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Academic research has yet to provide a comprehensive view on how to capture individuals’ attention when a promotional e-mail reaches their inbox. This study investigates the variables that influence consumers’ attention toward promotional e-mails, operationalized as open rates, and proposes an integrative model that combines and integrates visible, temporal, and contextual elements. The empirical analysis uses ordinary least squares linear regression to validate the model with data obtained from a multinational sample. The dataset, which is global in nature, comprises 5765 different promotional e-mails sent between 2013 and 2018 by different multinational companies to 455 million users located in 73 countries. The analysis provides information about the relative importance of the variables that influence individuals’ decisions to open a promotional e-mail and shows that the frequency of mailing and the use of segmentation techniques significantly affect the individual’s attention to e-mail marketing communications. The results also show a non-transparent opportunity cost associated with every e-mail sent and give advice on how to control that virtual cost. The research provides further recommendations to marketing professionals to improve the effectiveness of e-mail marketing campaigns.

Resumen Los pacientes con cancer presentan un riesgo elevado de trombosis, que condiciona una elevada morbimortalidad. Se han desarrollado diversas escalas predictivas para la identificacion de aquellos con alto riesgo trombotico, incorporando datos clinicos y biologicos, pero, en general, no permiten una seleccion optima de los sujetos candidatos para recibir tromboprofilaxis. Estudios recientes demuestran que el perfil mutacional tiene un alto impacto sobre el riesgo trombotico, lo que va a facilitar el desarrollo de nuevos modelos predictivos de trombosis en pacientes con cancer.

Patients with cancer present with an elevated risk of thrombosis, which entails high morbidity and mortality. Various predictive scales that incorporate clinical and biological data have been developed to identify those at high risk of thrombosis, but, in general, they do not allow for the optimal selection of subjects who are candidates for thromboprophylaxis. Recent studies have demonstrated that the mutation profile has a high impact on the risk of thrombosis; this will facilitate developing new predictive models of thrombosis in patients with cancer.

Resumen El sistema hemostático actúa en concierto con la inflamación, de forma que tras la respuesta inflamatoria diversos mediadores activan el sistema hemostático a través de disfunción endotelial, activación plaquetar y de coagulación, promoviendo la trombosis, lo que se ha denominado tromboinflamación. En este proceso adquiere especial relevancia el inflamasoma, cuya estimulación promueve respuestas inmunes innata y adaptativa. La activación del inflamasoma juega un papel fisiopatológico importante en diversas patologías que cursan con fenómenos inflamatorios y trombóticos. El papel de la tromboinflamación se ha puesto de relevancia en la pandemia por COVID-19, en la que se ha descrito una tormenta de citocinas como uno de los mecanismos responsables.

The haemostatic system acts in concert with inflammation, so that after inflammatory response various mediators activate the haemostatic system through endothelial dysfunction, platelet activation and coagulation promoting thrombosis, which is termed thromboinflammation. In this process, the inflammasome acquires special relevance; its stimulation promotes innate and adaptive immune responses. Inflammasome activation plays an important physiopathological role in several disorders with inflammatory and thrombotic phenomena. The role of thromboinflammation has become relevant in the COVID-19 pandemic, in which a cytokine storm has been described as one of the responsible mechanisms.

Haemophilia A and B are congenital bleeding disorders characterized by missing or defective factor VIII or factor IX, respectively. Factor replacement therapy has been the gold standard for prophylaxis and treatment of bleeding complications. However, the inconvenience of regular intravenous administration, along with progression of arthropathy and development of inhibitors has driven the need for alternative treatment options, such as extended half-life products, non-factor coagulation products, such as subcutaneous emicizumab, blocking natural anticoagulants (rebalancing haemostatic agents) and gene therapy, which have been useful to control bleeding or are currently under late-phase clinical investigation.

Resumen La hemofilia A y B son trastornos hemorragicos congenitos causados por deficiencia de los factores VIII y IX de la coagulacion, respectivamente. La terapia sustitutiva del factor deficitario ha sido clasicamente la base de la profilaxis y del tratamiento de las complicaciones hemorragicas, pero presenta varias limitaciones, como la administracion frecuente por via intravenosa, el desarrollo progresivo de artropatia y la presencia de inhibidores. Ello ha motivado la busqueda de alternativas terapeuticas para un control mas efectivo de la hemorragia y mayor facilidad de administracion, tales como los factores de vida media extendida, farmacos procoagulantes como emicizumab de administracion subcutanea, bloqueo de las vias anticoagulantes naturales (hemostasia rebalanceada) y la terapia genica, con las que se ha conseguido un control efectivo de la hemorragia o se encuentran en fase avanzada de investigacion clinica.

