Engaging national organizations for knowledge translation: Comparative case studies in knowledge value mapping

<p>Abstract</p> <p>Background</p> <p>Government sponsors of research and development, along with their funded investigators, are increasingly tasked with demonstrating evidence of knowledge use by nontraditional audiences. This requires efforts to translate their findings for effective communication. For technology-related knowledge, these audiences include clinicians, consumers, manufacturers, public policy agencies, and knowledge brokers. One potentially efficient approach is to communicate research findings through relevant national organizations. However, this requires an understanding of how such organizations view and treat research knowledge, which can be determined through knowledge-value mapping. Do knowledge values differ between national organizations representing different audiences? Can a deeper understanding of knowledge values help sponsors, investigators, and organizations better communicate research findings to stakeholders?</p> <p>Methods</p> <p>A series of comparative case studies on knowledge-value mapping were derived through interviews with spokespersons for six national organizations. The semi-structured interviews followed a 10-item questionnaire to characterize different ways in which each organization engages with research-based knowledge. Each participating organization represents a particular stakeholder group, while all share a common interest in the research subject matter.</p> <p>Results</p> <p>Each national organization considers the value of the research knowledge in the context of their organization's mission and the interests of their members. All are interested in collaborating with researchers to share relevant findings, while they vary along the following dimensions of knowledge engagement: create, identify, translate, adapt, communicate, use, promote, absorptive capacity, and recommendations for facilitation.</p> <p>Conclusions</p> <p>The principles of knowledge translation suggest that investigators can increase use by tailoring the format and context of their findings to the absorptive capacity of nonscholars. Greater absorption should result in higher levels of knowledge awareness, interest, and use, which can then be documented. National organizations and their members, in turn, can strive to optimize their absorptive capacities regarding the state of the sciences. This combination will ensure the highest possible return on public investment in research activities. This knowledge-value mapping study concludes that national organizations are appropriate channels for communicating research findings and for meeting statutory requirements and general expectations for generating and documenting knowledge use.</p

First documentation of malaria parasites (genus Plasmodium) in the Saltmarsh Sparrow (Ammodramus caudacutus) and patterns of infection with mercury exposure

Avian malaria parasites, protist parasites of the genus Plasmodium, are extremely common in birds worldwide and have the ability to dramatically impact sensitive populations and species. Mercury, a heavy metal that accumulates in the tissues of birds, is a common environmental pollutant that may reduce immune system function and increase susceptibility to malaria parasite infection. I surveyed the endangered Saltmarsh Sparrow (Ammodramus caudacutus), a species with high exposure to mercury, for malaria parasites. Specifically, I investigated the presence, diversity, and distribution of malaria parasites in the species, the degree of sharing of parasite lineages with other bird species, and the relationship between blood mercury levels and infection status. Through collaboration with researchers at the Biodiversity Research Institute (BRI) and the University of New Hampshire (UNH), blood samples were collected from 290 individuals across the entire breeding range of the species from Maine to Maryland, U.S. By sensitive nested PCR methods, I screened each sample for malaria parasite infection and each positive infection was sequenced at the mitochondrial cytochrome b gene to identify parasite lineages, the standard gene used in defining Plasmodium lineages. Overall, 16.5% of Saltmarsh Sparrows were found to be infected with a total of six Plasmodium lineages. Prevalence and diversity of parasite lineages varied across the breeding range of the Saltmarsh Sparrow, with greater prevalence and diversity in northern states. The skewed distribution of prevalence and parasite diversity may be due to mosquito control measures, habitat type, or possibly climate change. All six parasite lineages were found to be shared with other passerine species including those also found to nest in or near saltmarshes. Blood mercury levels varied in the Saltmarsh Sparrow, ranging from 0.18 ppm to 2.52 ppm with a mean of 0.86 ppm. Although a positive correlation was expected between blood mercury levels and infection status because mercury negatively impacts an individual’s ability to fight infection, I found a negative correlation. These results suggest that individuals with low blood mercury levels are more likely to be infected with malaria parasites. The discovery of a relatively high prevalence and diversity of malaria parasites in the Saltmarsh Sparrow, a species in rapid decline across its range, and the negative correlation relationship between mercury exposure and malaria parasite infection status, suggest the need for continued study of malaria parasite dynamics in the species. Further research will help elucidate the link between environmental pollution and infectious disease risk, which is a pressing topic as environmental contamination combined with climate change may heavily impact host, vector, and parasite distributions and host-parasite dynamics

