Current Fluctuations of the One Dimensional Symmetric Simple Exclusion Process with Step Initial Condition

For the symmetric simple exclusion process on an infinite line, we calculate exactly the fluctuations of the integrated current $Q_t$ during time $t$ through the origin when, in the initial condition, the sites are occupied with density $\rho_a$ on the negative axis and with density $\rho_b$ on the positive axis. All the cumulants of $Q_t$ grow like $\sqrt{t}$. In the range where $Q_t \sim \sqrt{t}$, the decay $\exp [-Q_t^3/t]$ of the distribution of $Q_t$ is non-Gaussian. Our results are obtained using the Bethe ansatz and several identities recently derived by Tracy and Widom for exclusion processes on the infinite line.Comment: 2 figure

Diagnosis and management of spinal muscular atrophy : Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder due to a defect in the survival motor neuron 1 (SMN1) gene. Its incidence is approximately 1 in 11,000 live births. In 2007, an International Conference on the Standard of Care for SMA published a consensus statement on SMA standard of care that has been widely used throughout the world. Here we report a two-part update of the topics covered in the previous recommendations. In part 1 we present the methods used to achieve these recommendations, and an update on diagnosis, rehabilitation, orthopedic and spinal management; and nutritional, swallowing and gastrointestinal management. Pulmonary management, acute care, other organ involvement, ethical issues, medications, and the impact of new treatments for SMA are discussed in part 2

Structural analysis of metal sites in proteins: non-heme iron sites as a case study

In metalloproteins, the protein environment modulates metal properties to achieve the required goal, which can be protein stabilization or function. The analysis of metal sites at the atomic level of detail provided by protein structures can thus be of benefit in functional and evolutionary studies of proteins. In this work, we propose a structural bioinformatics approach to the study of metalloproteins based on structural templates of metal sites that include the PDB coordinates of protein residues forming the first and the second coordination sphere of the metal. We have applied this approach to non-heme iron sites, which have been analyzed at various levels. Templates of sites located in different protein domains have been compared, showing that similar sites can be found in unrelated proteins as the result of convergent evolution. Templates of sites located in proteins of a large superfamily have been compared, showing possible mechanisms of divergent evolution of proteins to achieve different functions. Furthermore, template comparisons have been used to predict the function of uncharacterized proteins, showing that similarity searches focused on metal sites can be advantageously combined with typical whole-domain comparisons. Structural templates of metal sites, finally, may constitute the basis for a systematic classification of metalloproteins in databases

Effect of Cardiac Resynchronization Therapy in Patients With New York Heart Association Functional Class IV Heart Failure

Cardiac resynchronization therapy (CRT) is considered a class I indication in treatment of patients with New York Heart Association (NYHA) functional class III and IV heart failure. However, only small numbers of patients in large clinical trials have been in NYHA functional class IV. Therefore, little is known about the effects of CRT in this group. Therefore, we evaluated the effects of CRT in patients with NYHA functional class IV heart failure. Of all patients referred for CRT implantation, 61 patients with symptoms according to NYHA functional class IV were included. All patients were evaluated before implantation and at 6-month follow-up for clinical changes according to the clinical composite score and changes in left ventricular (LV) volumes and function. In addition, survival was evaluated during long-term follow-up. At 6-month follow-up, 9 patients (15%) had died and 2 patients (3%) were admitted for worsening heart failure. The remaining 39 patients (64%) showed improvement according to the clinical composite score. Decreases in LV end-systolic volume (from 167 +/- 88 to 147 +/- 93 ml, p = 0.009) and LV end-diastolic volume (from 211 +/- 100 to 199 +/- 113 ml, p = 0.135) were observed, as was a significant increase in LV ejection fraction (from 22 +/- 8% to 28 +/- 9%, p <0.001). During a mean follow-up of 30 +/- 26 months, 36 patients (59%) died, 27 (75%) from worsening heart failure. Respective 1- and 2-year mortality rates were 25% and 38%. In conclusion, CRT decreases LV volumes and improves cardiac function in patients with NYHA functional class IV heart failure. Nevertheless, (heart failure) mortality remains high in these patients. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:1146-1151)Cardiac Dysfunction and Arrhythmia

Noninvasive estimation of left ventricular filling pressures in patients with heart failure after surgical ventricular restoration and restrictive mitral annuloplasty

Objective: Doppler echocardiography, including tissue Doppler imaging, is widely applied to assess diastolic left ventricular function using early transmitral flow velocity combined with mitral annular velocity as a noninvasive estimate of left ventricular filling pressures. However, the accuracy of early transmitral flow velocity/mitral annular velocity in patients with heart failure, particularly after extensive cardiac surgery, is debated. Global diastolic strain rate during isovolumic relaxation obtained with 2-dimensional speckle-tracking analysis was recently proposed as an alternative approach to estimate left ventricular filling pressures. Methods: We analyzed diastolic function in patients with heart failure after surgical ventricular restoration and/or restrictive mitral annuloplasty. Echocardiography, including tissue Doppler imaging and speckle-tracking analysis, was performed to determine early transmitral flow velocity/atrial transmitral flow velocity, isovolumetric relaxation time, deceleration time, early transmitral flow velocity/mean mitral annular velocity, strain rate during isovolumic relaxation, and early transmitral flow velocity/strain rate during isovolumic relaxation. These noninvasive indices were correlated with relaxation time constant Tau, peak rate of pressure decline, and left ventricular end-diastolic pressure obtained in the catheterization room using high-fidelity pressure catheters. Results: Twenty-three patients were analyzed 6 months after restrictive mitral annuloplasty (n = 8), surgical ventricular restoration (n-4), or a combined procedure (n-11). The strongest correlation with invasive indices, in particular left ventricular end-diastolic pressure, was found for strain rate during isovolumic relaxation (r = -0.76, P < .001). Early transmitral flow velocity/mean mitral annular velocity did not correlate significantly with any of the invasive indices. Strain rate during isovolumic relaxation (cutoff value < 0.38 s(-1)) accurately predicted left ventricular end-diastolic pressure of 16 mm Hg or more with 100% sensitivity and 93% specificity. Conclusions: In a group of patients with heart failure who were investigated 6 months after cardiac surgery, early transmitral flow velocity/mean mitral annular velocity correlated poorly with invasively obtained diastolic indexes. Global strain rate during isovolumic relaxation, however, correlated well with left ventricular end-diastolic pressure and peak rate of pressure decline. Our data suggest that global strain rate during isovolumic relaxation is a promising noninvasive index to assess left ventricular filling pressures in patients with heart failure after extensive cardiac surgery, including restrictive mitral annuloplasty and surgical ventricular restoration. (J Thorac Cardiovasc Surg 2010;140:807-15)Cardiolog

