Bleeding phenotype and hemostatic evaluation by thrombin generation in children with Noonan syndrome: A prospective study.

BACKGROUND: This study aimed to evaluate the bleeding phenotype and to conduct a comprehensive hemostatic evaluation in individuals with Noonan syndrome (NS), a dominantly inherited disorder caused by pathogenic variants in genes associated with the Ras/MAPK signaling pathway. METHODS: Children with a genetically confirmed diagnosis of NS underwent clinical evaluation, routine laboratory tests, platelet function testing, and thrombin generation (TG) assessment. RESULTS: The study included 24 children. The most frequently reported bleeding symptoms were easy bruising and epistaxis, while bleeding complications were observed in 15% of surgical procedures. Various hemostatic abnormalities were identified, including platelet dysfunction, von Willebrand disease, and clotting factor deficiencies. Abnormal platelet function was observed in 50% of the patients, and significantly lower TG parameters were found compared to controls. However, no significant correlation was observed between bleeding symptoms and TG results. CONCLUSIONS: The study suggests that the bleeding diathesis in NS is multifactorial, involving both platelet dysfunction and deficiencies of plasma coagulation factors. The potential role of TG assay as an ancillary tool for predicting bleeding tendencies in individuals with NS undergoing surgery warrants further investigation.

Prothrombin consumption as an indicator of hemorrhagic phenotype in mild platelet function disorders.

BACKGROUND: The bleeding risk of patients with mild platelet function disorders is difficult to assess and their phenotype remains ill-explored. AIM: This study was designed to establish a comprehensive biological phenotype of patients with mild platelet function disorders. METHODS: Twenty patients were included with persistent abnormal light transmission aggregometry (LTA). The ISTH bleeding assessment tool (ISTH-BAT) was assessed to identify laboratory analyses associated with an abnormal hemorrhagic score. RESULTS: The majority of patients had defects that might affect Gαi protein signaling pathways or minor abnormalities. No LTA nor flow cytometry parameters were associated with an above-normal hemorrhagic score. However, prothrombin consumption, which corresponds to the ratio of serum residual factor II to plasma residual factor II, was significantly higher (p = .006) in the abnormal ISTH-BAT group (mean = 14%, SD = 6) compared with the normal ISTH-BAT group (mean = 8%, SD 4). Prothrombin consumption was significantly associated with ISTH-BAT score (r = .5287, IC 95% 0.0986-0.7924, p = .0165). CONCLUSION: In this group of patients, there was an association between a pathological bleeding score and increased prothrombin consumption. This test could be used as an additional indicator of platelet function abnormality liable to be related to bleeding risk.

Fiber Optic Sensor of Ammonia Gas Using Plasmonic Extraordinary Optical Transmission.

While standard surface plasmon resonance (bio) sensing, relaying on propagating surface plasmon polariton sensitivity on homogeneous metal/dielectric boundaries, represents nowadays a routine sensing technique, other alternatives, such as inverse designs with nanostructured plasmonic periodic hole arrays, have been far less studied, especially in the context of gas sensing applications. Here, we present a specific application of such a plasmonic nanostructured array for ammonia gas sensing, based on a combination of fiber optics, extraordinary optical transmission (EOT) effect, and chemo-optical transducer selectively sensitive to ammonia gas. The nanostructured array of holes is drilled in a thin plasmonic gold layer by means of focused ion beam technique. The structure is covered by chemo-optical transducer layer showing selective spectral sensitivity towards gaseous ammonia. Metallic complex of 5-(4'-dialkylamino-phenylimino)-quinoline-8-one dye soaked in polydimethylsiloxane (PDMS) matrix is used in place of the transducer. Spectral transmission of the resulting structure and its changes under exposition to ammonia gas of various concentrations is then interrogated by fiber optics tools. The observed VIS-NIR EOT spectra are juxtaposed to the predictions performed by the rigorous Fourier modal method (FMM), providing useful theoretical feedback to the experimental data, and ammonia gas sensing mechanism of the whole EOT system and its parameters are discussed.

Screening and diagnosis of inherited platelet disorders.