OH-Stretch Vibrational Spectroscopy of Hydroxymethyl Hydroperoxide

We report measurement and analysis of the photodissociation spectrum of hydroxymethyl hydroperoxide (HOCH_2OOH) and its partially deuterated analogue, HOCD_2OOH, in the OH-stretching region. Spectra are obtained by Fourier transform infrared spectroscopy in the 1ν_(OH) and 2ν_(OH) regions, and by laser induced fluorescence detection of the OH fragment produced from dissociation of HOCH_2OOH initiated by excitation of the 4ν_(OH) and 5ν_(OH) overtone regions (action spectroscopy). A one-dimensional local-mode model of each OH chromophore is used with ab initio calculated OH-stretching potential energy and dipole moment curves at the coupled-cluster level of theory. Major features in the observed absorption and photodissociation spectra are explained by our local-mode model. In the 4ν_(OH) region, explanation of the photodissocation spectrum requires a nonuniform quantum yield, which is estimated by assuming statistical energy distribution in the excited state. Based on the estimated dissociation threshold, overtone photodissociation is not expected to significantly influence the atmospheric lifetime of hydroxymethyl hydroperoxide

Translating three states of knowledge--discovery, invention, and innovation

<p>Abstract</p> <p>Background</p> <p>Knowledge Translation (KT) has historically focused on the proper use of knowledge in healthcare delivery. A knowledge base has been created through empirical research and resides in scholarly literature. Some knowledge is amenable to direct application by stakeholders who are engaged during or after the research process, as shown by the Knowledge to Action (KTA) model. Other knowledge requires multiple transformations before achieving utility for end users. For example, conceptual knowledge generated through science or engineering may become embodied as a technology-based invention through development methods. The invention may then be integrated within an innovative device or service through production methods. To what extent is KT relevant to these transformations? How might the KTA model accommodate these additional development and production activities while preserving the KT concepts?</p> <p>Discussion</p> <p>Stakeholders adopt and use knowledge that has perceived utility, such as a solution to a problem. Achieving a technology-based solution involves three methods that generate knowledge in three states, analogous to the three classic states of matter. Research activity generates discoveries that are intangible and highly malleable like a gas; development activity transforms discoveries into inventions that are moderately tangible yet still malleable like a liquid; and production activity transforms inventions into innovations that are tangible and immutable like a solid. The paper demonstrates how the KTA model can accommodate all three types of activity and address all three states of knowledge. Linking the three activities in one model also illustrates the importance of engaging the relevant stakeholders prior to initiating any knowledge-related activities.</p> <p>Summary</p> <p>Science and engineering focused on technology-based devices or services change the state of knowledge through three successive activities. Achieving knowledge implementation requires methods that accommodate these three activities and knowledge states. Accomplishing beneficial societal impacts from technology-based knowledge involves the successful progression through all three activities, and the effective communication of each successive knowledge state to the relevant stakeholders. The KTA model appears suitable for structuring and linking these processes.</p

Rigorous Computational and Experimental Investigations on MDM2/MDMX-Targeted Linear and Macrocyclic Peptides

There is interest in peptide drug design, especially for targeting intracellular protein–protein interactions. Therefore, the experimental validation of a computational platform for enabling peptide drug design is of interest. Here, we describe our peptide drug design platform (CMDInventus) and demonstrate its use in modeling and predicting the structural and binding aspects of diverse peptides that interact with oncology targets MDM2/MDMX in comparison to both retrospective (pre-prediction) and prospective (post-prediction) data. In the retrospective study, CMDInventus modules (CMDpeptide, CMDboltzmann, CMDescore and CMDyscore) were used to accurately reproduce structural and binding data across multiple MDM2/MDMX data sets. In the prospective study, CMDescore, CMDyscore and CMDboltzmann were used to accurately predict binding affinities for an Ala-scan of the stapled α-helical peptide ATSP-7041. Remarkably, CMDboltzmann was used to accurately predict the results of a novel D-amino acid scan of ATSP-7041. Our investigations rigorously validate CMDInventus and support its utility for enabling peptide drug design

Femtosecond photodissociation dynamics of 1,4-diiodobenzene by gas-phase X-ray scattering and photoelectron spectroscopy

We present a multifaceted investigation into the initial photodissociation dynamics of 1,4-diiodobenzene (DIB) following absorption of 267 nm radiation. We combine ultrafast time-resolved photoelectron spectroscopy and X-ray scattering experiments performed at the Linac Coherent Light Source (LCLS) to study the initial electronic excitation and subsequent rotational alignment, and interpret the experiments in light of Complete Active Space Self-Consistent Field (CASSCF) calculations of the excited electronic landscape. The initially excited state is found to be a bound 1B1 surface, which undergoes ultrafast population transfer to a nearby state in 35 ± 10 fs. The internal conversion most likely leads to one or more singlet repulsive surfaces that initiate the dissociation. This initial study is an essential and prerequisite component of a comprehensive study of the complete photodissociation pathway(s) of DIB at 267 nm. Assignment of the initially excited electronic state as a bound state identifies the mechanism as predissociative, and measurement of its lifetime establishes the time between excitation and initiation of dissociation, which is crucial for direct comparison of photoelectron and scattering experiments.</p

The structure of electroweak corrections due to extended gauge symmetries

This paper studies models with extended electroweak gauge sectors of the form SU(2) x SU(2) x U(1) x [SU(2) or U(1)]. We establish the general behavior of corrections to precision electroweak observables in this class of theories and connect our results to previous work on specific models whose electroweak sectors are special cases of our extended group.Comment: 18 pages, 2 figures; added a referenc

A mass spectrometry-based approach to distinguish annular and specific lipid binding to membrane proteins

Membrane proteins engage in a variety of contacts with theirsurrounding lipids, but distinguishing between specifically boundlipids, and non-specific annular interactionsis a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid binding properties, we explore the ability of detergents to compete with lipids bound in different environments. We show that lipids in annular positions on the Presenilin Homologue protease are subject to constant exchange with detergent. Bycontrast,detergent-resistantlipids bound at the dimer interface in the Leucine transportershowdecreased koffrates in molecular dynamics simulations.Turning tothe lipid flippase MurJ, we findthat addition of the natural substrate lipid-II results in the formation of a 1:1 protein-lipid complex, where the lipid cannot be displaced by detergentfromthe highly protected active site.In summary, we distinguish annular from non-annular lipids based on their exchange rates in solution. [Abstract copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High HIV Prevalence Among Men Who have Sex with Men in Soweto, South Africa: Results from the Soweto Men’s Study

The Soweto Men’s Study assessed HIV prevalence and associated risk factors among MSM in Soweto, South Africa. Using respondent driven sampling (RDS) recruitment methods, we recruited 378 MSM (including 15 seeds) over 30 weeks in 2008. All results were adjusted for RDS sampling design. Overall HIV prevalence was estimated at 13.2% (95% confidence interval 12.4–13.9%), with 33.9% among gay-identified men, 6.4% among bisexual-identified men, and 10.1% among straight-identified MSM. In multivariable analysis, HIV infection was associated with being older than 25 (adjusted odds ratio (AOR) 3.8, 95% CI 3.2–4.6), gay self-identification (AOR 2.3, 95% CI 1.8–3.0), monthly income less than ZAR500 (AOR 1.4, 95% CI 1.2–1.7), purchasing alcohol or drugs in exchange for sex with another man (AOR 3.9, 95% CI 3.2–4.7), reporting any URAI (AOR 4.4, 95% CI 3.5–5.7), reporting between six and nine partners in the prior 6 months (AOR 5.7, 95% CI 4.0–8.2), circumcision, (AOR 0.2, 95% CI 0.1–0.2), a regular female partner (AOR 0.2, 95% CI 0.2–0.3), smoking marijuana in the last 6 months (AOR 0.6, 95% CI 0.5–0.8), unprotected vaginal intercourse in the last 6 months (AOR 0.5, 95% CI 0.4–0.6), and STI symptoms in the last year (AOR 0.7, 95% CI 0.5–0.8). The results of the Soweto Men’s Study confirm that MSM are at high risk for HIV infection, with gay men at highest risk. HIV prevention and treatment for MSM are urgently needed