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

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

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

A study on the construct validity of the Parent-Child Conflict Tactics Scale (CTSPC) in an urban population in Northeast Brazil

The Parent-Child Conflict Tactics Scale (CTSPC) is one of the most widely used instruments in the world for investigating domestic violence against children, but targeted use has proven inadequate given the phenomenon's complexity. This study focused on the factor structure of CTSPC scales in an urban population in Northeast Brazil. We conducted a cross-sectional study in a cohort of 1,370 children in Salvador, Bahia State. Factor analysis with promax oblique rotation was performed, and the Kuder-Richardson coefficient was calculated. Factor analysis showed a different distribution of items in the factors as compared to the original instrument. Violence showed a gradual profile in each factor. The Kuder-Richardson coefficient was 0.63 for factor 1, 0.59 for factor 2, and 0.42 for factor 3. The items behaved differently from the original instrument, corroborating international studies. These findings support proposing a resizing of the CTSPC

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres