valid. Further research should seek to improve capture-recapture data through utilization of more than two data sources and improving accuracy of matches by minimizing missing data, application of geographic information systems, and use of names and civil registration numbers if available

    Dark sectors 2016 Workshop: community report

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    This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

    A FRET-Based High Throughput Screening Assay to Identify Inhibitors of Anthrax Protective Antigen Binding to Capillary Morphogenesis Gene 2 Protein

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    Anti-angiogenic therapies are effective for the treatment of cancer, a variety of ocular diseases, and have potential benefits in cardiovascular disease, arthritis, and psoriasis. We have previously shown that anthrax protective antigen (PA), a non-pathogenic component of anthrax toxin, is an inhibitor of angiogenesis, apparently as a result of interaction with the cell surface receptors capillary morphogenesis gene 2 (CMG2) protein and tumor endothelial marker 8 (TEM8). Hence, molecules that bind the anthrax toxin receptors may be effective to slow or halt pathological vascular growth. Here we describe development and testing of an effective homogeneous steady-state fluorescence resonance energy transfer (FRET) high throughput screening assay designed to identify molecules that inhibit binding of PA to CMG2. Molecules identified in the screen can serve as potential lead compounds for the development of anti-angiogenic and anti-anthrax therapies. The assay to screen for inhibitors of this protein–protein interaction is sensitive and robust, with observed Z' values as high as 0.92. Preliminary screens conducted with a library of known bioactive compounds identified tannic acid and cisplatin as inhibitors of the PA-CMG2 interaction. We have confirmed that tannic acid both binds CMG2 and has anti-endothelial properties. In contrast, cisplatin appears to inhibit PA-CMG2 interaction by binding both PA and CMG2, and observed cisplatin anti-angiogenic effects are not mediated by interaction with CMG2. This work represents the first reported high throughput screening assay targeting CMG2 to identify possible inhibitors of both angiogenesis and anthrax intoxication

    The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): illuminating the functional diversity of eukaryotic life in the oceans through transcriptome sequencing

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    International audienceCurrent sampling of genomic sequence data from eukaryotes is relatively poor, biased, and inadequate to address important questions about their biology, evolution, and ecology; this Community Page describes a resource of 700 transcriptomes from marine microbial eukaryotes to help understand their role in the world's oceans
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