Accuracy of UK Rapid Test Consortium (UK-RTC) "AbC-19 Rapid Test" for detection of previous SARS-CoV-2 infection in key workers: test accuracy study.

OBJECTIVE: To assess the accuracy of the AbC-19 Rapid Test lateral flow immunoassay for the detection of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Test accuracy study. SETTING: Laboratory based evaluation. PARTICIPANTS: 2847 key workers (healthcare staff, fire and rescue officers, and police officers) in England in June 2020 (268 with a previous polymerase chain reaction (PCR) positive result (median 63 days previously), 2579 with unknown previous infection status); and 1995 pre-pandemic blood donors. MAIN OUTCOME MEASURES: AbC-19 sensitivity and specificity, estimated using known negative (pre-pandemic) and known positive (PCR confirmed) samples as reference standards and secondly using the Roche Elecsys anti-nucleoprotein assay, a highly sensitive laboratory immunoassay, as a reference standard in samples from key workers. RESULTS: Test result bands were often weak, with positive/negative discordance by three trained laboratory staff for 3.9% of devices. Using consensus readings, for known positive and negative samples sensitivity was 92.5% (95% confidence interval 88.8% to 95.1%) and specificity was 97.9% (97.2% to 98.4%). Using an immunoassay reference standard, sensitivity was 94.2% (90.7% to 96.5%) among PCR confirmed cases but 84.7% (80.6% to 88.1%) among other people with antibodies. This is consistent with AbC-19 being more sensitive when antibody concentrations are higher, as people with PCR confirmation tended to have more severe disease whereas only 62% (218/354) of seropositive participants had had symptoms. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, 84 700 true positive and 18 900 false positive results would be projected. The probability that a positive result was correct would be 81.7% (76.8% to 85.8%). CONCLUSIONS: AbC-19 sensitivity was lower among unselected populations than among PCR confirmed cases of SARS-CoV-2, highlighting the scope for overestimation of assay performance in studies involving only PCR confirmed cases, owing to "spectrum bias." Assuming that 10% of the tested population have had SARS-CoV-2 infection, around one in five key workers testing positive with AbC-19 would be false positives. STUDY REGISTRATION: ISRCTN 56609224.The study was commissioned by the UK Government’s Department of Health and Social Care. It was funded and implemented by Public Health England, supported by the NIHR Clinical Research Network (CRN) Portfolio. The Department of Health and Social Care received a report containing these data on 10/9/2020, but had no role in the study design, data collection, analysis, interpretation of results, writing of the manuscript, or the decision to publish. DW acknowledges support from the NIHR Health Protection Research Unit in Genomics and Data Enabling at the University of Warwick. HEJ, AEA, MH and IO acknowledge support from the NIHR Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol. STP is supported by an NIHR Career Development Fellowship (CDF-2016-09-018). Participants in the COMPARE study were recruited with the active collaboration of NHS Blood and Transplant (NHSBT) England (www.nhsbt.nhs.uk). Funding for COMPARE was provided by NHSBT and the NIHR Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics (NIHR BTRU-2014-10024). The academic coordinating centre for COMPARE was supported by core funding from: NIHR BTRU, UK Medical Research Council (MR/L003120/1), British Heart Foundation (RG/13/13/30194) and the NIHR [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Division), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome. JD holds a British Heart Foundation Professorship and a National Institute for Health Research Senior Investigator Award. The views expressed are those of the author(s) and not necessarily those of the NHS, NIHR or the Department of Health and Social Care

Comparison of four methods to measure haemoglobin concentrations in whole blood donors (COMPARE): A diagnostic accuracy study.

