Mechanism of tricuspid regurgitation in paramembranous ventricular septal defect.

PubMed

Hagler, Donald J; Squarcia, Umberto; Cabalka, Allison K; Connolly, Heidi M; O'Leary, Patrick W

2002-04-01

Literature has been limited in regard to the mechanisms of tricuspid regurgitation (TR) in patients with paramembranous (perimembranous) ventricular septal defect (VSD). Most observations have noted tricuspid valve clefts or dysplasia. We describe another mechanism for production of TR in association with paramembranous VSD. In 8 patients, we found significant TR produced by the VSD jet pushing the tricuspid anterior leaflet forward to open the tricuspid valve orifice. In these patients, a moderate paramembranous VSD extended slightly below the septal tricuspid leaflet with only partial obstruction of the VSD jet. All patients had restrictive VSD with low right ventricular pressure. This mechanism to produce TR was best defined by intraoperative transesophageal echocardiography, but current higher resolution imaging should allow correct diagnosis. We believe that when this mechanism for TR is found in association with a moderate VSD, surgical VSD closure is warranted.

Circulating Matrix Metalloproteinase-2 and -9 Enzyme Activities in the Children with Ventricular Septal Defect

PubMed Central

Cheng, Kun-Shan; Liao, Yan-Chiou; Chen, Mu-Yuan; Kuan, Tang-Ching; Hong, Yi-Han; Ko, Li; Hsieh, Wen-Yeh; Wu, Chien-Liang; Chen, Ming-Ren; Lin, Chih-Sheng

2013-01-01

Ventricular septal defect (VSD) is the most common form of congenital heart diseases. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases involved in causal cardiac tissue remodeling. We studied the changes of circulating MMP-2 and MMP-9 activities in the patients with VSD severity and closure. There were 96 children with perimembranous VSD enrolled in this study. We assigned the patients into three groups according to the ratio of VSD diameter/diameter of aortic root (Ao). They were classified as below: Trivial (VSD/Ao ratio ≤ 0.2), Small (0.2 < VSD/Ao ≤ 0.3) and Median (0.3 < VSD/Ao) group. Plasma MMP-2 and MMP-9 activities were assayed by gelatin zymography. There was a significant higher MMP-2 activity in the VSD (Trivial, Small and Median) groups compared with that in Control group. The plasma MMP-9 activity showed a similar trend as the findings in MMP-2 activity. After one year follow-up, a significant difference in the MMP-9 activity was found between VSD spontaneous closure and non-closure groups. In conclusion, a positive trend between the severity of VSD and activities of MMP-2 and MMP-9 was found. Our data imply that MMP-2 and MMP-9 activities may play a role in the pathogenesis of VSD. PMID:23847438

Circulating matrix metalloproteinase-2 and -9 enzyme activities in the children with ventricular septal defect.

PubMed

Cheng, Kun-Shan; Liao, Yan-Chiou; Chen, Mu-Yuan; Kuan, Tang-Ching; Hong, Yi-Han; Ko, Li; Hsieh, Wen-Yeh; Wu, Chien-Liang; Chen, Ming-Ren; Lin, Chih-Sheng

2013-01-01

Ventricular septal defect (VSD) is the most common form of congenital heart diseases. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases involved in causal cardiac tissue remodeling. We studied the changes of circulating MMP-2 and MMP-9 activities in the patients with VSD severity and closure. There were 96 children with perimembranous VSD enrolled in this study. We assigned the patients into three groups according to the ratio of VSD diameter/diameter of aortic root (Ao). They were classified as below: Trivial (VSD/Ao ratio ≤ 0.2), Small (0.2 < VSD/Ao ≤ 0.3) and Median (0.3 < VSD/Ao) group. Plasma MMP-2 and MMP-9 activities were assayed by gelatin zymography. There was a significant higher MMP-2 activity in the VSD (Trivial, Small and Median) groups compared with that in Control group. The plasma MMP-9 activity showed a similar trend as the findings in MMP-2 activity. After one year follow-up, a significant difference in the MMP-9 activity was found between VSD spontaneous closure and non-closure groups. In conclusion, a positive trend between the severity of VSD and activities of MMP-2 and MMP-9 was found. Our data imply that MMP-2 and MMP-9 activities may play a role in the pathogenesis of VSD.

An error-resistant linguistic protocol for air traffic control

NASA Technical Reports Server (NTRS)

Cushing, Steven

1989-01-01

The research results described here are intended to enhance the effectiveness of the DATALINK interface that is scheduled by the Federal Aviation Administration (FAA) to be deployed during the 1990's to improve the safety of various aspects of aviation. While voice has a natural appeal as the preferred means of communication both among humans themselves and between humans and machines as the form of communication that people find most convenient, the complexity and flexibility of natural language are problematic, because of the confusions and misunderstandings that can arise as a result of ambiguity, unclear reference, intonation peculiarities, implicit inference, and presupposition. The DATALINK interface will avoid many of these problems by replacing voice with vision and speech with written instructions. This report describes results achieved to date on an on-going research effort to refine the protocol of the DATALINK system so as to avoid many of the linguistic problems that still remain in the visual mode. In particular, a working prototype DATALINK simulator system has been developed consisting of an unambiguous, context-free grammar and parser, based on the current air-traffic-control language and incorporated into a visual display involving simulated touch-screen buttons and three levels of menu screens. The system is written in the C programming language and runs on the Macintosh II computer. After reviewing work already done on the project, new tasks for further development are described.

The twisted ion-permeation pathway of a resting voltage-sensing domain.

PubMed

Tombola, Francesco; Pathak, Medha M; Gorostiza, Pau; Isacoff, Ehud Y

2007-02-01

Proteins containing voltage-sensing domains (VSDs) translate changes in membrane potential into changes in ion permeability or enzymatic activity. In channels, voltage change triggers a switch in conformation of the VSD, which drives gating in a separate pore domain, or, in channels lacking a pore domain, directly gates an ion pathway within the VSD. Neither mechanism is well understood. In the Shaker potassium channel, mutation of the first arginine residue of the S4 helix to a smaller uncharged residue makes the VSD permeable to ions ('omega current') in the resting conformation ('S4 down'). Here we perform a structure-guided perturbation analysis of the omega conductance to map its VSD permeation pathway. We find that there are four omega pores per channel, which is consistent with one conduction path per VSD. Permeating ions from the extracellular medium enter the VSD at its peripheral junction with the pore domain, and then plunge into the core of the VSD in a curved conduction pathway. Our results provide a model of the resting conformation of the VSD.

Genome-wide copy number variant analysis for congenital ventricular septal defects in Chinese Han population.

PubMed

An, Yu; Duan, Wenyuan; Huang, Guoying; Chen, Xiaoli; Li, Li; Nie, Chenxia; Hou, Jia; Gui, Yonghao; Wu, Yiming; Zhang, Feng; Shen, Yiping; Wu, Bailin; Wang, Hongyan

2016-01-08

Ventricular septal defects (VSDs) constitute the most prevalent congenital heart disease (CHD), occurs either in isolation (isolated VSD) or in combination with other cardiac defects (complex VSD). Copy number variation (CNV) has been highlighted as a possible contributing factor to the etiology of many congenital diseases. However, little is known concerning the involvement of CNVs in either isolated or complex VSDs. We analyzed 154 unrelated Chinese individuals with VSD by chromosomal microarray analysis. The subjects were recruited from four hospitals across China. Each case underwent clinical assessment to define the type of VSD, either isolated or complex VSD. CNVs detected were categorized into syndrom related CNVs, recurrent CNVs and rare CNVs. Genes encompassed by the CNVs were analyzed using enrichment and pathway analysis. Among 154 probands, we identified 29 rare CNVs in 26 VSD patients (16.9 %, 26/154) and 8 syndrome-related CNVs in 8 VSD patients (5.2 %, 8/154). 12 of the detected 29 rare CNVs (41.3 %) were recurrently reported in DECIPHER or ISCA database as associated with either VSD or general heart disease. Fifteen genes (5 %, 15/285) within CNVs were associated with a broad spectrum of complicated CHD. Among these15 genes, 7 genes were in "abnormal interventricular septum morphology" derived from the MGI (mouse genome informatics) database, and nine genes were associated with cardiovascular system development (GO:0072538).We also found that these VSD-related candidate genes are enriched in chromatin binding and transcription regulation, which are the biological processes underlying heart development. Our study demonstrates the potential clinical diagnostic utility of genomic imbalance profiling in VSD patients. Additionally, gene enrichment and pathway analysis helped us to implicate VSD related candidate genes.

Characterization of circulating microRNA expression in patients with a ventricular septal defect.

PubMed

Li, Dong; Ji, Long; Liu, Lianbo; Liu, Yizhi; Hou, Haifeng; Yu, Kunkun; Sun, Qiang; Zhao, Zhongtang

2014-01-01

Ventricular septal defect (VSD), one of the most common types of congenital heart disease (CHD), results from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in development of CHD. This study was to characterize the expression of miRNAs that might be involved in the development or reflect the consequences of VSD. MiRNA microarray analysis and reverse transcription-polymerase chain reaction (RT-PCR) were employed to determine the miRNA expression profile from 3 patients with VSD and 3 VSD-free controls. 3 target gene databases were employed to predict the target genes of differentially expressed miRNAs. miRNAs that were generally consensus across the three databases were selected and then independently validated using real time PCR in plasma samples from 20 VSD patients and 15 VSD-free controls. Target genes of validated 8 miRNAs were predicted using bioinformatic methods. 36 differentially expressed miRNAs were found in the patients with VSD and the VSD-free controls. Compared with VSD-free controls, expression of 15 miRNAs were up-regulated and 21 miRNAs were downregulated in the VSD group. 15 miRNAs were selected based on database analysis results and expression levels of 8 miRNAs were validated. The results of the real time PCR were consistent with those of the microarray analysis. Gene ontology analysis indicated that the top target genes were mainly related to cardiac right ventricle morphogenesis. NOTCH1, HAND1, ZFPM2, and GATA3 were predicted as targets of hsa-let-7e-5p, hsa-miR-222-3p and hsa-miR-433. We report for the first time the circulating miRNA profile for patients with VSD and showed that 7 miRNAs were downregulated and 1 upregulated when matched to VSD-free controls. Analysis revealed target genes involved in cardiac development were probably regulated by these miRNAs.

Simultaneous transcatheter treatment of perimembranous ventricular septal defect and other congenital cardiopathies.

PubMed

Xu, Xu-Dong; Bai, Yuan; Chen, Xiao-Li; Liu, Su-Xuan; Zhao, Xian-Xian; Qin, Yong-Wen

2014-12-01

To assess the efficacy and safety of simultaneous transcatheter corrections of perimembranous ventricular septal defect (VSD) and other congenital cardiopathies. From 2004 to 2012, 56 patients (25 male, 31 female), aged 14.2±10.1, with compound congenital cardiovascular abnormalities underwent simultaneous transcatheter interventional procedure. Of the 56 patients, 32 had VSD and atrial septal defects (ASD); 17 had VSD and patent ductus arteriosus (PDA); and seven had VSD and pulmonary valve stenosis (PS). Percutaneous balloon pulmonary valvuloplasty (PBPV) was performed before the closure of VSD, PDA, or ASD. The combined transcatheter interventional procedure was successfully performed in all patients. Among these, two occluders were implanted in each of 49 patients, seven patients with VSD combined with PS underwent successfully balloon valvuloplasty and VSD closure. The size of VSD, ASD and PDA detected by TTE was 4.8±1.7 mm, 9.0±5.0 mm and 4.5±2.5 mm, respectively. The occluder diameter of VSD, ASD and PDA was 7.6±2.2 mm, 14.3±6.2 mm and 7.9±3.2 mm, respectively. The peak-to-peak transpulmonary gradient decreased from 60.4±19.7 mmHg to 15.0±5.0 mmHg (p<0.001) in seven patients with VSD combined with PS. One patient with VSD and ASD had a permanent pacemaker implanted because of third-degree atrioventricular block two months after the procedure. There were not serious adverse events in relation to the combined procedures during the 23.8±20.7 months of follow-up in other 55 patients. The simultaneous treatment of VSD and other congenital cardiopathies using transcatheter-based procedures is safe and effective, which can provide satisfactory results. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Transcatheter closure of post-operative residual ventricular septal defect using a patent ductus arteriosus closure device in an adult: a case report.

PubMed

Djer, Mulyadi M; Idris, Nikmah S; Alwi, Idrus; Wijaya, Ika P

2014-07-01

Transcatheter closure of perimembranous and muscular ventricular septal defect (VSD) has been performed widely and it has more advantages compare to surgery. However, transcatheter closure of residual VSD post operation of complex congenital heart disease is still challenging because of the complexity of anatomy and concern about device stability, so the operator should meticulously choose the most appropriate technique and device. We would like to report a case of transcatheter closure of residual VSD post Rastelli operation in a patient with double outlet right ventricle (DORV), sub-aortic VSD, severe infundibulum pulmonary stenosis (PS) and single coronary artery. The patient had undergone operations for four times, but he still had intractable heart failure that did not response to medications. On the first attempt. we closed the VSD using a VSD occluder, unfortunately the device embolized into the descending aorta, but fortunately we was able to snare it out. Then we decided to close the VSD using a patent ductus arteriosus (PDA occluder). On transesophageal echocardiography (TEE) and angiography evaluation, the device position was stable. Post transcatheter VSD closure, the patient clinical condition improved significantly and he could finally be discharged after a long post-surgery hospitalization. Based on this experience we concluded that the transcatheter closure of residual VSD in complex CHD using PDA occluder could be an effective alternative treatment.

Neonatal factors among subjects diagnosed with a pervasive developmental disorder in the US.

PubMed

Geier, David; Kern, Janet; Geier, Mark

2018-07-01

Contradictory studies suggest that some neonatal factors may be associated with a pervasive developmental disorder (PDD) diagnosis, but limited data is available from longitudinal, prospective medical record assessments. The present hypothesis-testing longitudinal, case-control study evaluated birth characteristics among cases diagnosed with a PDD in comparison to controls by examining prospectively collected automated medical records within the Vaccine Safety Datalink (VSD) database. Cases were Health Maintenance Organization (HMO)-enrolled from birth until diagnosed with International Classification of Disease, 9th revision (ICD-9) PDD (299.xx) and controls were HMO-enrolled from birth for at least 4.75 years without a PDD diagnosis. The birth characteristics examined included: gender, gestational age in weeks at birth, mean birth weight in grams, Appearance-Pulse-Grimace-Activity-Respiration (APGAR) scores at 1 minute and 5 minutes, and maternal age in years at birth. Cases had a significantly increased male/female ratio relative to controls. By contrast, mean gestational age at birth, mean birth weight, mean maternal age at birth, and mean APGAR scores at 1 minute and 5 minutes were not statistically different among cases compared to controls. This study indicates that cases diagnosed with a PDD as compared to controls do not have significant differences in neonatal factors.

Unusual mechanism of tricuspid regurgitation in ventricular septal defect.

PubMed

Desai, Ravi V; Seghatol-Eslami, Frank; Nabavizadeh, Fatemeh; Lloyd, Steven G

2011-02-01

A 37-year-old woman was diagnosed to have a small ventricular septal defect (VSD) with high velocity tricuspid regurgitation (TR) that was attributed to atrio-VSD (Gerbode). Cardiac MR revealed a small subaortic VSD in the membranous portion of the interventricular septum. The atrioventricular portion was intact. Cardiac MR clearly showed flow jet through the VSD, impinging on the anterior tricuspid leaflet during systole, and bouncing back into the right atrium as TR. This ricochet mechanism of TR in VSD may be misinterpreted as Gerbode defect or as evidence of pulmonary hypertension. © 2011, Wiley Periodicals, Inc.

Modelling study of soil C, N and pH response to air pollution and climate change using European LTER site observations.

PubMed

Holmberg, Maria; Aherne, Julian; Austnes, Kari; Beloica, Jelena; De Marco, Alessandra; Dirnböck, Thomas; Fornasier, Maria Francesca; Goergen, Klaus; Futter, Martyn; Lindroos, Antti-Jussi; Krám, Pavel; Neirynck, Johan; Nieminen, Tiina Maileena; Pecka, Tomasz; Posch, Maximilian; Pröll, Gisela; Rowe, Ed C; Scheuschner, Thomas; Schlutow, Angela; Valinia, Salar; Forsius, Martin

2018-05-31

Current climate warming is expected to continue in coming decades, whereas high N deposition may stabilize, in contrast to the clear decrease in S deposition. These pressures have distinctive regional patterns and their resulting impact on soil conditions is modified by local site characteristics. We have applied the VSD+ soil dynamic model to study impacts of deposition and climate change on soil properties, using MetHyd and GrowUp as pre-processors to provide input to VSD+. The single-layer soil model VSD+ accounts for processes of organic C and N turnover, as well as charge and mass balances of elements, cation exchange and base cation weathering. We calibrated VSD+ at 26 ecosystem study sites throughout Europe using observed conditions, and simulated key soil properties: soil solution pH (pH), soil base saturation (BS) and soil organic carbon and nitrogen ratio (C:N) under projected deposition of N and S, and climate warming until 2100. The sites are forested, located in the Mediterranean, forested alpine, Atlantic, continental and boreal regions. They represent the long-term ecological research (LTER) Europe network, including sites of the ICP Forests and ICP Integrated Monitoring (IM) programmes under the UNECE Convention on Long-range Transboundary Air Pollution (LRTAP), providing high quality long-term data on ecosystem response. Simulated future soil conditions improved under projected decrease in deposition and current climate conditions: higher pH, BS and C:N at 21, 16 and 12 of the sites, respectively. When climate change was included in the scenario analysis, the variability of the results increased. Climate warming resulted in higher simulated pH in most cases, and higher BS and C:N in roughly half of the cases. Especially the increase in C:N was more marked with climate warming. The study illustrates the value of LTER sites for applying models to predict soil responses to multiple environmental changes. Copyright © 2017 Elsevier B.V. All rights reserved.

[Value of a novel categorization of congenital double-outlet right ventricle on guiding the choice of surgical approaches].

PubMed

Pang, Kunjing; Meng, Hong; Wang, Hao; Hu, Shengshou; Hua, Zhongdong; Pan, Xiangbin; Li, Shoujun

2015-11-01

To explore the feasibility and value of a new categorization of double outlet right ventricular (DORV) on guiding the optimal choices of surgical approaches. Five hundred and twenty one DORV patients diagnosed by echocardiography, angiocardiography and CT at Fuwai Hospital from May 2003 to September 2014 were enrolled in this retrospective study. Congenital DORV was categorized according to three basic factors as follows: the positional relationships of great arteries (normal relation or abnormal relation), the relationships of the ventricular septal defect (VSD) to the great arteries (committed VSD or remote VSD), the presence or absence of pulmonary outflow tract obstruction (POTO). Eight types of DORV were established: type I (normal relation, committed VSD, without POTO), type II (normal relation, committed VSD, POTO), type III (normal relation, remote VSD, without POTO), type IV (normal relation, remote VSD, POTO), type V (abnormal relation, committed VSD, without POTO), type VI (abnormal relation, committed VSD, POTO), type VII (abnormal relation, remote VSD, without POTO), type VIII (abnormal relation, remote VSD, POTO). Feasibility of this classification and the value of this classification on guiding the choice of surgical approaches were analyzed. Among the five hundred and twenty one patients, there were 90 patients (17.3%) with type I DORV, 94 patients (18.0%) with type II, 33 patients (6.3%) with type III, 34 patients (6.5%) with type IV, 64 patients (12.3%) with type V, 61 patients (11.7%) with type VI, 33 patients (6.3%) with type VII, 112 patients (21.5%) with type VIII. Thus, all patients could be typed by this classification method. The echocardiography diagnosis was consistent with the intra-operative and or cardiac catheterization/CT findings. Excluding the contraindications of bi-ventricular repair, different surgical approaches were performed in every subtype of DORV according the classification, which indicated that this novel categorization could accurately guide the clinic managements. This novel DORV categorization can accurately diagnose DORV lesions, and guide the clinic therapy choice.

NMR investigation of the isolated second voltage-sensing domain of human Nav1.4 channel.

PubMed

Paramonov, A S; Lyukmanova, E N; Myshkin, M Yu; Shulepko, M A; Kulbatskii, D S; Petrosian, N S; Chugunov, A O; Dolgikh, D A; Kirpichnikov, M P; Arseniev, A S; Shenkarev, Z O

2017-03-01

Voltage-gated Na + channels are essential for the functioning of cardiovascular, muscular, and nervous systems. The α-subunit of eukaryotic Na + channel consists of ~2000 amino acid residues and encloses 24 transmembrane (TM) helices, which form five membrane domains: four voltage-sensing (VSD) and one pore domain. The structural complexity significantly impedes recombinant production and structural studies of full-sized Na + channels. Modular organization of voltage-gated channels gives an idea for studying of the isolated second VSD of human skeletal muscle Nav1.4 channel (VSD-II). Several variants of VSD-II (~150a.a., four TM helices) with different N- and C-termini were produced by cell-free expression. Screening of membrane mimetics revealed low stability of VSD-II samples in media containing phospholipids (bicelles, nanodiscs) associated with the aggregation of electrically neutral domain molecules. The almost complete resonance assignment of 13 C, 15 N-labeled VSD-II was obtained in LPPG micelles. The secondary structure of VSD-II showed similarity with the structures of bacterial Na + channels. The fragment of S4 TM helix between the first and second conserved Arg residues probably adopts 3 10 -helical conformation. Water accessibility of S3 helix, observed by the Mn 2+ titration, pointed to the formation of water-filled crevices in the micelle embedded VSD-II. 15 N relaxation data revealed characteristic pattern of μs-ms time scale motions in the VSD-II regions sharing expected interhelical contacts. VSD-II demonstrated enhanced mobility at ps-ns time scale as compared to isolated VSDs of K + channels. These results validate structural studies of isolated VSDs of Na + channels and show possible pitfalls in application of this 'divide and conquer' approach. Copyright © 2017 Elsevier B.V. All rights reserved.

What values in design? The challenge of incorporating moral values into design.

PubMed

Manders-Huits, Noëmi

2011-06-01

Recently, there is increased attention to the integration of moral values into the conception, design, and development of emerging IT. The most reviewed approach for this purpose in ethics and technology so far is Value-Sensitive Design (VSD). This article considers VSD as the prime candidate for implementing normative considerations into design. Its methodology is considered from a conceptual, analytical, normative perspective. The focus here is on the suitability of VSD for integrating moral values into the design of technologies in a way that joins in with an analytical perspective on ethics of technology. Despite its promising character, it turns out that VSD falls short in several respects: (1) VSD does not have a clear methodology for identifying stakeholders, (2) the integration of empirical methods with conceptual research within the methodology of VSD is obscure, (3) VSD runs the risk of committing the naturalistic fallacy when using empirical knowledge for implementing values in design, (4) the concept of values, as well as their realization, is left undetermined and (5) VSD lacks a complimentary or explicit ethical theory for dealing with value trade-offs. For the normative evaluation of a technology, I claim that an explicit and justified ethical starting point or principle is required. Moreover, explicit attention should be given to the value aims and assumptions of a particular design. The criteria of adequacy for such an approach or methodology follow from the evaluation of VSD as the prime candidate for implementing moral values in design.

An investigation of air transportation technology at the Massachusetts Institute of Technology, 1992-1993

NASA Technical Reports Server (NTRS)

Simpson, Robert W.

1994-01-01

An investigation of air transportation technology at MIT during 1992 - 1993 is presented. One completed project and two continuing research activities are under the sponsorship of the FAA/NASA Joint University Program. The completed project was on tracking aircraft around a turn with wind effects. Active research projects are on ASLOTS - an interactive adaptive system of automated approach spacing of aircraft and alerting in automated and datalink capable cockpits.

Expression, purification, and reconstitution of the voltage-sensing domain from Ci-VSP.

PubMed

Li, Qufei; Jogini, Vishwanath; Wanderling, Sherry; Cortes, D Marien; Perozo, Eduardo

2012-10-16

The voltage-sensing domain (VSD) is the common scaffold responsible for the functional behavior of voltage-gated ion channels, voltage sensitive enzymes, and proton channels. Because of the position of the voltage dependence of the available VSD structures, at present, they all represent the activated state of the sensor. Yet in the absence of a consensus resting state structure, the mechanistic details of voltage sensing remain controversial. The voltage dependence of the VSD from Ci-VSP (Ci-VSD) is dramatically right shifted, so that at 0 mV it presumably populates the putative resting state. Appropriate biochemical methods are an essential prerequisite for generating sufficient amounts of Ci-VSD protein for high-resolution structural studies. Here, we present a simple and robust protocol for the expression of eukaryotic Ci-VSD in Escherichia coli at milligram levels. The protein is pure, homogeneous, monodisperse, and well-folded after solubilization in Anzergent 3-14 at the analyzed concentration (~0.3 mg/mL). Ci-VSD can be reconstituted into liposomes of various compositions, and initial site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopic measurements indicate its first transmembrane segment folds into an α-helix, in agreement with the homologous region of other VSDs. On the basis of our results and enhanced relaxation EPR spectroscopy measurement, Ci-VSD reconstitutes essentially randomly in proteoliposomes, precluding straightforward application of transmembrane voltages in combination with spectroscopic methods. Nevertheless, these results represent an initial step that makes the resting state of a VSD accessible to a variety of biophysical and structural approaches, including X-ray crystallography, spectroscopic methods, and electrophysiology in lipid bilayers.

Expression, Purification and Reconstitution of the Voltage Sensing Domain from Ci-VSP

PubMed Central

Li, Qufei; Jogini, Vishwanath; Wanderling, Sherry; Cortes, D. Marien; Perozo, Eduardo

2013-01-01

The voltage-sensing domain (VSD) is the common scaffold responsible for the functional behavior of voltage gated ion channels, voltage sensitive enzymes and proton channels. Because of the position of the voltage dependence of the available VSD structures, at present, they all represent the activated state of the sensor. Yet, in the absence of a consensus resting state structure, the mechanistic details of voltage sensing remain controversial. The voltage dependence of the VSD from Ci-VSP (Ci-VSD) is dramatically right shifted, so that at 0 mV It presumably populates the putative resting state. Appropriate biochemical methods are an essential prerequisite to generate sufficient amounts of Ci-VSD protein for high-resolution structural studies. Here, we present a simple and robust protocol for the Escherichia coli expression of eukaryotic Ci-VSD at milligram levels. The protein is pure, homogeneous, mono-disperse and well folded after solubilization in Anzergent 3-14 at the analyzed concentration (~ 0.3 mg/mL). Ci-VSD can be reconstituted into liposomes of various compositions and initial site-directed spin labeling and EPR spectroscopic measurements indicate its first transmembrane segment folds into an α-helix, in agreement to the homologous region of other VSDs. Based on current results and enhanced relaxation EPR spectroscopy measurement, Ci-VSD reconstitutes essentially randomly in proteo-liposomes, precluding straightforward application of transmembrane voltages in combination with spectroscopic methods. Nevertheless, the present results represent an initial step that makes the resting state of a VSD accessible to a variety of biophysical and structural approaches, including X-ray crystallography, spectroscopic methods and electrophysiology in lipid bilayers. PMID:22989304

Experimental Evaluation of an Integrated Datalink and Automation-Based Strategic Trajectory Concept

NASA Technical Reports Server (NTRS)

Mueller, Eric

2007-01-01

This paper presents research on the interoperability of trajectory-based automation concepts and technologies with modern Flight Management Systems and datalink communication available on many of today s commercial aircraft. A tight integration of trajectory-based ground automation systems with the aircraft Flight Management System through datalink will enable mid-term and far-term benefits from trajectory-based automation methods. A two-way datalink connection between the trajectory-based automation resident in the Center/TRACON Automation System and the Future Air Navigation System-1 integrated FMS/datalink in NASA Ames B747-400 Level D simulator has been established and extensive simulation of the use of datalink messages to generate strategic trajectories completed. A strategic trajectory is defined as an aircraft deviation needed to solve a conflict or honor a route request and then merge the aircraft back to its nominal preferred trajectory using a single continuous trajectory clearance. Engineers on the ground side of the datalink generated lateral and vertical trajectory clearances and transmitted them to the Flight Management System of the 747; the airborne automation then flew the new trajectory without human intervention, requiring the flight crew only to review and to accept the trajectory. This simulation established the protocols needed for a significant majority of the trajectory change types required to solve a traffic conflict or deviate around weather. This demonstration provides a basis for understanding the requirements for integration of trajectory-based automation with current Flight Management Systems and datalink to support future National Airspace System operations.

Model-Based Method for Terrain-Following Display Design

DTIC Science & Technology

1989-06-15

data into a more compact set of model parameters. These model parameters provide insights into the interpretation of the experimental results as well...2.8 presents the VSD display, and is taken from figure 1.95 of the B-IB Flight Manual , NA-77-400. There are two primary elements in the VSD: 1) the...baseline VSD based on figures such as these from the B-lB Flight Manual , a video tape of an operating VSD in the engineering - 21 - research simulator, and

Relative transmembrane segment rearrangements during BK channel activation resolved by structurally assigned fluorophore–quencher pairing

PubMed Central

Pantazis, Antonios

2012-01-01

Voltage-activated proteins can sense, and respond to, changes in the electric field pervading the cell membrane by virtue of a transmembrane helix bundle, the voltage-sensing domain (VSD). Canonical VSDs consist of four transmembrane helices (S1–S4) of which S4 is considered a principal component because it possesses charged residues immersed in the electric field. Membrane depolarization compels the charges, and by extension S4, to rearrange with respect to the field. The VSD of large-conductance voltage- and Ca-activated K+ (BK) channels exhibits two salient inconsistencies from the canonical VSD model: (1) the BK channel VSD possesses an additional nonconserved transmembrane helix (S0); and (2) it exhibits a “decentralized” distribution of voltage-sensing charges, in helices S2 and S3, in addition to S4. Considering these unique features, the voltage-dependent rearrangements of the BK VSD could differ significantly from the standard model of VSD operation. To understand the mode of operation of this unique VSD, we have optically tracked the relative motions of the BK VSD transmembrane helices during activation, by manipulating the quenching environment of site-directed fluorescent labels with native and introduced Trp residues. Having previously reported that S0 and S4 diverge during activation, in this work we demonstrate that S4 also diverges from S1 and S2, whereas S2, compelled by its voltage-sensing charged residues, moves closer to S1. This information contributes spatial constraints for understanding the BK channel voltage-sensing process, revealing the structural rearrangements in a non-canonical VSD. PMID:22802360

Electro-chemical coupling in the voltage-dependent phosphatase Ci-VSP

PubMed Central

Kohout, Susy C.; Bell, Sarah C.; Liu, Lijun; Xu, Qiang; Minor, Daniel L.; Isacoff, Ehud Y.

2010-01-01

In the voltage sensing phosphatase, Ci-VSP, a voltage sensing domain (VSD) controls a lipid phosphatase domain (PD). The mechanism by which the domains are allosterically coupled is not well understood. Using an in vivo assay, we find that the inter-domain linker that connects the VSD to the PD is essential for coupling the full-length protein. Biochemical assays show that the linker is also needed for activity in the isolated PD. We identify a late step of VSD motion in the full-length protein that depends on the linker. Strikingly, this VSD motion is found to require PI(4,5)P2, a substrate of Ci-VSP. These results suggest that the voltage-driven motion of the VSD turns the enzyme on by rearranging the linker into an activated conformation, and that this activated conformation is stabilized by PI(4,5)P2. We propose that Ci-VSP activity is self-limited because its decrease of PI(4,5)P2 levels decouples the VSD from the enzyme. PMID:20364128

Effectiveness of several dosage formula of oil and nano emulsion of citronella against vascular streak dieback (VSD) disease on cocoa

NASA Astrophysics Data System (ADS)

Noveriza, R.; Trisno, J.; Rahma, H.; Yuliani, S.; Reflin; Martinius

2018-02-01

The disease of Vascular streak dieback (VSD) is a deadly disease of cocoa plants, because it attacks the vascular tissue of cocoa at growing point of the plant. In West Sumatra the disease was first reported in 2015 with an incidence of disease range 58.82% - 100% and an intensity of disease range 24.29% - 44.7%. The purpose of this study was to examine the effectiveness of dosage application of oil formula and nano emulsion of citronella formula against Vascular streak dieback (VSD) disease on cocoa plants in West Sumatra (in Padang Pariaman District and Limapuluh Kota District). The results showed that the percentage of VSD disease attacks in both testing sites was 100%. The oil and nano emulsion of citronella formulas can reduce the intensity of VSD disease on cocoa plants in West Sumatra, particularly in Padang Pariaman District and Limapuluh Kota District. The reduction of VSD intensity in Padang Pariaman district ranged from 8.32 to 21.13%; while in Limapuluh Kota district ranged from 4.33 to 11.80%. The nano emulsion of citronella formulation is effective to suppress the intensity of VSD disease on cocoa plants at doses 0.1% (≥ 30% of effectiveness level).

Improved vacuum sealing drainage for treatment of surgical site infection following posterior spinal internal fixation

PubMed Central

Zhang, Hengyan; Li, Qiyi

2018-01-01

Abstract Rationale: Surgical site infection (SSI) following spine surgeries involving internal fixation often require removing the instrument; however, this can cause spinal instability. Previous reports have demonstrated the usefulness of vacuum sealing drainage (VSD) therapy, but the cases require wound opening, aseptic condition to replace the VSD device, and a secondary operation to close the wound. Thus, to improve the VSD treatment and develop a maneuverable procedure, make sense in spine surgery. Patients concerns: A 59-year-old male patient with a T12 vertebral fracture was affected by SSIs after spinal osteotomy with internal fixation. Diagnoses: The patient complained of wound exudation and had a fever 3 weeks after posterior spinal surgery. Initial serum investigations showed elevated white blood cell count and bacterial cultures of wound exudate were positive for Enterococcus faecalis. Therefore, SSI is confirmed. Interventions: The infection was not controlled after 2 debridements, so the patient was treated with VSD treatment. The VSD foam dressings containing a drainage tube were placed into the wound from the exudation site of the wound until they contacted the internal fixation devices. After covering external fixation devices, continuous drainage was performed for 24 h. The VSD device was replaced every 4 to 5 days until the wound effusion stopped. All of the operations were performed at the bedside without complex manipulation or secondary closure under harsh aseptic condition. Outcomes: Wound exudation decreased remarkably and the infection was controlled 2 weeks after the application of VSD treatment. After 5 weeks, inflammatory indicators all decreased to normal levels and the exudate of the wound had stopped. The VSD treatment was then terminated and the drainage site of the wound was sutured. After 7 weeks, complete wound healing was achieved and no infection recurred during the 6-month follow-up. Lessons: VSD could be a reliable treatment for SSIs that require preservation of internal fixation. Complete opening of the wound during the VSD treatment and secondary wound closure surgery were avoided. PMID:29443786

Evaluating efficiency and statistical power of self-controlled case series and self-controlled risk interval designs in vaccine safety.

PubMed

Li, Rongxia; Stewart, Brock; Weintraub, Eric

2016-01-01

The self-controlled case series (SCCS) and self-controlled risk interval (SCRI) designs have recently become widely used in the field of post-licensure vaccine safety monitoring to detect potential elevated risks of adverse events following vaccinations. The SCRI design can be viewed as a subset of the SCCS method in that a reduced comparison time window is used for the analysis. Compared to the SCCS method, the SCRI design has less statistical power due to fewer events occurring in the shorter control interval. In this study, we derived the asymptotic relative efficiency (ARE) between these two methods to quantify this loss in power in the SCRI design. The equation is formulated as [Formula: see text] (a: control window-length ratio between SCRI and SCCS designs; b: ratio of risk window length and control window length in the SCCS design; and [Formula: see text]: relative risk of exposed window to control window). According to this equation, the relative efficiency declines as the ratio of control-period length between SCRI and SCCS methods decreases, or with an increase in the relative risk [Formula: see text]. We provide an example utilizing data from the Vaccine Safety Datalink (VSD) to study the potential elevated risk of febrile seizure following seasonal influenza vaccine in the 2010-2011 season.

[A case report of a ventricular septal defect with congenital portosystemic venous shunt].

PubMed

Yoshino, Hiroomi; Kayashima, Kenji; Yamamoto, Katsumi; Okada, Hisano; Kataoka, Kazunori; Kinoshita, Yuki; Ikezaki, Akira

2010-11-01

A three-month-old baby boy was scheduled for a ventricular septal defect (VSD) repair. The patient was complicated with pulmonary hypertension (PH) and congenital portosystemic venous shunt (CPSVS). Because it was unclear whether the CPSVS was the main cause of the PH or not, the PH was treated with ordinary methods for the management of anesthesia for VSD patients with PH. He underwent the repair of the VSD, and his postoperative course was uneventful. The mechanism of PH in patients with CPSVS is different from that in those with VSD. We speculated that his pulmonary arteries were not affected with the CPSVS, because no PH was observed after the repair of VSD. Fresh frozen plasma was effective for hemostasis during weaning from cardiopulmonary bypass, because he could not produce enough coagulation factors.

[Vacuum sealing drainage for infection wound in earthquake].

PubMed

Liao, Dengbin; Ning, Ning; Liu, Xiaoyan; Gan, Chunlan

2009-10-01

To investigate the effect of vacuum sealing drainage (VSD) technology on prevention and treatment of infection wound and to repair the infectious fracture wound in earthquake. Twenty-two patients with limb fractures and open infection wound received VSD from May 12, 2008 to June 19, 2008 in West China Hospital of Sichuan University. Before the VSD, we debrided all wounds and gave effective systemic antibiotics. A -18 ~ -14 kPa pressure was exerted to the wound, and the VSD was used for 8-10 days. We took a germiculture regularly. The capacity, color, and nature of negative pressure drainage, the regression of limb swelling, and systemic inflammatory responses were observed. There was no active bleeding wound or transparent film off in all patients. Three patients had drainage clogging, and were kept flowing freely using the sterile saline pipe to remove the blockage of necrotic tissues. During the VSD, granulation tissues grew well in the 13 patients with bone exposure of the wounded. Two patients whose symptom of inflammatory was not obviously eased had another debridement to completely remove the necrosis, and the symptom was relieved. After 3-5 days of VSD, swelling and fever in the other 20 patients significantly subsided. VSD can alleviate the wound inflammation, facilitate the growth of the fresh granulation tissue from the surrounding to the center, and reduce the flap transfer area for the Stage II coverage of the exposed bone.

MicroRNA expression, target genes, and signaling pathways in infants with a ventricular septal defect.

PubMed

Chai, Hui; Yan, Zhaoyuan; Huang, Ke; Jiang, Yuanqing; Zhang, Lin

2018-02-01

This study aimed to systematically investigate the relationship between miRNA expression and the occurrence of ventricular septal defect (VSD), and characterize the miRNA target genes and pathways that can lead to VSD. The miRNAs that were differentially expressed in blood samples from VSD and normal infants were screened and validated by implementing miRNA microarrays and qRT-PCR. The target genes regulated by differentially expressed miRNAs were predicted using three target gene databases. The functions and signaling pathways of the target genes were enriched using the GO database and KEGG database, respectively. The transcription and protein expression of specific target genes in critical pathways were compared in the VSD and normal control groups using qRT-PCR and western blotting, respectively. Compared with the normal control group, the VSD group had 22 differentially expressed miRNAs; 19 were downregulated and three were upregulated. The 10,677 predicted target genes participated in many biological functions related to cardiac development and morphogenesis. Four target genes (mGLUR, Gq, PLC, and PKC) were involved in the PKC pathway and four (ECM, FAK, PI3 K, and PDK1) were involved in the PI3 K-Akt pathway. The transcription and protein expression of these eight target genes were significantly upregulated in the VSD group. The 22 miRNAs that were dysregulated in the VSD group were mainly downregulated, which may result in the dysregulation of several key genes and biological functions related to cardiac development. These effects could also be exerted via the upregulation of eight specific target genes, the subsequent over-activation of the PKC and PI3 K-Akt pathways, and the eventual abnormal cardiac development and VSD.

Recordings from human myenteric neurons using voltage-sensitive dyes.

PubMed

Vignali, Sheila; Peter, Nadine; Ceyhan, Güralp; Demir, Ihsan Ekin; Zeller, Florian; Senseman, David; Michel, Klaus; Schemann, Michael

2010-10-15

Voltage-sensitive dye (VSD) imaging became a powerful tool to detect neural activity in the enteric nervous system, including its routine use in submucous neurons in freshly dissected human tissue. However, VSD imaging of human myenteric neurons remained a challenge because of limited visibility of the ganglia and dye accessibility. We describe a protocol to apply VSD for recordings of human myenteric neurons in freshly dissected tissue and myenteric neurons in primary cultures. VSD imaging of guinea-pig myenteric neurons was used for reference. Electrical stimulation of interganglionic fiber tracts and exogenous application of nicotine or elevated KCl solution was used to evoke action potentials. Bath application of the VSDs Annine-6Plus, Di-4-ANEPPS, Di-8-ANEPPQ, Di-4-ANEPPDHQ or Di-8-ANEPPS revealed no neural signals in human tissue although most of these VSD worked in guinea-pig tissue. Unlike methylene blue and FM1-43, 4-Di-2-ASP did not influence spike discharge and was used in human tissue to visualize myenteric ganglia as a prerequisite for targeted intraganglionic VSD application. Of all VSDs, only intraganglionic injection of Di-8-ANEPPS by a volume controlled injector revealed neuronal signals in human tissue. Signal-to-noise ratio increased by addition of dipicrylamine to Di-8-ANEPPS (0.98±0.16 vs. 2.4±0.62). Establishing VSD imaging in primary cultures of human myenteric neurons led to a further improvement of signal-to-noise ratio. This allowed us to routinely record spike discharge after nicotine application. The described protocol enabled reliable VSD recordings from human myenteric neurons but may also be relevant for the use of other fluorescent dyes in human tissues. Copyright © 2010 Elsevier B.V. All rights reserved.

Structural basis for the inhibition of voltage-dependent K+ channel by gating modifier toxin

PubMed Central

Ozawa, Shin-ichiro; Kimura, Tomomi; Nozaki, Tomohiro; Harada, Hitomi; Shimada, Ichio; Osawa, Masanori

2015-01-01

Voltage-dependent K+ (Kv) channels play crucial roles in nerve and muscle action potentials. Voltage-sensing domains (VSDs) of Kv channels sense changes in the transmembrane potential, regulating the K+-permeability across the membrane. Gating modifier toxins, which have been used for the functional analyses of Kv channels, inhibit Kv channels by binding to VSD. However, the structural basis for the inhibition remains elusive. Here, fluorescence and NMR analyses of the interaction between VSD derived from KvAP channel and its gating modifier toxin, VSTx1, indicate that VSTx1 recognizes VSD under depolarized condition. We identified the VSD-binding residues of VSTx1 and their proximal residues of VSD by the cross-saturation (CS) and amino acid selective CS experiments, which enabled to build a docking model of the complex. These results provide structural basis for the specific binding and inhibition of Kv channels by gating modifier toxins. PMID:26382304

Construction of a multisite DataLink using electronic health records for the identification, surveillance, prevention, and management of diabetes mellitus: the SUPREME-DM project.

PubMed

Nichols, Gregory A; Desai, Jay; Elston Lafata, Jennifer; Lawrence, Jean M; O'Connor, Patrick J; Pathak, Ram D; Raebel, Marsha A; Reid, Robert J; Selby, Joseph V; Silverman, Barbara G; Steiner, John F; Stewart, W F; Vupputuri, Suma; Waitzfelder, Beth

2012-01-01

Electronic health record (EHR) data enhance opportunities for conducting surveillance of diabetes. The objective of this study was to identify the number of people with diabetes from a diabetes DataLink developed as part of the SUPREME-DM (SUrveillance, PREvention, and ManagEment of Diabetes Mellitus) project, a consortium of 11 integrated health systems that use comprehensive EHR data for research. We identified all members of 11 health care systems who had any enrollment from January 2005 through December 2009. For these members, we searched inpatient and outpatient diagnosis codes, laboratory test results, and pharmaceutical dispensings from January 2000 through December 2009 to create indicator variables that could potentially identify a person with diabetes. Using this information, we estimated the number of people with diabetes and among them, the number of incident cases, defined as indication of diabetes after at least 2 years of continuous health system enrollment. The 11 health systems contributed 15,765,529 unique members, of whom 1,085,947 (6.9%) met 1 or more study criteria for diabetes. The nonstandardized proportion meeting study criteria for diabetes ranged from 4.2% to 12.4% across sites. Most members with diabetes (88%) met multiple criteria. Of the members with diabetes, 428,349 (39.4%) were incident cases. The SUPREME-DM DataLink is a unique resource that provides an opportunity to conduct comparative effectiveness research, epidemiologic surveillance including longitudinal analyses, and population-based care management studies of people with diabetes. It also provides a useful data source for pragmatic clinical trials of prevention or treatment interventions.

