Considerations for Research Funders and Managers to Facilitate the Translation of Scientific Knowledge into Practice

Research funders and managers can play a critical role in supporting the translation of knowledge into action by facilitating the brokering of knowledge and partnerships. We use semi-structured interviews with a research funding agency, the Australian Centre for International Agricultural Research (ACIAR), to explore (i) ways that funders can facilitate knowledge brokering, the (ii) barriers to, and (iii) enablers for, facilitating knowledge brokering, and (iv) the individual skills and attributes for research program funders and managers to be effective brokers. Based on these findings, we generate three considerations for research funders elsewhere, in particular R4D funders, seeking to build capacity for knowledge brokering: (i) formalise the process and practice, (ii) develop shared language and understanding, and (iii) build individual competencies and capabilities. Our findings complement the existing literature with a context specific analysis of how research funders can facilitate knowledge brokering, and by identifying the barriers and enablers in doing so

Canadian oncogenic human papillomavirus cervical infection prevalence: Systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Oncogenic human papillomavirus (HPV) infection prevalence is required to determine optimal vaccination strategies. We systematically reviewed the prevalence of oncogenic cervical HPV infection among Canadian females prior to immunization.</p> <p>Methods</p> <p>We included studies reporting DNA-confirmed oncogenic HPV prevalence estimates among Canadian females identified through searching electronic databases (e.g., MEDLINE) and public health websites. Two independent reviewers screened literature results, abstracted data and appraised study quality. Prevalence estimates were meta-analyzed among routine screening populations, HPV-positive, and by cytology/histology results.</p> <p>Results</p> <p>Thirty studies plus 21 companion reports were included after screening 837 citations and 120 full-text articles. Many of the studies did not address non-response bias (74%) or use a representative sampling strategy (53%).</p> <p>Age-specific prevalence was highest among females aged < 20 years and slowly declined with increasing age. Across all populations, the highest prevalence estimates from the meta-analyses were observed for HPV types 16 (routine screening populations, 8 studies: 8.6% [95% confidence interval 6.5-10.7%]; HPV-infected, 9 studies: 43.5% [28.7-58.2%]; confirmed cervical cancer, 3 studies: 48.8% [34.0-63.6%]) and 18 (routine screening populations, 8 studies: 3.3% [1.5-5.1%]; HPV-infected, 9 studies: 13.6% [6.1-21.1%], confirmed cervical cancer, 4 studies: 17.1% [6.4-27.9%].</p> <p>Conclusion</p> <p>Our results support vaccinating females < 20 years of age, along with targeted vaccination of some groups (e.g., under-screened populations). The highest prevalence occurred among HPV types 16 and 18, contributing a combined cervical cancer prevalence of 65.9%. Further cancer protection is expected from cross-protection of non-vaccine HPV types. Poor study quality and heterogeneity suggests that high-quality studies are needed.</p

LDL-cholesterol lowering effect of a generic product of simvastatin compared to simvastatin (Zocor™) in Thai hypercholesterolemic subjects – a randomized crossover study, the first report from Thailand

BACKGROUND: It is commonly agreed that people with a high blood LDL-cholesterol will have a higher risk of coronary artery disease (CAD) than people with low blood LDL-cholesterol. Due to the increasingly high costs of medication in Thailand, the government has set up several measures to combat the problem. One of such strategies is to promote the utilization of locally manufactured drug products, especially those contained in the National Drug List. Simvastatin, an HMG-CoA reductase inhibitor, is listed as an essential drug for the treatment of hypercholesterolemia. Here, we reported the study on the LDL-cholesterol-lowering effect of a generic simvastatin product in comparison with the Zocor(©), in 43 healthy thai volunteers. METHOD: The generic product tested was Eucor(©), locally manufactured by Greater Pharma Ltd., Part, Thailand, and the reference product was Zocor(©) (Merck Sharp & Dohme, USA). The two products were administered as 10-mg single oral doses in a two-period crossover design. After drug administration, serial blood samples were collected every 4 weeks for 16 weeks. The major parameter monitored in this study was blood LDL-cholesterol. RESULT: After taking the drugs for the first 8 weeks, no statistically significant difference was dedected in blood LDL-cholesterol between the first (Zocor(©)-treated) and the second (Eucor(©)-treated) groups. After crossover and taking drugs for further 8 weeks, a similar result was obtained, i.e., no significant difference in blood LDL-cholesterol between the first (Eucor(©)-treated) and the second (Zocor(©)-treated) groups was observed. Upon completion of the 16-week study, there was also no statisticaly significant difference in the changes of all tested blood parameters between the two products (randomized block ANOVA, N = 37). Only minor side effects, mainly dizziness and nausea, were observed in both products. CONCLUSION: Our study demonstrated no significant differences in the therapeutic effect and safety between the generic and original simvastatin products

Guidelines on acute gastroenteritis in children: a critical appraisal of their quality and applicability in primary care

<p>Abstract</p> <p>Background</p> <p>Reasons for poor guideline adherence in acute gastroenteritis (AGE) in children in high-income countries are unclear, but may be due to inconsistency between guideline recommendations, lack of evidence, and lack of generalizability of the recommendations to general practice. The aim of this study was to assess the quality of international guidelines on AGE in children and investigate the generalizability of the recommendations to general practice.</p> <p>Methods</p> <p>Guidelines were retrieved from websites of professional medical organisations and websites of institutes involved in guideline development. In addition, a systematic search of the literature was performed. Articles were selected if they were a guideline, consensus statement or care protocol.</p> <p>Results</p> <p>Eight guidelines met the inclusion criteria, the quality of the guidelines varied. 242 recommendations on diagnosis and management were found, of which 138 (57%) were based on evidence.</p> <p>There is a large variety in the classification of symptoms to different categories of dehydration. No signs are generalizable to general practice.</p> <p>It is consistently recommended to use hypo-osmolar ORS, however, the recommendations on ORS-dosage are not evidence based and are inconsistent. One of 14 evidence based recommendations on therapy of AGE is based on outpatient research and is therefore generalizable to general practice.</p> <p>Conclusions</p> <p>The present study shows considerable variation in the quality of guidelines on AGE in children, as well as inconsistencies between the recommendations. It remains unclear how to asses the extent of dehydration and determine the preferred treatment or referral of a young child with AGE presenting in general practice.</p

GWAS Meets Microarray: Are the Results of Genome-Wide Association Studies and Gene-Expression Profiling Consistent? Prostate Cancer as an Example

Genome-wide association studies (GWASs) and global profiling of gene expression (microarrays) are two major technological breakthroughs that allow hypothesis-free identification of candidate genes associated with tumorigenesis. It is not obvious whether there is a consistency between the candidate genes identified by GWAS (GWAS genes) and those identified by profiling gene expression (microarray genes).We used the Cancer Genetic Markers Susceptibility database to retrieve single nucleotide polymorphisms from candidate genes for prostate cancer. In addition, we conducted a large meta-analysis of gene expression data in normal prostate and prostate tumor tissue. We identified 13,905 genes that were interrogated by both GWASs and microarrays. On the basis of P values from GWASs, we selected 1,649 most significantly associated genes for functional annotation by the Database for Annotation, Visualization and Integrated Discovery. We also conducted functional annotation analysis using same number of the top genes identified in the meta-analysis of the gene expression data. We found that genes involved in cell adhesion were overrepresented among both the GWAS and microarray genes.We conclude that the results of these analyses suggest that combining GWAS and microarray data would be a more effective approach than analyzing individual datasets and can help to refine the identification of candidate genes and functions associated with tumor development

Leaky doors: private captivity as a prominent source of bird introductions in Australia

The international pet trade is a major source of emerging invasive vertebrate species. We used online resources as a novel source of information for accidental bird escapes, and we investigated the factors that influence the frequency and distribution of bird escapes at a continental scale. We collected information on over 5,000 pet birds reported to be missing on animal websites during the last 15 years in Australia. We investigated whether variables linked to pet ownership successfully predicted bird escapes, and we assessed the potential distribution of these escapes. Most of the reported birds were parrots (> 90%), thus, we analysed factors associated with the frequency of parrot escapes. We found that bird escapes in Australia are much more frequent than previously acknowledged. Bird escapes were reported more frequently within, or around, large Australian capital cities. Socio-economic factors, such as the average personal income level of the community, and the level of human modification to the environment were the best predictors of bird escapes. Cheaper parrot species, Australian natives, and parrot species regarded as peaceful or playful were the most frequently reported escapees. Accidental introductions have been overlooked as an important source of animal incursions. Information on bird escapes is available online in many higher income countries and, in Australia, this is particularly apparent for parrot species. We believe that online resources may provide useful tools for passive surveillance for non-native pet species. Online surveillance will be particularly relevant for species that are highly reported, such as parrots, and species that are either valuable or highly commensal.Miquel Vall-llosera, Phillip Casse

Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer

<p>Abstract</p> <p>Background</p> <p>Genome wide association studies (GWAS) have identified several genetic variants that are associated with prostate cancer. Most of these variants, like other GWAS association signals, are located in non-coding regions of potential candidate genes, and thus could act at the level of the mRNA transcript.</p> <p>Methods</p> <p>We measured the expression and isoform usage of seven prostate cancer candidate genes in benign and malignant prostate by real-time PCR, and correlated these factors with cancer status and genotype at the GWAS risk variants.</p> <p>Results</p> <p>We determined that levels of <it>LMTK2 </it>transcripts in prostate adenocarcinomas were only 32% of those in benign tissues (p = 3.2 × 10^-7), and that an independent effect of genotype at variant rs6465657 on <it>LMTK2 </it>expression in benign (n = 39) and malignant tissues (n = 21) was also evident (P = 0.002). We also identified that whilst <it>HNF1B(C) </it>and <it>MSMB2 </it>comprised the predominant isoforms in benign tissues (90% and 98% of total <it>HNF1B </it>or <it>MSMB </it>expression)<it>, HNF1B(B) and MSMB1 </it>were predominant in malignant tissue (95% and 96% of total <it>HNF1B </it>or <it>MSMB </it>expression; P = 1.7 × 10^-7and 4 × 10^-4respectively), indicating major shifts in isoform usage.</p> <p>Conclusions</p> <p>Our results indicate that the amount or nature of mRNA transcripts expressed from the <it>LMTK2</it>, <it>HNF1B </it>and <it>MSMB </it>candidate genes is altered in prostate cancer, and provides further evidence for a role for these genes in this disorder. The alterations in isoform usage we detect highlights the potential importance of alternative mRNA processing and moderation of mRNA stability as potentially important disease mechanisms.</p

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

The insulin-like growth factor system is modulated by exercise in breast cancer survivors: a systematic review and meta-analysis

Abbreviations: CI, Confidence interval; ELISA, Enzyme-linked immunosorbent assay; IGF, Insulin-like growth factors; IGFBP, Insulin-like growth factor binding protein; MD, Mean difference; PEDro, Physiotherapy evidence database; RCT, Randomized controlled trials; SD, Standard deviation.Background: Insulin-like growth factors (IGF´s) play a crucial role in controlling cancer cell proliferation, differentiation and apoptosis. Exercise has been postulated as an effective intervention in improving cancerrelated outcomes and survival, although its effects on IGF´s are not well understood. This meta-analysis aimed to determine the effects of exercise in modulating IGF´s system in breast cancer survivors. Methods: Databases of PuMed, EMBASE, Cochrane Central Register of Controlled Trials, EMBASE, ClinicalTrials. gov, SPORTDiscus, LILACS and Scopus were systematically searched up to November 2014. Effect estimates were calculated through a random-effects model of meta-analysis according to the DerSimonian and Laird method. Heterogeneity was evaluated with the I2 test. Risk of bias and methodological quality were evaluated using the PEDro score. Results: Five randomized controlled trials (n = 235) were included. Most women were post-menopausal. Highquality and low risk of bias were found (mean PEDro score = 6.2 ± 1). Exercise resulted in significant improvements on IGF-I, IGF-II, IGFBP-I, IGFBP-3, Insulin and Insulin resistance (P < 0.05). Non-significant differences were found for Glucose. Aerobic exercise improved IGF-I, IGFBP-3 and Insulin. No evidence of publication bias was detected by Egger´s test (p = 0.12). Conclusions: Exercise improved IGF´s in breast cancer survivors. These findings provide novel insight regarding the molecular effects of exercise on tumoral microenvironment, apoptosis and survival in breast cancer survivors

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO