Is blockchain ready to revolutionize online advertising?

The 200-billion-dollar per annum online advertising ecosystem has become infested with thousands of intermediaries exploiting user data and advertising budgets. All key stakeholders in the value-chain are infected: advertisers with fraud, publishers with their diminishing share of advertising budgets, and users with their right to privacy. Blockchain presents a possible solution to addressing the critical issues in the online advertising supply chain. The question remains whether blockchain scalability, energy-efficiency, and token volatility issues can be solved in the coming years to the extent that online advertising could widely leverage trustlessness and the benefits gained from blockchain technology. This paper aims to review the current progress and to open a discussion to address the issues. We present new requirements for blockchain-based online advertising solutions. We have also analyzed the available solutions against the requirements and recommend directions for future research and solution development. Evidence from our research points out that blockchain is not yet ready to be widely implemented in online advertising. More research is needed, and new proof-of-concepts need to be developed before blockchain technology can be considered a trusted alternative for the current online advertising marketplace based on open real-time bidding

Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration

Huntington's disease (HD) is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt) protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%–4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to co-immunoprecipitate with full-length Htt from mouse brain. These studies demonstrate that high-throughput screening for protein interactions combined with genetic validation in a model organism is a powerful approach for identifying novel candidate modifiers of polyglutamine toxicity

Testing for hereditary thrombophilia: a retrospective analysis of testing referred to a national laboratory

<p>Abstract</p> <p>Background</p> <p>Predisposition to venous thrombosis may be assessed through testing for defects and/or deficiencies of a number of hereditary factors. There is potential for confusion about which of these tests are appropriate in which settings. At least one set of recommendations has been published to guide such testing, but it is unclear how widely these have been disseminated.</p> <p>Methods</p> <p>We performed a retrospective analysis of laboratory orders and results at a national referral laboratory to gain insight into physicians' ordering practices, specifically comparing them against the ordering practices recommended by a 2002 College of American Pathologists (CAP) consensus conference on thrombophilia testing. Measurements included absolute and relative ordering volumes and positivity rates from approximately 200,000 thrombophilia tests performed from September 2005 through August 2006 at a national reference laboratory. Quality control data were used to estimate the proportion of samples that may have been affected by anticoagulant therapy. A sample of ordering laboratories was surveyed in order to assess potential measurement bias.</p> <p>Results</p> <p>Total antigen assays for protein C, protein S and antithrombin were ordered almost as frequently as functional assays for these analytes. The DNA test for factor V Leiden was ordered much more often than the corresponding functional assay. In addition, relative positivity rates coupled with elevations in prothrombin time (PT) in many of these patients suggest that these tests are often ordered in the setting of oral anticoagulant therapy.</p> <p>Conclusion</p> <p>In this real-world setting, testing for inherited thrombophilia is frequently at odds with the recommendations of the CAP consensus conference. There is a need for wider dissemination of concise thrombophilia testing guidelines.</p

Evaluation of the Abbott Investigational Use Only RealTime Hepatitis C Virus (HCV) Assay and Comparison to the Roche TaqMan HCV Analyte-Specific Reagent Assay▿

The accurate and sensitive measurement of hepatitis C virus (HCV) RNA is essential for the clinical management and treatment of infected patients and as a research tool for studying the biology of HCV infection. We evaluated the linearity, reproducibility, precision, limit of detection, and concordance of viral genotype quantitation of the Abbott investigational use only RealTime HCV (RealTime) assay using the Abbott m2000 platform and compared the results to those of the Roche TaqMan Analyte-Specific Reagent (TaqMan) and Bayer Versant HCV bDNA 3.0 assay. Comparison of 216 samples analyzed by RealTime and TaqMan assays produced the following Deming regression equation: RealTime = 0.940 (TaqMan) + 0.175 log10 HCV RNA IU/ml. The average difference between the assays was 0.143 log10 RNA IU/ml and was consistent across RealTime's dynamic range of nearly 7 log10 HCV RNA IU/ml. There was no significant difference between genotypes among these samples. The limit of detection using eight replicates of the World Health Organization HCV standard was determined to be 7.74 HCV RNA IU/ml by probit analysis. Replicate measurements of commercial genotype panels were significantly higher than TaqMan measurements for most samples and showed that the RealTime assay is able to detect all genotypes with no bias. Additionally, we showed that the amplicon generated by the widely used Roche COBAS Amplicor Hepatitis C Virus Test, version 2.0, can act as a template in the RealTime assay, but potential cross-contamination could be mitigated by treatment with uracil-N-glycosylase. In conclusion, the RealTime assay accurately measured HCV viral loads over a broad dynamic range, with no significant genotype bias

