Exploring knowledge exchange: a useful framework for practice and policy

Knowledge translation is underpinned by a dynamic and social knowledge exchange process but there are few descriptions of how this unfolds in practice settings. This has hampered attempts to produce realistic and useful models to help policymakers and researchers understand how knowledge exchange works. This paper reports the results of research which investigated the nature of knowledge exchange. We aimed to understand whether dynamic and fluid definitions of knowledge exchange are valid and to produce a realistic, descriptive framework of knowledge exchange. Our research was informed by a realist approach. We embedded a knowledge broker within three service delivery teams across a large mental health organisation, each of whom was grappling with specific challenges. The knowledge broker participated in the team's problem-solving process and collected observational fieldnotes. We also interviewed the team members. Observational and interview data were analysed quantitatively and qualitatively in order to determine and describe the nature of the knowledge exchange process in more detail. This enabled us to refine our conceptual framework of knowledge exchange. We found that knowledge exchange can be understood as a dynamic and fluid process which incorporates distinct forms of knowledge from multiple sources. Quantitative analysis illustrated that five broadly-defined components of knowledge exchange (problem, context, knowledge, activities, use) can all be in play at any one time and do not occur in a set order. Qualitative analysis revealed a number of distinct themes which better described the nature of knowledge exchange. By shedding light on the nature of knowledge exchange, our findings problematise some of the linear, technicist approaches to knowledge translation. The revised model of knowledge exchange which we propose here could therefore help to reorient thinking about knowledge exchange and act as a starting point for further exploration and evaluation of the knowledge exchange process

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific

Single-shot single-gate RF spin readout in silicon

For solid-state spin qubits, single-gate RF readout can help minimise the number of gates required for scale-up to many qubits since the readout sensor can integrate into the existing gates required to manipulate the qubits (Veldhorst 2017, Pakkiam 2018). However, a key requirement for a scalable quantum computer is that we must be capable of resolving the qubit state within single-shot, that is, a single measurement (DiVincenzo 2000). Here we demonstrate single-gate, single-shot readout of a singlet-triplet spin state in silicon, with an average readout fidelity of $82.9\%$ at a $3.3~\text{kHz}$ measurement bandwidth. We use this technique to measure a triplet $T_-$ to singlet $S_0$ relaxation time of $0.62~\text{ms}$ in precision donor quantum dots in silicon. We also show that the use of RF readout does not impact the maximum readout time at zero detuning limited by the $S_0$ to $T_-$ decay, which remained at approximately $2~\text{ms}$. This establishes single-gate sensing as a viable readout method for spin qubits

Networks and the epidemiology of infectious disease

The science of networks has revolutionised research into the dynamics of interacting elements. It could be argued that epidemiology in particular has embraced the potential of network theory more than any other discipline. Here we review the growing body of research concerning the spread of infectious diseases on networks, focusing on the interplay between network theory and epidemiology. The review is split into four main sections, which examine: the types of network relevant to epidemiology; the multitude of ways these networks can be characterised; the statistical methods that can be applied to infer the epidemiological parameters on a realised network; and finally simulation and analytical methods to determine epidemic dynamics on a given network. Given the breadth of areas covered and the ever-expanding number of publications, a comprehensive review of all work is impossible. Instead, we provide a personalised overview into the areas of network epidemiology that have seen the greatest progress in recent years or have the greatest potential to provide novel insights. As such, considerable importance is placed on analytical approaches and statistical methods which are both rapidly expanding fields. Throughout this review we restrict our attention to epidemiological issues

Validating automated screening for psychological distress by means of computer touchscreens for use in routine oncology practice

The aim of the study was to confirm the validity of using touchscreen computers for screening for clinically significant levels of distress among cancer patients in routine oncology practice. The Hospital Anxiety and Depression Scale (HADS), EORTC Quality of Life questionnaire (QLQ-C30), Mental Health Inventory-MHI5 and a Concerns Checklist were administered via touchscreen computer to 172 chemotherapy out-patients, twice, 2–4 weeks apart. A standard psychiatric interview (Present State Examination – PSE) was conducted within a week of the second assessment. On interview, 23% of patients were identified as ‘cases’. Using the available data (questionnaires, sociodemographic details, self-reported past psychiatric history), the best screening strategy combined scores from MHI-5 and HADS from a single time-point with the following rules: if MHI-5 < 11 = non-case; if MHI-5 ≥ 11 then use HADS; then, if HADS ≥ 9 = ‘case’ (sensitivity 85%; specificity 71%; misclassification rate 26%; positive predictive value 47%). The computerized screening system enabled data to be collected, scored, collated and reported in real time to identify patients who warrant further clinical assessment. It offers the potential for improving ‘case’ detection in routine oncology practice while reducing the burden of questions put to ‘non-cases’. Further work is needed to develop optimal choice of screening questions for this purpose. © 2001 Cancer Research Campaign http://www.bjcancer.co

Advanced Development of the rF1V and rBV A/B Vaccines: Progress and Challenges

The development of vaccines for microorganisms and bacterial toxins with the potential to be used as biowarfare and bioterrorism agents is an important component of the US biodefense program. DVC is developing two vaccines, one against inhalational exposure to botulinum neurotoxins A1 and B1 and a second for Yersinia pestis, with the ultimate goal of licensure by the FDA under the Animal Rule. Progress has been made in all technical areas, including manufacturing, nonclinical, and clinical development and testing of the vaccines, and in assay development. The current status of development of these vaccines, and remaining challenges are described in this chapter

Subspecialty surveillance of long-term course of small and moderate muscular ventricular septal defect: heterogenous practices, low yield.

