Safety, Efficacy and Evidence Base for Use of the Subcutaneous Implantable Cardioverter Defibrillator

The trans-venous implantable cardioverter defibrillator (TV-ICD) is effective in treating life-threatening ventricular arrhythmia and reduces mortality in high-risk patients. However, there are significant short- and long-term complications that are associated with intravascular leads. These shortcomings are mostly relevant in young patients with long life expectancy and low risk of death from non-arrhythmic causes. Drawbacks of trans-venous leads recently led to the development of the entirely subcutaneous implantable cardioverter defibrillator (S-ICD). The S-ICD does not require vascular access or permanent intravascular defibrillation leads. Therefore, it is expected to overcome many complications associated with conventional ICDs. This review highlights data on safety and efficacy of the S-ICD and is envisioned to help in identifying the role of this device in clinical practice

Chapter Evaluation and monitoring of the Livorno’s Fossi System

The ditches and canals of Livorno, also called Fossi, are the most characterized elements the city, not only from a historical point of view, but also and above all from an urban landscape characterization point of view. Due to the overlapping of skills not yet resolved, fragmented information and data exist regarding the real extent of the pleasure craft, the status of the canals, the provision of services and general safety. The hypothesis is to succeed, through a multi-criteria assessment of scenarios, to support and quantify the displacement of vessels that negatively affect accessibility and the landscape of Livorno's Fossi system elsewhere

Chapter Strategic Planning Document of Port Authority System, a new city-ports agreement: the case of Northern Tyrrhenian Sea AdSP

Legislative Decrees 169/16 and 232/17 have modified Law 84/94. The changes introduces the Port System Regulatory Plan, composed of the PRPs of the individual ports and the Strategic System Planning Document. Among the contents of the DPSS, for which institutional agreements between AdSP and territorial bodies are envisaged, there is the identification of the so-called "Areas of port-city interaction". The objective of this research is to propose a methodology for identifying the areas of influence of the port on the city, measuring the degree of interaction through a system with indicators

Autonomic cardiovascular control and cardiac arrhythmia in two pregnant women with hypertrophic cardiomyopathy: Insights from ICD monitoring

In women with hypertrophic cardiomyopathy (HCM), pregnancy prompts major changes in hemodynamic and cardiac autonomic function that may precipitate heart failure (HF) or increase the risk of cardiac arrhythmia.We report the clinical follow-up of two patients with non-obstructive HCM implanted with a cardioverter defibrillator (ICD) allowing for continuous analysis of heart rate (HR), heart rate variability (HRV) and cardiac arrhythmia throughout the entire course of pregnancy.Both patients experienced increased HR and decreased HRV from the early stages of pregnancy, which persisted until delivery. Premature ventricular contractions (PVCs) and runs of non-sustained ventricular tachycardia (NSVT) reached a peak in the second and third trimesters, concurrent with sympathetic hyperactivity. In one patient with baseline NYHA class II HF symptoms, increased PVCs and NSVT were consistent with the deterioration of HF, supporting the decision to bring the delivery forward. While both patients experienced a persistent increase in sympathetic tone and ventricular ectopic activity, no life-threatening arrhythmias were documented.During pregnancy, patients with hypertrophic cardiomyopathy develop progressive neuroautonomic imbalance, prompting an increase in non-sustained ventricular arrhythmia. This enhanced arrhythmia burden warrants close follow-up and rhythm assessment during the third trimester, especially in women who have heart failure symptoms before pregnancy. Implantable cardioverter defibrillators provide a continuous analysis of heart rate variability and arrhythmia burden that supports therapeutic decision-making during follow-up. Resumo: Em mulheres com miocardiopatia hipertrófica, a gravidez aumenta as variações hemodinâmicas e as alterações da função autonómica cardíaca que podem provocar insuficiência cardíaca ou aumentar o risco de arritmia. Reportamos o acompanhamento clínico de duas pacientes com miocardiopatia hipertrófica não obstrutiva, ambas implantadas com cardioversor-desfibrilhador (CID). A monitoração com CID permite a análise contínua da frequência cardíaca, da variabilidade da frequência cardíaca (VFC) e da arritmia durante toda a gravidez. As duas pacientes manifestaram aumentos da FC e diminuições da VFC desde o início da gravidez até ao parto. Observou-se um pico de frequência de extrassístoles ventriculares (EV) e de taquicardias ventriculares não sustentadas (TVNS) no segundo e terceiro trimestres da gestação, em correspondência da hiperatividade simpática. Numa das pacientes com classe funcional NYHA II, antes da gravidez, o aumento de EV e de TVNS contemporaneamente ao agravamento da insuficiência cardíaca levou à decisão de antecipar o parto. As duas pacientes demonstraram um aumento persistente da atividade simpática e da atividade ectópica ventricular, não existiram casos de arritmias ventriculares malignas. Durante a gravidez as pacientes com miocardiopatia hipertrófica desenvolvem um progressivo desequilíbrio autonómico que causa um aumento das arritmias ventriculares não sustentadas. O aumento do risco arrítmico necessita de um constante e frequente controle clínico e do ritmo cardíaco durante o terceiro trimestre, especialmente em mulheres com sintomas de insuficiência cardíaca antes da gravidez. O cardioversor-desfibrilhador implantável fornece uma análise continua da variabilidade da frequência cardíaca e das arritmias que podem apoiar as decisões terapêuticas durante a gravidez. Keywords: Hypertrophic cardiomyopathy, Pregnancy, Implantable cardioverter defibrillator, Heart rate variability, Ventricular arrhythmia, Palavras-chave: Miocardiopatia hipertrófica, Gravidez, Cardioversor-desfibrilhador implantável, Variabilidade da frequência cardíaca, Arritmia ventricula

Left ventricular remodeling in hypertrophic cardiomyopathy: an overview of current knowledge

While most patients with hypertrophic cardiomyopathy (HCM) show a relatively stable morphologic and clinical phenotype, in some others, progressive changes in the left ventricular (LV) wall thickness, cavity size, and function, defined, overall, as "LV remodeling", may occur. The interplay of multiple pathophysiologic mechanisms, from genetic background to myocardial ischemia and fibrosis, is implicated in this process. Different patterns of LV remodeling have been recognized and are associated with a specific impact on the clinical course and management of the disease. These findings underline the need for and the importance of serial multimodal clinical and instrumental evaluations to identify and further characterize the LV remodeling phenomenon. A more complete definition of the stages of the disease may present a chance to improve the management of HCM patients

Targeted quantitative metabolic profiling of brain-derived cell cultures by semi-automated MEPS and LC-MS/MS

The accurate characterisation of metabolic profiles is an important prerequisite to determine the rate and the efficiency of the metabolic pathways taking place in the cells. Changes in the balance of metabolites involved in vital processes such as glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), as well as in the biochemical pathways related to amino acids, lipids, nucleotides, and their precursors reflect the physiological condition of the cells and may contribute to the development of various human diseases. The feasible and reliable measurement of a wide array of metabolites and biomarkers possesses great potential to elucidate physiological and pathological mechanisms, aid preclinical drug development and highlight potential therapeutic targets. An effective, straightforward, sensitive, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was developed for the simultaneous quali-quantitative analysis of 41 compounds in both cell pellet and cell growth medium obtained from brain-derived cell cultures. Sample pretreatment miniaturisation was achieved thanks to the development and optimisation of an original extraction/purification approach based on digitally programmed microextraction by packed sorbent (eVol®-MEPS). MEPS allows satisfactory and reproducible clean-up and preconcentration of both low-volume homogenate cell pellet lysate and cell growth medium with advantages including, but not limited to, minimal sample handling and method sustainability in terms of sample, solvents, and energy consumption. The MEPS-LC-MS/MS method showed good sensitivity, selectivity, linearity, and precision. As a proof of concept, the developed method was successfully applied to the analysis of both cell pellet and cell growth medium obtained from a line of mouse immortalised oligodendrocyte precursor cells (OPCs; Oli-neu cell line), leading to the unambiguous determination of all the considered target analytes. This method is thus expected to be suitable for targeted, quantitative metabolic profiling in most brain cell models, thus allowing accurate investigations on the biochemical pathways that can be altered in central nervous system (CNS) neuropathologies, including e.g., mitochondrial respiration and glycolysis, or use of specific nutrients for growth and proliferation, or lipid, amino acid and nucleotide metabolism

Hematopoietic progenitor cell liabilities and alarmins S100A8/A9-related inflammaging associate with frailty and predict poor cardiovascular outcomes in older adults

Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre‐frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10‐fold) and peripheral blood (>200‐fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multidomain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1‐year follow‐up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro‐inflammatory cytokines in pre‐frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes

Observation of the baryonic decay B¯0→Λ+cp¯K−K+

We report the observation of the baryonic decay (B) over bar (0) -> Lambda(+)(c)(p) over barK(-)K(+) using a data sample of 471 x 10(6) B (B) over bar pairs produced in e(+)e(-) annihilations at root s = 10.58 GeV. This data sample was recorded with the BABAR detector at the PEP- II storage ring at SLAC. We find B((B) over bar (0) -> Lambda(+)(c)(p) over barK(-)K(+)) = (2.5 +/- 0.4((stat)) +/- 0.2((syst)) +/- 0.6(B(Lambda c+)) ) x 10(-5) where the uncertainties are statistical, systematic, and due to the uncertainty of the Lambda(+)(c) -> (p) over barK(-)pi(+) branching fraction, respectively. The result has a significance corresponding to 5.0 standard deviations, including all uncertainties. For the resonant decay (B) over bar (0) -> Lambda(+)(c)(p) over bar phi, we determine the upper limit B((B) over bar (0) -> Lambda(+)(c)(p) over bar phi) < 1.2 x 10(-5) at 90% confidence level

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Physics case for an LHCb Upgrade II - Opportunities in flavour physics, and beyond, in the HL-LHC era

The LHCb Upgrade II will fully exploit the flavour-physics opportunities of the HL-LHC, and study additional physics topics that take advantage of the forward acceptance of the LHCb spectrometer. The LHCb Upgrade I will begin operation in 2020. Consolidation will occur, and modest enhancements of the Upgrade I detector will be installed, in Long Shutdown 3 of the LHC (2025) and these are discussed here. The main Upgrade II detector will be installed in long shutdown 4 of the LHC (2030) and will build on the strengths of the current LHCb experiment and the Upgrade I. It will operate at a luminosity up to 2×1034 cm−2s−1, ten times that of the Upgrade I detector. New detector components will improve the intrinsic performance of the experiment in certain key areas. An Expression Of Interest proposing Upgrade II was submitted in February 2017. The physics case for the Upgrade II is presented here in more depth. CP-violating phases will be measured with precisions unattainable at any other envisaged facility. The experiment will probe b → sl+l−and b → dl+l− transitions in both muon and electron decays in modes not accessible at Upgrade I. Minimal flavour violation will be tested with a precision measurement of the ratio of B(B0 → μ+μ−)/B(Bs → μ+μ−). Probing charm CP violation at the 10−5 level may result in its long sought discovery. Major advances in hadron spectroscopy will be possible, which will be powerful probes of low energy QCD. Upgrade II potentially will have the highest sensitivity of all the LHC experiments on the Higgs to charm-quark couplings. Generically, the new physics mass scale probed, for fixed couplings, will almost double compared with the pre-HL-LHC era; this extended reach for flavour physics is similar to that which would be achieved by the HE-LHC proposal for the energy frontier