scholarly journals Acquired autoimmune Haemophilia following SARS-CoV-2 vaccines: Dual drug effects on blood coagulation and the Scylla and Charybdis phenomenon

2021 ◽  
Author(s):  
Job Harenberg ◽  
Marina Marchetti ◽  
Anna Falanga
Keyword(s):  
Blood Coagulation ◽  
Drug Effects ◽  
Careful Analysis ◽  
Point Of View ◽  
Adequate Treatment ◽  
Arterial Thromboembolism ◽  
Coagulation Inhibitors ◽  
Immunologic Reactions ◽  
Statistical Risk ◽  
Dual Drug

Vaccination against the SARS-CoV-2 may lead to immunologic reactions activating the haemostatic system and resulting in both venous and arterial thromboembolism. Aquired autoimmune Haemophilia following SARS-CoV-2 vaccines were now reported 15 to 19 days (or later) after vaccination and resolution of symptoms by adequate treatment of the immunologic reaction. From patients’ point of view, anticoagulants and SARS-CoV-2 vaccines share their capacity to induce thrombosis as well as bleeding and clinicians are subjected to Scylla and Charybdis when they treat patients not only with anticoagulants but also with SARS-CoV-2 vaccines. Careful analysis of coincidence and causality requires attention when reporting on acquired coagulation inhibitors regarding severity, treatments, duration and statistical risk.

Reflective backward analysis to assess the operational performance and eco-efficiency of two industrial districts

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Andrea Appolloni ◽  
Idiano D'Adamo ◽  
Massimo Gastaldi ◽  
Morteza Yazdani ◽  
Davide Settembre-Blundo
Keyword(s):  
Economic Trend ◽  
Careful Analysis ◽  
Point Of View ◽  
Industrial Districts ◽  
Management Approach ◽  
Ceramic Tiles ◽  
Data Set ◽  
Content Type ◽  
Sectorial Analysis ◽  
Backward Analysis

PurposeThe best strategy to apply for the future cannot disregard a careful analysis of the past and is the one capable of seizing opportunities from outside. Manufacturing sectors are characterized by sudden changes, and in this work, we analyze the ceramic tiles sector characterized by a mature technology in which innovation has played a key role.Design/methodology/approachThis study aims to provide a sectorial analysis based on a historical data set (2004–2019) to highlight how an industry is performing both operationally and in terms of eco-efficiency. For this purpose, from a methodological point of view, the data envelopment analysis (DEA) was used.FindingsThe results of the analysis show that the Spanish ceramics industry shows a growing economic trend by taking advantage of lower industrial costs, while the Italian industry is characterized by a modest decline partially mitigated by exports. The industrial districts are an aggregation of companies that in the ceramic sector has allowed to combine innovation, sustainability and digitalization and is a model toward the maximization of sustainable efficiency because it is a place of aggregation of resources and ideas.Originality/valueThis study experiments with an innovative way of addressing traditional industry analysis, namely, integrating the reflective management approach with DEA-based backward analysis. This provides decision makers with the basis for new interpretations of variable trends.

scholarly journals Targeting exosites on blood coagulation proteases

2005 ◽  
Vol 77 (2) ◽  
pp. 275-280 ◽  
Author(s):  
Robson Q. Monteiro
Keyword(s):  
Blood Coagulation ◽  
High Specificity ◽  
Heparin Binding ◽  
Zymogen Activation ◽  
Prothrombinase Complex ◽  
Blood Sucking ◽  
Anticoagulant Drugs ◽  
Coagulation Inhibitors ◽  
Tissue Factor Pathway ◽  
Surface Domains

The high specificity of blood coagulation proteases has been attributed not only to residues surrounding the active site but also to other surface domains that are involved in recognizing and interacting with macromolecular substrates and inhibitors. Specific blood coagulation inhibitors obtained from exogenous sources such as blood sucking salivary glands and snake venoms have been identified. Some of these inhibitors interact with exosites on coagulation enzymes. Two examples are discussed in this short revision. Bothrojaracin is a snake venom-derived protein that binds to thrombin exosites 1 and 2. Complex formation impairs several exosite-dependent activities of thrombin including fibrinogen cleavage and platelet activation. Bothrojaracin also interacts with proexosite 1 on prothrombin thus decreasing the zymogen activation by the prothrombinase complex (FXa/FVa). Ixolaris is a two Kunitz tick salivary gland inhibitor, that is homologous to tissue factor pathway inhibitor. Recently it was demonstrated that ixolaris binds to heparin-binding exosite of FXa, thus impairing the recognition of prothrombin by the enzyme. In addition, ixolaris interacts with FX possibly through the heparin-binding proexosite. Differently from FX, the ixolaris-FX complex is not recognized as substrate by the intrinsic tenase complex (FIXa/FVIIIa). We conclude that these inhibitors may serve as tools for the study of coagulation exosites as well as prototypes for new anticoagulant drugs.

scholarly journals Current and Future Role of Tyrosine Kinases Inhibition in Thyroid Cancer: From Biology to Therapy

2020 ◽  
Vol 21 (14) ◽  
pp. 4951
Author(s):  
María San Román Gil ◽  
Javier Pozas ◽  
Javier Molina-Cerrillo ◽  
Joaquín Gómez ◽  
Héctor Pian ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Tyrosine Kinases ◽  
Genetic Alterations ◽  
Point Of View ◽  
Adequate Treatment ◽  
Comprehensive Review ◽  
Tumor Characterization ◽  
Therapeutic Algorithm ◽  
Clinical Point

Thyroid cancer represents a heterogenous disease whose incidence has increased in the last decades. Although three main different subtypes have been described, molecular characterization is progressively being included in the diagnostic and therapeutic algorithm of these patients. In fact, thyroid cancer is a landmark in the oncological approach to solid tumors as it harbors key genetic alterations driving tumor progression that have been demonstrated to be potential actionable targets. Within this promising and rapid changing scenario, current efforts are directed to improve tumor characterization for an accurate guidance in the therapeutic management. In this sense, it is strongly recommended to perform tissue genotyping to patients that are going to be considered for systemic therapy in order to select the adequate treatment, according to recent clinical trials data. Overall, the aim of this article is to provide a comprehensive review on the molecular biology of thyroid cancer focusing on the key role of tyrosine kinases. Additionally, from a clinical point of view, we provide a thorough perspective, current and future, in the treatment landscape of this tumor.

scholarly journals BÜCHI COMPLEMENTATION MADE TIGHTER

2006 ◽  
Vol 17 (04) ◽  
pp. 851-867 ◽  
Author(s):  
EHUD FRIEDGUT ◽  
ORNA KUPFERMAN ◽  
MOSHE Y. VARDI
Keyword(s):  
Lower Bound ◽  
Upper Bound ◽  
Blow Up ◽  
Careful Analysis ◽  
Point Of View ◽  
Upper And Lower Bounds ◽  
Theoretical Point ◽  
Infinite Words ◽  
Büchi Automata ◽  
Buchi Automata

The complementation problem for nondeterministic word automata has numerous applications in formal verification. In particular, the language-containment problem, to which many verification problems is reduced, involves complementation. For automata on finite words, which correspond to safety properties, complementation involves determinization. The 2n blow-up that is caused by the subset construction is justified by a tight lower bound. For Büchi automata on infinite words, which are required for the modeling of liveness properties, optimal complementation constructions are quite complicated, as the subset construction is not sufficient. From a theoretical point of view, the problem is considered solved since 1988, when Safra came up with a determinization construction for Büchi automata, leading to a 2O(n log n) complementation construction, and Michel came up with a matching lower bound. A careful analysis, however, of the exact blow-up in Safra's and Michel's bounds reveals an exponential gap in the constants hiding in the O( ) notations: while the upper bound on the number of states in Safra's complementary automaton is n2n, Michel's lower bound involves only an n! blow up, which is roughly (n/e)n. The exponential gap exists also in more recent complementation constructions. In particular, the upper bound on the number of states in the complementation construction of Kupferman and Vardi, which avoids determinization, is (6n)n. This is in contrast with the case of automata on finite words, where the upper and lower bounds coincides. In this work we describe an improved complementation construction for nondeterministic Büchi automata and analyze its complexity. We show that the new construction results in an automaton with at most (0.96n)n states. While this leaves the problem about the exact blow up open, the gap is now exponentially smaller. From a practical point of view, our solution enjoys the simplicity of the construction of Kupferman and Vardi, and results in much smaller automata.

Blood-coagulation Inhibitors after Snakebite

BMJ ◽  
1964 ◽  
Vol 1 (5398) ◽  
pp. 1639-1639
Author(s):  
J. Ghitis ◽  
G. Beltran
Keyword(s):  
Blood Coagulation ◽  
Coagulation Inhibitors

A STATISTICAL RISK ASSESSMENT OF BITCOIN AND ITS EXTREME TAIL BEHAVIOR

2017 ◽  
Vol 12 (01) ◽  
pp. 1750003 ◽  
Author(s):  
JOERG OSTERRIEDER ◽  
JULIAN LORENZ
Keyword(s):  
Extreme Value ◽  
Point Of View ◽  
Extreme Value Analysis ◽  
Return Distribution ◽  
Value Analysis ◽  
Risk Characteristics ◽  
The Us ◽  
Asset Class ◽  
Us Dollar ◽  
Statistical Risk

We provide an extreme value analysis of the returns of Bitcoin. A particular focus is on the tail risk characteristics and we will provide an in-depth univariate extreme value analysis. Those properties will be compared to the traditional exchange rates of the G10 currencies versus the US dollar. For investors, especially institutional ones, an understanding of the risk characteristics is of utmost importance. So for Bitcoin to become a mainstream investable asset class, studying these properties is necessary. Our findings show that the bitcoin return distribution not only exhibits higher volatility than traditional G10 currencies, but also stronger non-normal characteristics and heavier tails. This has implications for risk management, financial engineering (such as bitcoin derivatives) — both from an investor's as well as from a regulator's point of view. To our knowledge, this is the first detailed study looking at the extreme value behavior of the cryptocurrency Bitcoin.

scholarly journals NAM-supported read-across: From case studies to regulatory guidance in safety assessment

ALTEX ◽  
2021 ◽  
pp. 140-150
Author(s):  
Costanza Rovida
Keyword(s):  
Careful Analysis ◽  
Point Of View ◽  
Regulatory Agencies ◽  
Final Conclusion ◽  
Regulatory Guidance ◽  
Consumer Safety ◽  
European Regulatory ◽  
The Usa ◽  
Expert Analysis ◽  
Optimal Approach

The use of new approach methodologies (NAMs) in support of read-across (RAx) approaches for regulatory purposes is a main goal of the EU-ToxRisk project. To bring this forward, EU-ToxRisk partners convened a workshop in close collaboration with regulatory representatives from key organizations including European regulatory agencies, such as the European Chemicals Agency (ECHA) and the European Food Safety Authority (EFSA), as well as the Scientific Committee on Consumer Safety (SCCS), national agencies from several European countries, Japan, Canada and the USA, as well as the Organisation for Economic Cooperation and Development (OECD). More than a hundred people actively participated in the discussions, bringing together diverse viewpoints across academia, regulators and industry. The discussion was organized starting from five practical cases of RAx applied to specific problems that offered the oppor­tunity to consider real examples. There was general consensus that NAMs can improve confidence in RAx, in particular in defining category boundaries as well as characterizing the similarities/dissimilarities between source and target substances. In addition to describing dynamics, NAMs can be helpful in terms of kinetics and metabolism that may play an important role in the demonstration of similarity or dissimilarity among the members of a category. NAMs were also noted as effective in providing quanti­tative data correlated with traditional no observed adverse effect levels (NOAELs) used in risk assessment, while reducing the uncertainty on the final conclusion. An interesting point of view was the advice on calibrating the number of new tests that should be carefully selected, avoiding the allure of “the more, the better”. Unfortunately, yet unsurprisingly, there was no single approach befitting every case, requiring careful analysis delineating the optimal approach. Expert analysis and assessment of each specific case is still an important step in the process.

scholarly journals New Insight to Overcome Tumor Resistance: An Overview from Cellular to Clinical Therapies

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1131
Author(s):  
Giulia Mitola ◽  
Paolo Falvo ◽  
Francesco Bertolini
Keyword(s):  
Residual Disease ◽  
Drug Effects ◽  
Point Of View ◽  
Tumor Resistance ◽  
Cancer Treatments ◽  
Secondary Tumors ◽  
Molecular Features ◽  
Preclinical And Clinical Studies

Disease relapse caused by drug resistance still represents a major clinical hurdle in cancer treatments. Tumor cells may take advantage of different intracellular and genetic systems attenuating the drug effects. Resistant cells or minimal residual disease (MRD) cells have strong clinical relevance, as they might give rise to secondary tumors when the therapy is concluded. Thus, MRDs are crucial therapeutic targets in order to prevent tumor relapse. Therefore, several groups aim at understanding how MRDs are orginated, characterizing their molecular features, and eradicating them. In this review, we will describe MRD from a genetic, evolutionary, and molecular point of view. Moreover, we will focus on the new in vitro, in vivo, preclinical, and clinical studies that aim at eradicating tumor resistance.

scholarly journals Bulgarian vocative within HPSG framework

2003 ◽  
Author(s):  
Petya N. Osenova ◽  
Kiril Iv. Simov
Keyword(s):  
Point Of View ◽  
Dialogue Systems ◽  
Adequate Treatment ◽  
Semantic Properties ◽  
Linguistic Phenomenon

Crosslinguistically vocatives are an underexplored linguistic phenomenon and in different languages they can be highly idiosyncratic and complex (Levinson, 1987, p.71). Therefore, the problem, which is discussed in this paper, is not a language-specific one, in spite of the fact that most of the languages have their own repositories for marking the role of the addressee in the communicative utterances. In our opinion this linguistic phenomenon needs its adequate treatment in HPSG because of three main reasons:  The vocative is supposed to be present on two levels: syntax and pragmatics. Therefore it needs more elaborate interpretation on the interface side, which, in HPSG, is more developed for morphology/syntax and syntax/semantics than syntax/pragmatics. Note that a challenge for the theory is the semantic weight of the vocatives with respect to the head sentence.  It will be useful for HPSG-oriented implementations, especially treebanks and dialogue systems.  On prosodic grounds the vocatives are often viewed as being 'side or extended parts' of the sentence and therefore - very close to the parenthetical constructions. From our point of view, both phenomena are pragmatic and hence, the treatment of vocative, presented here, could be generalized to cover other phenomena of pragmatic nature.  In our work the vocatives are viewed through the possibility of the integration/separation of their pragmatic, syntactic and semantic properties.

scholarly journals Reconstruction as a Long-Term Process. Memory, Experiences and Cultural Heritage in the Irpinia Post-Earthquake (November 23, 1980)

Geosciences ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 316
Author(s):  
Gabriele Ivo Moscaritolo
Keyword(s):  
Cultural Heritage ◽  
Social Process ◽  
Careful Analysis ◽  
Small Towns ◽  
Point Of View ◽  
Special Focus ◽  
Cultural Backgrounds ◽  
Political Factors ◽  
Process Memory ◽  
Material Issue

Reconstruction after an earthquake is often seen as a material issue, which concerns “objects” such as houses, roofs, and streets. This point of view is supported by the mass media showing the work progress in the disaster areas, especially in conjunction with anniversaries. Rather, we should consider reconstruction as a complex social process in which cultural backgrounds, expectations, and ideas of the future come into play, without neglecting geological, historical, legislative, economic, and political factors. Combining oral history sources and archival records, the article shows the paths taken by two small towns among the most affected by the earthquake of 23rd November 1980 (Mw 6.9). These towns have made opposite reconstruction choices (in situ and ex novo) representing two classical and different ways in which human societies can face their past and think their own future. A careful analysis of these forty-year experiences, with a special focus on cultural heritage, provides useful indications for post-disaster reconstructions in which more attention to the process, and not just to the final product, should be paid.

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