A protocol for co-creating research project lay summaries with stakeholders:Guideline development for Canada's AGE-WELL Network

Background Funding bodies increasingly require researchers to write lay summaries to communicate projects’ real-world relevance to the public in an accessible way. However, research proposals and findings are generally not easily readable or understandable by non-specialist readers. Many researchers find writing lay summaries difficult because they typically write for fellow subject specialists or academics rather than the general public or a non-specialist audience. The primary objective of our project is to develop guidelines for researchers in Canada’s AGE-WELL Network of Centres of Excellence, and ultimately various other disciplines, sectors, and institutions, to co-create lay summaries of research projects with stakeholders. To begin, we produced a protocol for co-creating a lay summary based on workshops we organized and facilitated for an AGE-WELL researcher. This paper presents the lay summary co-creation protocol that AGE-WELL researchers will be invited to use. Methods Eligible participants in this project will be 24 AgeTech project researchers who are funded by the AGE-WELL network in its Core Research Program 2020. If they agree to participate in this project, we will invite them to use our protocol to co-produce a lay summary of their respective projects with stakeholders. The protocol comprises six steps: Investigate principles of writing a good lay summary, identify the target readership, identify stakeholders to collaborate with, recruit the identified stakeholders to work on a lay summary, prepare for workshop sessions, and execute the sessions. To help participants through the process, we will provide them with a guide to developing an accessible, readable research lay summary, help them make decisions, and host, and facilitate if needed, their lay summary co-creation workshops. Discussion Public-facing research outputs, including lay summaries, are increasingly important knowledge translation strategies to promote the impact of research on real-world issues. To produce lay summaries that include information that will interest a non-specialist readership and that are written in accessible language, stakeholder engagement is key. Furthermore, both researchers and stakeholders benefit by participating in the co-creation process. We hope the protocol helps researchers collaborate with stakeholders effectively to co-produce lay summaries that meet the needs of both the public and project funders

Vertex importance extension of betweenness centrality algorithm

Variety of real-life structures can be simplified by a graph. Such simplification emphasizes the structure represented by vertices connected via edges. A common method for the analysis of the vertices importance in a network is betweenness centrality. The centrality is computed using the information about the shortest paths that exist in a graph. This approach puts the importance on the edges that connect the vertices. However, not all vertices are equal. Some of them might be more important than others or have more significant influence on the behavior of the network. Therefore, we introduce the modification of the betweenness centrality algorithm that takes into account the vertex importance. This approach allows the further refinement of the betweenness centrality score to fulfill the needs of the network better. We show this idea on an example of the real traffic network. We test the performance of the algorithm on the traffic network data from the city of Bratislava, Slovakia to prove that the inclusion of the modification does not hinder the original algorithm much. We also provide a visualization of the traffic network of the city of Ostrava, the Czech Republic to show the effect of the vertex importance adjustment. The algorithm was parallelized by MPI (http://www.mpi-forum.org/) and was tested on the supercomputer Salomon (https://docs.it4i.cz/) at IT4Innovations National Supercomputing Center, the Czech Republic.808726

Structural and biophysical analysis of nuclease protein antibiotics

© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society. Protein antibiotics (bacteriocins) are a large and diverse family of multidomain toxins that kill specific Gram-negative bacteria during intraspecies competition for resources. Our understanding of the mechanism of import of such potent toxins has increased significantly in recent years, especially with the reporting of several structures of bacteriocin domains. Less well understood is the structural biochemistry of intact bacteriocins and how these compare across bacterial species. Here, we focus on endonuclease (DNase) bacteriocins that target the genomes of Escherichia coli and Pseudomonas aeruginosa, known as E-Type colicins and S-Type pyocins, respectively, bound to their specific immunity (Im) proteins. First, we report the 3.2 Å structure of the DNase colicin ColE9 in complex with its ultra-high affinity Im protein, Im9. In contrast with Im3, which when bound to the ribonuclease domain of the homologous colicin ColE3 makes contact with the translocation (T) domain of the toxin, we find that Im9 makes no such contact and only interactions with the ColE9 cytotoxic domain are observed. Second, we report small-Angle X-ray scattering data for two S-Type DNase pyocins, S2 and AP41, into which are fitted recently determined X-ray structures for isolated domains. We find that DNase pyocins and colicins are both highly elongated molecules, even though the order of their constituent domains differs. We discuss the implications of these architectural similarities and differences in the context of the translocation mechanism of protein antibiotics through the cell envelope of Gram-negative bacteria

Arterial Stiffness in a Cohort of Young People Living With Perinatal HIV and HIV Negative Young People in England

