Level Of False Positive Results Research Articles

"The importance of awareness for understanding language": Correction to Rabagliati, Robertson, and Carmel (2018).

Reports an error in "The importance of awareness for understanding language" by Hugh Rabagliati, Alexander Robertson and David Carmel (Journal of Experimental Psychology: General, 2018[Feb], Vol 147[2], 190-208). In the article, funding details for David Carmel were not included in the author note. The second sentence of the author note should appear as follows: David Carmel was supported by the European Research Council (ERC Advanced Grant XSPECT-DLV-692739, awarded to Andy Clark). The online version of the article has been corrected. (The following abstract of the original article appeared in record 2018-03118-002.) Is consciousness required for high level cognitive processes, or can the unconscious mind perform tasks that are as complex and difficult as, for example, understanding a sentence? Recent work has argued that, yes, the unconscious mind can: Sklar et al. (2012) found that sentences, masked from consciousness using the technique of continuous flash suppression (CFS), broke into awareness more rapidly when their meanings were more unusual or more emotionally negative, even though processing the sentences' meaning required unconsciously combining each word's meaning. This has motivated the important claim that consciousness plays little-to-no functional role in high-level cognitive operations. Here, we aimed to replicate and extend these findings, but instead, across 10 high-powered studies, we found no evidence that the meaning of a phrase or word could be understood without awareness. We did, however, consistently find evidence that low-level perceptual features, such as sentence length and familiarity of alphabet, could be processed unconsciously. Our null findings for sentence processing are corroborated by a meta-analysis that aggregates our studies with the prior literature. We offer a potential explanation for prior positive results through a set of computational simulations, which show how the distributional characteristics of this type of CFS data, in particular its skew and heavy tail, can cause an elevated level of false positive results when common data exclusion criteria are applied. Our findings thus have practical implication for analyzing such data. More importantly, they suggest that consciousness may well be required for high-level cognitive tasks such as understanding language. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Dried blood spot and mini-tube blood sample collection kits for postal HIV testing services: a comparative review of successes in a real-world setting

ObjectivesThis is a comparative review between using dried blood spot (DBS) and mini-tube (MT) HIV sampling kits as part of an online sexually transmitted infection (STI) postal testing service. England...

Identification of Single Amino Acid Substitutions in Proteogenomics.

An important aim of proteogenomics, which combines data of high throughput nucleic acid and protein analysis, is to reliably identify single amino acid substitutions representing a main type of coding genome variants. Exact knowledge of deviations from the consensus genome can be utilized in several biomedical fields, such as studies of expression of mutated proteins in cancer, deciphering heterozygosity mechanisms, identification of neoantigens in anticancer vaccine production, search for RNA editing sites at the level of the proteome, etc. Generation of this new knowledge requires processing of large data arrays from high-resolution mass spectrometry, where information on single-point protein variation is often difficult to extract. Accordingly, a significant problem in proteogenomic analysis is the presence of high levels of false positive results for variant-containing peptides in the produced results. Here we review recently suggested approaches of high quality proteomics data processing that may provide more reliable identification of single amino acid substitutions, especially contrary to residue modifications occurring in vitro and in vivo. Optimized methods for assessment of false discovery rate save instrumental and computational time spent for validation of interesting findings of amino acid polymorphism by orthogonal methods.

The importance of awareness for understanding language.

Is consciousness required for high level cognitive processes, or can the unconscious mind perform tasks that are as complex and difficult as, for example, understanding a sentence? Recent work has argued that, yes, the unconscious mind can: Sklar et al. (2012) found that sentences, masked from consciousness using the technique of continuous flash suppression (CFS), broke into awareness more rapidly when their meanings were more unusual or more emotionally negative, even though processing the sentences' meaning required unconsciously combining each word's meaning. This has motivated the important claim that consciousness plays little-to-no functional role in high-level cognitive operations. Here, we aimed to replicate and extend these findings, but instead, across 10 high-powered studies, we found no evidence that the meaning of a phrase or word could be understood without awareness. We did, however, consistently find evidence that low-level perceptual features, such as sentence length and familiarity of alphabet, could be processed unconsciously. Our null findings for sentence processing are corroborated by a meta-analysis that aggregates our studies with the prior literature. We offer a potential explanation for prior positive results through a set of computational simulations, which show how the distributional characteristics of this type of CFS data, in particular its skew and heavy tail, can cause an elevated level of false positive results when common data exclusion criteria are applied. Our findings thus have practical implication for analyzing such data. More importantly, they suggest that consciousness may well be required for high-level cognitive tasks such as understanding language. (PsycINFO Database Record

