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

Rival male chemical cues evoke changes in male pre- and post-copulatory investment in a flour beetle.

This is the final version of the article. Available from Oxford University Press via the DOI in this record.Males can gather information on the risk and intensity of sperm competition from their social environment. Recent studies have implicated chemosensory cues, for instance cuticular hydrocarbons (CHCs) in insects, as a key source of this information. Here, using the broad-horned flour beetle (Gnatocerus cornutus), we investigated the importance of contact-derived rival male CHCs in informing male perception of sperm competition risk and intensity. We experimentally perfumed virgin females with male CHCs via direct intersexual contact and measured male pre- and post-copulatory investment in response to this manipulation. Using chemical analysis, we verified that this treatment engendered changes to perfumed female CHC profiles, but did not make perfumed females "smell" mated. Despite this, males responded to these chemical changes. Males increased courtship effort under low levels of perceived competition (from 1-3 rivals), but significantly decreased courtship effort as perceived competition rose (from 3-5 rivals). Furthermore, our measurement of ejaculate investment showed that males allocated significantly more sperm to perfumed females than to control females. Together, these results suggest that changes in female chemical profile elicited by contact with rival males do not provide males with information on female mating status, but rather inform males of the presence of rivals within the population and thus provide a means for males to indirectly assess the risk of sperm competition.S.M.L.  was funded by a Natural Environment Research Council (NERC) studentship, J.H.S. was funded by NERC, a Royal Society Fellowship, and a Royal Society Equipment Grant (UF120087), and C.M.H. by a Leverhulme Early Career Fellowship (ECF/2010/0067)

Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis

Systemic amyloidosis is a fatal disorder caused by pathological extracellular deposits of amyloid fibrils that are always coated with the normal plasma protein, serum amyloid P component (SAP). The small-molecule drug, miridesap, [(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC)] depletes circulating SAP but leaves some SAP in amyloid deposits. This residual SAP is a specific target for dezamizumab, a fully humanized monoclonal IgG1 anti-SAP antibody that triggers immunotherapeutic clearance of amyloid. We report the safety, pharmacokinetics, and dose-response effects of up to three cycles of miridesap followed by dezamizumab in 23 adult subjects with systemic amyloidosis (ClinicalTrials.gov identifier: NCT01777243). Amyloid load was measured scintigraphically by amyloid-specific radioligand binding of 123I-labeled SAP or of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Organ extracellular volume was measured by equilibrium magnetic resonance imaging and liver stiffness by transient elastography. The treatment was well tolerated with the main adverse event being self-limiting early onset rashes after higher antibody doses related to whole body amyloid load. Progressive dose-related clearance of hepatic amyloid was associated with improved liver function tests. 123I-SAP scintigraphy confirmed amyloid removal from the spleen and kidneys. No adverse cardiac events attributable to the intervention occurred in the six subjects with cardiac amyloidosis. Amyloid load reduction by miridesap treatment followed by dezamizumab has the potential to improve management and outcome in systemic amyloidosis

The Impact of Non-Equipartition on Cosmological Parameter Estimation from Sunyaev-Zel'dovich Surveys

The collisionless accretion shock at the outer boundary of a galaxy cluster should primarily heat the ions instead of electrons since they carry most of the kinetic energy of the infalling gas. Near the accretion shock, the density of the intracluster medium is very low and the Coulomb collisional timescale is longer than the accretion timescale. Electrons and ions may not achieve equipartition in these regions. Numerical simulations have shown that the Sunyaev-Zel'dovich observables (e.g., the integrated Comptonization parameter Y) for relaxed clusters can be biased by a few percent. The Y-mass relation can be biased if non-equipartition effects are not properly taken into account. Using a set of hydrodynamical simulations, we have calculated three potential systematic biases in the Y-mass relations introduced by non-equipartition effects during the cross-calibration or self-calibration when using the galaxy cluster abundance technique to constraint cosmological parameters. We then use a semi-analytic technique to estimate the non-equipartition effects on the distribution functions of Y (Y functions) determined from the extended Press-Schechter theory. Depending on the calibration method, we find that non-equipartition effects can induce systematic biases on the Y functions, and the values of the cosmological parameters Omega_8, sigma_8, and the dark energy equation of state parameter w can be biased by a few percent. In particular, non-equipartition effects can introduce an apparent evolution in w of a few percent in all of the systematic cases we considered. Techniques are suggested to take into account the non-equipartition effect empirically when using the cluster abundance technique to study precision cosmology. We conclude that systematic uncertainties in the Y-mass relation of even a few percent can introduce a comparable level of biases in cosmological parameter measurements.Comment: 10 pages, 3 figures, accepted for publication in the Astrophysical Journal, abstract abridged slightly. Typos corrected in version

