Locally Self-Adjustive Smoothing for Measurement Noise Reduction with Application to Automated Peak Detection

Smoothing is widely used approach for measurement noise reduction in spectral analysis. However, it suffers from signal distortion caused by peak suppression. A locally self-adjustive smoothing method is developed that retains sharp peaks and less distort signals. The proposed method uses only one parameter that determines global smoothness, while balancing the local smoothness using data itself. Simulation and real experiments in comparison with existing convolution-based smoothing methods indicate both qualitatively and quantitatively improved noise reduction performance in practical scenarios. We also discuss parameter selection and demonstrate an application for the automated smoothing and detection of a given number of peaks from noisy measurement data

Lymph Node Stromal Cell Subsets

The spatiotemporal regulation of immune responses in the lymph node (LN) depends on its sophisticated tissue architecture, consisting of several subcompartments supported by distinct fibroblastic stromal cells (FSCs). However, the intricate details of stromal structures and associated FSC subsets are not fully understood. Using several gene reporter mice, we sought to discover unrecognized stromal structures and FSCs in the LN. The four previously identified FSC subsets in the cortex are clearly distinguished by the expression pattern of reporters including PDGFRb, CCL21-ser, and CXCL12. Herein, we identified a unique FSC subset expressing both CCL21-ser and CXCL12 in the deep cortex periphery (DCP) that is characterized by preferential B cell localization. This subset was clearly different fromCXCL12highLepRhigh FSCs in themedullary cord, which harbors plasma cells. B cell localization in the DCP was controlled chiefly by CCL21-ser and, to a lesser extent, CXCL12. Moreover, the optimal development of the DCP as well as medulla requires B cells. Together, our findings suggest the presence of a unique microenvironment in the cortex-medulla boundary and offer an advanced view of the multi-layered stromal framework constructed by distinct FSC subsets in the LN

Flecainide reduces ventricular arrhythmias via a mechanism that differs from that of β-blockers in catecholaminergic polymorphic ventricular tachycardia

AbstractBackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by episodic ventricular tachycardia induced by adrenergic stress. Although β-blockers are used as first-line therapy, their therapeutic effects are largely incomplete. Flecainide has recently been shown to modify the molecular defects in CPVT. The aim of this study was to investigate the effects of flecainide as an add-on to conventional therapy on exercise-induced ventricular arrhythmia and compare them with those of conventional therapy alone.MethodsThe study included 5 CPVT patients with a mutation in RYR2. They experienced episodic arrhythmic events despite conventional β-blocker therapy and were therefore given flecainide in addition. The effects of the addition of flecainide therapy on ventricular arrhythmia during exercise testing were compared with those of conventional therapy alone.ResultsBoth β-blockers alone and with additional flecainide increased the maximal workload attained at the onset of ventricular arrhythmia; however, only flecainide increased the sinus rate at the onset of ventricular arrhythmias. Furthermore, flecainide increased the exercise capacity by preventing exercise-induced arrhythmias. During a follow-up period of 17±2 months, 1 patient experienced recurrent arrhythmic episodes that were associated with noncompliance. All patients reported improvements in their ability to perform the activities of daily living.ConclusionFlecainide effectively reduced ventricular arrhythmias via a mechanism that differs from that of β-blockers in genotype-positive patients with CPVT. The specific effects of flecainide may be critical in the improvement noted in the patients' ability to perform daily activities

Postoperative supraventricular tachycardia and polymorphic ventricular tachycardia due to a novel SCN5A variant: a case report of a rare comorbidity that is difficult to diagnose.

