Aggregation Test Research Articles

Abstract 4139115: Genomic, Phenomic, and Geographic Relationships with Leukocyte Telomere Length in the U.S. Yields New Insights for Neoplasms and Cardiometabolic Disease

Background: Leukocyte telomere length (LTL) is an age-related marker strongly associated with neoplasms and cardiometabolic disease. LTL is also intimately linked with clonal hematopoiesis of indeterminate potential (CHIP), a recently described risk factor for cardiovascular disease (CVD). However, population-scale investigations of LTL in diverse backgrounds are limited, and geolocational variance has not been studied. Method: LTL and CHIP were derived using blood-derived whole genome sequencing data from 244,819 diverse U.S. residents in the NIH All of Us Research Program (AoU). We performed association analyses of LTL with CHIP and other available health-related traits, Phecode, as well as geolocation data by ZIP code. Genome-wide association study (GWAS) of LTL in AoU and meta-analysis with UK Biobank were performed. All association tests were adjusted for age, sex, sequencing site, and the first 10 genetic principal components with multiple test corrections. Mediation analysis was adjusted for additional risk factors for CVD. Result: Among 244,819 AoU participants, 146,717 (59.9%) were female with mean (standard deviation) age 51.8 (±16) years. Estimated LTL correlated strongly with age, sex, and genetic ancestry in AoU. Socioeconomic status, lifestyle variables, anthropometry, blood biomarkers (e.g., lipids and glucose), and vital signs were associated with LTL in AoU. Phecode analysis showed LTL is associated with neoplasms and age-related conditions, including CVDs. LTL mediated some of the observed increased coronary artery disease risk among individuals with hematologic malignancies ( P < 2 × 10 -16 ). Significantly longer LTL clustered in the West Coast and Central Midwest ( P = 0.001 and 0.033, respectively), while significantly shorter LTL clustered in the Southeast ( P = 0.001) (Figure). GWAS meta-analyses identified 197 loci, of which 36 (18%) were novel, including ancestry-specific loci. Rare variant aggregation test found 9 novel associated genes. Conclusions: LTL is a marker of biological age that is associated and interacts with neoplasms, CVDs, and its various risk factors, with notable geographic variability within the U.S. Germline genetic analyses of LTL yield new insights into drivers of LTL.

Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project.

Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p<5×10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p=1.9×10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p=7.2×10-8). We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD. We determine the association of genetic variants with Alzheimer's disease (AD) using 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. We identified genetic variants at apolipoprotein E (APOE), BIN1, PSEN1, and LINC00320 associated with AD. We observed rare non-coding variants in the promoter of TOMM40 distinct of APOE.

Correlation Analysis between Platelet Aggregation and Neurological Outcomes in Ischemic Stroke Patients

Ischemic stroke is a condition triggered by cerebral perfusion disorders with the risk factor of blood clotting disorders that can cause neurological deficits through a complex pathophysiological process of thrombus formation. The role of platelet aggregation as a blood clotting parameter has the potential to be used as a marker for the level of neurological deficit in patients with ischemic stroke in conjunction with the National Institutes of Health Stroke Scale (NIHSS). The study aimed to observe the correlation between platelet aggregation and the degree of neurological deficit calculated using NIHSS. The study utilized a cross-sectional design with 51 research subjects diagnosed with ischemic stroke based on CT Scan results, followed by platelet aggregation testing. Patients with a diagnosis of hemorrhagic stroke and cardiogenic ischemic stroke were excluded from this study. This study found variations in platelet aggregation among groups with different degrees of stroke severity. However, it was not statistically significant (p=0.427). Correlation analysis showed a mild positive correlation between platelet aggregation and the degree of neurological deficit (r=0.157), although it was not statistically significant (p=0.270). There are variations in platelet aggregation in assessing neurological deficits using NIHSS. There is a positive correlation between the percentage of platelet aggregation and the level of neurological deficit in patients with ischemic stroke.

Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height

The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P < 6×10−10\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$6\ imes {10}^{-10}$$\\end{document} after conditioning on previously reported variants, with effect sizes ranging from −7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based associations proximal to HMGA1 containing variants associated with a 5 cm taller height and of highly-conserved variants in MIR497HG on chromosome 17. We have developed an approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.

