1,721,093 research outputs found
The place of cyclical therapy for the treatment of membranous nephropathy in the era of rituximab
No full textPrimary membranous nephropathy (MN) is the most frequent cause of nephrotic syndrome in adults, due to a variety of autoantibodies, most frequently against phospholipase A2 receptor (PLA2R). In severe cases or when spontaneous remission is not achieved, immunosuppression is required. Cyclical therapy, based on glucocorticoids and cyclophosphamide on alternate months for 6 months, has proven effective to induce remission and reduce the risk of end-stage renal disease. Since the early 2000s, rituximab (RTX) has emerged as a key player in the management of MN, showing overall comparable effectiveness and likely better safety compared with the cyclical regimen, despite the lack of adequately powered trials comparing the two approaches head to head. For these reasons, RTX is now considered the agent of choice for most patients with MN. However, there are still uncertainties. Around 20-40% of patients are resistant to RTX, especially in the setting of high anti-PLA2R levels, and this drug remains relatively unexplored in patients with the most severe disease. In these scenarios, although the expanding therapeutic armamentarium is probably going to provide further options, the cyclical regimen still plays a key role as a safety net. The aim of this article is to illustrate the role of cyclical therapy in the RTX era
Window for preferred axion models
No full textWe discuss phenomenological criteria for defining "axion windows," namely regions in the parameter space of the axion-photon coupling where realistic models live. Currently, the boundaries of this region depend on somewhat arbitrary criteria, and it would be highly desirable to specify them in terms of precise phenomenological requirements. We first focus on hadronic axion models within post-inflationary scenarios, in which the initial abundance of the new vectorlike quarks Q is thermal. We classify their representations RQ by requiring that (i) the Q are sufficiently short lived to avoid issues with long-lived strongly interacting relics, (ii) the theory remains weakly coupled up to the Planck scale. The more general case of multiple RQ is also studied, and the absolute upper and lower bounds on the axion-photon coupling as a function of the axion mass is identified. Pre-inflationary scenarios in which the axion decay constant remains bounded as fa≤5×1011 GeV allow for axion-photon couplings only about 20% larger. Realistic Dine-Fischler-Srednicki-Zhitnitsky type of axion models also remain encompassed within the hadronic axion window. Some mechanisms that can allow to enhance the axion-photon coupling to values sizeably above the preferred window are discussed
STEC-HUS, atypical HUS and TTP are all diseases of complement activation
No full textHaemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP) are diseases characterized by microvascular thrombosis, with consequent thrombocytopaenia, haemolytic anaemia and dysfunction of affected organs. Advances in our understanding of the molecular pathology led to the recognition of three different diseases: typical HUS caused by Shiga toxin-producing Escherichia coli (STEC-HUS); atypical HUS (aHUS), associated with genetic or acquired disorders of regulatory components of the complement system; and TTP that results from a deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. In this Review, we discuss data indicating that complement hyperactivation is a common pathogenetic effector that leads to endothelial damage and microvascular thrombosis in all three diseases. In STEC-HUS, the toxin triggers endothelial complement deposition through the upregulation of P-selectin and possibly interferes with the activity of complement regulatory molecules. In aHUS, mutations in the genes coding for complement components predispose to hyperactivation of the alternative pathway of complement. In TTP, severe ADAMTS13 deficiency leads to generation of massive platelet thrombi, which might contribute to complement activation. More importantly, evidence is emerging that pharmacological targeting of complement with the anti-C5 monoclonal antibody eculizumab can effectively treat not only aHUS for which it is indicated, but also STEC-HUS and TTP in some circumstances. © 2012 Macmillan Publishers Limited. All rights reserved
U(1) flavour symmetries as Peccei-Quinn symmetries
Full text linkWe investigate to what extent a generic, generation-dependent U(1) symmetry acting on the quark Yukawa operators can reduce the number of free parameters by forcing some entries in the Yukawa matrices to vanish. The maximal reduction compatible with CP violation yields nine real parameters and one phase, which matches the number of physical observables, implying that such models have no free parameters. We derive a set of results: (i) the only possible structures have the form M 4 ⊕ M 5 , where the subscripts indicate the number of real parameters in the Yukawa matrices, (ii) there are only two inequivalent Yukawa structures, each one giving rise to six different models depending on quark flavour assignments, (iii) the U(1) symmetries that generate these textures all have a QCD anomaly, and hence are Peccei-Quinn symmetries, reinforcing the idea of a possible connection between the quark flavour puzzle and the axion solution to the strong CP problem, (iv) in some cases the contributions to the QCD anomaly of two generations cancels out, and this opens the possibility that the axion coupling to nucleons could be strongly suppressed. Flavour-violating axion couplings to quarks are completely fixed, up to the axion decay constant, providing a non-trivial complementarity between low-energy flavour-violating processes and standard axion searches
Lifetime ratios of beauty hadrons at the next-to-leading order in QCD
No full textWe compute the next-to-leading order QCD corrections to spectator effects in the lifetime ratios of beauty hadrons. With respect to previous calculations, we take into account the non-vanishing value of the charm quark mass. We obtain the predictions tau (B+)/tau(B-d) = 1.06+/-0.02, tau(B-s)/tau(B-d) = 1.00+/-0.0 1 and tau(Lambda(b))/tau(B-d) = 0.90+/-0.05, in good agreement with the experimental results. In the case of tau(B-s)/tau(B-d) and tau(Lambda(b))/tau(B-d), however, some contributions, which either vanish in the vacuum insertion approximation or represent a pure NLO correction, have not been determined yet. (C) 2002 Elsevier Science B.V. All rights reserved
First lattice calculation of the electromagnetic operator amplitude (Pi0|Q(+)gamma|K0)
No full textWe present the first lattice calculation of the matrix element of the electromagnetic operator [pi (0)|Q(+)(gamma)|K(0)], where = Q(+)(gamma) = (Q(d)e/16 pi (2))((s) over bar (L)sigma (mu nu) F(mu nu)d(R) + (s) over bar (R)sigma (mu nu) F(mu nu)d(L)) This matrix element plays an important roe, since it contributes to enhance the CP violating part of the K-L --> pi (0)e(+)e(-) amplitude in supersymmetric extensions of the Standard Model
Operator product expansion and quark condensate from LQCD in coordinate space
No full textWe perform an exploratory study of the operator product expansion of the quark propagator on the lattice at short distance in coordinate space. This permits a simple determination of the quark condensate, ^MS(2 GeV)=(-265 +- 5 +- 22 MeV)^3, and of the renormalization constant of the quark field, Z^MS(2 GeV)=0.871 +- 0.003 +- 0.020. This new method also provides a remarkable non-perturbative test of the OPE predictions at short distance in QCD
Lifetime differences and CP violation parameters of neutral B mesons at the next-to-leading order in QCD
No full textWe compute the next-to-leading order QCD corrections to the off-diagonal elements of the decay-width matrix Gamma entering the neutral B-meson oscillations. From this calculation the width differences DeltaGamma and the CP violation parameters (q/p) of B-d and B-s mesons are estimated, including the complete O(alpha(s)) QCD corrections and the 1/m(b) contributions. For the width difference DeltaGamma(s) we agree with previous results. By using the lattice determinations of the relevant hadronic matrix elements we obtain the theoretical predictions DeltaGamma(d)/Gamma(d) = (2.42 +/- 0.59) x 10(-3) and DeltaGamma(s)/Gamma(s) = (7.4 +/- 2.4) x 10(-2). For the CP violation parameters, we find (q/p)(d)\ - 1 = (2.96 +/- 0.67) x 10(-4) and (q/p)(s) - 1 = - (1.28 +/- 0.27) x 10(-5). These predictions are compatible with the experimental measurements which, however, suffer at present from large uncertainties
Coupling of the light vector meson to the vector and to the tensor current
No full textWe present results for the coupling of the light vector mesons to the tensor current, relative to the standard vector meson decay constants. From an O(a)-improved lattice study, performed at three values of the lattice spacing in the quenched approximation, our final values (in the continuum limit), in the (MS) over bar scheme at mu = 2 GeV, are: f(rho)(T)/f(rho) = 0.72(2)((+2)(-0)), f(K)(T)*/f(K)* = 0.74(2), f(phi)(T)/ f(phi) = 0.76(1)
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