Effective modeling for integrated water resource management: a guide to contextual practices by phases and steps and future opportunities

The effectiveness of Integrated Water Resource Management (IWRM) modeling hinges on the quality of practices employed through the process, starting from early problem definition all the way through to using the model in a way that serves its intended purpose. The adoption and implementation of effective modeling practices need to be guided by a practical understanding of the variety of decisions that modelers make, and the information considered in making these choices. There is still limited documented knowledge on the modeling workflow, and the role of contextual factors in determining this workflow and which practices to employ. This paper attempts to contribute to this knowledge gap by providing systematic guidance of the modeling practices through the phases (Planning, Development, Application, and Perpetuation) and steps that comprise the modeling process, positing questions that should be addressed. Practice-focused guidance helps explain the detailed process of conducting IWRM modeling, including the role of contextual factors in shaping practices. We draw on findings from literature and the authors’ collective experience to articulate what and how contextual factors play out in employing those practices. In order to accelerate our learning about how to improve IWRM modeling, the paper concludes with five key areas for future practice-related research: knowledge sharing, overcoming data limitations, informed stakeholder involvement, social equity and uncertainty management. © 2019 Elsevier Lt

Long-Term Functionality of Rural Water Services in Developing Countries: A System Dynamics Approach to Understanding the Dynamic Interaction of Causal Factors

Research has shown that sustainability of rural water infrastructure in developing countries is largely affected by the dynamic and systemic interactions of technical, social, financial, institutional, and environmental factors that can lead to premature water system failure. This research employs systems dynamic modeling, which uses feedback mechanisms to understand how these factors interact dynamically to influence long-term rural water system functionality. To do this, the research first identified and aggregated key factors from literature, then asked water sector experts to indicate the polarity and strength between factors through Delphi and cross impact survey questionnaires, and finally used system dynamics modeling to identify and prioritize feedback mechanisms. The resulting model identified 101 feedback mechanisms that were dominated primarily by three and four-factor loops that contained some combination of the factors: Water System Functionality, Community, Financial, Government, Management, and Technology. These feedback mechanisms were then scored and prioritized, with the most dominant feedback mechanism identified as Water System Functionality – Community – Finance – Management. This research offers insight into the dynamic interaction of factors impacting sustainability of rural water infrastructure through the identification of these feedback mechanisms and makes a compelling case for future research to longitudinally investigate the interaction of these factors in various contexts

Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life.

Neonates have heightened susceptibility to infections. The biological mechanisms are incompletely understood but thought to be related to age-specific adaptations in immunity due to resource constraints during immune system development and growth. We present here an extended analysis of our proteomics study of peripheral blood-plasma from a study of healthy full-term newborns delivered vaginally, collected at the day of birth and on day of life (DOL) 1, 3, or 7, to cover the first week of life. The plasma proteome was characterized by LC-MS using our established 96-well plate format plasma proteomics platform. We found increasing acute phase proteins and a reduction of respective inhibitors on DOL1. Focusing on the complement system, we found increased plasma concentrations of all major components of the classical complement pathway and the membrane attack complex (MAC) from birth onward, except C7 which seems to have near adult levels at birth. In contrast, components of the lectin and alternative complement pathways mainly decreased. A comparison to whole blood messenger RNA (mRNA) levels enabled characterization of mRNA and protein levels in parallel, and for 23 of the 30 monitored complement proteins, the whole blood transcript information by itself was not reflective of the plasma protein levels or dynamics during the first week of life. Analysis of immunoglobulin (Ig) mRNA and protein levels revealed that IgM levels and synthesis increased, while the plasma concentrations of maternally transferred IgG1-4 decreased in accordance with their in vivo half-lives. The neonatal plasma ratio of IgG1 to IgG2-4 was increased compared to adult values, demonstrating a highly efficient IgG1 transplacental transfer process. Partial compensation for maternal IgG degradation was achieved by endogenous synthesis of the IgG1 subtype which increased with DOL. The findings were validated in a geographically distinct cohort, demonstrating a consistent developmental trajectory of the newborn's immune system over the first week of human life across continents. Our findings indicate that the classical complement pathway is central for newborn immunity and our approach to characterize the plasma proteome in parallel with the transcriptome will provide crucial insight in immune ontogeny and inform new approaches to prevent and treat diseases