Not Your Daddy's Data Link: Musings on Datalink Communications

NASA Technical Reports Server (NTRS)

Branstetter, James

2004-01-01

Viewgraphs about musings on Datalink Communications are presented. Some of the topics include: 1) Keen Eye for a Straight Proposal (Next Gen Data Link); 2) So many datalinks so little funding!!!; 3) Brave New World; 4) Time marches on!; 5) Through the Looking Glass; 6) Dollars & Sense Cooking; 7) Economics 101; 8) The Missing Link(s); 9) Straight Shooting; and 10) All is not lost.

Cockpit display of hazardous wind shear information

NASA Technical Reports Server (NTRS)

Wanke, Craig; Hansman, R. John, Jr.

1990-01-01

Information on cockpit display of wind shear information is given in viewgraph form. Based on the current status of windshear sensors and candidate data dissemination systems, the near-term capabilities for windshear avoidance will most likely include: (1) Ground-based detection: TDWR (Terminal Doppler Weather Radar), LLWAS (Low-Level Windshear Alert System), Automated PIREPS; (2) Ground-Air datalinks: Air traffic control voice channels, Mode-S digital datalink, ACARS alphanumeric datalink. The possible datapaths for integration of these systems are illustrated in a diagram. In the future, airborne windshear detection systems such as lidars, passive IR detectors, or airborne Doppler radars may also become available. Possible future datalinks include satellite downlink and specialized en route weather channels.

Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation

PubMed Central

Conti, Luca; Renhorn, Jakob; Gabrielsson, Anders; Turesson, Fredrik; Liin, Sara I; Lindahl, Erik; Elinder, Fredrik

2016-01-01

Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions – a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd2+ bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K+ coordination, a hallmark for C-type inactivation. An engineered Cd2+ bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel. PMID:27278891

Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation

NASA Astrophysics Data System (ADS)

Conti, Luca; Renhorn, Jakob; Gabrielsson, Anders; Turesson, Fredrik; Liin, Sara I.; Lindahl, Erik; Elinder, Fredrik

2016-06-01

Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions - a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd2+ bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K+ coordination, a hallmark for C-type inactivation. An engineered Cd2+ bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel.

Long-term Associations of an Early Corrected Ventricular Septal Defect and Stress Systems of Child and Mother at Primary School Age.

PubMed

Stonawski, Valeska; Vollmer, Laura; Köhler-Jonas, Nicola; Rohleder, Nicolas; Golub, Yulia; Purbojo, Ariawan; Moll, Gunther H; Heinrich, Hartmut; Cesnjevar, Robert A; Kratz, Oliver; Eichler, Anna

2017-01-01

Ventricular septal defect (VSD) is the most common congenital heart defect, with larger VSDs typically being corrected with an open-heart surgery during infancy. Long-term consequences of a VSD-corrective surgery on stress systems of child and mother are still unknown. The aim of the present study is to investigate the associations of an early corrected VSD and diurnal cortisol release of child and mother. 26 children (12 boys) between 6 and 9 years old, who underwent surgery for an isolated VSD within the first 3 years of life, and their mothers participated in the study. Their diurnal cortisol profiles were compared to a sex-, age-, and socioeconomic status-matched healthy control group. Within the VSD group, associations between cortisol and characteristics of surgery and hospitalization were investigated. Child and mother psychopathological symptoms were considered as a possible interfering mechanism of altered cortisol profiles. Diurnal cortisol profiles of children with an early corrected VSD did not differ from those of controls. However, mothers of affected children exhibited higher cortisol levels in the morning ( p  < 0.001, [Formula: see text]) and a steeper diurnal cortisol slope ( p  = 0.016, [Formula: see text]) than mothers of healthy children. Results indicate a favorable development of children with an early corrected VSD, in terms of comparable diurnal cortisol profiles with healthy controls, according to a comparable mother-rated psychopathology. Mothers of affected children reveal altered diurnal cortisol levels, without differences in self-rated psychopathology. This divergence should be clarified in future research.

Decreased tricuspid regurgitation following percutaneous closure of congenital perimembranous ventricular septal defect: immediate and 6-month echocardiographic assessment.

PubMed

Xu, Xu-Dong; Liu, Su-Xuan; Bai, Yuan; Zhang, Min; Zhao, Xian-Xian; Qin, Yong-Wen

2015-09-01

As a common concomitant performance and the most frequent complications of transcatheter perimembranous ventricular septal defect (VSD) closure, tricuspid regurgitation (TR) has rarely been concerned. From January 2008 to December 2012, a total of 70 patients (men: 33, women: 37; mean age: 30.0 ± 17.1 years) with at least mild TR before VSD closure were examined in 508 consecutive congenital perimembranous VSD patients to investigate the outcomes of TR. After VSD closure, the jet area decreased from 3.4 ± 2.5 to 1.2 ± 2.5 cm(2) (p < 0.001); however, no significant decrease was found in 3 patients (mean age 59.7 ± 2.5 years) with severe TR (12.0 ± 1.2 versus 11.2 ± 3.2 cm(2), p = 0.668). Compared to the early outcome after VSD closure, the jet area detected by TTE at 6-month follow-up had further decreased (1.2 ± 2.5 versus 0.9 ± 2.2 cm(2), p < 0.001). In 6 patients, a slight residual shunt was detected immediately after VSD closure and diminished in 3 patients at 6-month follow-up. The hemolysis occurred in one of these six patients and recovered after 3 days. In conclusion, functional TR was ameliorated after percutaneous VSD closure, although persistent abundant TR was common in patients with severe TR before procedure.

Management of older single functioning ventricles with outlet obstruction due to a restricted "VSD" in double inlet left ventricle and in complex double outlet right ventricle.

PubMed

Lacour-Gayet, Francois

2009-01-01

The occurrence of a restriction of the bulbo-ventricular foramen (BVF) in older patient with double inlet left ventricle (DILV) or tricuspid atresia (TA) with ventriculo-arterial discordance is a well-known condition. Today, the surgical management is to perform a Damus-type operation at the time of the bi-directional Glenn or at the Fontan completion. The ventricular septal defect (VSD) enlargement, associated with muscular resection and a patch enlargement of the subaortic accessory ventricular chamber, is rarely performed but remains indicated in cases with pulmonary valve atresia or regurgitation. This condition is essentially prevented by doing an early Norwood-type operation in the presence of DILV/TA with transposition of the great arteries associated with an aortic arch obstruction. The palliative switch operation is an option that was abandoned because of poor control of the pulmonary blood flow. It is only in cases of large unobstructed BVF that pulmonary artery banding could be undertaken in neonates, followed by close echocardiographic follow-up. The occurrence of a restriction or a closure of the VSD in complex DORV following a Fontan operation is a dramatic event and is quite "new business." It has been recently recognized that the VSD becomes restricted in a number of patients with DORV-nc-VSD treated with a Fontan palliation. This new condition is not surprising knowing that 75% of the VSDs must be enlarged preventively in DORV-nc-VSD repair. In the setting of a Fontan circulation, the supra-systemic left ventricle has severe consequences the right ventricle performance. Attempts at surgical VSD enlargement or catheter-based procedures have resulted in almost constant recurrence. This recently reported complication is in favor of also performing a VSD enlargement at the time of the Fontan completion in complex DORV. It justifies the biventricular repair in complex DORV with two viable ventricles.

Variations in Party Line Information Requirements for Flight Crew Situation Awareness in the Datalink Environment

NASA Technical Reports Server (NTRS)

Pritchett, Amy R.; Hansman, R. John

1994-01-01

Current Air Traffic Control communications use shared very high frequency (VHF) voice frequencies from which pilots can obtain 'Party Line' Information (PLI) by overhearing communications addressed to other aircraft. A prior study has shown pilots perceive this PLI to be important. There is concern that some critical PLI may be lost in the proposed datalink environment where communications will be discretely addressed. Different types of flight operations will be, equipped with datalink equipment at different times, generating a 'mixed environment' where some pilots may rely on PLI while others will receive their information by datalink. To research the importance, availability and accuracy of PLI and to query pilots on the information they feel is necessary, a survey was distributed to pilots. The pilots were selected from four flight operation groups to study the variations in PLI requirements in the mixed datalink environment. Pilots perceived PLI to be important overall. Specific information elements pertaining to traffic and weather information were identified as Critical. Most PLI elements followed a pattern of higher perceived importance during terminal area operations, final approach and landing. Pilots from the different flight operation groups identified some elements as particularly important. Pilots perceived PLI to be only moderately available and accurate overall. Several PLI elements received very low availability and accuracy ratings but are perceived as important. In a free response question designed to find the information requirements for global situation awareness, pilots frequently indicated a need for traffic and weather information. These elements were also frequently cited by them as information that could be presented by a datalink system. The results of this survey identify specific concerns to be addressed when implementing datalink communications.

NMR structural and dynamical investigation of the isolated voltage-sensing domain of the potassium channel KvAP: implications for voltage gating.

PubMed

Shenkarev, Zakhar O; Paramonov, Alexander S; Lyukmanova, Ekaterina N; Shingarova, Lyudmila N; Yakimov, Sergei A; Dubinnyi, Maxim A; Chupin, Vladimir V; Kirpichnikov, Mikhail P; Blommers, Marcel J J; Arseniev, Alexander S

2010-04-28

The structure and dynamics of the isolated voltage-sensing domain (VSD) of the archaeal potassium channel KvAP was studied by high-resolution NMR. The almost complete backbone resonance assignment and partial side-chain assignment of the (2)H,(13)C,(15)N-labeled VSD were obtained for the protein domain solubilized in DPC/LDAO (2:1) mixed micelles. Secondary and tertiary structures of the VSD were characterized using secondary chemical shifts and NOE contacts. These data indicate that the spatial structure of the VSD solubilized in micelles corresponds to the structure of the domain in an open state of the channel. NOE contacts and secondary chemical shifts of amide protons indicate the presence of tightly bound water molecule as well as hydrogen bond formation involving an interhelical salt bridge (Asp62-R133) that stabilizes the overall structure of the domain. The backbone dynamics of the VSD was studied using (15)N relaxation measurements. The loop regions S1-S2 and S2-S3 were found mobile, while the S3-S4 loop (voltage-sensor paddle) was found stable at the ps-ns time scale. The moieties of S1, S2, S3, and S4 helices sharing interhelical contacts (at the level of the Asp62-R133 salt bridge) were observed in conformational exchange on the micros-ms time scale. Similar exchange-induced broadening of characteristic resonances was observed for the VSD solubilized in the membrane of lipid-protein nanodiscs composed of DMPC, DMPG, and POPC/DOPG lipids. Apparently, the observed interhelical motions represent an inherent property of the VSD of the KvAP channel and can play an important role in the voltage gating.

Transcatheter closure of ventricular septal defects with nitinol wire occluders of type patent ductus arteriosus.

PubMed

Wierzyk, Arkadiusz; Szkutnik, Małgorzata; Fiszer, Roland; Banaszak, Paweł; Pawlak, Szymon; Białkowski, Jacek

2014-01-01

Ventricular septal defects closure (VSD) depending on the anatomy and clinical setting can be performed surgically or by a hybrid and transcatheter approach. Two cases of children with VSD will be presented. Patients' defects were closed with various types of occluders made of nitinol wire mesh occluder, patent ductus arteriosus (PDA) type. The first case was a 2.5-year-old boy after cardiosurgical correction of tetralogy of Fallot (TOF). After the procedure, a significant haemodynamic residual VSD was observed, which was not successfully closed during the subsequent reoperation. Despite pharmacological treatment, symptoms of heart failure were observed in this patient. In echocardiographic images the residual VSD was presented as a tunnel-like dissection of the ventricular septum (length 6 mm and diameter 3.4 mm). The defect was closed via arterial access with an Amplatzer Duct Occluder II (ADO II). The procedure was successfully performed without any medical complications. In this child, a significant shunt reduction and a noticeable improvement in the patient's clinical status and diminished symptoms of heart failure were noticed. The second patient was a 4-year-old girl suffering from a multi-perforated perimembranous VSD accompanied by a ventricular septal defect with aneurysm. The defect was closed by a venous approach with a PDA Cardio-O-Fix occluder (very similar to ADO I). No short-term or long-term complications were visible during or after the procedure. Only a mild residual shunt through the VSD was observed 6 months afterwards. Transcatheter VSD closure with a proper morphology, with occluders of type Amplatzer Duct Occluder ADO I or ADO II, constitutes a safe and effective therapeutic alternative.

Intra-operative device closure of perimembranous ventricular septal defect without cardiopulmonary bypass under guidance of trans-epicardial echocardiography: a single center experience.

PubMed

Sun, Yong; Zhu, Peng; Zhou, Pengyu; Guo, Yilong; Zheng, Shao-Yi

2016-05-27

Intraoperative device closure of perimembranous ventricular septal defect(VSD) through a lower mini-sternotomy is safe, less invasive, and has excellent surgical and cosmetic outcomes. Our study is to evaluate the feasibility of closing VSD under guidance of trans-epicardial echocardiography. We reviewed the clinical course of 41 patients referred to our institution for minimally invasive closure of perimembranous VSD. The trans-epicardial echocardiography(TEE) was used to monitor the whole procedure to guide the positioning of device and evaluate the operative effect instantly after operation. The procedure was successfully done in 38 patients(92.6 %) with mean age of 1.2 ± 1.5 years(range 0.5-6.1 years),mean weight of 10.78 ± 6.87 kg(range 5.2 ~ 26 kg) and VSD size of 5.1 ± 1.13 mm(range 5 ~ 10 mm). Three cases failed, including two cases whose guide-wires could not pass through VSDs and one case whose occluder could not repair VSD well. Three patients had tiny residual shunts because of the shifting of occluders. There were no major complications such as arrhythmia, valve regurgitation and the failure of occluder during follow-up(Mean 2.3 ± 1.2 years). TEE provided superior imaging of shapes and surrounding structures of the VSDs, and guide-wires passing through VSDs. Intraoperative device closure of perimembranous VSD through a lower mini-sternotomy without cardiopulmonary bypass appears to be a safe and effective procedure. The use of trans-epicardial echocardiography provides useful information for intraoperative device closure of VSD.

KCNQ1 channel modulation by KCNE proteins via the voltage-sensing domain.

PubMed

Nakajo, Koichi; Kubo, Yoshihiro

2015-06-15

The gating of the KCNQ1 potassium channel is drastically regulated by auxiliary subunit KCNE proteins. KCNE1, for example, slows the activation kinetics of KCNQ1 by two orders of magnitude. Like other voltage-gated ion channels, the opening of KCNQ1 is regulated by the voltage-sensing domain (VSD; S1-S4 segments). Although it has been known that KCNE proteins interact with KCNQ1 via the pore domain, some recent reports suggest that the VSD movement may be altered by KCNE. The altered VSD movement of KCNQ1 by KCNE proteins has been examined by site-directed mutagenesis, the scanning cysteine accessibility method (SCAM), voltage clamp fluorometry (VCF) and gating charge measurements. These accumulated data support the idea that KCNE proteins interact with the VSDs of KCNQ1 and modulate the gating of the KCNQ1 channel. In this review, we will summarize recent findings and current views of the KCNQ1 modulation by KCNE via the VSD. In this context, we discuss our recent findings that KCNE1 may alter physical interactions between the S4 segment (VSD) and the S5 segment (pore domain) of KCNQ1. Based on these findings from ourselves and others, we propose a hypothetical mechanism for how KCNE1 binding alters the VSD movement and the gating of the channel. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Exploration of genetically encoded voltage indicators based on a chimeric voltage sensing domain.

PubMed

Mishina, Yukiko; Mutoh, Hiroki; Song, Chenchen; Knöpfel, Thomas

2014-01-01

Deciphering how the brain generates cognitive function from patterns of electrical signals is one of the ultimate challenges in neuroscience. To this end, it would be highly desirable to monitor the activities of very large numbers of neurons while an animal engages in complex behaviors. Optical imaging of electrical activity using genetically encoded voltage indicators (GEVIs) has the potential to meet this challenge. Currently prevalent GEVIs are based on the voltage-sensitive fluorescent protein (VSFP) prototypical design or on the voltage-dependent state transitions of microbial opsins. We recently introduced a new VSFP design in which the voltage-sensing domain (VSD) is sandwiched between a fluorescence resonance energy transfer pair of fluorescent proteins (termed VSFP-Butterflies) and also demonstrated a series of chimeric VSD in which portions of the VSD of Ciona intestinalis voltage-sensitive phosphatase are substituted by homologous portions of a voltage-gated potassium channel subunit. These chimeric VSD had faster sensing kinetics than that of the native Ci-VSD. Here, we describe a new set of VSFPs that combine chimeric VSD with the Butterfly structure. We show that these chimeric VSFP-Butterflies can report membrane voltage oscillations of up to 200 Hz in cultured cells and report sensory evoked cortical population responses in living mice. This class of GEVIs may be suitable for imaging of brain rhythms in behaving mammalians.

Vaccine Safety Datalink

Cancer.gov

The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.

Situational Awareness Issues in the Implementation of Datalink: Shared Situational Awareness in the Joint Flight Deck-ATC Aviation System

NASA Technical Reports Server (NTRS)

Hansman, Robert John, Jr.

1999-01-01

MIT has investigated Situational Awareness issues relating to the implementation of Datalink in the Air Traffic Control environment for a number of years under this grant activity. This work has investigated: 1) The Effect of "Party Line" Information. 2) The Effect of Datalink-Enabled Automated Flight Management Systems (FMS) on Flight Crew Situational Awareness. 3) The Effect of Cockpit Display of Traffic Information (CDTI) on Situational Awareness During Close Parallel Approaches. 4) Analysis of Flight Path Management Functions in Current and Future ATM Environments. 5) Human Performance Models in Advanced ATC Automation: Flight Crew and Air Traffic Controllers. 6) CDTI of Datalink-Based Intent Information in Advanced ATC Environments. 7) Shared Situational Awareness between the Flight Deck and ATC in Datalink-Enabled Environments. 8) Analysis of Pilot and Controller Shared SA Requirements & Issues. 9) Development of Robust Scenario Generation and Distributed Simulation Techniques for Flight Deck ATC Simulation. 10) Methods of Testing Situation Awareness Using Testable Response Techniques. The work is detailed in specific technical reports that are listed in the following bibliography, and are attached as an appendix to the master final technical report.

Study of CCT varying by volume scattering diffuser with moving and rotating white light LED

NASA Astrophysics Data System (ADS)

Ma, Shih-Hsin; Chen, Liang-Shiun; Huang, Wen-Chao

2014-09-01

In this study, the corrected color temperature (CCT) of white light, which originates from a white light LED (WLLED) and passes through a volume-scattering diffuser (VSD), is investigated. The VSD with thickness of 2mm is fabricated by mixing the 2um-sized PMMA scattering particles and the epoxy glue with different concentration values. Moreover, in order to understand the influences of the illuminated area and the scattering path of VSD on CCT values, the bulletheaded and lambertian-type WLLEDs are assembled for different positions and distinct orientations along the optical axis in a black cavity. A detailed comparison between results regarding the white light with and without passing through the VSD is offered. The results of this research will help to improve the colorful consistency of the LED lamps which use diffusers.

Governance and oversight of researcher access to electronic health data: the role of the Independent Scientific Advisory Committee for MHRA database research, 2006-2015.

PubMed

Waller, P; Cassell, J A; Saunders, M H; Stevens, R

2017-03-01

In order to promote understanding of UK governance and assurance relating to electronic health records research, we present and discuss the role of the Independent Scientific Advisory Committee (ISAC) for MHRA database research in evaluating protocols proposing the use of the Clinical Practice Research Datalink. We describe the development of the Committee's activities between 2006 and 2015, alongside growth in data linkage and wider national electronic health records programmes, including the application and assessment processes, and our approach to undertaking this work. Our model can provide independence, challenge and support to data providers such as the Clinical Practice Research Datalink database which has been used for well over 1,000 medical research projects. ISAC's role in scientific oversight ensures feasible and scientifically acceptable plans are in place, while having both lay and professional membership addresses governance issues in order to protect the integrity of the database and ensure that public confidence is maintained.

[Two stage surgical treatment of large ventricular septal defects (author's transl)].

PubMed

Hoffmeister, H E; Seybold-Epting, W; Stunkat, R

1976-12-01

Since March 1971, 51 infants were subjected to pulmonary artery banding (PAB) for a large ventricular septal defect (VSD) with pulmonary hypertension. 41 infants (80%) were under six months of age. Additional defects were present in 41%. Twelve babies died (24%). The lowest mortality was achieved in isolated VSD (6,7%). 28 patients subsequently underwent VSD closure and pulmonary artery debanding. Catheterization data revealed normal or slightly elevated pressures and normal vascular resistance in the pulmonary circuit in 22 children. The operative mortality rate was 10,7%.

Grafting voltage and pharmacological sensitivity in potassium channels.

PubMed

Lan, Xi; Fan, Chunyan; Ji, Wei; Tian, Fuyun; Xu, Tao; Gao, Zhaobing

2016-08-01

A classical voltage-gated ion channel consists of four voltage-sensing domains (VSDs). However, the roles of each VSD in the channels remain elusive. We developed a GVTDT (Graft VSD To Dimeric TASK3 channels that lack endogenous VSDs) strategy to produce voltage-gated channels with a reduced number of VSDs. TASK3 channels exhibit a high host tolerance to VSDs of various voltage-gated ion channels without interfering with the intrinsic properties of the TASK3 selectivity filter. The constructed channels, exemplified by the channels grafted with one or two VSDs from Kv7.1 channels, exhibit classical voltage sensitivity, including voltage-dependent opening and closing. Furthermore, the grafted Kv7.1 VSD transfers the potentiation activity of benzbromarone, an activator that acts on the VSDs of the donor channels, to the constructed channels. Our study indicates that one VSD is sufficient to voltage-dependently gate the pore and provides new insight into the roles of VSDs.

Unruptured Aneurysm of Sinus of Valsalva Coexisting with the Large Ventricular Septal Defect and Severe Aortic Regurgitation in a Young Man

PubMed Central

Nezafati, Pouya; Nezafati, Mohammad Hassan; Hoseinikhah, Hamid

2015-01-01

Introduction. Unruptured sinus of valsalva aneurysm (SVA) is a rare congenital anomaly, particularly, when it coexists with a ventricular septal defect (VSD) and aortic regurgitation due to the prolapse of the elongated aortic cusp into the VSD. In this report, we present the case of a 19-year-old young man with VSD challenging in spite of dyspnea and lower limb edema. Presentation of Case. Its diagnosis was made on the basis of transthoracic echocardiography results. Surgical management consisted of replacing the SVA with mechanical valve prosthesis. A Gore-Tex patch repaired the VSD. Discussion. In the follow-up periods, clinical and echocardiographic tests showed that the patient was in excellent status. Conclusion. SVA requires a surgical procedure due to its high risk of mortality in unoperated patients and a good safety of surgery. PMID:26236342

Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels.

PubMed

Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred; Flucher, Bernhard E

2016-06-01

Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3-S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3-S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3-S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3-S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3-S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms within the IV and I VSDs, respectively. © 2016 Tuluc et al.

Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels

PubMed Central

Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred

2016-01-01

Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3–S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3–S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3–S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3–S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3–S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms within the IV and I VSDs, respectively. PMID:27185857

ITS data management system : year one activities

DOT National Transportation Integrated Search

1997-08-01

This report documents research conducted in the development of an ITS data management system, hereafter referred to as ITS DataLink. The objective of the ITS DataLink system is to retain, manage, share, and analyze ITS data for a variety of tra...

Recent developments in VSD imaging of small neuronal networks

PubMed Central

Hill, Evan S.; Bruno, Angela M.

2014-01-01

Voltage-sensitive dye (VSD) imaging is a powerful technique that can provide, in single experiments, a large-scale view of network activity unobtainable with traditional sharp electrode recording methods. Here we review recent work using VSDs to study small networks and highlight several results from this approach. Topics covered include circuit mapping, network multifunctionality, the network basis of decision making, and the presence of variably participating neurons in networks. Analytical tools being developed and applied to large-scale VSD imaging data sets are discussed, and the future prospects for this exciting field are considered. PMID:25225295

Evaluation of bendectin embryotoxicity in nonhuman primates: I. Ventricular septal defects in prenatal macaques and baboon.

PubMed

Hendrickx, A G; Cukierski, M; Prahalada, S; Janos, G; Rowland, J

1985-10-01

Cynomolgus monkeys, rhesus monkeys and baboons were administered 10 to 40 times the human dose equivalent of Bendectin throughout the major period of organogenesis (22(+/-3)-50 days of gestation). In animals examined prenatally (100 +/- 2 days gestation) the total incidence of ventricular septal defects (VSD) was 40% in cynomolgus monkeys, 18% in rhesus monkeys, and 23% in baboons. The majority of VSD involved the muscular portion of the septum. No dose response was evident and there were no other cardiac or extracardiac defects found except for one baboon fetus with multiple defects. No defects were observed in cynomolgus monkeys administered Bendectin for 4-day periods between 22 and 41 days of gestation. There was no association of Bendectin treatment with any noncardiac defect. In cynomolgus and rhesus monkeys examined at term there was one mitral valve defect and no incidence of VSD. The increased incidence of VSD observed prenatally in all three species and the absence of defects in macaques at term suggests a delay in closure of the ventricular septum in treated animals. The Bendectin-treated monkey may be a suitable model for the study of the pathogenesis of VSD and the mechanism of spontaneous closure of the defect.

Direct Evidence of Conformational Changes Associated with Voltage Gating in a Voltage Sensor Protein by Time-Resolved X-ray/Neutron Interferometry

PubMed Central

2015-01-01

The voltage sensor domain (VSD) of voltage-gated cation (e.g., Na+, K+) channels central to neurological signal transmission can function as a distinct module. When linked to an otherwise voltage-insensitive, ion-selective membrane pore, the VSD imparts voltage sensitivity to the channel. Proteins homologous with the VSD have recently been found to function themselves as voltage-gated proton channels or to impart voltage sensitivity to enzymes. Determining the conformational changes associated with voltage gating in the VSD itself in the absence of a pore domain thereby gains importance. We report the direct measurement of changes in the scattering-length density (SLD) profile of the VSD protein, vectorially oriented within a reconstituted phospholipid bilayer membrane, as a function of the transmembrane electric potential by time-resolved X-ray and neutron interferometry. The changes in the experimental SLD profiles for both polarizing and depolarizing potentials with respect to zero potential were found to extend over the entire length of the isolated VSD’s profile structure. The characteristics of the changes observed were in qualitative agreement with molecular dynamics simulations of a related membrane system, suggesting an initial interpretation of these changes in terms of the VSD’s atomic-level 3-D structure. PMID:24697545

Data-linked pilot reply time on controller workload and communication in a simulated terminal option

DOT National Transportation Integrated Search

2001-05-01

This report describes an analysis of air traffic control communication and workload in a simulated terminal radar approach : control environment. The objective of this study was to investigate how pilot-to-controller data-link acknowledgment time : m...

[Effect of ozonated water on physical and chemical properties of vacuum sealing drainage material].

PubMed

Jiang, Nan; Ma, Yunfei; Lin, Qingrong; Chen, Anfu; Zhao, Peiran; Ni, Guoxin; Yu, Bin

2013-02-01

To investigate the influence of ozonated water on physical and chemical properties of vacuum sealing drainage (VSD) materials. VSD materials (foam and sealing membrane) were immersed in 10 µg/ml ozonated water for 1 h twice daily for 8 days. The foam appearance and microscopic structure of the materials were observed, and tensile tests and Raman spectrum scan were performed assess the effect of ozonated water. Simulated VSD devices were prepared and tested for leakproofness under negative pressure after ozonated water treatment. zonated water treatment for 8 days caused no obvious abnormal changes in the foam appearance or microscopic structure of the materials. The maximum tensile load of foam before and after ozonated water treatment was 4.25∓0.73 kgf and 2.44∓0.19 kgf (P=0.000), the momentary distance when the foam torn before and after intervention was 92.54∓12.83 mm and 64.44∓4.60 mm, respectively (P=0.000). The corresponding results for VSD sealing membrane were 0.70∓0.58 kgf and 0.71∓0.08 kgf (P=0.698), and 99.30∓10.27 mm and 100.95∓18.22 mm (P=0.966), respectively. Raman spectroscopy revealed changes in only several wave intensities and no new chemical groups appeared within the scan range of 400-4000 cm(-1). The VSD device was well hermetic after treatment with ozonated water. Except for a decreased stretch resistance property of the foam, VSD materials display no obvious changes in physical and chemical characteristics after treatment with ozonated water for 8 days.

The value of dual-source multidetector-row computed tomography in determining pulmonary blood supply in patients with pulmonary atresia with ventricular septal defect.

PubMed

Chaosuwannakit, N; Makarawate, P

2018-01-01

Primary evaluation of patients with pulmonary atresia with ventricular septal defect (PA-VSD) traditionally relies upon echocardiography and conventional cardiac angiography (CCA). Cardiac angiography is considered the gold standard for delineation of anatomy in children with PA-VSD. Data comparing CCA and dual-source multidetector-row computed tomography angiography (MDCT) in PA-VSD patients is limited. The objective of this study was to test the hypothesis that MDCT is equivalent to CCA for anatomic delineation in these patients. Twenty-eight patients with PA-VSD underwent CCA and MDCT in close proximity to each other without interval therapy. A retrospective review of these 28 patients was performed. All MDCT data of pulmonary artery morphology, major aortopulmonary collateral arteries (MAPCAs) and type of blood supply (dual vs. single supply) were evaluated by blinded experts and results were compared with CCA. Twenty-eight patients had adequate size right and left pulmonary arteries (21 confluent and 7 non-confluent). Seven patients had complete absence of native pulmonary artery and 3 patients had stenosis of distal branches of pulmonary arteries; all had MAPCAs from descending thoracic aorta and/or subclavian arteries. Sensitivity, specificity, positive and negative predictive value of MDCT for detecting confluent of pulmonary arteries, absence of native pulmonary artery and stenosis of pulmonary arteries were all 100%. Moreover, accuracy of detecting MAPCAs was excellent. These results suggest that MDCT and CCA are equivalent in their ability to delineate pulmonary artery anatomy and MAPCAs. Dual source MDCT provides high diagnostic accuracy in evaluation of pulmonary blood supply in patients with PA-VSD and allows precise characterisation of the condition of pulmonary arteries and MAPCAs which is of paramount importance in managing patients with PA-VSD. (Folia Morphol 2018; 77, 1: 116-122).

Directly ventricular septal defect closure without using arteriovenous wire loop: Our adult case series using transarterial retrograde approach

PubMed Central

Pekel, Nihat; Ercan, Ertuğrul; Özpelit, Mehmet Emre; Özyurtlu, Ferhat; Yılmaz, Akar; Topaloğlu, Caner; Saygı, Serkan; Yakan, Serkan; Tengiz, İstemihan

2017-01-01

Objective: The standard transcatheter ventricular septal defects (VSD) closure procedure is established with arteriovenous (AV) loop and is called as antegrade approach. The directly retrograde transarterial VSD closure without using AV loop might be better option as shortens the procedure time and decreases radiation exposure. Methods: Our series consist of twelve sequential adult cases with congenital VSDs (seven with perimembranous, four with muscular, one with postoperative residuel VSD). The mean age was 26.9 (Range 18–58), the mean height was 168.75 cm (Range 155–185cm), and the mean body mass index was 23.4 (Range 17.3–28.4). Maximum and minimum defect sizes were 10 and 5 mm and the mean defect size was 6.24 mm. The procedure was performed with left heart catheterization and advancing the delivery sheath over the stiff exchange wire then VSD occlusion from left side. Results: The defects were successfully closed with this technique in eleven patients. In sixth patient, the defect could not be cannulated by the delivery sheath, as the tip of the sheath did not reach the defect and VSD was closed with same sheath by standard transvenous approach using AV loop. We didn’t encounter any complication releated to semilunar or atrioventricular valves. Atrioventricular conduction system was not affected by the procedure in any patients. The median procedure and fluoroscopy times were 66 and 16.5 minutes respectively. Conclusion: Transarterial retrograde VSD closure without using AV loop simplifies the procedure, decreases the radiation exposure, and shortens the procedure time. The only limitation in adult patients is delivery sheath length. PMID:28315566

Surveillance and Datalink Communication Performance Analysis for Distributed Separation Assurance System Architectures

NASA Technical Reports Server (NTRS)

Chung, William W.; Linse, Dennis J.; Alaverdi, Omeed; Ifarraguerri, Carlos; Seifert, Scott C.; Salvano, Dan; Calender, Dale

2012-01-01

This study investigates the effects of two technical enablers: Automatic Dependent Surveillance - Broadcast (ADS-B) and digital datalink communication, of the Federal Aviation Administration s Next Generation Air Transportation System (NextGen) under two separation assurance (SA) system architectures: ground-based SA and airborne SA, on overall separation assurance performance. Datalink performance such as successful reception probability in both surveillance and communication messages, and surveillance accuracy are examined in various operational conditions. Required SA performance is evaluated as a function of subsystem performance, using availability, continuity, and integrity metrics to establish overall required separation assurance performance, under normal and off-nominal conditions.

Access to CAMAC from VxWorks and UNIX in DART

DOE Office of Scientific and Technical Information (OSTI.GOV)

Streets, J.; Meadows, J.; Moore, C.

1995-05-01

As part of the DART Project the authors have developed a package of software for CAMAC access from UNIX and VxWorks platforms, with support for several hardware interfaces. They report on developments for the CES CBD8210 VME to parallel CAMAC, the Hytec VSD2992 VME to serial CAMAC and Jorway 411S SCSI to parallel and serial CAMAC branch drivers, and give a summary of the timings obtained.

Induction of divalent cation permeability by heterologous expression of a voltage sensor domain.

PubMed

Arima, Hiroki; Tsutsui, Hidekazu; Sakamoto, Ayako; Yoshida, Manabu; Okamura, Yasushi

2018-01-06

The voltage sensor domain (VSD) is a protein domain that confers sensitivity to membrane potential in voltage-gated ion channels as well as the voltage-sensing phosphatase. Although VSDs have long been considered to function as regulatory units acting on adjacent effectors, recent studies have revealed the existence of direct ion permeation paths in some mutated VSDs and in the voltage-gated proton channel. In this study, we show that calcium currents are evoked upon membrane hyperpolarization in cells expressing a VSD derived from an ascidian voltage-gated ion channel superfamily. Unlike the previously reported omega-pore in the Shaker K + channel and rNav1.4, mutations are not required. From electrophysiological experiments in heterologous expression systems, we found that the conductance is directly mediated by the VSD itself and is carried by both monovalent and divalent cations. This is the first report of divalent cation permeation through a VSD-like structure. Copyright © 2018 Elsevier B.V. All rights reserved.

The isolated voltage sensing domain of the Shaker potassium channel forms a voltage-gated cation channel.

PubMed

Zhao, Juan; Blunck, Rikard

2016-10-06

Domains in macromolecular complexes are often considered structurally and functionally conserved while energetically coupled to each other. In the modular voltage-gated ion channels the central ion-conducting pore is surrounded by four voltage sensing domains (VSDs). Here, the energetic coupling is mediated by interactions between the S4-S5 linker, covalently linking the domains, and the proximal C-terminus. In order to characterize the intrinsic gating of the voltage sensing domain in the absence of the pore domain, the Shaker Kv channel was truncated after the fourth transmembrane helix S4 (Shaker-iVSD). Shaker-iVSD showed significantly altered gating kinetics and formed a cation-selective ion channel with a strong preference for protons. Ion conduction in Shaker-iVSD developed despite identical primary sequence, indicating an allosteric influence of the pore domain. Shaker-iVSD also displays pronounced 'relaxation'. Closing of the pore correlates with entry into relaxation suggesting that the two processes are energetically related.

Allosteric substrate switching in a voltage-sensing lipid phosphatase.

PubMed

Grimm, Sasha S; Isacoff, Ehud Y

2016-04-01

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We found that the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), has not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage-sensing domain (VSD). Using fast fluorescence resonance energy transfer (FRET) reporters of PIPs to monitor enzyme activity and voltage-clamp fluorometry to monitor conformational changes in the VSD, we found that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage-sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This two-step allosteric control over a dual-specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility, endocytosis and exocytosis.

Allosteric substrate switching in a voltage sensing lipid phosphatase

PubMed Central

Grimm, Sasha S.; Isacoff, Ehud Y.

2016-01-01

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We find the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), to have not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage sensing domain (VSD). Using fast FRET reporters of PIPs to monitor enzyme activity and voltage clamp fluorometry to monitor conformational changes in the VSD, we find that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This novel 2-step allosteric control over a dual specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility and endo/exocytosis. PMID:26878552

New control strategies for longwall armored face conveyors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Broadfoot, A.R.; Betz, R.E.

1998-03-01

This paper investigates a new control approach for longwall armored face conveyors (AFC`s) using variable-speed drives (VSD`s). Traditionally, AFC`s have used fixed-speed or two-speed motors, with various mechanical solutions employed to try to solve the problems that this causes. The VSD approach to the control problem promises to solve all the significant problems associated with the control of AFC`s. This paper will present the control algorithms developed for a VSD-based AFC drive system and demonstrate potential performance via computer simulation. A full discussion of the problems involved with the control of AFC`s can be found in the companion paper.

Structural characterization of the voltage sensor domain and voltage-gated K+- channel proteins vectorially-oriented within a single bilayer membrane at the solid/vapor and solid/liquid interfaces via neutron interferometry

PubMed Central

Gupta, S.; Dura, J.A.; Freites, J.A.; Tobias, D.J.; Blasie, J. K.

2012-01-01

The voltage-sensor domain (VSD) is a modular 4-helix bundle component that confers voltage sensitivity to voltage-gated cation channels in biological membranes. Despite extensive biophysical studies and the recent availability of x-ray crystal structures for a few voltage-gated potassium (Kv-) channels and a voltage-gate sodium (Nav-) channel, a complete understanding of the cooperative mechanism of electromechanical coupling, interconverting the closed-to-open states (i.e. non-conducting to cation conducting) remains undetermined. Moreover, the function of these domains is highly dependent on the physical-chemical properties of the surrounding lipid membrane environment. The basis for this work was provided by a recent structural study of the VSD from a prokaryotic Kv-channel vectorially-oriented within a single phospholipid (POPC; 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) membrane investigated by x-ray interferometry at the solid/moist He (or solid/vapor) and solid/liquid interfaces thus achieving partial to full hydration, respectively (Gupta et. al. Phys. Rev E. 2011, 84). Here, we utilize neutron interferometry to characterize this system in substantially greater structural detail at the sub-molecular level, due to its inherent advantages arising from solvent contrast variation coupled with the deuteration of selected sub-molecular membrane components, especially important for the membrane at the solid/liquid interface. We demonstrate the unique vectorial orientation of the VSD and the retention of its molecular conformation manifest in the asymmetric profile structure of the protein within the profile structure of this single bilayer membrane system. We definitively characterize the asymmetric phospholipid bilayer solvating the lateral surfaces of the VSD protein within the membrane. The profile structures of both the VSD protein and phospholipid bilayer depend upon the hydration state of the membrane. We also determine the distribution of water and exchangeable hydrogen throughout the profile structure of both the VSD itself and the VSD:POPC membrane. These two experimentally-determined water and exchangeable hydrogen distribution profiles are in good agreement with molecular dynamics simulations of the VSD protein vectorially-oriented within a fully hydrated POPC bilayer membrane, supporting the existence of the VSD’s water pore. This approach was extended to the full-length Kv-channel (KvAP) at solid/liquid interface, providing the separate profile structures of the KvAP protein and the POPC bilayer within the reconstituted KvAP:POPC membrane. PMID:22686684

Atomistic Modeling of Ion Conduction through the Voltage-Sensing Domain of the Shaker K+ Ion Channel.

PubMed

Wood, Mona L; Freites, J Alfredo; Tombola, Francesco; Tobias, Douglas J

2017-04-20

Voltage-sensing domains (VSDs) sense changes in the membrane electrostatic potential and, through conformational changes, regulate a specific function. The VSDs of wild-type voltage-dependent K + , Na + , and Ca 2+ channels do not conduct ions, but they can become ion-permeable through pathological mutations in the VSD. Relatively little is known about the underlying mechanisms of conduction through VSDs. The most detailed studies have been performed on Shaker K + channel variants in which ion conduction through the VSD is manifested in electrophysiology experiments as a voltage-dependent inward current, the so-called omega current, which appears when the VSDs are in their resting state conformation. Only monovalent cations appear to permeate the Shaker VSD via a pathway that is believed to be, at least in part, the same as that followed by the S4 basic side chains during voltage-dependent activation. We performed μs-time scale atomistic molecular dynamics simulations of a cation-conducting variant of the Shaker VSD under applied electric fields in an experimentally validated resting-state conformation, embedded in a lipid bilayer surrounded by solutions containing guanidinium chloride or potassium chloride. Our simulations provide insights into the Shaker VSD permeation pathway, the protein-ion interactions that control permeation kinetics, and the mechanism of voltage-dependent activation of voltage-gated ion channels.

Enzyme domain affects the movement of the voltage sensor in ascidian and zebrafish voltage-sensing phosphatases.

PubMed

Hossain, Md Israil; Iwasaki, Hirohide; Okochi, Yoshifumi; Chahine, Mohamed; Higashijima, Shinichi; Nagayama, Kuniaki; Okamura, Yasushi

2008-06-27

The ascidian voltage-sensing phosphatase (Ci-VSP) consists of the voltage sensor domain (VSD) and a cytoplasmic phosphatase region that has significant homology to the phosphatase and tensin homolog deleted on chromosome TEN (PTEN). The phosphatase activity of Ci-VSP is modified by the conformational change of the VSD. In many proteins, two protein modules are bidirectionally coupled, but it is unknown whether the phosphatase domain could affect the movement of the VSD in VSP. We addressed this issue by whole-cell patch recording of gating currents from a teleost VSP (Dr-VSP) cloned from Danio rerio expressed in tsA201 cells. Replacement of a critical cysteine residue, in the phosphatase active center of Dr-VSP, by serine sharpened both ON- and OFF-gating currents. Similar changes were produced by treatment with phosphatase inhibitors, pervanadate and orthovanadate, that constitutively bind to cysteine in the active catalytic center of phosphatases. The distinct kinetics of gating currents dependent on enzyme activity were not because of altered phosphatidylinositol 4,5-bisphosphate levels, because the kinetics of gating current did not change by depletion of phosphatidylinositol 4,5-bisphosphate, as reported by coexpressed KCNQ2/3 channels. These results indicate that the movement of the VSD is influenced by the enzymatic state of the cytoplasmic domain, providing an important clue for understanding mechanisms of coupling between the VSD and its effector.

DATALINK. Records Inventory Data Collection Software

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cole, B.

1995-03-01

DATALINK was created to provide an easy to use data collection program for records management software products. It provides several useful tools for capturing and validating record index data in the field. It also allows users to easily create a comma delimited, ASCII text file for data export into most records management software products.

Experimental studies on the effect of automation on pilot situational awareness in the datalink ATC environment

NASA Technical Reports Server (NTRS)

Hahn, Edward C.; Hansman, R. J., Jr.

1992-01-01

An experiment to study how automation, when used in conjunction with datalink for the delivery of ATC clearance amendments, affects the situational awareness of aircrews was conducted. The study was focused on the relationship of situational awareness to automated Flight Management System (FMS) programming of datalinked clearances and the readback of ATC clearances. Situational awareness was tested by issuing nominally unacceptable ATC clearances and measuring whether the error was detected by the subject pilots. The experiment also varied the mode of clearance delivery: Verbal, Textual, and Graphical. The error detection performance and pilot preference results indicate that the automated programming of the FMS may be superior to manual programming. It is believed that automated FMS programming may relieve some of the cognitive load, allowing pilots to concentrate on the strategic implications of a clearance amendment. Also, readback appears to have value, but the small sample size precludes a definite conclusion. Furthermore, because textual and graphical modes of delivery offer different but complementary advantages for cognitive processing, a combination of these modes of delivery may be advantageous in a datalink presentation.

Recent Developments in VSD Imaging of Small Neuronal Networks

ERIC Educational Resources Information Center

Hill, Evan S.; Bruno, Angela M.; Frost, William N.

2014-01-01

Voltage-sensitive dye (VSD) imaging is a powerful technique that can provide, in single experiments, a large-scale view of network activity unobtainable with traditional sharp electrode recording methods. Here we review recent work using VSDs to study small networks and highlight several results from this approach. Topics covered include circuit…

Assessing the mean strength and variations of the time-to-time fluctuations of resting-state brain activity.