Comparison of Platelet Aggregation Test before and after Hemodialysis in Patients with Kidney Failure

Comparison of Platelet Aggregation Test before and after Hemodialysis in Patients with Kidney Failure

Hypometric genetics: Improved power in genetic discovery by incorporating quality control flags.

Balancing the tradeoff between quantity and quality of phenotypic data is critical in omics studies. Measurements below the limit of quantification (BLQ) are often tagged in quality control fields, but these flags are currently underutilized in human genetics studies. Extreme phenotype sampling is advantageous for mapping rare variant effects. We hypothesize that genetic drivers, along with environmental and technical factors, contribute to the presence of BLQ flags. Here, we introduce "hypometric genetics" (hMG) analysis and uncover a genetic basis for BLQ flags, indicating an additional source of genetic signal for genetic discovery, especially from phenotypic extremes. Applying our hMG approach to n= 227,469UK Biobank individuals with metabolomic profiles, we reveal more than 5% heritability for BLQ flags and report biologically relevant associations, for example, at APOC3, APOA5, and PDE3B loci. For common variants, polygenic scores trained only for BLQ flags predict the corresponding quantitative traits with 91% accuracy, validating the genetic basis. For rare coding variant associations, we find an asymmetric 65.4% higher enrichment of metabolite-lowering associations for BLQ flags, highlighting the impact of putative loss-of-function variants with large effects on phenotypic extremes. Joint analysis of binarized BLQ flags and the corresponding quantitative metabolite measurements improves power in Bayesian rare variant aggregation tests, resulting in an average of 181% more prioritized genes. Our approach is broadly applicable to omics profiling. Overall, our results underscore the benefit of integrating quality control flags and quantitative measurements and highlight the advantage of joint analysis of population-based samples and phenotypic extremes in human genetics studies.

Performance Assessment of Basic Oxygen Furnace Slag (BOFS) as an Ice-Melting Abrasive Material

Abrasives play a crucial role in surface blasting, especially in cold climates, where snow and ice significantly challenge transportation infrastructure and road safety. The main purpose of this research is to address the critical need for effective and sustainable winter maintenance techniques. This study examined the possibilities of Basic Oxygen Furnace Slag (BOFS) as a substitute (an abrasive substance) for conventional aggregates in ice-melting applications. Thus, this research assessed the physical properties of BOFS, such as absorption capacity, tested at -5°C, and aggregate angularity test, and designed for evaluation of the surface texture, friction, and percentage of fractured faces in uncompacted voids (SSD%) of the aggregates. Moreover, the potential use of a blend of BOFS with de-icing salts, specifically sodium chloride (NaCl) and calcium chloride (CaCl2), was investigated as an effective ice-melting agent. For this purpose, three tests were carried out: the petri dish test according to SHRP H-205.1, the polishing ice melting test using a modified ASTM C 944 (rotational cutter), and the surface temperature measurement test. By assessing the performance of BOFS, our goal was to justify its efficacy, offering a practical alternative for regions experiencing severe winter conditions. Eventually, the findings from this study assert that BOFS can be used for surface blasting, indicating its potential as a substitute for traditional abrasives.

Feasibility Assessment of Mudstone Aggregate as an Alternative Material for Colored Asphalt Pavement in South Korea

Colored asphalt pavements have been implemented in South Korea to enhance visibility and lane distinction; however, color fading, accelerated deterioration, and increased pothole occurrence have been noticed. As a solution, alternative materials that can be used for the construction of colored asphalt pavements are being explored. This study evaluates the feasibility of using mudstone aggregate in constructing colored asphalt pavement in South Korea. Initially, aggregate quality tests were conducted on mudstone samples to assess their suitability compared to standard criteria. To enhance the visibility and color retention of colored asphalt, addition of pigment in the colored asphalt pavement mixture was considered and evaluated. The asphalt mixtures were evaluated for deformation, crack and viscoelastic properties using the Kim test, indirect tensile (IDT) strength test, and dynamic modulus test, respectively. Results showed that mudstone aggregate exceeded quality standards and the colored asphalt mixtures demonstrated superior deformation strength and crack resistance compared to typical SMA. However, the addition of pigment slightly reduced these properties. Overall, the findings suggest mudstone aggregate as a viable alternative for constructing colored asphalt pavements, offering potential improvements in durability and color retention.

Combined potential of copaifera officinalis oleoresin and chitosan against oral pathogens.

Copaifera officinalis Oleoresin (COR) and Chitosan (CH) were combined to test the potential to inhibit oral bacteria. First, COR was analyzed by GC-MS to identify its main constituents and then Minimum Inhibitory Concentration (MIC) assays and Minimum Microbiocidal Concentration (MMC) of the compounds alone against 17 pathogens were performed. Sixteen primary compounds were identified in COR, but the major constituent was β-Caryophyllene (40.5%). COR showed MIC concentrations of 26.04 to 46.87µg/mL and CH 0.1mg/mL to 0.8mg/mL. Second, the combination against oral bacteria strains was tested using a checkerboard test with the determination of Fractional Inhibitory Concentration (FIC) for synergistic effect, followed by the bacterial biofilm aggregation test using monospecies and mixed biofilm. The combination of COR and CH showed a synergistic effect for S. oralis (ATCC 10557) and an additive effect for the other strains tested, promoting bactericidal activity, as well as reducing the concentrations needed to cause bacterial inhibition. In addition, it showed good activity in inhibiting biofilm formation, with inhibition percentages close to Azithromycin. The results of this study highlight the synergistic potential of COR and CH combination as a promising strategy in the search for innovative antimicrobial therapies for infections related to oral bacterial biofilms.

Characterization of probiotic strains of Bacillus sp. from fermented palm wine (Nypa fructicans sp.) and exploration of cellulolytic potential for use as an addition in animal feed.

The main objective of this study was to assess cellulolytic probiotic strains from traditional fermented beverages such as palm wine in order to supplement the animal feed and strengthen the gut health of the animal for better digestibility and absorption. In the present study, different types of microbes were isolated from traditionally prepared palm wine and analyzed for their probiotic nature. For any microbe to be probiotic in nature, it has to sustain the harsh conditions of the human gastrointestinal tract such as acid tolerance, bile tolerance at the lower range of pH, and other properties like auto aggregation test, cell surface hydrophobicity test with non-polar hydrocarbons for evaluating its capabilities to adhere to the intestinal cells and antimicrobial nature against pathogens. Bacillus mycoides strain PR04 and Bacillus subtilis strain PR21 were found to be resistant to acid and bile in simulated artificial gastrointestinal tract model, found to be than 55% hydrophobic with xylene and n-hexadecane and also showed antimicrobial activity greater towards pathogenic strains like Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Salmonella typhimurium respectively. The cellulolytic activity of the isolates PR04 and PR21 was evaluated in (0.2-2) % CMC (carboxymethyl cellulose) plate. Bacillus mycoides PR04 and Bacillus subtilis PR21 could degrade carboxymethyl cellulose, filter paper, and sugarcane bagasse. The degradation of sugarcane bagasse was confirmed by Scanning electron microscopy and filter paper degradation after 4days of incubation at 37°C. Cellulase gene of the identified Bacillus sp. strains was amplified by primers CF5'-ACAGGATCCGATGAAAACGGTCAATTTCTATTTT-3' and CR5'-ACTCTCGAGATTGGGTTCTGTTCCCAAT-3'. This study proposes potential probiotic Bacillus mycoides PR04 (Accession no. OR625070) and Bacillus subtilis PR21 (Accession no. OR625072) in the application as an animal feed additive to assist in its digestibility and encourage the gut health.

Unraveling the Genetics of Shared Clinical and Serological Manifestations in Patients With Systemic Inflammatory Autoimmune Diseases.