Vectorlike Confinement at the LHC

We argue for the plausibility of a broad class of vectorlike confining gauge theories at the TeV scale which interact with the Standard Model predominantly via gauge interactions. These theories have a rich phenomenology at the LHC if confinement occurs at the TeV scale, while ensuring negligible impact on precision electroweak and flavor observables. Spin-1 bound states can be resonantly produced via their mixing with Standard Model gauge bosons. The resonances promptly decay to pseudo-Goldstone bosons, some of which promptly decay to a pair of Standard Model gauge bosons, while others are charged and stable on collider time scales. The diverse set of final states with little background include multiple photons and leptons, missing energy, massive stable charged particles and the possibility of highly displaced vertices in dilepton, leptoquark or diquark decays. Among others, a novel experimental signature of resonance reconstruction out of massive stable charged particles is highlighted. Some of the long-lived states also constitute Dark Matter candidates.Comment: 33 pages, 6 figures. v4: expanded discussion of Z_2 symmetry for stability, one reference adde

Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression

OBJECTIVES: The purpose of this study was to determine the effect of patisiran on the cardiac amyloid load as measured by cardiac magnetic resonance and extracellular volume (ECV) mapping in cases of transthyretin cardiomyopathy (ATTR-CM). BACKGROUND: Administration of patisiran, a TTR-specific small interfering RNA (siRNA), has been shown to benefit neuropathy in patients with hereditary ATTR amyloidosis, but its effect on ATTR-CM remains uncertain. METHODS: Patisiran was administered to 16 patients with hereditary ATTR-CM who underwent assessment protocols at the UK National Amyloidosis Centre. Twelve of those patients concomitantly received diflunisal as a "TTR-stabilizing" drug. Patients underwent serial monitoring using cardiac magnetic resonance, echocardiography, cardiac biomarkers, bone scintigraphy, and 6-min walk tests (6MWTs). Findings of amyloid types and extracellular volumes were compared with those of 16 patients who were retrospectively matched based on cardiac magnetic resonance results. RESULTS: Patisiran was well tolerated. Median serum TTR knockdown among treated patients was 86% (interquartile range [IQR]: 82% to 90%). A total of 82% of cases showed >80% knockdown. Patisiran therapy was typically associated with a reduction in ECV (adjusted mean difference between groups: -6.2% [95% confidence interval [CI]: -9.5% to -3.0%]; p = 0.001) accompanied by a fall in N-terminal pro-B-type natriuretic peptide concentrations (adjusted mean difference between groups: -1,342 ng/l [95% CI: -2,364 to -322]; p = 0.012); an increase in 6MWT distances (adjusted mean differences between groups: 169 m [95% CI: 57 to 2,80]; p = 0.004) after 12 months of therapy; and a median reduction in cardiac uptake by bone scintigraphy of 19.6% (IQR: 9.8% to 27.1%). CONCLUSIONS: Reductions in ECV by cardiac magnetic resonance provided evidence for ATTR cardiac amyloid regression in a proportion of patients receiving patisiran

The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster

The regulatory protein NsrR, a member of the Rrf2 family of transcription repressors, is specifically dedicated to sensing nitric oxide (NO) in a variety of pathogenic and non-pathogenic bacteria. It has been proposed that NO directly modulates NsrR activity by interacting with a predicted [Fe-S] cluster in the NsrR protein, but no experimental evidence has been published to support this hypothesis. Here we report the purification of NsrR from the obligate aerobe Streptomyces coelicolor. We demonstrate using UV-visible, near UV CD and EPR spectroscopy that the protein contains an NO-sensitive [2Fe-2S] cluster when purified from E. coli. Upon exposure of NsrR to NO, the cluster is nitrosylated, which results in the loss of DNA binding activity as detected by bandshift assays. Removal of the [2Fe-2S] cluster to generate apo-NsrR also resulted in loss of DNA binding activity. This is the first demonstration that NsrR contains an NO-sensitive [2Fe-2S] cluster that is required for DNA binding activity