Inherited platelet disorders are important conditions that often manifest with bleeding. These disorders have heterogeneous underlying pathologies. Some are syndromic disorders with non-blood phenotypic features, and others are associated with an increased predisposition to developing myelodysplasia and leukemia. Platelet disorders can present with thrombocytopenia, defects in platelet function, or both. As the underlying pathogenesis of inherited thrombocytopenias and platelet function disorders are quite diverse, their evaluation requires a thorough clinical assessment and specialized diagnostic tests, that often challenge diagnostic laboratories. At present, many of the commonly encountered, non-syndromic platelet disorders do not have a defined molecular cause. Nonetheless, significant progress has been made over the past few decades to improve the diagnostic evaluation of inherited platelet disorders, from the assessment of the bleeding history to improved standardization of light transmission aggregometry, which remains a "gold standard" test of platelet function. Some platelet disorder test findings are highly predictive of a bleeding disorder and some show association to symptoms of prolonged bleeding, surgical bleeding, and wound healing problems. Multiple assays can be required to diagnose common and rare platelet disorders, each requiring control of preanalytical, analytical, and post-analytical variables. The laboratory investigations of platelet disorders include evaluations of platelet counts, size, and morphology by light microscopy; assessments for aggregation defects; tests for dense granule deficiency; analyses of granule constituents and their release; platelet protein analysis by immunofluorescent staining or flow cytometry; tests of platelet procoagulant function; evaluations of platelet ultrastructure; high-throughput sequencing and other molecular diagnostic tests. The focus of this article is to review current methods for the diagnostic assessment of platelet function, with a focus on contemporary, best diagnostic laboratory practices, and relationships between clinical and laboratory findings.

The porcine abattoir blood model-Evaluation of platelet function for in-vitro hemocompatibility investigations.

BACKGROUND: The major obstacle of blood-contacting medical devices is insufficient hemocompatibility, particularly thrombogenicity and platelet activation. Pre-clinical in-vitro testing allows for the evaluation of adverse thrombogenicity-related events, but is limited, among others, by the availability and quantity of human blood donations. The use of animal blood is an accepted alternative for several tests; however, animal and particularly abattoir blood might present species-specific differences to human blood as well as elevated blood values, and pre-activated platelets due to stressed animals and non-standardized blood collection. MATERIAL & METHODS: To this end, we investigated porcine abattoir blood in comparison to human donor blood with the focus on platelet pre-activation and remaining activation potential. By means of light transmission aggregometry, aggregation kinetics of platelet rich plasma after stimulation with three different concentrations of each adenosine diphosphate (ADP) (5 µM, 10 µM, 20 µM) and collagen (2.5 µg/ml, 5 µg/ml, 10 µg/ml) were monitored. RESULTS: The activation with collagen revealed no significant differences in platelet behavior of the two species. In contrast, stimulation with ADP resulted in a lower maximum aggregation and a high disaggregation for porcine abattoir blood. The latter is a species-specific phenomenon of porcine platelets. Variations within each study cohort were comparable for human and abattoir pig. CONCLUSION: The similarities in platelet activation following collagen stimulation and the preservation of the porcine-specific reaction to ADP prove a general functionality of the abattoir blood. This finding provides a first step towards the complete validation of the porcine abattoir blood model.

The influence of inorganic fillers on the light transmission through resin-matrix composites during the light-curing procedure: an integrative review.

PURPOSE: The objective of this study was to perform an integrative review on the effect the inorganic fillers on the light transmission through the resin-matrix composites during the light-curing procedure. METHOD: A bibliographic review was performed on PubMed using the following search terms: "fillers" OR "particle" AND "light curing" OR "polymerization" AND "light transmission" OR "light absorption" OR "light irradiance" OR "light attenuation" OR "light diffusion" AND "resin composite." The search involved articles published in English language in the last 10 years. RESULTS: Selected studies reported a decrease in biaxial strength and hardness in traditional resin-matrix composites in function of the depth of polymerization. However, there were no significant differences in biaxial strength and hardness recorded along the polymerization depth of Bulk-Fill™ composites. Strength and hardness were enhanced by increasing the size and content of inorganic fillers although some studies revealed a progressive decrease in the degree of conversion on increasing silica particle size. The translucency of glass-ceramic spherical fillers promoted light diffusion mainly in critical situations such as in the case of deep proximal regions of resin-matrix composites. CONCLUSIONS: The amount of light transmitted through the resin-matrix composites is influenced by the size, content, microstructure, and shape of the inorganic filler particles. The decrease of the degree of conversion affects negatively the physical and mechanical properties of the resin-matrix composites. CLINICAL RELEVANCE: The type and content of inorganic fillers in the chemical composition of resin-matrix composites do affect their polymerization. As a consequence, the clinical performance of resin-matrix composites can be compromised leading to variable physical properties and degradation. The polymerization mode of resin-matrix composites can be improved according to the type of inorganic fillers in their chemical composition.