Framework for sustained climate assessment in the United States

Author Posting. © American Meteorological Society, 2019. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society, 100(5), (2019): 897-908, doi:10.1175/BAMS-D-19-0130.1.As states, cities, tribes, and private interests cope with climate damages and seek to increase preparedness and resilience, they will need to navigate myriad choices and options available to them. Making these choices in ways that identify pathways for climate action that support their development objectives will require constructive public dialogue, community participation, and flexible and ongoing access to science- and experience-based knowledge. In 2016, a Federal Advisory Committee (FAC) was convened to recommend how to conduct a sustained National Climate Assessment (NCA) to increase the relevance and usability of assessments for informing action. The FAC was disbanded in 2017, but members and additional experts reconvened to complete the report that is presented here. A key recommendation is establishing a new nonfederal “climate assessment consortium” to increase the role of state/local/tribal government and civil society in assessments. The expanded process would 1) focus on applied problems faced by practitioners, 2) organize sustained partnerships for collaborative learning across similar projects and case studies to identify effective tested practices, and 3) assess and improve knowledge-based methods for project implementation. Specific recommendations include evaluating climate models and data using user-defined metrics; improving benefit–cost assessment and supporting decision-making under uncertainty; and accelerating application of tools and methods such as citizen science, artificial intelligence, indicators, and geospatial analysis. The recommendations are the result of broad consultation and present an ambitious agenda for federal agencies, state/local/tribal jurisdictions, universities and the research sector, professional associations, nongovernmental and community-based organizations, and private-sector firms.This report would not have been possible without the support and participation of numerous organizations and individuals. We thank New York State Governor Andrew M. Cuomo for announcing in his 2018 State of the State agenda that the IAC would be reconvened. The New York State Energy Research and Development Authority (Contract ID 123416), Columbia University’s Earth Institute, and the American Meteorological Society provided essential financial support and much more, including sage advice and moral support from John O’Leary, Shara Mohtadi, Steve Cohen, Alex Halliday, Peter deMenocal, Keith Seitter, Paul Higgins, and Bill Hooke. We thank the attendees of a workshop, generously funded by the Kresge Foundation in November of 2017, that laid a foundation for the idea to establish a civil-society-based assessment consortium. During the course of preparing the report, IAC members consulted with individuals too numerous to list here—state, local, and tribal officials; researchers; experts in nongovernmental and community-based organizations; and professionals in engineering, architecture, public health, adaptation, and other areas. We are so grateful for their time and expertise. We thank the members and staff of the National Academy of Sciences, Engineering, and Medicine’s Committee to Advise the U.S. Global Change Research Program for providing individual comments on preliminary recommendations during several discussions in open sessions of their meetings. The following individuals provided detailed comments on an earlier version of this report, which greatly sharpened our thinking and recommendations: John Balbus, Tom Dietz, Phil Duffy, Baruch Fischhoff, Brenda Hoppe, Melissa Kenney, Linda Mearns, Claudia Nierenberg, Kathleen Segerson, Soroosh Sorooshian, Chris Weaver, and Brian Zuckerman. Mary Black provided insightful copy editing of several versions of the report. We also thank four anonymous reviewers for their effort and care in critiquing and improving the report. It is the dedication, thoughtful feedback, expertise, care, and commitment of all these people and more that not only made this report possible, but allow us all to continue to support smart and insightful actions in a changing climate. We are grateful as authors and as global citizens. Author contributions: RM, SA, KB, MB, AC, JD, PF, KJ, AJ, KK, JK, ML, JM, RP, TR, LS, JS, JW, and DZ were members of the IAC and shared in researching, discussing, drafting, and approving the report. BA, JF, AG, LJ, SJ, PK, RK, AM, RM, JN, WS, JS, PT, GY, and RZ contributed to specific sections of the report

Evaluating knowledge to support climate action: A framework for sustained assessment. report of an independent advisory committee on applied climate assessment.

