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Coronary artery bypass graft (CABG) surgery still represents the gold standard for patients with complex multivessel coronary artery disease. However, graft occlusion still occurs in a significant proportion of CABG conduits, and oxidative stress is currently considered to be a potential contributor. Human serum albumin (HSA) represents the main antioxidant in plasma through its reduced amino acid Cys34, which can efficiently scavenge several oxidants. In a nested case-control study including 36 patients with occluded grafts and 38 age- and sex-matched patients without occlusion, we assessed the levels of the native mercaptoalbumin (HSA-SH) and oxidized thiolated form of albumin (Thio-HSA) in relation with graft occlusion within 5 years after CABG. We found that the plasma level of preoperative HSA-SH was significantly lower in patients with occluded graft at 5 years follow-up than in patients with graft patency. Furthermore, low HSA-SH remained independently associated with graft occlusion even after adjusting for preoperative D-dimer, a well-known marker of activated coagulation recently found to be associated with graft occlusion. In conclusion, the preoperative level of HSA-SH is independently associated with graft occlusion in CABG and represents a measurable and potentially druggable predictor.

Using only image-sentence pairs, weakly-supervised visual-textual grounding aims to learn region-phrase correspondences of the respective entity mentions. Compared to the supervised approach, learning is more difficult since bounding boxes and textual phrases correspondences are unavailable. In light of this, we propose the Semantic Prior Refinement Model (SPRM), whose predictions are obtained by combining the output of two main modules. The first untrained module aims to return a rough alignment between textual phrases and bounding boxes. The second trained module is composed of two sub-components that refine the rough alignment to improve the accuracy of the final phrase-bounding box alignments. The model is trained to maximize the multimodal similarity between an image and a sentence, while minimizing the multimodal similarity of the same sentence and a new unrelated image, carefully selected to help the most during training. Our approach shows state-of-the-art results on two popular datasets, Flickr30k Entities and ReferIt, shining especially on ReferIt with a 9.6% absolute improvement. Moreover, thanks to the untrained component, it reaches competitive performances just using a small fraction of training examples.

Disaggregation in optical networks is particularly relevant to be considered for the deployment of 5G services and towards the support of 6G. Particularly in the metro area network (MAN), this is especially crucial, as is the adoption of suitable photonic technologies enabling dense integration to design a sustainable network architecture. Furthermore, to dynamically allocate the ever-increasing traffic, supporting multiterabit capacity, an optimal usage of the available resources by properly exploiting the multiple dimensions (including the spectral and spatial ones), with programmable and adaptive data plane solutions, is key. In this work, we assess the capabilities of a disaggregated MAN that relies on new photonic devices, node architectures, and sliceable bandwidth/bit-rate-variable transceivers, approaching wavelength division multiplexing and space division multiplexing. A hierarchical network topology is attained and the feasibility of a cross-hierarchy optical continuum is demonstrated. In fact, we experimentally demonstrate the successful transmission of multiterabits/second capacity across multiple nodes corresponding to different hierarchy levels that have different implementation schemes and support different technologies. For the top tier hierarchy level nodes, we demonstrate the transmission of up to 8×11 = {88} spatial/spectral channels, for a total capacity of 1.676 Tb/s, employing a node architecture able to handle up to 2560 spatial/spectral channels at different aggregation levels and granularities.

Significant coronary artery disease (CAD) is a frequent finding in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI), and the management of these two conditions becomes of particular importance with the extension of the procedure to younger and lower-risk patients. Yet, the preprocedural diagnostic evaluation and the indications for treatment of significant CAD in TAVI candidates remain a matter of debate. In this clinical consensus statement, a group of experts from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the European Society of Cardiology (ESC) Working Group on Cardiovascular Surgery aims to review the available evidence on the topic and proposes a rationale for the diagnostic evaluation and indications for percutaneous revascularisation of CAD in patients with severe aortic stenosis undergoing transcatheter treatment. Moreover, it also focuses on commissural alignment of transcatheter heart valves and coronary re-access after TAVI and redo-TAVI., Significant coronary artery disease (CAD) is a frequent finding in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI), and the management of these two conditions becomes of particular importance with the extension of the procedure to younger and lower-risk patients. Yet, the preprocedural diagnostic evaluation and the indications for treatment of significant CAD in TAVI candidates remain a matter of debate. In this clinical consensus statement, a group of experts from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the European Society of Cardiology (ESC) Working Group on Cardiovascular Surgery aims to review the available evidence on the topic and proposes a rationale for the diagnostic evaluation and indications for percutaneous revascularisation of CAD in patients with severe aortic stenosis undergoing transcatheter treatment. Moreover, it also focuses on commissural alignment of transcatheter heart valves and coronary re-access after TAVI and redo-TAVI.

Internet-generated traffic growth is forcing the development of new low-cost solutions in metropolitan area networks (MANs), in particular in the transceiver and network node architectures. Semiconductor optical amplifier (SOA)-based wavelength blockers can be used as fundamental building blocks to add and drop optical channels in the node architecture of several network hierarchical levels. Even if its employment is advantageous in terms of costs and amplification bandwidth, the SOA can operate in a nonlinear regime. This work analyzes the impact of SOA-based node crossing on high-capacity discrete multitone (DMT) signals. In order to properly evaluate the interplay between optical channels and SOA self-gain modulation, both external and direct modulations are considered. Dual-sideband (DSB) and single-sideband (SSB) DMT variants are taken into account, showing no significant difference in the impact of SOA crossing for external modulation of a DFB laser. On the other hand, an important effect of subcarrier suppression arises on DSB DMT direct modulation of a vertical cavity surface emitting laser (VCSEL), less consistent for SSB DMT direct modulation. The analysis allowed to properly choose the bias current for the SOA employed in an experimental setup used to evaluate the transmission performance in a MAN scenario including add-drop lossless switch nodes. The experimental results demonstrate that a target capacity of more than 50 Gb/s per channel can be achieved in a 116-km MAN network composed of an SOA-based metro-access node and two metro-core aggregators, considering the transmission of three 25-GHzspaced DMT channels.

Background: To assess early and late mortality in patients with isolated acute tricuspid valve infective endocarditis (TVIE) using data from a multicenter registry. Methods: From 1983 to 2018, isolated acute TVIE was surgically treated in 157 (3.8%) patients [mean age 47 ± 16 years (range 15–86 years), 25% females]. Of these, 142 (90%) had native tricuspid regurgitation, 7 (5%) native tricuspid valve (TV) steno-regurgitation, and 8 (5%) prosthetic TVIE. Intravenous drug use (IVDU) was recorded in 38% of patients, infection involved cardiac implantable electronic device leads in 21%, and vascular catheters for dialysis in 1%; in the remaining cases, the cause was unknown. The primary endpoint was in-hospital outcome, long-term freedom from recurrence and overall survival. Results: Overall, 77 (49%) patients underwent TV repair, 72 (46%) TV replacement, and 8 (5%) prosthetic TV replacement. Early mortality was 11% (n = 17). Expected early mortality according to EndoSCORE was 12%, with age (odds ratio 1.06) and redo (odds ratio 6.64) as risk factors. Late deaths occurred in 31 patients and TVIE recurrences in 4. Survival rates at 10, 20, and 25 years were 66%, 60%, and 44%, respectively. Risk factors were age [hazard ratio (HR) 1.06], mycotic TVIE (HR 4.2), IVDU (HR 4.90), infected prosthesis replacement (HR 4.4), and presence of cardiac implantable electronic device leads (HR 3.0). No significant difference was found in valve repair vs. replacement and in IVDUs vs. non-IVDUs. Conclusions: Patients with isolated acute TVIE undergoing surgical treatment show acceptable early and late outcomes. TVIE recurrence was low, and repair of the affected valve does not seem to confer any advantage either at early or long term up to 25 years.

This thesis investigates the crisis responses of Italy and the European Union towards the Libyan Civil War, from its outbreak in 2011 to its recent developments. The aim is to explain the actors’ challenges to implement a cohesive foreign policy that leads to a resolution of the conflict. To research that, this thesis will investigate to what extent the conceptions of sovereignty of Italy and the EU prevent the Union to implement a cohesive foreign policy towards the Libyan Crisis. This will be done through an interdisciplinary research approach. The method will consist of integrating the historical analysis of the actors’ crisis responses with a theoretical framework from political philosophy, defining different conceptions of sovereignty. Findings indicate that the actors’ conceptions of sovereignty evolved throughout the different phases of the Libyan Crisis. The found divergence in sovereignty conceptions for two of the three crisis response contexts indicates the effective impact on the EU’s challenges to implement a cohesive foreign policy towards the Libyan Crisis.

This thesis investigates the crisis responses of Italy and the European Union towards the Libyan Civil War, from its outbreak in 2011 to its recent developments. The aim is to explain the actors’ challenges to implement a cohesive foreign policy that leads to a resolution of the conflict. To research that, this thesis will investigate to what extent the conceptions of sovereignty of Italy and the EU prevent the Union to implement a cohesive foreign policy towards the Libyan Crisis. This will be done through an interdisciplinary research approach. The method will consist of integrating the historical analysis of the actors’ crisis responses with a theoretical framework from political philosophy, defining different conceptions of sovereignty. Findings indicate that the actors’ conceptions of sovereignty evolved throughout the different phases of the Libyan Crisis. The found divergence in sovereignty conceptions for two of the three crisis response contexts indicates the effective impact on the EU’s challenges to implement a cohesive foreign policy towards the Libyan Crisis.

OBJECTIVES: Healthcare systems worldwide have been overburdened by the coronavirus disease 2019 (COVID-19) outbreak. Accordingly, hospitals had to implement strategies to profoundly reshape both non-COVID-19 medical care and surgical activities. Knowledge about the impact of the COVID-19 pandemic on cardiac surgery practice is pivotal. The goal of the present study was to describe the changes in cardiac surgery practices during the health emergency at the national level. METHODS: A 26-question web-enabled survey including all adult cardiac surgery units in Italy was conducted to assess how their clinical practice changed during the national lockdown. Data were compared to data from the corresponding period in 2019. RESULTS: All but 2 centres (94.9%) adopted specific protocols to screen patients and personnel. A significant reduction in the number of dedicated cardiac intensive care unit beds (-35.4%) and operating rooms (-29.2%), along with healthcare personnel reallocation to COVID departments (nurses-15.4%, anaesthesiologists-7.7%), was noted. Overall adult cardiac surgery volumes were dramatically reduced (1734 procedures vs 3447; P 0.001), with a significant drop in elective procedures [580 (33.4%) vs 2420 (70.2%)]. CONCLUSIONS: This national survey found major changes in cardiac surgery practice as a response to the COVID-19 pandemic. This experience should lead to the development of permanent systems-based plans to face possible future pandemics. These data may effectively help policy decision-making in prioritizing healthcare resource reallocation during the ongoing pandemic and once the healthcare emergency is over. © 2021 The Author(s). Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Perioperative management of antithrombotic therapy in patients treated with coronary stents undergoing surgery remains poorly defined. Importantly, surgery represents a common reason for premature treatment discontinuation, which is associated with an increased risk in mortality and major adverse cardiac events. However, maintaining antithrombotic therapy to minimize the incidence of perioperative ischemic complications may increase the risk of bleeding complications. Although guidelines provide some recommendations with respect to the perioperative management of antithrombotic therapy, these have been largely developed according to the thrombotic risk of the patient and a definition of the hemorrhagic risk specific to each surgical procedure, key to defining the trade-off between ischemia and bleeding, is not provided. These observations underscore the need for a multidisciplinary collaboration among cardiologists, anesthesiologists, hematologists and surgeons to reach this goal. The present document is an update on practical recommendations for standardizing management of antithrombotic therapy management in patients treated with coronary stents (Surgery After Stenting 2) in various types of surgery according to the predicted individual risk of thrombotic complications against the anticipated risk of surgical bleeding complications. Cardiologists defined the thrombotic risk using a “combined ischemic risk” approach, while surgeons classified surgeries according to their inherent hemorrhagic risk. Finally, a multidisciplinary agreement on the most appropriate antithrombotic treatment regimen in the perioperative phase was reached for each surgical procedure.

The authors regret that the first name and last name of the author Sandro Sponga was published incorrectly in the original version and this has now been corrected.

Objective In this observational prospective study, we assessed the role of clinical variables and circulating biomarkers in graft occlusion at 18 months to identify a signature for graft occlusion. Methods A total of 330 patients undergoing primary elective coronary artery bypass grafting were enrolled. Blood collection for biomarker assessment was performed before surgery and discharge. Patients were then scheduled to undergo coronary computed tomography angiography at 18 months follow-up, and 179 patients underwent coronary computed tomography angiography 18 ± 2 months postoperatively. Results There were 46 of 503 (9.1%) occluded grafts; of these, 29 (63%) were venous and 17 (37%) were arterial grafts; overall, 43 of 179 patients (24%) had at least 1 occluded graft. Logistic mixed effects model assessing independent factors associated with graft occlusion identified that lower D-dimer levels at baseline (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.36-4.89; P =.00) and total protein content at discharge (OR, 1.09; 95% CI, 1.01-1.19; P =.028) were related to overall graft occlusion at follow-up, along with an arterial graft other than the left internal thoracic artery (OR, 2.92; 95% CI, 1.24-6.9; P =.078); moreover, a venous graft emerged was possibly associated with graft occlusion (OR, 1.51; 95% CI, 0.95-2.39; P =.078). By separately analyzing saphenous vein and arterial grafts, D-dimer levels (OR, 2.67; 95% CI, 1.15-6.2; P =.022 and OR, 2.5; 95% CI, 1.01-7.0; P =.05 for venous and arterial graft, respectively) were still associated with arterial and venous graft occlusion at follow-up. Conclusions We identified D-dimer as a biomarker associated with arterial and venous grafts occlusion. This may help stratify patients at risk of graft failure and identify new molecular targets to prevent this complication.

Perioperative management of antithrombotic therapy in patients treated with coronary stents undergoing surgery remains poorly defined. Importantly, surgery represents a common reason for premature treatment discontinuation, which is associated with an increased risk in mortality and major adverse cardiac events. However, maintaining antithrombotic therapy to minimize the incidence of perioperative ischemic complications may increase the risk of bleeding complications. Although guidelines provide some recommendations with respect to the perioperative management of antithrombotic therapy, these have been largely developed according to the thrombotic risk of the patient and a definition of the hemorrhagic risk specific to each surgical procedure, key to defining the trade-off between ischemia and bleeding, is not provided. These observations underscore the need for a multidisciplinary collaboration among cardiologists, anesthesiologists, hematologists and surgeons to reach this goal. The present document is an update on practical recommendations for standardizing management of antithrombotic therapy management in patients treated with coronary stents (Surgery After Stenting 2) in various types of surgery according to the predicted individual risk of thrombotic complications against the anticipated risk of surgical bleeding complications. Cardiologists defined the thrombotic risk using a “combined ischemic risk” approach, while surgeons classified surgeries according to their inherent hemorrhagic risk. Finally, a multidisciplinary agreement on the most appropriate antithrombotic treatment regimen in the perioperative phase was reached for each surgical procedure.

OBJECTIVES: We described clinical-epidemiological features of prosthetic valve endocarditis (PVE) and assessed the determinants of early surgical outcomes in multicentre design. METHODS: Data regarding 2823 patients undergoing surgery for endocarditis at 19 Italian Centers between 1979 and 2015 were collected in a database. Of them, 582 had PVE: in this group, the determinants of early mortality and complications were assessed, also taking into account the different chronological eras encompassed by the study. RESULTS: Overall hospital (30-day) mortality was 19.2% (112 patients). Postoperative complications of any type occurred in 256 patients (44%). Across 3 eras (1980-2000, 2001-08 and 2009-14), early mortality did not significantly change (20.4%, 17.1%, 20.5%, respectively, P = 0.60), whereas complication rate increased (18.5%, 38.2%, 52.8%, P < 0.001), consistent with increasing mean patient age (56 ± 14, 64 ± 15, 65 ± 14 years, respectively, P < 0.001) and median logistic EuroSCORE (14%, 21%, 23%, P = 0.025). Older age, female sex, preoperative serum creatinine > -2 mg/dl, chronic pulmonary disease, low ejection fraction, non-streptococcal aetiology, active endocarditis, preoperative intubation, preoperative shock and triple valve surgery were significantly associated with mortality. In multivariable analysis, age (OR = 1.02; P = 0.03), renal insufficiency (OR = 2.1; P = 0.05), triple valve surgery (OR = 6.9; P = 0.004) and shock (OR = 4.5; P < 0.001) were independently associated with mortality, while streptococcal aetiology, healed endocarditis and ejection fraction with survival. Adjusting for study era, preoperative shock (OR = 3; P < 0.001), Enterococcus (OR = 2.3; P = 0.01) and female sex (OR = 1.5; P = 0.03) independently predicted complications, whereas ejection fraction was protective. CONCLUSIONS: PVE surgery remains a high-risk one. The strongest predictors of early outcome of PVE surgery are related to patient's haemodynamic status an