PubMed

Li, Zhengjun; Zang, Yu-Feng; Ding, Jianping; Wang, Ze

2017-04-01

The time-to-time fluctuations (TTFs) of resting-state brain activity as captured by resting-state fMRI (rsfMRI) have been repeatedly shown to be informative of functional brain structures and disease-related alterations. TTFs can be characterized by the mean and the range of successive difference. The former can be measured with the mean squared successive difference (MSSD), which is mathematically similar to standard deviation; the latter can be calculated by the variability of the successive difference (VSD). The purpose of this study was to evaluate both the resting state-MSSD and VSD of rsfMRI regarding their test-retest stability, sensitivity to brain state change, as well as their biological meanings. We hypothesized that MSSD and VSD are reliable in resting brain; both measures are sensitive to brain state changes such as eyes-open compared to eyes-closed condition; both are predictive of age. These hypotheses were tested with three rsfMRI datasets and proven true, suggesting both MSSD and VSD as reliable and useful tools for resting-state studies.

Super-Resolution Scanning Laser Microscopy Based on Virtually Structured Detection

PubMed Central

Zhi, Yanan; Wang, Benquan; Yao, Xincheng

2016-01-01

Light microscopy plays a key role in biological studies and medical diagnosis. The spatial resolution of conventional optical microscopes is limited to approximately half the wavelength of the illumination light as a result of the diffraction limit. Several approaches—including confocal microscopy, stimulated emission depletion microscopy, stochastic optical reconstruction microscopy, photoactivated localization microscopy, and structured illumination microscopy—have been established to achieve super-resolution imaging. However, none of these methods is suitable for the super-resolution ophthalmoscopy of retinal structures because of laser safety issues and inevitable eye movements. We recently experimentally validated virtually structured detection (VSD) as an alternative strategy to extend the diffraction limit. Without the complexity of structured illumination, VSD provides an easy, low-cost, and phase artifact–free strategy to achieve super-resolution in scanning laser microscopy. In this article we summarize the basic principles of the VSD method, review our demonstrated single-point and line-scan super-resolution systems, and discuss both technical challenges and the potential of VSD-based instrumentation for super-resolution ophthalmoscopy of the retina. PMID:27480461

The isolated voltage sensing domain of the Shaker potassium channel forms a voltage-gated cation channel

PubMed Central

Zhao, Juan; Blunck, Rikard

2016-01-01

Domains in macromolecular complexes are often considered structurally and functionally conserved while energetically coupled to each other. In the modular voltage-gated ion channels the central ion-conducting pore is surrounded by four voltage sensing domains (VSDs). Here, the energetic coupling is mediated by interactions between the S4-S5 linker, covalently linking the domains, and the proximal C-terminus. In order to characterize the intrinsic gating of the voltage sensing domain in the absence of the pore domain, the Shaker Kv channel was truncated after the fourth transmembrane helix S4 (Shaker-iVSD). Shaker-iVSD showed significantly altered gating kinetics and formed a cation-selective ion channel with a strong preference for protons. Ion conduction in Shaker-iVSD developed despite identical primary sequence, indicating an allosteric influence of the pore domain. Shaker-iVSD also displays pronounced 'relaxation'. Closing of the pore correlates with entry into relaxation suggesting that the two processes are energetically related. DOI: http://dx.doi.org/10.7554/eLife.18130.001 PMID:27710769

Coupling of the phosphatase activity of Ci-VSP to its voltage sensor activity over the entire range of voltage sensitivity

PubMed Central

Sakata, Souhei; Hossain, Md. Israil; Okamura, Yasushi

2011-01-01

Abstract The voltage sensing phosphatase Ci-VSP is composed of a voltage sensor domain (VSD) and a cytoplasmic phosphatase domain. Upon membrane depolarization, movement of the VSD triggers the enzyme's phosphatase activity. To gain further insight into its operating mechanism, we studied the PI(4,5)P2 phosphatase activity of Ci-VSP expressed in Xenopus oocytes over the entire range of VSD motion by assessing the activity of coexpressed Kir2.1 channels or the fluorescence signal from a pleckstrin homology domain fused with green fluorescent protein (GFP) (PHPLC-GFP). Both assays showed greater phosphatase activity at 125 mV than at 75 mV, which corresponds to ‘sensing’ charges that were 90% and 75% of maximum, respectively. On the other hand, the activity at 160 mV (corresponding to 98% of the maximum ‘sensing’ charge) was indistinguishable from that at 125 mV. Modelling the kinetics of the PHPLC-GFP fluorescence revealed that its time course was dependent on both the level of Ci-VSP expression and the diffusion of PHPLC-GFP beneath the plasma membrane. Enzyme activity was calculated by fitting the time course of PHPLC-GFP fluorescence into the model. The voltage dependence of the enzyme activity was superimposable on the Q–V curve, which is consistent with the idea that the enzyme activity is tightly coupled to VSD movement over the entire range of membrane potentials that elicit VSD movement. PMID:21486809

Voltage-sensing domain mode shift is coupled to the activation gate by the N-terminal tail of hERG channels.

PubMed

Tan, Peter S; Perry, Matthew D; Ng, Chai Ann; Vandenberg, Jamie I; Hill, Adam P

2012-09-01

Human ether-a-go-go-related gene (hERG) potassium channels exhibit unique gating kinetics characterized by unusually slow activation and deactivation. The N terminus of the channel, which contains an amphipathic helix and an unstructured tail, has been shown to be involved in regulation of this slow deactivation. However, the mechanism of how this occurs and the connection between voltage-sensing domain (VSD) return and closing of the gate are unclear. To examine this relationship, we have used voltage-clamp fluorometry to simultaneously measure VSD motion and gate closure in N-terminally truncated constructs. We report that mode shifting of the hERG VSD results in a corresponding shift in the voltage-dependent equilibrium of channel closing and that at negative potentials, coupling of the mode-shifted VSD to the gate defines the rate of channel closure. Deletion of the first 25 aa from the N terminus of hERG does not alter mode shifting of the VSD but uncouples the shift from closure of the cytoplasmic gate. Based on these observations, we propose the N-terminal tail as an adaptor that couples voltage sensor return to gate closure to define slow deactivation gating in hERG channels. Furthermore, because the mode shift occurs on a time scale relevant to the cardiac action potential, we suggest a physiological role for this phenomenon in maximizing current flow through hERG channels during repolarization.

Managing Ventricular Septal Defect with Associated Aortic Regurgitation: Two Decades of Experience.

PubMed

Sanoussi, Ahmed; Demanet, Helene; Dessy, Hughes; Massin, Martial; Biarent, Dominique; Deville, Andree; Wauthy, Pierre

2015-09-01

Ventricular septal defect (VSD) with aortic regurgitation (AR) is a well-known association. However, there is still no agreement about its management, particularly regarding the technical details of its operative treatment. The study aim was to describe all components of the syndrome and to evaluate the various techniques used with regards to its anatomical and functional features. A total of 31 patients (mean age 7.4 years; range: 1.0-14.3 years) who underwent repair of VSD and AR between 1990 and 2013 was reviewed. The VSD was perimembranous in 22 patients, and subarterial in nine. Trusler's valvuloplasty technique was used in 15 patients, Yacoub's technique in seven, and Carpentier's technique (triangular resection) in four. Two patients underwent aortic valve replacement (AVR), and three patients with no significant aortic valve lesions underwent a simple patch repair of the VSD. The aortic valvuloplasty results were generally good, with an initial aortic valvuloplasty avoiding AVR. During the immediate postoperative period, valvuloplasty failure occurred in three patients, regardless of the technique used, and all three patients were reoperated on. The mean duration of follow up was 8.5 years (range: 3.2-20.6 years). The initial result was maintained in all patients, except for four who underwent late AVR. The study findings contributed to an analysis of VSD and AR, and helped to clarify the best surgical strategy. The results obtained suggest that adequacy of the initial repair is the most important determinant of subsequent evolution.

Characterization of the Functional Domains of a Mammalian Voltage-Sensitive Phosphatase.

PubMed

Rosasco, Mario G; Gordon, Sharona E; Bajjalieh, Sandra M

2015-12-15

Voltage-sensitive phosphatases (VSPs) are proteins that directly couple changes in membrane electrical potential to inositol lipid phosphatase activity. VSPs thus couple two signaling pathways that are critical for cellular functioning. Although a number of nonmammalian VSPs have been characterized biophysically, mammalian VSPs are less well understood at both the physiological and biophysical levels. In this study, we aimed to address this gap in knowledge by determining whether the VSP from mouse, Mm-VSP, is expressed in the brain and contains a functional voltage-sensing domain (VSD) and a phosphatase domain. We report that Mm-VSP is expressed in neurons and is developmentally regulated. To address whether the functions of the VSD and phosphatase domain are retained in Mm-VSP, we took advantage of the modular nature of these domains and expressed each independently as a chimeric protein in a heterologous expression system. We found that the Mm-VSP VSD, fused to a viral potassium channel, was able to drive voltage-dependent gating of the channel pore. The Mm-VSP phosphatase domain, fused to the VSD of a nonmammalian VSP, was also functional: activation resulted in PI(4,5)P2 depletion that was sufficient to inhibit the PI(4,5)P2-regulated KCNQ2/3 channels. While testing the functionality of the VSD and phosphatase domain, we observed slight differences between the activities of Mm-VSP-based chimeras and those of nonmammalian VSPs. Although the properties of VSP chimeras may not completely reflect the properties of native VSPs, the differences we observed in voltage-sensing and phosphatase activity provide a starting point for future experiments to investigate the function of Mm-VSP and other mammalian VSPs. In conclusion, our data reveal that both the VSD and the lipid phosphatase domain of Mm-VSP are functional, indicating that Mm-VSP likely plays an important role in mouse neurophysiology. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Optical mapping of conduction in early embryonic quail hearts with light-sheet microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ma, Pei; Gu, Shi; Wang, Yves T.; Jenkins, Michael W.; Rollins, Andrew M.

2016-03-01

Optical mapping (OM) using fluorescent voltage-sensitive dyes (VSD) to measure membrane potential is currently the most effective method for electrophysiology studies in early embryonic hearts due to its noninvasiveness and large field-of-view. Conventional OM acquires bright-field images, collecting signals that are integrated in depth and projected onto a 2D plane, not capturing the 3D structure of the sample. Early embryonic hearts, especially at looping stages, have a complicated, tubular geometry. Therefore, conventional OM cannot provide a full picture of the electrical conduction circumferentially around the heart, and may result in incomplete and inaccurate measurements. Here, we demonstrate OM of Hamburger and Hamilton stage 14 embryonic quail hearts using a new commercially-available VSD, Fluovolt, and depth sectioning using a custom built light-sheet microscopy system. Axial and lateral resolution of the system is 14µm and 8µm respectively. For OM imaging, the field-of-view was set to 900µm×900µm to cover the entire heart. 2D over time OM image sets at multiple cross-sections through the looping-stage heart were recorded. The shapes of both atrial and ventricular action potentials acquired were consistent with previous reports using conventional VSD (di-4-ANNEPS). With Fluovolt, signal-to-noise ratio (SNR) is improved significantly by a factor of 2-10 (compared with di-4-ANNEPS) enabling light-sheet OM, which intrinsically has lower SNR due to smaller sampling volumes. Electrophysiologic parameters are rate dependent. Optical pacing was successfully integrated into the system to ensure heart rate consistency. This will also enable accurately gated reconstruction of full four dimensional conduction maps and 3D conduction velocity measurements.

Access to CAMAC from VxWorks and UNIX in DART

NASA Astrophysics Data System (ADS)

Streets, J.; Meadows, J.; Moore, C.; Pordes, R.; Slimmer, D.; Vittone, M.; Stern, E.

1996-02-01

As part of the DART Project [Data acquisition for the next Generation Fermilab Fixed Target Experiments] we have developed a package of software for CAMAC access from UNIX and VxWorks platforms, with support for several hardware interfaces. We report on developments for the CES CBD8210 VME to parallel CAMAC, the Hytec VSD2992 VME to serial CAMAC and Jorway 411s SCSI to parallel and serial CAMAC branch drivers, and give a summary of the timings obtained.

Design and evaluation of an advanced air-ground data-link system for air traffic control

NASA Technical Reports Server (NTRS)

Denbraven, Wim

1992-01-01

The design and evaluation of the ground-based portion of an air-ground data-link system for air traffic control (ATC) are described. The system was developed to support the 4D Aircraft/ATC Integration Study, a joint simulation experiment conducted at NASA's Ames and Langley Research Centers. The experiment focused on airborne and ground-based procedures for handling aircraft equipped with a 4D-Flight Management System (FMS) and the system requirements needed to ensure conflict-free traffic flow. The Center/TRACON Automation System (CTAS) at Ames was used for the ATC part of the experiment, and the 4D-FMS-equipped aircraft was simulated by the Transport Systems Research Vehicle (TSRV) simulator at Langley. The data-link system supported not only conventional ATC communications, but also the communications needed to accommodate the 4D-FMS capabilities of advanced aircraft. Of great significance was the synergism gained from integrating the data link with CTAS. Information transmitted via the data link was used to improve the monitoring and analysis capability of CTAS without increasing controller input workload. Conversely, CTAS was used to anticipate and create prototype messages, thus reducing the workload associated with the manual creation of data-link messages.

Vaccination and 30-Day Mortality Risk in Children, Adolescents, and Young Adults.

PubMed

McCarthy, Natalie L; Gee, Julianne; Sukumaran, Lakshmi; Weintraub, Eric; Duffy, Jonathan; Kharbanda, Elyse O; Baxter, Roger; Irving, Stephanie; King, Jennifer; Daley, Matthew F; Hechter, Rulin; McNeil, Michael M

2016-03-01

This study evaluates the potential association of vaccination and death in the Vaccine Safety Datalink (VSD). The study cohort included individuals ages 9 to 26 years with deaths between January 1, 2005, and December 31, 2011. We implemented a case-centered method to estimate a relative risk (RR) for death in days 0 to 30 after vaccination.Deaths due to external causes (accidents, homicides, and suicides) were excluded from the primary analysis. In a secondary analysis, we included all deaths regardless of cause. A team of physicians reviewed available medical records and coroner's reports to confirm cause of death and assess the causal relationship between death and vaccination. Of the 1100 deaths identified during the study period, 76 (7%) occurred 0 to 30 days after vaccination. The relative risks for deaths after any vaccination and influenza vaccination were significantly lower for deaths due to nonexternal causes (RR 0.57, 95% confidence interval [CI] 0.38-0.83, and RR 0.44, 95% CI 0.24-0.80, respectively) and deaths due to all causes (RR 0.72, 95% CI 0.56-0.91, and RR 0.44, 95% CI 0.28-0.65). No other individual vaccines were significantly associated with death. Among deaths reviewed, 1 cause of death was unknown, 25 deaths were due to nonexternal causes, and 34 deaths were due to external causes. The causality assessment found no evidence of a causal association between vaccination and death. Risk of death was not increased during the 30 days after vaccination, and no deaths were found to be causally associated with vaccination. Copyright © 2016 by the American Academy of Pediatrics.

Near Real-Time Surveillance for Influenza Vaccine Safety: Proof-of-Concept in the Vaccine Safety Datalink Project

PubMed Central

Greene, Sharon K.; Kulldorff, Martin; Lewis, Edwin M.; Li, Rong; Yin, Ruihua; Weintraub, Eric S.; Fireman, Bruce H.; Lieu, Tracy A.; Nordin, James D.; Glanz, Jason M.; Baxter, Roger; Jacobsen, Steven J.; Broder, Karen R.; Lee, Grace M.

2010-01-01

The emergence of pandemic H1N1 influenza in 2009 has prompted public health responses, including production and licensure of new influenza A (H1N1) 2009 monovalent vaccines. Safety monitoring is a critical component of vaccination programs. As proof-of-concept, the authors mimicked near real-time prospective surveillance for prespecified neurologic and allergic adverse events among enrollees in 8 medical care organizations (the Vaccine Safety Datalink Project) who received seasonal trivalent inactivated influenza vaccine during the 2005/06–2007/08 influenza seasons. In self-controlled case series analysis, the risk of adverse events in a prespecified exposure period following vaccination was compared with the risk in 1 control period for the same individual either before or after vaccination. In difference-in-difference analysis, the relative risk in exposed versus control periods each season was compared with the relative risk in previous seasons since 2000/01. The authors used Poisson-based analysis to compare the risk of Guillian-Barré syndrome following vaccination in each season with that in previous seasons. Maximized sequential probability ratio tests were used to adjust for repeated analyses on weekly data. With administration of 1,195,552 doses to children under age 18 years and 4,773,956 doses to adults, no elevated risk of adverse events was identified. Near real-time surveillance for selected adverse events can be implemented prospectively to rapidly assess seasonal and pandemic influenza vaccine safety. PMID:19965887

Sequential therapy with "vacuum sealing drainage-artificial dermis implantation-thin partial thickness skin grafting" for deep and infected wound surfaces in children.

PubMed

Yuan, X-G; Zhang, X; Fu, Y-X; Tian, X-F; Liu, Y; Xiao, J; Li, T-W; Qiu, L

2016-05-01

To evaluate the efficacy of a "vacuum sealing drainage (VSD) - artificial dermis implantation (ADI) - thin partial thickness skin grafting (TSG)" sequential therapy for deep and infected wounds in children. Fifty-three pediatric patients with deep and infected wounds were treated with sequential VSD-ADI-TSG therapy. The efficacy of this treatment was compared with that of the surgical debridement-change dressings-thin partial thickness skin grafting previously performed on 20 patients. Survival of tissue grafts, color and flexibility, subcutaneous fullness and scar formation of the graft site were examined and compared. The sequential therapy combined the advantages of the VSD treatment, in reducing tissue necrosis and infection on the wound surfaces and promoting the growth of granulation tissue, with the enhancement of grafting by artificial dermis. Compared with the 20 controls, skin grafted on the artificial dermis was more smooth and glossy, while the textures of the region were more elastic, and the scars were significantly lighter in Vancouver scale. The sequential VSD-ADI-TSG therapy is a simple and effective treatment for children with deep and infected wounds. IV. Copyright © 2016. Published by Elsevier Masson SAS.

Regulation of Na+ channel inactivation by the DIII and DIV voltage-sensing domains.

PubMed

Hsu, Eric J; Zhu, Wandi; Schubert, Angela R; Voelker, Taylor; Varga, Zoltan; Silva, Jonathan R

2017-03-06

Functional eukaryotic voltage-gated Na + (Na V ) channels comprise four domains (DI-DIV), each containing six membrane-spanning segments (S1-S6). Voltage sensing is accomplished by the first four membrane-spanning segments (S1-S4), which together form a voltage-sensing domain (VSD). A critical Na V channel gating process, inactivation, has previously been linked to activation of the VSDs in DIII and DIV. Here, we probe this interaction by using voltage-clamp fluorometry to observe VSD kinetics in the presence of mutations at locations that have been shown to impair Na V channel inactivation. These locations include the DIII-DIV linker, the DIII S4-S5 linker, and the DIV S4-S5 linker. Our results show that, within the 10-ms timeframe of fast inactivation, the DIV-VSD is the primary regulator of inactivation. However, after longer 100-ms pulses, the DIII-DIV linker slows DIII-VSD deactivation, and the rate of DIII deactivation correlates strongly with the rate of recovery from inactivation. Our results imply that, over the course of an action potential, DIV-VSDs regulate the onset of fast inactivation while DIII-VSDs determine its recovery. © 2017 Hsu et al.

UAV Data-Links: Tasks, Types, Technologies and Examples

DTIC Science & Technology

2000-04-01

Services Mercedes - Benz *Clapra Mercedes - Benz Al cmercial *Leasing *rinancial R ail Systams aftrs Services *smar * lpmoser F reightliner commerciali...highlighting the basic variants of data-links Blohm, MTU and others to form Daimler- Benz and their general advantages and disadvantages a Aerospace (now...bandwidth devices for the consumer market . antenna characteristics Generally speaking, the data-rate of a digital-link signal processing. using BPSK

DATALINK: Records inventory data collection software. User`s guide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cole, B.A.

1995-03-01

DATALINK was created to provide an easy to use data collection program for records management software products. It provides several useful tools for capturing and validating record index data in the field. It also allows users to easily create a comma delimited, ASCII text file for data export into most records management software products. It runs on virtually any computer us MS-DOS.

[Mechanism of vacuum sealing drainage therapy attenuating ischemia-reperfusion injury of skeletal muscle in rabbit].

PubMed

Wang, Xiang; Yang, Fan; Guan, Zhen; Wang, Dongfang; Bai, Xiangjun; Gao, Wei

2016-04-01

To investigate the mechanism of how vacuum sealing drainage (VSD) ameliorating ischemia reperfusion (I/R) injury in skeletal muscle I/R model. Thirty New Zealand white rabbits were divided into three groups: control (sham operation) group, I/R group, VSD+ I/R group.The ischemia of the left hind limb of the animal was induced by clamping the common femoral artery and vein. After 4 hours of ischemia, the clamp was removed and the hind limp underwent 6 hours reperfusion. VSD treated animals received the treatment at the beginning of reperfusion. The concentrations of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) in muscular tissues were assayed. HE stained pathological section was used to evaluate the degree of edema of muscular tissues, and the immunohistochemistry was used to detect the percentage of positive cells expressing high mobility group protein B1 (HMGB1). Q-RT-PCR and Western Blot were used to detect the mRNA levels and protein expression of HMGB1 in myocyte respectively. The experimental data was tested using variance analysis. The levels of inflammatory factors and antioxidant factors in muscular tissues were significantly different in the I/R group compared to the VSD group and control group (the levels of MPO in I/R group, I/R+ VSD group and control group were 0.91±0.22, 0.53±0.08, 0.31±0.10, respectively, F=26.48, P=0.000; MDA were 2.04±0.92, 1.65±1.02, 1.01±0.12, F=4.250, P=0.040; SOD were 35.97±9.23, 55.99±18.97, 61.83±14.91, F=5.240, P=0.020; CAT were 31.42±16.27, 48.50±17.86, 75.95±13.09, F=9.720, P=0.002; GSH were 1.48±0.90, 3.54±1.88, 3.84±2.08, F=5.240, P=0.020). HE staining showed an increased intercellular space ratio in the I/R group (F=16.47, P<0.05). Immunohistochemistry staining showed that percentage of HMGB1 positive myocytes in control, I/R and I/R+ VSD group are 1.94%, 18.63% and 61.36%, respectively. There was significant difference among groups (F=853.886, P<0.01). A significantly inhibited HMGB1 expression by VSD therapy was also validated by the results of Q-RT-PCR (F=50.653, P<0.01) and Western blot (F=963.489, P<0.01). The results from the present research suggest that VSD may attenuate skeletal muscles I/R injury by increasing the cellular antioxidative stress reaction and inhibiting the reactive oxygen species as well as the inflammatory mediators.

Identification of Important "Party Line" Information Elements and the Implications for Situational Awareness in the Datalink Environment

NASA Technical Reports Server (NTRS)

Midkiff, Alan H.; Hansman, R. John, Jr.

1992-01-01

Air/ground digital datalink communications are an integral component of the FAA's Air Traffic Control (ATC) modernization strategy. With the introduction of datalink into the ATC system, there is concern over the potential loss of situational awareness by flight crews due to the reduction in the "party line" information available to the pilot. "Party line" information is gleaned by flight crews overhearing communications between ATC and other aircraft. In the datalink environment, party line information may not be available due to the use of discrete addressing. Information concerning the importance, availability, and accuracy of party line elements was explored through an opinion survey of active air carrier flight crews. The survey identified numerous important party line elements. These elements were scripted into a full-mission flight simulation. The flight simulation experiment examined the utilization of party line information by studying subject responses to the specific information elements. Some party line elements perceived as important were effectively utilized by flight crews in the simulated operational environment. However, other party line elements stimulated little or no increase in situational awareness. The ability to assimilate and use party line information appeared to be dependent on workload, time availability, and the tactical/strategic nature of the situations. In addition, the results of both the survey and the simulation indicated that the importance of party line information appeared to be greatest for operations near or on the airport. This indicates that caution must be exercised when implementing datalink communications in these high workload, tactical sectors. This document is based on the thesis of Alan H. Midkiff submitted in partial fulfillment of the degree of Master of Science in Aeronautics and Astronautics at the Massachusetts Institute of Technology.

Describing the linkages of the immigration, refugees and citizenship Canada permanent resident data and vital statistics death registry to Ontario's administrative health database.

PubMed

Chiu, Maria; Lebenbaum, Michael; Lam, Kelvin; Chong, Nelson; Azimaee, Mahmoud; Iron, Karey; Manuel, Doug; Guttmann, Astrid

2016-10-21

Ontario, the most populous province in Canada, has a universal healthcare system that routinely collects health administrative data on its 13 million legal residents that is used for health research. Record linkage has become a vital tool for this research by enriching this data with the Immigration, Refugees and Citizenship Canada Permanent Resident (IRCC-PR) database and the Office of the Registrar General's Vital Statistics-Death (ORG-VSD) registry. Our objectives were to estimate linkage rates and compare characteristics of individuals in the linked versus unlinked files. We used both deterministic and probabilistic linkage methods to link the IRCC-PR database (1985-2012) and ORG-VSD registry (1990-2012) to the Ontario's Registered Persons Database. Linkage rates were estimated and standardized differences were used to assess differences in socio-demographic and other characteristics between the linked and unlinked records. The overall linkage rates for the IRCC-PR database and ORG-VSD registry were 86.4 and 96.2 %, respectively. The majority (68.2 %) of the record linkages in IRCC-PR were achieved after three deterministic passes, 18.2 % were linked probabilistically, and 13.6 % were unlinked. Similarly the majority (79.8 %) of the record linkages in the ORG-VSD were linked using deterministic record linkage, 16.3 % were linked after probabilistic and manual review, and 3.9 % were unlinked. Unlinked and linked files were similar for most characteristics, such as age and marital status for IRCC-PR and sex and most causes of death for ORG-VSD. However, lower linkage rates were observed among people born in East Asia (78 %) in the IRCC-PR database and certain causes of death in the ORG-VSD registry, namely perinatal conditions (61.3 %) and congenital anomalies (81.3 %). The linkages of immigration and vital statistics data to existing population-based healthcare data in Ontario, Canada will enable many novel cross-sectional and longitudinal studies to be conducted. Analytic techniques to account for sub-optimal linkage rates may be required in studies of certain ethnic groups or certain causes of death among children and infants.

Perventricular double-device closure of wide-spaced multi-hole perimembranous ventricular septal defect.

PubMed

Liang, Fei; Hongxin, Li; Zhang, Hai-Zhou; Wenbin, Guo; Zou, Cheng-Wei; Farhaj, Zeeshan

2017-04-17

Device closure of a wide-spaced multi-hole PmVSD is difficult to succeed in percutaneous approach. This study is to evaluate the feasibility, safety and efficacy of perventricular device closure of wide-spaced multi-hole PmVSD using a double-device implanting technique. Sixteen patients with wide-spaced multi-hole PmVSD underwent perventricular closure with two devices through an inferior median sternotomy approach under transesophageal echocardiographic guidance. The largest hole and its adjacent small holes were occluded with an optimal-sized device. The far-away residual hole was occluded with the other device using a probe-assisted delivery system. All patients were followed up for a period of 1 to 4 years to determine the residual shunt, atrioventricular block and the adjacent valvular function. The number of the holes of the PmVSD was 2 to 4. The maximum distance between the holes was 5.0 to 10.0 mm (median, 6.4 mm). The diameter of the largest hole was 2.5 to 7.0 mm (median, 3.6 mm). The success rate of double-device closure was 100%. Immediate residual shunts were found in 6 patients (38%), and incomplete right bundle branch block at discharge occurred in 3 cases (19%). Both complications decreased to 6% at 1-year follow-up. Neither of them had a severe device-related complication. Perventricular closure of a wide-spaced multi-hole PmVSD using a double-device implanting technique is feasible, safe, and efficacious. In multi-hole PmVSDs with the distance between the holes of more than 5 mm, double-device implantation may achieve a complete occlusion.

Hybrid approach for closure of muscular ventricular septal defects

PubMed Central

Haponiuk, Ireneusz; Chojnicki, Maciej; Jaworski, Radoslaw; Steffek, Mariusz; Juscinski, Jacek; Sroka, Mariusz; Fiszer, Roland; Sendrowska, Aneta; Gierat-Haponiuk, Katarzyna; Maruszewski, Bohdan

2013-01-01

Background The complexity of ventricular septal defects in early infancy led to development of new mini-invasive techniques based on collaboration of cardiac surgeons with interventional cardiologists, called hybrid procedures. Hybrid therapies aim to combine the advantages of surgical and interventional techniques in an effort to reduce the invasiveness. The aim of this study was to present our approach with mVSD patients and initial results in the development of a mini-invasive hybrid procedure in the Gdansk Hybrid Heartlink Programme (GHHP) at the Department of Pediatric Cardiac Surgery, Pomeranian Centre of Traumatology in Gdansk, Poland. Material/Methods The group of 11 children with mVSDs was enrolled in GHHP and 6 were finally qualified to hybrid trans-ventricular mVSD device closure. Mean age at time of hybrid procedure was 8.22 months (range: from 2.7 to 17.8 months, SD=5.1) and mean body weight was 6.3 kg (range: from 3.4 to 7.5 kg, SD=1.5). Results The implants of choice were Amplatzer VSD Occluder and Amplatzer Duct Occluder II (AGA Med. Corp, USA). The position of the implants was checked carefully before releasing the device with both transesophageal echocardiography and epicardial echocardiography. All patients survived and their general condition improved. No complications occurred. The closure of mVSD was complete in all children. Conclusions Hybrid procedures of periventricular muscular VSD closure appear feasible and effective for patients with septal defects with morphology unsuitable for classic surgical or interventional procedures. The modern strategy of joint cardiac surgical and interventional techniques provides the benefits of close cooperation between cardiac surgeon and interventional cardiologist for selected patients in difficult clinical settings. PMID:23892911

[Good reproducibility of a 14-item food frequency questionnaire for cardiovascular prevention in students].

PubMed

Balquet, L; Noury-Desvaux, B; Jaquinandi, V; Mahé, G

2015-02-01

Diet is a modifiable risk factor of atherosclerosis. A 14-item food frequency questionnaire (FFQ) has been developed. The reproducibility of this FFQ is unknown in a student population whereas its use could be of interest. This FFQ allows calculating different scores for different food groups involved in cardiovascular disease. The vascular dietary score (VDS) can be calculated. The VSD ranges from -17 to +19. The higher the VSD, the better diet. Reproducibility was assessed in sports faculty students using mean tests comparing measurement 1 and 2 (minimum time interval ≥ 7 days) and intra-class correlation (ICC) tests. Thirty students (50% men) were included in a French Sports Faculty. Time between two FFQ assessments was 19 ± 9 days. Mean VSD was 0.50 ± 3.70 for the first assessment and 0.30 ± 3.14 for the second one (non significant). Any score for each food group was statistically significant between the first and the second measurement. ICC of VSD was 0.68 [95% confidence interval: 0.43-0.83]. This FFQ that assesses a risky vascular diet has good reproducibility. This tool could be useful for large studies involving students. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Disulfide mapping the voltage-sensing mechanism of a voltage-dependent potassium channel.

PubMed

Nozaki, Tomohiro; Ozawa, Shin-Ichiro; Harada, Hitomi; Kimura, Tomomi; Osawa, Masanori; Shimada, Ichio

2016-11-17

Voltage-dependent potassium (Kv) channels allow for the selective permeability of potassium ions in a membrane potential dependent manner, playing crucial roles in neurotransmission and muscle contraction. Kv channel is a tetramer, in which each subunit possesses a voltage-sensing domain (VSD) and a pore domain (PD). Although several lines of evidence indicated that membrane depolarization is sensed as the movement of helix S4 of the VSD, the detailed voltage-sensing mechanism remained elusive, due to the difficulty of structural analyses at resting potential. In this study, we conducted a comprehensive disulfide locking analysis of the VSD using 36 double Cys mutants, in order to identify the proximal residue pairs of the VSD in the presence or absence of a membrane potential. An intramolecular SS-bond was formed between 6 Cys pairs under both polarized and depolarized environment, and one pair only under depolarized environment. The multiple conformations captured by the SS-bond can be divided by two states, up and down, where S4 lies on the extracellular and intracellular sides of the membrane, respectively, with axial rotation of 180°. The transition between these two states is caused by the S4 translocation of 12 Å, enabling allosteric regulation of the gating at the PD.

Simultaneous transcatheter therapy for perimembranous ventricular septal defect combined with patent ductus arteriosus.

PubMed

Wang, Qiguang; Zhu, Xianyang; Duanzhen, Zhang; Zhang, Po; Chen, Huoyuan; Han, Xiumin; Sheng, Xiaotang; Meng, Lili

2017-06-01

This study aims to assess the clinical efficiency and safety of simultaneous transcatheter interventional treatment for perimembranous ventricular septal defect (pmVSD) combined with patent ductus arteriosus (PDA). Twenty-five patients with pmVSD and PDA treated with simultaneous transcatheter interventions from April 2004 to December 2015 were included in this study. The mean age was 9.80 ± 8.14 years and the mean weight was 29.76 ± 14.82 Kg. Transthoracic echocardiography (TTE) and angiography were performed immediately after the procedure. Patients were re-examined by electrocardiogram, X-ray, and TTE at 2 days, 1 month, 3 months, and 6 months postoperatively. The interventional procedure was successfully performed in all 25 patients. No intraoperative complication was noted. TTE examination of the VSD and PDA immediately after the procedure showed no residual shunt and the occluder was well positioned. Among these patients, four patients showed electrocardiogram changes after the procedure that resolved after drug therapy. The cardiothoracic ratio, left atrial diameter, left ventricular end-systolic diameter, and left ventricular end-diastolic diameter recovered to normal in most patients at 6 months postoperatively. Simultaneously transcatheter interventional therapy is a safe and effective method for pmVSD combined with PDA. © 2017 Wiley Periodicals, Inc.

Dynamic Neurovascular Coupling and Uncoupling during Ictal Onset, Propagation, and Termination Revealed by Simultaneous In Vivo Optical Imaging of Neural Activity and Local Blood Volume

PubMed Central

Zhao, Mingrui; Schwartz, Theodore H.

2013-01-01

Traditional models of ictal propagation involve the concept of an initiation site and a progressive outward march of activation. The process of neurovascular coupling, whereby the brain supplies oxygenated blood to metabolically active neurons presumably results in a similar outward cascade of hyperemia. However, ictal neurovascular coupling has never been assessed in vivo using simultaneous measurements of membrane potential change and hyperemia with wide spatial sampling. In an acute rat ictal model, using simultaneous intrinsic optical signal (IOS) and voltage-sensitive dye (VSD) imaging of cerebral blood volume and membrane potential changes, we demonstrate that seizures consist of multiple dynamic multidirectional waves of membrane potential change with variable onset sites that spread through a widespread network. Local blood volume evolves on a much slower spatiotemporal scale. At seizure onset, the VSD waves extend beyond the IOS signal. During evolution, spatial correlation with hemodynamic signal only exists briefly at the maximal spread of the VSD signal. At termination, the IOS signal extends spatially and temporally beyond the VSD waves. Hence, vascular reactivity evolves in a separate but parallel fashion to membrane potential changes resulting in a mechanism of neurovascular coupling and uncoupling, which is as dynamic as the seizure itself. PMID:22499798

Charge of a quasiparticle in a superconductor.

PubMed

Ronen, Yuval; Cohen, Yonatan; Kang, Jung-Hyun; Haim, Arbel; Rieder, Maria-Theresa; Heiblum, Moty; Mahalu, Diana; Shtrikman, Hadas

2016-02-16

Nonlinear charge transport in superconductor-insulator-superconductor (SIS) Josephson junctions has a unique signature in the shuttled charge quantum between the two superconductors. In the zero-bias limit Cooper pairs, each with twice the electron charge, carry the Josephson current. An applied bias VSD leads to multiple Andreev reflections (MAR), which in the limit of weak tunneling probability should lead to integer multiples of the electron charge ne traversing the junction, with n integer larger than 2Δ/eVSD and Δ the superconducting order parameter. Exceptionally, just above the gap eVSD ≥ 2Δ, with Andreev reflections suppressed, one would expect the current to be carried by partitioned quasiparticles, each with energy-dependent charge, being a superposition of an electron and a hole. Using shot-noise measurements in an SIS junction induced in an InAs nanowire (with noise proportional to the partitioned charge), we first observed quantization of the partitioned charge q = e*/e = n, with n = 1-4, thus reaffirming the validity of our charge interpretation. Concentrating next on the bias region eVSD ~ 2Δ, we found a reproducible and clear dip in the extracted charge to q ~ 0.6, which, after excluding other possibilities, we attribute to the partitioned quasiparticle charge. Such dip is supported by numerical simulations of our SIS structure.

An Infectious Pseudoaneurysm Caused by Ventricular Septal Defect Occluder in Patent Ductus Arteriosus Closure in a Two-Year-Old Child.

PubMed

Li, Dingyang; Qiu, Qiu; Jin, Jing; Zhang, Changdong; Wang, Lijun; Zhang, Gangcheng

2017-12-12

We present a case of an infectious pseudoaneurysm after patent ductus arteriosus (PDA) closure with a ventricular septal defect (VSD) occluder in a two-year-old child. The aneurysm grew rapidly but was successfully removed in time and the patient survived. To our knowledge, this is the first report of an infectious pseudoaneurysm caused by VSD occluder in PDA closure.

Spin Transport in Carbon Nanotubes

NASA Astrophysics Data System (ADS)

Schoenenberger, Christian

2005-03-01

We report on spin transport in carbon nanotubes. First, spin injection in arc-discharge grown multi-walled carbon nanotubes (MWNTs) is achieved by using a ferromagnetic PdNi alloy as contact material. The two contacts, i.e. source and drain, have different shape rendering different magnetic switching fields. Typical two-terminal resistances are in the range of 5-100 kOhm. We find a tunneling magneto resistance (TMR) signal amounting to 2.5-3%. Secondly, we explore the TMR signal as a function of temperature T, source-drain voltage Vsd, and gate voltage Vg. As expected the TMR signal decays with T and Vsd. Remarkably, however, we find a sign change in the spin signal (the TMR signal) as a function of both Vsd and Vg. This work has been done in collaboration with: S. Sahoo and T. Kontos (Univ. of Basel), C. Sürgers (Univ. of Karlsruhe), and L. Forro (EPFL Lausanne).

A double-sided microscope to realize whole-ganglion imaging of membrane potential in the medicinal leech

PubMed Central

Wagenaar, Daniel A

2017-01-01

Studies of neuronal network emergence during sensory processing and motor control are greatly facilitated by technologies that allow us to simultaneously record the membrane potential dynamics of a large population of neurons in single cell resolution. To achieve whole-brain recording with the ability to detect both small synaptic potentials and action potentials, we developed a voltage-sensitive dye (VSD) imaging technique based on a double-sided microscope that can image two sides of a nervous system simultaneously. We applied this system to the segmental ganglia of the medicinal leech. Double-sided VSD imaging enabled simultaneous recording of membrane potential events from almost all of the identifiable neurons. Using data obtained from double-sided VSD imaging, we analyzed neuronal dynamics in both sensory processing and generation of behavior and constructed functional maps for identification of neurons contributing to these processes. PMID:28944754

Profile structures of the voltage-sensor domain and the voltage-gated K+-channel vectorially oriented in a single phospholipid bilayer membrane at the solid-vapor and solid-liquid interfaces determined by x-ray interferometry

PubMed Central

Gupta, S.; Liu, J.; Strzalka, J.; Blasie, J. K.

2011-01-01

One subunit of the prokaryotic voltage-gated potassium ion channel from Aeropyrum pernix (KvAP) is comprised of six transmembrane α helices, of which S1–S4 form the voltage-sensor domain (VSD) and S5 and S6 contribute to the pore domain (PD) of the functional homotetramer. However, the mechanism of electromechanical coupling interconverting the closed-to-open (i.e., nonconducting-to-K+-conducting) states remains undetermined. Here, we have vectorially oriented the detergent (OG)-solubilized VSD in single monolayers by two independent approaches, namely “directed-assembly” and “self-assembly,” to achieve a high in-plane density. Both utilize Ni coordination chemistry to tether the protein to an alkylated inorganic surface via its C-terminal His6 tag. Subsequently, the detergent is replaced by phospholipid (POPC) via exchange, intended to reconstitute a phospholipid bilayer environment for the protein. X-ray interferometry, in which interference with a multilayer reference structure is used to both enhance and phase the specular x-ray reflectivity from the tethered single membrane, was used to determine directly the electron density profile structures of the VSD protein solvated by detergent versus phospholipid, and with either a moist He (moderate hydration) or bulk aqueous buffer (high hydration) environment to preserve a native structure conformation. Difference electron density profiles, with respect to the multilayer substrate itself, for the VSD-OG monolayer and VSD-POPC membranes at both the solid-vapor and solid-liquid interfaces, reveal the profile structures of the VSD protein dominating these profiles and further indicate a successful reconstitution of a lipid bilayer environment. The self-assembly approach was similarly extended to the intact full-length KvAP channel for comparison. The spatial extent and asymmetry in the profile structures of both proteins confirm their unidirectional vectorial orientation within the reconstituted membrane and indicate retention of the protein’s folded three-dimensional tertiary structure upon completion of membrane bilayer reconstitution. Moreover, the resulting high in-plane density of vectorially oriented protein within a fully hydrated single phospholipid bilayer membrane at the solid-liquid interface will enable investigation of their conformational states as a function of the transmembrane electric potential. PMID:22060407

Contested Technologies and Design for Values: The Case of Shale Gas.

PubMed

Dignum, Marloes; Correljé, Aad; Cuppen, Eefje; Pesch, Udo; Taebi, Behnam

2016-08-01

The introduction of new energy technologies may lead to public resistance and contestation. It is often argued that this phenomenon is caused by an inadequate inclusion of relevant public values in the design of technology. In this paper we examine the applicability of the value sensitive design (VSD) approach. While VSD was primarily introduced for incorporating values in technological design, our focus in this paper is expanded towards the design of the institutions surrounding these technologies, as well as the design of stakeholder participation. One important methodological challenge of VSD is to identify the relevant values related to new technological developments. In this paper, we argue that the public debate can form a rich source from which to retrieve the values at stake. To demonstrate this, we have examined the arguments used in the public debate regarding the exploration and exploitation of shale gas in the Netherlands. We identified two important sets of the underlying values, namely substantive and procedural values. This paper concludes with two key findings. Firstly, contrary to what is often suggested in the literature, both proponents and opponents seem to endorse the same values. Secondly, contestation seems to arise in the precise operationalization of these values among the different stakeholders. In other words, contestation in the Dutch shale gas debate does not arise from inter-value conflict but rather from intra-value conflicts. This multi-interpretability should be incorporated in VSD processes.

Reconstruction of the pulmonary posterior wall using in situ autologous tissue for the treatment of pulmonary atresia with ventricular septal defect.

PubMed

Fan, Chengming; Yang, Yifeng; Xiong, Lian; Yin, Ni; Wu, Qin; Tang, Mi; Yang, Jinfu

2017-02-23

To evaluate the early and mid-term results of pulmonary trunk reconstruction using a technique in which autogenous tissue is preserved in situ in pulmonary atresia patients with a ventricular septal defect (PA-VSD). The pulmonary artery was reconstructed using autogenous tissue that had been preserved in situ and a bovine jugular venous patch in 24 patients who were diagnosed with PA-VSD (the observation group). The traditional operation using a bovine jugular venous conduit was performed in 40 other cases of PA-VSD (the control group). In the observation group, all patients survived and recovered successfully without complications. Follow-up echocardiography 2-10 years after the procedure showed that the reconstructed right ventricular outflow tract (RVOT) and pulmonary artery were patent, showing no evidence of flow obstruction. Only mild regurgitation of the bovine jugular vein valve was observed. In the control group, early postoperative death occurred in two cases. Another two patients had obstruction of the anastomotic stoma and underwent conduit replacement surgery within 2 weeks of the initial procedure. During the 2-10 years of follow-up care, six patients presented with valvular stenosis of the BJVC, with a pressure gradient of more than 50 mmHg. The technique for preserving autogenous tissue to reconstruct the pulmonary posterior wall is a satisfactory method for treating PA-VSD.

Left-to-right shunt reduction with intra-aortic balloon pump in postmyocardial infarction ventricular septal defect.