Author Posting. © American Meteorological Society, 2019. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Weather Climate and Society 11(3), (2019):465-487, doi: 10.1175/WCAS-D-18-0134.1.As states, cities, tribes, and private interests cope with climate damages and seek to increase preparedness and resilience, they will need to navigate myriad choices and options available to them. Making these choices in ways that identify pathways for climate action that support their development objectives will require constructive public dialogue, community participation, and flexible and ongoing access to science- and experience-based knowledge. In 2016, a Federal Advisory Committee (FAC) was convened to recommend how to conduct a sustained National Climate Assessment (NCA) to increase the relevance and usability of assessments for informing action. The FAC was disbanded in 2017, but members and additional experts reconvened to complete the report that is presented here. A key recommendation is establishing a new nonfederal “climate assessment consortium” to increase the role of state/local/tribal government and civil society in assessments. The expanded process would 1) focus on applied problems faced by practitioners, 2) organize sustained partnerships for collaborative learning across similar projects and case studies to identify effective tested practices, and 3) assess and improve knowledge-based methods for project implementation. Specific recommendations include evaluating climate models and data using user-defined metrics; improving benefit–cost assessment and supporting decision-making under uncertainty; and accelerating application of tools and methods such as citizen science, artificial intelligence, indicators, and geospatial analysis. The recommendations are the result of broad consultation and present an ambitious agenda for federal agencies, state/local/tribal jurisdictions, universities and the research sector, professional associations, nongovernmental and community-based organizations, and private-sector firms.This report would not have been possible without the support and participation of numerous organizations and individuals. We thank New York State Governor Andrew M. Cuomo for announcing in his 2018 State of the State agenda that the IAC would be reconvened. The New York State Energy Research and Development Authority (Contract ID 123416), Columbia University’s Earth Institute, and the American Meteorological Society provided essential financial support and much more, including sage advice and moral support from John O’Leary, Shara Mohtadi, Steve Cohen, Alex Halliday, Peter deMenocal, Keith Seitter, Paul Higgins, and Bill Hooke. We thank the attendees of a workshop, generously funded by the Kresge Foundation in November of 2017, that laid a foundation for the idea to establish a civil-society-based assessment consortium. During the course of preparing the report, IAC members consulted with individuals too numerous to list here—state, local, and tribal officials; researchers; experts in nongovernmental and community-based organizations; and professionals in engineering, architecture, public health, adaptation, and other areas. We are so grateful for their time and expertise. We thank the members and staff of the National Academy of Sciences, Engineering, and Medicine’s Committee to Advise the U.S. Global Change Research Program for providing individual comments on preliminary recommendations during several discussions in open sessions of their meetings. The following individuals provided detailed comments on an earlier version of this report, which greatly sharpened our thinking and recommendations: John Balbus, Tom Dietz, Phil Duffy, Baruch Fischhoff, Brenda Hoppe, Melissa Kenney, Linda Mearns, Claudia Nierenberg, Kathleen Segerson, Soroosh Sorooshian, Chris Weaver, and Brian Zuckerman. Mary Black provided insightful copy editing of several versions of the report. We also thank four anonymous reviewers for their effort and care in critiquing and improving the report. It is the dedication, thoughtful feedback, expertise, care, and commitment of all these people and more that not only made this report possible, but allow us all to continue to support smart and insightful actions in a changing climate. We are grateful as authors and as global citizens. Author contributions: RM, SA, KB, MB, AC, JD, PF, KJ, AJ, KK, JK, ML, JM, RP, TR, LS, JS, JW, and DZ were members of the IAC and shared in researching, discussing, drafting, and approving the report. BA, JF, AG, LJ, SJ, PK, RK, AM, RM, JN, WS, JS, PT, GY, and RZ contributed to specific sections of the report.2020-05-2

Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants.

Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.This work was supported by a Canadian Institute of Health Research (CIHR) team grant awarded to E.G., A.T., M.C.V. and M.L. (TEC-128093) and the CIHR funded Epigeneome Mapping Centre at McGill University (EP1-120608) awarded to T.P. and M.L., and the Swedish Research Council, Knut and Alice Wallenberg Foundation and the Torsten Söderberg Foundation awarded to L.R. F.A. holds studentship from The Research Institute of the McGill University Health Center (MUHC). F.G. is a recipient of a research fellowship award from the Heart and Stroke Foundation of Canada. A.T. is the director of a Research Chair in Bariatric and Metabolic Surgery. M.C.V. is the recipient of the Canada Research Chair in Genomics Applied to Nutrition and Health (Tier 1). E.G. and T.P. are recipients of a Canada Research Chair Tier 2 award. The MuTHER Study was funded by a programme grant from the Wellcome Trust (081917/Z/07/Z) and core funding for the Wellcome Trust Centre for Human Genetics (090532). TwinsUK was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. T.D.S. is a holder of an ERC Advanced Principal Investigator award. SNP genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. Finally, we thank the NIH Roadmap Epigenomics Consortium and the Mapping Centers (http://nihroadmap.nih.gov/epigenomics/) for the production of publicly available reference epigenomes. Specifically, we thank the mapping centre at MGH/BROAD for generation of human adipose reference epigenomes used in this study.This is the final version. It was first published by NPG at http://www.nature.com/ncomms/2015/150529/ncomms8211/full/ncomms8211.html#abstrac

Biological and clinical insights from genetics of insomnia symptoms

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal glands. Evidence of shared genetic factors was found between frequent insomnia symptoms and restless legs syndrome, aging, and cardiometabolic, behavioral, psychiatric, and reproductive traits. Evidence was found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms, and subjective well-being

Combined point of care nucleic acid and antibody testing for SARS-CoV-2 following emergence of D614G Spike Variant

Rapid COVID-19 diagnosis in hospital is essential, though complicated by 30-50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant now dominates the pandemic and it is unclear how serological tests designed to detect anti-Spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95CI 57.8-92.9%) by rapid NAAT alone. Combined point of care antibody test and rapid NAAT is not impacted by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity