The Role of GIS to Enable Public-Sector Decision Making Under Conditions of Uncertainty

Uncertainty is inherent in environmental planning and decision making. For example, water managers in arid regions are attuned to the uncertainty of water supply due to prolonged periods of drought. To contend with multiple sources and forms of uncertainty, resource managers implement strategies and tools to aid in the exploration and interpretation of data and scenarios. Various GIS capabilities, such as statistical analysis, modeling and visualization are available to decision makers who face the challenge of making decisions under conditions of deep uncertainty. While significant research has lead to the inclusion and representation of uncertainty in GIS, existing GIS literature does not address how decision makers implement and utilize GIS as an assistive technology to contend with deep uncertainty. We address this gap through a case study of water managers in the Phoenix Metropolitan Area, examining how they engage with GIS in making decisions and coping with uncertainty. Findings of a qualitative analysis of water mangers reveal the need to distinguish between implicit and explicit uncertainty. Implicit uncertainty is linked to the decision-making process, and while understood, it is not displayed or revealed separately from the data. In contrast, explicit uncertainty is conceived as separate from the process and is something that can be described or displayed. Developed from twelve interviews with Phoenix-area water managers in 2005, these distinctions of uncertainty clarify the use of GIS in decision making. Findings show that managers use the products of GIS for exploring uncertainty (e.g., cartographic products). Uncertainty visualization emerged as a current practice, but definitions of what constitutes such visualizations were not consistent across decision makers. Additionally, uncertainty was a common and even sometimes helpful element of decision making; rather than being a hindrance, it is seen as an essential component of the process. These findings contradict prior research relating to uncertainty visualization where decision makers often express discomfort with the presence of uncertainty.

Special issue introduction: Approaching spatial uncertainty visualization to support reasoning and decision making

While research on uncertainty and decision-making has a long history across several disciplines, recent technological developments compel researchers to rethink how to best address and advance the understanding of how humans reason and make decisions under spatial uncertainty. This introduction presents a visual summary graphic to provide an overview of each article in this special issue. Upon viewing these visual summaries, the reader will find that each of these articles covers different topics in the uncertainty visualization domain, offering complementary research in this field. Extending this body of research and finding new ways to explore how these visualizations may help or hinder the analytical and reasoning process of humans continues to be a necessary step towards designing more effective uncertainty visualizations to support reasoning and decision-making

High-throughput sequencing of SARS-CoV-2 in wastewater provides insights into circulating variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) likely emerged from a zoonotic spill-over event and has led to a global pandemic. The public health response has been predominantly informed by surveillance of symptomatic individuals and contact tracing, with quarantine, and other preventive measures have then been applied to mitigate further spread. Non-traditional methods of surveillance such as genomic epidemiology and wastewater-based epidemiology (WBE) have also been leveraged during this pandemic. Genomic epidemiology uses high-throughput sequencing of SARS-CoV-2 genomes to inform local and international transmission events, as well as the diversity of circulating variants. WBE uses wastewater to analyse community spread, as it is known that SARS-CoV-2 is shed through bodily excretions. Since both symptomatic and asymptomatic individuals contribute to wastewater inputs, we hypothesized that the resultant pooled sample of population-wide excreta can provide a more comprehensive picture of SARS-CoV-2 genomic diversity circulating in a community than clinical testing and sequencing alone. In this study, we analysed 91 wastewater samples from 11 states in the USA, where the majority of samples represent Maricopa County, Arizona (USA). With the objective of assessing the viral diversity at a population scale, we undertook a single-nucleotide variant (SNV) analysis on data from 52 samples with \u3e90% SARS-CoV-2 genome coverage of sequence reads, and compared these SNVs with those detected in genomes sequenced from clinical patients. We identified 7973 SNVs, of which 548 were “novel” SNVs that had not yet been identified in the global clinical-derived data as of 17th June 2020 (the day after our last wastewater sampling date). However, between 17th of June 2020 and 20th November 2020, almost half of the novel SNVs have since been detected in clinical-derived data. Using the combination of SNVs present in each sample, we identified the more probable lineages present in that sample and compared them to lineages observed in North America prior to our sampling dates. The wastewater-derived SARS-CoV-2 sequence data indicates there were more lineages circulating across the sampled communities than represented in the clinical-derived data. Principal coordinate analyses identified patterns in population structure based on genetic variation within the sequenced samples, with clear trends associated with increased diversity likely due to a higher number of infected individuals relative to the sampling dates. We demonstrate that genetic correlation analysis combined with SNVs analysis using wastewater sampling can provide a comprehensive snapshot of the SARS-CoV-2 genetic population structure circulating within a community, which might not be observed if relying solely on clinical cases

