Search

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.

PDF file - 41K

PDF file - 212K

The relevance of the study is due to the change of activity of organized criminal groups involved in the circulation of psychoactive substances towards the organization of the mentioned activity through the Internet. The purpose of this work is to investigate the current problems of combating drug trafficking by using the worldwide web through contactless sale of narcotic drugs and psychotropic substances. It is necessary to strengthen the analytical component of law enforcement activities in the detection and analysis of content on the Internet through the introduction of information technology in law enforcement activities, the dissemination of knowledge about OSINT. The materials of the article are of practical value for the higher education graduates of police specialties, police officers of the criminal block and specialists in the field of operational search activities.

Hepatic cell death occurs in response to diverse stimuli such as chemical and physical damage. The exposure of intracellular contents such as DNA during necrosis induces a severe inflammatory response that has yet to be fully explored therapeutically. Here, we sought means to neutralize the ability of extracellular DNA to induce deleterious tissue inflammation when drug‐induced liver injury had already ensued. DNA exposure and inflammation were investigated in vivo in drug‐induced liver injury using intravital microscopy. The necrotic DNA debris was studied in murine livers in vivo and in DNA debris models in vitro by using a positively charged chemokine‐derived peptide (MIG30; CXCL9[74‐103]). Acetaminophen‐induced liver necrosis was associated with massive DNA accumulation, production of CXC chemokines, and neutrophil activation inside the injured tissue. The MIG30 peptide bound the healthy liver vasculature and, to a much greater extent, to DNA‐rich necrotic tissue. Moreover, MIG30 bound extracellular DNA directly in vivo in a charge‐dependent manner and independently of glycosaminoglycans and chemokines. Post‐treatment of mice with MIG30 reduced mortality, liver damage, and inflammation significantly. These effects were not observed with a control peptide that does not bind DNA. Mechanistically, MIG30 inhibited the interaction between DNA and histones, and promoted the dissociation of histones from necrotic debris. MIG30 also inhibited the pro‐inflammatory effect of CpG DNA, as measured by a reduction in CXCL8 production, indicating that MIG30 disturbs the ability of DNA to induce hepatic inflammation. Conclusion: The use of DNA‐binding peptides reduces necrotic liver injury and inflammation, even at late timepoints., Marques et al. used a small chemokine‐derived positively‐charged peptide (MIG30) to neutralize the deleterious effects of extracellular DNA during drug‐induced liver injury. Treatment with MIG30 rescued mice from injury, inflammation and mortality by binding DNA avidly, dissociating it from histones and reducing the pro‐inflammatory activity of CpG DNA.

The article deals with the problems of withstanding harsh temperatures by steel and iron. The authors of the work discuss iron denser high-temperature of γ modification and maximums and minimums of impact. In addition, the article analyses the transformations of iron and anomalies of properties: peak of heat capacity, acceleration of diffusion, etc. The authors take into account the consensus on the causes of polymorphism and the theoretical model of ferromagnetism. Besides, there is a consideration of "transformation" in interaction between Fe atoms that produce anomalies of steel properties. It is necessary to note the transformation detected by anomalies of any properties including mechanical. In the presented work the authors have made an attempt to prove transformations in iron at ~650 °C on the basis of extreme values of hardness and microhardness, metallographic structure, parameters of fine structure, precipitation resistance force depending on temperature. Therefore, the analysis of literature sources on physical and mechanical properties of iron and its derivatives has been made.

Prioritizing genes for translation to therapeutics for common diseases has been challenging. Here, we propose an approach to identify drug targets with high probability of success by focusing on genes with both gain of function (GoF) and loss of function (LoF) mutations associated with opposing effects on phenotype (Bidirectional Effect Selected Targets, BEST). We find 98 BEST genes for a variety of indications. Drugs targeting those genes are 3.8-fold more likely to be approved than non-BEST genes. We focus on five genes (IGF1R, NPPC, NPR2, FGFR3, and SHOX) with evidence for bidirectional effects on stature. Rare protein-altering variants in those genes result in significantly increased risk for idiopathic short stature (ISS) (OR = 2.75, p = 3.99 × 10−8). Finally, using functional experiments, we demonstrate that adding an exogenous CNP analog (encoded by NPPC) rescues the phenotype, thus validating its potential as a therapeutic treatment for ISS. Our results show the value of looking for bidirectional effects to identify and validate drug targets., Prioritising genes as potential drug targets is challenging and often unsuccessful once testing efficacy in humans. Here, the authors propose an approach to identifying drug targets that uses evidence from gain- or loss-of-function mutations associated with bidirectional effects on phenotypes.

The objective of the article is to conduct a study of the role of criminal analysis in modern models of police activity. To achieve this objective, several methods were used, namely: analysis of official documentation, scientific literature, logical analysis, concrete-historical, dialectic, or empirical methods. The article presents the most common classifications of police models today, as well as the interpretation of criminal analysis in them. It is concluded that a relatively new model of intelligence-led surveillance needs to be implemented in the police. Within the police model of social orientation, specific ways of solving various problems are carried out by carefully and detailed analysis of the causes of such problems, actors, and characteristics of the area, as well as the prevention of serious crimes through the approach of police work in places of concentration of minor infringements (model of "broken windows"). It was noted that Comp Stat focuses on street crime and in series with short-term responsibility for addressing new criminal challenges; for its part, the intelligence-led surveillance (ILP) model includes a long-term strategic component that can be applied to transnational organized crime operations.

In the presented work on the basis of extrema on curves: efforts of resistance of draft, parameters of thin structure, metalgraphic structure depending on temperature and also numerous literary data on anomalies of physicomechanical properties of iron and staly transformation is declared at ~ 650 C. The research was conducted on samples from almost pure iron (0,008% C). An experiment (the metalgraphic research, the X-ray diffraction analysis, resistance to draft (Gleeble-3800) carried out through each 20 C.

Adeno-associated virus 5 (AAV5)-human factor VIII-SQ (hFVIII-SQ; valoctocogene roxaparvovec) is an AAV-mediated product under evaluation for treatment of severe hemophilia A, which contains a B-domain-deleted hFVIII (hFVIII-SQ) transgene and a hybrid liver-specific promotor (HLP). To increase FVIII-SQ expression and reduce the vector dose required, a stronger promoter may be considered. However, because FVIII-SQ is a protein known to be difficult to fold and secrete, this could potentially induce endoplasmic reticulum (ER) stress. We evaluated the effect of two AAV5-hFVIII-SQ vectors with different liver-specific promoter strength (HLP << 100ATGB) on hepatic ER stress in mice. Five weeks after receiving vehicle or vector, the percentage of transduced hepatocytes and levels of liver hFVIII-SQ DNA and RNA increased dose dependently for both vectors. At lower doses, plasma hFVIII-SQ protein levels were higher for 100ATGB. This difference was attenuated at the highest dose. For 100ATGB, liver hFVIII-SQ protein accumulated dose dependently, with increased expression of ER stress markers at the highest dose, suggesting hepatocytes reached or exceeded their capacity to fold/secrete hFVIII-SQ. These data suggest that weaker promoters may require relatively higher doses to distribute expression load across a greater number of hepatocytes, whereas relatively stronger promoters may produce comparable levels of FVIII in fewer hepatocytes, with potential for ER stress., Graphical Abstract, Fong and colleagues evaluated the effect of hepatic-specific promoter strength on AAV5-hFVIII-SQ gene therapy in mice. Vectors with weaker promoters may require higher doses to distribute expression load across greater numbers of hepatocytes, whereas stronger promoters may produce comparable levels of FVIII in fewer hepatocytes, with potential for ER stress induction.

In addition to property anomalies, a distinguishing feature of the intermediate phase is the qualitative change of the crystallization or recrystallization interval (Q∆LS) that occurs at congruent and incongruent melting phases, at eutectic or eutectoid points, at the ends of eutectic or eutectoid horizontals, and also at any nonmonotonicity of the liquidus, since the solidus or solidoid is a horizontal in eutectic or eutectoid systems. A technique has been developed that allows us to associate anomalies in the properties of industrial alloys with state diagrams based on the first established criterion - a qualitative change (length in temperature) of the crystallization (recrystallization) interval (Q∆LS), as well as with a difference in the structural heredity (genealogy) of the component atoms that make up dual system. A joint analysis of the anomalies in the properties of binary alloys with state diagrams (based on the established criterion (Q∆LS)) allows us to relate the latter to the presence of intermediate phases in Al − Si, Fe − C, Al − Cu systems. The intermediate phases AnBm-Q∆LS explaining the anomalies of properties are declared: ~Al7Si, Al41Cu9 − correspond to the eutectic point; Fe24C − eutectoid point; Al11Si, AlSi6 − the bend of the liquidus; Fe42C − bending liquidoid; Al49Cu, Al98.5Si1.5 − the end of the eutectic horizontal; Cu4Al, Cu7Al3 − to the ends of the eutectoid horizontal.

Peptidylarginine deiminases (PADs) are calcium-dependent enzymes that mediate citrullination, an irreversible post-translational modification (PTM). PAD enzymes have received increasing attention in (patho-)physiology since multi-omics analysis accelerated their expression profiling. Here, we provide a comprehensive overview of PAD expression at the RNA and protein levels, and a list of annotated substrates per PAD isozyme. We discuss novel roles of citrullination in cellular growth, epigenetic regulation, tissue remodeling, inflammation, and cancer in mouse models and humans. Additionally, we cluster similar effects of protein deimination to offer a different perspective and improve our understanding of citrullination in health and disease. Citrullination should no longer be considered as a rare PTM, but as an important regulatory mechanism in physiology and pathology. ispartof: TRENDS IN CELL BIOLOGY vol:32 issue:9 pages:746-761 ispartof: location:England status: published

Correction to: Nature Human Behaviour https://doi.org/10.1038/s41562-021-01173-x, published online 2 August 2021.In the version of this article initially published, the following authors were omitted from the author list and the Author contributionssection for “investigation” and “writing and editing”: Nandor Hajdu (Institute of Psychology, ELTE Eötvös Loránd University, Budapest,Hungary), Jordane Boudesseul (Facultad de Psicología, Instituto de Investigación Científica, Universidad de Lima, Lima, Perú), RafałMuda (Faculty of Economics, Maria Curie-Sklodowska University, Lublin, Poland) and Sandersan Onie (Black Dog Institute, UNSWSydney, Sydney, Australia & Emotional Health for All Foundation, Jakarta, Indonesia). In addition, Saeideh FatahModares’ name wasoriginally misspelled as Saiedeh FatahModarres in the author list. Further, affiliations have been corrected for Maria Terskova (NationalResearch University Higher School of Economics, Moscow, Russia), Susana Ruiz Fernandez (FOM University of Applied Sciences,Essen; Leibniz-Institut fur Wissensmedien, Tubingen, and LEAD Research Network, Eberhard Karls University, Tubingen, Germany),Hendrik Godbersen (FOM University of Applied Sciences, Essen, Germany), Gulnaz Anjum (Department of Psychology, Simon FraserUniversity, Burnaby, Canada, and Department of Economics & Social Sciences, Institute of Business Administration, Karachi, Pakistan).

ObjectivesTo explore posttranslational modifications (PTMs), including proteolytic activation, multimerization, complex formation and citrullination of gelatinases, in particular of gelatinase B/MMP-9, and to detect in gelatin-Sepharose affinity-purified synovial fluids, the presence of specific MMP proteoforms in relation to arthritis.MethodsLatent, activated, complexed and truncated gelatinase-A/MMP-2 and gelatinase B/MMP-9 proteoforms were detected with the use of zymography analysis to compare specific levels, with substrate conversion assays, to test net proteolytic activities and by Western blot analysis to decipher truncation variants. Citrullination was detected with enhanced sensitivity, by the use of a new monoclonal antibody against modified citrullines.ResultsAll MMP-9 and MMP-2 proteoforms were identified in archival synovial fluids with the use of zymography analysis and the levels of MMP-9 versus MMP-2 were studied in various arthritic diseases, including rheumatoid arthritis (RA). Secondly, we resolved misinterpretations of MMP-9 levels versus proteolytic activities. Thirdly, a citrullinated, truncated proteoform of MMP-9 was discovered in archival RA synovial fluid samples and its presence was corroborated as citrullinated hemopexin-less MMP-9 in a small prospective RA sample cohort.ConclusionSynovial fluids from rheumatoid arthritis contain high levels of MMP-9, including its truncated and citrullinated proteoform. The combination of MMP-9 as analyte and its PTM by citrullination could be of clinical interest, especially in the field of arthritic diseases.

The inflammatory human chemokine CXCL5 interacts with the G protein-coupled receptor CXCR2 to induce chemotaxis and activation of neutrophils. CXCL5 also has weak agonist activity toward CXCR1. The N-terminus of CXCL5 can be modified by proteolytic cleavage or deimination of Arg9 to citrulline (Cit), and these modifications can occur separately or together. Here, we chemically synthesized native CXCL5(1-78), truncated CXCL5 [CXCL5(9-78)], and the citrullinated (Cit9) versions and characterized their functions in vitro and in vivo. Compared with full-length CXCL5, N-terminal truncation resulted in enhanced potency to induce G protein signaling and β-arrestin recruitment through CXCR2, increased CXCL5-initiated internalization of CXCR2, and greater Ca2+ signaling downstream of not only CXCR2 but also CXCR1. Citrullination did not affect the capacity of CXCL5 to activate classical or alternative signaling pathways. Administering the various CXCL5 forms to mice revealed that in addition to neutrophils, CXCL5 exerted chemotactic activity toward monocytes and that this activity was increased by N-terminal truncation. These findings were confirmed by in vitro chemotaxis and Ca2+ signaling assays with primary human CD14+ monocytes and human THP-1 monocytes. In vitro and in vivo analyses suggested that CXCL5 targeted monocytes through CXCR1 and CXCR2. Thus, truncation of the N-terminus makes CXCL5 a more potent chemoattractant for both neutrophils and monocytes that acts through CXCR1 and CXCR2.

Supplemental Material, sj-docx-1-tpx-10.1177_0192623321991469 for Quantitative Assessment of Neuroinflammation, Myelinogenesis, Demyelination, and Nerve Fiber Regeneration in Immunostained Sciatic Nerves From Twitcher Mice With a Tissue Image Analysis Platform by Irene Wilson, Cathy Vitelli, Guoying Karen Yu, Glenn Pacheco, Jon Vincelette, Stuart Bunting and Sílvia Sisó in Toxicologic Pathology

Libraries are actively exploring ways to use Linked Open Data (LOD) services to enhance discovery and facilitate the use of collections. Emblematica Online , which provides integrated discovery of digitized emblem books, incorporates LOD in its design. As an implementation prerequisite, the Virtual International Authority File (VIAF) and Library of Congress (LC) Linked Data Service APIs were used to reconcile name and subject strings from legacy catalog records with global authoritative links from LOD resources. This case study reports on the automated reconciliation process used and examines the efficacy of the APIs in reconciling name and subject heading entities. While a majority of strings were successfully reconciled, analysis suggests that data cleanup, rigorously consistent formatting of metadata strings, and addressing challenges in existing LOD resources and services could improve results for this corpus.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. The predominant subtypes, oligoarticular and polyarticular JIA, are traditionally considered to be autoimmune diseases with a central role for T cells and autoantibodies. Mounting evidence suggests an important role for neutrophils in JIA pathogenesis. We undertook this study to investigate the phenotypic features of neutrophils present in the blood and inflamed joints of patients. METHODS: JIA synovial fluid (SF) and parallel blood samples from JIA patients and healthy children were collected. SF-treated neutrophils from healthy donors and pleural neutrophils from patients with pleural effusion were investigated as controls for SF exposure and extravasation. Multicolor flow cytometry panels allowed for in-depth phenotypic analysis of neutrophils, focusing on the expression of adhesion molecules, activation, and maturation markers and chemoattractant receptors. Multiplex technology was used to quantify cytokines in plasma and SF. RESULTS: SF neutrophils displayed an activated, hypersegmented phenotype with decreased CD62L expression, up-regulation of adhesion molecules CD66b, CD11b, and CD15, and down-regulation of CXCR1/2. An elevated percentage of CXCR4-positive neutrophils was detected in SF from patients. Pleural neutrophils showed less pronounced maturation differences. Strikingly, significant percentages of SF neutrophils showed a profound up-regulation of atypical neutrophil markers, including CXCR3, intercellular adhesion molecule 1, and HLA-DR. CONCLUSION: Our data show that neutrophils in inflamed joints of JIA patients have an activated phenotype. This detailed molecular analysis supports the notion that a complex intertwining between these innate immune cells and adaptive immune events drives JIA. ispartof: ARTHRITIS & RHEUMATOLOGY vol:73 issue:5 pages:896-897 ispartof: location:United States status: published

The relevance of the study is due to the change of activity of organized criminal groups involved in the circulation of psychoactive substances towards the organization of the mentioned activity through the Internet. The article is an examination of current problems of combating drug trafficking by using the Internet. The purpose of this work is to investigate the current problems of combating drug trafficking by using the worldwide web through contactless sale of narcotic drugs and psychotropic substances. To achieve this goal, a number of methods were used, namely: theoretical – to study and analyze statistical information, scientific and methodological literature, generalization of information to determine the theoretical and methodological bases of the study; logical analysis – to formulate basic concepts and conduct classification; specifically historical – to demonstrate the dynamics of development; dialectics – to determine the content and features of the constituent elements; empirical methods – to summarize the experience. The materials of the article are of practical value for the higher education graduates of police specialties, police officers of the criminal block and specialists in the field of operational search activities.

Matrix metalloproteinases (MMPs) are enzymes with critical roles in biology and pathology. Glycosylation, nitrosylation and proteolysis are known posttranslational modifications (PTMs) regulating intrinsically the activities of MMPs. We discovered MMP citrullination by peptidyl arginine deiminases (PADs) as a new PTM. Upon hypercitrullination, MMP-9 acquired a higher affinity for gelatin than control MMP-9. Furthermore, hypercitrullinated proMMP-9 was more efficiently activated by MMP-3 compared to control MMP-9. JNJ0966, a specific therapeutic inhibitor of MMP-9 activation, inhibited the activation of hypercitrullinated proMMP-9 by MMP-3 significantly less in comparison with control proMMP-9. The presence of citrullinated/homocitrullinated MMP-9 was detected in vivo in neutrophil-rich sputum samples of cystic fibrosis patients. In addition to citrullination of MMP-9, we report efficient citrullination of MMP-1 and lower citrullination levels of MMP-3 and MMP-13 by PAD2 in vitro. In conclusion, citrullination of MMPs is a new PTM worthy of additional biochemical and biological studies. ispartof: MATRIX BIOLOGY vol:95 pages:68-83 ispartof: location:Netherlands status: published

Fluorescence anisotropy method was applied to characterize the interactions of DNA minor groove binder Hoechst 33258 with different solvents without and in the presence of DNA. It is important to study the interaction of small molecules with DNA for the purpose of better understanding the mechanism of their action, as well as to design novel and more effective compounds. Spectroscopic study of the ligand in different binary mixed solvents containing DMSO, alcohols and buffer was carried out. Studies were performed without and in the presence of DNA. Fluorescence anisotropy studies reveal the characteristics of Hoechst 33258 in different mixed solvents. The results show the strong dependence of the anisotropy of Hoechst 33258 on solvent content, viscosity and intermolecular interactions. Communicated by Ramaswamy H. Sarma.