Optical and Mechanical Properties of Layered Infrared Interference Filters.

The design and manufacturing technology of interference-absorbing short-wave filters based on a layered composition of Si-SiO on a sapphire substrate of various shapes was developed. A transition layer of SiO was applied to the surface of the substrate, alternating with layers of Si-SiO with an odd number of quarter-wave layers of materials with high (Si) and low refractive indices (SiO), and the application of an outer layer of SiO as an appropriate control of the materials' thickness. The optical properties of the infrared light filter were studied. It was established that the created design of the light filter provides the minimum light transmission in the visible region of the spectrum from 0.38 to 0.78 µm and the maximum in the near infrared region from 1.25 to 5 µm and has stable optical indicators. A method for studying the stress-strain state and strength of a multilayer coating of a light filter under the action of a local arbitrarily oriented load was developed. For simplicity in the analysis and for obtaining results in the analytical form, the one-dimensional model of the configuration "multilayer covering-firm substrate" constructed earlier by authors was used. From a mechanical point of view, the upper protective layer of the multilayer coating was modeled by a flexible plate, and the inner operational composite N-layer was subjected to Winkler's hypothesis about the proportionality of stresses and elastic displacements.

Impact of Copper-Doped Mesoporous Bioactive Glass Nanospheres on the Polymerisation Kinetics and Shrinkage Stress of Dental Resin Composites.

We embedded copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) with antibacterial and ion-releasing properties into experimental dental composites and investigated the effect of Cu-MBGN on the polymerisation properties. We prepared seven composites with a BisGMA/TEGDMA (60/40) matrix and 65 wt.% total filler content, added Cu-MBGN or a combination of Cu-MBGN and silanised silica to the silanised barium glass base, and examined nine parameters: light transmittance, degree of conversion (DC), maximum polymerisation rate (Rmax), time to reach Rmax, linear shrinkage, shrinkage stress (PSS), maximum PSS rate, time to reach maximum PSS rate, and depth of cure. Cu-MBGN without silica accelerated polymerisation, reduced light transmission, and had the highest DC (58.8 ± 0.9%) and Rmax (9.8 ± 0.2%/s), but lower shrinkage (3 ± 0.05%) and similar PSS (0.89 ± 0.07 MPa) versus the inert reference (0.83 ± 0.13 MPa). Combined Cu-MBGN and silica slowed the Rmax and achieved a similar DC but resulted in higher shrinkage. However, using a combined 5 wt.% Cu-MBGN and silica, the PSS resembled that of the inert reference. The synergistic action of 5 wt.% Cu-MBGN and silanised silica in combination with silanised barium glass resulted in a material with the highest likelihood for dental applications in future.

Platelet reactivity in response to aspirin and ticagrelor in African-Americans and European-Americans.

Platelet gene polymorphisms are associated with variable on-treatment platelet reactivity and vary by race. Whether differences in platelet reactivity and aspirin or ticagrelor exist between African-American and European-Americans remains poorly understood. Biological samples from three prior prospective antiplatelet challenge studies at the Duke Clinical Research Unit were used to compare platelet reactivity between African-American and European-American subjects. Platelet reactivity at baseline, on-aspirin, on-ticagrelor, and the treatment effect of aspirin or ticagrelor were compared between groups using an adjusted mixed effects model. Compared with European-Americans (n = 282; 50% female; mean ± standard deviation age, 50 ± 16), African-Americans (n = 209; 67% female; age 48 ± 12) had lower baseline platelet reactivity with platelet function analyzer-100 (PFA-100) (p < 0.01) and with light transmission aggregometry (LTA) in response to arachidonic acid (AA), adenosine diphosphate (ADP), and epinephrine agonists (p < 0.05). African-Americans had lower platelet reactivity on aspirin in response to ADP, epinephrine, and collagen (p < 0.05) and on ticagrelor in response to AA, ADP, and collagen (p < 0.05). The treatment effect of aspirin was greater in European-Americans with an AA agonist (p = 0.002). Between-race differences with in vitro aspirin mirrored those seen in vivo. The treatment effect of ticagrelor was greater in European-Americans in response to ADP (p < 0.05) but with collagen, the treatment effect was greater for African-Americans (p < 0.05). Platelet reactivity was overall lower in African-Americans off-treatment, on aspirin, and on ticagrelor. European-Americans experienced greater platelet suppression on aspirin and on ticagrelor. The aspirin response difference in vivo and in vitro suggests a mechanism intrinsic to the platelet. Whether the absolute level of platelet reactivity or the degree of platelet suppression after treatment is more important for clinical outcomes is uncertain.