PubMed

Testuz, Ariane; Roffi, Marco; Bonvini, Robert Francis

2013-03-01

This case aims to describe the hemodynamic effects of intra-aortic balloon pump (IABP) in patients with ventricular septal defect (VSD) complicating myocardial infarction (MI). A 79-year-old man with no previous cardiovascular history presented to the emergency department with subacute inferior myocardial infarction associated with mild signs of systemic hypoperfusion. A transthoracic echocardiography revealed a large akinesia of the left ventricular inferior wall with preserved global left ventricular ejection fraction, as well as a large VSD in the midinferior portion of the interventricular septum. Coronary angiography showed an occlusion of the mid portion of a dominant circumflex coronary artery. The invasive hemodynamic evaluation showed a sizable left-to-right shunt (Q(p)/Q(s) = 3.1). Activation of the IABP led to an immediate reduction of the shunt (Q(p)/Q(s) = 2.4 = 22% reduction), an increase in systemic cardiac output (from 2.1 L/min to 2.4 L/min = +12%) and a decrease in the systemic vascular resistances (from 2240 to 1920 dyne-sec/cm(5) = 15% reduction). In patients with post-MI VSD, placement of IABP leads to an immediate reduction in left-to-right shunt and as a consequence to an increase in systemic cardiac output, which may allow hemodynamic stabilization of the patient prior to surgical VSD closure. Copyright © 2012 Wiley Periodicals, Inc.

Hazard alerting and situational awareness in advanced air transport cockpits

NASA Technical Reports Server (NTRS)

Hansman, R. John; Wanke, Craig; Kuchar, James; Mykityshyn, Mark; Hahn, Edward; Midkiff, Alan

1993-01-01

Advances in avionics and display technology have significantly changed the cockpit environment in current 'glass cockpit' aircraft. Recent developments in display technology, on-board processing, data storage, and datalinked communications are likely to further alter the environment in second and third generation 'glass cockpit' aircraft. The interaction of advanced cockpit technology with human cognitive performance has been a major area of activity within the MIT Aeronautical Systems Laboratory. This paper presents an overview of the MIT Advanced Cockpit Simulation Facility. Several recent research projects are briefly reviewed and the most important results are summarized.

Engineering of a genetically encodable fluorescent voltage sensor exploiting fast Ci-VSP voltage-sensing movements.

PubMed

Lundby, Alicia; Mutoh, Hiroki; Dimitrov, Dimitar; Akemann, Walther; Knöpfel, Thomas

2008-06-25

Ci-VSP contains a voltage-sensing domain (VSD) homologous to that of voltage-gated potassium channels. Using charge displacement ('gating' current) measurements we show that voltage-sensing movements of this VSD can occur within 1 ms in mammalian membranes. Our analysis lead to development of a genetically encodable fluorescent protein voltage sensor (VSFP) in which the fast, voltage-dependent conformational changes of the Ci-VSP voltage sensor are transduced to similarly fast fluorescence read-outs.

Surface Map Traffic Intent Displays and Net-Centric Data-link Communications for NextGen

NASA Technical Reports Server (NTRS)

Shelton, Kevin J.; Prinzel, Lawrence J., III; Jones, Denise R.; Allamandola, Angela S.; Arthur, Jarvis J., III; Bailey, Randall E.

2009-01-01

By 2025, U.S. air traffic is predicted to increase three fold and may strain the current air traffic management system, which may not be able to accommodate this growth. In response to this challenge, a revolutionary new concept has been proposed for U.S. aviation operations, termed the Next Generation Air Transportation System or "NextGen". Many key capabilities are being identified to enable NextGen, including the use of data-link communications. Because NextGen represents a radically different approach to air traffic management and requires a dramatic shift in the tasks, roles, and responsibilities for the flight deck, there are numerous research issues and challenges that must be overcome to ensure a safe, sustainable air transportation system. Flight deck display and crew-vehicle interaction concepts are being developed that proactively investigate and overcome potential technology and safety barriers that might otherwise constrain the full realization of NextGen. The paper describes simulation research, conducted at National Aeronautics and Space Administration (NASA) Langley Research Center, examining data-link communications and traffic intent data during envisioned four-dimensional trajectory (4DT)-based and equivalent visual (EV) surface operations. Overall, the results suggest that controller pilot data-link communications (CPDLC) with the use of mandatory pilot read-back of all clearances significantly enhanced situation awareness for 4DT and EV surface operations. The depiction of graphical traffic state and intent information on the surface map display further enhanced off-nominal detection and pilot qualitative reports of safety and awareness.

Microscopic origin of gating current fluctuations in a potassium channel voltage sensor.

PubMed

Freites, J Alfredo; Schow, Eric V; White, Stephen H; Tobias, Douglas J

2012-06-06

Voltage-dependent ion channels open and close in response to changes in membrane electrical potential due to the motion of their voltage-sensing domains (VSDs). VSD charge displacements within the membrane electric field are observed in electrophysiology experiments as gating currents preceding ionic conduction. The elementary charge motions that give rise to the gating current cannot be observed directly, but appear as discrete current pulses that generate fluctuations in gating current measurements. Here we report direct observation of gating-charge displacements in an atomistic molecular dynamics simulation of the isolated VSD from the KvAP channel in a hydrated lipid bilayer on the timescale (10-μs) expected for elementary gating charge transitions. The results reveal that gating-charge displacements are associated with the water-catalyzed rearrangement of salt bridges between the S4 arginines and a set of conserved acidic side chains on the S1-S3 transmembrane segments in the hydrated interior of the VSD. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Current harmonics elimination control method for six-phase PM synchronous motor drives.

PubMed

Yuan, Lei; Chen, Ming-liang; Shen, Jian-qing; Xiao, Fei

2015-11-01

To reduce the undesired 5th and 7th stator harmonic current in the six-phase permanent magnet synchronous motor (PMSM), an improved vector control algorithm was proposed based on vector space decomposition (VSD) transformation method, which can control the fundamental and harmonic subspace separately. To improve the traditional VSD technology, a novel synchronous rotating coordinate transformation matrix was presented in this paper, and only using the traditional PI controller in d-q subspace can meet the non-static difference adjustment, the controller parameter design method is given by employing internal model principle. Moreover, the current PI controller parallel with resonant controller is employed in x-y subspace to realize the specific 5th and 7th harmonic component compensation. In addition, a new six-phase SVPWM algorithm based on VSD transformation theory is also proposed. Simulation and experimental results verify the effectiveness of current decoupling vector controller. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Voltage-sensing domain of voltage-gated proton channel Hv1 shares mechanism of block with pore domains.

PubMed

Hong, Liang; Pathak, Medha M; Kim, Iris H; Ta, Dennis; Tombola, Francesco

2013-01-23

Voltage-gated sodium, potassium, and calcium channels are made of a pore domain (PD) controlled by four voltage-sensing domains (VSDs). The PD contains the ion permeation pathway and the activation gate located on the intracellular side of the membrane. A large number of small molecules are known to inhibit the PD by acting as open channel blockers. The voltage-gated proton channel Hv1 is made of two VSDs and lacks the PD. The location of the activation gate in the VSD is unknown and open channel blockers for VSDs have not yet been identified. Here, we describe a class of small molecules which act as open channel blockers on the Hv1 VSD and find that a highly conserved phenylalanine in the charge transfer center of the VSD plays a key role in blocker binding. We then use one of the blockers to show that Hv1 contains two intracellular and allosterically coupled gates. Copyright © 2013 Elsevier Inc. All rights reserved.

Perforation of the right aortic valve cusp: complication of ventricular septal defect closure with a modified Rashkind umbrella.

PubMed

Vogel, M; Rigby, M L; Shore, D

1996-01-01

An 18-month-old boy with a perimembranous ventricular septal defect (VSD) had undergone transcatheter closure of the defect with a modified 17 mm Rashkind umbrella device at age 4 months (weight 3.8 kg). The clinical signs of a VSD persisted, and he developed aortic incompetence, first detected 5 months after the procedure, which progressed from mild to moderate. A three-dimensional echocardiographic study demonstrated that one of the four arms holding the umbrella was protruding into the aortic valve and had perforated the right aortic valve cusp. This diagnosis was confirmed at subsequent surgery. Surgical repair of the perforated right aortic valve leaflet was necessary. The umbrella was adherent to the tricuspid valve and could not be removed. Instead it was left in situ, but three of the stainless steel arms were cut off. When umbrella closure of a perimembranous VSD is undertaken, the close proximity of part of the distal umbrella to the aortic valve can lead to aortic regurgitation.

Vaginal surgery for pelvic organ prolapse using mesh and a vaginal support device.

PubMed

Carey, M; Slack, M; Higgs, P; Wynn-Williams, M; Cornish, A

2008-02-01

To describe a new surgical procedure for pelvic organ prolapse using mesh and a vaginal support device (VSD) and to report the results of surgery. A prospective observational study. Two tertiary referral Urogynaecology practices. Ninety-five women with International Continence Society pelvic organ prolapse quantification stage 2 or more pelvic organ prolapse who underwent vaginal surgery using mesh augmentation and a VSD. Surgery involved a vaginal approach with mesh reinforcement and placement of a VSD for 4 weeks. At 6 and 12 months, women were examined for prolapse recurrence, and visual analogue scales for satisfaction were completed. Women completed quality-of-life (QOL) questionnaires preoperatively and at 6 and 12 months. Objective success of surgery at 6 and 12 months following surgery. Secondary outcomes were subjective success, complications, QOL outcomes and patients' satisfaction. Objective success rate was 92 and 85% at 6 and 12 months, respectively. Subjective success rate was 91 and 87% at 6 and 12 months, respectively. New prolapse in nonrepaired compartments accounted for 7 of 12 (58%) failures at 12 months. Two of 4 mesh exposures required surgery. Sexual dysfunction was reported by 58% of sexually active women preoperatively and 23% at 12 months. QOL scores significantly improved at 12 months compared with baseline (P < 0.0001). Vaginal surgery using mesh and a VSD is an effective procedure for pelvic organ prolapse. However, further studies are required to establish the role of the surgery described in this study.

Laminar circuit organization and response modulation in mouse visual cortex

PubMed Central

Olivas, Nicholas D.; Quintanar-Zilinskas, Victor; Nenadic, Zoran; Xu, Xiangmin

2012-01-01

The mouse has become an increasingly important animal model for visual system studies, but few studies have investigated local functional circuit organization of mouse visual cortex. Here we used our newly developed mapping technique combining laser scanning photostimulation (LSPS) with fast voltage-sensitive dye (VSD) imaging to examine the spatial organization and temporal dynamics of laminar circuit responses in living slice preparations of mouse primary visual cortex (V1). During experiments, LSPS using caged glutamate provided spatially restricted neuronal activation in a specific cortical layer, and evoked responses from the stimulated layer to its functionally connected regions were detected by VSD imaging. In this study, we first provided a detailed analysis of spatiotemporal activation patterns at specific V1 laminar locations and measured local circuit connectivity. Then we examined the role of cortical inhibition in the propagation of evoked cortical responses by comparing circuit activity patterns in control and in the presence of GABAa receptor antagonists. We found that GABAergic inhibition was critical in restricting layer-specific excitatory activity spread and maintaining topographical projections. In addition, we investigated how AMPA and NMDA receptors influenced cortical responses and found that blocking AMPA receptors abolished interlaminar functional projections, and the NMDA receptor activity was important in controlling visual cortical circuit excitability and modulating activity propagation. The NMDA receptor antagonist reduced neuronal population activity in time-dependent and laminar-specific manners. Finally, we used the quantitative information derived from the mapping experiments and presented computational modeling analysis of V1 circuit organization. Taken together, the present study has provided important new information about mouse V1 circuit organization and response modulation. PMID:23060751

Evaluation of Mixed-Mode Data-Link Communications for NextGen 4DT and Equivalent Visual Surface Operations

NASA Technical Reports Server (NTRS)

Prinzel, Lawrence J., III; Shelton, Kevin J.; Jones, Denise R.; Allamandola, Angela S.; Arthur, Jarvis, J., III; Bailey, Randall E.

2010-01-01

By 2025, U.S. air traffic is predicted to increase 3-fold and may strain the current air traffic management system, which may not be able to accommodate this growth. In response to this challenge, a revolutionary new concept has been proposed for U.S. aviation operations, termed the Next Generation Air Transportation System or NextGen. Many key capabilities are being identified to enable NextGen, including the use of data-link communications. Because NextGen represents a radically different approach to air traffic management and requires a dramatic shift in the tasks, roles, and responsibilities for the flight deck, there are numerous research issues and challenges that must be overcome to ensure a safe, sustainable air transportation system. Flight deck display and crew-vehicle interaction concepts are being developed that proactively investigate and overcome potential technology and safety barriers that might otherwise constrain the full realization of NextGen. The paper describes simulation research examining data-link communications during 4DT and equivalent visual surface operations.

Datalink in air traffic management: Human factors issues in communications.

PubMed

Stedmon, Alex W; Sharples, Sarah; Littlewood, Robert; Cox, Gemma; Patel, Harshada; Wilson, John R

2007-07-01

This paper examines issues underpinning the potential move in aviation away from real speech radiotelephony (R/T) communications towards datalink communications involving text and synthetic speech communications. Using a novel air traffic control (ATC) task, two experiments are reported. Experiment 1 compared the use of speech and text while Experiment 2 compared the use of real and synthetic speech communications. Results indicated that generally there were no significant differences between speech and text communications and that either type could be used without any main effects on performance. However, a number of specific differences were observed across the different phases of the scenarios indicating that workload levels may be more varied when speech communications are used. Experiment 2 illustrated that participants placed a greater level of trust in real speech than synthetic speech, and trusted true communications more than false communications (regardless of whether they were real or synthetic voices). The findings are considered in terms of datalink initiatives for future air traffic management, the importance placed on real speech R/T communications, and the need to develop more natural synthetic speech in this application area.

An Experimental Study of the Effects of Automation on Pilot Situational Awareness in the Datalink ATC Environment

NASA Technical Reports Server (NTRS)

Hahn, Edward C.; Hansman, R. John, Jr.

1992-01-01

An experiment to study how automation, when used in conjunction with datalink for the delivery of air traffic control (ATC) clearance amendments, affects the situational awareness of aircrews was conducted. The study was focused on the relationship of situational awareness to automated Flight Management System (FMS) programming and the readback of ATC clearances. Situational awareness was tested by issuing nominally unacceptable ATC clearances and measuring whether the error was detected by the subject pilots. The experiment also varied the mode of clearance delivery: Verbal, Textual, and Graphical. The error detection performance and pilot preference results indicate that the automated programming of the FMS may be superior to manual programming. It is believed that automated FMS programming may relieve some of the cognitive load, allowing pilots to concentrate on the strategic implications of a clearance amendment. Also, readback appears to have value, but the small sample size precludes a definite conclusion. Furthermore, because textual and graphical modes of delivery offer different but complementary advantages for cognitive processing, a combination of these modes of delivery may be advantageous in a datalink presentation.

Real-time differential GPS/GLONASS trials in Europe using all-in-view 20-channel receivers

NASA Astrophysics Data System (ADS)

Capaccio, S.; Lowe, D.; Walsh, D. M. A.; Daly, P.

Following the initial development of 20-channel, all-in-view Global Navigation Satellite System (GNSS), GPS/GLONASS/Inmarsat-3, receivers at the Institute of Satellite Navigation (ISN), University of Leeds, a modification programme has been undertaken to allow real-time differential corrections to be sent from one 20-channel receiver to another identical receiver using a serial link between them. The differential correction software incorporates the RTCM SC-104 and RTCA DO-217 format developed specifically for GPS and adjusted by the ISN to allow simultaneous GLONASS operation.After successful laboratory testing, real-time differential GNSS tests were successfully completed in static mode between Aberdeen and Leeds via the SkyFix differential data-link, and in dynamic mode at DTEO Boscombe Down using a C-band data-link between the ground and a receiver on board the DRA BAC 1-11 aircraft. The aims of the tests were, (i) to demonstrate real-time differential GNSS position-fixing, (ii) to establish the accuracy improvements brought about, and (iii) to examine the effects of data-link latency and satellite PDOP on the solution accuracy.

Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling

PubMed Central

Liu, Jinyan; Hu, Feng; Tang, Jintian; Tang, Shijie; Xia, Kun; Wu, Song; Yin, Chaoqi; Wang, Shaohua; He, Quanyong; Xie, Huiqing; Zhou, Jianda

2017-01-01

Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our home-made device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)-1β expression, and downregulating IL-10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)-β and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen I and III were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)-13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP-1 and TIMP-2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD-induced PP on wound healing by regulating inflammation, secretion, proliferation and the distribution of different cells in wound tissue. PMID:28290607

Imaging the Spatio-Temporal Dynamics of Supragranular Activity in the Rat Somatosensory Cortex in Response to Stimulation of the Paws

PubMed Central

Morales-Botello, M. L.; Aguilar, J.; Foffani, G.

2012-01-01

We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli. PMID:22829873

Utilizing Three-Dimensional Printing Technology to Assess the Feasibility of High-Fidelity Synthetic Ventricular Septal Defect Models for Simulation in Medical Education.

PubMed

Costello, John P; Olivieri, Laura J; Krieger, Axel; Thabit, Omar; Marshall, M Blair; Yoo, Shi-Joon; Kim, Peter C; Jonas, Richard A; Nath, Dilip S

2014-07-01

The current educational approach for teaching congenital heart disease (CHD) anatomy to students involves instructional tools and techniques that have significant limitations. This study sought to assess the feasibility of utilizing present-day three-dimensional (3D) printing technology to create high-fidelity synthetic heart models with ventricular septal defect (VSD) lesions and applying these models to a novel, simulation-based educational curriculum for premedical and medical students. Archived, de-identified magnetic resonance images of five common VSD subtypes were obtained. These cardiac images were then segmented and built into 3D computer-aided design models using Mimics Innovation Suite software. An Objet500 Connex 3D printer was subsequently utilized to print a high-fidelity heart model for each VSD subtype. Next, a simulation-based educational curriculum using these heart models was developed and implemented in the instruction of 29 premedical and medical students. Assessment of this curriculum was undertaken with Likert-type questionnaires. High-fidelity VSD models were successfully created utilizing magnetic resonance imaging data and 3D printing. Following instruction with these high-fidelity models, all students reported significant improvement in knowledge acquisition (P < .0001), knowledge reporting (P < .0001), and structural conceptualization (P < .0001) of VSDs. It is feasible to use present-day 3D printing technology to create high-fidelity heart models with complex intracardiac defects. Furthermore, this tool forms the foundation for an innovative, simulation-based educational approach to teach students about CHD and creates a novel opportunity to stimulate their interest in this field. © The Author(s) 2014.

The Mammalian Cervical Vertebrae Blueprint Depends on the T (brachyury) Gene

PubMed Central

Kromik, Andreas; Ulrich, Reiner; Kusenda, Marian; Tipold, Andrea; Stein, Veronika M.; Hellige, Maren; Dziallas, Peter; Hadlich, Frieder; Widmann, Philipp; Goldammer, Tom; Baumgärtner, Wolfgang; Rehage, Jürgen; Segelke, Dierck; Weikard, Rosemarie; Kühn, Christa

2015-01-01

A key common feature of all but three known mammalian genera is the strict seven cervical vertebrae blueprint, suggesting the involvement of strong conserving selection forces during mammalian radiation. This is further supported by reports indicating that children with cervical ribs die before they reach reproductive age. Hypotheses were put up, associating cervical ribs (homeotic transformations) to embryonal cancer (e.g., neuroblastoma) or ascribing the constraint in cervical vertebral count to the development of the mammalian diaphragm. Here, we describe a spontaneous mutation c.196A > G in the Bos taurus T gene (also known as brachyury) associated with a cervical vertebral homeotic transformation that violates the fundamental mammalian cervical blueprint, but does not preclude reproduction of the affected individual. Genome-wide mapping, haplotype tracking within a large pedigree, resequencing of target genome regions, and bioinformatic analyses unambiguously confirmed the mutant c.196G allele as causal for this previously unknown defect termed vertebral and spinal dysplasia (VSD) by providing evidence for the mutation event. The nonsynonymous VSD mutation is located within the highly conserved T box of the T gene, which plays a fundamental role in eumetazoan body organization and vertebral development. To our knowledge, VSD is the first unequivocally approved spontaneous mutation decreasing cervical vertebrae number in a large mammal. The spontaneous VSD mutation in the bovine T gene is the first in vivo evidence for the hypothesis that the T protein is directly involved in the maintenance of the mammalian seven-cervical vertebra blueprint. It therefore furthers our knowledge of the T-protein function and early mammalian notochord development. PMID:25614605

The Fate of the Tricuspid Valve Following the Transatrial Closure of the Ventricular Septal Defect.

PubMed

Giordano, Raffaele; Cantinotti, Massimiliano; Di Tommaso, Luigi; Comentale, Giuseppe; Tozzi, Andrea; Pilato, Emanuele; Iannelli, Gabriele; Palma, Gaetano

2018-05-17

The transatrial repair of the ventricular septal defect (VSD) requires an adequate exposure of its rim. We retrospectively evaluated the impact of adopting the tricuspid valve incision (TVI) technique, either with detachment or radial incision, on the postoperative outcome of children undergoing surgical VSD repair. From January 2008 to September 2017 we retrospectively enrolled 141 patients, divided into two groups: 97 patients were subjected to TVI (68.8%) and 44 patients (31.2%) were not subjected to TVI. All patients received an echocardiogram upon discharge from the hospital and after 1 month, 3 months, 6 months and a year from the treatment. No perioperative or late deaths resulted in our dataset. TVI was associated with a slightly longer cardio-pulmonary bypass and cross-clamp time but there were no differences in the surgical outcome between the two groups. Moreover, no differences occurred concerning residual VSD, atrioventricular block or tricuspid regurgitation at discharge. Echocardiograms at follow-up were available for 134 patients (95%) with a median of 5.3 years (range 0.5-9.3) and the degree of tricuspid regurgitation did not differ between groups. No patient required reoperation for tricuspid regurgitation or residual interventricular shunt. Finally, no difference was found even when comparing the two TVI subgroups. TVI should be used whenever intraoperative exposure of VSD is compromised in order to avoid a residual shunt and atrioventricular block. Here we show that this procedure does not significantly compromise the tricuspid function although a large, multicenter, randomized controlled trial is advised to validate this hypothesis. Copyright © 2018. Published by Elsevier Inc.

Recording membrane potential changes through photoacoustic voltage sensitive dye

NASA Astrophysics Data System (ADS)

Zhang, Haichong K.; Kang, Jeeun; Yan, Ping; Abou, Diane S.; Le, Hanh N. D.; Thorek, Daniel L. J.; Kang, Jin U.; Gjedde, Albert; Rahmim, Arman; Wong, Dean F.; Loew, Leslie M.; Boctor, Emad M.

2017-03-01

Monitoring of the membrane potential is possible using voltage sensitive dyes (VSD), where fluorescence intensity changes in response to neuronal electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. In contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near infrared light excitation and ultrasound detection. In this work, we develop the theoretical concept whereby the voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. Based on this concept, we synthesized a novel near infrared photoacoustic VSD (PA-VSD) whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. With a 3-9 μM VSD concentration, we measured a PA signal increase in the range of 5.3 % to 18.1 %, and observed a corresponding signal reduction in fluorescence emission of 30.0 % to 48.7 %. A theoretical model successfully accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate the voltage sensing capability of the dye, but also indicate the necessity of considering both fluorescence and absorbance spectral sensitivities in order to optimize the characteristics of improved photoacoustic probes. Together, our results demonstrate photoacoustic sensing as a potential new modality for sub-second recording and external imaging of electrophysiological and neurochemical events in the brain.

KCNE1 remodels the voltage sensor of Kv7.1 to modulate channel function.

PubMed

Wu, Dick; Pan, Hua; Delaloye, Kelli; Cui, Jianmin

2010-12-01

The KCNE1 auxiliary subunit coassembles with the Kv7.1 channel and modulates its properties to generate the cardiac I(Ks) current. Recent biophysical evidence suggests that KCNE1 interacts with the voltage-sensing domain (VSD) of Kv7.1. To investigate the mechanism of how KCNE1 affects the VSD to alter the voltage dependence of channel activation, we perturbed the VSD of Kv7.1 by mutagenesis and chemical modification in the absence and presence of KCNE1. Mutagenesis of S4 in Kv7.1 indicates that basic residues in the N-terminal half (S4-N) and C-terminal half (S4-C) of S4 are important for stabilizing the resting and activated states of the channel, respectively. KCNE1 disrupts electrostatic interactions involving S4-C, specifically with the lower conserved glutamate in S2 (Glu(170) or E2). Likewise, Trp scanning of S4 shows that mutations to a cluster of residues in S4-C eliminate current in the presence of KCNE1. In addition, KCNE1 affects S4-N by enhancing MTS accessibility to the top of the VSD. Consistent with the structure of Kv channels and previous studies on the KCNE1-Kv7.1 interaction, these results suggest that KCNE1 alters the interactions of S4 residues with the surrounding protein environment, possibly by changing the protein packing around S4, thereby affecting the voltage dependence of Kv7.1. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Smart Sensor for Online Detection of Multiple-Combined Faults in VSD-Fed Induction Motors

PubMed Central

Garcia-Ramirez, Armando G.; Osornio-Rios, Roque A.; Granados-Lieberman, David; Garcia-Perez, Arturo; Romero-Troncoso, Rene J.

2012-01-01

Induction motors fed through variable speed drives (VSD) are widely used in different industrial processes. Nowadays, the industry demands the integration of smart sensors to improve the fault detection in order to reduce cost, maintenance and power consumption. Induction motors can develop one or more faults at the same time that can be produce severe damages. The combined fault identification in induction motors is a demanding task, but it has been rarely considered in spite of being a common situation, because it is difficult to identify two or more faults simultaneously. This work presents a smart sensor for online detection of simple and multiple-combined faults in induction motors fed through a VSD in a wide frequency range covering low frequencies from 3 Hz and high frequencies up to 60 Hz based on a primary sensor being a commercially available current clamp or a hall-effect sensor. The proposed smart sensor implements a methodology based on the fast Fourier transform (FFT), RMS calculation and artificial neural networks (ANN), which are processed online using digital hardware signal processing based on field programmable gate array (FPGA).

Molecular Dynamics Simulations of Voltage-Gated Cation Channels: Insights on Voltage-Sensor Domain Function and Modulation

PubMed Central

Delemotte, Lucie; Klein, Michael L.; Tarek, Mounir

2012-01-01

Since their discovery in the 1950s, the structure and function of voltage-gated cation channels (VGCC) has been largely understood thanks to results stemming from electrophysiology, pharmacology, spectroscopy, and structural biology. Over the past decade, computational methods such as molecular dynamics (MD) simulations have also contributed, providing molecular level information that can be tested against experimental results, thereby allowing the validation of the models and protocols. Importantly, MD can shed light on elements of VGCC function that cannot be easily accessed through “classical” experiments. Here, we review the results of recent MD simulations addressing key questions that pertain to the function and modulation of the VGCC’s voltage-sensor domain (VSD) highlighting: (1) the movement of the S4-helix basic residues during channel activation, articulating how the electrical driving force acts upon them; (2) the nature of the VSD intermediate states on transitioning between open and closed states of the VGCC; and (3) the molecular level effects on the VSD arising from mutations of specific S4 positively charged residues involved in certain genetic diseases. PMID:22654756

Spider toxin inhibits gating pore currents underlying periodic paralysis.

PubMed

Männikkö, Roope; Shenkarev, Zakhar O; Thor, Michael G; Berkut, Antonina A; Myshkin, Mikhail Yu; Paramonov, Alexander S; Kulbatskii, Dmitrii S; Kuzmin, Dmitry A; Sampedro Castañeda, Marisol; King, Louise; Wilson, Emma R; Lyukmanova, Ekaterina N; Kirpichnikov, Mikhail P; Schorge, Stephanie; Bosmans, Frank; Hanna, Michael G; Kullmann, Dimitri M; Vassilevski, Alexander A

2018-04-24

Gating pore currents through the voltage-sensing domains (VSDs) of the skeletal muscle voltage-gated sodium channel Na V 1.4 underlie hypokalemic periodic paralysis (HypoPP) type 2. Gating modifier toxins target ion channels by modifying the function of the VSDs. We tested the hypothesis that these toxins could function as blockers of the pathogenic gating pore currents. We report that a crab spider toxin Hm-3 from Heriaeus melloteei can inhibit gating pore currents due to mutations affecting the second arginine residue in the S4 helix of VSD-I that we have found in patients with HypoPP and describe here. NMR studies show that Hm-3 partitions into micelles through a hydrophobic cluster formed by aromatic residues and reveal complex formation with VSD-I through electrostatic and hydrophobic interactions with the S3b helix and the S3-S4 extracellular loop. Our data identify VSD-I as a specific binding site for neurotoxins on sodium channels. Gating modifier toxins may constitute useful hits for the treatment of HypoPP. Copyright © 2018 the Author(s). Published by PNAS.

Functional diversity of potassium channel voltage-sensing domains.

PubMed

Islas, León D

2016-01-01

Voltage-gated potassium channels or Kv's are membrane proteins with fundamental physiological roles. They are composed of 2 main functional protein domains, the pore domain, which regulates ion permeation, and the voltage-sensing domain, which is in charge of sensing voltage and undergoing a conformational change that is later transduced into pore opening. The voltage-sensing domain or VSD is a highly conserved structural motif found in all voltage-gated ion channels and can also exist as an independent feature, giving rise to voltage sensitive enzymes and also sustaining proton fluxes in proton-permeable channels. In spite of the structural conservation of VSDs in potassium channels, there are several differences in the details of VSD function found across variants of Kvs. These differences are mainly reflected in variations in the electrostatic energy needed to open different potassium channels. In turn, the differences in detailed VSD functioning among voltage-gated potassium channels might have physiological consequences that have not been explored and which might reflect evolutionary adaptations to the different roles played by Kv channels in cell physiology.

Functional diversity of potassium channel voltage-sensing domains

PubMed Central

Islas, León D.

2016-01-01

Abstract Voltage-gated potassium channels or Kv's are membrane proteins with fundamental physiological roles. They are composed of 2 main functional protein domains, the pore domain, which regulates ion permeation, and the voltage-sensing domain, which is in charge of sensing voltage and undergoing a conformational change that is later transduced into pore opening. The voltage-sensing domain or VSD is a highly conserved structural motif found in all voltage-gated ion channels and can also exist as an independent feature, giving rise to voltage sensitive enzymes and also sustaining proton fluxes in proton-permeable channels. In spite of the structural conservation of VSDs in potassium channels, there are several differences in the details of VSD function found across variants of Kvs. These differences are mainly reflected in variations in the electrostatic energy needed to open different potassium channels. In turn, the differences in detailed VSD functioning among voltage-gated potassium channels might have physiological consequences that have not been explored and which might reflect evolutionary adaptations to the different roles played by Kv channels in cell physiology. PMID:26794852

Annual Targets, UAVs and Range Operations Symposium and Exhibition (49th) Held in Fort Walton Beach, Florida on October 25-27, 2011

DTIC Science & Technology

2011-10-27

COMP Mountain Home COMP Shaw COMP Barksdale COMP Hill COMP Homestead ARB COMP Savannah CRTC COMP Gulfport CRTC COMP Alpena CRTC COMP Montana...Spangdahlem AB Aviano AB Kadena AB Programmed: 165 Baseline Pods purchase in FY12 (del FY13) Alpena CRTC Holloman AFB Eielson AFB Planned: 368...ARQ-52(V)2 ARQ-52B(V)2 ARDS (HDIS) ASQ- T35A P4NS (NACTS-RSI) KITS (Kadena) ASQ-T34 ASQ-T46 AKITS ( Alpena ) Israel No Datalink No Datalink P4R1 ASQ

Internet over the VDL-2 Subnetwork: the VDL-2/IP Aviation Datalink System

NASA Technical Reports Server (NTRS)

Grappel, R. D.

2000-01-01

This report describes the design to operate the standard Internet communications protocols (IP) over the VHF aviation Data Link Mode 2 (VDL-2) subnetwork. The VDL-2/IP system specified in this report can operate transparently with the current aviation users of VDL-2 (Airline Communications and Reporting System, ACARS and Aeronautical Telecommunications Network, ATN) and proposed users (Flight Information Service via Broadcast, FIS-B). The VDL-2/IP system provides a straightforward mechanisms to utilize inexpensive, commercial off-the-shelf (COTS) communications packages developed for the Internet as part of the aviation datalink system.

Successful two-stage correction of ventricular septal defect and patent ductus arteriosus in a patient with fixed pulmonary hypertension.

PubMed

Pac, Aysenur; Polat, Tugcin Bora; Vural, Kerem; Pac, Mustafa

2010-01-01

We report a case of a 6-year-old boy with fixed severe pulmonary artery hypertension secondary to a ventricular septal defect (VSD) together with a patent ductus arteriosus (PDA). As a preliminary step, PDA embolization was performed following therapy with inhaled prostacyclin over a period of 6 months. Further, the patient underwent successful surgical VSD closure. We postulate that a staged procedure with long-term prostaglandin therapy might be capable of reducing pulmonary artery resistance and permitting total correction in a patient once considered to have inoperable pulmonary arteriopathy.

Dental management of pediatric patients affected by pulmonary atresia with ventricular septal defect: A scoping review.

PubMed

Garrocho-Rangel, A; Echavarría-García, A-C; Rosales-Bérber, M-A; Flores-Velázquez, J; Pozos-Guillén, A

2017-07-01

Congenital Heart Diseases (CHD) involves a wide range of pathological conditions, such as Pulmonary Atresia with Ventricle Septal Defect (PA/VSD). This disorder leads to the systemic circulation of oxygen-poor blood (cyanosis), with associated features and consequences in the oral cavity. Using scoping review methodology for screening and article selection, the primary objectives of this paper were as follows: first, to pose a research question; second, to identify relevant studies in order to answer the research question; third, to select and retrieve the studies; fourth, to chart the critical data, and finally, to collate, summarize, and report the results from the most important articles on the dental management of children affected with PA/VSD. Relevant articles (Randomized Controlled Trials [RCT], reviews, observational studies, and clinical case reports) published over a 10-year period were identified and retrieved from four Internet databases: PubMed; Embase/Ovid; Cochrane Library, and Google Scholar. By title and abstract screening and after removing duplicates, 24 articles were finally included in the present scoping review. According to the extracted data, the following are the most important clinical issues to be considered when treating children with PA/VSD in the dental setting: prevalence of dental caries; prevention of dental disease (oral hygiene and diet); bacteremia and infective endocarditis risk, and child behavior control and treatment under general anesthesia. Pediatric Dentists should bear in mind that early diagnosis and treatment, together a long-term follow-up of children with PA/VSD, continue to be the best approaches for achieving enhanced patient psychological well-being and, in consequence, their good quality of life.

Novel application of vacuum sealing drainage with continuous irrigation of potassium permanganate for managing infective wounds of gas gangrene.

PubMed

Hu, Ning; Wu, Xing-Huo; Liu, Rong; Yang, Shu-Hua; Huang, Wei; Jiang, Dian-Ming; Wu, Qiang; Xia, Tian; Shao, Zeng-Wu; Ye, Zhe-Wei

2015-08-01

Traumatic gas gangrene is a fatal infection mainly caused by Clostridium perfringens. It is a challenge to manage gas gangrene in open wounds and control infection after debridement or amputation. The aim of the present study was to use vacuum sealing drainage (VSD) with continuous irrigation of potassium permanganate to manage infective wounds of gas gangrene and observe its clinical efficacy. A total of 48 patients with open traumatic gas gangrene infection were included in this study. Amputations were done for 27 patients, and limb salvage procedures were performed for the others. After amputation or aggressive debridement, the VSD system, including polyvinyl alcohol (PVA) foam dressing and polyurethane (PU) film, with continuous irrigation of 1:5000 potassium permanganate solutions, was applied to the wounds. During the follow-up, all the patients healed without recurrence within 8-18 months. There were four complications. Cardiac arrest during amputation surgery occurred in one patient who suffered from severe septic shock. Emergent resuscitation was performed and the patient returned to stable condition. One patient suffered from mixed infection of Staphylococcal aureus, and a second-stage debridement was performed. One patient suffered from severe pain of the limb after the debridement. Exploratory operation was done and the possible reason was trauma of a local peripheral nerve. Three cases of crush syndrome had dialysis treatment for concomitant renal failure. In conclusion, VSD can convert open wound to closed wound, and evacuate necrotic tissues. Furthermore, potassium permanganate solutions help eliminate anaerobic microenvironment and achieve good therapeutic effect on gas gangrene and mixed infection. VSD with continuous irrigation of potassium permanganate is a novel, simple and feasible alternative for severe traumatic open wounds with gas gangrene infection.

A new mechanism of voltage-dependent gating exposed by KV10.1 channels interrupted between voltage sensor and pore.

PubMed

Tomczak, Adam P; Fernández-Trillo, Jorge; Bharill, Shashank; Papp, Ferenc; Panyi, Gyorgy; Stühmer, Walter; Isacoff, Ehud Y; Pardo, Luis A

2017-05-01

Voltage-gated ion channels couple transmembrane potential changes to ion flow. Conformational changes in the voltage-sensing domain (VSD) of the channel are thought to be transmitted to the pore domain (PD) through an α-helical linker between them (S4-S5 linker). However, our recent work on channels disrupted in the S4-S5 linker has challenged this interpretation for the KCNH family. Furthermore, a recent single-particle cryo-electron microscopy structure of K V 10.1 revealed that the S4-S5 linker is a short loop in this KCNH family member, confirming the need for an alternative gating model. Here we use "split" channels made by expression of VSD and PD as separate fragments to investigate the mechanism of gating in K V 10.1. We find that disruption of the covalent connection within the S4 helix compromises the ability of channels to close at negative voltage, whereas disconnecting the S4-S5 linker from S5 slows down activation and deactivation kinetics. Surprisingly, voltage-clamp fluorometry and MTS accessibility assays show that the motion of the S4 voltage sensor is virtually unaffected when VSD and PD are not covalently bound. Finally, experiments using constitutively open PD mutants suggest that the presence of the VSD is structurally important for the conducting conformation of the pore. Collectively, our observations offer partial support to the gating model that assumes that an inward motion of the C-terminal S4 helix, rather than the S4-S5 linker, closes the channel gate, while also suggesting that control of the pore by the voltage sensor involves more than one mechanism. © 2017 Tomczak et al.

A new mechanism of voltage-dependent gating exposed by KV10.1 channels interrupted between voltage sensor and pore

PubMed Central

Fernández-Trillo, Jorge; Bharill, Shashank; Panyi, Gyorgy; Stühmer, Walter; Isacoff, Ehud Y.

2017-01-01

Voltage-gated ion channels couple transmembrane potential changes to ion flow. Conformational changes in the voltage-sensing domain (VSD) of the channel are thought to be transmitted to the pore domain (PD) through an α-helical linker between them (S4–S5 linker). However, our recent work on channels disrupted in the S4–S5 linker has challenged this interpretation for the KCNH family. Furthermore, a recent single-particle cryo-electron microscopy structure of KV10.1 revealed that the S4–S5 linker is a short loop in this KCNH family member, confirming the need for an alternative gating model. Here we use “split” channels made by expression of VSD and PD as separate fragments to investigate the mechanism of gating in KV10.1. We find that disruption of the covalent connection within the S4 helix compromises the ability of channels to close at negative voltage, whereas disconnecting the S4–S5 linker from S5 slows down activation and deactivation kinetics. Surprisingly, voltage-clamp fluorometry and MTS accessibility assays show that the motion of the S4 voltage sensor is virtually unaffected when VSD and PD are not covalently bound. Finally, experiments using constitutively open PD mutants suggest that the presence of the VSD is structurally important for the conducting conformation of the pore. Collectively, our observations offer partial support to the gating model that assumes that an inward motion of the C-terminal S4 helix, rather than the S4–S5 linker, closes the channel gate, while also suggesting that control of the pore by the voltage sensor involves more than one mechanism. PMID:28360219

Access to CAMAC from VxWorks and UNIX in DART

DOE Office of Scientific and Technical Information (OSTI.GOV)

Streets, J.; Meadows, J.; Moore, C.

1996-02-01

All High Energy Physics experiments at Fermilab include CAMAC modules which need to be read out for each triggered event. There is also a need to access CAMAC modules for control and monitoring of the experiment. As part of the DART Project the authors have developed a package of software for CAMAC access from UNIX and VxWorks platforms, with support for several hardware interfaces. The authors report on developments for the CES CBD8210 VME to parallel CAMAC, the Hytec VSD2992 VME to serial CAMAC and Jorway 411S SCSI to parallel and serial CAMAC branch drivers, and give a summary ofmore » the timings obtained.« less

ECMO and cytokine removal for bridging to surgery in a patient with ischemic ventricular septal defect - a case report.

PubMed

Marek, Stefanie; Gamper, Gunnar; Reining, Georg; Bergmann, Peter; Mayr, Harald; Kliegel, Andreas

2017-09-15

Even in the modern era of percutaneous coronary intervention, postinfarction ventricular septal defect (VSD) remains a serious and often lethal complication. Whether or not immediate surgical repair or delaying surgery a few days aided by intra-aortic counterpulsation provides the optimal strategy remains a matter of debate. An interdisciplinary approach of intensivists and cardiac surgeons in this setting is mandatory. We report the use of veno-arterial extracorporeal membrane oxygenation and extracorporeal blood purification therapy (CytoSorb®) as bridging to surgical closure in a patient with an ischemic VSD leading to protracted cardiogenic shock after posterior myocardial infarction.

Using LDR as Sensing Element for an External Fuzzy Controller Applied in Photovoltaic Pumping Systems with Variable-Speed Drives.

PubMed

Maranhão, Geraldo Neves De A; Brito, Alaan Ubaiara; Leal, Anderson Marques; Fonseca, Jéssica Kelly Silva; Macêdo, Wilson Negrão

2015-09-22

In the present paper, a fuzzy controller applied to a Variable-Speed Drive (VSD) for use in Photovoltaic Pumping Systems (PVPS) is proposed. The fuzzy logic system (FLS) used is embedded in a microcontroller and corresponds to a proportional-derivative controller. A Light-Dependent Resistor (LDR) is used to measure, approximately, the irradiance incident on the PV array. Experimental tests are executed using an Arduino board. The experimental results show that the fuzzy controller is capable of operating the system continuously throughout the day and controlling the direct current (DC) voltage level in the VSD with a good performance.

[Percutaneous closure of ductus arteriosus and muscular ventricular defect with amplatzer occluder in a patient with severe pulmonary hypertension].

PubMed

García-Montes, José Antonio; Zabal Cerdeira, Carlos; Calderón-Colmenero, Juan; Espínola, Nilda; Fernández de la Reguera, Guillermo; Buendía Hernández, Alfonso

2005-01-01

Surgical treatment of multiple muscular ventricular septal defects with associated lesions and severe pulmonary hypertension has a high morbility and mortality. Closure of these defects by the Amplatzer muscular VSD occluder is an alternative to surgery, avoiding the need of cardiopulmonary bypass. We present the case of a 38 year-old woman with signs of heart failure in NYHA functional class IV, with two muscular ventricular septal defects, patent ductus arteriosus and severe pulmonary hypertension, that were treated with three Amplatzer muscular VSD occluders, with significant reduction of pulmonary pressure and functional class improvement.

Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

PubMed Central

Armstrong, Craig T.; Mason, Philip E.; Anderson, J. L. Ross; Dempsey, Christopher E.

2016-01-01

Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD. PMID:26899474

Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

NASA Astrophysics Data System (ADS)

Armstrong, Craig T.; Mason, Philip E.; Anderson, J. L. Ross; Dempsey, Christopher E.

2016-02-01

Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD.

Vitrification of mature mouse oocytes in a 6 M Me2SO solution supplemented with antifreeze glycoproteins: the effect of temperature.

PubMed

O'Neil, L; Paynter, S J; Fuller, B J; Shaw, R W; DeVries, A L

1998-08-01

Oocytes have been successfully cryopreserved using rapid and slow freezing procedures. However, variability in the success of replicates has limited its practical application. In the present study, mature mouse oocytes were vitrified in 6 M dimethyl sulfoxide supplemented with 1 mg/ml antifreeze glycoproteins (AFGP) (solution known as VSD + AFGP) from the blood of Antarctic notothenioid fish. Such AFGPs have been used to protect mammalian cells during hypothermia and cryopreservation. However, the degree of protection afforded is a contentious issue. Stepwise addition of cryoprotectant was performed either at room temperature (19-21 degreesC) or on ice (2-4 degreesC), at the final stage of which oocytes were pipetted into 0.25 ml plastic insemination straws and held in liquid nitrogen vapor at -140 degreesC for 3 min before being plunged into liquid nitrogen. Thawing involved holding the straw in the air for 10 s and then in water at 20 degreesC for 10 s before dilution of the VSD solution with 1 M sucrose. Viability was assessed by in vitro fertilization; results have been quoted as median (range). Statistical analyses were performed using Kruskall-Wallis and Mann-Whitney U tests (P < 0.05). Of the oocytes cryopreserved following exposure to VSD + AFGP at room temperature (n = 518, 15 experimental runs), 78% (0-94%) retained normal morphology and, of these, 53% (0-100%) cleaved to two cells. Of these two-cell embryos, 56% (0-100%) went on to develop to blastocyst. The overall percentage development to blastocyst, i.e., number of blastocysts/total number of oocytes treated x 100, was 20% (0-76%). Exposure of oocytes to the VSD + AFGP on ice prior to cryopreservation yielded significantly improved rates of fertilization (94%, 82-100%) and overall development to blastocyst (66%, 24-89%) when compared with oocytes cryopreserved following exposure to the VSD + AFGP at room temperature. Rates of normality (86%, 35-95%) and development to blastocyst (89%, 64-100%) were also improved. Cryopreservation in 6 M dimethyl sulfoxide supplemented with 1 mg/ml AFGP resulted in poor rates of survival which were highly variable when exposure to cryoprotective agent (CPA) was performed at room temperature. Lowering the temperature of exposure to CPA prior to cryopreservation resulted in improved viability. Copyright 1998 Academic Press.

Using LDR as Sensing Element for an External Fuzzy Controller Applied in Photovoltaic Pumping Systems with Variable-Speed Drives

PubMed Central

Maranhão, Geraldo Neves De A.; Brito, Alaan Ubaiara; Leal, Anderson Marques; Fonseca, Jéssica Kelly Silva; Macêdo, Wilson Negrão

2015-01-01

In the present paper, a fuzzy controller applied to a Variable-Speed Drive (VSD) for use in Photovoltaic Pumping Systems (PVPS) is proposed. The fuzzy logic system (FLS) used is embedded in a microcontroller and corresponds to a proportional-derivative controller. A Light-Dependent Resistor (LDR) is used to measure, approximately, the irradiance incident on the PV array. Experimental tests are executed using an Arduino board. The experimental results show that the fuzzy controller is capable of operating the system continuously throughout the day and controlling the direct current (DC) voltage level in the VSD with a good performance. PMID:26402688

Anomalous origin of the left coronary artery from the pulmonary artery with patent ductus arteriosus: a must to recognize entity.

PubMed

Awasthy, Neeraj; Marwah, Ashutosh; Sharma, Rajesh; Dalvi, Bharat

2010-09-01

Anomalous left coronary artery from the pulmonary trunk (ALCAPA) presents in early infancy with a clinical picture of congestive heart failure with left ventricular (LV) dysfunction and mitral insufficiency. These manifestations of myocardial ischaemia may be masked in the presence of an associated patent ductus arteriosus (PDA) or ventricular septal defect (VSD) which prevents the fall of pulmonary artery pressures and allows perfusion of the anomalous coronary artery. We present a case of a patient with large PDA-associated ALCAPA and preserved LV function. The importance of such a finding lies in the fact that VSD closure or PDA ligation in such cases would unmask the ALCAPA.

Aerospace Communications Security Technologies Demonstrated

NASA Technical Reports Server (NTRS)

Griner, James H.; Martzaklis, Konstantinos S.

2003-01-01

In light of the events of September 11, 2001, NASA senior management requested an investigation of technologies and concepts to enhance aviation security. The investigation was to focus on near-term technologies that could be demonstrated within 90 days and implemented in less than 2 years. In response to this request, an internal NASA Glenn Research Center Communications, Navigation, and Surveillance Aviation Security Tiger Team was assembled. The 2-year plan developed by the team included an investigation of multiple aviation security concepts, multiple aircraft platforms, and extensively leveraged datalink communications technologies. It incorporated industry partners from NASA's Graphical Weather-in-the-Cockpit research, which is within NASA's Aviation Safety Program. Two concepts from the plan were selected for demonstration: remote "black box," and cockpit/cabin surveillance. The remote "black box" concept involves real-time downlinking of aircraft parameters for remote monitoring and archiving of aircraft data, which would assure access to the data following the loss or inaccessibility of an aircraft. The cockpit/cabin surveillance concept involves remote audio and/or visual surveillance of cockpit and cabin activity, which would allow immediate response to any security breach and would serve as a possible deterrent to such breaches. The datalink selected for the demonstrations was VDL Mode 2 (VHF digital link), the first digital datalink for air-ground communications designed for aircraft use. VDL Mode 2 is beginning to be implemented through the deployment of ground stations and aircraft avionics installations, with the goal of being operational in 2 years. The first demonstration was performed December 3, 2001, onboard the LearJet 25 at Glenn. NASA worked with Honeywell, Inc., for the broadcast VDL Mode 2 datalink capability and with actual Boeing 757 aircraft data. This demonstration used a cockpitmounted camera for video surveillance and a coupling to the intercom system for audio surveillance. Audio, video, and "black box" data were simultaneously streamed to the ground, where they were displayed to a Glenn audience of senior management and aviation security team members.

Pado, a fluorescent protein with proton channel activity can optically monitor membrane potential, intracellular pH, and map gap junctions.

PubMed

Kang, Bok Eum; Baker, Bradley J

2016-04-04

An in silico search strategy was developed to identify potential voltage-sensing domains (VSD) for the development of genetically encoded voltage indicators (GEVIs). Using a conserved charge distribution in the S2 α-helix, a single in silico search yielded most voltage-sensing proteins including voltage-gated potassium channels, voltage-gated calcium channels, voltage-gated sodium channels, voltage-gated proton channels, and voltage-sensing phosphatases from organisms ranging from mammals to bacteria and plants. A GEVI utilizing the VSD from a voltage-gated proton channel identified from that search was able to optically report changes in membrane potential. In addition this sensor was capable of manipulating the internal pH while simultaneously reporting that change optically since it maintains the voltage-gated proton channel activity of the VSD. Biophysical characterization of this GEVI, Pado, demonstrated that the voltage-dependent signal was distinct from the pH-dependent signal and was dependent on the movement of the S4 α-helix. Further investigation into the mechanism of the voltage-dependent optical signal revealed that inhibiting the dimerization of the fluorescent protein greatly reduced the optical signal. Dimerization of the FP thereby enabled the movement of the S4 α-helix to mediate a fluorescent response.

Pado, a fluorescent protein with proton channel activity can optically monitor membrane potential, intracellular pH, and map gap junctions

PubMed Central

Kang, Bok Eum; Baker, Bradley J.

2016-01-01

An in silico search strategy was developed to identify potential voltage-sensing domains (VSD) for the development of genetically encoded voltage indicators (GEVIs). Using a conserved charge distribution in the S2 α-helix, a single in silico search yielded most voltage-sensing proteins including voltage-gated potassium channels, voltage-gated calcium channels, voltage-gated sodium channels, voltage-gated proton channels, and voltage-sensing phosphatases from organisms ranging from mammals to bacteria and plants. A GEVI utilizing the VSD from a voltage-gated proton channel identified from that search was able to optically report changes in membrane potential. In addition this sensor was capable of manipulating the internal pH while simultaneously reporting that change optically since it maintains the voltage-gated proton channel activity of the VSD. Biophysical characterization of this GEVI, Pado, demonstrated that the voltage-dependent signal was distinct from the pH-dependent signal and was dependent on the movement of the S4 α-helix. Further investigation into the mechanism of the voltage-dependent optical signal revealed that inhibiting the dimerization of the fluorescent protein greatly reduced the optical signal. Dimerization of the FP thereby enabled the movement of the S4 α-helix to mediate a fluorescent response. PMID:27040905

Charge of a quasiparticle in a superconductor

PubMed Central

Ronen, Yuval; Cohen, Yonatan; Kang, Jung-Hyun; Haim, Arbel; Rieder, Maria-Theresa; Heiblum, Moty; Mahalu, Diana; Shtrikman, Hadas

2016-01-01

Nonlinear charge transport in superconductor–insulator–superconductor (SIS) Josephson junctions has a unique signature in the shuttled charge quantum between the two superconductors. In the zero-bias limit Cooper pairs, each with twice the electron charge, carry the Josephson current. An applied bias VSD leads to multiple Andreev reflections (MAR), which in the limit of weak tunneling probability should lead to integer multiples of the electron charge ne traversing the junction, with n integer larger than 2Δ/eVSD and Δ the superconducting order parameter. Exceptionally, just above the gap eVSD ≥ 2Δ, with Andreev reflections suppressed, one would expect the current to be carried by partitioned quasiparticles, each with energy-dependent charge, being a superposition of an electron and a hole. Using shot-noise measurements in an SIS junction induced in an InAs nanowire (with noise proportional to the partitioned charge), we first observed quantization of the partitioned charge q = e*/e=n, with n = 1–4, thus reaffirming the validity of our charge interpretation. Concentrating next on the bias region eVSD∼2Δ, we found a reproducible and clear dip in the extracted charge to q ∼0.6, which, after excluding other possibilities, we attribute to the partitioned quasiparticle charge. Such dip is supported by numerical simulations of our SIS structure. PMID:26831071

Coupled 0D-1D CFD Modeling of Right Heart and Pulmonary Artery Morphometry Tree

NASA Astrophysics Data System (ADS)

Dong, Melody; Yang, Weiguang; Feinstein, Jeffrey A.; Marsden, Alison

2017-11-01

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery (PA) pressure and remodeling of the distal PAs resulting in right ventricular (RV) dysfunction and failure. It is hypothesized that patients with untreated ventricular septal defects (VSD) may develop PAH due to elevated flows and pressures in the PAs. Wall shear stress (WSS), due to elevated flows, and circumferential stress, due to elevated pressures, are known to play a role in vascular mechanobiology. Thus, simulating VSD hemodynamics and wall mechanics may facilitate our understanding of mechanical stimuli leading to PAH initiation and progression. Although 3D CFD models can capture detailed hemodynamics in the proximal PAs, they cannot easily model hemodynamics and wave propagation in the distal PAs, where remodeling occurs. To improve current PA models, we will present a new method that couples distal PA hemodynamics with RV function. Our model couples a 0D lumped parameter model of the RV to a 1D model of the PA tree, based on human PA morphometry data, to characterize RV performance and WSS changes in the PA tree. We will compare a VSD 0D-1D model and a 0D-3D model coupled to a mathematical morphometry tree model to quantify WSS in the entire PA vascular tree.

Swiss cheese ventricular septal defect with myocarditis - a rare coexistence in a neonate.

PubMed

Saboo, A R; Vijaykumar, R; Malik, S; Warke, C

2012-01-01

Myocarditis is defined as acute inflammation of the myocardium, usually following a non-specific flu-like illness, and encompasses a wide range of clinical presentations ranging from mild or subclinical disease to heart failure. We report a 12-day-old healthy full-term neonate who presented with abrupt onset of congestive cardiac failure (CCF) following a viral prodrome. Examination revealed persistent sinus tachycardia, lymphocytosis, gross cardiomegaly, nonspecific electrocardiogram changes with echocardiography showing Swiss cheese ventricular septal defect (VSD). VSD alone very rarely presents as early-onset cardiac failure in the absence of other precipitating factors like anemia, sepsis, hypoglycemia etc. Myocarditis, however, can mimic VSD and can present as fulminant cardiac failure in an otherwise healthy newborn. Myocarditis is usually diagnosed based on circumstantial evidence such as a recent viral infection and the sudden onset of cardiac dysfunction while ruling out other diagnostic possibilities. Elevated troponin T level is one of the most crucial noninvasive diagnostic modalities. Several trials have concluded that levels >0.055 ng/ml are statistically significant for diagnosing myocarditis in children. In our case an abrupt onset of cardiac failure following a viral prodrome and markedly elevated cardiac troponin T without sepsis and in the presence of normal coronary anatomy clinched the diagnosis of myocarditis. An early and aggressive treatment for CCF along with regular long-term follow-up plays a key role in the management of myocarditis. Role of high-dose Intravenous immunoglobulin in myocarditis has been studied by many trials with different outcomes. This is the first case report showing coexistence of VSD with myocarditis in a neonate presenting as early-onset acute cardiac failure. The report highlights the importance of screening for myocarditis in all previously normal babies presenting primarily with cardiogenic symptoms even if a structural heart disease is coexistent early in life. A simplified algorithm for work-up of CCF in a neonate is proposed.

Estimation of Methane Emissions from Slurry Pits below Pig and Cattle Confinements

PubMed Central

Petersen, Søren O.; Olsen, Anne B.; Elsgaard, Lars; Triolo, Jin Mi; Sommer, Sven G.

2016-01-01

Quantifying in-house emissions of methane (CH4) from liquid manure (slurry) is difficult due to high background emissions from enteric processes, yet of great importance for correct estimation of CH4 emissions from manure management and effects of treatment technologies such as anaerobic digestion. In this study CH4 production rates were determined in 20 pig slurry and 11 cattle slurry samples collected beneath slatted floors on six representative farms; rates were determined within 24 h at temperatures close to the temperature in slurry pits at the time of collection. Methane production rates in pig and cattle slurry differed significantly at 0.030 and 0.011 kg CH4 kg-1 VS (volatile solids). Current estimates of CH4 emissions from pig and cattle manure management correspond to 0.032 and 0.015 kg CH4 kg-1, respectively, indicating that slurry pits under animal confinements are a significant source. Fractions of degradable volatile solids (VSd, kg kg-1 VS) were estimated using an aerobic biodegradability assay and total organic C analyses. The VSd in pig and cattle slurry averaged 0.51 and 0.33 kg kg-1 VS, and it was estimated that on average 43 and 28% of VSd in fresh excreta from pigs and cattle, respectively, had been lost at the time of sampling. An empirical model of CH4 emissions from slurry was reparameterised based on experimental results. A sensitivity analysis indicated that predicted CH4 emissions were highly sensitive to uncertainties in the value of lnA of the Arrhenius equation, but much less sensitive to uncertainties in VSd or slurry temperature. A model application indicated that losses of carbon in VS as CO2 may be much greater than losses as CH4. Implications of these results for the correct estimation of CH4 emissions from manure management, and for the mitigation potential of treatments such as anaerobic digestion, are discussed. PMID:27529692

[Clinical application of continuous douche and vacuum sealing drainage in refractory tissue, bone and joint infections after debridement].

PubMed

Yang, Ping-lin; He, Xi-jing; Li, Hao-peng; Wang, Guo-yu; Zang, Quan-jin

2010-01-01

To explore effect and the application value of continuous douche and vacuum sealing drainage (VSD) in refractory tissue, and joint infections after complete debridement. As retrospective analysis of treatment time and restoration or recurrence, from Jan. 2006 to Dec. 2007, 61 cases of refractory tissue, bone and joint infections underwent continuous douche and VSD combined with the treatment of anti-inflammatory and rehabilitation training after debridement in our hospital. The 61 patients included 39 males and 22 females with age ranging from 10 to 58 years with an average of (35 +/- 12) years, among whom 61 identified to have ankle ulcers combined with infections,open fracture combined with infections, sacrococcygeal pressure ulcers combined with infections, infections after hip replacement, infections after open fracture, and infections after skin avulsion postoperation were 11, 15, 9, 3, 5 and 18 cases respectively. The course was from 2 weeks to 11 months with an average of 4 months. In all 61 patients,the mean healing time was 17, 36, 42, 24, 32, 29 and 28 days in ankle ulcers and infections, tibia and fibula open fracture and infections, femoral shaft fracture and infections, sacrococcygeal pressure ulcers and infections, infections after hip replacement, infections after open fracture, and infections after skin avulsion postoperation respectively. The replacement of VSD was 1, 2-4, 3-5, 1-3, 2-4, 2-3 and 1-3 times in each group respectively. There was no wound recurrence except for 2 cases with recurrent in 61 cases with external fixation nail hole semi-pathological fracture in 1 case of femoral shaft fracture and infection and 1 case of tibia and fibula fracture and infection after follow-up at least one year. Application of continuous douche and VSD can effectively decrease incidence of complications and promote the refractory tissue, bone and joint infections wound growth, healing and considerably shorten the healing time.

First trimester combined screening biochemistry in detection of congenital heart defects.

PubMed

Alanen, Julia; Korpimaki, Teemu; Kouru, Heikki; Sairanen, Mikko; Leskinen, Markku; Gissler, Mika; Ryynanen, Markku; Nevalainen, Jaana

2018-04-22

To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs). During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down's syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland. Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively. Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.

Arrhythmias after transcatheter closure of perimembranous ventricular septal defects with a modified double-disk occluder: early and long-term results.

PubMed

Li, Pan; Zhao, Xian-xian; Zheng, Xing; Qin, Yong-wen

2012-07-01

With the development of interventional techniques and devices, transcatheter closure of perimembranous ventricular septal defect has been widely performed. However, there has been a lack of long-term follow-up results about postoperative ECG changes of PmVSD patients. We report our experience of early and late arrhythmias after transcatheter closure of PmVSD with a modified double-disk occluder (MDVO). We performed a retrospective review of 79 patients (47 males, 32 females) between September 2002 and May 2007 who underwent transcatheter closure of perimembranous ventricular septal defect. Symmetric and asymmetric PmVSD occluders were used. The diameter of the evaluated defects ranged from 3 to 12 mm, as measured by TTE and 3 to 15 mm by left ventriculography. Most cases of PmVSD were treated successfully with a single procedure, resulting in a successful closure rate of 97% (77/79 patients). There was no death in any of the patients. After the operation, 79 patients were followed-up for a range of 10-76 months (35.3 ± 17.4 months). In this series, 11 cases of incomplete right bundle branch block and five cases of complete right bundle branch block occurred during the early period after operation. During long-term follow-up, these issues declined in prevalence to five and four cases, respectively. Moreover, reversible third-degree AVB occurred during closure or after the procedure, and two of the three patients with reversible AVB received a temporary heart pacemaker implantation. These patients recovered 1 h, 6 days, and 9 days later, respectively. During 10-76 months of follow-up, no complications occurred in any of the patients, including residual shunt, severe aortic valve, or tricuspid valve regurgitation. Device closure of perimembranous ventricular septal defects with a modified double-disk occluder (MDVO) resulted in excellent closure rates and acceptably low arrhythmia rates.

A second prosthesis as a procedural rescue option in trans-apical aortic valve implantation.

PubMed

Kempfert, Jörg; Rastan, Ardawan J; Schuler, Gerhard; Linke, Axel; Holzhey, David; van Linden, Arnaud; Mohr, Friedrich-W; Walther, Thomas

2011-07-01

Trans-apical aortic valve implantation (TA-AVI) using the Edwards SAPIEN™ prosthesis has evolved to a routine procedure for selected high-risk elderly patients. In rare cases, misplacement of the SAPIEN™ valve (too low a position), dysfunction of the leaflets or perforation of the interventricular septum (ventricular septal defect, VSD) occurs and requires immediate implantation of a second prosthesis within the first one. Results of this 'bailout' maneuver have not been reported yet. Of 305 TA-AVI procedures, 15 patients required a second prosthesis due to dysfunctional leaflets (n = 6), low position (n = 7), or VSD (n = 2). Mean age was 82.5 ± 1.3 years, mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was 45.5 ± 5.4, and Society of Thoracic Surgeons (STS) Score was 13.5 ± 1.5. All second SAPIEN™ valves could be implanted successfully within the first one. The second prosthesis solved leaflet dysfunction, sealed the VSD (lower position of the second prosthesis), or corrected the initial misplacement (higher position of the second prosthesis) in all patients. Within 30 days, four patients died (low cardiac output n = 3, all with preoperative ejection fraction (EF) <35%; intestinal ischemia n = 1). Intra-operative echocardiogram and angiogram revealed mild paravalvular leak in three and none/trace in 12 patients. Transvalvular gradients were low despite the implantation of the second valve (P(max)/mean 13.7 ± 4.3/6.4 ± 2.0). Placement of a second SAPIEN™ valve is a valuable 'bailout' technique in case of VSD, dysfunctional leaflets, or too low placement of the first prosthesis. The technique leads to an excellent functional result with low transvalvular gradients. The simple, straight, tubular stent design of the SAPIEN™ prosthesis may be the ideal design for such valve-in-valve procedures. Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Conformational changes of an ion-channel during gating and emerging electrophysiologic properties: Application of a computational approach to cardiac Kv7.1.

PubMed

Nekouzadeh, Ali; Rudy, Yoram

2016-01-01

Ion channels are the "building blocks" of the excitation process in excitable tissues. Despite advances in determining their molecular structure, understanding the relationship between channel protein structure and electrical excitation remains a challenge. The Kv7.1 potassium channel is an important determinant of the cardiac action potential and its adaptation to rate changes. It is subject to beta adrenergic regulation, and many mutations in the channel protein are associated with the arrhythmic long QT syndrome. In this theoretical study, we use a novel computational approach to simulate the conformational changes that Kv7.1 undergoes during activation gating and compute the resulting electrophysiologic function in terms of single-channel and macroscopic currents. We generated all possible conformations of the S4-S5 linker that couples the S3-S4 complex (voltage sensor domain, VSD) to the pore, and all associated conformations of VSD and the pore (S6). Analysis of these conformations revealed that VSD-to-pore mechanical coupling during activation gating involves outward translation of the voltage sensor, accompanied by a translation away from the pore and clockwise twist. These motions cause pore opening by moving the S4-S5 linker upward and away from the pore, providing space for the S6 tails to move away from each other. Single channel records, computed from the simulated motion trajectories during gating, have stochastic properties similar to experimentally recorded traces. Macroscopic current through an ensemble of channels displays two key properties of Kv7.1: an initial delay of activation and fast inactivation. The simulations suggest a molecular mechanism for fast inactivation; a large twist of the VSD following its outward translation results in movement of the base of the S4-S5 linker toward the pore, eliminating open pore conformations to cause inactivation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Aviation Communications Emulation Testbed

NASA Technical Reports Server (NTRS)

Sheehe, Charles; Mulkerin, Tom

2004-01-01

Aviation related applications that rely upon datalink for information exchange are increasingly being developed and deployed. The increase in the quantity of applications and associated data communications will expose problems and issues to resolve. NASA Glenn Research Center has prepared to study the communications issues that will arise as datalink applications are employed within the National Airspace System (NAS) by developing a aviation communications emulation testbed. The Testbed is evolving and currently provides the hardware and software needed to study the communications impact of Air Traffic Control (ATC) and surveillance applications in a densely populated environment. The communications load associated with up to 160 aircraft transmitting and receiving ATC and surveillance data can be generated in real time in a sequence similar to what would occur in the NAS.

Closed-chest transthoracic magnetic resonance imaging-guided ventricular septal defect closure in swine.

PubMed

Ratnayaka, Kanishka; Saikus, Christina E; Faranesh, Anthony Z; Bell, Jamie A; Barbash, Israel M; Kocaturk, Ozgur; Reyes, Christine A; Sonmez, Merdim; Schenke, William H; Wright, Victor J; Hansen, Michael S; Slack, Michael C; Lederman, Robert J

2011-12-01

The aim of this study was to close ventricular septal defects (VSDs) directly through the chest wall using magnetic resonance imaging (MRI) guidance, without cardiopulmonary bypass, sternotomy, or radiation exposure. Surgical, percutaneous, and hybrid management of VSD each have limitations and known morbidity. Percutaneous muscular VSDs were created in 10 naive Yorkshire swine using a transjugular laser catheter. Under real-time MRI guidance, a direct transthoracic vascular access sheath was introduced through the chest into the heart along a trajectory suitable for VSD access and closure. Through this transthoracic sheath, muscular VSDs were occluded using a commercial nitinol device. Finally, the right ventricular free wall was closed using a commercial collagen plug intended for arterial closure. Anterior, posterior, and mid-muscular VSDs (6.8 ± 1.8 mm) were created. VSDs were closed successfully in all animals. The transthoracic access sheath was displaced in 2, both fatal. Thereafter, we tested an intracameral retention sheath to prevent this complication. Right ventricular access ports were closed successfully in all, and after as many as 30 days, healed successfully. Real-time MRI guidance allowed closed-chest transthoracic perventricular muscular VSD closure in a clinically meaningful animal model. Once applied to patients, this approach may avoid traditional surgical, percutaneous, or open-chest transcatheter ("hybrid") risks. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Closed-Chest Transthoracic Magnetic Resonance Imaging-Guided Ventricular Septal Defect Closure in Swine

PubMed Central

Ratnayaka, Kanishka; Saikus, Christina E.; Faranesh, Anthony Z.; Bell, Jamie A.; Barbash, Israel M.; Kocaturk, Ozgur; Reyes, Christine A.; Sonmez, Merdim; Schenke, William H.; Wright, Victor J.; Hansen, Michael S.; Slack, Michael C.; Lederman, Robert J.

2012-01-01

Objectives The aim of this study was to close ventricular septal defects (VSDs) directly through the chest wall using magnetic resonance imaging (MRI) guidance, without cardiopulmonary bypass, sternotomy, or radiation exposure. Background Surgical, percutaneous, and hybrid management of VSD each have limitations and known morbidity. Methods Percutaneous muscular VSDs were created in 10 naive Yorkshire swine using a transjugular laser catheter. Under real-time MRI guidance, a direct transthoracic vascular access sheath was introduced through the chest into the heart along a trajectory suitable for VSD access and closure. Through this transthoracic sheath, muscular VSDs were occluded using a commercial nitinol device. Finally, the right ventricular free wall was closed using a commercial collagen plug intended for arterial closure. Results Anterior, posterior, and mid-muscular VSDs (6.8 ± 1.8 mm) were created. VSDs were closed successfully in all animals. The transthoracic access sheath was displaced in 2, both fatal. Thereafter, we tested an intracameral retention sheath to prevent this complication. Right ventricular access ports were closed successfully in all, and after as many as 30 days, healed successfully. Conclusions Real-time MRI guidance allowed closed-chest transthoracic perventricular muscular VSD closure in a clinically meaningful animal model. Once applied to patients, this approach may avoid traditional surgical, percutaneous, or open-chest transcatheter (“hybrid”) risks. PMID:22192373

Caution is required in interpretation of mutations in the voltage sensing domain of voltage gated channels as evidence for gating mechanisms.

PubMed

Kariev, Alisher M; Green, Michael E

2015-01-12

The gating mechanism of voltage sensitive ion channels is generally considered to be the motion of the S4 transmembrane segment of the voltage sensing domains (VSD). The primary supporting evidence came from R → C mutations on the S4 transmembrane segment of the VSD, followed by reaction with a methanethiosulfonate (MTS) reagent. The cys side chain is -SH (reactive form -S-); the arginine side chain is much larger, leaving space big enough to accommodate the MTS sulfonate head group. The cavity created by the mutation has space for up to seven more water molecules than were present in wild type, which could be displaced irreversibly by the MTS reagent. Our quantum calculations show there is major reorientation of three aromatic residues that face into the cavity in response to proton displacement within the VSD. Two phenylalanines reorient sufficiently to shield/unshield the cysteine from the intracellular and extracellular ends, depending on the proton positions, and a tyrosine forms a hydrogen bond to the cysteine sulfur with its side chain -OH. These could produce the results of the experiments that have been interpreted as evidence for physical motion of the S4 segment, without physical motion of the S4 backbone. The computations strongly suggest that the interpretation of cysteine substitution reaction experiments be re-examined in the light of these considerations.

Delayed diagnosis of traumatic ventricular septal defect in penetrating chest injury: small evidence on echocardiography makes big difference.

PubMed

Jeon, Kihyun; Lim, Woo-Hyun; Kang, Si-Hyuck; Cho, Iksung; Kim, Kyung-Hee; Kim, Hyung-Kwan; Kim, Yong-Jin; Sohn, Dae-Won

2010-03-01

Cardiac trauma from penetrating chest injury is a life-threatening condition. It was reported that < 10% of patients arrives at the emergency department alive. Penetrating chest injury can cause serious damage in more than 1 cardiac structure, including myocardial lacerations, ventricular septal defect (VSD), fistula between aorta and right cardiac chamber and valves. The presence of pericardial effusion (even a small amount) on the initial echocardiography might be the only clue to serious cardiac damage in the absence of definite evidence of anatomical defect in heart. We here present a case, in which clear diagnosis of VSD and pseudoaneurysmal formation was delayed a few days after penetrating chest injury due to the lack of anatomical evidence of damage.

Efficacy of combined treatment with vacuum sealing drainage and recombinant human epidermal growth factor for refractory wounds in the extremities and its effect on serum levels of IL-6, TNF-α and IL-2

PubMed Central

Tan, Lei; Hou, Zhongyu; Gao, Yanzhi

2018-01-01

The objective of this study was to investigate the efficacy of combined treatment with vacuum sealing drainage (VSD) and recombinant human epidermal growth factor (rhEGF) for refractory wounds in the extremities, and its effect on serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-2. Ninety-eight patients with refractory wounds in the extremities were recruited and randomly divided into the combined treatment group (underwent VSD and rhEGF treatment) and control group (underwent VSD only) with 49 cases each. Formation of granulation tissue on the wound surface was assessed and scored. The wound healing rate was calculated after 1 week of treatment, and the time of complete healing was recorded. Serum levels of IL-6, IL-2, and TNF-α were measured using enzyme-linked immunosorbent assay. After 1 week of treatment, granulation tissue formation on wound surfaces was significantly improved (p<0.05) compared with that before treatment in both groups. Moreover, granulation tissue formation on wound surfaces was superior in the combined treatment group than in the control group (p<0.05). The wound healing rate was 63.50±4.75% in the combined treatment group and 31.79±3.52% in the control group, and the difference was statistically significant (p<0.05). The time of complete healing was 15.11±2.24 days in the combined treatment group and 19.63±2.76 days in the control group, and the difference was statistically significant (p<0.05). The serum levels of IL-6, IL-2, and TNF-α, in the two groups were significantly lower than those before treatment (p<0.05). Moreover, the levels in the combined treatment group were significantly lower than those in the control group (p<0.05). In conclusion, combined treatment with VSD and rhEGF reduced inflammation and shortened the time of complete healing of refractory wounds in the extremities. Measurement of the levels of related inflammatory factors provided a reference for the prognosis of refractory wounds. PMID:29250151

[The influence of oxygen partial pressure change and vascularization of rabbit wound through negative pressure wound therapy].

PubMed

Yang, Fan; Hu, Duan; Bai, Xiang-jun; Zhang, Kun; Li, Ren-jie; Xue, Chen-chen

2012-07-01

To investigate the effect of vacuum sealing drainage (VSD) on variation of oxygen partial pressure (PtO2) and vascularization. The 12 cases of rabbit's wound models were undergoing the VSD (vacuum group, n = 6) or conventional therapy (conventional group, n = 6). Variation of PtO2 was measured by oxygen partial pressure admeasuring apparatus, expression of hypoxia inducible factor 1α (HIF-1α) mRNA was measured by real-time fluorescent quantitative PCR, content of vascular endothelial growth factor (VEGF) was measured by ELISA after tissue homogenate in 7 days. Vascular endothelial cell (VEC) and new blood capillary (NBC) of hematoxylin-eosin slice of tissue were counted by using light microscope. Average value of PtO2 of vacuum group was significant lower than conventional group (t = -99.780 to -5.305, P < 0.01). Expression of HIF-1α (30 minutes, 1, 6, 12 hours were 3.11 ± 0.07, 3.68 ± 0.26, 4.16 ± 0.13 and 3.91 ± 0.26 respectively) and content of VEGF (30 minutes, 1, 6, 12 hours were 103.3 ± 2.4, 134.2 ± 9.0, 167.8 ± 3.8 and 232.1 ± 9.5 respectively) of vacuum group were increased after 30 minutes and significant lower than conventional group (t = 13.038 - 80.208, P < 0.01), and both of them were reduced after 24 hours (P < 0.05). Counting numbers of VEC (2.47 ± 0.45 to 4.70 ± 0.38) and NBC (1.33 ± 0.49 to 4.33 ± 0.68) of vacuum group were increased at the same time-point and significant higher than conventional group (t = -0.670 to 16.500, P < 0.05). PtO2 of wound surface could be reduced significantly by VSD. Expression of HIF-1α and content of VEGF were increased by VSD for enhancing differentiated state of VEC and construction of NBC, which were better for vascularization and wound healing.

[Effects of vacuum sealing drainage combined with irrigation of oxygen loaded fluid on wounds of pa- tients with chronic venous leg ulcers].

PubMed

Wen, Huangding; Li, Zhiqing; Zhang, Meiguang; Wang, Jiahan; Wang, Guifang; Wu, Qi; Tong, Sen

2015-04-01

To evaluate the therapeutic effects of VSD combined with irrigation of oxygen loaded fluid on the growth of granulation tissue and macrophage polarization in chronic venous leg ulcers. Thiry-four patients with chronic venous leg ulcers hospitalized in our department from December 2010 to July 2014 were divided into VSD group ( A, n = 11) , VSD + irrigation group ( B, n = 11) , and VSD + oxygen loaded fluid irrigation group ( C, n = 12) according to the random number table. After admissian, debridement was performed, and granulation tissue in the center of the wound was harvested during the operation. After dehridement, the patients in group A were treated with VSD only (negative pressure from -30 to -25 kPa, the same below) ; the patients in group B were treated with VSD combining irrigation of normal saline; the patients in group C were treated with VSD combining normal saline loaded with oxygen irrigation (flow of 1 L/min) . On post treatment day (PTD) 7, the VSD devices were removed. Cross observation was conducted before debridement and on PTD 7. On PTD 7, the granulation tissue in the center of the wound was harvested for histopathological observation with HE staining and Masson staining, following calculation of granulation tissue coverage rate. After debridement but before the negative pressure therapy (hereinafter referred to as before treatment) and on PTD 7, partial pressure of oxygen of the skin around the wound was measured by transcutaneous tissue oxygen tension survey meter. On PTD 7, expression of vascular endothelial growth factor (VECF) was determined with immunohistochemistry. Before treatment and on PTD 7, cells with double positive expressions of induced nitric oxide synthase plus CD68 ( type I macro- phage) and arginase 1 plus CD68 ( type II macrophage) were observed with immunofluorescence staining and quantified. Data were processed with Fisher's exact test, one-way analysis of variance, covariance analysis, paired test, and LSD test. (1) The gross observation showed that before debridement there was a certain amount of necrotic tissue and little granulation tissue in the wounds of patients in all the 3 groups. On PTD 7, new granulation tissue was found in the wounds of patients in all the 3 groups, and in group C its amount was the largest. (2) On PTD 7, the granulation tissue coverage rate of wounds in pa- tients of group C was higher than that of group A or B ( P <0.05 or P <0.01). (3) On PTD 7, HE staining showed that there appeared more abundant new born microvessels and fibroblasts in the wounds of patients in group C than those in groups A and B; Masson staining showed that there was more abundant fresh collagen distributed orderly in the wounds of patients in group C compared with group A or B. (4) On PTD 7, it was found that partial pressure of oxygen of the skin around the wounds in patients of group C [(40.7 +/- 4.1) mmHg, 1 mmHg = 0.133 kPa] was higher than that of group A [ (35.0 +/- 3.1) mmHg] or B [(35.4 +/- 2.7) mmHg, with P values below 0.01]; the partial pressure of oxygen of the skin around the wounds of patients in all the 3 groups was increased significantly compared with that before treatment (with values from 10.38 to 22.52, P values below 0.01). (5) On PTD 7, the expression of VECF in the wounds of patients in group C was higher than that in group A or B ( P <0.05 or P < 0.01). (6) On PTD 7, the number of type I macrophages in granulation tissue of patients was respectively 14.3 +/- 2.3, 11.5 +/- 3.0, and 10.7 +/- 2.3 per 400 times vision field in groups A , B, and C ( F = 25.14, P < 0.01), while the number in group C was less than that in group A or B ( P < 0.05 or P < 0.01). Compared with that before treatment, the number of type I macrophages was significantly decreased on PTD 7 in all the 3 groups (with values from 14.76 to 23. 73, P values below 0. 01). On PTD 7, the number of type II macrophages in granulation tissue of patients was respectively 32.7 +/- 3.2, 35.1 +/- 3.3 , and 41.3 +/- 3.2 per 400 times vision field in groups A, B, and C ( F = 81.10, P < 0.01), and the number in group C was lager than that in group A or B ( with P values below 0. 01). Compared with that before treatment, the number of type II macrophages in all the 3 groups was significantly increased (with t values from -69.34 to -47.95, P values below 0.01). VSD combined with irrigation of oxygen loaded fluid can raise the partial pressure of oxygen of the skin around the wounds effectively, promoting the transition of macrophages from type I to type II, thus it may promote the growth of granulation tissue, resulting in a better recipient for skin grafting or epithelization.

In Vivo Voltage-Sensitive Dye Study of Lateral Spreading of Cortical Activity in Mouse Primary Visual Cortex Induced by a Current Impulse

PubMed Central

Fehérvári, Tamás Dávid; Sawai, Hajime; Yagi, Tetsuya

2015-01-01

In the mammalian primary visual cortex (V1), lateral spreading of excitatory potentials is believed to be involved in spatial integrative functions, but the underlying cortical mechanism is not well understood. Visually-evoked population-level responses have been shown to propagate beyond the V1 initial activation site in mouse, similar to higher mammals. Visually-evoked responses are, however, affected by neuronal circuits prior to V1 (retina, LGN), making the separate analysis of V1 difficult. Intracortical stimulation eliminates these initial processing steps. We used in vivo RH1691 voltage-sensitive dye (VSD) imaging and intracortical microstimulation in adult C57BL/6 mice to elucidate the spatiotemporal properties of population-level signal spreading in V1 cortical circuits. The evoked response was qualitatively similar to that measured in single-cell electrophysiological experiments in rodents: a fast transient fluorescence peak followed by a fast and a slow decrease or hyperpolarization, similar to EPSP and fast and slow IPSPs in single cells. The early cortical response expanded at speeds commensurate with long horizontal projections (at 5% of the peak maximum, 0.08–0.15 m/s) however, the bulk of the VSD signal propagated slowly (at half-peak maximum, 0.05–0.08 m/s) suggesting an important role of regenerative multisynaptic transmission through short horizontal connections in V1 spatial integrative functions. We also found a tendency for a widespread and fast cortical response suppression in V1, which was eliminated by GABAA-antagonists gabazine and bicuculline methiodide. Our results help understand the neuronal circuitry involved in lateral spreading in V1. PMID:26230520

Flight Test Results of VDL-3, 1090ES, and UAT Datalinks for Weather Information Communication

NASA Technical Reports Server (NTRS)

Griner, James

2006-01-01

This presentation describes final test results for the Weather Information Communications (WINCOMM) program at the NASA Glenn Research Center on flight testing of the 1090 Extended Squitter (1090ES), VDL Mode 3, and Universal Access Transceiver (UAT) data links as a medium for weather data exchange. It presents an architectural description of the use of 1090ES to meet the program objectives of sending turbulence information, the use of VDL Mode 3 to send graphical weather images, and the use of UAT for transmitting weather sensor data. This presentation provides a high level definition of the changes made to both avionics and ground-based receivers as well as the ground infrastructure used to support flight testing and future implementation. Summary of results from flight tests of these datalinks will also be presented.

System and Method for Aiding Pilot Preview, Rehearsal, Review, and Real-Time Visual Acquisition of Flight Mission Progress

NASA Technical Reports Server (NTRS)

Prinzel, III, Lawrence J. (Inventor); Pope, Alan T. (Inventor); Williams, Steven P. (Inventor); Bailey, Randall E. (Inventor); Arthur, Jarvis J. (Inventor); Kramer, Lynda J. (Inventor); Schutte, Paul C. (Inventor)

2012-01-01

Embodiments of the invention permit flight paths (current and planned) to be viewed from various orientations to provide improved path and terrain awareness via graphical two-dimensional or three-dimensional perspective display formats. By coupling the flight path information with a terrain database, uncompromising terrain awareness relative to the path and ownship is provided. In addition, missed approaches, path deviations, and any navigational path can be reviewed and rehearsed before performing the actual task. By rehearsing a particular mission, check list items can be reviewed, terrain awareness can be highlighted, and missed approach procedures can be discussed by the flight crew. Further, the use of Controller Pilot Datalink Communications enables data-linked path, flight plan changes, and Air Traffic Control requests to be integrated into the flight display of the present invention.

Training General Aviation Pilots for Convective Weather Situations.

PubMed

Blickensderfer, Elizabeth L; Lanicci, John M; Vincent, Michael J; Thomas, Robert L; Smith, MaryJo; Cruit, Jessica K

2015-10-01

Over the past 10-15 yr, considerable research has occurred for the development, testing, and fielding of real-time Datalink weather products for general aviation (GA) pilots to use before and during flight. As is the case with the implementation of most new technologies, work is needed to ensure that the users (in this case, the pilots) understand both the capabilities and limitations of the new technologies as well as how to use the new systems to improve their task performance. The purpose of this study was to replicate and extend a previous study on training pilots how and when to use these new weather technologies. This field study used a quasi-experimental design (pre- vs. post-test with a control group). There were 91 GA pilots from the Midwest, Northeastern, and Southeastern United States who participated in a 2-h short course or a control activity. The lecture-based short course covered radar basics, Next Generation Weather Radar (NEXRAD), NEXRAD specifics/limitations, thunderstorm basics, radar products, and decision making. The pilots who participated in the course earned higher knowledge test scores, improved at applying the concepts in paper-based flight scenarios, had higher self-efficacy in post-training assessments as compared to pre-training assessments, and also performed better than did control subjects on post-test knowledge and skills assessments. GA pilots lack knowledge about real-time Datalink weather technology. This study indicates that a relatively short training program was effective for fostering Datalink weather-related knowledge and skills in GA pilots.

Ventricular Septal Defect (For Teens)

MedlinePlus

... a VSD are at greater risk for developing endocarditis , an infection of the inner surface of the ... The best way to protect the heart from endocarditis is to reduce oral bacteria by brushing and ...

Ventricular Septal Defect (For Parents)

MedlinePlus

... a VSD are at greater risk for developing endocarditis , an infection of the inner surface of the ... The best way to protect the heart from endocarditis is to reduce oral bacteria by brushing and ...

Caution Is Required in Interpretation of Mutations in the Voltage Sensing Domain of Voltage Gated Channels as Evidence for Gating Mechanisms

PubMed Central

Kariev, Alisher M.; Green, Michael E.

2015-01-01

The gating mechanism of voltage sensitive ion channels is generally considered to be the motion of the S4 transmembrane segment of the voltage sensing domains (VSD). The primary supporting evidence came from R→C mutations on the S4 transmembrane segment of the VSD, followed by reaction with a methanethiosulfonate (MTS) reagent. The cys side chain is –SH (reactive form –S−); the arginine side chain is much larger, leaving space big enough to accommodate the MTS sulfonate head group. The cavity created by the mutation has space for up to seven more water molecules than were present in wild type, which could be displaced irreversibly by the MTS reagent. Our quantum calculations show there is major reorientation of three aromatic residues that face into the cavity in response to proton displacement within the VSD. Two phenylalanines reorient sufficiently to shield/unshield the cysteine from the intracellular and extracellular ends, depending on the proton positions, and a tyrosine forms a hydrogen bond to the cysteine sulfur with its side chain –OH. These could produce the results of the experiments that have been interpreted as evidence for physical motion of the S4 segment, without physical motion of the S4 backbone. The computations strongly suggest that the interpretation of cysteine substitution reaction experiments be re-examined in the light of these considerations. PMID:25588216

Histotripsy for Pediatric Cardiac Applications: In Vivo Neonatal Pig Model

NASA Astrophysics Data System (ADS)

Miller, Ryan M.; Owens, Gabe; Ensing, Gregory; Ludomirsky, Achiau; Cain, Charles; Xu, Zhen

2010-03-01

This study investigated the in vivo feasibility of using histotripsy to non-invasively create a flow channel between the ventricles by generating a perforation of the ventricular septum, clinically referred to as a ventricular septum defect (VSD). The overall goal is to develop a non-invasive procedure to aid in the treatment of neonatal patients with complex congenital heart diseases such as Hypoplastic Left Heart Syndrome (HLHS). Histotripsy is a therapeutic ultrasound technique that produces mechanical fractionation of soft tissue through controlled cavitation. The study was conducted in a live and intact neonatal pig model. The ventricular septum in the neonatal pig heart was treated with histotripsy delivered by a spherically focused 1 MHz transducer positioned outside the chest wall. Histotripsy treatment was applied using 5-cycle ultrasound pulses at 1 kHz pulse repetition frequency with 12-18 MPa peak negative pressure. The treatment was guided and monitored with ultrasound imaging. In all nine subjects treated, a bubble cloud was generated on the ventricular septum using histotripsy, and visualized with ultrasound imaging. Within 20 seconds to 4 minutes following the initiation of a bubble cloud, a VSD was created in all nine pigs and confirmed by the detection of blood flow through the ventricular septum with color Doppler ultrasound. Gross morphology and histology on all hearts showed a demarcated perforation in the ventricular septum. This study shows that a VSD can be created in an intact neonatal animal using extracorporeal histotripsy under real-time ultrasound guidance.