Effect of Cardiac Resynchronization Therapy on Cerebral Blood Flow

Decreased cerebral blood flow is frequently observed in patients with heart failure, and this could be the result of impaired cardiac systolic function. Cardiac resynchronization therapy (CRT) improves cardiac function and heart failure symptoms in selected patients. The effects of CRT on cerebral blood flow have not been previously evaluated. In the present study, left ventricular systolic function and cerebral blood flow were assessed in 35 patients with heart failure, before and 6 months after CRT. Additionally, 15 patients with heart failure, who were not candidates for CRT, were included as a control group. The peak systolic velocity, end-diastolic velocity, mean velocity, and pulsatility index ((peak systolic velocity end-diastolic velocity]/mean velocity) were obtained using transcranial Doppler from the right middle cerebral artery from the temporal window in all subjects. Response to CRT was defined as a reduction in the left ventricular end-systolic volume of >= 15%. At 6 months of follow-up, the peak systolic velocity had significantly increased from 83 +/- 20 cm/s to 100 +/- 20 cm/s (p = 0.001), the end-diastolic velocity had increased from 29 +/- 7 cm/s to 37 +/- 8 cm/s (p <0.001), and the mean velocity had increased from 47 +/- 10 cm/s to 58 +/- 11 cm/s (p <0.001) only in the responders to CRT. In contrast, no significant changes in cerebral blood flow were observed in the nonresponders and the controls. In conclusion, CRT induced an increase in cerebral blood flow in patients with heart failure. This increase in cerebral blood flow was related to the improvement in left ventricular systolic function. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:73-77)Cardiac Dysfunction and Arrhythmia

Value of Tissue Doppler Echocardiography in Predicting Response to Cardiac Resynchronization Therapy in Patients With Heart Failure

Several studies have demonstrated a relation between left ventricular (LV) dyssynchrony and response to cardiac resynchronization therapy (CRT). Many methods of determining LV dyssynchrony have been proposed, including a value of 65 ms as assessed by tissue Doppler imaging. The aim of the present validation study was to prospectively test the predictive accuracy of the 65-ms cutoff for LV dyssynchrony in a large cohort of patients with heart failure undergoing CRT. The study included 361 patients who had undergone CRT. The clinical and echocardiographic parameters were assessed at baseline and at 6 months of follow-up. The clinical response was defined as an improvement of New York Heart Association class, and the echocardiographic response was defined as a reduction in LV end-systolic volume of >= 15%. At 6 months of follow-up, 259 patients (72%) had a clinical response and 187 patients (52%) had an echocardiographic response. The patients with a response had more LV dyssynchrony than did those without a response (91 +/- 49 ms vs 50 +/- 44 ms for the clinical response and 101 +/- 46 ms vs 55 +/- 45 ms for the echocardiographic response). On multivariate analysis, LV dyssynchrony remained predictive of the response, independent of other characteristics. In conclusion, LV dyssynchrony of >= 65 ins was an independent predictor of both the clinical and the echocardiographic response in patients with heart failure who underwent CRT in this validation study. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:1153-1158)Cardiac Dysfunction and Arrhythmia

Morbidity and mortality in heart failure patients treated with cardiac resynchronization therapy: influence of pre-implantation characteristics on long-term outcome

Aims Cardiac resynchronization therapy (CRT) improves cardiac function, heart failure symptoms, and prognosis in selected patients. Many baseline characteristics associated with heart failure may influence prognosis after CRT. The objective of this study was to evaluate the effect of several baseline characteristics in relation to long-term prognosis in heart failure patients treated with CRT. Methods and results A total of 716 consecutive heart failure patients treated with CRT were included in an observational registry. All available data, including clinical and echocardiographic measurements, were analysed in relation to two endpoints: all-cause mortality and a combined endpoint of all-cause mortality or major cardiovascular event. Outcome data were collected by chart review, device interrogation, and telephone contact. Mean follow-up was 25 +/- 19 months. During follow-up, 141 patients (20%) died (primary endpoint). Most of these patients (61%) died due to worsening heart failure. A total of 214 patients (30%) reached the secondary endpoint. Larger left ventricular end-systolic volume, less distance covered in the 6 min walking test, poor renal function, more severe heart failure, male gender, presence of atrial fibrillation, no posterolateral left ventricular (LV) lead, and no LV dyssynchrony were associated with poor prognosis after CRT. Conclusions In this large single-centre registry, several baseline clinical and echocardiographic characteristics were associated with prognosis after CRT. Worsening heart failure was the main cause of death in heart failure patients treated with CRT.Cardiac Dysfunction and Arrhythmia