BACKGROUND: No expert consensus guides practice for intensity of ongoing pediatric cardiology surveillance of hemodynamically insignificant small and moderate muscular ventricular septal defect (mVSD). Therefore, despite the well-established benign natural history of mVSD, there is potential for widely divergent follow up practices. The purpose of this investigation was to evaluate (1) variations in follow up of mVSD within an academic children\u27s hospital based pediatric cardiology practice, and (2) the frequency of active medical or surgical management resulting from follow up of mVSD. METHODS: We retrospectively reviewed records of 600 patients with isolated mVSD echocardiographically diagnosed between 2006 and 2012. Large mVSD were excluded (n = 4). Patient age, gender, echocardiographic findings, provider, recommendations for follow up, and medical and surgical management were tabulated at initial and follow up visits. Independent associations with follow up recommendations were sought using multivariate analysis. RESULTS: Initial echocardiography showed small single mVSD in 509 (85%), multiple small mVSD in 60 (10%), and small-to-moderate or moderate single mVSD in 31 (5%). The mean age at diagnosis was 15.9 months (0-18.5 years) and 25.7 months (0-18.5 years) at last follow up. There was slight female predominance (56.3%). Fourteen pediatric cardiology providers recommended 316 follow up visits, 259 of which were actually accomplished. There were 37 other unplanned follow up visits. No medical or surgical management changes were associated with any of the follow up visits. The proportion of patients for whom follow up was advised varied among providers from 11 to 100%. Independent associations with recommendation for follow up were limited to the identity and clinical volume of the provider, age of the patient, and the presence of multiple, small-to-moderate, or moderate mVSD. CONCLUSIONS: In this large series of moderate or smaller mVSD, pediatric cardiology follow up was commonly recommended but resulted in no active medical or surgical management. Major provider based inconsistency in intensity of follow up of mVSD was identified, but is difficult to justify

Elucidation of the substrate binding site of Siah ubiquitin ligase

The Siah family of RING proteins function as ubiquitin ligase components, contributing to the degradation of multiple targets involved in cell growth, differentiation, angiogenesis, oncogenesis, and inflammation. Previously, a binding motif (degron) was recognized in many of the Siah degradation targets, suggesting that Siah itself may facilitate substrate recognition. We report the crystal structure of the Siah in complex with a peptide containing the degron motif. Binding is within a groove formed in part by the zinc fingers and the first two ß strands of the TRAF-C domain of Siah. We show that residues in the degron, previously described to facilitate binding to Siah, interact with the protein. Mutagenesis of Siah at sites of interaction also abrogates both in vitro peptide binding and destabilization of a known Siah target

Colloidal gas aphron extraction of bioactive compounds from brazilian pinot noir grape pomace.

Residues from the food industry are a problem worldwide. Alternatives have been developed in an attempted to extract compounds from fruit pomace in other to apply those as a natural component in different products. This work has the objective to produce two extracts: (1) ethanolic extract and (2) hot water extract; and characterize the chemical composition of these extracts for future application. In sequence an extraction using surfactants (Colloidal Gas Aphron) was applied in order to obtain a more concentrate and pure extract, in a foam form with better physical properties. The ethanolic extraction was more efficient, obtaining 4 times more bioactive compound (in 100g of pomace: 2670.63 mg Gallic Acid; 65.70 mg anthocyanins and 45,564.78 mmol of Trolox). However the CGA was able to concentrate more the compounds from hot water extract, 61.62% of phenolics compounds were concentrated in the Aphron phase

Can Abbreviated Cardiac Magnetic Resonance Imaging Adequately Support Clinical Decision Making After Repair of Tetralogy of Fallot?

Quantification of pulmonary regurgitation (PR), pulmonary flow distribution, and ventricular function is important for clinical surveillance in repaired Tetralogy of Fallot (TOF). Cardiovascular magnetic resonance (CMR) is the established reference, but cost, test duration, and patient discomfort are potential limitations to its serial use. We investigated whether an Abbreviated CMR protocol would alter clinical decisions in TOF from those that would have been made using a full protocol. Patients > 7 years with repaired TOF were identified. CMR was performed according to standard complete imaging protocol. CMRs were prepared in two ways, Full and Abbreviated and submitted for review by two imaging specialists. In conjunction with clinical information and case-specific quantitative CMR data (PR fraction, ventricular volumes, ejection fraction, branch pulmonary artery flow), Full and Abbreviated image sets were anonymized and uploaded for review. For the first half, Imager 1 received Abbreviated, and Imager 2 Full and for the remaining, Imager 1 received Full and Imager 2 received Abbreviated. Blinded to the other’s choices, Imagers provided clinical decisions. Inter-rater agreement for each decision was measured. In all, 124 studies from 80 patients (mean 17.8 years) were analyzed. For ‘intervention versus no-intervention’ decision, the inter-rater agreement was strong [κ 0.75, p < 0.0001, 95% CI (0.630, 0.869)]. Agreement for recommended timing of follow-up imaging was good (κ 0.64, p < 0.0001, 95% CI (0.474, 0.811)] in the ‘no-intervention’ group. When raters were asked whether or not further imaging was necessary, agreement was modest [κ 0.363 (p < 0.0001), 95% CI (0.038, 0.687)]. In conclusion, Abbreviated CMR yield decisions for clinical care similar to those made using the standard full protocol. These results suggest a potential enhancement of clinical practice in which efficiency and cost saving might be achieved using Abbreviated CMR for routine follow-up surveillance of TOF