Harmonizing light transmission aggregometry in the Netherlands by implementation of the SSC-ISTH guideline.

Light transmission aggregometry (LTA) is considered the gold standard method for evaluation of platelet function. However, there are a lot of variation in protocols (pre-analytical procedures and agonist concentrations) and results. The aim of our study was to establish a national LTA protocol, to investigate the effect of standardization and to define national reference values for LTA. The SSC guideline was used as base for a national procedure. Almost all recommendations of the SSC were followed e.g. no adjustment of PRP, citrate concentration of 109 mM, 21 needle gauge, fasting, resting time for whole blood and PRP, centrifugation time, speed and agonists concentrations. LTA of healthy volunteers was measured in a total of 16 hospitals with 5 hospitals before and after standardization. Results of more than 120 healthy volunteers (maximum aggregation %) were collected, with participating laboratories using 4 different analyzers with different reagents. Use of low agonist concentrations showed high variation before and after standardization, with the exception of collagen. For most high agonist concentrations (ADP, collagen, ristocetin, epinephrine and arachidonic acid) variability in healthy subjects decreased after standardization. We can conclude that a standardized Dutch protocol for LTA, based on the SSC guideline, does not result in smaller variability in healthy volunteers for all agonist concentrations.

Impact of high on-treatment platelet reactivity after angioplasty in patients with peripheral arterial disease.

Objective: High on-treatment platelet reactivity (HTPR) to dual antiplatelet therapy (DAPT) predicts adverse events in coronary artery disease patients. In peripheral artery disease (PAD) patients, data concerning the clinical impact of HTPR are limited. Therefore, we evaluated the incidence of (i) HTPR to DAPT and (ii) its impact on 6 months outcome after angioplasty.Methods and results: In this prospective single center analysis, we investigated 102 consecutive patients with PAD from 2016 to 2017. All patients underwent peripheral endovascular treatment due to intermittent claudication (Fontaine IIb). Clopidogrel effects were measured using vasodilator-stimulated protein phosphorylation (VASP) assay, aspirin effects by light-transmission aggregometry (LTA). Major adverse limb events (MALE), major adverse cardiac and cerebrovascular events (MACCE) and BARC bleeding (bleeding academic research consortium classification) within 6 months were assessed. HTPR to clopidogrel (n = 37, 36%), to aspirin (n = 11, 11%) and to both (n = 11, 11%) were frequent. Compared to sufficient platelet inhibition by aspirin and clopidogrel (n = 43, 42%), patients with dual HTPR showed a higher risk of MALE at 6 months (27% vs. 7%; hazard ratio [HR]: 4.45; 95% confidence interval [CI]: 1.1 to 67.8; p = .03). This was independent of diabetes, creatinine, body mass index, and age as well as of procedural details in a multivariate logistic regression analysis. MACCE (n = 2) and BARC bleeding rates (n = 2) were low.Conclusion: In this small exploratory study, HTPR was frequent in PAD patients. Furthermore, the results are suggestive that MALE might be associated with dual HTPR. This leads to the hypothesis that optimized antithrombotic regimens post percutaneous transluminal angioplasty should be tested in clinical trials.

Light Transmission for a Novel Chairside CAD/CAM Lithium Disilicate Ceramic.