Thrombosis is often present in the microcirculation in a variety of significant human diseases, such as disseminated intravascular coagulation, thrombotic microangiopathy, sickle cell disease, and others. Microvascular thrombosis has also recently been demonstrated in patients with COVID-19 and has been proposed to mediate the pathogenesis of organ injury in the lung and other organs. In many of these conditions, microvascular thrombosis is accompanied by inflammation, an association referred to as thromboinflammation or immunothrombosis. A greater understanding of the links between inflammation and thrombosis in the microcirculation will provide new therapeutic options for human diseases accompanied by microvascular thrombosis.

Cherax quadricarinatus is a decapod crustacean of interest to the aquaculture industry. In Mexico, a significant effort has been made to improve biological requirements, but the genetic characteristics are unknown. We examined the genetic diversity and differentiation in four populations in Mexico (three commercial farms and one feral population), as well as one research line from Argentina, used as reference. To initiate a founder stock in a genetic improvement program, we analyzed five microsatellite markers. The genetic diversity in terms of the number of alleles was low to moderate (2.8-6.2) in Mexican populations than the Argentinean sample (8.8). A pairwise Wright's Fst analysis showed that all populations were significantly different (P < 0.5). Cross-breeding organisms from a different population are suggested to increase genetic variability before initiating a founder stock with higher genetic variation.

[EN] Despite the importance and pervasiveness of e-mail marketing, improving the effectiveness of e-mail marketing programs continues to be a priority for most businesses due to their revenue-generating potential. However, the study of e-mail marketing has been mostly neglected by academic research. More notably, the lack of holistic approaches and conceptual frameworks to tackle this challenge stand in the way of helping companies to better plan and deploy their e-mail marketing strategies and campaigns. This study addresses this issue by proposing a comprehensive model for the study of e-mail marketing effectiveness based on the hierarchy-of-effects theory. The effectiveness model is built by linking the stages of the AIDA (Attention, Interest, Desire, Action) model to the sequence of steps that consumers undergo when they interact with promotional e-mails. This approach allows identifying different partial effectiveness metrics associated with the cognitive, emotional and conative stages, which are later operationalized through key performance indicators with widespread adoption in the industry (open rate, clickthrough rate, retention rate and conversion rate). Thus, attention is linked to open effectiveness, interest is linked both to click effectiveness and subscriber retention effectiveness, and action is linked to conversion effectiveness. The stage of desire is dropped from the model because it usually takes place outside the e-mail marketing process. The study includes a practical illustration of the adequateness of the framework based on data and results from prior studies. [ES] Pese a la importancia y difusión del e-mail marketing, la mejora de su efectividad continúa siendo una prioridad para la mayoría de anunciantes dado su potencial para la generación de ingresos. Sin embargo, el estudio del e-mail marketing ha sido en gran parte ignorado por la comunidad científica. En concreto, la ausencia de enfoques holísticos y marcos conceptuales de estudio impiden a las compañías mejorar la planificación y ejecución de estrategias de e-mail marketing. Este estudio responde a este problema mediante la propuesta de un modelo general de efectividad de e-mail marketing basado en la teoría de jerarquía de efectos. Así, cada una de las fases del modelo AIDA (Atención, Interés, Deseo, Acción) se vincula a las diversas etapas del proceso secuencial experimentado por los consumidores en su interacción con los correos electrónicos promocionales. Esto permite identificar diferentes métricas parciales de efectividad asociadas a las etapas cognitiva, afectiva y conativa, que a su vez pueden ser operacionalizadas a través de tasas habitualmente utilizadas por la industria (apertura, clic, retención y conversión). En concreto, la etapa de atención queda vinculada a la efectividad de apertura, la etapa de interés a la efectividad de clic y de retención de suscriptores, y la etapa de acción a la efectividad de conversión. El modelo no asocia ninguna métrica a la etapa de deseo dado que ésta ocurre habitualmente fuera del proceso del e-mail marketing. El estudio incluye un ejemplo de la adecuación del modelo conceptual a partir de datos y resultados de estudios previos.

Resumen La terapia anticoagulante conlleva un riesgo aumentado de complicaciones hemorragicas. Las escalas predictivas son un componente importante en la estratificacion del riesgo de sangrado en pacientes anticoagulados con fibrilacion auricular y tromboembolismo venoso. La combinacion de diversos marcadores clinicos, biologicos y geneticos permite construir escalas que ayudan al clinico en la toma de decision sobre intensidad y duracion del tratamiento. El correcto tratamiento de la hemorragia implica la aplicacion de estas escalas en combinacion con estrategias de reversion del efecto anticoagulante.

Major bleeding is a common complication of anticoagulant treatment. Risk assessment tools are relevant in the management of patients with atrial fibrillation and venous thromboembolism. The combination of clinical, biological and genetic markers is incorporated to build predictive scores to help in the decision process about intensity and duration of treatment. The optimal management of bleeding involves the application of predictive scores in combination with anticoagulant reversal strategies.

One of the most significant negative prognostic factors in patients suffering from the disease caused by SARS-CoV-2 (COVID-19) is the development of coagulopathy, associated with abnormal laboratory findings, such as increased D-dimer, and venous thromboembolic complications, requiring thromboprophylactic strategies. The main clinical characteristics of COVID-19 patients are revised here as compared to other coronavirus infections, such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), emphasizing clinical, diagnostic and therapeutic aspects.

Matrix metalloproteinases (MMPs) are proteolytic zinc-endopeptidases regulated by tissue Inhibitors of matrix metalloproteinases (TIMPs). We evaluated the potential of MMPs and TIMPs as clinical tools for Intracranial Haemorrhage (ICH). Spontaneous non‐traumatic ICH patients were recruited from two hospitals: Complejo Hospitalario de Navarra (CHN = 29) and Vall d´Hebron (VdH = 76). Plasmatic levels of MMP-1, −2, −7, −9, −10 and TIMP-1 and their relationship with clinical, radiological and functional variables were evaluated. We further studied the effect of TIMP-1 (0.05–0.2 mg/Kg) in an experimental tail-bleeding model. In CHN, TIMP-1 was associated with admission-hematoma volume and MMP-7 was elevated in patients with deep when compared to lobar hematoma. In VdH, admission-hematoma volume was associated with TIMP-1 and MMP-7. When data from both hospitals were combined, we observed that an increase in 1 ng/ml in TIMP-1 was associated with an increase of 0.14 ml in haemorrhage (combined β = 0.14, 95% CI = 0.08–0.21). Likewise, mice receiving TIMP-1 (0.2 mg/Kg) showed a shorter bleeding time (p

Thromboinflammation or immunothrombosis is a concept that explains the existing link between coagulation and inflammatory response present in many situations, such as sepsis, venous thromboembolism, or COVID-19 associated coagulopathy. The purpose of this review is to provide an overview of the current data regarding the mechanisms involved in immunothrombosis in order to understand the new therapeutic strategies focused in reducing thrombotic risk by controlling the inflammation.

Resumen Se presenta un trabajo multidisciplinar realizado por especialistas de Cardiologia, Hemostasia y Trombosis, Medicina Interna y Neurologia en el que se exponen las evidencias cientificas actuales que demuestran el mejor perfil de seguridad de los anticoagulantes orales de accion directa (ACOD) frente a los antivitamina K (AVK) y se discuten indicaciones y el papel de los antidotos especificos y hemostaticos para la reversion del efecto anticoagulante. El analisis sugiere que el mejor perfil de seguridad de los ACOD los hace especialmente utiles en pacientes con alto riesgo hemorragico.

A multidisciplinary panel of cardiologists, neurologists, internal medicine and specialists in haemostasis and thrombosis has elaborated this document showing recent scientific evidences supporting a better profile of direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKA), as well as the indications of specific antidotes and haemostatic agents to reverse the anticoagulant effects of DOACs. The analysis reinforces the best profile of DOACs and its special benefit in patients with basal high haemorrhagic risk.

One of the main goals of the Spanish Society of Arteriosclerosis is to contribute to a wider and greater knowledge of vascular disease, its prevention and treatment. Cardiovascular diseases are the leading cause of death in our country and also lead to a high degree of disability and health expenditure. Arteriosclerosis is a multifactorial disease, this is why its prevention requires a global approach that takes into account the different risk factors with which it is associated. Thus, this document summarizes the current level of knowledge and integrates recommendations and procedures to be followed for patients with established cardiovascular disease or high vascular risk. Specifically, this document reviews the main symptoms and signs to be evaluated during the clinical visit, the laboratory and imaging procedures to be routinely requested or those in special situations. It also includes the estimation of vascular risk, the diagnostic criteria of the different entities that are cardiovascular risk factors, and presents general and specific recommendations for the treatment of the different cardiovascular risk factors and their final objectives. Finally, the document includes aspects that are not often mentioned in the literature, such as the organisation of a vascular risk consultation.

Monocytes play an important role in atherosclerotic progression having both pro and anti-inflammatory effects depending on different circulating monocyte subpopulations. The objective of this study is to characterize these subpopulations and their association with cardiovascular risk factors.Transversal study including 102 selected patients, mean age: 65 years-old (range 41-86), 69% males. A set of specific antibodies against classical monocytes (Mon1, CD14+CD16- CD300e+HLADR+), intermediate (Mon2, CD14+CD16+CD300e+HLADR+) and non-classical (Mon3, CD14-CD16+CD300e+HLADR+) was assayed. Three groups of patients were included: 17 asymptomatic with more than one cardiovascular risk factor (group 1), 56 subjects asymptomatic but with vascular pathology assessed by ultrasound or microalbuminuria (group 2) and 19 patients with a previous atherothrombotic event (group 3). The cardiovascular risk was determined by Framingham and REGICOR scores.An association between study groups and the percentage of Mon1 and Mon2 was observed (ANOVA, p.05), being independent of age and sex for Mon2. Likewise Mon1 and Mon2 subpopulations were associated with cardiovascular adverse events (β=0.86, p=.02 y β=0.1 p=.002, respectively), independently of age and sex in the case of Mon2. Moreover the percentage of Mon3 was associated with the presence of several cardiovascular risk factors (β=0.21, p=.04) in the univariate analysis. In addition, there was a correlation between the levels of Mon1 and Mon2 and leukocytes (r=0.7, p.001 and r=0.26, p=.01, respectively).The analysis of monocyte subpopulations may be clinically useful to stratify the inflammatory profile related to the different cardiovascular risk groups.

Resumen Introduccion La participacion monocitaria en la progresion aterosclerotica y sus efectos pro- o antiinflamatorios dependen de las subpoblaciones circulantes. El objetivo de este estudio es la caracterizacion de dichas subpoblaciones y su asociacion con los factores de riesgo cardiovascular. Metodos Estudio transversal que incluye 102 pacientes seleccionados; edad media: 65 anos (rango 41-86 anos), 69% varones. Se utilizo un panel de anticuerpos especificos frente a monocitos clasicos (Mon1, CD14+CD16− CD300e+HLADR+), intermedios (Mon2, CD14+CD16+CD300e+HLADR+) y no clasicos (Mon3, CD14−CD16+CD300e+HLADR+). Se establecieron tres grupos de estudio; grupo 1: sujetos asintomaticos con mas de un factor de riesgo cardiovascular (n = 17); grupo 2: sujetos asintomaticos, pero con patologia vascular por ecografia o microalbuminuria (n = 56); y grupo 3: pacientes con algun evento vascular aterotrombotico previo (n = 19). Asimismo, se calculo el riesgo cardiovascular mediante las escalas Framingham y REGICOR. Resultados Se observo una asociacion entre las subpoblaciones Mon1 y Mon2 y los grupos del estudio (ANOVA, p Conclusiones El analisis de subpoblaciones monocitarias es de gran interes clinico, ya que permite establecer un diferente perfil inflamatorio segun los grupos de riesgo cardiovascular establecidos.

BACKGROUND: Atherosclerosis is the main etiology of cardiovascular diseases (CVD), associated to systemic inflammation. Matrix metalloproteinases (MMPs) are related to atherosclerosis progression through the SDF1/CXCR4 axis promoting macrophages recruitment within the vascular wall. The goal was to assess new circulatory inflammatory markers in relation to atherosclerosis. METHODS: Measurement of SDF1, MMP12 and CRP in blood samples of 298 prospective patients with cardiovascular risk. To explore atherosclerosis progression, CXCR4/SDF1 axis and MMP12 expression were determined by RT-qPCR and by immunohistochemistry in the aorta of accelerated and delayed atherosclerosis mice models (Apoe-/- and Apoe-/-Mmp10-/-). RESULTS: SDF1, MMP12 and CRP were elevated in patients with clinical atherosclerosis, but after controlling by confounding factors, only SDF1 and CRP remained increased. Having high levels of both biomarkers showed 2.8-fold increased risk of presenting clinical atherosclerosis (p = 0.022). Patients with elevated SDF1, MMP12 and CRP showed increased risk of death in follow-up (HR = 3.2, 95%CI: 1.5–7.0, p = 0.004). Gene and protein expression of CXCR4 and MMP12 were increased in aortas from Apoe-/- mice. CONCLUSIONS: The combination of high circulating SDF1, MMP12 and CRP identified patients with particular inflammatory cardiovascular risk and increased mortality. SDF1/CXCR4 axis and MMP12 involvement in atherosclerosis development suggests that they could be possible atherosclerotic targets.

International audience; In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research(1) aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1-2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally funded future for European hematology research. The 11 EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cell-based Immune Therapies; and Gene Therapy.

Thrombosis is often present in the microcirculation in a variety of significant human diseases, such as disseminated intravascular coagulation, thrombotic microangiopathy, sickle cell disease, and others. Microvascular thrombosis has also recently been demonstrated in patients with COVID-19 and has been proposed to mediate the pathogenesis of organ injury in the lung and other organs. In many of these conditions, microvascular thrombosis is accompanied by inflammation, an association referred to as thromboinflammation or immunothrombosis. A greater understanding of the links between inflammation and thrombosis in the microcirculation will provide new therapeutic options for human diseases accompanied by microvascular thrombosis.