A Software Suite for Testing SpaceWire Devices and Networks

NASA Astrophysics Data System (ADS)

Mills, Stuart; Parkes, Steve

2015-09-01

SpaceWire is a data-handling network for use on-board spacecraft, which connects together instruments, mass-memory, processors, downlink telemetry, and other on-board sub-systems. SpaceWire is simple to implement and has some specific characteristics that help it support data-handling applications in space: high-speed, low-power, simplicity, relatively low implementation cost, and architectural flexibility making it ideal for many space missions. SpaceWire provides high-speed (2 Mbits/s to 200 Mbits/s), bi-directional, full-duplex data-links, which connect together SpaceWire enabled equipment. Data-handling networks can be built to suit particular applications using point-to-point data-links and routing switches. STAR-Dundee’s STAR-System software stack has been designed to meet the needs of engineers designing and developing SpaceWire networks and devices. This paper describes the aims of the software and how those needs were met.

Finalizing the CCSDS Space-Data Link Layer Security Protocol: Setup and Execution of the Interoperability Testing

NASA Technical Reports Server (NTRS)

Fischer, Daniel; Aguilar-Sanchez, Ignacio; Saba, Bruno; Moury, Gilles; Biggerstaff, Craig; Bailey, Brandon; Weiss, Howard; Pilgram, Martin; Richter, Dorothea

2015-01-01

The protection of data transmitted over the space-link is an issue of growing importance also for civilian space missions. Through the Consultative Committee for Space Data Systems (CCSDS), space agencies have reacted to this need by specifying the Space Data-Link Layer Security (SDLS) protocol which provides confidentiality and integrity services for the CCSDS Telemetry (TM), Telecommand (TC) and Advanced Orbiting Services (AOS) space data-link protocols. This paper describes the approach of the CCSDS SDLS working group to specify and execute the necessary interoperability tests. It first details the individual SDLS implementations that have been produced by ESA, NASA, and CNES and then the overall architecture that allows the interoperability tests between them. The paper reports on the results of the interoperability tests and identifies relevant aspects for the evolution of the test environment.

[Effectiveness of vacuum sealing drainage combined with anti-taken skin graft for primary closing of open amputation wound].

PubMed

Liao, Qiande; Xu, Jian; Weng, Xiao-Jun; Zhong, Da; Liu, Zhiqin; Wang, Chenggong

2012-05-01

To observe the effectiveness of vacuum sealing drainage (VSD) combined with anti-taken skin graft on open amputation wound by comparing with direct anti-taken skin graft. Between March 2005 and June 2010, 60 cases of amputation wounds for limbs open fractures were selected by using the random single-blind method. The amputation wounds were treated with VSD combined with anti-taken skin graft (test group, n = 30) and direct anti-taken skin graft (control group, n = 30). No significant difference was found in age, gender, injury cause, amputation level, defect size, preoperative albumin index, or injury time between 2 groups (P > 0.05). In test group, the redundant stump skin was used to prepare reattached staggered-meshed middle-thickness skin flap by using a drum dermatome dealing after amputation, which was transplanted amputation wounds, and then the skin surface was covered with VSD for continuous negative pressure drainage for 7-10 days. In control group, wounds were covered by anti-taken thickness skin flap directly after amputation, and conventional dress changing was given. To observe the survival condition of the skin graft in test group, the VSD device was removed at 8 days after operation. The skin graft survival rate, wound infection rate, reamputation rate, times of dressing change, and the hospitalization days in test group were significantly better than those in control group [ 90.0% vs. 63.3%, 3.3% vs. 20.0%, 0 vs. 13.3%, (2.0 +/- 0.5) times vs. (8.0 +/- 1.5) times, and (12.0 +/- 2.6) days vs. (18.0 +/- 3.2) days, respectively] (P < 0.05). The patients were followed up 1-3 years with an average of 2 years. At last follow-up, the scar area and grading, and two-point discrimination of wound in test group were better than those in control group, showing significant differences (P < 0.05). No obvious swelling occurred at the residual limbs in 2 groups. The limb pain incidence and the residual limb length were better in test group than those in control group (P < 0.05). Whereas, no significant difference was found in the shape of the residual limbs between 2 groups (P > 0.05). In comparison with the contralateral limbs, the muscle had disuse atrophy and decreased strength in residual limbs of 2 groups. There was significant difference in the muscle strength between normal and affected limbs (P < 0.05), but no significant difference was found in affected limbs between 2 groups (P > 0.05). Compared with direct anti-taken skin graft on amputation wound, the wound could be closed primarily by using the VSD combined with anti-taken skin graft. At the same time it could achieve better wound drainage, reduce infection rate, promote good adhesion of wound, improve skin survival rate, and are beneficial to lower the amputation level, so it is an ideal way to deal with amputation wound in the phase I.

Ventricular Septal Defect (VSD)

MedlinePlus

... hears a murmur while listening to your baby's heart with a stethoscope. Sometimes VSDs can be detected by ultrasound before ... murmur your doctor hears when listening to your heart with a stethoscope. When to see a doctor Call your doctor ...

FASTSIM2: a second-order accurate frictional rolling contact algorithm

NASA Astrophysics Data System (ADS)

Vollebregt, E. A. H.; Wilders, P.

2011-01-01

In this paper we consider the frictional (tangential) steady rolling contact problem. We confine ourselves to the simplified theory, instead of using full elastostatic theory, in order to be able to compute results fast, as needed for on-line application in vehicle system dynamics simulation packages. The FASTSIM algorithm is the leading technology in this field and is employed in all dominant railway vehicle system dynamics packages (VSD) in the world. The main contribution of this paper is a new version "FASTSIM2" of the FASTSIM algorithm, which is second-order accurate. This is relevant for VSD, because with the new algorithm 16 times less grid points are required for sufficiently accurate computations of the contact forces. The approach is based on new insights in the characteristics of the rolling contact problem when using the simplified theory, and on taking precise care of the contact conditions in the numerical integration scheme employed.

Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain.

PubMed

Li, Qufei; Wanderling, Sherry; Paduch, Marcin; Medovoy, David; Singharoy, Abhishek; McGreevy, Ryan; Villalba-Galea, Carlos A; Hulse, Raymond E; Roux, Benoît; Schulten, Klaus; Kossiakoff, Anthony; Perozo, Eduardo

2014-03-01

The transduction of transmembrane electric fields into protein motion has an essential role in the generation and propagation of cellular signals. Voltage-sensing domains (VSDs) carry out these functions through reorientations of positive charges in the S4 helix. Here, we determined crystal structures of the Ciona intestinalis VSD (Ci-VSD) in putatively active and resting conformations. S4 undergoes an ~5-Å displacement along its main axis, accompanied by an ~60° rotation. This movement is stabilized by an exchange in countercharge partners in helices S1 and S3 that generates an estimated net charge transfer of ~1 eo. Gating charges move relative to a ''hydrophobic gasket' that electrically divides intra- and extracellular compartments. EPR spectroscopy confirms the limited nature of S4 movement in a membrane environment. These results provide an explicit mechanism for voltage sensing and set the basis for electromechanical coupling in voltage-dependent enzymes and ion channels.

The voltage-sensing domain of a phosphatase gates the pore of a potassium channel.

PubMed

Arrigoni, Cristina; Schroeder, Indra; Romani, Giulia; Van Etten, James L; Thiel, Gerhard; Moroni, Anna

2013-03-01

The modular architecture of voltage-gated K(+) (Kv) channels suggests that they resulted from the fusion of a voltage-sensing domain (VSD) to a pore module. Here, we show that the VSD of Ciona intestinalis phosphatase (Ci-VSP) fused to the viral channel Kcv creates Kv(Synth1), a functional voltage-gated, outwardly rectifying K(+) channel. Kv(Synth1) displays the summed features of its individual components: pore properties of Kcv (selectivity and filter gating) and voltage dependence of Ci-VSP (V(1/2) = +56 mV; z of ~1), including the depolarization-induced mode shift. The degree of outward rectification of the channel is critically dependent on the length of the linker more than on its amino acid composition. This highlights a mechanistic role of the linker in transmitting the movement of the sensor to the pore and shows that electromechanical coupling can occur without coevolution of the two domains.

Structural basis of lipid-driven conformational transitions in the KvAP voltage-sensing domain.

PubMed

Li, Qufei; Wanderling, Sherry; Sompornpisut, Pornthep; Perozo, Eduardo

2014-02-01

Voltage-gated ion channels respond to transmembrane electric fields through reorientations of the positively charged S4 helix within the voltage-sensing domain (VSD). Despite a wealth of structural and functional data, the details of this conformational change remain controversial. Recent electrophysiological evidence showed that equilibrium between the resting ('down') and activated ('up') conformations of the KvAP VSD from Aeropyrum pernix can be biased through reconstitution in lipids with or without phosphate groups. We investigated the structural transition between these functional states, using site-directed spin-labeling and EPR spectroscopic methods. Solvent accessibility and interhelical distance determinations suggest that KvAP gates through S4 movements involving an ∼3-Å upward tilt and simultaneous ∼2-Å axial shift. This motion leads to large accessibly changes in the intracellular water-filled crevice and supports a new model of gating that combines structural rearrangements and electric-field remodeling.

Analysis of reportable events in Kansas City air route traffic control center

DOT National Transportation Integrated Search

2017-02-10

The implementation of ControllerPilot Datalink Communications (CPDLC) in domestic en route airspace will change the controllers and pilots : tasks, which will, in turn change the types of observed errors. This study characterizes the current...

Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics

PubMed Central

Kozyrev, Vladislav; Eysel, Ulf T.; Jancke, Dirk

2014-01-01

Transcranial magnetic stimulation (TMS) is widely used in clinical interventions and basic neuroscience. Additionally, it has become a powerful tool to drive plastic changes in neuronal networks. However, highly resolved recordings of the immediate TMS effects have remained scarce, because existing recording techniques are limited in spatial or temporal resolution or are interfered with by the strong TMS-induced electric field. To circumvent these constraints, we performed optical imaging with voltage-sensitive dye (VSD) in an animal experimental setting using anaesthetized cats. The dye signals reflect gradual changes in the cells' membrane potential across several square millimeters of cortical tissue, thus enabling direct visualization of TMS-induced neuronal population dynamics. After application of a single TMS pulse across visual cortex, brief focal activation was immediately followed by synchronous suppression of a large pool of neurons. With consecutive magnetic pulses (10 Hz), widespread activity within this “basin of suppression” increased stepwise to suprathreshold levels and spontaneous activity was enhanced. Visual stimulation after repetitive TMS revealed long-term potentiation of evoked activity. Furthermore, loss of the “deceleration–acceleration” notch during the rising phase of the response, as a signature of fast intracortical inhibition detectable with VSD imaging, indicated weakened inhibition as an important driving force of increasing cortical excitability. In summary, our data show that high-frequency TMS changes the balance between excitation and inhibition in favor of an excitatory cortical state. VSD imaging may thus be a promising technique to trace TMS-induced changes in excitability and resulting plastic processes across cortical maps with high spatial and temporal resolutions. PMID:25187557

Modulating the Voltage-sensitivity of a Genetically Encoded Voltage Indicator

PubMed Central

Jung, Arong; Rajakumar, Dhanarajan; Yoon, Bong-June

2017-01-01

Saturation mutagenesis was performed on a single position in the voltage-sensing domain (VSD) of a genetically encoded voltage indicator (GEVI). The VSD consists of four transmembrane helixes designated S1-S4. The V220 position located near the plasma membrane/extracellular interface had previously been shown to affect the voltage range of the optical signal. Introduction of polar amino acids at this position reduced the voltage-dependent optical signal of the GEVI. Negatively charged amino acids slightly reduced the optical signal by 33 percent while positively charge amino acids at this position reduced the optical signal by 80%. Surprisingly, the range of V220D was similar to that of V220K with shifted optical responses towards negative potentials. In contrast, the V220E mutant mirrored the responses of the V220R mutation suggesting that the length of the side chain plays in role in determining the voltage range of the GEVI. Charged mutations at the 219 position all behaved similarly slightly shifting the optical response to more negative potentials. Charged mutations to the 221 position behaved erratically suggesting interactions with the plasma membrane and/or other amino acids in the VSD. Introduction of bulky amino acids at the V220 position increased the range of the optical response to include hyperpolarizing signals. Combining The V220W mutant with the R217Q mutation resulted in a probe that reduced the depolarizing signal and enhanced the hyperpolarizing signal which may lead to GEVIs that only report neuronal inhibition. PMID:29093633

Modulating the Voltage-sensitivity of a Genetically Encoded Voltage Indicator.

PubMed

Jung, Arong; Rajakumar, Dhanarajan; Yoon, Bong-June; Baker, Bradley J

2017-10-01

Saturation mutagenesis was performed on a single position in the voltage-sensing domain (VSD) of a genetically encoded voltage indicator (GEVI). The VSD consists of four transmembrane helixes designated S1-S4. The V220 position located near the plasma membrane/extracellular interface had previously been shown to affect the voltage range of the optical signal. Introduction of polar amino acids at this position reduced the voltage-dependent optical signal of the GEVI. Negatively charged amino acids slightly reduced the optical signal by 33 percent while positively charge amino acids at this position reduced the optical signal by 80%. Surprisingly, the range of V220D was similar to that of V220K with shifted optical responses towards negative potentials. In contrast, the V220E mutant mirrored the responses of the V220R mutation suggesting that the length of the side chain plays in role in determining the voltage range of the GEVI. Charged mutations at the 219 position all behaved similarly slightly shifting the optical response to more negative potentials. Charged mutations to the 221 position behaved erratically suggesting interactions with the plasma membrane and/or other amino acids in the VSD. Introduction of bulky amino acids at the V220 position increased the range of the optical response to include hyperpolarizing signals. Combining The V220W mutant with the R217Q mutation resulted in a probe that reduced the depolarizing signal and enhanced the hyperpolarizing signal which may lead to GEVIs that only report neuronal inhibition.

Estimating pressure gradients by auscultation: How technology (echocardiography) can help improve clinical skills

PubMed Central

Kadle, Rohini L; Phoon, Colin K L

2017-01-01

AIM To extend our previously-published experience in estimating pressure gradients (PG) via physical examination in a large patient cohort. METHODS From January 1, 1997 through December 31, 2009, an attending pediatric cardiologist compared clinical examination (EXAM) with Doppler-echo (ECHO), in 1193 patients with pulmonic stenosis (PS, including tetralogy of Fallot), aortic stenosis (AS), and ventricular septal defect (VSD). EXAM PG estimates were based primarily on a murmur’s pitch, grade, and length. ECHO peak instantaneous PG was derived from the modified Bernoulli equation. Patients were 0-38.4 years old (median 4.8). RESULTS For all patients, EXAM correlated highly with ECHO: ECHO = 0.99 (EXAM) + 3.2 mmHg; r = +0.89; P < 0.0001. Agreement was excellent (mean difference = -2.9 ± 16.1 mmHg). In 78% of all patients, agreement between EXAM and ECHO was within 15 mmHg and within 5 mmHg in 45%. Clinical estimates of PS PG were more accurate than of AS and VSD. A palpable precordial thrill and increasing loudness of the murmur predicted higher gradients (P < 0.0001). Weight did not influence accuracy. A learning curve was evident, such that the most recent quartile of patients showed ECHO = 1.01 (EXAM) + 1.9, r = +0.92, P < 0.0001; during this time, the attending pediatric cardiologist had been > 10 years in practice. CONCLUSION Clinical examination can accurately estimate PG in PS, AS, or VSD. Continual correlation of clinical findings with echocardiography can lead to highly accurate diagnostic skills. PMID:28932358

Results of comparing transthoracic device closure and surgical repair with right infra-axillary thoracotomy for perimembranous ventricular septal defects.

PubMed

Hu, Yijie; Li, Zhiping; Chen, Jianming; Li, Fuping; Shen, Cheng; Song, Yi; Zhao, Shulin; Peng, Caijing; Chen, Mingxiang; Zhong, Qianjin

2015-04-01

Transthoracic device closure (TTDC) and surgical repair with right infra-axillary thoracotomy (SRRIAT) are two main alternative minimally invasive approaches for restrictive perimembranous ventricular septal defect (VSD); however, few studies have compared them with each other in terms of effectiveness and cost. Patients with perimembranous VSD undergoing TTDC or SRRIAT from January 2012 to July 2013 were reviewed in a comparative investigation between the two procedures. Success from the procedures was achieved in 30 TTDC (30/33, 91%) and 96 SRRIAT patients (100%). Operation duration in the TTDC group was significantly shorter than that of the SRRIAT group (115.8 ± 43.8 vs 175.6 ± 41.3 min, P < 0.01). The total perioperative drainage, use of red blood cells, mechanical ventilation time, stay in the intensive care unit and hospital stay for the TTDC group were significantly less than those in the SRRIAT group. No deaths or complete atrioventricular block occurred in either group. One SRRIAT patient accepted a second surgery for residual shunt. TTDC costs slightly more than SRRIAT (40270.6 ± 2741.3 renmingbi [RMB] vs 32964.5 ± 8221.6 RMB, P < 0.01). Both TTDC and SRRIAT showed excellent outcomes and cosmetic appearance for suitable VSD candidates. Although its costs were higher, TTDC had the advantages over SRRIAT of a short operation duration and intensive care unit stay and fewer days in the hospital. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

The Role of a Novel Long Noncoding RNA TUC40- in Cardiomyocyte Induction and Maturation in P19 Cells.

PubMed

Li, Huijuan; Jiang, Li; Yu, Zhangbin; Han, Shuping; Liu, Xuehua; Li, Mengmeng; Zhu, Chun; Qiao, Lixing; Huang, Li

2017-12-01

In previous studies, TUC40-, a new long noncoding RNA, was found to be overexpressed in human ventricular septal defect (VSD) embryonic heart samples. In this article, we carried out experiments on the P19 cell line to elucidate the effects of TUC40- overexpression on cardiomyocyte development relevant to VSD pathogenesis. We established the overexpression cell model by plasmid transfection, and explored the expression profile of Pbx1, the sense gene of TUC40-, and the marker genes of cardiomyocyte linage commitment (Nkx2.5 and GATA4) and maturation (cardiac troponin T). In addition, we combined cell cycle and Cell Counting Kit-8 analysis to detect cell proliferation and used flow cytometry and caspase-3 assays to test apoptosis. At last, bioinformatics analysis was performed to show the possible role of TUC40-. In the control group, Pbx1 elevated steadily during cardiomyocyte induction; whereas in the overexpression group, it showed significantly lower expression at day 6, 8 and 10 of induction. Cells in the overexpression group failed to induce cardiomyocytes indicated by GATA4 and cardiac troponin T. Proliferation was inhibited possibly owing to G2/M cell cycle arrest and the induced apoptosis rate was higher in the overexpression group. TUC40- overexpression reduced Pbx1 expression, cardiomyocyte induction and differentiation, inhibited proliferation and promoted apoptosis. Combining the results and previous studies, we propose TUC40- as a potential pathologic factor for VSD. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Down-state model of the voltage-sensing domain of a potassium channel.

PubMed

Schow, Eric V; Freites, J Alfredo; Gogna, Karun; White, Stephen H; Tobias, Douglas J

2010-06-16

Voltage-sensing domains (VSDs) of voltage-gated potassium (Kv) channels undergo a series of conformational changes upon membrane depolarization, from a down state when the channel is at rest to an up state, all of which lead to the opening of the channel pore. The crystal structures reported to date reveal the pore in an open state and the VSDs in an up state. To gain insights into the structure of the down state, we used a set of experiment-based restraints to generate a model of the down state of the KvAP VSD using molecular-dynamics simulations of the VSD in a lipid bilayer in excess water. The equilibrated VSD configuration is consistent with the biotin-avidin accessibility and internal salt-bridge data used to generate it, and with additional biotin-avidin accessibility data. In the model, both the S3b and S4 segments are displaced approximately 10 A toward the intracellular side with respect to the up-state configuration, but they do not move as a rigid body. Arginine side chains that carry the majority of the gating charge also make large excursions between the up and down states. In both states, arginines interact with water and participate in salt bridges with acidic residues and lipid phosphate groups. An important feature that emerges from the down-state model is that the N-terminal half of the S4 segment adopts a 3(10)-helical conformation, which appears to be necessary to satisfy a complex salt-bridge network. (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Down-State Model of the Voltage-Sensing Domain of a Potassium Channel

PubMed Central

Schow, Eric V.; Freites, J. Alfredo; Gogna, Karun; White, Stephen H.; Tobias, Douglas J.

2010-01-01

Abstract Voltage-sensing domains (VSDs) of voltage-gated potassium (Kv) channels undergo a series of conformational changes upon membrane depolarization, from a down state when the channel is at rest to an up state, all of which lead to the opening of the channel pore. The crystal structures reported to date reveal the pore in an open state and the VSDs in an up state. To gain insights into the structure of the down state, we used a set of experiment-based restraints to generate a model of the down state of the KvAP VSD using molecular-dynamics simulations of the VSD in a lipid bilayer in excess water. The equilibrated VSD configuration is consistent with the biotin-avidin accessibility and internal salt-bridge data used to generate it, and with additional biotin-avidin accessibility data. In the model, both the S3b and S4 segments are displaced ∼10 Å toward the intracellular side with respect to the up-state configuration, but they do not move as a rigid body. Arginine side chains that carry the majority of the gating charge also make large excursions between the up and down states. In both states, arginines interact with water and participate in salt bridges with acidic residues and lipid phosphate groups. An important feature that emerges from the down-state model is that the N-terminal half of the S4 segment adopts a 310-helical conformation, which appears to be necessary to satisfy a complex salt-bridge network. PMID:20550898

Three pledget technique for closure of muscular ventricular septal defects.

PubMed

Sharma, Rajesh; Katewa, Ashish

2012-07-01

We propose a modification of the simple, horizontal mattress, pledgetted suture technique for closing the small muscular ventricular septal defect (VSD) by interposing an oversized third pledget on the left ventricular (LV) aspect of the defect.

Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling.

PubMed

Liu, Jinyan; Hu, Feng; Tang, Jintian; Tang, Shijie; Xia, Kun; Wu, Song; Yin, Chaoqi; Wang, Shaohua; He, Quanyong; Xie, Huiqing; Zhou, Jianda

2017-04-01

Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our homemade device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)‑1β expression, and downregulating IL‑10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)‑β and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen Ⅰ and Ⅲ were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)‑13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)‑1 and TIMP‑2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP‑1 and TIMP‑2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD‑induced PP on wound healing by regulating inflammation, secretion, proliferation and the distribution of different cells in wound tissue.

Multi-Gigabit Free-Space Optical Data Communication and Network System

DTIC Science & Technology

2016-04-01

IR), Ultraviolet ( UV ), Laser Transceiver, Adaptive Beam Tracking, Electronic Attack (EA), Cyber Attack, Multipoint-to-Multipoint Network, Adaptive...FileName.pptx Free Space Optical Datalink Timeline Phase 1 Point-to-point demonstration 2012 Future Adaptive optic & Quantum Cascade Laser

Analysis of Controller-Pilot Voice Communications from Kansas City Air Route Traffic Control Center

DOT National Transportation Integrated Search

2017-07-01

The implementation of Controller Pilot Datalink Communications (CPDLC) in domestic en route airspace is a key enabling technology in the Next Generation Air Transportation System. The Federal Aviation Administration plans to implement en route CPDLC ...

Chapter 22: Compressed Air Evaluation Protocol. The Uniform Methods Project: Methods for Determining Energy Efficiency Savings for Specific Measures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurnik, Charles W; Benton, Nathanael; Burns, Patrick

Compressed-air systems are used widely throughout industry for many operations, including pneumatic tools, packaging and automation equipment, conveyors, and other industrial process operations. Compressed-air systems are defined as a group of subsystems composed of air compressors, air treatment equipment, controls, piping, pneumatic tools, pneumatically powered machinery, and process applications using compressed air. A compressed-air system has three primary functional subsystems: supply, distribution, and demand. Air compressors are the primary energy consumers in a compressed-air system and are the primary focus of this protocol. The two compressed-air energy efficiency measures specifically addressed in this protocol are: High-efficiency/variable speed drive (VSD) compressormore » replacing modulating, load/unload, or constant-speed compressor; and Compressed-air leak survey and repairs. This protocol provides direction on how to reliably verify savings from these two measures using a consistent approach for each.« less

GOLD assessment of COPD severity in the Clinical Practice Research Datalink (CPRD).

PubMed

Rebordosa, Cristina; Plana, Estel; Aguado, Jaume; Thomas, Steven; García-Gil, Esther; Perez-Gutthann, Susana; Castellsague, Jordi

2018-05-08

To evaluate availability of spirometry and symptom data in the Clinical Practice Research Datalink (United Kingdom) to assess COPD severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016 definition and comparing it with an algorithm used in other studies. This was a descriptive, noninterventional, secondary database cohort study of patients with COPD aged 40 years or older, who initiated treatment with specific COPD medications. Patients were classified according to COPD severity (1) in GOLD 2016 "ABCD" categories based on symptoms (Medical Research Council dyspnea grade, COPD Assessment Test, breathlessness), percent predicted FEV1, and exacerbation history and (2) as mild, moderate, severe, or very severe based on treatment and exacerbation history. The study included 63 900 patients with COPD aged 40 years or older that were new users of 1 or more COPD medication of interest. Percent predicted FEV1 was available for 80.9% of patients; symptoms for 75.6% of patients. Classification into GOLD 2016 ABCD categories was possible for 75.6% of the patients. The GOLD 2016 ABCD definition classified more patients under the high-risk categories (22.1%, A; 18.8%, B; 21.3%, C; 37.9%, D) than did the adapted algorithm (7.9%, mild; 48.6%, moderate; 42.1%, severe; 1.4%, very severe). Using our adaptation of the GOLD 2016 COPD severity classification, the information in the Clinical Practice Research Datalink allowed us to ascertain COPD severity in approximately 75% of patients with COPD. Algorithms that include medication use tend to misclassify patients with the extreme COPD severity categories. Copyright © 2018 John Wiley & Sons, Ltd.

Aviation Communications Emulation Testbed

NASA Technical Reports Server (NTRS)

Sheehe, Charles; Mulkerin, Tom

2004-01-01

Aviation related applications that rely upon datalink for information exchange are increasingly being developed and deployed. The increase in the quantity of applications and associated data communications will expose problems and issues to resolve. NASA s Glenn Research Center has prepared to study the communications issues that will arise as datalink applications are employed within the National Airspace System (NAS) by developing an aviation communications emulation testbed. The Testbed is evolving and currently provides the hardware and software needed to study the communications impact of Air Traffic Control (ATC) and surveillance applications in a densely populated environment. The communications load associated with up to 160 aircraft transmitting and receiving ATC and surveillance data can be generated in realtime in a sequence similar to what would occur in the NAS. The ATC applications that can be studied are the Aeronautical Telecommunications Network s (ATN) Context Management (CM) and Controller Pilot Data Link Communications (CPDLC). The Surveillance applications are Automatic Dependent Surveillance - Broadcast (ADS-B) and Traffic Information Services - Broadcast (TIS-B).

"Party Line" Information Use Studies and Implications for ATC Datalink Communications

NASA Technical Reports Server (NTRS)

Hansman, R. John; Pritchett, Amy; Midkiff, Alan

1995-01-01

The perceived importance and utilization of 'party line' information by air carrier flight crews was investigated through pilot surveys and a flight simulation study. The importance, availability, and accuracy of party line information elements were explored through surveys of pilots of several operational types. The survey identified numerous traffic and weather party line information elements which were considered important. These elements were scripted into a full-mission flight simulation which examined the utilization of party line information by studying subject responses to specific information element stimuli. The awareness of the different Party Line elements varied, and awareness was also affected by pilot workload. In addition, pilots were aware of some traffic information elements, but were reluctant to act on Party Line Information alone. Finally, the results of both the survey and the simulation indicated that the importance of party line information appeared to be greatest for operations near or on the airport. This indicates that caution should be exercised when implementing datalink communications in tower and close-in terminal control sectors.

'Party Line' Information Use Studies and Implications for ATV Datalink Communications

NASA Technical Reports Server (NTRS)

Pritchett, Amy; Hansman, R. John; Midkiff, Alan

1995-01-01

The perceived importance and utilization of 'party line' information by air carrier flight crews was investigated through pilot surveys and a flight simulation study. The Importance, Availability, and Accuracy of party line information elements were explored through surveys of pilots of several operational types. The survey identified numerous traffic and weather party line information elements which were considered important. These elements were scripted into a full-mission flight simulation which examined the utilization of party line information by studying subject responses to specific information element stimuli. The awareness of the different Party Line elements varied, and awareness was also affected by pilot workload. In addition, pilots were aware of some traffic information elements, but were reluctant to act on Party Line Information alone. Finally, the importance of party line information appears to be greatest for operations near or on the airport. This indicates that caution should be exercised when implementing datalink communications in tower and close-in terminal control sectors.

A Voltage-Sensitive Dye-Based Assay for the Identification of Differentiated Neurons Derived from Embryonic Neural Stem Cell Cultures

PubMed Central

Emirandetti, Amanda; Lewicka, Michalina; Hermanson, Ola; Fisahn, André

2010-01-01

Background Pluripotent and multipotent stem cells hold great therapeutical promise for the replacement of degenerated tissue in neurological diseases. To fulfill that promise we have to understand the mechanisms underlying the differentiation of multipotent cells into specific types of neurons. Embryonic stem cell (ESC) and embryonic neural stem cell (NSC) cultures provide a valuable tool to study the processes of neural differentiation, which can be assessed using immunohistochemistry, gene expression, Ca2+-imaging or electrophysiology. However, indirect methods such as protein and gene analysis cannot provide direct evidence of neuronal functionality. In contrast, direct methods such as electrophysiological techniques are well suited to produce direct evidence of neural functionality but are limited to the study of a few cells on a culture plate. Methodology/Principal Findings In this study we describe a novel method for the detection of action potential-capable neurons differentiated from embryonic NSC cultures using fast voltage-sensitive dyes (VSD). We found that the use of extracellularly applied VSD resulted in a more detailed labeling of cellular processes compared to calcium indicators. In addition, VSD changes in fluorescence translated precisely to action potential kinetics as assessed by the injection of simulated slow and fast sodium currents using the dynamic clamp technique. We further demonstrate the use of a finite element model of the NSC culture cover slip for optimizing electrical stimulation parameters. Conclusions/Significance Our method allows for a repeatable fast and accurate stimulation of neurons derived from stem cell cultures to assess their differentiation state, which is capable of monitoring large amounts of cells without harming the overall culture. PMID:21079795

Functional characterization of Kv11.1 (hERG) potassium channels split in the voltage-sensing domain.

PubMed

de la Peña, Pilar; Domínguez, Pedro; Barros, Francisco

2018-03-23

Voltage-dependent KCNH family potassium channel functionality can be reconstructed using non-covalently linked voltage-sensing domain (VSD) and pore modules (split channels). However, the necessity of a covalent continuity for channel function has not been evaluated at other points within the two functionally independent channel modules. We find here that by cutting Kv11.1 (hERG, KCNH2) channels at the different loops linking the transmembrane spans of the channel core, not only channels split at the S4-S5 linker level, but also those split at the intracellular S2-S3 and the extracellular S3-S4 loops, yield fully functional channel proteins. Our data indicate that albeit less markedly, channels split after residue 482 in the S2-S3 linker resemble the uncoupled gating phenotype of those split at the C-terminal end of the VSD S4 transmembrane segment. Channels split after residues 514 and 518 in the S3-S4 linker show gating characteristics similar to those of the continuous wild-type channel. However, breaking the covalent link at this level strongly accelerates the voltage-dependent accessibility of a membrane impermeable methanethiosulfonate reagent to an engineered cysteine at the N-terminal region of the S4 transmembrane helix. Thus, besides that of the S4-S5 linker, structural integrity of the intracellular S2-S3 linker seems to constitute an important factor for proper transduction of VSD rearrangements to opening and closing the cytoplasmic gate. Furthermore, our data suggest that the short and probably rigid characteristics of the extracellular S3-S4 linker are not an essential component of the Kv11.1 voltage sensing machinery.

Mapping the membrane-aqueous border for the voltage-sensing domain of a potassium channel.

PubMed

Neale, Edward J; Rong, Honglin; Cockcroft, Christopher J; Sivaprasadarao, Asipu

2007-12-28

Voltage-sensing domains (VSDs) play diverse roles in biology. As integral components, they can detect changes in the membrane potential of a cell and couple these changes to activity of ion channels and enzymes. As independent proteins, homologues of the VSD can function as voltage-dependent proton channels. To sense voltage changes, the positively charged fourth transmembrane segment, S4, must move across the energetically unfavorable hydrophobic core of the bilayer, which presents a barrier to movement of both charged species and protons. To reduce the barrier to S4 movement, it has been suggested that aqueous crevices may penetrate the protein, reducing the extent of total movement. To investigate this hypothesis in a system containing fully functional channels in a native environment with an intact membrane potential, we have determined the contour of the membrane-aqueous border of the VSD of KvAP in Escherichia coli by examining the chemical accessibility of introduced cysteines. The results revealed the contour of the membrane-aqueous border of the VSD in its activated conformation. The water-inaccessible regions of S1 and S2 correspond to the standard width of the membrane bilayer (~28 A), but those of S3 and S4 are considerably shorter (> or = 40%), consistent with aqueous crevices pervading both the extracellular and intracellular ends. One face of S3b and the entire S3a were water-accessible, reducing the water-inaccessible region of S3 to just 10 residues, significantly shorter than for S4. The results suggest a key role for S3 in reducing the distance S4 needs to move to elicit gating.

Functional diversity of voltage-sensing phosphatases in two urodele amphibians.

PubMed

Mutua, Joshua; Jinno, Yuka; Sakata, Souhei; Okochi, Yoshifumi; Ueno, Shuichi; Tsutsui, Hidekazu; Kawai, Takafumi; Iwao, Yasuhiro; Okamura, Yasushi

2014-07-16

Voltage-sensing phosphatases (VSPs) share the molecular architecture of the voltage sensor domain (VSD) with voltage-gated ion channels and the phosphoinositide phosphatase region with the phosphatase and tensin homolog (PTEN), respectively. VSPs enzymatic activities are regulated by the motions of VSD upon depolarization. The physiological role of these proteins has remained elusive, and insights may be gained by investigating biological variations in different animal species. Urodele amphibians are vertebrates with potent activities of regeneration and also show diverse mechanisms of polyspermy prevention. We cloned cDNAs of VSPs from the testes of two urodeles; Hynobius nebulosus and Cynops pyrrhogaster, and compared their expression and voltage-dependent activation. Their molecular architecture is highly conserved in both Hynobius VSP (Hn-VSP) and Cynops VSP (Cp-VSP), including the positively-charged arginine residues in the S4 segment of the VSD and the enzymatic active site for substrate binding, yet the C-terminal C2 domain of Hn-VSP is significantly shorter than that of Cp-VSP and other VSP orthologs. RT-PCR analysis showed that gene expression pattern was distinct between two VSPs. The voltage sensor motions and voltage-dependent phosphatase activities were investigated electrophysiologically by expression in Xenopus oocytes. Both VSPs showed "sensing" currents, indicating that their voltage sensor domains are functional. The phosphatase activity of Cp-VSP was found to be voltage dependent, as shown by its ability to regulate the conductance of coexpressed GIRK2 channels, but Hn-VSP lacked such phosphatase activity due to the truncation of its C2 domain. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

The cardiac proteome in patients with congenital ventricular septal defect: A comparative study between right atria and right ventricles.

PubMed

Bond, A R; Iacobazzi, D; Abdul-Ghani, S; Ghorbel, M T; Heesom, K J; George, S J; Caputo, M; Suleiman, M-S; Tulloh, R M

2018-03-20

Right ventricle (RV) remodelling occurs in neonatal patients born with ventricular septal defect (VSD). The presence of a defect between the two ventricles allows for shunting of blood from the left to right side. The resulting RV hypertrophy leads to molecular remodelling which has thus far been largely investigated using right atrial (RA) tissue. In this study we used proteomic and phosphoproteomic analysis in order to determine any difference between the proteomes for RA and RV. Samples were therefore taken from the RA and RV of five infants (0.34 ± 0.05 years, mean ± SEM) with VSD who were undergoing cardiac surgery to repair the defect. Significant differences in protein expression between RV and RA were seen. 150 protein accession numbers were identified which were significantly lower in the atria, whereas none were significantly higher in the atria compared to the ventricle. 19 phosphorylation sites (representing 19 phosphoproteins) were also lower in RA. This work has identified differences in the proteome between RA and RV which reflect differences in contractile activity and metabolism. As such, caution should be used when drawing conclusions based on analysis of the RA and extrapolating to the hypertrophied RV. RV hypertrophy occurs in neonatal patients born with VSD. Very little is known about how the atria responds to RV hypertrophy, especially at the protein level. Access to tissue from age-matched groups of patients is very rare, and we are in the unique position of being able to get tissue from both the atria and ventricle during reparative surgery of these infants. Our findings will be beneficial to future research into heart chamber malformations in congenital heart defects. Copyright © 2018. Published by Elsevier B.V.

Assessing the accuracy of different simplified frictional rolling contact algorithms

NASA Astrophysics Data System (ADS)

Vollebregt, E. A. H.; Iwnicki, S. D.; Xie, G.; Shackleton, P.

2012-01-01

This paper presents an approach for assessing the accuracy of different frictional rolling contact theories. The main characteristic of the approach is that it takes a statistically oriented view. This yields a better insight into the behaviour of the methods in diverse circumstances (varying contact patch ellipticities, mixed longitudinal, lateral and spin creepages) than is obtained when only a small number of (basic) circumstances are used in the comparison. The range of contact parameters that occur for realistic vehicles and tracks are assessed using simulations with the Vampire vehicle system dynamics (VSD) package. This shows that larger values for the spin creepage occur rather frequently. Based on this, our approach is applied to typical cases for which railway VSD packages are used. The results show that particularly the USETAB approach but also FASTSIM give considerably better results than the linear theory, Vermeulen-Johnson, Shen-Hedrick-Elkins and Polach methods, when compared with the 'complete theory' of the CONTACT program.

Expression of the voltage-sensing phosphatase gene in the chick embryonic tissues and in the adult cerebellum.

PubMed

Yamaguchi, Shinji; Aoki, Naoya; Kitajima, Takaaki; Okamura, Yasushi; Homma, Koichi J

2014-10-01

Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor domain (VSD) and the cytoplasmic domain with phosphoinositide-phosphatase activities. It operates as the voltage sensor and directly translates membrane potential into phosphoinositide turnover by coupling VSD to the cytoplasmic domain. VSPs are evolutionarily conserved from marine invertebrate up to humans. Recently, we demonstrated that ectopic expression of the chick ortholog of VSP, Gg-VSP, in a fibroblast cell line caused characteristic cell process outgrowths. Co-expression of chick PTEN suppressed such morphological change, suggesting that VSP regulates cell shape by increasing PI(3,4)P2. However, the in vivo function of Gg-VSP remains unclear. Here, we showed that in chick embryos Gg-VSP is expressed in the stomach, mesonephros, pharyngeal arch, limb bud, somites, floor plate of neural tube, and notochord. In addition, both Gg-VSP transcripts and the protein were found in the cerebellar Purkinje neurons. These findings provide an insight into the physiological functions of VSP.

Structural Mechanism of Voltage-Dependent Gating in an Isolated Voltage-Sensing Domain

PubMed Central

Li, Qufei; Wanderling, Sherry; Paduch, Marcin; Medovoy, David; Singharoy, Abhishek; McGreevy, Ryan; Villalba-Galea, Carlos; Hulse, Raymond E.; Roux, Benoit; Schulten, Klaus; Kossiakoff, Anthony; Perozo, Eduardo

2014-01-01

SUMMARY The transduction of transmembrane electric fields into protein motion plays an essential role in the generation and propagation of cellular signals. Voltage-sensing domains (VSD) carry out these functions through reorientations of S4 helix with discrete gating charges. Here, crystal structures of the VSD from Ci-VSP were determined in both, active (Up) and resting (Down) conformations. The S4 undergoes a ~5 Å displacement along its main axis accompanied by a ~60o rotation, consistent with the helix-screw gating mechanism. This movement is stabilized by a change in countercharge partners in helices S1 and S3, generating an estimated net charge transfer of ~1 eo. Gating charges move relative to a “hydrophobic gasket” that electrically divides intra and extracellular compartments. EPR spectroscopy confirms the limited nature of S4 movement in a membrane environment. These results provide an explicit mechanism for voltage sensing and set the basis for electromechanical coupling in voltage-dependent cellular activities. PMID:24487958

The voltage-sensing domain of a phosphatase gates the pore of a potassium channel

PubMed Central

Arrigoni, Cristina; Schroeder, Indra; Romani, Giulia; Van Etten, James L.; Thiel, Gerhard

2013-01-01

The modular architecture of voltage-gated K+ (Kv) channels suggests that they resulted from the fusion of a voltage-sensing domain (VSD) to a pore module. Here, we show that the VSD of Ciona intestinalis phosphatase (Ci-VSP) fused to the viral channel Kcv creates KvSynth1, a functional voltage-gated, outwardly rectifying K+ channel. KvSynth1 displays the summed features of its individual components: pore properties of Kcv (selectivity and filter gating) and voltage dependence of Ci-VSP (V1/2 = +56 mV; z of ∼1), including the depolarization-induced mode shift. The degree of outward rectification of the channel is critically dependent on the length of the linker more than on its amino acid composition. This highlights a mechanistic role of the linker in transmitting the movement of the sensor to the pore and shows that electromechanical coupling can occur without coevolution of the two domains. PMID:23440279

Expression and testing in plants of ArcLight, a genetically-encoded voltage indicator used in neuroscience research.

PubMed

Matzke, Antonius J M; Matzke, Marjori

2015-10-12

It is increasingly appreciated that electrical controls acting at the cellular and supra-cellular levels influence development and initiate rapid responses to environmental cues. An emerging method for non-invasive optical imaging of electrical activity at cell membranes uses genetically-encoded voltage indicators (GEVIs). Developed by neuroscientists to chart neuronal circuits in animals, GEVIs comprise a fluorescent protein that is fused to a voltage-sensing domain. One well-known GEVI, ArcLight, undergoes strong shifts in fluorescence intensity in response to voltage changes in mammalian cells. ArcLight consists of super-ecliptic (SE) pHluorin (pH-sensitive fluorescent protein) with an A227D substitution, which confers voltage sensitivity in neurons, fused to the voltage-sensing domain of the voltage-sensing phosphatase of C iona i ntestinalis (Ci-VSD). In an ongoing effort to adapt tools of optical electrophysiology for plants, we describe here the expression and testing of ArcLight and various derivatives in different membranes of root cells in Arabidopsis thaliana. Transgenic constructs were designed to express ArcLight and various derivatives targeted to the plasma membrane and nuclear membranes of Arabidopsis root cells. In transgenic seedlings, changes in fluorescence intensity of these reporter proteins following extracellular ATP (eATP) application were monitored using a fluorescence microscope equipped with a high speed camera. Coordinate reductions in fluorescence intensity of ArcLight and Ci-VSD-containing derivatives were observed at both the plasma membrane and nuclear membranes following eATP treatments. However, similar responses were observed for derivatives lacking the Ci-VSD. The dispensability of the Ci-VSD suggests that in plants, where H(+) ions contribute substantially to electrical activities, the voltage-sensing ability of ArcLight is subordinate to the pH sensitivity of its SEpHluorin base. The transient reduction of ArcLight fluorescence triggered by eATP most likely reflects changes in pH and not membrane voltage. The pH sensitivity of ArcLight precludes its use as a direct sensor of membrane voltage in plants. Nevertheless, ArcLight and derivatives situated in the plasma membrane and nuclear membranes may offer robust, fluorescence intensity-based pH indicators for monitoring concurrent changes in pH at these discrete membrane systems. Such tools will assist analyses of pH as a signal and/or messenger at the cell surface and the nuclear periphery in living plants.

Development and Validation of a Controlled Virtual Environment for Guidance, Navigation and Control of Quadrotor UAV

DTIC Science & Technology

2013-09-01

Width Modulation QuarC Quanser Real-time Control RC Remote Controlled RPV Remotely Piloted Vehicles SLAM Simultaneous Localization and Mapping UAV...development of the following systems: 1. Navigation (GPS, Lidar , etc.) 2. Communication (Datalink) 3. Ground Control Station (GUI, software programming

New Technologies for Reducing Aviation Weather-Related Accidents

NASA Technical Reports Server (NTRS)

Stough, H. Paul, III; Watson, James F., III; Jarrell, Michael A.

2006-01-01

The National Aeronautics and Space Administration (NASA) has developed technologies to reduce aviation weather-related accidents. New technologies are presented for data-link and display of weather information to aircraft in flight, for detection of turbulence ahead of aircraft in flight, and for automated insitu reporting of atmospheric conditions from aircraft.

Records Inventory Data Collection Software

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cole, Brian A.

1995-03-01

DATALINK was created to provide an easy to use data collection program for records management software products. It provides several useful tools for capturing and validating record index data in the field. It also allows users to easily create a comma delimited, ASCII text file for data export into most records management software products.

Flu Vaccine and People with Egg Allergies

MedlinePlus

... 12 through 2014–15 reported maximum amounts of ≤1 µg/0.5 mL dose for flu shots and 0.24 µg/0.2 mL dose ... reactions, including anaphylaxis. In a Vaccine Safety Datalink study, there were ... other vaccines, (rate of 1.35 per one million doses). Most of these ...

Cross-layer Joint Relay Selection and Power Allocation Scheme for Cooperative Relaying System

NASA Astrophysics Data System (ADS)

Zhi, Hui; He, Mengmeng; Wang, Feiyue; Huang, Ziju

2018-03-01

A novel cross-layer joint relay selection and power allocation (CL-JRSPA) scheme over physical layer and data-link layer is proposed for cooperative relaying system in this paper. Our goal is finding the optimal relay selection and power allocation scheme to maximize system achievable rate when satisfying total transmit power constraint in physical layer and statistical delay quality-of-service (QoS) demand in data-link layer. Using the concept of effective capacity (EC), our goal can be formulated into an optimal joint relay selection and power allocation (JRSPA) problem to maximize the EC when satisfying total transmit power limitation. We first solving optimal power allocation (PA) problem with Lagrange multiplier approach, and then solving optimal relay selection (RS) problem. Simulation results demonstrate that CL-JRSPA scheme gets larger EC than other schemes when satisfying delay QoS demand. In addition, the proposed CL-JRSPA scheme achieves the maximal EC when relay located approximately halfway between source and destination, and EC becomes smaller when the QoS exponent becomes larger.

The Effect of Ownship Information and NexRad Resolution on Pilot Decision Making in the Use of a Cockpit Weather Information Display

NASA Technical Reports Server (NTRS)

Novacek, Paul F.; Burgess, Malcolm A.; Heck, Michael L.; Stokes, Alan F.; Stough, H. Paul, III (Technical Monitor)

2001-01-01

A two-phase experiment was conducted to explore the effects of data-link weather displays upon pilot decision performance. The experiment was conducted with 49 instrument rated pilots who were divided into four groups and placed in a simulator with a realistic flight scenario involving weather containing convective activity. The inflight weather display depicted NEXRAD images, with graphical and textual METARs over a moving map display. The experiment explored the effect of weather information, ownship position symbology and NEXRAD cell size resolution. The phase-two experiment compared two groups using the data-linked weather display with ownship position symbology. These groups were compared to the phase-one group that did not have ownship position symbology. The phase-two pilots were presented with either large NEXRAD cell size (8 km) or small cell size (4 km). Observations noted that the introduction of ownship symbology did not appear to significantly impact the decision making process, however, the introduction of ownship did reduce workload. Additionally, NEXRAD cell size resolution did appear to influence the tactical decision making process.

Estimating the diagnostic accuracy of rheumatoid factor in UK primary care: a study using the Clinical Practice Research Datalink.

PubMed

Miller, Anne; Nightingale, Alison L; Sammon, Cormac J; Mahtani, Kamal R; Holt, Tim A; McHugh, Neil J; Luqmani, Raashid A

2015-10-01

To investigate the diagnostic accuracy of RF as a test for RA in primary care and its impact on referral times using the Clinical Practice Research Datalink. We identified all patients with a first RF test recorded in the Clinical Practice Research Datalink between 1 January 2000 and 31 December 2008 and those diagnosed with RA within 2 years of testing. We calculated likelihood ratios (LRs), sensitivity, specificity and predictive values of RF for a diagnosis of RA. We compared time to hospital referral in those testing positive and negative using Kaplan-Meier failure curves and log-rank tests. Of 62 436 first RF tests, 4679 (7.5%) were positive. There were 1753 incident cases of RA, of which 57.8% were seropositive. The positive LR for RF was 9.5 (95% CI 9.0, 10.0) and the negative LR was 0.5 (95% CI 0.4, 0.5). Sensitivity and specificity were 57.8% (95% CI 55.4%, 60.1%) and 93.9% (95% CI 93.7%, 94.1%) and the positive predictive value and negative predictive value were 21.4% (95% CI 20.3%, 22.6%) and 98.7% (95% CI 98.6%, 98.8%), respectively. Median time to first hospital contact after the first RF test in those with seropositive vs seronegative results was 54 days (95% CI 49, 58) vs 150 (95% CI 147, 152). Only 2.8% of patients undergoing RF testing were diagnosed with RA, suggesting that RF is used to screen patients with musculoskeletal symptoms rather than those with more specific features of RA. A positive RF test may be helpful in diagnosing RA in primary care but performs badly in excluding RA and may delay referral. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Vascular Streak Dieback of cacao in Southeast Asia detection and Melanesia: in planta detection of the pathogen and a new taxonomy

USDA-ARS?s Scientific Manuscript database

Vascular Streak Dieback (VSD) disease of cacao (Theobroma cacao) in Southeast Asia and Melanesia is caused by a basidiomycete (Ceratobasidiales) fungus described in a monotypic genus as Oncobasidium theobromae (syn. =Thanatephorus theobromae). The symptoms of the disease include green-spotted chloro...

Appreciative Inquiry: From Positive Narrative to Systemic Change

ERIC Educational Resources Information Center

Filleul, Mary

2009-01-01

As one of two newly-hired Learning & Development (L&D) consultants for the Vancouver School District (VSD), the author, along with an administrator, was tasked to design and implement a new district-wide focus around two core questions: "What Do We Know About Learning?" and "What Are We Doing About It?" In the spring of…

The ventral tegmental area modulates intracortical microstimulation (ICMS)-evoked M1 activity in a time-dependent manner.

PubMed

Kunori, Nobuo; Kajiwara, Riichi; Takashima, Ichiro

2016-03-11

Intracortical microstimulation (ICMS)-evoked neural activity combined with ventral tegmental area (VTA) stimulation was studied in rat primary motor cortex (M1). We used voltage-sensitive dye (VSD) imaging to analyze the spatiotemporal dynamics of M1 activity following VTA-M1 paired stimulation. VTA stimulation was preceded by M1 ICMS at inter-stimulus intervals (ISIs) of 15-350ms. VSD imaging showed an excitatory-inhibitory sequence of neural activity after composing VTA stimulus- and ICMS-induced M1 neural activity. To evaluate the net ICMS M1 response, the optical response to unpaired VTA stimulation was subtracted from the VTA-M1 paired response. This revealed that the net ICMS-evoked M1 neural activity was inhibited when the ISI was 30-50ms, but highly facilitated when the ISI was 100-350ms. These results suggest that VTA modulates M1 excitability in the order of tens to hundreds of milliseconds and might directly affect the motor command generation process in the M1. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PIP2-dependent coupling is prominent in Kv7.1 due to weakened interactions between S4-S5 and S6

NASA Astrophysics Data System (ADS)

Kasimova, Marina A.; Zaydman, Mark A.; Cui, Jianmin; Tarek, Mounir

2015-01-01

Among critical aspects of voltage-gated potassium (Kv) channels' functioning is the effective communication between their two composing domains, the voltage sensor (VSD) and the pore. This communication, called coupling, might be transmitted directly through interactions between these domains and, as recently proposed, indirectly through interactions with phosphatidylinositol-4,5-bisphosphate (PIP2), a minor lipid of the inner plasma membrane leaflet. Here, we show how the two components of coupling, mediated by protein-protein or protein-lipid interactions, both contribute in the Kv7.1 functioning. On the one hand, using molecular dynamics simulations, we identified a Kv7.1 PIP2 binding site that involves residues playing a key role in PIP2-dependent coupling. On the other hand, combined theoretical and experimental approaches have shown that the direct interaction between the segments of the VSD (S4-S5) and the pore (S6) is weakened by electrostatic repulsion. Finally, we conclude that due to weakened protein-protein interactions, the PIP2-dependent coupling is especially prominent in Kv7.1.

APPLICATION OF VACUUM SALT DISTILLATION TECHNOLOGY FOR THE REMOVAL OF FLUORIDE AND CHLORIDE FROM LEGACY FISSILE MATERIALS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pierce, R.; Peters, T.

2011-11-01

Between September 2009 and January 2011, the Savannah River National Laboratory (SRNL) and the Savannah River Site (SRS) HB-Line Facility designed, developed, tested, and successfully deployed a production-scale system for the distillation of sodium chloride (NaCl) and potassium chloride (KCl) from plutonium oxide (PuO{sub 2}). Subsequent efforts adapted the vacuum salt distillation (VSD) technology for the removal of chloride and fluoride from less-volatile halide salts at the same process temperature and vacuum. Calcium chloride (CaCl{sub 2}), calcium fluoride (CaF{sub 2}), and plutonium fluoride (PuF{sub 3}) were of particular concern. To enable the use of the same operating conditions for themore » distillation process, SRNL employed in situ exchange reactions to convert the less-volatile halide salts to compounds that facilitated the distillation of halide without removal of plutonium. SRNL demonstrated the removal of halide from CaCl{sub 2}, CaF{sub 2} and PuF{sub 3} below 1000 C using VSD technology.« less

Sensing charges of the Ciona intestinalis voltage-sensing phosphatase.

PubMed

Villalba-Galea, Carlos A; Frezza, Ludivine; Sandtner, Walter; Bezanilla, Francisco

2013-11-01

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to R232H, mediate voltage-dependent proton translocation across the membrane, indicating that these residues transit through the hydrophobic core of Ci-VSP as a function of the membrane potential. These observations indicate that the charges carried by these residues are sensing charges. Furthermore, our results also show that the electrical field in VSPs is focused in a narrow hydrophobic region that separates the extracellular and intracellular space and constitutes the energy barrier for charge crossing.

Virtual reality 3D echocardiography in the assessment of tricuspid valve function after surgical closure of ventricular septal defect.

PubMed

Bol Raap, Goris; Koning, Anton H J; Scohy, Thierry V; ten Harkel, A Derk-Jan; Meijboom, Folkert J; Kappetein, A Pieter; van der Spek, Peter J; Bogers, Ad J J C

2007-02-16

This study was done to investigate the potential additional role of virtual reality, using three-dimensional (3D) echocardiographic holograms, in the postoperative assessment of tricuspid valve function after surgical closure of ventricular septal defect (VSD). 12 data sets from intraoperative epicardial echocardiographic studies in 5 operations (patient age at operation 3 weeks to 4 years and bodyweight at operation 3.8 to 17.2 kg) after surgical closure of VSD were included in the study. The data sets were analysed as two-dimensional (2D) images on the screen of the ultrasound system as well as holograms in an I-space virtual reality (VR) system. The 2D images were assessed for tricuspid valve function. In the I-Space, a 6 degrees-of-freedom controller was used to create the necessary projectory positions and cutting planes in the hologram. The holograms were used for additional assessment of tricuspid valve leaflet mobility. All data sets could be used for 2D as well as holographic analysis. In all data sets the area of interest could be identified. The 2D analysis showed no tricuspid valve stenosis or regurgitation. Leaflet mobility was considered normal. In the virtual reality of the I-Space, all data sets allowed to assess the tricuspid leaflet level in a single holographic representation. In 3 holograms the septal leaflet showed restricted mobility that was not appreciated in the 2D echocardiogram. In 4 data sets the posterior leaflet and the tricuspid papillary apparatus were not completely included. This report shows that dynamic holographic imaging of intraoperative postoperative echocardiographic data regarding tricuspid valve function after VSD closure is feasible. Holographic analysis allows for additional tricuspid valve leaflet mobility analysis. The large size of the probe, in relation to small size of the patient, may preclude a complete data set. At the moment the requirement of an I-Space VR system limits the applicability in virtual reality 3D echocardiography in clinical practice.

Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

PubMed

Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M; Schulten, Klaus; Roux, Benoît

2015-10-01

The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with the consensus model of the resting state VSD and the spin-spin distance histograms from ESR/DEER experiments on T4 lysozyme are accurately reproduced.

The ladder-shaped polyether toxin gambierol anchors the gating machinery of Kv3.1 channels in the resting state

PubMed Central

Kopljar, Ivan; Labro, Alain J.; de Block, Tessa; Rainier, Jon D.; Tytgat, Jan

2013-01-01

Voltage-gated potassium (Kv) and sodium (Nav) channels are key determinants of cellular excitability and serve as targets of neurotoxins. Most marine ciguatoxins potentiate Nav channels and cause ciguatera seafood poisoning. Several ciguatoxins have also been shown to affect Kv channels, and we showed previously that the ladder-shaped polyether toxin gambierol is a potent Kv channel inhibitor. Most likely, gambierol acts via a lipid-exposed binding site, located outside the K+ permeation pathway. However, the mechanism by which gambierol inhibits Kv channels remained unknown. Using gating and ionic current analysis to investigate how gambierol affected S6 gate opening and voltage-sensing domain (VSD) movements, we show that the resting (closed) channel conformation forms the high-affinity state for gambierol. The voltage dependence of activation was shifted by >120 mV in the depolarizing direction, precluding channel opening in the physiological voltage range. The (early) transitions between the resting and the open state were monitored with gating currents, and provided evidence that strong depolarizations allowed VSD movement up to the activated-not-open state. However, for transition to the fully open (ion-conducting) state, the toxin first needed to dissociate. These dissociation kinetics were markedly accelerated in the activated-not-open state, presumably because this state displayed a much lower affinity for gambierol. A tetrameric concatemer with only one high-affinity binding site still displayed high toxin sensitivity, suggesting that interaction with a single binding site prevented the concerted step required for channel opening. We propose a mechanism whereby gambierol anchors the channel’s gating machinery in the resting state, requiring more work from the VSD to open the channel. This mechanism is quite different from the action of classical gating modifier peptides (e.g., hanatoxin). Therefore, polyether toxins open new opportunities in structure–function relationship studies in Kv channels and in drug design to modulate channel function. PMID:23401573

A complicated complex: Ion channels, voltage sensing, cell membranes and peptide inhibitors.

PubMed

Zhang, Alan H; Sharma, Gagan; Undheim, Eivind A B; Jia, Xinying; Mobli, Mehdi

2018-04-21

Voltage-gated ion channels (VGICs) are specialised ion channels that have a voltage dependent mode of action, where ion conduction, or gating, is controlled by a voltage-sensing mechanism. VGICs are critical for electrical signalling and are therefore important pharmacological targets. Among these, voltage-gated sodium channels (Na V s) have attracted particular attention as potential analgesic targets. Na V s, however, comprise several structurally similar subtypes with unique localisations and distinct functions, ranging from amplification of action potentials in nociception (e.g. Na V 1.7) to controlling electrical signalling in cardiac function (Na V 1.5). Understanding the structural basis of Na V function is therefore of great significance, both to our knowledge of electrical signalling and in development of subtype and state selective drugs. An important tool in this pursuit has been the use of peptides from animal venoms as selective Na V modulators. In this review, we look at peptides, particularly from spider venoms, that inhibit Na V s by binding to the voltage sensing domain (VSD) of this channel, known as gating modifier toxins (GMT). In the first part of the review, we look at the structural determinants of voltage sensing in VGICs, the gating cycle and the conformational changes that accompany VSD movement. Next, the modulation of the analgesic target Na V 1.7 by GMTs is reviewed to develop bioinformatic tools that, based on sequence information alone, can identify toxins that are likely to inhibit this channel. The same approach is also used to define VSD sequences, other than that from Na V 1.7, which are likely to be sensitive to this class of toxins. The final section of the review focuses on the important role of the cellular membrane in channel modulation and also how the lipid composition affects measurements of peptide-channel interactions both in binding kinetics measurements in solution and in cell-based functional assays. Copyright © 2018 Elsevier B.V. All rights reserved.

[Outcome of transcatheter closure of perimembranous ventricular septal defect with modified double-disk occluder device].

PubMed

Liu, Jing; You, Xiao-hua; Zhao, Xian-xian; Hu, Jian-qiang; Cao, Jiang; Xu, Rong-liang; Wu, Hong; Chen, Shao-ping; Zhang, Jian-liang; Zheng, Xing; Qin, Yong-wen

2010-04-01

To evaluate the efficacy and adverse effects of transcatheter closure of perimembranous ventricular septal defect (pmVSD) with modified double-disk occluder device (MDVO). Clinical data including clinical examination, electrocardiography daily after the procedure for a week, chest-X-rays and TTE before discharge and at 3-5 days after the procedure were analyzed from 604 patients underwent percutaneous closure of a pmVSD with MDVO at our department between December 2001 and December 2008. Procedure was successful in 576 out of 604 patients (95.4%) and 583 VSD occluders were placed. Endocarditis, thromboembolism, or deaths were not observed after procedure. Conduction block occurred in 81 patients (56 RBBB, 14 LBBB) and transient nonparoxysmal ventricular tachycardia in 31 patients after the procedure. Complete heart block occurred in 11 patients, 9 of them recovered in 3 weeks, permanent pacemaker was implanted in 2 patients (one had transient III degrees AVB before the procedure, the other underwent simultaneous closure of ventricular septal defect and atrial septal defect). Trivial/small residual shunts were found in 69 patients (12.0%). The residual shunts disappeared in 31 patients and remained unchanged in 38 patients (6.6%) 7 days after procedures. Aortic regurgitation developed in 5 patients (2 trivial/small, 3 small/moderate), and tricuspid regurgitation was present in 35 patients (32 trivial/small, 3 moderate). Five patients developed haemolysis (device retrieved via catheter in 1 patient due to persistent haemolysis, the other 4 patients recovered 3-14 days post procedure). Pseudoaneurysm of femoral artery occurred in 1 patient, and disappeared by pressure dressing. Device was successfully replaced in 2 patients with either device embolization (n = 1) or device misplacement (n = 1) after device retrieval by catheter. It is safe and effective to close congenital perimembranous ventricular septal defect with domestic-made occluder device.

Endophytic Association of Trichoderma asperellum within Theobroma cacao Suppresses Vascular Streak Dieback Incidence and Promotes Side Graft Growth

PubMed Central

Nasaruddin, Nasaruddin; Hendarto, Hendarto; Hakkar, Andi Akbar; Agriansyah, Nursalim

2016-01-01

Trichoderma species are able to persist on living sapwood and leaves of cacao (Theobroma cacao) in an endophytic relationship. In this research, we evaluated the ability of Trichodema asperellum introduced at the incision site in the bark for side grafting with the concentration of 4 g/10 mL, 4 g/100 mL, and 4 g/1,000 mL (suspended in water) in suppressing vascular streak dieback (VSD) incidence and promoting growth of side grafts in the field. The incidence of VSD in two local clones of cacao, MCC1 and M04, without application of T. asperellum was 71.2% and 70.1% at 21 wk after grafting, respectively. However, when the two clones were treated with a concentration of 4 g/10 mL T. asperellum, the incidence was 20.6% and 21.7%, respectively, compared to 29.1% and 20.9% at 4 g/100 mL and 18.2% and 15.6% at 4 g/1,000 mL. By comparing to the control, the treatment with the same concentrations of T. asperellum listed above, the total number of stomata in MCC1 decreased by 41.9%, 30.2%, and 14.0% and in M04 by 30.5%, 21.9%, and -2.5% (exception), respectively. Otherwise, the total area of stomata opening increased by 91.4%, 99.7%, and 28.6% in MCC1 and by 203.8%, 253.5%, and 35.9% in M04, respectively. Furthermore, the number of buds and branches treated with a mixture concentration on the the two clones increased by 90.7% and 21.7%, respectively. These data showed that the application of T. asperellum to cacao scions while grafting can decrease VSD incidence in side grafts and increase growth of grafts in addition to decreasing total number of stomata, increasing total area of opened stomata, and increasing number of buds and branches. PMID:27790069

Endophytic Association of Trichoderma asperellum within Theobroma cacao Suppresses Vascular Streak Dieback Incidence and Promotes Side Graft Growth.

PubMed

Rosmana, Ade; Nasaruddin, Nasaruddin; Hendarto, Hendarto; Hakkar, Andi Akbar; Agriansyah, Nursalim

2016-09-01

Trichoderma species are able to persist on living sapwood and leaves of cacao ( Theobroma cacao ) in an endophytic relationship. In this research, we evaluated the ability of Trichodema asperellum introduced at the incision site in the bark for side grafting with the concentration of 4 g/10 mL, 4 g/100 mL, and 4 g/1,000 mL (suspended in water) in suppressing vascular streak dieback (VSD) incidence and promoting growth of side grafts in the field. The incidence of VSD in two local clones of cacao, MCC1 and M04, without application of T. asperellum was 71.2% and 70.1% at 21 wk after grafting, respectively. However, when the two clones were treated with a concentration of 4 g/10 mL T. asperellum , the incidence was 20.6% and 21.7%, respectively, compared to 29.1% and 20.9% at 4 g/100 mL and 18.2% and 15.6% at 4 g/1,000 mL. By comparing to the control, the treatment with the same concentrations of T. asperellum listed above, the total number of stomata in MCC1 decreased by 41.9%, 30.2%, and 14.0% and in M04 by 30.5%, 21.9%, and -2.5% (exception), respectively. Otherwise, the total area of stomata opening increased by 91.4%, 99.7%, and 28.6% in MCC1 and by 203.8%, 253.5%, and 35.9% in M04, respectively. Furthermore, the number of buds and branches treated with a mixture concentration on the the two clones increased by 90.7% and 21.7%, respectively. These data showed that the application of T. asperellum to cacao scions while grafting can decrease VSD incidence in side grafts and increase growth of grafts in addition to decreasing total number of stomata, increasing total area of opened stomata, and increasing number of buds and branches.

Automated Aerial Refueling Concept of Operations

DTIC Science & Technology

2017-06-09

and their associated contractors . This document is suitable for release in the public domain; it may be included in DOD and NATO databases such as...5.3.5 TENSION DISCONNECT (BOOM/RECEPTACLE ONLY) ..................22 5.3.6 FUEL LEAKAGE...Navigation System (INS) technology to provide high -availability, high integrity, four dimensional guidance. A robust datalink will be needed with the

Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project

NASA Technical Reports Server (NTRS)

Shively, Jay

2017-01-01

Over the past 5 years, the UAS integration into the NAS project has worked to reduce technical barriers to integration. A major focus of this work has been in support of RTCA SC-228. This committee has recently published the first UAS integration minimum performance standards (MOPS). This work has spanned detect and avoid (DAA) as well as command and control comm datalinks. I will discuss DAA efforts with focus on the human systems work. I will discuss how automation was discussed and addressed within this context. ICAO stood up a remotely piloted aircraft systems (RPAS) panel in 2014. They have developed an RPAS manual and are now working to revise existing annexes and standards and recommended practices. The Human In The System (HITS) has worked to infuse human factors guidelines into those documents. I will discuss that effort as well as how ICAO has defined and address autonomy. There is a great deal of interest in the control of multiple vehicles by a single operator. The UAS EXCOM Science and Research Panel (SARP) is holding a workshop on this topic in late June. I will discuss research performed on this topic when I worked for the Army and on-going work within the division and a NATO working group on Human-Autonomy Teaming.

Trajectory Specification for Automation of Terminal Air Traffic Control

NASA Technical Reports Server (NTRS)

Paielli, Russell A.

2016-01-01

"Trajectory specification" is the explicit bounding and control of aircraft tra- jectories such that the position at each point in time is constrained to a precisely defined volume of space. The bounding space is defined by cross-track, along-track, and vertical tolerances relative to a reference trajectory that specifies position as a function of time. The tolerances are dynamic and will be based on the aircraft nav- igation capabilities and the current traffic situation. A standard language will be developed to represent these specifications and to communicate them by datalink. Assuming conformance, trajectory specification can guarantee safe separation for an arbitrary period of time even in the event of an air traffic control (ATC) sys- tem or datalink failure, hence it can help to achieve the high level of safety and reliability needed for ATC automation. As a more proactive form of ATC, it can also maximize airspace capacity and reduce the reliance on tactical backup systems during normal operation. It applies to both enroute airspace and the terminal area around airports, but this paper focuses on arrival spacing in the terminal area and presents ATC algorithms and software for achieving a specified delay of runway arrival time.

Support of Helicopter 'Free Flight' Operations in the 1996 Olympics

NASA Technical Reports Server (NTRS)

Branstetter, James R.; Cooper, Eric G.

1996-01-01

The microcosm of activity surrounding the 1996 Olympic Games provided researchers an opportunity for demonstrating state-of-the art technology in the first large-scale deployment of a prototype digital communication/navigation/surveillance system in a confined environment. At the same time it provided an ideal opportunity for transportation officials to showcase the merits of an integrated transportation system in meeting the operational needs to transport time sensitive goods and provide public safety services under real-world conditions. Five aeronautical CNS functions using a digital datalink system were chosen for operational flight testing onboard 91 aircraft, most of them helicopters, participating in the Atlanta Short-Haul Transportation System. These included: GPS-based Automatic Dependent Surveillance, Cockpit Display of Traffic Information, Controller-Pilot Communications, Graphical Weather Information (uplink), and Automated Electronic Pilot Reporting (downlink). Atlanta provided the first opportunity to demonstrate, in an actual operating environment, key datalink functions which would enhance flight safety and situational awareness for the pilot and supplement conventional air traffic control. The knowledge gained from such a large-scale deployment will help system designers in development of a national infrastructure where aircraft would have the ability to navigate autonomously.

Trajectory Specification for Terminal Air Traffic: Pairwise Conflict Detection and Resolution

NASA Technical Reports Server (NTRS)

Paielli, Russ; Erzberger, Heinz

2017-01-01

Trajectory specification is the explicit bounding and control of aircraft trajectories such that the position at each point in time is constrained to a precisely defined volume of space. The bounding space is defined by cross-track, along-track, and vertical tolerances relative to a reference trajectory that specifies position as a function of time. The tolerances are dynamic and will be based on the aircraft navigation capabilities and the current traffic situation. A standard language will be developed to represent these specifications and to communicate them by datalink. Assuming conformance, trajectory specification can guarantee safe separation for an arbitrary period of time even in the event of an air traffic control (ATC) system or datalink failure, hence it can help to achieve the high level of safety and reliability needed for ATC automation. As a more proactive form of ATC, it can also maximize airspace capacity and reduce the reliance on tactical backup systems during normal operation. It applies to both enroute airspace and the terminal area around airports, but this paper focuses on the terminal area and presents algorithms and software for spacing arrivals and deconflicting both arrivals and departures.

Structure of Voltage-gated Two-pore Channel TPC1 from Arabidopsis thaliana

PubMed Central

Guo, Jiangtao; Zeng, Weizhong; Chen, Qingfeng; Lee, Changkeun; Chen, Liping; Yang, Yi; Cang, Chunlei; Ren, Dejian; Jiang, Youxing

2015-01-01

Two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in both animals and plants as organellar cation channels. Here, we present the first crystal structure of a vacuolar two-pore channel from Arabidopsis thaliana, AtTPC1, which functions as a homodimer. AtTPC1 activation requires both voltage and cytosolic Ca2+. Ca2+ binding to the cytosolic EF-hand domain triggers conformational changes coupled to the pair of pore-lining inner helices (IS6 helices) from the first 6-TM domains, whereas membrane potential only activates the second voltage-sensing domain (VSD2) whose conformational changes are coupled to the pair of inner helices (IIS6 helices) from the second 6-TM domains. Luminal Ca2+ or Ba2+ can modulate voltage activation by stabilizing VSD2 in the resting state and shifts voltage activation towards more positive potentials. Our Ba2+ bound AtTPC1 structure reveals a voltage sensor in the resting state, providing hitherto unseen structural insight into the general voltage-gating mechanism among voltage-gated channels. PMID:26689363

CFIT Prevention Using Synthetic Vision

NASA Technical Reports Server (NTRS)

Arthur, Jarvis J., III; Prinzel, Lawrence J., III; Kramer, Lynda J.; Bailey, Randall E.; Parrish, Russell V.

2003-01-01

In commercial aviation, over 30-percent of all fatal accidents worldwide are categorized as Controlled Flight Into Terrain (CFIT) accidents where a fully functioning airplane is inadvertently flown into the ground, water, or an obstacle. An experiment was conducted at NASA Langley Research Center investigating the presentation of a synthetic terrain database scene to the pilot on a Primary Flight Display (PFD). The major hypothesis for the experiment is that a synthetic vision system (SVS) will improve the pilot s ability to detect and avoid a potential CFIT compared to conventional flight instrumentation. All display conditions, including the baseline, contained a Terrain Awareness and Warning System (TAWS) and Vertical Situation Display (VSD) enhanced Navigation Display (ND). Sixteen pilots each flew 22 approach - departure maneuvers in Instrument Meteorological Conditions (IMC) to the terrain challenged Eagle County Regional Airport (EGE) in Colorado. For the final run, the flight guidance cues were altered such that the departure path went into the terrain. All pilots with a SVS enhanced PFD (12 of 16 pilots) noticed and avoided the potential CFIT situation. All of the pilots who flew the anomaly with the baseline display configuration (which included a TAWS and VSD enhanced ND) had a CFIT event.

Sensing charges of the Ciona intestinalis voltage-sensing phosphatase

PubMed Central

Frezza, Ludivine; Sandtner, Walter

2013-01-01

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to R232H, mediate voltage-dependent proton translocation across the membrane, indicating that these residues transit through the hydrophobic core of Ci-VSP as a function of the membrane potential. These observations indicate that the charges carried by these residues are sensing charges. Furthermore, our results also show that the electrical field in VSPs is focused in a narrow hydrophobic region that separates the extracellular and intracellular space and constitutes the energy barrier for charge crossing. PMID:24127524

Molecular basis of the interaction between gating modifier spider toxins and the voltage sensor of voltage-gated ion channels

NASA Astrophysics Data System (ADS)

Lau, Carus H. Y.; King, Glenn F.; Mobli, Mehdi

2016-09-01

Voltage-sensor domains (VSDs) are modular transmembrane domains of voltage-gated ion channels that respond to changes in membrane potential by undergoing conformational changes that are coupled to gating of the ion-conducting pore. Most spider-venom peptides function as gating modifiers by binding to the VSDs of voltage-gated channels and trapping them in a closed or open state. To understand the molecular basis underlying this mode of action, we used nuclear magnetic resonance to delineate the atomic details of the interaction between the VSD of the voltage-gated potassium channel KvAP and the spider-venom peptide VSTx1. Our data reveal that the toxin interacts with residues in an aqueous cleft formed between the extracellular S1-S2 and S3-S4 loops of the VSD whilst maintaining lipid interactions in the gaps formed between the S1-S4 and S2-S3 helices. The resulting network of interactions increases the energetic barrier to the conformational changes required for channel gating, and we propose that this is the mechanism by which gating modifier toxins inhibit voltage-gated ion channels.

Listening to membrane potential: photoacoustic voltage-sensitive dye recording.

PubMed

Zhang, Haichong K; Yan, Ping; Kang, Jeeun; Abou, Diane S; Le, Hanh N D; Jha, Abhinav K; Thorek, Daniel L J; Kang, Jin U; Rahmim, Arman; Wong, Dean F; Boctor, Emad M; Loew, Leslie M

2017-04-01

Voltage-sensitive dyes (VSDs) are designed to monitor membrane potential by detecting fluorescence changes in response to neuronal or muscle electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. By contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near-infrared light excitation and ultrasound detection. Here, we show that voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. We synthesized a near-infrared photoacoustic VSD (PA-VSD), whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. A theoretical model accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate PA voltage sensing but also emphasize the interplay of both fluorescence and absorbance properties in the design of optimized PA probes. Together, our results demonstrate PA sensing as a potential new modality for recording and external imaging of electrophysiological and neurochemical events in the brain.

Preliminary study of gaze toward humans in photographs by individuals with autism, Down syndrome, or other intellectual disabilities: implications for design of visual scene displays.

PubMed

Wilkinson, Krista M; Light, Janice

2014-06-01

Visual scene displays (VSDs) are a form of augmentative and alternative communication display in which language concepts are embedded into an image of a naturalistic event. VSDs are based on the theory that language learning occurs through interactions with other people, and recommendations for VSD design have emphasized using images of these events that include humans. However, many VSDs also include other items that could potentially be distracting. We examined gaze fixation in 18 school-aged participants with and without severe intellectual/developmental disabilities (i.e., individuals with typical development, autism, Down syndrome and other intellectual disabilities) while they viewed photographs with human figures of various sizes and locations in the image, appearing alongside other interesting, and potentially distracting items. In all groups, the human figures attracted attention rapidly (within 1.5 seconds). The proportions of each participant's own fixation time spent on the human figures were similar across all groups, as were the proportions of total fixations made to the human figures. Although the findings are preliminary, this initial evidence supports the inclusion of humans in VSD images.

Voltage-gated proton (H(v)1) channels, a singular voltage sensing domain.

PubMed

Castillo, Karen; Pupo, Amaury; Baez-Nieto, David; Contreras, Gustavo F; Morera, Francisco J; Neely, Alan; Latorre, Ramon; Gonzalez, Carlos

2015-11-14

The main role of voltage-gated proton channels (Hv1) is to extrude protons from the intracellular milieu when, mediated by different cellular processes, the H(+) concentration increases. Hv1 are exquisitely selective for protons and their structure is homologous to the voltage sensing domain (VSD) of other voltage-gated ion channels like sodium, potassium, and calcium channels. In clear contrast to the classical voltage-dependent channels, Hv1 lacks a pore domain and thus permeation necessarily occurs through the voltage sensing domain. Hv1 channels are activated by depolarizing voltages, and increases in internal proton concentration. It has been proposed that local conformational changes of the transmembrane segment S4, driven by depolarization, trigger the molecular rearrangements that open Hv1. However, it is still unclear how the electromechanical coupling is achieved between the VSD and the potential pore, allowing the proton flux from the intracellular to the extracellular side. Here we provide a revised view of voltage activation in Hv1 channels, offering a comparative scenario with other voltage sensing channels domains. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Listening to membrane potential: photoacoustic voltage-sensitive dye recording

NASA Astrophysics Data System (ADS)

Zhang, Haichong K.; Yan, Ping; Kang, Jeeun; Abou, Diane S.; Le, Hanh N. D.; Jha, Abhinav K.; Thorek, Daniel L. J.; Kang, Jin U.; Rahmim, Arman; Wong, Dean F.; Boctor, Emad M.; Loew, Leslie M.

2017-04-01

Voltage-sensitive dyes (VSDs) are designed to monitor membrane potential by detecting fluorescence changes in response to neuronal or muscle electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. By contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near-infrared light excitation and ultrasound detection. Here, we show that voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. We synthesized a near-infrared photoacoustic VSD (PA-VSD), whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. A theoretical model accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate PA voltage sensing but also emphasize the interplay of both fluorescence and absorbance properties in the design of optimized PA probes. Together, our results demonstrate PA sensing as a potential new modality for recording and external imaging of electrophysiological and neurochemical events in the brain.

Comparison of the effects of mobile technology AAC apps on programming visual scene displays.

PubMed

Caron, Jessica; Light, Janice; Davidoff, Beth E; Drager, Kathryn D R

2017-12-01

Parents and professionals who work with individuals who use augmentative and alternative communication (AAC) face tremendous time pressures, especially when programming vocabulary in AAC technologies. System design (from programming functions to layout options) necessitates a range of skills related to operational competence and can impose intensive training demands for communication partners. In fact, some AAC applications impose considerable learning demands, which can lead to increased time to complete the same programming tasks. A within-subject design was used to investigate the comparative effects of three visual scene display AAC apps (GoTalk Now, AutisMate, EasyVSD) on the programming times for three off-line programming activities, by adults who were novices to programming AAC apps. The results indicated all participants were able to create scenes and add hotspots during off-line programming tasks with minimal self-guided training. The AAC app that had the least number of programming steps, EasyVSD, resulted in the fastest completion times across the three programming tasks. These results suggest that by simplifying the operational requirements of AAC apps the programming time is reduced, which may allow partners to better support individuals who use AAC.

Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice.

PubMed

Wang, Hao; Shun, Ming-Chieh; Dickson, Amy K; Engelman, Alan N

2015-01-01

Hepatoma-derived growth factor (HDGF) related protein 2 (HRP2) and lens epithelium-derived growth factor (LEDGF)/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human pathologies including cancer, autoimmunity, and infectious disease. Knockout of the Psip1 gene, which encodes for LEDGF/p75 and the shorter LEDGF/p52 isoform, was previously shown to cause perinatal lethality in mice. The function of HRP2 was by contrast largely unknown. To learn about the role of HRP2 in development, we knocked out the Hdgfrp2 gene, which encodes for HRP2, in both normal and Psip1 knockout mice. Hdgfrp2 knockout mice developed normally and were fertile. By contrast, the double deficient mice died at approximate embryonic day (E) 13.5. Histological examination revealed ventricular septal defect (VSD) associated with E14.5 double knockout embryos. To investigate the underlying molecular mechanism(s), RNA recovered from ventricular tissue was subjected to RNA-sequencing on the Illumina platform. Bioinformatic analysis revealed several genes and biological pathways that were significantly deregulated by the Psip1 knockout and/or Psip1/Hdgfrp2 double knockout. Among the dozen genes known to encode for LEDGF/p75 binding factors, only the expression of Nova1, which encodes an RNA splicing factor, was significantly deregulated by the knockouts. However the expression of other RNA splicing factors, including the LEDGF/p52-interacting protein ASF/SF2, was not significantly altered, indicating that deregulation of global RNA splicing was not a driving factor in the pathology of the VSD. Tumor growth factor (Tgf) β-signaling, which plays a key role in cardiac morphogenesis during development, was the only pathway significantly deregulated by the double knockout as compared to control and Psip1 knockout samples. We accordingly speculate that deregulated Tgf-β signaling was a contributing factor to the VSD and prenatal lethality of Psip1/Hdgfrp2 double-deficient mice.

Catch-up growth in term and preterm infants after surgical closure of ventricular septal defect in the first year of life.

PubMed

Correia Martins, Luísa; Lourenço, Rita; Cordeiro, Susana; Carvalho, Nuno; Mendes, Inês; Loureiro, Marisa; Patrício, Miguel; Anjos, Rui

2016-04-01

Growth impairment in infants with unrestrictive ventricular septal defects (VSD) is common, and normalisation of growth has been reported after surgical correction. Literature is inconsistent about growth velocity after surgery in term and preterm infants. We aimed to establish the pattern of catch-up growth in term and preterm infants submitted to VSD surgical correction before 1 year of age. Fifty-two infants (41 term, 11 preterm) were studied. Anthropometric data at birth, surgery and 3, 6, 12 and 24 months after surgery were collected retrospectively. Statistic analyses were performed in SPSS® version 21. At the time of surgery, growth was severely impaired in term and preterm infants. Term infants underwent a period of fast growth within the first 6 months after surgery, achieving posteriorly a normal growth pattern, as both weight and height were not significantly different from the reference population at 24 months after surgery. Preterms caught-up later than term infants but with a significant weight gain within 3 months after surgery. Early surgical repair of VSD leads to a significant acceleration of growth within 3 to 6 months after surgery, for both groups. • Growth impairment in infants with unrestrictive ventricular septal defects is well documented in literature. • Surgical correction in the first months of life is the current option for most ventricular septal defects, leading to a more favourable growth pattern. • Rapid growth during infancy may be associated with the development of insulin resistance, metabolic syndrome, obesity and cardiovascular disease later in life. What is New: • Literature is inconsistent about catch-up growth velocities after ventricular correction for term infants. • Preterm infants have never been enrolled in previous studies that aimed to establish a pattern of growth after surgery. • This group of children, who underwent a rapid post-surgery catch-up growth that follows a period of failure to thrive, may be at a higher risk of insulin resistance, metabolic syndrome, obesity and cardiovascular disease.

Voltage-sensing phosphatase modulation by a C2 domain.

PubMed

Castle, Paul M; Zolman, Kevin D; Kohout, Susy C

2015-01-01

The voltage-sensing phosphatase (VSP) is the first example of an enzyme controlled by changes in membrane potential. VSP has four distinct regions: the transmembrane voltage-sensing domain (VSD), the inter-domain linker, the cytosolic catalytic domain, and the C2 domain. The VSD transmits the changes in membrane potential through the inter-domain linker activating the catalytic domain which then dephosphorylates phosphatidylinositol phosphate (PIP) lipids. The role of the C2, however, has not been established. In this study, we explore two possible roles for the C2: catalysis and membrane-binding. The Ci-VSP crystal structures show that the C2 residue Y522 lines the active site suggesting a contribution to catalysis. When we mutated Y522 to phenylalanine, we found a shift in the voltage dependence of activity. This suggests hydrogen bonding as a mechanism of action. Going one step further, when we deleted the entire C2 domain, we found voltage-dependent enzyme activity was no longer detectable. This result clearly indicates the entire C2 is necessary for catalysis as well as for modulating activity. As C2s are known membrane-binding domains, we tested whether the VSP C2 interacts with the membrane. We probed a cluster of four positively charged residues lining the top of the C2 and suggested by previous studies to interact with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] (Kalli et al., 2014). Neutralizing those positive charges significantly shifted the voltage dependence of activity to higher voltages. We tested membrane binding by depleting PI(4,5)P2 from the membrane using the 5HT2C receptor and found that the VSD motions as measured by voltage clamp fluorometry (VCF) were not changed. These results suggest that if the C2 domain interacts with the membrane to influence VSP function it may not occur exclusively through PI(4,5)P2. Together, this data advances our understanding of the VSP C2 by demonstrating a necessary and critical role for the C2 domain in VSP function.

Voltage-sensing phosphatase modulation by a C2 domain

PubMed Central

Castle, Paul M.; Zolman, Kevin D.; Kohout, Susy C.

2015-01-01

The voltage-sensing phosphatase (VSP) is the first example of an enzyme controlled by changes in membrane potential. VSP has four distinct regions: the transmembrane voltage-sensing domain (VSD), the inter-domain linker, the cytosolic catalytic domain, and the C2 domain. The VSD transmits the changes in membrane potential through the inter-domain linker activating the catalytic domain which then dephosphorylates phosphatidylinositol phosphate (PIP) lipids. The role of the C2, however, has not been established. In this study, we explore two possible roles for the C2: catalysis and membrane-binding. The Ci-VSP crystal structures show that the C2 residue Y522 lines the active site suggesting a contribution to catalysis. When we mutated Y522 to phenylalanine, we found a shift in the voltage dependence of activity. This suggests hydrogen bonding as a mechanism of action. Going one step further, when we deleted the entire C2 domain, we found voltage-dependent enzyme activity was no longer detectable. This result clearly indicates the entire C2 is necessary for catalysis as well as for modulating activity. As C2s are known membrane-binding domains, we tested whether the VSP C2 interacts with the membrane. We probed a cluster of four positively charged residues lining the top of the C2 and suggested by previous studies to interact with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] (Kalli et al., 2014). Neutralizing those positive charges significantly shifted the voltage dependence of activity to higher voltages. We tested membrane binding by depleting PI(4,5)P2 from the membrane using the 5HT2C receptor and found that the VSD motions as measured by voltage clamp fluorometry (VCF) were not changed. These results suggest that if the C2 domain interacts with the membrane to influence VSP function it may not occur exclusively through PI(4,5)P2. Together, this data advances our understanding of the VSP C2 by demonstrating a necessary and critical role for the C2 domain in VSP function. PMID:25904865

[Analysis and follow-up study on 8 children with combined congenital heart disease treated with simultaneous trans-catheter therapy].

PubMed

Cheng, Sheng-Quan; Liu, Jian-Ping; Sun, Xin; Li, Jun; Zhang, Jun; Liu, Li-Wen; Deng, Yue-Lin; Niu, Yong-Chun

2008-10-01

Interventional treatment for childhood combined congenital heart disease (CHD) has developed very quickly and more new types of occluders have emerged in recent years. The aim of this study is to investigate the efficiency and safety of interventional treatment for combined CHD in children. Eight children with combined CHD (4 boys and 4 girls), aged 6.1+/-2.9 years, underwent simultaneous transcatheter therapy. Of the 8 children with CHD, 1 case had atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), 1 case had ASD, PDA and pulmonary stenosis (PS), 1 case had ASD and PDA, 1 case had patent foramen ovale (PFO) and PS, and 4 cases had ASD and PS. The methods of transcatheter intervention for these patients were as follows: in patients with ASD,VSD and PDA, the occlusion of VSD was performed first, followed by PDA and ASD occlusions; in patients with ASD, PDA and PS, the occlusion of percutaneous balloon pulmonary valvuloplasty (PBPV) was performed first, followed by PDA and ASD occlusions; in patients with PFO and PS, the occlusion of PBPV was performed first, and PFO occlusion followed; in patients with ASD and PS, the occlusion of PBPV was performed first, and ASD occlusion followed. The intervention operation was successfully performed in all of the 8 patients. No serious adverse events occurred during the operation. No residual shunt was found and all the occlusion devices were in the suitable sites shown by transthoracic echocardiography (TTE) and X-ray right after the operation. In the 6 patients with PS, the systolic pressure across the pulmonary valve decreased from 75.3+/-15.6 mmHg (before operation) to 14.0+/-5.6 mmHg after operation (P<0.05).A 3.4+/-1.2 years follow-up demonstrated that no residual shunt occurred and gradients across valve or coarctation sites were within the limit of satisfactory results. No complications were observed during the follow-up. Transcatheter interventional therapy for childhood combined CHD can obtain satisfactory results by proper procedures.