Background: Antiretroviral therapy (ART) has increased life expectancy and consequently the risk of cardiovascular disease (CVD) in adults living with HIV. We investigated the levels and predictors of arterial stiffness in young people (YP) living with perinatal HIV (PHIV) and HIV negative YP in the Adolescents and Adults Living with Perinatal HIV (AALPHI) study. Methods: AALPHI was a prospective study evaluating the impact of HIV infection and exposure to ART on YP living with PHIV (aged 13-21 years) who had known their HIV status for at least 6 months, and HIV negative YP (aged 13-23 years) who either had a sibling, friend or parent living with HIV. Participants were enrolled from HIV clinics and community services in England. Two hundred and thirteen PHIV and 65 HIV negative YP (42% siblings of PHIV) had pulse wave velocity (PWV) measurements taken (Vicorder software) from the supra-sternal notch to the middle of the thigh cuff, at their second interview in the study between 2015 and 2017. Average PWV was calculated from the three closest readings (≥3 and ≤ 12 m/s) within 0.6 m/s of each other. Linear regression examined predictors of higher (worse) PWV, including age, sex, HIV status and height as a priori, ethnicity, born outside UK/Ireland, alcohol/nicotine/drug use, weight, waist-to-hip-ratio, mean arterial pressure (MAP), caffeine 2 h before PWV and nicotine on day of PWV. A separate PHIV model included CD4, viral load, years taking ART and ART regimen. Findings: One hundred and twenty eight (60%) PHIV and 45 (69%) HIV negative YP were female (p = 0.18), with median (IQR) age 18 (16, 20) and 18 (16, 21) years (p = 0.48) respectively. Most PHIV were taking a combination of three ART drugs from two classes. There was a trend toward higher (worse) mean PWV in the PHIV group than the HIV negative group [unvariable analysis 6.15 (SD 0.83) m/s vs. 5.93 (0.70) m/s, respectively, unadjusted p = 0.058], which was statistically significant in the multivariable analysis [adjusted p (ap) = 0.020]. In multivariable analysis being male (ap = 0.002), older age (ap < 0.001), higher MAP (ap < 0.001) and nicotine use on day of measurement (ap = 0.001) were also predictors of higher PWV. The predictors were the same in the PHIV model. Interpretation: By late adolescence PHIV had worse PWV in comparison to HIV negative peers, and traditional risk factors for CVD (higher arterial pressure, being male and older age) were associated with higher PWV values. Regular detailed monitoring of cardiovascular risk factors should become standard of care for every young person with PHIV worldwide

Direct intra-tumoral injection of zinc-acetate halts tumor growth in a xenograft model of prostate cancer

Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral injection of zinc could impact prostate cancer growth. In this study, we evaluated the cytotoxic properties of the pH neutral salt zinc acetate on the prostate cancer cell lines PC3, DU145 and LNCaP. Zinc acetate killed prostate cancer cell lines in vitro, independent of androgen sensitivity, in a dose-dependent manner in a range between 200 and 600 μM. Cell death occurred rapidly with 50% cell death by six hours and maximal cell death by 18 hours. We next established a xenograft model of prostate cancer and tested an experimental treatment protocol of direct intra-tumoral injection of zinc acetate. We found that zinc treatments halted the growth of the prostate cancer tumors and substantially extended the survival of the animals, whilst causing no detectable cytoxicity to other tissues. Thus, our studies form a solid proof-of-concept that direct intra-tumoral injection of zinc acetate could be a safe and effective treatment strategy for prostate cancer

Diminished temperature and vegetation seasonality over northern high latitudes

Global temperature is increasing, especially over northern lands (>50° N), owing to positive feedbacks1. As this increase is most pronounced in winter, temperature seasonality (ST)—conventionally defined as the difference between summer and winter temperatures—is diminishing over time2, a phenomenon that is analogous to its equatorward decline at an annual scale. The initiation, termination and performance of vegetation photosynthetic activity are tied to threshold temperatures3. Trends in the timing of these thresholds and cumulative temperatures above them may alter vegetation productivity, or modify vegetation seasonality (SV), over time. The relationship between ST and SV is critically examined here with newly improved ground and satellite data sets. The observed diminishment of ST and SV is equivalent to 4° and 7° (5° and 6°) latitudinal shift equatorward during the past 30 years in the Arctic (boreal) region. Analysis of simulations from 17 state-of-the-art climate models4 indicates an additional STdiminishment equivalent to a 20° equatorward shift could occur this century. How SV will change in response to such large projected ST declines and the impact this will have on ecosystem services5 are not well understood. Hence the need for continued monitoring6 of northern lands as their seasonal temperature profiles evolve to resemble thosefurther south.Lopullinen vertaisarvioitu käsikirjoitu

