Deficiencies in the transfer and availability of clinical trials evidence: A review of existing systems and standards

Background: Decisions concerning drug safety and efficacy are generally based on pivotal evidence provided by clinical trials. Unfortunately, finding the relevant clinical trials is difficult and their results are only available in text-based reports. Systematic reviews aim to provide a comprehensive overview of the evidence in a specific area, but may not provide the data required for decision making. Methods: We review and analyze the existing information systems and standards for aggregate level clinical trials information from the perspective of systematic review and evidence-based decision making. Results: The technology currently used has major shortcomings, which cause deficiencies in the transfer, traceability and availability of clinical trials information. Specifically, data available to decision makers is insufficiently structured, and consequently the decisions cannot be properly traced back to the underlying evidence. Regulatory submission, trial publication, trial registration, and systematic review produce unstructured datasets that are insufficient for supporting evidence-based decision making. Conclusions: The current situation is a hindrance to policy decision makers as it prevents fully transparent decision making and the development of more advanced decision support systems. Addressing the identified deficiencies would enable more efficient, informed, and transparent evidence-based medical decision making

Benchmarking Ontologies: Bigger or Better?

A scientific ontology is a formal representation of knowledge within a domain, typically including central concepts, their properties, and relations. With the rise of computers and high-throughput data collection, ontologies have become essential to data mining and sharing across communities in the biomedical sciences. Powerful approaches exist for testing the internal consistency of an ontology, but not for assessing the fidelity of its domain representation. We introduce a family of metrics that describe the breadth and depth with which an ontology represents its knowledge domain. We then test these metrics using (1) four of the most common medical ontologies with respect to a corpus of medical documents and (2) seven of the most popular English thesauri with respect to three corpora that sample language from medicine, news, and novels. Here we show that our approach captures the quality of ontological representation and guides efforts to narrow the breach between ontology and collective discourse within a domain. Our results also demonstrate key features of medical ontologies, English thesauri, and discourse from different domains. Medical ontologies have a small intersection, as do English thesauri. Moreover, dialects characteristic of distinct domains vary strikingly as many of the same words are used quite differently in medicine, news, and novels. As ontologies are intended to mirror the state of knowledge, our methods to tighten the fit between ontology and domain will increase their relevance for new areas of biomedical science and improve the accuracy and power of inferences computed across them

Secondary osteosarcoma arising after treatment for childhood hematologic malignancies

Secondary osteosarcoma arising after the treatment of hematologic malignancies other than Hodgkin's lymphoma is rare. We report two cases of secondary osteosarcoma arising after treatment for childhood hematologic malignancies (non-Hodgkin's lymphoma and lymphoblastic leukemia). A 10-year-old boy, at the age of 3, was diagnosed with non-Hodgkin's lymphoma. He received chemotherapy, radiation, and bone-marrow transplantation and then was in complete remission. At 6 years, he complained of increasing pain of the right thigh and was diagnosed with osteoblastic osteosarcoma. A 26-year-old man, at the age of 6, was diagnosed as having acute lymphoblastic leukemia (ALL). He received chemotherapy, radiation, and peripheral blood stem cell transplantation (PBSCT). At 11 years after PBSCT, he visited with the complaint of left lumbar swelling. He was diagnosed with chondroblastic osteosarcoma. In both cases alkaline phosphatase (ALP) had already increased prior to the onset of the symptom. We should rule out secondary osteosarcoma at the abnormal elevation of ALP during clinical follow-up of patients after treatment of childhood hematologic malignancies

Mometasone and desloratadine additive effect on eosinophil survival and cytokine secretion from epithelial cells

Although antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated. The aim was investigate the antiinflammatory additive effect of mometasone and desloratadine on cytokine and sICAM-1 secretion by epithelial cells, and on eosinophil survival stimulated by human epithelial cells secretions from nasal mucosa and polyps. Methods Epithelial cells obtained from nasal mucosa or polyps were stimulated with 10% fetal bovine serum in presence of mometasone (10-11M-10-5M) with/without desloratadine (10-5M). Cytokine and sICAM-1 concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated during 4 days with epithelial cell secretions with (10-11M-10-5M) and/or desloratadine (10-5M) and survival assessed by Trypan blue. Results are expressed as percentage (mean ± SEM) compared to control. Results Fetal bovine serum stimulated IL-6, IL-8, GM-CSF and sICAM-1 secretion. In mucosa and polyp epithelial cells, mometasone inhibited this induced secretion while desloratadine inhibited IL-6 and IL-8. The combination of 10-5M desloratadine and 10-9M mometasone reduced IL-6 secretion (48 ± 11%, p < 0.05) greater extent than mometasone alone (68 ± 10%) compared to control (100%). Epithelial cell secretions induced eosinophil survival from day 1 to 4, this effect being inhibited by mometasone. At day 4, the combination of mometasone (10-11M) and desloratadine (10-5M) provoked an increased inhibition of eosinophil survival induced by cell secretions (27 ± 5%, p < 0.01) than mometasone (44 ± 7%) or desloratadine (46 ± 7%) alone. Conclusions These results suggest that the combination of desloratadine and mometasone furoate have a greater antinflammatory effect in an in vitro model of eosinophil inflammation than those drugs administered alone

First Direct Evidence of Chalcolithic Footwear from the Near Eastern Highlands

In 2008, a well preserved and complete shoe was recovered at the base of a Chalcolithic pit in the cave of Areni-1, Armenia. Here, we discuss the chronology of this find, its archaeological context and its relevance to the study of the evolution of footwear. Two leather samples and one grass sample from the shoe were dated at the Oxford Radiocarbon Accelerator Unit (ORAU). A third leather sample was dated at the University of California-Irvine Accelerator Mass Spectrometry Facility (UCIAMS). The R_Combine function for the three leather samples provides a date range of 3627–3377 Cal BC (95.4% confidence interval) and the calibrated range for the straw is contemporaneous (3627–3377 Cal BC). The shoe was stuffed with loose, unfastened grass (Poaceae) without clear orientation which was more than likely used to maintain the shape of the shoe and/or prepare it for storage. The shoe is 24.5 cm long (European size 37), 7.6 to 10 cm wide, and was made from a single piece of leather that wrapped around the foot. It was worn and shaped to the wearer's right foot, particularly around the heel and hallux where the highest pressure is exerted in normal gait. The Chalcolithic shoe provides solid evidence for the use of footwear among Old World populations at least since the Chalcolithic. Other 4th millennium discoveries of shoes (Italian and Swiss Alps), and sandals (Southern Israel) indicate that more than one type of footwear existed during the 4th millennium BC, and that we should expect to discover more regional variations in the manufacturing and style of shoes where preservation conditions permit

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

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

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns