Transforming care for rare and inherited cardiovascular diseases through education and training

The European Union defines a rare disease as a condition that affects less than 5 in 10,000 of the general population. By this definition, there are between 6000 and 8000 known rare disorders that together affect 1 in 17 Europeans. For this reason, rare disorders are the subject of intense scrutiny by governments and healthcare organisations that are developing new systems for clinical care, research and patient involvement

The 18 kDa cytosolic acid phosphatase from bovine liver has phosphotyrosine phosphatase activity on the autophosphorylated epidermal growth factor receptor

AbstractIn this paper we demonstrate that the cytosofic low-Mr acid phosphatase purified from bovine liver has phosphotyrosine protein phosphatase acitivity on 32P-autophosphorylated epidermal growth factor (EGF) receptor. This activity was significantly inhibited by orthovanadate and p-hydroxymercuribenzoate; the latter result indicates that free sulfhydryl groups are required for phosphotyrosine phosphatase activity. The enzyme was active in a broad pH range, with maximum activity between pH 5.5 and 7.5. The apparent Km for 32P-EGF receptor dephosphorylation was 4 nM. The enzyme appeared to be specific for phosphotyrosine in that it dephosphorylated the autophosphorylated EGF receptor and L-phosphotyrosine, but not 32P-Ser-casein, L-phosphoserine or L-phosphothreonine. These data suggest that the cytosolic low-Mr acid phosphatase might play a regulatory role in EGF receptor-dependent transmembrane signalling

Expanding running coupling effects in the hard Pomeron

We study QCD hard processes at scales of order k^2 > Lambda^2 in the limit in which the beta-function coefficient - b is taken to be small, but alphas(k) is kept fixed. The (nonperturbative) Pomeron is exponentially suppressed in this limit, making it possible to define purely perturbative high-energy Green's functions. The hard Pomeron exponent acquires diffusion and running coupling corrections which can be expanded in the b parameter and turn out to be dependent on the effective coupling b alphas^2 Y. We provide a general setup for this b-expansion and we calculate the first few terms both analytically and numerically.Comment: 36 pages, 15 figures, additional references adde

Role of ivabradine in management of stable angina in patients with different clinical profiles

In chronic stable angina, elevated heart rate contributes to the development of symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand and reducing diastolic perfusion time. Accordingly, heart rate reduction is a well-known strategy for improving both symptoms of myocardial ischaemia and quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and selective inhibitor of the I f current, decreases myocardial oxygen consumption while increasing diastolic time, without affecting myocardial contractility or coronary vasomotor tone. Ivabradine is indicated for treatment of stable angina and chronic heart failure (HF). This review examines available evidence regarding the efficacy and safety of ivabradine in stable angina, when used as monotherapy or in combination with beta-blockers, in particular angina subgroups and in patients with stable angina with left ventricular systolic dysfunction (LVSD) or HF. Trials involving more than 45 000 patients receiving treatment with ivabradine have shown that this agent has antianginal and anti-ischaemic effects, regardless of age, sex, severity of angina, revascularisation status or comorbidities. This heart rate-lowering agent might also improve prognosis, reduce hospitalisation rates and improve QOL in angina patients with chronic HF and LVSD

Bloch-Nordsieck Violation in Spontaneously Broken Abelian Theories

We point out that, in a spontaneously broken U(1) gauge theory, inclusive processes, whose primary particles are mass eigenstates that do not coincide with the gauge eigenstates, are not free of infrared logarithms. The charge mixing allowed by symmetry breaking and the ensuing Bloch-Nordsieck violation are here analyzed in a few relevant cases and in particular for processes initiated by longitudinal gauge bosons. Of particular interest is the example of weak hypercharge in the Standard Model where, in addition, left-right mixing effects arise in transversely polarized fermion beams.Comment: 4 pages, 1 figur

NLO BFKL Equation, Running Coupling and Renormalization Scales

I examine the solution of the BFKL equation with NLO corrections relevant for deep inelastic scattering. Particular emphasis is placed on the part played by the running of the coupling. It is shown that the solution factorizes into a part describing the evolution in Q^2, and a constant part describing the input distribution. The latter is infrared dominated, being described by a coupling which grows as x decreases, and thus being contaminated by infrared renormalons. Hence, for this part we agree with previous assertions that predictive power breaks down for small enough x at any Q^2. However, the former is ultraviolet dominated, being described by a coupling which falls like 1/(\ln(Q^2/\Lambda^2) + A(\bar\alpha_s(Q^2)\ln(1/x))^1/2)with decreasing x, and thus is perturbatively calculable at all x. Therefore, although the BFKL equation is unable to predict the input for a structure function for small x, it is able to predict its evolution in Q^2, as we would expect from the factorization theory. The evolution at small x has no true powerlike behaviour due to the fall of the coupling, but does have significant differences from that predicted from a standard NLO in alpha_s treatment. Application of the resummed splitting functions with the appropriate coupling constant to an analysis of data, i.e. a global fit, is very successful.Comment: Tex file, including a modification of Harvmac, 46 pages, 8 figures as .ps files. Correction of typos, updating of references, very minor corrections to text and fig.

Indications of beta-adrenoceptor blockers in Takotsubo syndrome and theoretical reasons to prefer agents with vasodilating activity

Takotsubo syndrome (TTS) is estimated to account for 1–3% of all patients presenting with suspected ST-segment elevation myocardial infarction. A sudden surge in sympathetic nervous system is considered the cause of TTS. Nonetheless, no specific recommendations have been provided regarding β-blocking therapy. Apart from specific contra-indications (severe LV dysfunction, hypotension, bradycardia and corrected QT interval >500 ms), treatment with a β-blocker seems reasonable until full recovery of LV ejection fraction, though evidence is limited to a few animal studies, case reports or observational studies. In this review, we will reappraise the rationale for β-blocker therapy in TTS and speculate on the pathophysiologic basis for preferring non-selective agents with vasodilating activity over β1-selective drugs

BFKL at next-to-leading order

This is a summary of the contributions on the next-to-leading order corrections to the BFKL equation which were presented to the `Small-x and Diffraction' working group at the 1998 Durham Workshop on HERA Physics.Comment: 6 pages, 2 figure

Rapidity-Separation Dependence and the Large Next-to-Leading Corrections to the BFKL Equation

Recent concerns about the very large next-to-leading logarithmic (NLL) corrections to the BFKL equation are addressed by the introduction of a physical rapidity-separation parameter $\Delta$. At the leading logarithm (LL) this parameter enforces the constraint that successive emitted gluons have a minimum separation in rapidity, $y_{i+1}-y_i>\Delta$. The most significant effect is to reduce the BFKL Pomeron intercept from the standard result as $\Delta$ is increased from 0 (standard BFKL). At NLL this $\Delta$-dependence is compensated by a modification of the BFKL kernel, such that the total dependence on $\Delta$ is formally next-to-next-to-leading logarithmic. In this formulation, as long as $\Delta\gtrsim2.2$ (for $\alpha_{s}=0.15$): (i) the NLL BFKL pomeron intercept is stable with respect to variations of $\Delta$, and (ii) the NLL correction is small compared to the LL result. Implications for the applicability of the BFKL resummation to phenomenology are considered.Comment: 16 pages, 3 figures, Late