AIM: To evaluate light transmission in a novel chairside CAD/CAM lithium disilicate ceramic with different thicknesses and with and without polishing. MATERIALS AND METHODS: Sixty flat samples (10 specimens/group) were fabricated from novel chairside CAD/CAM lithium disilicate ceramic blocks (Amber Mill, Hass Bio) with different thicknesses and with and without polishing as follows: (1) 1.0 mm thickness without polishing (1.0NoP); (2) 1.0 mm thickness with polishing (1.0Po); (3) 1.5 mm thickness without polishing (1.5NoP); (4) 1.5 mm thickness with polishing (1.5Po); (5) 2.0 mm thickness without polishing (2.0NoP); and (6) 2.0 mm thickness with polishing (2.0Po). Specimens were polished with a polishing system for lithium disilicate restorations following the manufacturer's recommendations. Light transmission was evaluated with a curing radiometer. Obtained data were subjected to two-way ANOVA followed by Tukey's post hoc tests (α = 0.05). SEM observations were conducted to evaluate surface microstructure. RESULTS: The light intensity through the lithium disilicate blocks with and without polishing was 200.9 mW/cm2 (16.1%) and 194.4 mW/cm2 (15.6%) for 1.0 mm specimens, 119.3 mW/cm2 (9.5%) and 111.9 mW/cm2 (9.0%) for 1.5 mm specimens, and 102.3 mW/cm2 (8.2%) and 96.0 mW/cm2 (7.7%) for 2.0 mm specimens. SEM images showed a smoother surface with polishing compared to nonpolished specimens. CONCLUSION: The thickness and polishing of the restorations were both significant influential factors in light transmission. CLINICAL SIGNIFICANCE: The range of light transmission percentage through the novel chairside CAD/CAM lithium disilicate blocks was 7.7-16.1%, suggesting that light attenuation through the material may influence the polymerization reaction of resin luting cement in the bonding process.

ß-Amyloid and mitochondrial-derived peptide-c are additive predictors of adverse outcome to high-on-treatment platelet reactivity in type 2 diabetics with revascularized coronary artery disease.

BACKGROUND AND AIMS: Increased ß-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization. PATIENTS AND METHODS: In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) ß-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up. RESULTS: Out of 121 patients, 32 showed HPR (LTAmax > 48%,). At baseline, HPR was associated with ß-amyloid > 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, ß-amyloid > 51 pg/ml and MOTS-c < 167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p < 0.05) after adjusting for confounders and medication. There was significant interaction between HPR and ß-amyloid or MOTS-c for the prediction of MACE (p < 0.05). Patients with HPR and ß-amyloid > 51 mg/dl or HPR and MOTS-c concentration < 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p < 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD. CONCLUSIONS: Increased ß-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712.

Inhibition of agonist-induced platelet aggregation by magnesium sulfate warrants its use as an alternative in vitro anticoagulant in pseudothrombocytopenia.

MgSO4 is effective in preventing spontaneous in vitro platelet agglutination in anticoagulant-induced pseudothrombocytopenia (PTCP). In order to learn more about its potential as an in vitro anticoagulant, platelets from MgSO4-anticoagulated blood were stimulated by several differentially-acting agonists (ADP, ARA, TRAP, epinephrine, collagen and ristocetin). Platelet aggregation in blood samples from 11 and 17 volunteers was measured by light-transmission aggregometry (LTA) according to Born and impedance aggregometry (MultiplateTM), respectively. Agonist-induced platelet aggregation was markedly lower in MgSO4-anticoagulated samples when compared with citrate-anticoagulated samples (decrease of 95.75% (ristocetin), 69.02% (collagen) and 75.73% (epinephrine)) or hirudin-anticoagulated samples (decrease of 85.99% (ADP), 80.98% (ARA), 77.24% (ristocetin), 54.37% (collagen) and 50.14% (TRAP)). The anti-aggregatory effect of MgSO4 is dose-dependent and readily detectable at a concentration of 7.5 mmol/l. Analysis of the agonist signaling pathways suggest that MgSO4 interferes with the final step of platelet aggregation, namely the intracellular mobilization of Ca2+.

Pitfall of Light Transmission Aggregometry-Based Assessment of Platelet Function in Acute Ischemic Stroke Patients.

BACKGROUND: The utility of light transmission aggregometry (LTA)-based assessment of platelet function in acute ischemic stroke patients remains controversial. This study aimed to clarify why LTA failed to estimate platelet function in acute ischemic stroke patients. METHODS: Using LTA, we evaluated the platelet aggregation abilities of citrated blood samples from 22 acute noncardiogenic ischemic stroke patients prior to treatment and compared them with those of 65 heathy volunteer controls. Platelet counts and mean platelet volumes (MPV) of citrated blood and platelet-rich plasma (PRP) prepared for LTA were evaluated simultaneously. Using a hematology analyzer, we also measured and compared the aggregation-prone properties of platelets in the hematology analysis process between patient and control samples. RESULTS: Although platelets aggregated more easily and frequently in patient samples (P < .01), the maximum aggregation rate (MA%) of LTA was paradoxically lower in patients than in controls (P < .05). The PRP/citrated blood ratio of platelet counts and MPV were significantly lower in patients than in controls (P < .05). CONCLUSIONS: Our results suggest that MA% of LTA is erroneously displayed as lower values than the actual status in patients with increased platelet aggregation ability such as acute ischemic stroke because activated large platelets are preaggregated and thus decreased in the PRP on LTA.

Ticagrelor as an Alternative Antiplatelet Therapy in Cardiac Patients Non-Sensitive to Aspirin.

Background and Objectives: Aspirin (acetylsalicylic acid-ASA) is a first-line antiplatelet therapy provided to patients with coronary artery disease (CAD). However, it has been demonstrated that 20-30% of these patients are non-sensitive to their ASA therapy. ASA non-sensitivity is a phenomenon where low-dose ASA (81-325 mg) does not completely inhibit arachidonic-acid-induced platelet aggregation, putting patients at risk of adverse cardio-thrombotic events. Ticagrelor is a P2Y12 receptor inhibitor and alternative antiplatelet that has been approved to reduce the risk of stroke, myocardial infarction, and overall cardiovascular-related death. In this study, we aimed to identify ASA non-sensitive patients and evaluate if they would be sensitive to ticagrelor. Materials and Methods: For this pilot study, thirty-eight patients with CAD taking 81 mg ASA were recruited. Blood samples were collected from each patient and platelet rich plasma (PRP) from each sample was isolated. Light-transmission aggregometry (LTA) was used to determine baseline ASA sensitivity in each patient using 0.5 mg/mL arachidonic acid as a platelet agonist. Patients with ≥20% maximal platelet aggregation after activation were considered ASA non-sensitive. Fresh PRP samples from all patients were then spiked with a clinical dosage of ticagrelor (3 µM-approximately equivalent to a loading dose of 180 mg ticagrelor). Sensitivity was determined using LTA and 5 µM ADP as a platelet agonist. Patients with ≥46% maximal platelet aggregation were considered ticagrelor non-sensitive. Results: Of the 38 CAD patients taking 81 mg ASA, 32% (12/38) were non-sensitive to their 81 mg ASA therapy. All 38 of the recruited patients (100%) were sensitive to ticagrelor ex vivo. In conclusion, we were able to identify ASA non-sensitivity using LTA and determine that ASA non-sensitive patients were sensitive to ticagrelor. Conclusions: Our results suggest that ticagrelor is a promising alternative therapy for patients who are non-sensitive to ASA.

Assessment of light transmission aggregometry on the routine coagulation analyzer Sysmex CS-2500 using CE-marked agonists from Hyphen Biomed.

Light transmission aggregometry (LTA) is still considered as the "gold standard" for platelet function assessment but, as acompletely manual technology, it is labour intensive. This challenge can be overcome by performing platelet aggregometry in anautomated method on a routine coagulation analyzer. We aimed to compare and correlate results obtained from a traditional manual LTA solution realized in our Reference Center with an optimized automated system using CE-marked agonist reagents. Platelet rich plasma from patients with suspected platelet disorders, von Willebrand disease or antiplatelet therapy have been assessed using a wide range of agonist concentrations. Results were expressed as Maximal Platelet Aggregation and correlation was analyzed using the Passing and Bablok regression test. Platelet aggregometry studies were performed in 49 samples. Maximal aggregation response with ADP (0.5-10 µM), collagen (2 mg/µL), ristocetin (1.2 mg/mL) and arachidonic acid (1 mM) agonists showed significant correlation between the two aggregometers (p< .001). We observed a more variable response using lowconcentrations of ADP (≤5 µM). Moreover, we also noted discrepancies with the low dose of ristocetin, showing excessive paradoxical agglutination with the CS-2500, suggesting that a lower ristocetin dose should be used with this system. These data show that CS-2500 has the advantages of a walk-away technology and the use of CE-marked reagents also permit the possibility of an easier certification.

Evaluation of the Total Thrombus-Formation System (T-TAS): application to human and mouse blood analysis.

The Total Thrombus-formation Analyser System (T-TAS) is a whole blood flow chamber system for the measurement of in vitro thrombus formation under variable shear stress conditions. Our current study sought to evaluate the potential utility of the T-TAS for the measurement of thrombus formation within human and mouse whole blood. T-TAS microchips (collagen, PL chip; collagen/tissue thromboplastin, AR chip) were used to analyze platelet (PL) or fibrin-rich thrombus formation, respectively. Blood samples from humans (healthy and patients with mild bleeding disorders) and wild-type (WT), mice were tested. Light transmission lumi-aggregometer (lumi-LTA) was performed in PRP using several concentrations of ADP, adrenaline, arachidonic acid, collagen, PAR-1 peptide and ristocetin. Thrombus growth (N = 22) increased with shear within PL (4:40 ± 1.11, 3:25 ± 0.43 and 3:12 ± 0.48 mins [1000, 1500 and 2000s-1]) and AR chips (3:55 ± 0.42 and 1:49 ± 0.19 [240s-1 and 600s-1]). The area under the curve (AUC) on the PL chip was also reduced at 1000s-1 compared to 1500/2000s-1 (260 ± 51.7, 317 ± 55.4 and 301 ± 66.2, respectively). In contrast, no differences in the AUC between 240s-1 and 600s-1 were observed in the AR chip (1593 ± 122 and 1591 ± 158). The intra-assay coefficient of variation (CV) (n = 10) in the PL chip (1000s-1) and AR chip (240s-1) were T1014.1%, T6016.7%, T10-6022.8% and AUC1024.4% or T10 9.03%, T808.64%, T10-8023.8% and AUC305.1%. AR chip thrombus formation was inhibited by rivaroxaban (1 µM), but not with ticagrelor (10 µM). In contrast, PL chip thrombus formation was totally inhibited by ticagrelor. T-TAS shows an overall agreement with lumi-LTA in 87% of patients (n = 30) with normal PL counts recruited into the genotyping and phenotyping of platelet (GAPP) study and suspected to have a PL function defect. The onset (T10) of thrombus formation in WT mice (N = 4) was shorter when compared to humans e.g. PL chip (1000s-1) T10 were 02:02 ± 00:23 and 03:30 ± 0:45, respectively). T-TAS measures in vitro thrombus formation and can be used for monitoring antithrombotic therapy, investigating patients with suspected PL function defects and monitoring PL function within mice.

Self-Sensing Polymer Composite: White-Light-Illuminated Reinforcing Fibreglass Bundle for Deformation Monitoring.

The goal of our research was to develop a continuous glass fibre-reinforced epoxy matrix self-sensing composite. A fibre bundle arbitrarily chosen from the reinforcing glass fabric in the composite was prepared to guide white light. The power of the light transmitted by the fibres changes as a result of tensile loading. In our research, we show that a selected fibre bundle even without any special preparation can be used as a sensor to detect deformation even before the composite structure is damaged (before fibre breaking).

Deep Learning-Based Multinational Banknote Type and Fitness Classification with the Combined Images by Visible-Light Reflection and Infrared-Light Transmission Image Sensors.

Automatic sorting of banknotes in payment facilities, such as automated payment machines or vending machines, consists of many tasks such as recognition of banknote type, classification of fitness for recirculation, and counterfeit detection. Previous studies addressing these problems have mostly reported separately on each of these classification tasks and for a specific type of currency only. In other words, there has been little research conducted considering a combination of these multiple tasks, such as classification of banknote denomination and fitness of banknotes, as well as considering a multinational currency condition of the method. To overcome this issue, we propose a multinational banknote type and fitness classification method that both recognizes the denomination and input direction of banknotes and determines whether the banknote is suitable for reuse or should be replaced by a new one. We also propose a method for estimating the fitness value of banknotes and the consistency of the estimation results among input trials of a banknote. Our method is based on a combination of infrared-light transmission and visible-light reflection images of the input banknote and uses deep-learning techniques with a convolutional neural network. The experimental results on a dataset composed of Indian rupee (INR), Korean won (KRW), and United States dollar (USD) banknote images with mixture of two and three fitness levels showed that the proposed method gives good performance in the combination condition of currency types and classification tasks.