OBJECTIVE: To compare four haemoglobin measurement methods in whole blood donors. BACKGROUND: To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant's (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT's customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold). METHODS: We compared the following four methods in 21 840 blood donors (aged ≥18 years) recruited from 10 NHSBT centres in England, with the Sysmex XN-2000 haematology analyser, the reference standard: (1) NHSBT's customary method; (2) "post donation" approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor's most recent prior donation; (3) "portable haemoglobinometry" (using capillary HemoCue); (4) non-invasive spectrometry (using MBR Haemospect or Orsense NMB200). We assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation ("deferred") incorrectly; and test preference. RESULTS: Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women. For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT's customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT's customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT's customary method to 20.3% in women for OrSense. Most donors preferred non-invasive spectrometry. CONCLUSION: In the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of NHSBT's customary method with portable haemoglobinometry

Erratum: Internet and mobile-based psychological interventions: Applications, efficacy and potential for improving mental health. A report of the EFPA E-Health Taskforce (European Psychologist (2018) 23 (167-187) DOI: 10.1027/1016-9040/a000318)

© 2018 2018 Hogrefe Publishing. The article entitled Internet and mobile-based psychological interventions: Applications, efficacy and potential for improving mental health. A report of the EFPA E-Health Taskforce. by Ebert, D. D., Van Daele, T., Nordgreen, T., Karekla, M., Compare, A., Zarbo, C., Brugnera, B., Overland, S., Trebbi, G., Jensen, K. L., Kaehlke, F. (on behalf of the EFPA E-Health Taskforce), & Baumeister, H. (2018, European Psychologist, 23(2), 167-187. https://doi.org/ 10.1027/1016-9040/a000318) contained an error on the first page: The author Jacqui Taylor is missing and the list of authors should correctly read as follows: David Daniel Ebert1, Tom Van Daele2, Tine Nordgreen3, Maria Karekla4, Angelo Compare6, Cristina Zarbo5, Agostino Brugnera5, Svein Overland7, Glauco Trebbi8, Kit L. Jensen9, Fanny Kaehlke (on behalf of the EFPA E-Health Taskforce)1, Harald Baumeister10, and Jacqui Taylor11 1Department of Clinical Psychology and Psychotherapy, Friedrich-Alexander University of Erlangen- Nrnberg, Erlangen, Germany 2Department of Applied Psychology, Thomas More University of Applied Sciences, Antwerp, Belgium 3Division of Psychiatry, Haukeland University Hospital, Bergen, Norway 4Department of Psychology, University of Cyprus, Nicosia, Republic of Cyprus 5Department of Human and Social Science, University of Bergamo, Bergamo, Italy 6Human Factors and Technology in Healthcare, University of Bergamo, Bergamo, BG, Italy 7SuperEgo AS, Trondheim, Norway 8Trebbipsicologie, Luxembourg & Societe Luxembourgeoise de Psychologie SLP, Luxembourg 9Private Practice, Skagen, Denmark 10Department of Clinical Psychology and Psychotherapy, University of Ulm, Germany 11Psychology Department, Bournemouth University, UK The authors regret any inconvenience or confusion this error may have caused

Understanding and predicting ciprofloxacin minimum inhibitory concentration in Escherichia coli with machine learning

It is important that antibiotics prescriptions are based on antimicrobial susceptibility data to ensure effective treatment outcomes. The increasing availability of next-generation sequencing, bacterial whole genome sequencing (WGS) can facilitate a more reliable and faster alternative to traditional phenotyping for the detection and surveillance of AMR. This work proposes a machine learning approach that can predict the minimum inhibitory concentration (MIC) for a given antibiotic, here ciprofloxacin, on the basis of both genome-wide mutation profiles and profiles of acquired antimicrobial resistance genes. We analysed 704 Escherichia coli genomes combined with their respective MIC measurements for ciprofloxacin originating from different countries. The four most important predictors found by the model, mutations in gyrA residues Ser83 and Asp87, a mutation in parC residue Ser80 and presence of the qnrS1 gene, have been experimentally validated before. Using only these four predictors in a linear regression model, 65% and 93% of the test samples' MIC were correctly predicted within a two- and a four-fold dilution range, respectively. The presented work does not treat machine learning as a black box model concept, but also identifies the genomic features that determine susceptibility. The recent progress in WGS technology in combination with machine learning analysis approaches indicates that in the near future WGS of bacteria might become cheaper and faster than a MIC measurement

Preliminary Evidence for the Cross-Cultural Utility of the Type D Personality Construct in the Ukraine

Link to publicatio

Cognition-Enhancing Drugs: Can We Say No?

Normative analysis of cognition-enhancing drugs frequently weighs the liberty interests of drug users against egalitarian commitments to a level playing field. Yet those who would refuse to engage in neuroenhancement may well find their liberty to do so limited in a society where such drugs are widespread. To the extent that unvarnished emotional responses are world-disclosive, neurocosmetic practices also threaten to provide a form of faulty data to their users. This essay examines underappreciated liberty-based and epistemic rationales for regulating cognition-enhancing drugs

A Functional NQO1 609C>T Polymorphism and Risk of Gastrointestinal Cancers: A Meta-Analysis

Background: The functional polymorphism (rs1800566) in the NQO1 gene, a 609C.T substitution, leading to proline-toserine amino-acid and enzyme activity changes, has been implicated in cancer risk, but individually published studies showed inconclusive results. Methodology/Principal Findings: We performed a meta-analysis of 20 publications with a total of 5,491 cases and 5,917 controls, mainly on gastrointestinal (GI) cancers. We summarized the data on the association between the NQO1 609C.T polymorphism and risk of GI cancers and performed subgroup analyses by ethnicity, cancer site, and study quality. We found that the variant CT heterozygous and CT/TT genotypes of the NQO1 609 C.T polymorphism were associated with a modestly increased risk of GI cancers (CT vs. CC: OR = 1.10, 95 % CI = 1.01 – 1.19, P heterogeneity = 0.27, I 2 = 0.15; CT/TT vs. CC: OR = 1.11, 95%CI = 1.02 – 1.20, Pheterogeneity = 0.14; I 2 = 0.27). Following further stratified analyses, the increased risk was only observed in subgroups of Caucasians, colorectal cancer in Caucasians, and high quality studies. Conclusions: This meta-analysis suggests that the NQO1 609T allele is a low-penetrance risk factor for GI cancers. Although the effect on GI cancers may be modified by ethnicity and cancer sites, small sample seizes of the subgroup analyse

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

<p>Abstract</p> <p>Background</p> <p>Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.</p> <p>Methods</p> <p>Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.</p> <p>Results</p> <p>Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.</p> <p>Conclusions</p> <p>The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.</p

Variations in Helicobacter pylori Cytotoxin-Associated Genes and Their Influence in Progression to Gastric Cancer: Implications for Prevention

Helicobacter pylori (HP) is a bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa. Persistent Hp infection often induces gastritis and is associated with the development of peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Virulent HP isolates harbor the cag (cytotoxin-associated genes) pathogenicity island (cagPAI), a 40 kb stretch of DNA that encodes components of a type IV secretion system (T4SS). This T4SS forms a pilus for the injection of virulence factors into host target cells, such as the CagA oncoprotein. We analyzed the genetic variability in cagA and other selected genes of the HP cagPAI (cagC, cagE, cagL, cagT, cagV and cag Gamma) using DNA extracted from frozen gastric biopsies or from clinical isolates. Study subjects were 95 cagA+ patients that were histologically diagnosed with chronic gastritis or gastric cancer in Venezuela and Mexico, areas with high prevalence of Hp infection. Sequencing reactions were carried out by both Sanger and next-generation pyrosequencing (454 Roche) methods. We found a total of 381 variants with unambiguous calls observed in at least 10% of the originally tested samples and reference strains. We compared the frequencies of these genetic variants between gastric cancer and chronic gastritis cases. Twenty-six SNPs (11 non-synonymous and 14 synonymous) showed statistically significant differences (P<0.05), and two SNPs, in position 1039 and 1041 of cagE, showed a highly significant association with cancer (p-value = 2.07×10−6), and the variant codon was located in the VirB3 homology domain of Agrobacterium. The results of this study may provide preliminary information to target antibiotic treatment to high-risk individuals, if effects of these variants are confirmed in further investigations