Background:Loss-of-function mutations of human cardiac sodium channel gene SCN5A induce a wide range of arrhythmic disorders. Mutation carriers with co-existing conditions such as congenital heart diseases and histories of cardiac surgeries, could develop complex arrhythmic events that are difficult to diagnose.Case presentation:A 41-year-old Japanese male with a history of a surgical closure of an ASD presented impairment of consciousness by wide QRS tachycardia. Because the patient\u27s baseline ECG in sinus rhythm showed similar QRS axis with right bundle brunch block morphology, we suspected supraventricular tachycardia (SVT). During hospitalization, the patient developed polymorphic ventricular tachycardia that was induced by bradycardia. In an electrophysiological study, the SVT was identified as right atrial incisional tachycardia circulating around the scar in the right atrium. The genetic analysis revealed a heterozygous SCN5A c.4037-4038 del TC, p. L1346HfsX38 variant. We diagnosed this patient as having progressive cardiac conduction disorder (PCCD) and polymorphic VT caused by the mutation. Incisional tachycardia with wide QRS morphology was a by-standing comorbidity related to the history of cardiac surgery which could miss lead the diagnosis. The patient\u27s SVT was eliminated by radiofrequency catheter ablation. An implantable cardioverter defibrillator (ICD) was implanted for the secondary prevention of polymorphic VT. Cardiac pace-making therapy by the ICD to avoid bradycardia effectively suppressed the patient\u27s arrhythmic events.Conclusions:We treated a patient with a sodium channel gene variant. Co-existing SVT originated by a scar in the right atrium made the diagnosis extremely difficult. A multilateral diagnostic approach using an ECG analysis, an electrophysiological study, and genetic screening enabled effective combination therapy comprised of catheter ablation and an ICD

Inappropriate implantable cardioverter defibrillator shocks—incidence, effect, and implications for driver licensing

PurposePatients with implantable cardioverter defibrillators (ICDs) have an ongoing risk of sudden incapacitation that may cause traffic accidents. However, there are limited data on the magnitude of this risk after inappropriate ICD therapies. We studied the rate of syncope associated with inappropriate ICD therapies to provide a scientific basis for formulating driving restrictions.MethodsInappropriate ICD therapy event data between 1997 and 2014 from 50 Japanese institutions were analyzed retrospectively. The annual risk of harm (RH) to others posed by a driver with an ICD was calculated for private driving habits. We used a commonly employed annual RH to others of 5 in 100,000 (0.005%) as an acceptable risk threshold.ResultsOf the 4089 patients, 772 inappropriate ICD therapies occurred in 417 patients (age 61 ± 15 years, 74% male, and 65% secondary prevention). Patients experiencing inappropriate therapies had a mean number of 1.8 ± 1.5 therapy episodes during a median follow-up period of 3.9 years. No significant differences were found in the age, sex, or number of inappropriate therapies between patients receiving ICDs for primary or secondary prevention. Only three patients (0.7%) experienced syncope associated with inappropriate therapies. The maximum annual RH to others after the first therapy in primary and secondary prevention patients was calculated to be 0.11 in 100,000 and 0.12 in 100,000, respectively.ConclusionsWe found that the annual RH from driving was far below the commonly cited acceptable risk threshold. Our data provide useful information to supplement current recommendations on driving restrictions in ICD patients with private driving habits

A Distinct Subset of Fibroblastic Stromal Cells Constitutes the Cortex-Medulla Boundary Subcompartment of the Lymph Node

The spatiotemporal regulation of immune responses in the lymph node (LN) depends on its sophisticated tissue architecture, consisting of several subcompartments supported by distinct fibroblastic stromal cells (FSCs). However, the intricate details of stromal structures and associated FSC subsets are not fully understood. Using several gene reporter mice, we sought to discover unrecognized stromal structures and FSCs in the LN. The four previously identified FSC subsets in the cortex are clearly distinguished by the expression pattern of reporters including PDGFRβ, CCL21-ser, and CXCL12. Herein, we identified a unique FSC subset expressing both CCL21-ser and CXCL12 in the deep cortex periphery (DCP) that is characterized by preferential B cell localization. This subset was clearly different from CXCL12highLepRhigh FSCs in the medullary cord, which harbors plasma cells. B cell localization in the DCP was controlled chiefly by CCL21-ser and, to a lesser extent, CXCL12. Moreover, the optimal development of the DCP as well as medulla requires B cells. Together, our findings suggest the presence of a unique microenvironment in the cortex-medulla boundary and offer an advanced view of the multi-layered stromal framework constructed by distinct FSC subsets in the LN

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension