Possible role of SCN4A skeletal muscle mutation in apnoea during seizure

SCN4A gene mutations cause a number of neuromuscular phenotypes including myotonia. A subset of infants with myotonia‐causing mutations experience severe life‐threatening episodic laryngospasm with apnea. We have recently identified similar SCN4A mutations in association with sudden infant death syndrome. Laryngospasm has also been proposed as a contributory mechanism to some cases of sudden unexpected death in epilepsy (SUDEP). We report an infant with EEG‐confirmed seizures and recurrent apneas. Whole‐exome sequencing identified a known pathogenic mutation in the SCN4A gene that has been reported in several unrelated families with myotonic disorder. We propose that the SCN4A mutation contributed to the apneas in our case, irrespective of the underlying cause of the epilepsy. We suggest this supports the notion that laryngospasm may contribute to some cases of SUDEP, and implicates a possible shared mechanism between a proportion of sudden infant deaths and sudden unexpected deaths in epilepsy

Pitfalls in genetic testing: the story of missed SCN1A mutations

BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated in epilepsy, are found in the majority of Dravet syndrome (DS) patients, we focused on missed SCN1A mutations. METHODS: We sent out a survey to 16 genetic centers performing SCN1A testing. RESULTS: We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN1A mutation-negative, both due to technical limitations and human errors. CONCLUSION: We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A mutations are an even more frequent cause of DS than already anticipated

Pitfalls in genetic testing: the story of missed SCN1A mutations

Peer reviewe

International nosocomial infection control consortium (INICC) report, data summary of 36 countries, for 2004-2009

The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium (INICC) from January 2004 through December 2009 in 422 intensive care units (ICUs) of 36 countries in Latin America, Asia, Africa, and Europe are reported. During the 6-year study period, using Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infections, we gathered prospective data from 313,008 patients hospitalized in the consortium's ICUs for an aggregate of 2,194,897 ICU bed-days. Despite the fact that the use of devices in the developing countries' ICUs was remarkably similar to that reported in US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs. The overall rate of ventilator-associated pneumonia also was far higher (15.8 vs 3.3 per 1,000 ventilator-days), as was the rate of catheter-associated urinary tract infection (6.3 vs. 3.3 per 1,000 catheter-days). Notably, the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem (47.2% vs 23.0%), Klebsiella pneumoniae isolates to ceftazidime (76.3% vs 27.1%), Escherichia coli isolates to ceftazidime (66.7% vs 8.1%), Staphylococcus aureus isolates to methicillin (84.4% vs 56.8%), were also higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 7.3% (for catheter-associated urinary tract infection) to 15.2% (for ventilator-associated pneumonia). Copyright © 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved

Investigation on series active filter compensated high power grid-connected voltage source inverters with LCL filter

This paper deals with Series Active Filter (SAF) based damping methods for the LCL filters of three-phase, grid connected, low voltage, high power Voltage Source Inverters (VSIs). The inherent resonance problem of LCL filters is damped via passive or active damping methods. Passive damping methods employing damping resistors create significant power losses reducing the overall system's efficiency for high power inverters. Active damping methods, on the other hand, are not applicable due to inverter's limited controller bandwidth. Unlike passive and active damping approaches, the proposed Series Active Filter (SAF) based systems maintain the stability of the inverter while eliminating the resistive power losses. The steady-state and dynamic performances of the SAF compensated VSIs are investigated and viability of them are demonstrated. Two novel methods, one superior than the other in terms of design simplicity are investigated providing efficiency, line current THD and dynamic response results. The developed methods are proven by theory and computer simulations

Series Active Filter Based Resonance Damping of High Power Three-phase, LCL Filtered, Grid Connected Voltage Source Inverters

A series active filter (SAF) based method for the damping of resonant harmonics created by the LCL-filter of the grid connected PWM-VSI is proposed. Oscillations in multi-megawatt rated high power inverters with LCL-filters are damped with resistors which create undesired power losses typically up to 1% of the rated power of the system. The method stated in this paper overcomes the stability/oscillation problem while providing a solution to the resistive power loss. The proposed SAF compensated system performs satisfactorily under rated load conditions and the transition from passive damping to SAF is flawless. Adaptability of the proposed method to dynamic loads is also advantageous as opposed to passive damping methods. Simplified circuit diagrams and schematics are provided through the paper. Mathematical model of the passively damped filter is compared and contrasted with the SAF compensated system. The validity of the proposed method is proven via simulations

A novel high-contrast ratio electrochromic material from spiro[cyclododecane-1,9'-fluorene]bicarbazole

A novel electroactive spirocyclododecylfluorene monomer named 2,7-bis(carbazol-9-yl)-9,9'-spiro[cyclododecane-1,9'-fluorene] (SFC) was synthesized and electrochemically polymerized to give a very stable multi-electrochromic polymer (poly-SFC). Two separate oxidation processes were observed for both SFC monomer and poly-SFC that carries two carbazole units. The polymeric film of poly-SFC was coated onto ITO/glass surface, and it shows different colors (transparent, yellowish green, green, and dark green) upon stepwise oxidations. An electrochromic device based on poly-SFC was assembled in the sandwich cell configuration of ITO/poly-SFC//gel electrolyte//PEDOT/ITO. Poly-SFC exhibits 90% of transparency at neutral state and a high contrast ratio (ÎT = 58% at 800 nm). This device constructed from it represents a response time of about 1 s, high coloration efficiency (1377 cm2 C-1) and retained its performance by 96.4% even after 1000 cycles. Exhibiting high transparency at neutral state, reversible redox behavior, resistance to overoxidation, and especially high contrast ratio at near IR region can make poly-SFC be useful and promising candidate for electrochromic applications despite having a relatively slow response time. © 2010 Wiley Periodicals, Inc

Series active filter based resonance damping of high power three-phase, LCL filtered, grid connected voltage source inverters

A series active filter (SAF) based method for the damping of resonant harmonics created by the LCL-filter of the grid connected PWM-VSI is proposed. Oscillations in multi-megawatt rated high power inverters with LCL-filters are damped with resistors which create undesired power losses typically up to 1% of the rated power of the system. The method stated in this paper overcomes the stability/oscillation problem while providing a solution to the resistive power loss. The proposed SAF compensated system performs satisfactorily under rated load conditions and the transition from passive damping to SAF is flawless. Adaptability of the proposed method to dynamic loads is also advantageous as opposed to passive damping methods. Simplified circuit diagrams and schematics are provided through the paper. Mathematical model of the passively damped filter is compared and contrasted with the SAF compensated system. The validity of the proposed method is proven via simulations