Aims Epidemiological studies strongly suggest a link between stress, depression, and cardiovascular diseases (CVDs); the mechanistic correlation, however, is poorly understood. A single-nucleotide polymorphism in the BDNF gene (BDNFVal66Met), associated with depression and anxiety, has been proposed as a genetic risk factor for CVD. Using a knock-in mouse carrying the BDNFVal66Met human polymorphism, which phenocopies psychiatric-related symptoms found in humans, we investigated the impact of this SNP on thrombosis. Methods and results BDNFMet/Met mice displayed a depressive-like phenotype concomitantly with hypercoagulable state and platelet hyperreactivity. Proteomic analysis of aorta secretome from BDNFMet/Met and wild-type (WT) mice showed differential expression of proteins involved in the coagulation and inflammatory cascades. The BDNF Met allele predisposed to carotid artery thrombosis FeCl3-induced and to death after collagen/epinephrine injection. Interestingly, transfection with BDNFMet construct induced a prothrombotic/proinflammatory phenotype in WT cells. SIRT1 activation, using resveratrol and/or CAY10591, prevented thrombus formation and restored the physiological levels of coagulation and of platelet markers in BDNFMet/Met mice and/or cells transfected with the Met allele. Conversely, inhibition of SIRT1 by sirtinol and/or by specific siRNA induced the prothrombotic/proinflammatory phenotype inWT mice and cells. Finally, we found that BDNF Met homozygosity is associated with increased risk of acute myocardial infarction (AMI) in humans. Conclusion Activation of platelets, alteration in coagulation pathways, and changes in vessel wall protein expression in BDNFMet/Met mice recapitulate well the features occurring in the anxiety/depression condition. Furthermore, our data suggest that the BDNFVal66Met polymorphism contribute to the individual propensity for arterial thrombosis related to AMI.

Background The aim of this large retrospective study was to provide a logistic risk model along an additive score to predict early mortality after surgical treatment of patients with heart valve or prosthesis infective endocarditis (IE). Methods From 2000 to 2015, 2715 patients with native valve endocarditis (NVE) or prosthesis valve endocarditis (PVE) were operated on in 26 Italian Cardiac Surgery Centers. The relationship between early mortality and covariates was evaluated with logistic mixed effect models. Fixed effects are parameters associated with the entire population or with certain repeatable levels of experimental factors, while random effects are associated with individual experimental units (centers). Results Early mortality was 11.0% (298/2715); At mixed effect logistic regression the following variables were found associated with early mortality: age class, female gender, LVEF, preoperative shock, COPD, creatinine value above 2 mg/dl, presence of abscess, number of treated valve/prosthesis (with respect to one treated valve/prosthesis) and the isolation of Staphylococcus aureus, Fungus spp., Pseudomonas Aeruginosa and other micro-organisms, while Streptococcus spp., Enterococcus spp. and other Staphylococci did not affect early mortality, as well as no micro-organisms isolation. LVEF was found linearly associated with outcomes while non-linear association between mortality and age was tested and the best model was found with a categorization into four classes (AUC = 0.851). Conclusions The following study provides a logistic risk model to predict early mortality in patients with heart valve or prosthesis infective endocarditis undergoing surgical treatment, called “The EndoSCORE”.

Background: To assess early and late mortality in patients with isolated acute tricuspid valve infective endocarditis (TVIE) using data from a multicenter registry. Methods: From 1983 to 2018, isolated acute TVIE was surgically treated in 157 (3.8%) patients [mean age 47 ± 16 years (range 15–86 years), 25% females]. Of these, 142 (90%) had native tricuspid regurgitation, 7 (5%) native tricuspid valve (TV) steno-regurgitation, and 8 (5%) prosthetic TVIE. Intravenous drug use (IVDU) was recorded in 38% of patients, infection involved cardiac implantable electronic device leads in 21%, and vascular catheters for dialysis in 1%; in the remaining cases, the cause was unknown. The primary endpoint was in-hospital outcome, long-term freedom from recurrence and overall survival. Results: Overall, 77 (49%) patients underwent TV repair, 72 (46%) TV replacement, and 8 (5%) prosthetic TV replacement. Early mortality was 11% (n = 17). Expected early mortality according to EndoSCORE was 12%, with age (odds ratio 1.06) and redo (odds ratio 6.64) as risk factors. Late deaths occurred in 31 patients and TVIE recurrences in 4. Survival rates at 10, 20, and 25 years were 66%, 60%, and 44%, respectively. Risk factors were age [hazard ratio (HR) 1.06], mycotic TVIE (HR 4.2), IVDU (HR 4.90), infected prosthesis replacement (HR 4.4), and presence of cardiac implantable electronic device leads (HR 3.0). No significant difference was found in valve repair vs. replacement and in IVDUs vs. non-IVDUs. Conclusions: Patients with isolated acute TVIE undergoing surgical treatment show acceptable early and late outcomes. TVIE recurrence was low, and repair of the affected valve does not seem to confer any advantage either at early or long term up to 25 years.

Starting from a critical analysis of The Council of Europe Convention on Preventing and Combating Violence against Women and Domestic Violence (Istanbul Convention), the article deals with the issue of violence against women in two respects. In particular, on the one hand, it underlines the structural and (trans)cultural character of violence against women as a worldwide social and political problem. On the other, it focuses on the specific issue of violence against women in the multicultural contexts of European immigration countries, calling for a deeper investigation on the best instruments (beyond criminal law only) to grant the protection of the rights of women belonging to cultural minorities., A partir de un análisis crítico del Convenio del Consejo de Europa sobre Prevención y Lucha contra la Violencia contra las Mujeres y Violencia Doméstica (Convenio de Estambul), el articulo aborda la cuestión de la violencia contra las mujeres en dos aspectos. Por una parte, subraya el carácter estructural y (trans)cultural de la violencia contra las mujeres como problema social y político difundido en todo el mundo. Por otro lado, se enfoca en la cuestión especifica de la violencia contra las mujeres en los contextos multiculturales de los países europeos que son destino de flujos migratorios, haciendo un llamado a la pertinencia de una investigación más profunda sobre las medidas que, más allá del estricto ámbito del derecho penal, puedan revelarse más idóneas para garantizar los derechos de las mujeres pertenecientes a minorías culturales.

The standard development of 5G wireless communication culminated between 2017 and 2019, followed by the worldwide deployment of 5G networks, which is expected to result in very high data rate for enhanced mobile broadband, support ultra-reliable and low-latency services and accommodate massive number of connections. Research attention is shifting to future generation of wireless communications, for instance, beyond 5G or 6G. Unlike previous papers, which discussed the use cases, deployment scenarios, or new network architectures of 6G in depth, this paper focuses on a few potential technologies for 6G wireless communications, all of which represent certain fundamental breakthrough at the physical layer-technical hardcore of any new generation of wireless communications. Some of them, such as holographic radio, terahertz communication, large intelligent surface, and orbital angular momentum, are of revolutionary nature and many related studies are still at their scientific exploration stage. Several technical areas, such as advanced channel coding and modulation, visible light communication, and advanced duplex, while having been studied, may find more opportunities in 6G., Comment: SCIENCE CHINA Information Sciences, 28 pages, 7 figures

Due to its ability to irreversibly inactivate platelet cyclooxygenase, low-dose aspirin (ASA) is the most widely used antithrombotic agent. Although, studies in specific types of patients with cardiovascular disease (CVD) have shown an incomplete inhibition of platelet's cyclooxygenase, which may increase the variability in drug response. Some aspects of ASA pharmacokinetics (PK) still need further investigation. In this study, we aimed to characterise the contribution of esterase enzymes to ASA hydrolysis in the peripheral blood and to assess their activity in 36 healthy subjects (Ctrl) and 77 CVD patients. To this aim, an in vitro assay testing esterase activity in parallel to a liquid chromatography-tandem mass spectrometry method simultaneously detecting ASA and its main metabolites salicylic (SA) and gentisic acids, have been developed. Michaelis-Menten constant (Km) calculation, ASA esterase isoforms characterisation, and ASA PK study were then achieved. The calculated Km identified plasma esterases as the enzymes with the higher affinity for the substrate compared to the RBC ones. Both rivastigmine and 4-bis-nitrophenyl phosphate inhibited plasma esterase activities, suggesting that acetylcholinesterase and carboxylesterase largely contribute to ASA hydrolysis. The feasibility of the method here developed has been explored in Ctrl and CVD patients. The effect of ASA treatment on enzyme activity was further evaluated on an age, sex and BMI matched subgroup of patients and Ctrl (n = 10 for each subgroup, on and off ASA). No overall variations were evidenced in both CVD and Ctrl groups, even when the effect of ASA treatment was tested. This result suggests the absence of any influence of disease state, drug treatments, and comorbidities on plasma esterase and the inability of ASA intake to induce esterase function. In conclusion, the method here developed allows a better characterisation of ASA esterase activity and could be helpful to define the PK-related dete

The authors regret that the first name and last name of the author Sandro Sponga was published incorrectly in the original version and this has now been corrected.

New percutaneous technologies are rapidly emerging for the treatment of structural heart disease including mitral valve disease. Preliminary data suggest a potential clinical benefit of percutaneous treatment of mitral regurgitation by the MitraClip procedure in selected patients. Until final data are available from randomized, controlled, multicenter clinical trials, there is an urgent need for a consensus among all the operators involved in the treatment of patients with mitral regurgitation, including clinical cardiologists, heart failure specialists, surgeons, interventional cardiologists, and imaging experts. In the absence of evidence-based guidelines, the heart-team approach is the most reliable method of making proper decisions. This study is the result of multidisciplinary consensus activity, and has the aim of helping physicians in the difficult task of making decisions for the treatment of patients with mitral regurgitation. It is the result of a joint effort of the major Italian Cardiology and Cardiac Surgery Societies, working together to find a proper balance between the points of view of the clinical cardiologist, the interventional cardiologist, and the cardiac surgeon.

OBJECTIVES: We described clinical-epidemiological features of prosthetic valve endocarditis (PVE) and assessed the determinants of early surgical outcomes in multicentre design. METHODS: Data regarding 2823 patients undergoing surgery for endocarditis at 19 Italian Centers between 1979 and 2015 were collected in a database. Of them, 582 had PVE: in this group, the determinants of early mortality and complications were assessed, also taking into account the different chronological eras encompassed by the study. RESULTS: Overall hospital (30-day) mortality was 19.2% (112 patients). Postoperative complications of any type occurred in 256 patients (44%). Across 3 eras (1980-2000, 2001-08 and 2009-14), early mortality did not significantly change (20.4%, 17.1%, 20.5%, respectively, P = 0.60), whereas complication rate increased (18.5%, 38.2%, 52.8%, P < 0.001), consistent with increasing mean patient age (56 ± 14, 64 ± 15, 65 ± 14 years, respectively, P < 0.001) and median logistic EuroSCORE (14%, 21%, 23%, P = 0.025). Older age, female sex, preoperative serum creatinine > -2 mg/dl, chronic pulmonary disease, low ejection fraction, non-streptococcal aetiology, active endocarditis, preoperative intubation, preoperative shock and triple valve surgery were significantly associated with mortality. In multivariable analysis, age (OR = 1.02; P = 0.03), renal insufficiency (OR = 2.1; P = 0.05), triple valve surgery (OR = 6.9; P = 0.004) and shock (OR = 4.5; P < 0.001) were independently associated with mortality, while streptococcal aetiology, healed endocarditis and ejection fraction with survival. Adjusting for study era, preoperative shock (OR = 3; P < 0.001), Enterococcus (OR = 2.3; P = 0.01) and female sex (OR = 1.5; P = 0.03) independently predicted complications, whereas ejection fraction was protective. CONCLUSIONS: PVE surgery remains a high-risk one. The strongest predictors of early outcome of PVE surgery are related to patient's haemodynamic status an

On-pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase-1 renewal, thereby modifying low-dose aspirin pharmacodynamics. Thirty-seven patients on standard aspirin 100 mg once-daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once-daily, 100 mg twice-daily, or 200 mg once-daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased. Interleukin-6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once-daily showed a significant increase in serum thromboxane (TX)B2within the 24-hour dosing interval and urinary TXA2metabolite (TXM) excretion. Aspirin 100 mg twice-daily lowered serum TXB2and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once-daily dose, rescues the impaired antiplatelet effect of low-dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover.

On-pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase-1 renewal, thereby modifying low-dose aspirin pharmacodynamics. Thirty-seven patients on standard aspirin 100mg once-daily were studied before surgery and randomized within 36 hours post-surgery to 100mg once-daily, 100mg twice-daily or 200mg once-daily for 90 days. On day 7 post-surgery, immature and mature platelets, platelet mass, thrombopoieitin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased. Interleukin-6 significantly correlated with immature platelets. At day 7, patients randomized to 100mg once-daily showed a significant increase in serum thromboxane (TX)B2 within the 24-hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100mg twice-daily lowered serum TXB2 and prevented post-surgery TXM increase (p<0.01), without affecting prostacyclin metabolite excretion. Following cardiac surgery, shortening the dosing interval, but not doubling the once-daily dose, rescues the impaired antiplatelet effect of low-dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover. This article is protected by copyright. All rights reserved.

OBJECTIVES: We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency. METHODS: In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis. RESULTS: Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis. CONCLUSIONS: Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve reg

Nitrogen limits leaf gas exchange, canopy development, and evapotranspiration in many ecosystems. In dryland ecosystems, it is unclear whether increased anthropogenic nitrogen inputs alter the widely recognized dominance of water and energy constraints on ecohydrology. We use observations from a factorial irrigation and fertilization experiment in a nitrogen-limited southern California annual grassland to explore this hypothesis. Our analysis shows growing season soil moisture and canopy-scale water vapor conductance are equivalent in control and fertilized plots. This consistency arises as fertilization-induced increases in leaf area index (LAI) are offset by reduced leaf area-based stomatal conductance,g s . We interpret this as evidence of a hydraulic feedback between LAI, plant water status, and g s , not commonly implemented in evapotranspiration models. These results support the notion that canopy physiology and structure are coordinated in water-limited ecosystems to maintain a transpiration flux tightly controlled by hydraulic constraints in the soil-vegetation-atmosphere pathway.

Nitrogen limits leaf gas exchange, canopy development, and evapotranspiration in many ecosystems. In dryland ecosystems, it is unclear whether increased anthropogenic nitrogen inputs alter the widely recognized dominance of water and energy constraints on ecohydrology. We use observations from a factorial irrigation and fertilization experiment in a nitrogen-limited southern California annual grassland to explore this hypothesis. Our analysis shows growing season soil moisture and canopy-scale water vapor conductance are equivalent in control and fertilized plots. This consistency arises as fertilization-induced increases in leaf area index (LAI) are offset by reduced leaf area-based stomatal conductance,g s . We interpret this as evidence of a hydraulic feedback between LAI, plant water status, and g s , not commonly implemented in evapotranspiration models. These results support the notion that canopy physiology and structure are coordinated in water-limited ecosystems to maintain a transpiration flux tightly controlled by hydraulic constraints in the soil-vegetation-atmosphere pathway.

Increased oxidative stress in a failing heart may contribute to the pathogenesis of heart failure (HF). The aim of this study was to identify the oxidised proteins in the myocardium of HF patients and analyse the consequences of oxidation on protein function. The carbonylated proteins in left ventricular tissue from failing (n = 14) and non-failing human hearts (n = 13) were measured by immunoassay and identified by proteomics. HL-1 cardiomyocytes were incubated in the presence of stimuli relevant for HF in order to assess the generation of reactive oxygen species (ROS), the induction of protein carbonylation, and its consequences on protein function. The levels of carbonylated proteins were significantly higher in the HF patients than in the controls (p<0.01). We identified two proteins that mainly underwent carbonylation: M-type creatine kinase (M-CK), whose activity is impaired, and, to a lesser extent, alpha-cardiac actin. Exposure of cardiomyocytes to angiotensin II and norepinephrine led to ROS generation and M-CK carbonylation with loss of its enzymatic activity. Our findings indicate that protein carbonylation is increased in the myocardium during HF and that these oxidative changes may help to explain the decreased CK activity and consequent defects in energy metabolism observed in HF.

Human societies are increasingly altering the water and biogeochemical cycles to both improve ecosystem productivity and reduce risks associated with the unpredictable variability of climatic drivers. These alterations, however, often cause large negative environmental consequences, raising the question as to how societies can ensure a sustainable use of natural resources for the future. Here we discuss how ecohydrological modeling may address these broad questions with special attention to agroecosystems. The challenges related to modeling the two-way interaction between society and environment are illustrated by means of a dynamical model in which soil and water quality supports the growth of human society but is also degraded by excessive pressure, leading to critical transitions and sustained societal growth-collapse cycles. We then focus on the coupled dynamics of soil water and solutes (nutrients or contaminants), emphasizing the modeling challenges, presented by the strong nonlinearities in the soil and plant system and the unpredictable hydroclimatic forcing, that need to be overcome to quantitatively analyze problems of soil water sustainability in both natural and agricultural ecosystems. We discuss applications of this framework to problems of irrigation, soil salinization, and fertilization and emphasize how optimal solutions for large-scale, long-term planning of soil and water resources in agroecosystems under uncertainty could be provided by methods from stochastic control, informed by physically and mathematically sound descriptions of ecohydrological and biogeochemical interactions.

Optimal perioperative antiplatelet therapy in patients with coronary stents undergoing surgery still remains poorly defined and a matter of debate among cardiologists, surgeons and anaesthesiologists. Surgery represents one of the most common reasons for premature antiplatelet therapy discontinuation, which is associated with a significant increase in mortality and major adverse cardiac events, in particular stent thrombosis. Clinical practice guidelines provide little support with regard to managing antiplatelet therapy in the perioperative phase in the case of patients with non-deferrable surgical interventions and/or high haemorrhagic risk. Moreover, a standard definition of ischaemic and haemorrhagic risk has never been determined. Finally, recommendations shared by cardiologists, surgeons and anaesthesiologists are lacking. The present consensus document provides practical recommendations on the perioperative management of antiplatelet therapy in patients with coronary stents undergoing surgery. Cardiologists, surgeons and anaesthesiologists have contributed equally to its creation. On the basis of clinical and angiographic data, the individual thrombotic risk has been defined. All surgical interventions have been classified according to their inherent haemorrhagic risk. A consensus on the optimal antiplatelet regimen in the perioperative phase has been reached on the basis of the ischaemic and haemorrhagic risk. Aspirin should be continued perioperatively in the majority of surgical operations, whereas dual antiplatelet therapy should not be withdrawn for surgery in the case of low bleeding risk. In selected patients at high risk for both bleeding and ischaemic events, when oral antiplatelet therapy withdrawal is required, perioperative treatment with short-acting intravenous glycoprotein IIb/IIIa inhibitors (tirofiban or eptifibatide) should be taken into consideration.

Thesis (Ph. D. in the Field of Hydrology)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, February 2013., "February 2012." Cataloged from PDF version of thesis., Includes bibliographical references (p. 155-172)., This thesis addresses the coupling of hydrologic and biogeochemical processes and, specifically, the organization of ecosystem traits with the water, carbon, and nitrogen cycles. Observations from a factorial irrigation-fertilization experiment in a seasonally dry annual grassland are combined with a simple ecosystem model to identify relationships between vegetation, nitrogen availability, and hydrology. Assuming primary productivity is water-limited, data analysis indicates that soil moisture and canopy conductance are insensitive to nitrogen supply, owing to a trade-off between canopy density and leaf conductance that maximizes efficient use of available water. That is, fertilization-induced increases in leaf area index are offset by reduced leaf area-based stomatal conductance. When primary productivity is assumed to be co-limited by water and nitrogen availability, total surface conductance is estimated to be insensitive to nitrogen supply, but added nitrogen increases the ratio of transpiration to evaporation. This coupled water-carbon-nitrogen model is then extended to predict ecosystem sensitivity across independently varied gradients of water and nitrogen supply rates. This analysis reveals two distinct regimes of plant-resource organization. In arid climates, rooting depths decrease with increasing aridity, while in humid climates, rooting depths increase with aridity. In all climates, rooting depths increase with increased nitrogen supply. Further, relative root-carbon allocation always increases with aridity and decreases with nitrogen supply. These resource use strategies result in an efficient use of available water in arid climates and efficient use of available nitrogen in humid climates. The associated ecosystem process rates indicate that nitrogen supply is an important determinant of surface water and carbon fluxes in humid climates, but only of carbon fluxes in arid climates., by Anthony Joseph Parolari., Ph.D.in the Field of Hydrology

Thesis (Ph. D. in the Field of Hydrology)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, February 2013., "February 2012." Cataloged from PDF version of thesis., Includes bibliographical references (p. 155-172)., This thesis addresses the coupling of hydrologic and biogeochemical processes and, specifically, the organization of ecosystem traits with the water, carbon, and nitrogen cycles. Observations from a factorial irrigation-fertilization experiment in a seasonally dry annual grassland are combined with a simple ecosystem model to identify relationships between vegetation, nitrogen availability, and hydrology. Assuming primary productivity is water-limited, data analysis indicates that soil moisture and canopy conductance are insensitive to nitrogen supply, owing to a trade-off between canopy density and leaf conductance that maximizes efficient use of available water. That is, fertilization-induced increases in leaf area index are offset by reduced leaf area-based stomatal conductance. When primary productivity is assumed to be co-limited by water and nitrogen availability, total surface conductance is estimated to be insensitive to nitrogen supply, but added nitrogen increases the ratio of transpiration to evaporation. This coupled water-carbon-nitrogen model is then extended to predict ecosystem sensitivity across independently varied gradients of water and nitrogen supply rates. This analysis reveals two distinct regimes of plant-resource organization. In arid climates, rooting depths decrease with increasing aridity, while in humid climates, rooting depths increase with aridity. In all climates, rooting depths increase with increased nitrogen supply. Further, relative root-carbon allocation always increases with aridity and decreases with nitrogen supply. These resource use strategies result in an efficient use of available water in arid climates and efficient use of available nitrogen in humid climates. The associated ecosystem process rates indicate that nitrogen supply is an important determinant of surface water and carbon fluxes in humid climates, but only of carbon fluxes in arid climates., by Anthony Joseph Parolari., Ph.D.in the Field of Hydrology

Legacy effects of past land use and disturbance are increasingly recognized, yet consistent definitions of and criteria for defining them do not exist. To address this gap in biological- and ecosystem-assessment frameworks, we propose a general metric for evaluating potential legacy effects, which are computed by normalizing altered system function persistence with duration of disturbance. We also propose two distinct legacy-effect categories: signal effects from lags in transport and structural effects from physical landscape changes. Using flux records for water, sediment, nitrogen, and carbon from long-term study sites in the eastern United States from 1500 to 2000, we identify gaps in our understanding of legacy effects and reveal that changes in basin sediment dynamics precede instrumented records. These sediment dynamics are not generally incorporated into interpretations of contemporary records, although their potential legacy effects are substantial. The identification of legacy effects may prove to be a fundamental component of landscape management and effective conservation and restoration practice., National Science Foundation (U.S.) (Cooperative Agreement DEB-0236154), National Science Foundation (U.S.). Long-Term Ecological Research Network (Grant NSF-OCE-0423565)

Nitrogen limits leaf gas exchange, canopy development, and evapotranspiration in many ecosystems. In dryland ecosystems, it is unclear whether increased anthropogenic nitrogen inputs alter the widely recognized dominance of water and energy constraints on ecohydrology. We use observations from a factorial irrigation and fertilization experiment in a nitrogen-limited southern California annual grassland to explore this hypothesis. Our analysis shows growing season soil moisture and canopy-scale water vapor conductance are equivalent in control and fertilized plots. This consistency arises as fertilization-induced increases in leaf area index (LAI) are offset by reduced leaf area-based stomatal conductance, g[subscript s]. We interpret this as evidence of a hydraulic feedback between LAI, plant water status, and g[subscript s], not commonly implemented in evapotranspiration models. These results support the notion that canopy physiology and structure are coordinated in water-limited ecosystems to maintain a transpiration flux tightly controlled by hydraulic constraints in the soil-vegetation-atmosphere pathway., National Science Foundation (U.S.) (Grant EAR 0962253)

Long-term monitoring studies of non-commercial marine organisms are rare, especially studies of zooplankton populations. This study was undertaken to test the feasibility of monitoring meroplankton from a fixed platform, a less expensive and less weather dependent mode of sampling than the traditional method of towed collections. The fixed platform selected for the study was the fishing pier adjacent to Thimble Shoal Channel on the southernmost tunnel island of the Chesapeake Bay Bridge-Tunnel. This site was chosen because it was near several stations being sampled from a boat by towed nets in a companion study, and being located in the Bay mouth, it seemed an appropriate monitoring site. Here we report on a statistical comparison of the pier collections with the towed collections and evaluate the fixed platform sampling technique. Conclusion is that fixed platform sampling is as good an estimator of density of dominant meroplanktons as that provided by towed samples. Advantage of fixed sampling is that it is less expensive, less weather dependent and will provide continuity of data over time (valuable in long-term monitoring).

Long-term monitoring studies of non-commercial marine organisms are rare, especially studies of zooplankton populations. Where such data bases exist they are frequently the source of unique and valuable information. The importance of long-term data bases is the continuity of data over time hence their maximum value is only realized after a number of iterations of the ecological cycle under study. This report constitutes a preliminary look at the first two years of data from what we hope will become a continuing study of meroplankters in the Chesapeake Bay mouth. Among the objectives of this research were to compare the technique of monitoring zooplankton from a fixed platform, (the fishing pier on the South Island of the Chesapeake Bay Bridge-Tunnel) with towed collections. The fixed platform sampling approach was selected for testing because it is both less expensive and, not being weather dependent, more reliable than boat towed collections. These are both important considerations in the establishment of a long-term program.