591 research outputs found
Learning Personalized Decision Support Policies
Individual human decision-makers may benefit from different forms of support
to improve decision outcomes. However, a key question is which form of support
will lead to accurate decisions at a low cost. In this work, we propose
learning a decision support policy that, for a given input, chooses which form
of support, if any, to provide. We consider decision-makers for whom we have no
prior information and formalize learning their respective policies as a
multi-objective optimization problem that trades off accuracy and cost. Using
techniques from stochastic contextual bandits, we propose , an
online algorithm to personalize a decision support policy for each
decision-maker, and devise a hyper-parameter tuning strategy to identify a
cost-performance trade-off using simulated human behavior. We provide
computational experiments to demonstrate the benefits of
compared to offline baselines. We then introduce , an
interactive tool that provides with an interface. We conduct
human subject experiments to show how learns policies
personalized to each decision-maker and discuss the nuances of learning
decision support policies online for real users.Comment: Working pape
Institutional Repositories for Public Engagement: Creating a Common Good Model for an Engaged Campus
Most higher-education institutions strive to be publicly engaged and community centered. These institutions leverage faculty, researchers, librarians, community liaisons, and communication specialists to meet this mission, but they have largely underutilized the potential of institutional repositories. Academic institutions can use institutional repositories to provide open access and long-term preservation to institutional gray literature, research data, university publications, and campus research products that have tangible, real-world applications for the communities they serve. Using examples from the University of Minnesota, this article demonstrates how making this content discoverable, openly accessible, and preserved for the future through an institutional repository not only increases the value of this publicly-engaged work but also creates a lasting record of a university’s public engagement efforts and contributes to the mission of the institution.Ope
FeedbackLogs: Recording and Incorporating Stakeholder Feedback into Machine Learning Pipelines
Even though machine learning (ML) pipelines affect an increasing array of
stakeholders, there is little work on how input from stakeholders is recorded
and incorporated. We propose FeedbackLogs, addenda to existing documentation of
ML pipelines, to track the input of multiple stakeholders. Each log records
important details about the feedback collection process, the feedback itself,
and how the feedback is used to update the ML pipeline. In this paper, we
introduce and formalise a process for collecting a FeedbackLog. We also provide
concrete use cases where FeedbackLogs can be employed as evidence for
algorithmic auditing and as a tool to record updates based on stakeholder
feedback
Citrobacter rodentium Relies on Commensals for Colonization of the Colonic Mucosa.
We investigated the role of commensals at the peak of infection with the colonic mouse pathogen Citrobacter rodentium. Bioluminescent and kanamycin (Kan)-resistant C. rodentium persisted avirulently in the cecal lumen of mice continuously treated with Kan. A single Kan treatment was sufficient to displace C. rodentium from the colonic mucosa, a phenomenon not observed following treatment with vancomycin (Van) or metronidazole (Met). Kan, Van, and Met induce distinct dysbiosis, suggesting C. rodentium relies on specific commensals for colonic colonization. Expression of the master virulence regulator ler is induced in germ-free mice, yet C. rodentium is only seen in the cecal lumen. Moreover, in conventional mice, a single Kan treatment was sufficient to displace C. rodentium constitutively expressing Ler from the colonic mucosa. These results show that expression of virulence genes is not sufficient for colonization of the colonic mucosa and that commensals are essential for a physiological infection course
Prospective study design and data analysis in UK Biobank
Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.</p
Synchronous vegetation response to the last glacial-interglacial transition in northwest Europe
The North Atlantic region experienced abrupt high-amplitude cooling at the onset of the Younger Dryas stadial. However, due to chronological uncertainties in the available terrestrial records it is unclear whether terrestrial ecosystem response to this event was instantaneous and spatially synchronous, or whether regional or time-transgressive lags existed. Here we use new palynological results from a robustly dated lake sediment sequence retrieved from lake Hämelsee (north Germany) to show that vegetation change started at 12,820 cal. yr BP, concurrent with the onset of changes in local climate. A comparison of the Hämelsee results to a compilation of precisely dated palynological records shows instant and, within decadal-scale dating uncertainty, synchronous response of the terrestrial plant community to Late-Glacial climate change across northwest Europe. The results indicate that the environmental impact of climate cooling was more severe than previously thought and illustrates the sensitivity of natural terrestrial ecosystems to external forcing. © 2022, The Author(s)
Closing the gap between science and management of cold-water refuges in rivers and streams
Human activities and climate change threaten coldwater organisms in freshwater eco-systems by causing rivers and streams to warm, increasing the intensity and frequency of warm temperature events, and reducing thermal heterogeneity. Cold-water refuges are discrete patches of relatively cool water that are used by coldwater organisms for thermal relief and short-term survival. Globally, cohesive management approaches are needed that consider interlinked physical, biological, and social factors of cold-water refuges. We review current understanding of cold-water refuges, identify gaps between science and management, and evaluate policies aimed at protecting thermally sensitive species. Existing policies include designating cold-water habitats, restricting fishing during warm periods, and implementing threshold temperature standards or guidelines. However, these policies are rare and uncoordinated across spatial scales and often do not consider input from Indigenous peoples. We propose that cold-water refuges be managed as dis-tinct operational landscape units, which provide a social and ecological context that is relevant at the watershed scale. These operational landscape units provide the founda-tion for an integrated framework that links science and management by (1) mapping and characterizing cold-water refuges to prioritize management and conservation actions, (2) leveraging existing and new policies, (3) improving coordination across jurisdictions, and (4) implementing adaptive management practices across scales. Our findings show that while there are many opportunities for scientific advancement, the current state of the sciences is sufficient to inform policy and management. Our proposed framework pro-vides a path forward for managing and protecting cold-water refuges using existing and new policies to protect coldwater organisms in the face of global change. behavioral thermoregulation, climate change adaptation, lotic ecosystem management, refugia, salmonids, temperature, thermal heterogeneity, thermal refugespublishedVersio
Lynch syndrome: barriers to and facilitators of screening and disease management
Background
Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing.
Methods
The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management.
Results
Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers.
Conclusions
Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology
A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family
The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, evaluate cell cycle perturbations upon knockdown in normal and cancer cells, and analyse their protein and mRNA expression in normal and cancer tissues. Using a novel FUSION algorithm, we integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality
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