Limited Applicability of Direct Fluorescent-Antibody Testing for Bordetella sp. and Legionella sp. Specimens for the Clinical Microbiology Laboratory▿

The rapid diagnosis of infections with Bordetella and Legionella species is important for patient management. With observed increases in direct fluorescent-antibody (DFA) testing volumes, we retrospectively compared the performance characteristics of DFA testing to those of culture and PCR. For Bordetella sp., samples were classified as positive by DFA testing (184 [3%] of 6,195 samples) and culture (150 [2%] of 6,251 samples) significantly less often than by PCR (2,557 [10%] of 26,929 samples). Of 360 samples tested by both DFA and PCR methods, 81 (16 by DFA testing and 79 by PCR) were determined to be positive for Bordetella, with a sensitivity and specificity of DFA testing of 18% and 99%, respectively. Of 1,426 samples tested by both DFA and culture methods, 48 (44 by DFA testing and 15 by culture) were determined to be positive for Bordetella, with a sensitivity and specificity of DFA testing of 73% and 98%, respectively. For Legionella sp., samples were identified as positive by DFA testing (31 [0.25%] of 12,597 samples) and culture (85 [0.6%] of 13,572 samples) significantly less often than by PCR (27 [4%] of 716 samples). Of 62 samples tested by both DFA and PCR methods, none were positive for Legionella sp. by DFA testing and 3 were positive by PCR. Of 3,923 samples tested by both DFA and culture methods, 22 (3 by DFA testing and 21 by culture) were positive for Legionella sp., with a sensitivity and specificity of DFA testing of 9.5% and 100%. Overall, DFA testing for Bordetella sp. and Legionella sp. is an insensitive method, and despite its continued popularity, clinical microbiology laboratories should not offer it when more sensitive tests like PCR are available

Evaluation of the Abbott Investigational Use Only RealTime HIV-1 Assay and Comparison to the Roche Amplicor HIV-1 Monitor Test, Version 1.5

Abbott Molecular's m2000 system and RealTime HIV-1 assay (RealTime) were evaluated for sensitivity, reproducibility, linearity, ability to detect diverse HIV-1 subtypes/groups, and correlation to the Roche AMPLICOR HIV-1 MONITOR Test, Version 1.5 (Amplicor). The limit of detection was determined using the second International World Health Organization Standard and Viral Quality Assurance standard material. Serial dilutions of four patient samples were used to determine inter- and intra-assay reproducibility and linearity. Samples representing HIV-1 groups M, N, and O were evaluated in the RealTime, Amplicor, and Siemens Versant HIV-1 branched chain DNA 3.0 (Versant) assays. Archived Amplicor-tested samples were tested with the 1 ml, 0.5 ml, and 0.6 ml versions of the RealTime assay. Probit analysis predicts a limit of detection of 21.94 IU/ml using the World Health Organization Standard and 26.54 copies/ml using Viral Quality Assurance material with the 1 ml assay. Linearity and reproducibility were very good between ∼1.60 to 6.0 log10 copies/ml. All three assays produced similar measurements for all Group M subtypes tested; the RealTime assay was the only assay that detected all three Group O samples tested. Correlation with the Amplicor assay was good, although the RealTime assay measured between 0.342 and 0.716 log10 copies/ml lower on average, depending on the input volume. The automated RealTime assay exhibits excellent sensitivity, dynamic range, reproducibility, and group/subtype detection, albeit with consistently lower values than Amplicor

Clinical and Analytical Sensitivities in Hereditary Hemorrhagic Telangiectasia Testing and a Report of de Novo Mutations

Hereditary hemorrhagic telangiectasia is a vascular dysplasia with variable onset and expression. Through identification of a mutation in a proband, mutation testing can be offered to family members. Mutation carriers can receive medical surveillance and treatment before potentially fatal complications arise. In this study, we assessed the significance of clinical evaluations as part of hereditary hemorrhagic telangiectasia diagnostic testing to determine the clinical sensitivity of molecular testing and to report novel mutations. Based on reported clinical symptoms, we classified 142 consecutive cases as affected, suspected, or unlikely affected. We performed temperature gradient capillary electrophoresis and full gene sequencing of both ACVRL1 and ENG genes. We then compared the mutation detection rates between these groups, categorizing sequence variants as mutations, variants of uncertain significance (VUS), or known polymorphisms. Our mutation and VUS detection rate in affected individuals was 74% and 16% in the suspected/unlikely affected group. Sixty-one percent of the mutations and all VUS were novel. The mutation detection rate for temperature gradient capillary electrophoresis was 97%. Our results suggest that a careful clinical evaluation increases the mutation detection rate. We have confirmed the occurrence of de novo mutations in three patients. Our results also show that temperature gradient capillary electrophoresis is an efficient mutation screening method