Life Beyond the Solar System: Remotely Detectable Biosignatures

For the first time in human history, we will soon be able to apply to the scientific method to the question "Are We Alone?" The rapid advance of exoplanet discovery, planetary systems science, and telescope technology will soon allow scientists to search for life beyond our Solar System through direct observation of extrasolar planets. This endeavor will occur alongside searches for habitable environments and signs of life within our Solar System. While these searches are thematically related and will inform each other, they will require separate observational techniques. The search for life on exoplanets holds potential through the great diversity of worlds to be explored beyond our Solar System. However, there are also unique challenges related to the relatively limited data this search will obtain on any individual world

Discovery and Structural Optimization of Acridones as Broad-Spectrum Antimalarials.

Malaria remains one of the deadliest diseases in the world today. Novel chemoprophylactic and chemotherapeutic antimalarials are needed to support the renewed eradication agenda. We have discovered a novel antimalarial acridone chemotype with dual-stage activity against both liver-stage and blood-stage malaria. Several lead compounds generated from structural optimization of a large library of novel acridones exhibit efficacy in the following systems: (1) picomolar inhibition of in vitro Plasmodium falciparum blood-stage growth against multidrug-resistant parasites; (2) curative efficacy after oral administration in an erythrocytic Plasmodium yoelii murine malaria model; (3) prevention of in vitro Plasmodium berghei sporozoite-induced development in human hepatocytes; and (4) protection of in vivo P. berghei sporozoite-induced infection in mice. This study offers the first account of liver-stage antimalarial activity in an acridone chemotype. Details of the design, chemistry, structure-activity relationships, safety, metabolic/pharmacokinetic studies, and mechanistic investigation are presented herein

Discovery and Structural Optimization of Acridones as Broad-Spectrum Antimalarials

Malaria remains one of the deadliest diseases in the world today. Novel chemoprophylactic and chemotherapeutic antimalarials are needed to support the renewed eradication agenda. We have discovered a novel antimalarial acridone chemotype with dual-stage activity against both liver-stage and blood-stage malaria. Several lead compounds generated from structural optimization of a large library of novel acridones exhibit efficacy in the following systems: (1) picomolar inhibition of in vitro Plasmodium falciparum blood-stage growth against multidrug-resistant parasites; (2) curative efficacy after oral administration in an erythrocytic Plasmodium yoelii murine malaria model; (3) prevention of in vitro Plasmodium berghei sporozoite-induced development in human hepatocytes; and (4) protection of in vivo P. berghei sporozoite-induced infection in mice. This study offers the first account of liver-stage antimalarial activity in an acridone chemotype. Details of the design, chemistry, structure–activity relationships, safety, metabolic/pharmacokinetic studies, and mechanistic investigation are presented herein

Life Beyond the Solar System: Remotely Detectable Biosignatures

For the first time in human history, we will soon be able to apply the scientific method to the question "Are We Alone?" The rapid advance of exoplanet discovery, planetary systems science, and telescope technology will soon allow scientists to search for life beyond our Solar System through direct observation of extrasolar planets. This endeavor will occur alongside searches for habitable environments and signs of life within our Solar System. While the searches are thematically related and will inform each other, they will require separate observational techniques. The search for life on exoplanets holds potential through the great diversity of worlds to be explored beyond our Solar System. However, there are also unique challenges related to the relatively limited data this search will obtain on any individual world. This white paper reviews the scientific community's ability to use data from future telescopes to search for life on exoplanets. This material summarizes products from the Exoplanet Biosignatures Workshop Without Walls (EBWWW). The EBWWW was constituted by a series of online and in person activities, with participation from the international exoplanet and astrobiology communities, to assess state of the science and future research needs for the remote detection of life on planets outside our Solar System

Lead Optimization of Second-Generation Acridones as Broad-Spectrum Antimalarials.

The global impact of malaria remains staggering despite extensive efforts to eradicate the disease. With increasing drug resistance and the absence of a clinically available vaccine, there is an urgent need for novel, affordable, and safe drugs for prevention and treatment of malaria. Previously, we described a novel antimalarial acridone chemotype that is potent against both blood-stage and liver-stage malaria parasites. Here, we describe an optimization process that has produced a second-generation acridone series with significant improvements in efficacy, metabolic stability, pharmacokinetics, and safety profiles. These findings highlight the therapeutic potential of dual-stage targeting acridones as novel drug candidates for further preclinical development