Systematic errors in detecting biased agonism: Analysis of current methods and development of a new model-free approach

Discovering biased agonists requires a method that can reliably distinguish the bias in signalling due to unbalanced activation of diverse transduction proteins from that of differential amplification inherent to the system being studied, which invariably results from the non-linear nature of biological signalling networks and their measurement. We have systematically compared the performance of seven methods of bias diagnostics, all of which are based on the analysis of concentration-response curves of ligands according to classical receptor theory. We computed bias factors for a number of β-adrenergic agonists by comparing BRET assays of receptor-transducer interactions with Gs, Gi and arrestin. Using the same ligands, we also compared responses at signalling steps originated from the same receptor-transducer interaction, among which no biased efficacy is theoretically possible. In either case, we found a high level of false positive results and a general lack of correlation among methods. Altogether this analysis shows that all tested methods, including some of the most widely used in the literature, fail to distinguish true ligand bias from “system bias” with confidence. We also propose two novel semi quantitative methods of bias diagnostics that appear to be more robust and reliable than currently available strategies.

Quantitation of intrathecal immunoglobulin synthesis - a new empirical formula.

Intrathecal immunoglobulin (Ig) synthesis occurs in various chronic inflammatory neurological diseases. Different formulae have been developed for quantitative determination of Ig synthesis within the cerebrospinal fluid (CSF) compartment. The hyperbolic formula of Reiber is frequently used which, however, returns a considerable number of false positive results in empirical observations. A computerized database of more than 19 000 paired CSF and serum samples was screened for patients presumed negative for local Ig synthesis and a new formula characterizing this collective was calculated. The validity of this formula was confirmed by several validation steps. A cohort of 1173 patients with normal CSF findings was used for quantile regression. The 97.5th quantile of the formula Qlim(IgX)=a×Qalbb was considered as the cut-off curve for intrathecal Ig synthesis using different constants a and b for IgG, IgA and IgM. Compared to the Reiber formula, a lower level of false positive results was produced especially for IgM and IgA which was confirmed in a separate clinically well defined validation cohort. In 77 patients with discrepant findings between Reiber and our formula no specific diagnoses were found confirming the low diagnostic value of borderline Ig synthesis. A new approximation formula was developed for determination of intrathecal Ig synthesis which produces fewer false positive results without reducing diagnostic sensitivity.

Simultaneous determination of bromate, chlorite and haloacetic acids by two-dimensional matrix elimination ion chromatography with coupled conventional and capillary columns

A new, highly sensitive and reliable two-dimensional matrix elimination ion chromatography (IC) method was developed for simultaneous detection of bromate, chlorite and five haloacetic acids. This method combined the conventional IC in first dimension with capillary IC in the second dimension coupled with suppressed conductivity detection. The first dimension utilizes a high capacity column to partially resolve matrix from target analytes. By optimizing the cut window, the target analytes were selectively cut and trapped in a trap column through the use of a six-port valve, while the separated matrix were diverted to waste. The trapped target analytes were delivered on to the capillary column for further separation and detection. Temperature programming was used to improve selectivity in second dimension column to obtain complete resolution of the target analytes. Compared to the performance of one-dimensional IC, the two-dimensional approach resulted in a significant increase in sensitivity for all target analytes with limit of detection ranging from 0.30 to 0.64μg/L and provided more reliable analysis due to second column confirmation. Good linearity was obtained for all the target analytes with correlation coefficients >0.998. The proposed method was successfully applied to the determination of oxyhalides and haloacetic acids in various matrices with recoveries ranging from 90 to 116% and RSD less than 6.1%. The method allows direct injection of samples and the use of columns with different selectivity, thus significantly reduces the level of false positive results. The method is fully automated and simple, making it practical for routine monitoring of water quality. The satisfactory results also demonstrated that the two-dimensional matrix elimination method coupled with capillary IC is a promising approach for detection of trace substances in complex matrices.