Entropy bounds in terms of the w parameter

In a pair of recent articles [PRL 105 (2010) 041302 - arXiv:1005.1132; JHEP 1103 (2011) 056 - arXiv:1012.2867] two of the current authors have developed an entropy bound for equilibrium uncollapsed matter using only classical general relativity, basic thermodynamics, and the Unruh effect. An odd feature of that bound, S <= A/2, was that the proportionality constant, 1/2, was weaker than that expected from black hole thermodynamics, 1/4. In the current article we strengthen the previous results by obtaining a bound involving the (suitably averaged) w parameter. Simple causality arguments restrict this averaged parameter to be <= 1. When equality holds, the entropy bound saturates at the value expected based on black hole thermodynamics. We also add some clarifying comments regarding the (net) positivity of the chemical potential. Overall, we find that even in the absence of any black hole region, we can nevertheless get arbitrarily close to the Bekenstein entropy.Comment: V1: 14 pages. V2: One reference added. V3: This version accepted for publication in JHE

Nutrition education: a questionnaire for assessment and teaching

It is generally recognized that there is a need for improved teaching of nutrition in medical schools and for increased education of the general population. A questionnaire, derived in part from a study of physician knowledge, was administered to first year medical students in order to assess their knowledge of various aspects of nutrition and metabolism, and as a teaching tool to transmit information about the subject. The performance of first year students was consistent with a generally educated population but there were surprising deficits in some fundamental areas of nutrition. Results of the questionnaire are informative about student knowledge, and immediate reinforcement from a questionnaire may provide a useful teaching tool. In addition, some of the subject matter can serve as a springboard for discussion of critical issues in nutrition such as obesity and markers for cardiovascular disease. A major barrier to improved teaching of nutrition is the lack of agreement on some of these critical issues and there are apparent inconsistencies in recommendations of government and health agencies. It seems reasonable that improved teaching should address the lack of knowledge of nutrition, rather than knowledge of official guidelines. Student awareness of factual information should be the primary goal

Two-sample mendelian randomization analysis of associations between periodontal disease and risk of cancer.

Background: Observational studies indicate that periodontal disease may increase the risk of colorectal, lung, and pancreatic cancers. Using a 2-sample Mendelian randomization (MR) analysis, we assessed whether a genetic predisposition index for periodontal disease was associated with colorectal, lung, or pancreatic cancer risks. Methods: Our primary instrument included single nucleotide polymorphisms with strong genome-wide association study evidence for associations with chronic, aggressive, and/or severe periodontal disease (rs729876, rs1537415, rs2738058, rs12461706, rs16870060, rs2521634, rs3826782, and rs7762544). We used summary-level genetic data for colorectal cancer (n = 58 131 cases; Genetics and Epidemiology of Colorectal Cancer Consortium, Colon Cancer Family Registry, and Colorectal Transdisciplinary Study), lung cancer (n = 18 082 cases; International Lung Cancer Consortium), and pancreatic cancer (n = 9254 cases; Pancreatic Cancer Consortia). Four MR approaches were employed for this analysis: random-effects inverse-variance weighted (primary analyses), Mendelian Randomization-Pleiotropy RESidual Sum and Outlier, simple median, and weighted median. We conducted secondary analyses to determine if associations varied by cancer subtype (colorectal cancer location, lung cancer histology), sex (colorectal and pancreatic cancers), or smoking history (lung and pancreatic cancer). All statistical tests were 2-sided. Results: The genetic predisposition index for chronic or aggressive periodontitis was statistically significantly associated with a 3% increased risk of colorectal cancer (per unit increase in genetic index of periodontal disease; P = .03), 3% increased risk of colon cancer (P = .02), 4% increased risk of proximal colon cancer (P = .01), and 3% increased risk of colorectal cancer among females (P = .04); however, it was not statistically significantly associated with the risk of lung cancer or pancreatic cancer, overall or within most subgroups. Conclusions: Genetic predisposition to periodontitis may be associated with colorectal cancer risk. Further research should determine whether increased periodontitis prevention and increased cancer surveillance of patients with periodontitis is warranted

Single Photon Signals for Warped Quantum Gravity at a Linear e+-e- Collider

We study the `single photon' process e+- e- -> gamma nu nubar with contributions due to exchange of massive gravitons in the Randall- Sundrum model of low-scale quantum gravity. It is shown that for significant regions in the parameter space, this process unambiguously highlights the resonance structure of the graviton sector. Even in the non-resonant part of the parameter space, we show that comparison with the benchmark process e+- e- -> mu+- mu- can clearly distinguish signals for warped gravity from similar signals for large extra dimensions.Comment: Published version; figures change