Exercise intolerance and fatigue in chronic heart failure: is there a role for group III/IV afferent feedback?

Exercise intolerance and early fatiguability are hallmark symptoms of chronic heart failure. While the malfunction of the heart is certainly the leading cause of chronic heart failure, the patho-physiological mechanisms of exercise intolerance in these patients are more complex, multifactorial and only partially understood. Some evidence points towards a potential role of an exaggerated afferent feedback from group III/IV muscle afferents in the genesis of these symptoms. Overactivity of feedback from these muscle afferents may cause exercise intolerance with a double action: by inducing cardiovascular dysregulation, by reducing motor output and by facilitating the development of central and peripheral fatigue during exercise. Importantly, physical inactivity appears to affect the progression of the syndrome negatively, while physical training can partially counteract this condition. In the present review, the role played by group III/IV afferent feedback in cardiovascular regulation during exercise and exercise-induced muscle fatigue of healthy people and their potential role in inducing exercise intolerance in chronic heart failure patients will be summarised

Improved Renormalization of Lattice Operators: A Critical Reappraisal

We systematically examine various proposals which aim at increasing the accuracy in the determination of the renormalization of two-fermion lattice operators. We concentrate on three finite quantities which are particularly suitable for our study: the renormalization constants of the vector and axial currents and the ratio of the renormalization constants of the scalar and pseudoscalar densities. We calculate these quantities in boosted perturbation theory, with several running boosted couplings, at the "optimal" scale q*. We find that the results of boosted perturbation theory are usually (but not always) in better agreement with non-perturbative determinations of the renormalization constants than those obtained with standard perturbation theory. The finite renormalization constants of two-fermion lattice operators are also obtained non-perturbatively, using Ward Identities, both with the Wilson and the tree-level Clover improved actions, at fixed cutoff ($\beta$=6.4 and 6.0 respectively). In order to amplify finite cutoff effects, the quark masses (in lattice units) are varied in a large interval 0<am<1. We find that discretization effects are always large with the Wilson action, despite our relatively small value of the lattice spacing ($a^{-1} \simeq 3.7$ GeV). With the Clover action discretization errors are significantly reduced at small quark mass, even though our lattice spacing is larger ($a^{-1} \simeq 2$ GeV). However, these errors remain substantial in the heavy quark region. We have implemented a proposal for reducing O(am) effects, which consists in matching the lattice quantities to their continuum counterparts in the free theory. We find that this approach still leaves appreciable, mass dependent, discretization effects.Comment: 54 pages, Latex, 5 figures. Minor changes in text between eqs.(86) and (88

Non-perturbative Renormalization of Lattice Operators

We briefly review and compare three methods (one perturbative, one based on Ward Identities and one non-perturbative) for the calculation of the renormalization constants of lattice operators. The following results are presented: (a) non perturbative renormalization of the operators with light quarks; (b) the renormalization constants with a heavy (charm) quark mass and its KLM improvement; (c) the non perturbative determination of the mixing of the $\Delta S = 2$ operator.Comment: 9 pages, uuencoded PS file, 8 figures included, 1 tabl

Efficient reinsurance strategies considering counterparty default risk

Insurance companies pursue the objective of increasing their technical profit, but in doing so, they expose themselves to more risks, increasing the variability of their result. In order to balance the potential profitability deriving from the underwriting activity with the related risks, insurers typically resort to reinsurance treaties. In this context arises the problem of finding the optimal treaty which jointly satisfies multiple objectives, typically represented by risk and return metrics. The classical approaches consider only the characteristics of the treaty, neglecting the ones of the reinsurance provider. However, this approach could lead to sub-optimal choices, since it does not consider counterparty default risk. The purpose of this thesis is threefold. Firstly, we extend classical formulas of technical profit of an insurance company to a partial internal model of Solvency II, including the potential default of the reinsurance counterparty. Secondly, we develop a stochastic simulation approach that includes counterparty default risk and potentially other features, for estimating the efficient frontier of reinsurance strategies for a non-life insurance company. Finally, we propose the application of a neural network model for finding the efficient frontier in a multi-objective optimization problem, requiring limited observations and preserving the possibility of deriving the strategies which generate the Pareto front. Numerical applications are performed assuming a multi-line non-life insurer with parameters from the Italian market. The results show the importance of the rating of reinsurers, i.e. counterparty default risk, for the assessment of the optimal reinsurance strategies. Moreover, we show how this risk could become an opportunity in case the reinsurer with high risk offers a discounted price that more than compensate the potential default effect. Finally, the neural network model offers another perspective for determining optimal reinsurance strategies, which can be especially useful in case of high number of potential combinations defining each strategy

Characters and consequences of the evolution of tourism in Malta

One of the most important aspects that has recently been at the center of the geographical debate is the development of tourism1, since it has had a series of repercussions on a social, economic2, political and territorial level.This process has manifested itself in different ways, since man has shown different interests over time; moreover it has been favored by the evolution of the means of transport that have allowed the progressive widening of horizons; the affirmation of an organization of tourist activity has also been significant, with the creation of specific reference figures such as tour operators.The current different types of tourism reflect the many interests of contemporary man such as cultural tourism, food and wine tourism, experience tourism, religious tourism, seaside tourism that today make the tourist organization much more complex than in the past.The tourist phenomenon. One of the most important aspects that has recently been at the center of thegeographical debate is the development of tourism1, since it has had a series of repercussions on a social, economic2, political and territorial level.This process3 has manifested itself in different ways, since man has showndifferent interests over time; moreover it has been favored by the evolution of the means of transport that have allowed the progressive widening of horizons; the affirmation of an organization of tourist activity has also been significant, with the creation of specific reference figures such as tour operators.The current different types of tourism reflect the many interests ofcontemporary man such as cultural tourism, food and wine tourism, experience tourism, religious tourism, seaside tourism that today make the tourist organization much more complex than in the past

Evaluation of OASL and HERC5’s role in the non-lytic clearance of influenza A virus from club cells

Influenza A virus (IAV) is a highly infectious pathogen responsible for causing severe respiratory illness and death in humans and animals worldwide. Due to highly effective strategies to negate host antiviral defenses, IAV leads to the death of nearly all infected cells. Furthermore, IAV induces high levels of genome-damaging oxidative stress within infected cells and suppresses the cellular mismatch repair (MMR) mechanism, thereby inhibiting expression of key antiviral genes, which further contributes to cell death. However, recent studies have demonstrated that a subset of respiratory epithelial cells, called club cells, are able to non-lytically clear IAV and continue to survive following direct infection. These cells are able to maintain genome integrity during IAV infection using MMR activity, thus allowing for sufficient expression of antiviral genes. We hypothesize that several of these antiviral genes are critical to the non-lytic clearance of IAV, particularly HERC5 and OSAL. Through siRNA gene knockdown techniques, we have evaluated the impact of these genes on the non-lytic clearance mechanism of IAV-infected club cells