Provenance evidence for Roman lead artefacts of distinct chronology from Portuguese archaeological sites

A set of 24 glandes plumbeae found at Alto dos Cacos, a Roman Republican military camp located in the Tagus valley, Portugal, was analysed by a quadrupole based ICP-MS to determine the tin (Sn) content and lead (Pb) isotope ratios. Results were compared with similar data previously obtained for fistulae plumbeae aquariae from Conimbriga, an important Lusitanian Roman centre during the Empire. Low Sn contents (≤0.01 wt%) were observed in 25% of glandes plumbeae indicating that were probably made with non-recycled lead. A similar situation was perceived for the set of fistulae aquariae, although most of the remaining fistulae present systematically higher Sn concentrations than those of glandes suggesting that lead recycling increased during the Empire. Pb isotope ratios distribution differentiated the analysed samples into two distinct groups: one composed by most of glandes plumbeae (15) and the other by the remaining glandes plumbeae (9) and all fistulae aquariae. The comparison with Pb isotope ratios of the published data for several lead ore deposits, exploited by the Roman in Iberian Peninsula, suggests that lead used in the manufacture of most of the glandes plumbeae would come from Linares-La Carolina, Alcudia Valley and Ossa Morena Zone. Also, some glandes could have been made using these ores, probably mixed with lead ores from Gallia Narbonensis (Southern France) or from Sardinia in the Mediterranean region. On the other hand, lead used in most fistulae aquariae came from Iberian mines, namely from Sierra Morena (Alcudia Valley and Linares-La Carolina mines) and Ossa Morena mining district, although in some cases, probably mixed with lead from the Iberian Pyrite Belt.info:eu-repo/semantics/publishedVersio

What carcinoembryonic antigen level should trigger further investigation during colorectal cancer follow-up? A systematic review and secondary analysis of a randomised controlled trial

Background Following primary surgical and adjuvant treatment for colorectal cancer, many patients are routinely followed up with blood carcinoembryonic antigen (CEA) testing. Objective To determine how the CEA test result should be interpreted to inform the decision to undertake further investigation to detect treatable recurrences. Design Two studies were conducted: (1) a Cochrane review of existing studies describing the diagnostic accuracy of blood CEA testing for detecting colorectal recurrence; and (2) a secondary analysis of data from the two arms of the FACS (Follow-up After Colorectal Surgery) trial in which CEA testing was carried out. Setting and participants The secondary analysis was based on data from 582 patients recruited into the FACS trial between 2003 and 2009 from 39 NHS hospitals in England with access to high-volume services offering surgical treatment of metastatic recurrence and followed up for 5 years. CEA testing was undertaken in general practice. Results In the systematic review we identified 52 studies for meta-analysis, including in aggregate 9717 participants (median study sample size 139, interquartile range 72–247). Pooled sensitivity at the most commonly recommended threshold in national guidelines of 5 µg/l was 71% [95% confidence interval (CI) 64% to 76%] and specificity was 88% (95% CI 84% to 92%). In the secondary analysis of FACS data, the diagnostic accuracy of a single CEA test was less than was suggested by the review [area under the receiver operating characteristic curve (AUC) 0.74, 95% CI 0.68 to 0.80]. At the commonly recommended threshold of 5 µg/l, sensitivity was estimated as 50.0% (95% CI 40.1% to 59.9%) and lead time as about 3 months. About four in 10 patients without a recurrence will have at least one false alarm and six out of 10 tests will be false alarms (some patients will have multiple false alarms, particularly smokers). Making decisions to further investigate based on the trend in serial CEA measurements is better (AUC for positive trend 0.85, 95% CI 0.78 to 0.91), but to maintain approximately 70% sensitivity with 90% specificity it is necessary to increase the frequency of testing in year 1 and to apply a reducing threshold for investigation as measurements accrue. Limitations The reference standards were imperfect and the main analysis was subject to work-up bias and had limited statistical precision and no external validation. Conclusions The results suggest that (1) CEA testing should not be used alone as a triage test; (2) in year 1, testing frequency should be increased (to monthly for 3 months and then every 2 months); (3) the threshold for investigating a single test result should be raised to 10 µg/l; (4) after the second CEA test, decisions to investigate further should be made on the basis of the trend in CEA levels; (5) the optimal threshold for investigating the CEA trend falls over time; and (6) continuing smokers should not be monitored with CEA testing. Further research is needed to explore the operational feasibility of monitoring the trend in CEA levels and to externally validate the proposed thresholds for further investigation. Study registration This study is registered as PROSPERO CRD42015019327 and Current Controlled Trials ISRCTN93652154. Funding The main FACS trial and this substudy were funded by the National Institute for Health Research Health Technology Assessment programme

Identification and characterization by LC-UV-MS/MS of melanotan II skin-tanning products sold illegally on the Internet

New methods were developed and validated to determine the identity, contents, and purity of samples of melanotan II, asynthetic melanocortin receptor agonist, sold in vials as injectable skin-tanning products that were purchased from three online shops. Methods were based on liquid chromatography with ultra-violet detection (LC-UV) at wavelength 218 nm, and tandem mass spectrometric detection (MS/MS) after collision-induced fragmentation of the double charged [M+2H]²⁺precursor ion (m/z ²⁺513). Identification of melanotan II was verified by correct chromatographic retention time, and relative abundance ratios of five qualifying fragment ions. LC-UV was used to quantify melanotan II as well as impurities. Method validation was performed with reference to guidelines for assessing active substances in authorized medicinal products to reach acceptable accuracy and precision. Vials from two shops contained unknown impurities ranging from 4.1 to 5.9%; impurities from one shop were below the quantification limit. The total amount of melanotan II in vials ranged between 4.32 and 8.84 mg, although each shop claimed that vials contained 10 mg melanotan II. A broad range of drugs used for enhancement purposes can be obtained from the illicit market. However, users of these drugs may be exposed to a range of potential harms, as shown in this study, given that these products are manufactured, distributed and supplied from an illicit market

The use of interim data and Data Monitoring Committee recommendations in randomized controlled trial reports: frequency, implications and potential sources of bias

Background: Interim analysis of accumulating trial data is important to protect participant safety during randomized controlled trials (RCTs). Data Monitoring Committees (DMCs) often undertake such analyses, but their widening role may lead to extended use of interim analysis or recommendations that could potentially bias trial results.Methods: Systematic search of eight major publications: Annals of Internal Medicine, BMJ, Circulation, CID, JAMA, JCO, Lancet and NEJM, including all randomised controlled trials ( RCTs) between June 2000 and May 2005 to identify RCTs that reported use of interim analysis, with or without DMC involvement. Recommendations made by the DMC or based on interim analysis were identified and potential sources of bias assessed. Independent double data extraction was performed on all included trials.Results: We identified 1772 RCTs, of which 470 (27%; 470/1772) reported the use of a DMC and a further 116 (7%; 116/1772) trials reported some form of interim analysis without explicit mention of a DMC. There were 28 trials ( 24 with a formal DMC), randomizing a total of 79396 participants, identified as recommending changes to the trial that may have lead to biased results. In most of these, some form of sample size re-estimation was recommended with four trials also reporting changes to trial endpoints. The review relied on information reported in the primary publications and methods papers relating to the trials, higher rates of use may have occurred but not been reported.Conclusion: The reported use of interim analysis and DMCs in clinical trials has been increasing in recent years. It is reassuring that in most cases recommendations were made in the interest of participant safety. However, in practice, recommendations that may lead to potentially biased trial results are being made