Are Researchers Registering Systematic Reviews in ClinicalTrials.gov?

BACKGROUND: ClinicalTrials.gov (CT) is an increasingly important resource for systematic reviewers attempting to identify published and unpublished clinical studies. In addition to clinical studies, however, some searches of the CT database also return systematic reviews (SRs). When I inquired about the SRs appearing in the results, the NLM Help Desk responded that “We do not recommend that systematic reviews be entered in ClinicalTrials.gov, since we only want the results of a clinical trial entered once. However, we will not refuse them if they are entered.” I wanted to find out how many SRs are included, describe their characteristics, and suggest search strategies for those wishing to exclude them. METHODS: Conduct a CT search for “systematic review” without limiting by field in case an SR was not explicitly titled as such. Screen the results for those records representing SRs as opposed to, e.g., mentioning one in the background to a clinical trial. Identify the total number of SRs. Test strategies for their ability to exclude them and calculate sensitivity, precision and specificity. RESULTS: I ran a search for “systematic review” (in quotes) in the advanced search \u3e Search Terms (field) on July 14, 2016, and applying no other limits, downloaded 181 results for analysis from among the 220,113 total number of records in the CT database. Of the 181 records, 47 (26%) were systematic reviews. All 47 were listed as Study Type: Observational. The remaining 134 records that were not SRs included a mix of Observational (21, 15.7%) and Interventional (113, 84.3%) study types. Title searching offers an effective way to avoid SRs: all but two true SRs had “systematic review” or “meta-analysis” in the Brief or Official Title. So in the expert search you could add the filter: NOT ( systematic review [TITLES] OR metaanalysis [TITLES] ). This filter has a sensitivity of 94.8%, precision of 96.9%, and specificity of 91.5%. CONCLUSION: The number of systematic reviews registered in CT is small at this time. They can be accurately avoided if you are looking for interventional studies by using the Study Type field, but not if you are looking for observational studies. Using the proposed title searching filter offers an effective way to avoid them. Librarians should advise their teams to register systematic reviews in appropriate sources such as PROSPERO (http://www.crd.york.ac.uk/PROSPERO/), but not ClinicalTrials.gov

Replacement for the 10 page paper? A pilot project using blogs and wikis for a collaborative EBM assignment in a 3rd year internal medical clerkship

Objective Pilot a group assignment using blogs and wikis to develop evidence-based medicine skills in third year medical students on an internal medicine clerkship. Instead of the clerkship’s previous individual ten-page paper assignment, the students were divided into four groups of sixteen. During the clerkship, students are on geographically dispersed rotations. The earlier ten-page paper had required the students to complete a patient history and physical write-up. With the pilot project, each group was assigned a librarian and a physician faculty mentor. Each student recorded on the blog a clinical scenario and question they encountered. They were encouraged to communicate with the librarian to construct a well formed clinical question. Each student group then came to consensus on which question to pursue and collaborated on a wiki including a list of citations to the best available evidence, a critique of the studies, and implications for the patient

Supporting the Occupational Therapy Student in the Production and Dissemination of Systematic Reviews: An Interprofessional Collaboration among Librarians and Occupational Therapy Faculty

Objectives This poster describes the outcomes of a curriculum-based collaboration between librarians and OT faculty (‘collaboration’) to enhance graduate student skills for conducting a systematic review (SR); the collaboration included database instruction, bibliographic management software, and culminated in student presentations to healthcare practitioners for continuing education credit. Three outcome areas are discussed: impact of the collaboration on student satisfaction and perceived competence; characteristics of the included literature; and the dissemination of SR findings to healthcare practitioners. Methods Three librarians participated in the instruction and the institutional repository (Jefferson Digital Commons; JDC) deposits. A total of 132 students over a period of two years (2013-2014) completed the curriculum, engaging with librarians and OT faculty to iteratively build on skills. At the conclusion of their curriculum, the capstone presentations were recorded and made freely available through the JDC. Quantitative data were examined with descriptive statistics in SPSS, and qualitative data were thematically coded by hand: course evaluations, practitioner attendance, bibliographic evaluations of the systematic reviews, and download statistics from the institutional repository. Results Students reported on open-ended course evaluation questions that among the top three concepts learned was ‘how to conduct a replicable and effective search.’ On multiple answer questions 83.6% of students selected the ‘collaborative librarian-faculty lecture’ as among the most helpful lectures offered, and 78.2% selected ‘working with librarian staff and course mentors to develop a search strategy’ as highly rated among course activities. Bibliographic data were extracted from 22 of 28 capstone presentations available for analysis (2013-2014) in the institutional repository, which contained 305 citations from 157 journals. The average of age of included articles was 4.8 years (SD=4.2, Range=0-24). Among the top 10 cited journals were 2 occupational therapy, 5 rehabilitation, and 3 specialty. Overall health care practitioner attendance at student capstones from 2012-2014 was 323. JDC recordings (as of 1/6/2015) had been accessed from 25 different countries, and are located most frequently via Google, JDC, and GoogleScholar. The total number of views was 1,446, and the total number of hours viewed was 163 hours. Conclusions Librarian-faculty collaborations resulted in high student perception of competence to conduct systematic reviews, utilization of a broad variety of peer-reviewed journals, and enhanced dissemination of evidence

Detection of weak gravitational lensing distortions of distant galaxies by cosmic dark matter at large scales

Most of the matter in the universe is not luminous and can be observed directly only through its gravitational effect. An emerging technique called weak gravitational lensing uses background galaxies to reveal the foreground dark matter distribution on large scales. Light from very distant galaxies travels to us through many intervening overdensities which gravitationally distort their apparent shapes. The observed ellipticity pattern of these distant galaxies thus encodes information about the large-scale structure of the universe, but attempts to measure this effect have been inconclusive due to systematic errors. We report the first detection of this ``cosmic shear'' using 145,000 background galaxies to reveal the dark matter distribution on angular scales up to half a degree in three separate lines of sight. The observed angular dependence of this effect is consistent with that predicted by two leading cosmological models, providing new and independent support for these models.Comment: 18 pages, 5 figures: To appear in Nature. (This replacement fixes tex errors and typos.

VEZF1 elements mediate protection from DNA methylation

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Enhancing Occupational Therapy Student Systematic Reviews: An Occupational Therapy Faculty and Librarian Collaboration

Objective: To describe the outcomes of a curriculum-based collaboration between Occupational Therapy faculty and librarians (‘collaboration’) to enhance graduate student skills for conducting and disseminating a systematic review (SR

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Measurement of triple gauge boson couplings from W⁺W⁻ production at LEP energies up to 189 GeV

A measurement of triple gauge boson couplings is presented, based on W-pair data recorded by the OPAL detector at LEP during 1998 at a centre-of-mass energy of 189 GeV with an integrated luminosity of 183 pb⁻¹. After combining with our previous measurements at centre-of-mass energies of 161–183 GeV we obtain κ = 0.97_{-0.16}^{+0.20}, g_{1}^{z} = 0.991_{-0.057}^{+0.060} and λ = -0.110_{-0.055}^{+0.058}, where the errors include both statistical and systematic uncertainties and each coupling is determined by setting the other two couplings to their Standard Model values. These results are consistent with the Standard Model expectations