Circulating free DNA in plasma is an alternative source of tumor-derived DNA that can be a surrogate for tissue epidermal growth factor receptor (EGFR) testing. We evaluated the analytical performance of the cobas® EGFR Mutation Test v2 (cobas test), a real-time polymerase chain reaction assay designed to detect defined EGFR gene mutations in plasma from patients with advanced non-small cell lung cancer (NSCLC). We used K2-ethylenediaminetetraacetic acid plasma samples from NSCLC patients and healthy donors (HDs), along with cell line DNA. Results from a complete technical performance evaluation are described, including a comparison between NSCLC and HD plasma to support the use of surrogate samples and an independent confirmation of the limit of detection (LoD). The cobas test reported an overall percent agreement of approximately 88% for plasma samples when compared with a next-generation sequencing method. The LoD for all EGFR mutations was ≤ 100 copies/mL for plasma samples. An external study confirmed the LoD for exon 19 deletion, L858R, and T790M at ≤ 100 copies/mL using samples derived from NSCLC patient specimens. The cobas test showed linearity between at least 50 and 10,000 copies/mL for plasma samples. An internal repeatability study reported a correct call accuracy of 99.2% for plasma samples. The performance of the cobas test is equivalent when using sheared or intact cell line DNA diluted into either HD plasma or NSCLC patient plasma. The cobas test is a sensitive, robust, and accurate assay that delivers reproducible results.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.

While GWAS of common diseases has delivered thousands of novel genetic findings, prioritizing genes for translation to therapeutics has been challenging. Here, we propose an approach to resolve that issue by identifying genes that have both gain of function (GoF) and loss of function (LoF) mutations associated with opposing effects on phenotype (Bidirectional Effect Selected Targets, BEST). Bidirectionality is a desirable feature of the best targets because it implies both a causal role on the phenotype in one direction and that modulating the target activity might be safe and therapeutically beneficial in the other.We used height, a highly heritable trait and a model of complex diseases, to test our approach. Using 34,231 individuals with exome sequence data and height, we identified five genes (IGF1R, NPPC, NPR2, FGFR3, and SHOX) with evidence for bidirectional effects on stature. Rare protein-altering variants significantly increased risk for idiopathic short stature (ISS) (OR=2.75, p= 3.99×10−8). These genes are key members of the only two pathways successfully targeted for short stature: Growth Hormone/Insulin-like growth factor 1 axis and C-type Natriuretic peptide (CNP) for Achondroplasia, a monogenic form of dwarfism. We assayed a subset of NPR2 mutations and identified those with elevated (GoF) and diminished (LoF) activity and found that a polygenic score for height modulates the penetrance of pathogenic variants. We also demonstrated that adding exogenous CNP (encoded by NPPC) rescues the NPR2 haploinsufficiency molecular phenotype in a CRISPR-engineered cell line, thus validating its potential therapeutic treatment for inherited forms of short stature. Finally, we found that these BEST targets increase the probability of success in clinical trials above and beyond targets with other genetic evidence. Our results show the value of looking for bidirectional effects to identify and validate drug targets.

Contains fulltext : 228242.pdf (Publisher’s version ) (Open Access) Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents’ reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void - reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article. 19 p.

Laboratory testing for thrombophilia is complicated but essential for diagnosis. In 2017, the cobas® Factor II and Factor V Test (cobas F2F5 test) was launched for use with the cobas z 480 analyzer. This qualitative polymerase chain reaction test enables multiplex Factor II and Factor V testing with flexible reporting and workflow efficiency. Here, we report the results from studies investigating the performance of the cobas F2F5 test. Technical performance verification, clinical validation, external laboratory performance, and workflow comparison studies were performed. Fresh and frozen whole-blood and genomic DNA (gDNA) samples were tested, and several manual and automated DNA isolation methods were used. Bidirectional Sanger sequencing was used to verify genotypes identified by the cobas F2F5 test. One hundred percent agreement between the cobas F2F5 test and Sanger sequencing was observed for all genotypes. An external laboratory using remnant clinical samples also yielded 100% agreement between cobas F2F5 test results and their routine testing method. The cobas F2F5 test reduced the total sample processing time compared with the LightCycler® 1.2 platform (98.6 vs 420.2 min; 96 samples). Hemoglobin, extraction buffer, and ethanol contamination of the gDNA sample can lead to invalid results. The cobas F2F5 test has a high degree of accuracy for identification of Factor II and Factor V genotypes. This multiplex testing with short sample processing time can reduce handling errors and increase efficiency. Both manual and automated DNA isolation methods can be used with the cobas F2F5 test. Electronic supplementary material The online version of this article (10.1007/s11239-018-1745-8) contains supplementary material, which is available to authorized users.