Rheological Behavior and Manufacturing Simulation of Prepreg Platelet Molding Systems

Molding systems formed by cutting and slitting prepreg composite tape into the form of platelets have been shown to be beneficial in producing parts with moderate performance with moderate processing characteristics. However, the platelets forming the molding system are typically quite large compared to typical part thicknesses. Therefore, a challenge of scales exists in platelet molding systems that is absent in traditionally considered well dispersed fiber molding systems used in injection molding. In this dissertation, we consider the specific problem of determining the final orientation state of parts manufactured in compression molding from platelet molding systems along with identifying parameters which affect ease of processing. A multi-scale approach is taken addressing necessary descriptors of platelet orientation state, evolution relationships for platelet orientations, constitutive model forms along with anisotropic viscosity predictions, and finite element based implementations to analyze complex problems. The major result is then a holistic modeling approach applied to a pin bracket geometry which is then validated versus experimental measurements

Quality in coagulation and haemostasis testing

The essential elements of a quality program, specifically internal quality control (IQC) and external quality assurance (EQA), should be applied to each laboratory assay performed in order to ensure test result accuracy and precision. The coagulation laboratory plays an important role in the diagnosis and treatment of individuals with bleeding or clotting (i.e., thrombotic) disorders. Test methodologies used to assess common disorders or diseases of haemostasis are reviewed as well as the clinical relevance of each assay. The preanalytical phase of testing offers the greatest opportunity for introducing result error in the haemostasis laboratory and it is therefore imperative that samples are properly collected, transported and stored. Samples for haemostasis testing should be collected in 3.2% sodium citrate at a 9:1 blood to anticoagulant ratio and maintained at room temperature until processed. Some test processes such as platelet function testing have special processing and testing requirements. For plasma-based tests, centrifugation to obtain platelet poor plasma and testing should ideally be completed within 4 hours or the plasma frozen. IQC must be performed with each assay, at appropriate levels of the analyte and at appropriate time intervals as a means for assessing ongoing assay performance. EQA, a peer group assessment process that is supplementary to IQC, offers in addition the opportunity for evaluation of long-term performance of laboratories, including comparisons with like and unlike methodologies, and often serves as an educational resource. Participation in an EQA program is often a requirement of laboratory accreditation and there are a multitude of EQA organizations that offer programs specific to haemostasis testing with international programs providing assessment of the more specialized haemostasis assays. These programs provide invaluable information on assay specific diagnostic error rate, assay precision, accuracy, sensitivity and assessment of overall assay performance. The incorporation of IQC and EQA into a laboratory program can not only assist in the assurance that testing is reliable and accurate but also improve the quality of the testing

Anti-Endothelial Cell Antibodies are not frequently elevated in hospitalized patients with COVID-19

COVID-19 is now established to be associated with a thrombotic phenomenon, now called COVID-19 associated coagulopathy (CAC). Anti-Endothelial Cell Antibodies (AECA) are a heterogenous group of autoantibodies targeting various endothelial cell antigens or antigens adhering to endothelial cells, They are commonly observed in a variety of auto-immune and rheumatologic conditions, and were observed in patients with the severe acute respiratory syndrome (SARS) in 2005. We aimed to assess AECA status in patients with COVID-19 and their potential contributing role to endothelial injury and CAC. AECA identification was a relatively infrequent finding in COVID-19 patients on admission, and their presence, albeit in only 2/33 patients, was not associated with disease severity. However, as the autoantibodies were only measured at admission, we cannot exclude the possibility of pathogenic AECA developing later in the course of diseaseFurther studies using additional methods are needed to evaluate the presence and potential pathogenic role of AECA in later stages of COVID-19

The new oral anticoagulants and the future of haemostasis laboratory testing

The tests currently employed within most haemostasis laboratories to monitor anticoagulant therapy largely comprise the prothrombin time (PT)/International Normalised Ratio (INR) and the activated partial thromboplastin time (APTT). These are respectively used to monitor Vitamin K antagonists (VKAs) such as warfarin, and unfractionated heparin. Additional tests that laboratories may also employ for assessing or monitoring unfractionated heparin include thrombin time (TT) and the anti-Xa assay, which can also be used to monitor low molecular weight heparin. Several new anti-thrombotic agents have recently emerged, or are in the final process of clinical evaluation. These novel drugs that include Dabigatran etexilate and Rivaroxaban would not theoretically require monitoring; however, testing is useful in specific situations. The tests currently used to monitor VKAs and heparin are typically either too sensitive or too insensitive to the new drugs to be used as ‘typically performed in laboratories’, and may thus require some methodological adjustments to increase or decrease their sensitivity. Alternately, different tests may be better employed in these assessments. Whatever the case, laboratories may soon be performing a reduced or possibly increased number of tests, the same kind of tests but perhaps differently, or conceivably different assay panels. Specific laboratory guidance on the choice of the appropriate test to be ordered according to the drug being administered, as well as on appropriate interpretation of test results, will also be necessary. The current report reviews the current state of play and provides a glimpse to the possible future of the coagulation laboratory

The missing link between genotype, phenotype and clinics

Broj genetskih testova bilježi eksponencijalan rast u kliničkim laboratorijima, zahvaljujući izvanrednim znanstvenim i tehnološkim dostignućima, uz potporu relativno jeftinih, brzih, pouzdanih i visoko propulzivnih tehnika. Sasvim je neupitno da je genetsko testiranje pomoglo u identi%ciranju molekularne osnove monogenskih bolesti, kao i mnoštva gena upletenih u većinu poligen-skih patologija. To je pak omogućilo individualizaciju liječenja i farmakološke terapije. Međutim, to je isto tako stvorilo jedan paradoks u upravljanom liječenju bolesnika prema kojemu se genetsko testiranje sad često vidi kao panacea, „lijek za sve", pretpostavljajući kako je svaki pojedini genetski po-limor%zam udružen sa speci%čnim, pojedinim fenotipom i/ili kliničkom slikom. Nažalost, više procesa koji reguliraju ekspresiju proteina ostaje i dalje nepoznato, dok njihova biološka osnova još nije konačno prepoznata, pa veza između genotipa, fenotipa i kliničkih nalaza nije uvijek očita te je često još teže ispitati u kojoj će mjeri veza između gena i okoline utjecati na liječenje bolesnika. Cilj ovoga članka je pružiti kritički osvrt na složen i višeslojan odnos koji povezuje gene, biokemiju i kliničke podatke, s naglaskom na prednosti i nedostatke genetskog testiranja kod monogenskih i poligenskih bolesti, te u predviđanju farmakološkog odgovora.Due to outstanding scientific and technological progresses, the number of genetic tests is growing exponentially in clinical laboratories, supported by relatively inexpensive, fast, reliable, high-throughput techniques. It is unquestionable that genetic testing has helped to identify the molecular bases of monogenic disorders as well as a variety of genes involved in most multifactorial pathologies. This in turn has allowed for personalized treatments and pharmacological therapies. However, it has also produced a paradox in the managed care of patients, in that genetic testing is now often perceived as a panacea, with assumptions that each single genetic polymorphism is associated with a specific, individual phenotype and/or clinical picture. Unfortunately, several processes regulating protein expression are still unknown, and their biological background has not been definitely recognized, so that the link between the genotype, the phenotype and the clinics is not always obvious, and it is often even more challenging to address how much the link between genes and environment will impact on the managed care of the patients. The present article aims to critically review the complex and multifaceted relationship linking genes, biochemistry and clinics, highlighting advantages and drawbacks of genetic testing in monogenic disorders, polygenic pathology and in the prediction of the pharmacological response

The missing link between genotype, phenotype and clinics

Broj genetskih testova bilježi eksponencijalan rast u kliničkim laboratorijima, zahvaljujući izvanrednim znanstvenim i tehnološkim dostignućima, uz potporu relativno jeftinih, brzih, pouzdanih i visoko propulzivnih tehnika. Sasvim je neupitno da je genetsko testiranje pomoglo u identi%ciranju molekularne osnove monogenskih bolesti, kao i mnoštva gena upletenih u većinu poligen-skih patologija. To je pak omogućilo individualizaciju liječenja i farmakološke terapije. Međutim, to je isto tako stvorilo jedan paradoks u upravljanom liječenju bolesnika prema kojemu se genetsko testiranje sad često vidi kao panacea, „lijek za sve", pretpostavljajući kako je svaki pojedini genetski po-limor%zam udružen sa speci%čnim, pojedinim fenotipom i/ili kliničkom slikom. Nažalost, više procesa koji reguliraju ekspresiju proteina ostaje i dalje nepoznato, dok njihova biološka osnova još nije konačno prepoznata, pa veza između genotipa, fenotipa i kliničkih nalaza nije uvijek očita te je često još teže ispitati u kojoj će mjeri veza između gena i okoline utjecati na liječenje bolesnika. Cilj ovoga članka je pružiti kritički osvrt na složen i višeslojan odnos koji povezuje gene, biokemiju i kliničke podatke, s naglaskom na prednosti i nedostatke genetskog testiranja kod monogenskih i poligenskih bolesti, te u predviđanju farmakološkog odgovora.Due to outstanding scientific and technological progresses, the number of genetic tests is growing exponentially in clinical laboratories, supported by relatively inexpensive, fast, reliable, high-throughput techniques. It is unquestionable that genetic testing has helped to identify the molecular bases of monogenic disorders as well as a variety of genes involved in most multifactorial pathologies. This in turn has allowed for personalized treatments and pharmacological therapies. However, it has also produced a paradox in the managed care of patients, in that genetic testing is now often perceived as a panacea, with assumptions that each single genetic polymorphism is associated with a specific, individual phenotype and/or clinical picture. Unfortunately, several processes regulating protein expression are still unknown, and their biological background has not been definitely recognized, so that the link between the genotype, the phenotype and the clinics is not always obvious, and it is often even more challenging to address how much the link between genes and environment will impact on the managed care of the patients. The present article aims to critically review the complex and multifaceted relationship linking genes, biochemistry and clinics, highlighting advantages and drawbacks of genetic testing in monogenic disorders, polygenic pathology and in the prediction of the pharmacological response

the missing link between genotype phenotype and clinics

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Treg and Oligoclonal Expansion of Terminal Effector CD8+ T Cell as Key Players in Multiple Myeloma

The classical paradigm of host-tumor interaction, i.e. elimination, equilibrium, and escape (EEE), is reflected in the clinical behavior of myeloma which progresses from the premalignant condition, Monoclonal Gammopathy of Unknown Significance (MGUS). Despite the role of other immune cells, CD4+ regulatory T cells (Treg) and cytotoxic CD8+ T cells have emerged as the dominant effectors of host control of the myeloma clone. Progression from MGUS to myeloma is associated with alterations in Tregs and terminal effector CD8+ T cells (TTE). These changes involve CD39 and CD69 expression, affecting the adenosine pathway and residency in the bone marrow (BM) microenvironment, together with oligoclonal expansion within CD8+ TTE cells. In this mini-review article, in the context of earlier data, we summarize our recent understanding of Treg involvement in the adenosine pathway, the significance of oligoclonal expansion within CD8+ TTE cells and BM-residency of CD8+ TTE cells in MGUS and newly diagnosed multiple myeloma patients

Impact of experimental hypercalcemia on routine haemostasis testing

The blood to anticoagulant ratio is standardized according to the physiological calcium concentration in blood samples conventionally used for hemostasis testing. Specifically, one fixed volume of 0.109 mmol/L sodium citrate is added to 9 volumes of blood. Since little is known about the impact of hypercalcemia on the calcium-binding capacity of citrate, this study was planned to investigate the effect of experimental hypercalcemia on routine hemostasis testing