Characterizing Patient Engagement in Research Funded by the Patient-Centered Outcomes Research Institute and Exploring the Moral Importance of Patient Engagement in Research

Patient engagement in research includes a range of activities in which researchers involve patients in ways other than as subjects of research. Research funders and researchers are increasingly recognizing patient engagement as a strategy that can lead to beneficial effects including the production of research that is more relevant to patients or of higher quality. The Patient-Centered Outcomes Research Institute (PCORI), a large research funding organization Congressionally authorized under the Patient Protection and Affordable Care Act, requires engagement of patients and other stakeholders in its funded comparative effectiveness research. Despite growing support for engagement, there is little empirical research and little conceptual scholarship examining patient engagement. This dissertation seeks to advance current understanding of patient engagement through three aims. Aim one seeks to characterize researchers’ experiences with patient engagement in research funded by PCORI, and aim two seeks to characterize patients’ experiences being engaged in PCORI-funded research. To address these empirical aims, interviews were conducted with both researchers and with the patients they were engaging in their PCORI-funded research. The results of these aims are reported in two papers. The first describes patient engagement in PCORI-funded projects including how, when, and why patients were engaged, and the extent to which patient input was reported to impact the relevance, feasibility, acceptability, and quality of the research. Findings suggest that the particular approach researchers use to engage patients may be less relevant to achieving desired outcomes than the manner in which engagement strategies are implemented. The second empirical paper focuses on challenges to and successful strategies for patient engagement as reported in interviews. This paper also provides suggested actions to address challenges and bolster infrastructure for engagement including modifications to institutional policies, development of programs and researcher networks, and provision of resources and training. Aim three explores the value of patient engagement from a normative perspective and ascertains the circumstances in which patient engagement is morally important. Drawing on interview findings, this conceptual paper analyzes the moral importance of the instrumental effects of engagement—namely, enhanced relevance, accountability, and respect—and whether engagement can be said to have intrinsic moral value

Inventory of wildlife use of mortality pits as feeding sites: implications of pathogen exposure

To better understand the use of mortality pits by wildlife and possible pathogen dissemination from the resulting wildlife contact in these areas, we used 8 camera traps on 4 mortality pits in Colorado from June to December 2014 to create a species inventory and establish use estimates for those species. We observed 43 species visiting (in or near) the mortality pits during 1,168 total camera trap days. Of these, 24 species directly interacted with the mortality pits or carcasses contained within them. The most common visitors to mortality pits were raccoons (Procyon lotor), coyotes (Canis latrans), domestic dogs (Canis lupus familiaris), mule deer (Odocoileus hemionus), bald eagles (Haliaeetus leucocephalus), blackbilled magpies (Pica hudsonia), corvid species (i.e., American crows [Corvus brachyrhynchos] or common ravens [Corvus corax]), great blue herons (Ardea herodias), house sparrows (Passer domesticus), and turkey vultures (Cathartes aura). Mammals were often solitary visitors to mortality pits, while birds often visited mortality pits in mixed flocks of 2 to 5 species, putting them at a higher risk of interspecific pathogen spread. Our findings indicate that many animals come into direct and indirect contact with interspecific and conspecific species at mortality pits

A social network analysis of actors involved in wild pig (\u3ci\u3eSus scrofa\u3c/i\u3e) management in Missouri

Wild pigs (Sus scrofa) cause significant damage to agriculture and native ecosystems and can transmit diseases to animals and people. Management responses designed to reduce population numbers are needed to mitigate these threats. Identifying networks of key actors, including the ways in which they interact, is valuable for purposes of better understanding opportunities or constraints that generate or impede effective management responses. The goal of our study was to understand the network of organizations, and the personnel working within them, that were active in wild pig management, research, or policy initiatives in Missouri during 2018–2020 by 1) identifying individuals and organizations involved in the network, 2) investigating the attributes of relevant personnel, 3) determining the structural patterns of the network, and 4) examining how the network structure could be optimized to improve communication and collaboration efforts. Results from a social network analysis identified 150 personnel affiliated with 26 organizations actively working on wild pig issues in Missouri. The network was largely homogenous based on respondents\u27 attributes, had low density, and was relatively fragmented, small, decentralized with few ties per node, and separated with few brokers. We emphasize the importance of understanding the strengths and weaknesses of a network\u27s structure in facilitating effective collective action to manage wild pigs

Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey‐Holden Prostate Cancer Academy Meeting

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138883/1/pros23424.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138883/2/pros23424_am.pd

Texas Hunters’ Perceptions Regarding the Acceptability of Toxicants to Control Wild Pig Populations

Wild pigs (Sus scrofa) are an invasive species in the United States. They damage agriculture, degrade water quality and ecological communities, and host a number of viruses, parasites, and bacteria transmissible to humans and animals. In states such as Texas, USA, where wild pigs cause extensive damage to agriculture and property, officials have considered allowing for the use of toxicants to control wild pig populations. To provide decision-makers with information regarding stakeholders’ perceptions of the use of toxicants to control wild pigs, we surveyed Texas hunters in 2019 to assess the level of acceptance of a hypothetical wild pig toxicant, the sociodemographic and other factors most closely associated with acceptability of such a toxicant, and the specific concerns that underlie hunters’ positions on the use of such a toxicant. We received 37,317 completed responses to an online, self-administered survey. Respondents were divided over the use of a toxicant, with 43% finding a toxicant acceptable, 18% neutral, and 39% finding a toxicant unacceptable. The factor most closely associated with acceptance of a wild pig toxicant was respondents’ desired wild pig population size in Texas (χ2 = 3,657.7, P \u3c 0.001, V = 0.26), with 70% of respondents who preferred that wild pigs be completely removed from Texas finding the use of a toxicant to be acceptable, compared to 14% of respondents who preferred that wild pig populations increase or stay the same. The most commonly raised concerns in connection with toxicant usage were potential negative impacts to nontarget animals (33%) and negative impacts to human health (24%). Our research suggests that while achieving a consensus among Texas hunters on toxicant usage is unrealistic, building majority support may be possible if the identified concerns are sufficiently addressed in product development and outreach

py4DSTEM: a software package for multimodal analysis of four-dimensional scanning transmission electron microscopy datasets

Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full 2D image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields and other sample-dependent properties. However, extracting this information requires complex analysis pipelines, from data wrangling to calibration to analysis to visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail, and present results from several experimental datasets. We have also implemented a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open source HDF5 standard. We hope this tool will benefit the research community, helps to move the developing standards for data and computational methods in electron microscopy, and invite the community to contribute to this ongoing, fully open-source project

Developmental phosphoproteomics identifies the kinase CK2 as a driver of Hedgehog signaling and a therapeutic target in medulloblastoma

A major limitation of targeted cancer therapy is the rapid emergence of drug resistance, which often arises through mutations at or downstream of the drug target or through intrinsic resistance of subpopulations of tumor cells. Medulloblastoma (MB), the most common pediatric brain tumor, is no exception, and MBs that are driven by sonic hedgehog (SHH) signaling are particularly aggressive and drug-resistant. To find new drug targets and therapeutics for MB that may be less susceptible to common resistance mechanisms, we used a developmental phosphoproteomics approach in murine granule neuron precursors (GNPs), the developmental cell of origin of MB. The protein kinase CK2 emerged as a driver of hundreds of phosphorylation events during the proliferative, MB-like stage of GNP growth, including the phosphorylation of three of the eight proteins commonly amplified in MB. CK2 was critical to the stabilization and activity of the transcription factor GLI2, a late downstream effector in SHH signaling. CK2 inhibitors decreased the viability of primary SHH-type MB patient cells in culture and blocked the growth of murine MB tumors that were resistant to currently available Hh inhibitors, thereby extending the survival of tumor-bearing mice. Because of structural interactions, one CK2 inhibitor (CX-4945) inhibited both wild-type and mutant CK2, indicating that this drug may avoid at least one common mode of acquired resistance. These findings suggest that CK2 inhibitors may be effective for treating patients with MB and show how phosphoproteomics may be used to gain insight into developmental biology and pathology

Diet-Induced Obesity Impairs Endothelium-Derived Hyperpolarization via Altered Potassium Channel Signaling Mechanisms

BACKGROUND: The vascular endothelium plays a critical role in the control of blood flow. Altered endothelium-mediated vasodilator and vasoconstrictor mechanisms underlie key aspects of cardiovascular disease, including those in obesity. Whilst the mechanism of nitric oxide (NO)-mediated vasodilation has been extensively studied in obesity, little is known about the impact of obesity on vasodilation to the endothelium-derived hyperpolarization (EDH) mechanism; which predominates in smaller resistance vessels and is characterized in this study. METHODOLOGY/PRINCIPAL FINDINGS: Membrane potential, vessel diameter and luminal pressure were recorded in 4(th) order mesenteric arteries with pressure-induced myogenic tone, in control and diet-induced obese rats. Obesity, reflecting that of human dietary etiology, was induced with a cafeteria-style diet (∼30 kJ, fat) over 16-20 weeks. Age and sexed matched controls received standard chow (∼12 kJ, fat). Channel protein distribution, expression and vessel morphology were determined using immunohistochemistry, Western blotting and ultrastructural techniques. In control and obese rat vessels, acetylcholine-mediated EDH was abolished by small and intermediate conductance calcium-activated potassium channel (SK(Ca)/IK(Ca)) inhibition; with such activity being impaired in obesity. SK(Ca)-IK(Ca) activation with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) and 1-ethyl-2-benzimidazolinone (1-EBIO), respectively, hyperpolarized and relaxed vessels from control and obese rats. IK(Ca)-mediated EDH contribution was increased in obesity, and associated with altered IK(Ca) distribution and elevated expression. In contrast, the SK(Ca)-dependent-EDH component was reduced in obesity. Inward-rectifying potassium channel (K(ir)) and Na(+)/K(+)-ATPase inhibition by barium/ouabain, respectively, attenuated and abolished EDH in arteries from control and obese rats, respectively; reflecting differential K(ir) expression and distribution. Although changes in medial properties occurred, obesity had no effect on myoendothelial gap junction density. CONCLUSION/SIGNIFICANCE: In obese rats, vasodilation to EDH is impaired due to changes in the underlying potassium channel signaling mechanisms. Whilst myoendothelial gap junction density is unchanged in arteries of obese compared to control, increased IK(Ca) and Na(+)/K(+)-ATPase, and decreased K(ir) underlie changes in the EDH mechanism

Priorities for synthesis research in ecology and environmental science

ACKNOWLEDGMENTS We thank the National Science Foundation grant #1940692 for financial support for this workshop, and the National Center for Ecological Analysis and Synthesis (NCEAS) and its staff for logistical support.Peer reviewedPublisher PD