Systemic inflammatory autoimmune diseases (SIADs) such as systemic lupus erythematosus (SLE), primary Sjögren disease (pSS), and idiopathic inflammatory myopathies (myositis) are complex conditions characterized by shared circulating autoantibodies and clinical manifestations, including skin rashes, among others. This study was aimed at elucidating the genetics underlying these common features. We performed targeted DNA sequencing of coding and regulatory regions from approximately 1,900 immune-related genes in a large cohort of 2,292 well-characterized Scandinavian patients with SIADs with SLE, pSS, and myositis as well as 1,252 controls. A gene-based functionally weighted genetic score for aggregate testing of all genetic variants, including rare variants, was complemented by in silico functional analyses and in vitro reporter experiments. Case-control association analysis detected known and potentially novel genetic loci in agreement with previous genetic and transcriptomics findings linked to the SIAD autoimmune background. Intriguingly, case-case comparisons between patient subgroups with and without specific autoantibodies revealed that the subgroups defined by antinuclear antibodies and anti-double-stranded DNA antibodies have unique genetic profiles reflecting their heterogeneity. When focusing on clinical features, we overall showed that dual-specificity phosphatase 1 (DUSP1) protective genetic variants lead to increased gene expression and potentially to anti-inflammatory effects on the SIAD-associated skin phenotype. This is consistent with recent genetic findings on eczema and with the previously reported down-regulation of the MAPK signaling-related gene DUSP1 in other skin disorders. Together, this suggests common molecular mechanisms potentially underlying overlapping clinical manifestations shared among different disorders and informs clinical heterogeneity, which could be translated to improve disease diagnostic and treatment, also in more generalized disease frameworks.

SCAMPI: A scalable statistical framework for genome-wide interaction testing harnessing cross-trait correlations.

Family-based heritability estimates of complex traits are often considerably larger than their single-nucleotide polymorphism (SNP) heritability estimates. This discrepancy may be due to non-additive effects of genetic variation, including variation that interacts with other genes or environmental factors to influence the trait. Variance-based procedures provide a computationally efficient strategy to screen for SNPs with potential interaction effects without requiring the specification of the interacting variable. While valuable, such variance-based tests consider only a single trait and ignore likely pleiotropy among related traits that, if present, could improve power to detect such interaction effects. To fill this gap, we propose SCAMPI (Scalable Cauchy Aggregate test using Multiple Phenotypes to test Interactions), which screens for variants with interaction effects across multiple traits. SCAMPI is motivated by the observation that SNPs with pleiotropic interaction effects induce genotypic differences in the patterns of correlation among traits. By studying such patterns across genotype categories among multiple traits, we show that SCAMPI has improved performance over traditional univariate variance-based methods. Like those traditional variance-based tests, SCAMPI permits the screening of interaction effects without requiring the specification of the interaction variable and is further computationally scalable to biobank data. We employed SCAMPI to screen for interacting SNPs associated with four lipid-related traits in the UK Biobank and identified multiple gene regions missed by existing univariate variance-based tests. SCAMPI is implemented in software for public use.

Cationic tannins as aggregation agents in the flocculation on hematite–silica system

ABSTRACT This study aims to evaluate the use of commercial tannin derivatives, namely, tannin 1 (CT1), tannin 2 (CT2), tannin 3 (CT3), and extract of tannin produced from angico bark, as aggregation agent in hematite–silica systems. Hematite and quartz were used in aggregation tests at dosages of 1, 10, and 100 mg/L at pH values of 6–9. The zeta potential and Jar tests were conducted in the best conditions of aggregation tests. The condensed tannin content of the commercial reagents is approximately similar, and it exceeds the content found in the extract obtained from angico bark. CT3 demonstrated superior percentages of sedimented material for both minerals at a dosage of 10 mg/L and pH 7 (97.12% and 95.68% for hematite and quartz, respectively). The aggregation agent produced from the angico bark displayed good sedimentation results for hematite (>90%); however, the results for quartz were unsatisfactory. The isoelectric point shifts to pH 8 when each mineral was conditioned with CT3. The jar test revealed higher sedimentation of the compositions for the lowest velocity gradient (60 rpm) with low turbidity values in the supernatant; however, the lowest turbidity (24.71 NTU) is observed in the sample with a higher percentage of hematite.

Assessment of Platelet Aggregation and Thrombin Generation in Patients with Familial Chylomicronemia Syndrome Treated with Volanesorsen: A Cross-Sectional Study.

The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat Familial Chylomicronemia Syndrome (FCS). Cases of decreased platelet count are reported among patients treated with volanesorsen. The aim of the study was to evaluate platelet function and thrombin generation (TG) assessment in FCS patients receiving volanesorsen. We performed a cross-sectional study on FCS patients treated with volanesorsen. Changes in platelet count PLC were assessed from baseline to Tw12 and Tw36. To assess TG, samples were processed by CAT (with PPP-reagent LOW). The results were expressed by the thrombogram graphic (thrombin variation over time); LagTime; endogenous thrombin potential (ETP); peak; time to reach peak (ttpeak), StartTail and Velocity Index. Platelet aggregation was assessed by testing different agonists using the turbidimetry method. Four FCS patients and four matched healthy controls were included in the present study. Changes in PLC were 30% at Tw12 and 34% at Tw36. Thrombin generation results showed values in the normal range (for patients and controls, respectively, LagTime:10.42 ± 4.40 and 9.25 ± 0.99; ttPeak:14.33 ± 4.01 and 13.10 ± 0.67; StartTail: 32.13 ± 3.54 and 29.46 ± 1.69; Velocity Index: 20.21 ± 3.63 and 33.05 ± 13.21; ETP: 599.80 ± 73.47 and 900.2 ± 210.99; peak value: 76.84 ± 1.07 and 123.30 ± 39.45) and no significant difference between cases and controls. Platelet aggregation test showed values in range, with no significant difference compared to healthy controls. Our study showed for the first time that no significant changes in general hemostasis assessed by TG and in platelet function were observed in FCS patients receiving volanesorsen.

Enhancing High-Temperature Performance of Flexible Pavement with Plastic-Modified Asphalt.

Previous studies indicate that traditional asphalt mixtures lack the ability to withstand the stresses caused by heavy traffic volumes under high temperatures. To enhance the rutting resistance of flexible pavement under high levels of temperature and loading, extensive laboratory experiments were carried out. A 60/70 grade bitumen was used as a neat sample for comparison. The study introduced three distinct polymers, polypropylene (PP), low-density polyethylene (LDPE), and acrylonitrile butadiene styrene (ABS), at varying concentrations by weight into the neat bitumen. Initially, conventional tests were performed to evaluate the conventional properties of both the neat and modified bitumen, while aggregate tests assessed the mechanical properties of the aggregates. Subsequently, a Marshall mix design was performed to determine the optimum bitumen content (OBC) in the asphalt mixture. Finally, wheel-tracking tests were performed under a specific load and temperature to investigate the rutting behavior of the modified asphalt mixtures. The results of this comprehensive study revealed that the modified asphalt mixtures displayed improved resistance to rutting compared to the neat asphalt mixture. Furthermore, it was also observed that the LDPE exhibited a superior performance against rutting, followed by the PP and ABS. At polymer contents of 3%, 5%, and 7%, the LDPE achieved reductions in rut depth of 13%, 24%, and 33%, respectively, outperforming both PP- and ABS-modified asphalt. These findings not only enhance our understanding of asphalt behavior under diverse conditions but also highlight the potential of plastic-modified asphalt as an effective solution for mitigating rutting problems in road pavements. By incorporating plastic modifiers into asphalt mixtures, this approach aligns with the principles of sustainable construction by reducing plastic waste while improving pavement durability and performance.

Federated learning implementation based on DDS data distribution service

Federated learning allows multiple local private clients to collaborate on training the same model without sharing each client's private data. It can achieve collaborative training between users while protecting data privacy and security. Therefore, it is advocated for use in the fields of Internet of Things, Internet of Vehicles, etc. There are security issues in the transmission process of federated learning models. How to ensure data privacy during local data collection, local model parameter transmission, model aggregation and performance testing while maximizing the use of private data is a question that people have been exploring. This paper proposes a DDS-based FL framework (FL-DDS) to achieve secure transmission of model parameters. The client and server are used as nodes in the DDS security domain, and the DDS data distribution mechanism is used to transmit model parameters. Through the DDS topic-based publish-subscribe mechanism, the global model and local model are transmitted through the DDS topic. At the same time, the DDS authentication component, access control component and encryption component are used to achieve domain-level security and intra-domain security of model transmission. Experiments show that (FL-DDS) can protect the privacy of model parameters without affecting communication performance.

Evaluation of Haemostatic Potential and HPTLC Fingerprinting of Annona squamosa Linn. Bark Extract

Objectives: The present work focuses on exploring and evaluating the hemostatic property of Annona squamosa Linn. bark. Being a renewable resource, it has the potential to contribute to the hemostatic agent. Hemostatic efficacy of the cold and hot bark extract at different concentrations of 10, 50, 100 &amp; 250 mg/ml of saline were evaluated using whole blood clotting, platelet aggregation test, prothrombin time CAMAG HPTLC system. The hemostatic efficacy. At 250 mg/ml saline, both the extracts showed excellent hemostatic efficacy by clotting blood in 1.2 s and 3 s, respectively. The prothrombin time of cold and hot were 5 s and 5.1 s which were less than that of Liquiplastin partial prothrombin time which was Liquicelin E (13.85 s). Annona squamosa Linn. to be used as a topical hemostatic agent. Saponins, which are known to be antihemorrhagic, were detected by HPTLC. hemostatic efficacy of Annona squamosa Linn. bark was evaluated, which can contribute to the development of a fast-acting, cost-effective, easy-to-use, and sustainable topical hemostat. Keywords: Annona squamosa Linn, Hemostatic activity, Prothrombin time, Activated partial thromboplastin time, HPTLC fingerprint

Risk factor aggregation and stress testing

Stress testing refers to the application of adverse financial or macroeconomic scenarios to a portfolio. For this purpose, financial or macroeconomic risk factors are linked with asset returns, typically via a factor model. We expand the range of risk factors by adapting dimension-reduction techniques from unsupervised learning, namely PCA and autoencoders. This results in aggregated risk factors, encompassing a global factor, factors representing broad geographical regions, and factors specific to cyclical and defensive industries. As the adapted PCA and autoencoders provide an interpretation of the latent factors, this methodology is also valuable in other areas where dimension-reduction and explainability are critical.

Heterogeneity of Item-Treatment Interactions Masks Complexity and Generalizability in Randomized Controlled Trials

Researchers compare aggregate test data across treatment and control group in randomized controlled trials to determine intervention impact on student achievement. We show that item-level data and analyses can provide information about item-level treatment effect heterogeneity; such findings may be useful for improving interventions and making decisions about outcomes in subsequent studies. We apply Differential Item Functioning techniques to examine variation in the degree to which items show treatment effects. Based on our analysis of 7,244,566 item responses (265,732 students responding to 2,119 items) from 15 RCTs, we find evidence for variation in gains across items. These analyses identify items that are highly sensitive to the interventions—in one case, a single item drives nearly 40% of the observed treatment effect. Our analyses also identifies items that are insensitive and cases wherein treatment effects are consistent across items. We also show that the variation of item-level treatment sensitivity has implications for effect estimate precision. Of the treatments with significant effect estimates, 31% have patterns of item-level treatment sensitivity that may lead to a null effect when considering this source of uncertainty.

Combination of 2 Quantitative Immunoassays and Clinical Score Algorithm to Reduce False-Negative Results in Heparin-Induced Thrombocytopenia: Prevalence Study of Mauriziano Hospital in Turin, Italy.

Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin treatment caused by platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies. Accurate diagnosis of HIT is essential but remains challenging. The aim of our study was to explore the performance of our optimized diagnostic laboratory algorithm, based on Chemiluminescence (CliA) and ELISA immunoassays, on suspected HIT patients. The study compared the prevalence of HIT diagnosis in A.O. Mauriziano with the literature. 163 consecutive patients were investigated for suspected HIT with CliA HemosIL Acustar HIT-IgG, Werfen. HIT was ruled out in all patients with CliA <0.13 U/mL. All patients with CliA >0.13 U/mL were further investigated with Zymutest-HIA anti-PF4 IgG ELISA immunoassay. In these patients, HIT was ruled out on the combination of CliA between 0.13 and 1.0 U/mL followed by ELISA assay <0.300 OD. HIT was ruled in patients whose plasma tested positive or doubtful with CliA and positive with ELISA immunoassay and confirmed positive with a platelet aggregation test (PAT). Suspicion of HIT was revealed with clinical 4Ts score or recent suggestive anamnestic history. Our diagnostic algorithm ruled out HIT diagnosis in 144/163 patients (88%) and predicted a positive PAT in 5/19 (26%) of CliA positive (4/5) or ELISA positive and CliA doubtful (1/5) patients. Our prevalence was 3.1%, comparable with the literature. The approach combining 2 quantitative immunoassays' (CliA and ELISA) results and 4Ts score probability was able to rule out the diagnosis within 1 h in 66% of patients with suspected HIT and within 24 h in 88% of patients. In the remaining 12% of cases, management decisions have to be based on individualized judgment while awaiting functional confirming results (48-72 h).