Preeclampsia: modern laboratory capabilities for the prognosis of the risk of this complication in the first trimester

Preeclampsia is a pathological syndrome that develops during pregnancy and complicates 3–5% of all pregnancies, being one of the main causes of premature birth, maternal and perinatal mortality. Fetal Medicine Foundation recommended to assess the risk of developing preeclampsia used in the first trimester of a comprehensive assessment, including data about the pregnant woman, the presence of clinical risk factors, ultrasound features, data on the level of blood pressure, as well as level of two biochemical markers: placental growth factor (PlGF) and plasma protein A, associated with pregnancy (PAPP-A) that significantly reduced when there is a high risk of preeclampsia. This assessment allows predicting the development of early preeclampsia in 90% of cases, the level of false-positive results in 5% of cases and should be performed in all pregnant women in the first trimester in terms of 11–13 weeks.

Insensitivity to the growth inhibitory effects of activin A: An acquired capability in prostate cancer progression

Prostate cancer (PCa), the most common non-skin cancer in men, is a worldwide health concern. Treatment options for aggressive PCa are limited to androgen deprivation therapies (ADT), which are ineffective, with robust diagnostic options also being limited. The prostate specific antigen (PSA) test, for instance, is subject to high levels of false positive results and cannot distinguish between cancer confined to the prostate and aggressive metastatic cancer. As such, additional therapeutic and diagnostic options are urgently required. In recent years, a clear association between activins and prostate cancer has become evident. Activins are members of the TGF-β superfamily and are responsible for a plethora of physiological processes, including cell proliferation, apoptosis, immune surveillance, embryonic development, and follicle stimulating hormone (FSH) regulation. Activin A normally inhibits cancer development and progression, however, cancer cell growth in high-grade PCa is not inhibited by this protein. The mechanism for this apparent acquired capability to resist activin A-mediated growth inhibition is currently not well understood. Thus, the aim of this review is to analyse the role of activin A in PCa progression and to present mechanisms by which transformed cells may escape its effects. The overarching hypothesis is that insensitivity to the growth inhibitory effects of activin A is an acquired capability in PCa progression. Therefore, local and genetic elements that may be responsible for this change in cellular sensitivity to activin A during cancer progression will be highlighted with a view to identifying potential diagnostic or therapeutic targets.

Utility of the Etest GRD for detecting Staphylococcus aureus with reduced susceptibility to glycopeptides in cystic fibrosis patients

Glycopeptide-intermediate S. aureus (GISA), particularly heterogeneous GISA (hGISA), remain difficult to detect in the routine practice of medical microbiology. Novel tools have been evaluated comparatively to the population analysis profile-area under the curve (PAP-AUC) reference method for detecting GISA/hGISA. Among them, the Etest GRD showed relatively high specificity (85.8-97%) and negative predictive value (97%) but lower sensibility (57-95%) and positive predictive value (30.8%). We investigated the utility of the Etest GRD for detecting GISA/hGISA among 180 strains isolated from 106 cystic fibrosis (CF) patients. Etest GRD was performed on all isolates, and those exhibiting a GISA/hGISA phenotype were further tested by PAP-AUC and other agar routine assays for GISA/hGISA detection. The Etest GRD allowed the detection of 15 GISA/hGISA strains, of which eight were confirmed by the reference method. Despite the 3.9% level of false positive results, the Etest GRD constitutes a useful routine tool for detecting GISA/hGISA overlooked by other routine assays, two strains being detected by the Etest GRD only. GISA/hGISA represented 7.7% of MRSA and 2.1% of MSSA, and were found in 4.7% of CF patients colonized/infected by S. aureus, which is the highest rate reported to date in this population.

Phase II Trials in Journal of Clinical Oncology

Phase II Trials in <i>Journal of Clinical Oncology</i>