DaCHS: Data Center Helper Suite

NASA Astrophysics Data System (ADS)

Demleitner, Markus

2018-04-01

DaCHS, the Data Center Helper Suite, is an integrated package for publishing astronomical data sets to the Virtual Observatory. Network-facing, it speaks the major VO protocols (SCS, SIAP, SSAP, TAP, Datalink, etc). Operator-facing, many input formats, including FITS/WCS, ASCII files, and VOTable, can be processed to publication-ready data. DaCHS puts particular emphasis on integrated metadata handling, which facilitates a tight integration with the VO's Registry

The future of secondary surveillance radar - Mode S and TCAS

NASA Astrophysics Data System (ADS)

Lambert, Jean

The principles of Mode S and TCAS operation are discussed and it is noted that the main characteristic of Mode S is selective addressing, in which each aircraft is given a unique address and thus can be interrogated individually. This leads to a real data-link channel combined with secondary surveillance radar; the availability of this channel paves the way for TCAS. Mode S development in France is detailed.

TRIGA: Telecommunications Protocol Processing Subsystem Using Reconfigurable Interoperable Gate Arrays

NASA Technical Reports Server (NTRS)

Pang, Jackson; Pingree, Paula J.; Torgerson, J. Leigh

2006-01-01

We present the Telecommunications protocol processing subsystem using Reconfigurable Interoperable Gate Arrays (TRIGA), a novel approach that unifies fault tolerance, error correction coding and interplanetary communication protocol off-loading to implement CCSDS File Delivery Protocol and Datalink layers. The new reconfigurable architecture offers more than one order of magnitude throughput increase while reducing footprint requirements in memory, command and data handling processor utilization, communication system interconnects and power consumption.

Flight assessment of a data-link-based navigation-guidance concept

NASA Technical Reports Server (NTRS)

Abbott, T. S.

1983-01-01

With the proposed introduction of a data-link provision into the Air-Traffic-control (ATC) system, the capability will exist to supplement the ground-air, voice (radio) link with digital, data-link information. Additionally, ATC computers could provide, via the data link guidance and navigation information to the pilot which could then be presented in much the same manner as conventional navigation information. The primary objective of this study was to assess the feasibility and acceptability of using 4-sec and 12-sec information updating to drive conventional cockpit-navigation-instrument formats for path-tracking guidance. A flight test, consisting of 19 tracking tasks, was conducted and, through the use of pilot questionnaires and performance data, the following results were obtained. From a performance standpoint, the 4-sec and 12-sec updating led to a slight degradation in path-tracking performance, relative to continuous updating. From the pilot's viewpoint, the 12-sec data interval was suitable for long path segments (greater than 2 min of flight time), but it was difficult to use on shorter segments because of higher work load and insufficient stabilization time. Overall, it was determined that the utilization of noncontinuous data for navigation was both feasible and acceptable for the prescribed task.

Data-Link and Surface Map Traffic Intent Displays for NextGen 4DT and Equivalent Visual Surface Operations

NASA Technical Reports Server (NTRS)

Shelton, Kevin J.; Prinzel, Lawrence J., III; Arthur, Jarvis J., III; Jones, Deise R.; Allamandola, Angela S.; Bailey, Randall E.

2009-01-01

By 2025, U.S. air traffic is predicted to increase 3-fold and may strain the current air traffic management system, which may not be able to accommodate this growth. In response to this challenge, a consortium of industry, academia and government agencies have proposed a revolutionary new concept for U.S. aviation operations, termed the Next Generation Air Transportation System or "NextGen". Many key capabilities are being identified to enable NextGen, including the concept of "net-centric" operations whereby each aircraft and air services provider shares information to allow real-time adaptability to ever-changing factors such as weather, traffic, flight trajectories, and security. Data-link is likely to be the primary source of communication in NextGen. Because NextGen represents a radically different approach to air traffic management and requires a dramatic shift in the tasks, roles, and responsibilities for the flight deck, there are numerous research issues and challenges that must be overcome to ensure a safe, sustainable air transportation system. Flight deck display and crew-vehicle interaction concepts are being developed that proactively investigate and overcome potential technology and safety barriers that might otherwise constrain the full realization of NextGen.

Evaluation of Trajectory Errors in an Automated Terminal-Area Environment

NASA Technical Reports Server (NTRS)

Oseguera-Lohr, Rosa M.; Williams, David H.

2003-01-01

A piloted simulation experiment was conducted to document the trajectory errors associated with use of an airplane's Flight Management System (FMS) in conjunction with a ground-based ATC automation system, Center-TRACON Automation System (CTAS) in the terminal area. Three different arrival procedures were compared: current-day (vectors from ATC), modified (current-day with minor updates), and data link with FMS lateral navigation. Six active airline pilots flew simulated arrivals in a fixed-base simulator. The FMS-datalink procedure resulted in the smallest time and path distance errors, indicating that use of this procedure could reduce the CTAS arrival-time prediction error by about half over the current-day procedure. Significant sources of error contributing to the arrival-time error were crosstrack errors and early speed reduction in the last 2-4 miles before the final approach fix. Pilot comments were all very positive, indicating the FMS-datalink procedure was easy to understand and use, and the increased head-down time and workload did not detract from the benefit. Issues that need to be resolved before this method of operation would be ready for commercial use include development of procedures acceptable to controllers, better speed conformance monitoring, and FMS database procedures to support the approach transitions.

Comparability of the age and sex distribution of the UK Clinical Practice Research Datalink and the total Dutch population.

PubMed

de Jong, Roy G P J; Gallagher, Arlene M; Herrett, Emily; Masclee, Ad A M; Janssen-Heijnen, Maryska L G; de Vries, Frank

2016-12-01

The UK Clinical Practice Research Datalink (CPRD) is increasingly being used by Dutch researchers in epidemiology and pharmacoepidemiology. It is however unclear if the UK CPRD is representative of the Dutch population and whether study results would apply to the Dutch population. Therefore, as first step, our objective was to compare the age and sex distribution of the CPRD with the total Dutch population. As a measure of representativeness, the age and sex distribution of the UK CPRD were visually and numerically compared with Dutch census data from the StatLine database of the Dutch National Bureau of Statistics in 2011. The age distribution of men and women in the CPRD population was comparable to the Dutch male and female population. Differences of more than 10% only occurred in older age categories (75+ in men and 80+ in women). Results from observational studies that have used CPRD data are applicable to the Dutch population, and a useful resource for decision making in the Netherlands. Nevertheless, differences in drug exposure likelihood between countries should be kept in mind, as these could still cause variations in the actual population studied, thereby decreasing its generalizability. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Pulsed Neutron Powder Diffraction for Materials Science

NASA Astrophysics Data System (ADS)

Kamiyama, T.

2008-03-01

The accelerator-based neutron diffraction began in the end of 60's at Tohoku University which was succeeded by the four spallation neutron facilities with proton accelerators at the High Energy Accelerator Research Organization (Japan), Argonne National Laboratory and Los Alamos Laboratory (USA), and Rutherford Appleton Laboratory (UK). Since then, the next generation source has been pursued for 20 years, and 1MW-class spallation neutron sources will be appeared in about three years at the three parts of the world: Japan, UK and USA. The joint proton accelerator project (J-PARC), a collaborative project between KEK and JAEA, is one of them. The aim of the talk is to describe about J-PARC and the neutron diffractometers being installed at the materials and life science facility of J-PARC. The materials and life science facility of J-PARC has 23 neutron beam ports and will start delivering the first neutron beam of 25 Hz from 2008 May. Until now, more than 20 proposals have been reviewed by the review committee, and accepted proposal groups have started to get fund. Those proposals include five polycrystalline diffractometers: a super high resolution powder diffractometer (SHRPD), a 0.2%-resolution powder diffractometer of Ibaraki prefecture (IPD), an engineering diffractometers (Takumi), a high intensity S(Q) diffractometer (VSD), and a high-pressure dedicated diffractometer. SHRPD, Takumi and IPD are being designed and constructed by the joint team of KEK, JAEA and Ibaraki University, whose member are originally from the KEK powder group. These three instruments are expected to start in 2008. VSD is a super high intensity diffractometer with the highest resolution of Δd/d = 0.3%. VSD can measure rapid time-dependent phenomena of crystalline materials as well as glass, liquid and amorphous materials. The pair distribution function will be routinely obtained by the Fourier transiformation of S(Q) data. Q range of VSD will be as wide as 0.01 Å-1

Association of the missense variant p.Arg203Trp in PACS1 as a cause of intellectual disability and seizures.

PubMed

Stern, D; Cho, M T; Chikarmane, R; Willaert, R; Retterer, K; Kendall, F; Deardorff, M; Hopkins, S; Bedoukian, E; Slavotinek, A; Schrier Vergano, S; Spangler, B; McDonald, M; McConkie-Rosell, A; Burton, B K; Kim, K H; Oundjian, N; Kronn, D; Chandy, N; Baskin, B; Guillen Sacoto, M J; Wentzensen, I M; McLaughlin, H M; McKnight, D; Chung, W K

2017-08-01

Graphical abstract key: ADHD, attention deficit hyperactivity disorder; ASD, atrial septal defect; DD, developmental delay; EEG, electroencephalogram; Ht, height; ID, intellectual disability; OCD, obsessive-compulsive disorder; OFC, open fontanelle; PDA, patent ductus arteriosis; PFO, patent foramen ovale; VSD, ventricular septal defect; Wt, weight. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pregnacy and Delivery in a Patient After Tetralogy of Fallot Surgery Being Undergone

PubMed Central

Cerovac, Anis; Ljuca, Dzenita; Khodary, Bedreldin; Grgic, Gordana

2018-01-01

Aim The aim of the paper is to present the risk of pregnancy for mother and her child in a young patient who had a surgery to repair Tetralogy of Fallot (ToF), who gave a birth to her firstborn by having a cesarean section. Case report 23 years old patient, in 28 weeks of pregnancy was admitted to the clinic due to her medical record. She did not have any subjective complaints. She had two surgeries to repair ToF. After the surgery, she had residual ventricular septal defect (VSD). She had her first surgery 20 years ago (she was 3 years old), and second 7 years ago (she was 16). She had regular check-ups since, and her heart condition was unchanged. Due to her heart surgeries and VSD, a cardiologist indicates that she should deliver by having a c-section when she is 36 weeks pregnant. The patient’s heart condition was stabilized and the patient was sent home. She was recommended to have her cardiologist check up on her as she leaves the hospital and to have a gynecological examination in 6 weeks. Conclusion It can be concluded that team work and prenatal care, in most cases, lead to delivery without complication, both for mother and fetus. PMID:29416223

Pregnacy and Delivery in a Patient After Tetralogy of Fallot Surgery Being Undergone.

PubMed

Cerovac, Anis; Ljuca, Dzenita; Khodary, Bedreldin; Grgic, Gordana

2018-02-01

The aim of the paper is to present the risk of pregnancy for mother and her child in a young patient who had a surgery to repair Tetralogy of Fallot (ToF), who gave a birth to her firstborn by having a cesarean section. 23 years old patient, in 28 weeks of pregnancy was admitted to the clinic due to her medical record. She did not have any subjective complaints. She had two surgeries to repair ToF. After the surgery, she had residual ventricular septal defect (VSD). She had her first surgery 20 years ago (she was 3 years old), and second 7 years ago (she was 16). She had regular check-ups since, and her heart condition was unchanged. Due to her heart surgeries and VSD, a cardiologist indicates that she should deliver by having a c-section when she is 36 weeks pregnant. The patient's heart condition was stabilized and the patient was sent home. She was recommended to have her cardiologist check up on her as she leaves the hospital and to have a gynecological examination in 6 weeks. It can be concluded that team work and prenatal care, in most cases, lead to delivery without complication, both for mother and fetus.

Flight Simulator Evaluation of Synthetic Vision Display Concepts to Prevent Controlled Flight Into Terrain (CFIT)

NASA Technical Reports Server (NTRS)

Arthur, Jarvis J., III; Prinzel, Lawrence J., III; Kramer, Lynda J.; Parrish, Russell V.; Bailey, Randall E.

2004-01-01

In commercial aviation, over 30-percent of all fatal accidents worldwide are categorized as Controlled Flight Into Terrain (CFIT) accidents, where a fully functioning airplane is inadvertently flown into the ground. The major hypothesis for a simulation experiment conducted at NASA Langley Research Center was that a Primary Flight Display (PFD) with synthetic terrain will improve pilots ability to detect and avoid potential CFITs compared to conventional instrumentation. All display conditions, including the baseline, contained a Terrain Awareness and Warning System (TAWS) and Vertical Situation Display (VSD) enhanced Navigation Display (ND). Each pilot flew twenty-two approach departure maneuvers in Instrument Meteorological Conditions (IMC) to the terrain challenged Eagle County Regional Airport (EGE) in Colorado. For the final run, flight guidance cues were altered such that the departure path went into terrain. All pilots with a synthetic vision system (SVS) PFD (twelve of sixteen pilots) noticed and avoided the potential CFIT situation. The four pilots who flew the anomaly with the conventional baseline PFD configuration (which included a TAWS and VSD enhanced ND) had a CFIT event. Additionally, all the SVS display concepts enhanced the pilot s situational awareness, decreased workload and improved flight technical error (FTE) compared to the baseline configuration.

Engineers and Active Responsibility.

PubMed

Pesch, Udo

2015-08-01

Knowing that technologies are inherently value-laden and systemically interwoven with society, the question is how individual engineers can take up the challenge of accepting the responsibility for their work? This paper will argue that engineers have no institutional structure at the level of society that allows them to recognize, reflect upon, and actively integrate the value-laden character of their designs. Instead, engineers have to tap on the different institutional realms of market, science, and state, making their work a 'hybrid' activity combining elements from the different institutional realms. To deal with this institutional hybridity, engineers develop routines and heuristics in their professional network, which do not allow societal values to be expressed in a satisfactory manner. To allow forms of 'active' responsibility, there have to be so-called 'accountability forums' that guide moral reflections of individual actors. The paper will subsequently look at the methodologies of value-sensitive design (VSD) and constructive technology assessment (CTA) and explore whether and how these methodologies allow engineers to integrate societal values into the design technological artifacts and systems. As VSD and CTA are methodologies that look at the process of technological design, whereas the focus of this paper is on the designer, they can only be used indirectly, namely as frameworks which help to identify the contours of a framework for active responsibility of engineers.

Independent and cooperative motions of the Kv1.2 channel: voltage sensing and gating.

PubMed

Yeheskel, Adva; Haliloglu, Turkan; Ben-Tal, Nir

2010-05-19

Voltage-gated potassium (Kv) channels, such as Kv1.2, are involved in the generation and propagation of action potentials. The Kv channel is a homotetramer, and each monomer is composed of a voltage-sensing domain (VSD) and a pore domain (PD). We analyzed the fluctuations of a model structure of Kv1.2 using elastic network models. The analysis suggested a network of coupled fluctuations of eight rigid structural units and seven hinges that may control the transition between the active and inactive states of the channel. For the most part, the network is composed of amino acids that are known to affect channel activity. The results suggested allosteric interactions and cooperativity between the subunits in the coupling between the motion of the VSD and the selectivity filter of the PD, in accordance with recent empirical data. There are no direct contacts between the VSDs of the four subunits, and the contacts between these and the PDs are loose, suggesting that the VSDs are capable of functioning independently. Indeed, they manifest many inherent fluctuations that are decoupled from the rest of the structure. In general, the analysis suggests that the two domains contribute to the channel function both individually and cooperatively. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Utility of dual source CT with ECG-triggered high-pitch spiral acquisition (Flash Spiral Cardio mode) to evaluate morphological features of ventricles in children with complex congenital heart defects.

PubMed

Nakagawa, Motoo; Ozawa, Yoshiyuki; Nomura, Norikazu; Inukai, Sachiko; Tsubokura, Satoshi; Sakurai, Keita; Shimohira, Masashi; Ogawa, Masaki; Shibamoto, Yuta

2016-04-01

We evaluated the ability of dual source CT (DSCT) with ECG-triggered high-pitch spiral acquisition (Flash Spiral Cardio mode) to depict the morphological features of ventricles in pediatric patients with congenital heart defects (CHD). Between July 2013 and April 2015, 78 pediatric patients with CHD (median age 4 months) were examined using DSCT with the Flash Spiral Cardio mode. The types of ventricular abnormalities were ventricular septal defect (VSD) in 42 (the malaligned type in 11, perimembranous type in 23, supracristal type in 2, atrioventricular type in 2, and muscular type in 4), single ventricle (SV) in 11, and congenital corrected transposition of the great arteries (ccTGA) in 4. We evaluated the accuracy of the diagnosis of the VSD type. In cases of SV and ccTGA, we assessed the detectability of the anatomical features of both ventricles for a diagnosis of ventricular situs. DSCT confirmed the diagnoses for all VSDs. The type of defect was precisely diagnosed for all patients. The anatomical features of both ventricles were also depicted and ventricular situs of SV and ccTGA was correctly diagnosed. The results suggest that DSCT has the ability to clearly depict the configuration of ventricles.

Neonatal repair of right interrupted aortic arch with cerebro-myocardial perfusion technique.

PubMed

Takeuchi, Koh; Masuzawa, Akihiro; Kobayashi, Jotaro; Tsuchiya, Keiji

2011-10-01

Right interrupted aortic arch and descending aorta is exceedingly rare and most likely cause respiratory presentation, since patent ductus arteriosus (PDA) courses over the right mainstem bronchus. We report a case of successful neonatal biventricular repair of a right interrupted aortic arch (type B), with an aberrant right subclavian artery ventricular septal defect (VSD) in a 2.7 kg term neonate with DiGeorge syndrome. Patient presented in severe respiratory distress and acidosis at one day old. Two-dimensional (2D) echocardiography revealed aortic arch interruption beyond the common carotid arteries with large perimembranous outlet VSD. Aortic annulus diameter was 4.8 mm and there was no left ventricle (LV) outflow tract obstruction. Three-dimensional (3D) CT-scan confirmed these findings and identified a right-sided ductal arch that continued over the right mainstem bronchus into a right-sided descending aorta and aberrant right subclavian artery. Brachiocephalic perfusion and ductal perfusion was employed for cooling during cardiopulmonary bypass. Under deep hypothermia (27 °C rectal temperature), selective cerebro-myocardial perfusion was used for successful aortic arch repair without sacrificing the aberrant right subclavian artery. A direct tension-free anastomosis was attained. Her postoperative course was uneventful and her respiratory symptoms disappeared postoperatively. Early surgical correction is mandatory for these patients with unique anatomy and presentation.

Surface degassing and modifications to vesicle size distributions in active basalt flows

USGS Publications Warehouse

Cashman, K.V.; Mangan, M.T.; Newman, S.

1994-01-01

The character of the vesicle population in lava flows includes several measurable parameters that may provide important constraints on lava flow dynamics and rheology. Interpretation of vesicle size distributions (VSDs), however, requires an understanding of vesiculation processes in feeder conduits, and of post-eruption modifications to VSDs during transport and emplacement. To this end we collected samples from active basalt flows at Kilauea Volcano: (1) near the effusive Kupaianaha vent; (2) through skylights in the approximately isothermal Wahaula and Kamoamoa tube systems transporting lava to the coast; (3) from surface breakouts at different locations along the lava tubes; and (4) from different locations in a single breakout from a lava tube 1 km from the 51 vent at Pu'u 'O'o. Near-vent samples are characterized by VSDs that show exponentially decreasing numbers of vesicles with increasing vesicle size. These size distributions suggest that nucleation and growth of bubbles were continuous during ascent in the conduit, with minor associated bubble coalescence resulting from differential bubble rise. The entire vesicle population can be attributed to shallow exsolution of H2O-dominated gases at rates consistent with those predicted by simple diffusion models. Measurements of H2O, CO2 and S in the matrix glass show that the melt equilibrated rapidly at atmospheric pressure. Down-tube samples maintain similar VSD forms but show a progressive decrease in both overall vesicularity and mean vesicle size. We attribute this change to open system, "passive" rise and escape of larger bubbles to the surface. Such gas loss from the tube system results in the output of 1.2 ?? 106 g/day SO2, an output representing an addition of approximately 1% to overall volatile budget calculations. A steady increase in bubble number density with downstream distance is best explained by continued bubble nucleation at rates of 7-8/cm3s. Rates are ???25% of those estimated from the vent samples, and thus represent volatile supersaturations considerably less than those of the conduit. We note also that the small total volume represented by this new bubble population does not: (1) measurably deplete the melt in volatiles; or (2) make up for the overall vesicularity decrease resulting from the loss of larger bubbles. Surface breakout samples have distinctive VSDs characterized by an extreme depletion in the small vesicle population. This results in samples with much lower number densities and larger mean vesicle sizes than corresponding tube samples. Similar VSD patterns have been observed in solidified lava flows and are interpreted to result from either static (wall rupture) or dynamic (bubble rise and capture) coalescence. Through comparison with vent and tube vesicle populations, we suggest that, in addition to coalescence, the observed vesicle populations in the breakout samples have experienced a rapid loss of small vesicles consistent with 'ripening' of the VSD resulting from interbubble diffusion of volatiles. Confinement of ripening features to surface flows suggests that the thin skin that forms on surface breakouts may play a role in the observed VSD modification. ?? 1994.

Proceedings of the Fifth Integrated Communications, Navigation, and Surveillance (ICNS) Conference and Workshop

NASA Technical Reports Server (NTRS)

Fujikawa, Gene (Compiler)

2005-01-01

Contents includes papers on the following: JPDO: Inter-Agency Cooperation for the Next Generation ATS; R&T Programs; Integrated CNS Systems and Architectures; Datalink Communication Systems; Navigation, System Demonstrations and Operations; Safety and Security Initiatives Impacting CNS; Global Communications Initiatives; Airborne Internet; Avionics for System-Level Enhancements; SWIM (System Wide Information Management); Weather Products and Data Dissemination Technologies; Airsapce Communication Networks; Surveillance Systems; Workshop Breakouts Sessions and ; ICNS Conference Information.

Depot Maintenance: Actions Needed to Identify and Establish Core Capability at Military Depots

DTIC Science & Technology

2009-05-01

and the original equipment manufacturer is still repairing the equipment. • The Navy’s Advanced Tactical Air Reconnaissance System ( ATARS ), which...radar sensor data and control a data-link subsystem for real-time and near-real-time transmission. Although ATARS was determined to have core...systems and the unique tools needed for the complex repairs. Thus, funding to establish core capabilities for ATARS has been requested by the

Advanced Distributed Simulation Technology II (ADST-II) Dismounted Warrior Network Front End Analysis Experiments

DTIC Science & Technology

1997-12-19

Resource Consultants Inc. (RCI) Science Applications InternatT Corp (SAIC) Veda Inc. Virtual Space Devices (VSD) 1.1 Background The Land Warrior...network. The VICs included: • VIC Alpha - a fully immersive Dismounted Soldier System developed by Veda under a STRICOM applied research effort...consists of the Dismounted Soldier System (DSS), which is characterized as follows: • Developed by Veda under a STRICOM applied research effort

Developing and Testing SpaceWire Devices and Networks

NASA Astrophysics Data System (ADS)

Parkes, Steve; Mills, Stuart

2014-08-01

SpaceWire is a data-handling network for use on-board spacecraft, which connects together instruments, mass- memory, processors, downlink telemetry, and other on- board sub-systems [1]. SpaceWire is simple to implement and has some specific characteristics that help it support data-handling applications in space: high-speed, low-power, simplicity, relatively low implementation cost, and architectural flexibility making it ideal for many space missions. SpaceWire provides high-speed (2 Mbits/s to 200 Mbits/s), bi- directional, full-duplex data-links, which connect together SpaceWire enabled equipment. Data-handling networks can be built to suit particular applications using point-to-point data-links and routing switches.Since the SpaceWire standard was published in January 2003, it has been adopted by ESA, NASA, JAXA and RosCosmos for many missions and is being widely used on scientific, Earth observation, commercial and other spacecraft. High-profile missions using SpaceWire include: Gaia, ExoMars rover, Bepi- Colombo, James Webb Space Telescope, GOES-R, Lunar Reconnaissance Orbiter and Astro-H.The development and testing of the SpaceWire links and networks used on these and many other spacecraft currently under development, requires a comprehensive array of test equipment. In this paper the requirements for test equipment fulfilling key test functions are outlined and then equipment that meets these requirements is described. Finally the all-important software that operates with the test equipment is introduced.

Associations of NSAID and paracetamol use with risk of primary liver cancer in the Clinical Practice Research Datalink.

PubMed

Yang, Baiyu; Petrick, Jessica L; Chen, Jie; Hagberg, Katrina Wilcox; Sahasrabuddhe, Vikrant V; Graubard, Barry I; Jick, Susan; McGlynn, Katherine A

2016-08-01

Liver cancer incidence has been rising rapidly in Western countries. Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are widely-used analgesics that may modulate the risk of liver cancer, but population-based evidence is limited. We conducted a case-control study (1195 primary liver cancer cases and 4640 matched controls) within the United Kingdom's Clinical Practice Research Datalink to examine the association between the use of prescription NSAIDs and paracetamol and development of liver cancer. Multivariable-adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Overall, ever-use of NSAIDs was not associated with risk of liver cancer (aOR=1.05, 95% CI=0.88-1.24), regardless of recency and intensity of use. Use of paracetamol was associated with a slightly increased risk of liver cancer (aOR=1.18, 95% CI=1.00-1.39), particularly among individuals with body mass index<25kg/m(2) (aOR=1.56, 95% CI=1.17-2.09). Our results suggest that NSAID use was not associated with liver cancer risk in this population. Ever-use of paracetamol may be associated with slightly higher liver cancer risk, but results should be interpreted cautiously due to methodological limitations. Given that paracetamol is a widely-used analgesic, further examination of its relationship with liver cancer is warranted. Published by Elsevier Ltd.

Prognostic significance of anaplasia and angiogenesis in childhood medulloblastoma: a pediatric oncology group study.

PubMed

Ozer, Erdener; Sarialioglu, Faik; Cetingoz, Riza; Yüceer, Nurullah; Cakmakci, Handan; Ozkal, Sermin; Olgun, Nur; Uysal, Kamer; Corapcioglu, Funda; Canda, Serefettin

2004-01-01

The purpose of this study was to investigate whether quantitative assessment of cytologic anaplasia and angiogenesis may predict the clinical prognosis in medulloblastoma and stratify the patients to avoid both undertreatment and overtreatment. Medulloblastomas from 23 patients belonging to the Pediatric Oncology Group were evaluated with respect to some prognostic variables, including histologic assessment of nodularity and desmoplasia, grading of anaplasia, measurement of nuclear size, mitotic cell count, quantification of angiogenesis, including vascular surface density (VSD) and microvessel number (NVES), and immunohistochemical scoring of vascular endothelial growth factor (VEGF) expression. Univariate and multivariate analyses for prognostic indicators for survival were performed. Univariate analysis revealed that extensive nodularity was a significant favorable prognostic factor, whereas the presence of anaplasia, increased nuclear size, mitotic rate, VSD, and NVES were significant unfavorable prognostic factors. Using multivariate analysis, increased nuclear size was found to be an independent unfavorable prognostic factor for survival. Neither the presence of desmoplasia nor VEGF expression was significantly related to patient survival. Although care must be taken not to overstate the importance of the results of this single-institution preliminary report, pathologic grading of medulloblastomas with respect to grading of anaplasia and quantification of nodularity, nuclear size, and microvessel profiles may be clinically useful for the treatment of medulloblastomas. Further validation of the independent prognostic significance of nuclear size in stratifying patients is required.

Beyond voltage-gated ion channels: Voltage-operated membrane proteins and cellular processes.

PubMed

Zhang, Jianping; Chen, Xingjuan; Xue, Yucong; Gamper, Nikita; Zhang, Xuan

2018-04-18

Voltage-gated ion channels were believed to be the only voltage-sensitive proteins in excitable (and some non-excitable) cells for a long time. Emerging evidence indicates that the voltage-operated model is shared by some other transmembrane proteins expressed in both excitable and non-excitable cells. In this review, we summarize current knowledge about voltage-operated proteins, which are not classic voltage-gated ion channels as well as the voltage-dependent processes in cells for which single voltage-sensitive proteins have yet to be identified. Particularly, we will focus on the following. (1) Voltage-sensitive phosphoinositide phosphatases (VSP) with four transmembrane segments homologous to the voltage sensor domain (VSD) of voltage-gated ion channels; VSPs are the first family of proteins, other than the voltage-gated ion channels, for which there is sufficient evidence for the existence of the VSD domain; (2) Voltage-gated proton channels comprising of a single voltage-sensing domain and lacking an identified pore domain; (3) G protein coupled receptors (GPCRs) that mediate the depolarization-evoked potentiation of Ca 2+ mobilization; (4) Plasma membrane (PM) depolarization-induced but Ca 2+ -independent exocytosis in neurons. (5) Voltage-dependent metabolism of phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P 2 , PIP 2 ) in the PM. These recent discoveries expand our understanding of voltage-operated processes within cellular membranes. © 2018 Wiley Periodicals, Inc.

Feasibility of coupled empirical and dynamic modeling to assess climate change and air pollution impacts on temperate forest vegetation of the eastern United States.

PubMed

McDonnell, T C; Reinds, G J; Sullivan, T J; Clark, C M; Bonten, L T C; Mol-Dijkstra, J P; Wamelink, G W W; Dovciak, M

2018-03-01

Changes in climate and atmospheric nitrogen (N) deposition caused pronounced changes in soil conditions and habitat suitability for many plant species over the latter half of the previous century. Such changes are expected to continue in the future with anticipated further changing air temperature and precipitation that will likely influence the effects of N deposition. To investigate the potential long-term impacts of atmospheric N deposition on hardwood forest ecosystems in the eastern United States in the context of climate change, application of the coupled biogeochemical and vegetation community model VSD+PROPS was explored at three sites in New Hampshire, Virginia, and Tennessee. This represents the first application of VSD+PROPS to forest ecosystems in the United States. Climate change and elevated (above mid-19th century) N deposition were simulated to be important factors for determining habitat suitability. Although simulation results suggested that the suitability of these forests to support the continued presence of their characteristic understory plant species might decline by the year 2100, low data availability for building vegetation response models with PROPS resulted in uncertain results at the extremes of simulated N deposition. Future PROPS model development in the United States should focus on inclusion of additional foundational data or alternate candidate predictor variables to reduce these uncertainties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synchronization analysis of voltage-sensitive dye imaging during focal seizures in the rat neocortex

NASA Astrophysics Data System (ADS)

Takeshita, Daisuke; Bahar, Sonya

2011-12-01

Seizures are often assumed to result from an excess of synchronized neural activity. However, various recent studies have suggested that this is not necessarily the case. We investigate synchronization during focal neocortical seizures induced by injection of 4-aminopyridine (4AP) in the rat neocortex in vivo. Neocortical activity is monitored by field potential recording and by the fluorescence of the voltage-sensitive dye RH-1691. After removal of artifacts, the voltage-sensitive dye (VSD) signal is analyzed using the nonlinear dynamics-based technique of stochastic phase synchronization in order to determine the degree of synchronization within the neocortex during the development and spread of each seizure event. Results show a large, statistically significant increase in synchronization during seizure activity. Synchrony is typically greater between closer pixel pairs during a seizure event; the entire seizure region is synchronized almost exactly in phase. This study represents, to our knowledge, the first application of synchronization analysis methods to mammalian VSD imaging in vivo. Our observations indicate a clear increase in synchronization in this model of focal neocortical seizures across a large area of the neocortex; a sharp increase in synchronization during seizure events was observed in all 37 seizures imaged. The results are consistent with a recent computational study which simulates the effect of 4AP in a neocortical neuron model.

A new coated nitinol occluder for transcatheter closure of ventricular septal defects in a canine model.

PubMed

Zhou, Yong; Chen, Feng; Huang, Xinmiao; Zhao, Xianxian; Wu, Hong; Bai, Yuan; Qin, Yongwen

2013-01-01

This study evaluated feasibility and safety of implanting the polyester-coated nitinol ventricular septal defect occluder (pcVSDO) in the canine model. VSD models were successfully established by transseptal ventricular septal puncture via the right jugular vein in 15 out of 18 canines. Two types of VSDOs were implanted, either with pcVSDOs (n = 8) as the new type occluder group or with the commercial ventricular septal defect occluders (VSDOs, n = 7, Shanghai Sharp Memory Alloy Co. Ltd.) as the control group. Sheath size was 10 French (10 Fr) in two groups. Then the general state of the canines was observed after implantation. ECG and TTE were performed, respectively, at 7, 30, 90 days of follow-up. The canines were sacrificed at these time points for pathological and scanning electron microscopy examination. The devices were successfully implanted in all 15 canines and were retrievable and repositionable. There was no thrombus formation on the device or occurrence of complete heart block. The pcVSDO surface implanted at day 7 was already covered with neotissue by gross examination, and it completed endothelialization at day 30, while the commercial VSDO was covered with the neotissue in 30th day and the complete endothelialization in 90th day. The study shows that pcVSDO is feasible and safe to close canine VSD model and has good biocompatibility and shorter time of endothelialization.

N400 brain responses to spoken phrases paired with photographs of scenes: implications for visual scene displays in AAC systems.

PubMed

Wilkinson, Krista M; Stutzman, Allyson; Seisler, Andrea

2015-03-01

Augmentative and alternative communication (AAC) systems are often implemented for individuals whose speech cannot meet their full communication needs. One type of aided display is called a Visual Scene Display (VSD). VSDs consist of integrated scenes (such as photographs) in which language concepts are embedded. Often, the representations of concepts on VSDs are perceptually similar to their referents. Given this physical resemblance, one may ask how well VSDs support development of symbolic functioning. We used brain imaging techniques to examine whether matches and mismatches between the content of spoken messages and photographic images of scenes evoke neural activity similar to activity that occurs to spoken or written words. Electroencephalography (EEG) was recorded from 15 college students who were shown photographs paired with spoken phrases that were either matched or mismatched to the concepts embedded within each photograph. Of interest was the N400 component, a negative deflecting wave 400 ms post-stimulus that is considered to be an index of semantic functioning. An N400 response in the mismatched condition (but not the matched) would replicate brain responses to traditional linguistic symbols. An N400 was found, exclusively in the mismatched condition, suggesting that mismatches between spoken messages and VSD-type representations set the stage for the N400 in ways similar to traditional linguistic symbols.

[Magnetic resonance imaging and pathological evaluation of vacuum sealing drainage efficacy of early treated limb gunshot].

PubMed

Li, Ronggang; Liu, Xingyan; Chen, Keming; Ye, Jianjun; Gao, Mingxuan; Ge, Baofeng; Wang, Yong; Xiong, Faming; Liang, Jianping

2010-03-01

Gunshot wound spreads to the surrounding tissues and organs, it is difficult to debride and easy to infect. The conventional treatment is thorough, extensive debridement, fully open drainage, which often causes normal tissue damage and complications. To evaluate the effectiveness of vacuum sealing drainage (VSD) treating the penetrating wound in porcine extremity by MRI and pathological methods so as to provide theoretical basis for future clinical use. Eight healthy adult pigs, weighing (45 +/- 5) kg, were selected. Eight pairs of hind limb penetrating wounds (16 wounds) were made by using Chinese-made 95-type rifle at 25 meters distance, which were randomly divided into experimental group (left side, n=8) and the control group (right side, n=8). After debriding and disinfecting the penetrating wounds at 6 hours after injury, wounds were treated with VSD in experimental group. The ballistics exports of the wounds were covered with single-layer gauze and imports were directly sutured and covered with sterile gauze in control group. The trajectory and the general condition of the adjacent skin were observed. MRI and histological observation were taken at 5, 24, 48, and 72 hours after injury, bacterial counting analysis was done at 0, 12, 24, 48, and 72 hours after injury. The aperture of the trajectory exit and entry were (5.00 +/- 2.50) cm and (0.30 +/- 0.15) cm immediately after injury. The wound surface was clean, rosy without leakage and swelling after 72 hours in experimental group; wound and adjacent tissue were swelling obviously, pus, muscle necrosis and exfoliative tissue was observed, and deep defect cavity at the trajectory exit could be seen in control group. MRI showed that pairs of linear low signal in T1WI and T2WI was seen in trajectory of experimental group at 5 hours after injury, and signal in T1WI gradually increased at disrupted area and tissue deformation area at 24, 48, and 72 hours; in control group, low signal in T1WI was observed at 5 hours after injury, and signal in T2WI gradually increased and a clear boundary between edema and surrounding tissue, and the increase of signal in T1WI was not obvious at 24, 48, and 72 hours. The histological observation showed that wound was dominated by effusion at 5 hours after injury, granulation tissue gradually increased, muscle tissue dissolved and inflammatory cell infiltration was not obvious at 24, 48, and 72 hours in experimental group; in control group, the gradual dissolution of muscle fibers and inflammatory cell infiltration were observed at 5, 24, and 48 hours, muscle tissue became swelling, dissolving and degeneration and a large number of inflammatory cell infiltration gathered into the bacteria group at 72 hours. There was no significant difference in the number of bacteria per gram of tissue (P > 0.05) between experimental group and control group at 0 hour after injury; the numbers of bacteria in control group were significantly higher than those in experimental group at 12, 24, 48, and 72 hours (P < 0.05). MRI combined with pathology show diagnostic meaning in treatment of gunshot wound with VSD. MRI can accurately reflect the scope of limb gunshot wound 72 hours after injury. VSD may be an approach to delay infective time, shorten wound healing time, and promote the growth of healthy granulation tissue.

Low Cost Anti-Jam Digital Data-Links Techniques Investigations. Volume II.

DTIC Science & Technology

1979-05-01

to spectrum-spreading factors of the order of lO 3 to 104. It is also shown that the amount of gain is a function not only of the interference to...from a standard coherent product demodulation of the band-pass radio-frequency signal. A vector-Markov data generating model is hypothesized, as in...E/N( where S is total carrier power, K is number of samples per symbol, and L(AO) is a modulation loss factor of the modulation index, A . L(AO

Two Dimensional Scattering Analysis of Data-Linked Support Strings for Bistatic Measurement Systems

DTIC Science & Technology

2009-03-01

track the aircraft before engaging. In the case of the AAA system, the targets position, velocity, and direction are used to aim the guns . SAM systems...radio frequency (RF) cable which feeds the received RF to the receiver for measurement. Because it is a shielded coaxial cable, its clutter contribution...878–887, Jun 2002. ISSN 0018-926X. 23. Swarner, W. and Jr. Peters, L. “Radar cross sections of dielectric or plasma coated conducting spheres and

Technological advances for studying human behavior

NASA Technical Reports Server (NTRS)

Roske-Hofstrand, Renate J.

1990-01-01

Technological advances for studying human behavior are noted in viewgraph form. It is asserted that performance-aiding systems are proliferating without a fundamental understanding of how they would interact with the humans who must control them. Two views of automation research, the hardware view and the human-centered view, are listed. Other viewgraphs give information on vital elements for human-centered research, a continuum of the research process, available technologies, new technologies for persistent problems, a sample research infrastructure, the need for metrics, and examples of data-link technology.

A flight investigation of simulated data-link communications during single-pilot IFR flight. Volume 1: Experimental design and initial test

NASA Technical Reports Server (NTRS)

Parker, J. F., Jr.; Duffy, J. W.; Christensen, D. G.

1981-01-01

A Flight Data Console simulation of a digital communication link to replace the current voice communication system used in air traffic control (ATC) was developed. The study determined how a digital communications system reduces cockpit workload, improve, flight proficiency, and is acceptable to general aviation pilots. It is shown that instrument flight, including approach and landing, can be accomplished by using a digital data link system for ATC communication.

Needs, Effectiveness, and Gap Assessment for Key A-10C Missions: An Overview of Findings

DTIC Science & Technology

2016-01-01

weapons, further decreasing capacity. The GPS-guided SDB I ( GBU - 39 ) and the multimode SDB II ( GBU -53) begin to be highly useful in these circumstances...fairly close to friendly forces.8 It is specifically designed for use against moving targets; a Link 16 datalink permits target updates in flight, if...not jammed, and a laser-guidance mode allows it to be guided to specific targets if a JTAC is available to provide laser designation . It also has

Toward Large-Graph Comparison Measures to Understand Internet Topology Dynamics

DTIC Science & Technology

2013-09-01

continuously from randomly selected vantage points in these monitors to destination IP addresses . From each IPv4 /24 prefix on the Internet, a destination is...expected to be more similar. This was verified when the esd and vsd measures applied to this dataset gave a low reading 5 An IPv4 address is a 32-bit...integer value. /24 is the prefix of the IPv4 network starting at a given address , having 24 bits allocated for the network prefix. 6 This utility

A study on aircraft map display location and orientation

NASA Technical Reports Server (NTRS)

Baty, D. L.; Wempe, T.; Huff, E.

1973-01-01

Six airline pilots participated in a fixed-based simulator study to determine the effects of two horizontal situation display (HSD/map) panel locations relative to the vertical situation display (VSD), and of three map orientations on manual piloting performance. Pilot comments and opinions were formally obtained. Significant performance differences were found between wind conditions and among pilots but not between map locations and orientations. The results also illustrate the potential tracking accuracy of such a display. Recommendations concerning display location and map orientation are made.

Heat-flux gage measurements on a flat plate at a Mach number of 4.6 in the VSD high speed wind tunnel, a feasibility test (LA28). [wind tunnel tests of measuring instruments for boundary layer flow

NASA Technical Reports Server (NTRS)

1975-01-01

The feasibility of employing thin-film heat-flux gages was studied as a method of defining boundary layer characteristics at supersonic speeds in a high speed blowdown wind tunnel. Flow visualization techniques (using oil) were employed. Tabulated data (computer printouts), a test facility description, and photographs of test equipment are given.

A study on aircraft map display location and orientation

NASA Technical Reports Server (NTRS)

Baty, D. L.; Wempe, T. E.; Huff, E. M.

1974-01-01

Six airline pilots participated in a fixed-base simulator study to determine the effects of two horizontal situation display (HSD/map) panel locations relative to the vertical situation display (VSD), and of three map orientations on manual piloting performance. Pilot comments and opinions were formally obtained. Significant performance differences were found between wind conditions and among pilots, but not between map locations and orientations. The results also illustrate the potential tracking accuracy of such a display. Recommendations concerning display location and map orientation are made.

Trivalent inactivated influenza vaccine is not associated with sickle cell crises in children.

PubMed

Hambidge, Simon J; Ross, Colleen; Glanz, Jason; McClure, David; Daley, Matthew F; Xu, Stan; Shoup, Jo Ann; Narwaney, Komal; Baggs, James; Weintraub, Eric

2012-01-01

Children with sickle cell disease are considered at high risk for complications from influenza infection and are recommended to receive annual influenza vaccination. However, data on the safety of influenza vaccination in children with sickle cell anemia are sparse. Using a retrospective cohort of children aged 6 months to 17 years in 8 managed care organizations that comprise the Vaccine Safety Datalink and who had a diagnosis of sickle cell anemia from 1999 to 2006, we conducted matched case-control and self-controlled case series studies to examine the association of trivalent inactivated influenza vaccination with hospitalization for sickle cell crisis in the 2 weeks after vaccination. From an original pool of 1085 pediatric subjects with a diagnosis of sickle cell anemia, we identified 179 children with at least 1 sickle cell crisis during any influenza season (October 1-March 31). In the matched case-control study (matching on age category, gender, Vaccine Safety Datalink site, and season), the odds ratio of hospitalization for a crisis in vaccinated compared with unvaccinated children was not significant: 1.3 (95% confidence interval 0.8-2.2). In the self-controlled case series study of hospitalized cases, the incident rate ratio for hospitalization with sickle cell crisis in the 2 weeks after trivalent inactivated influenza vaccination was also not significant: 1.2 (95% confidence interval 0.75-1.95). This large cohort study did not find an association of influenza vaccination and hospitalization for sickle cell crises in children with sickle cell anemia.

Acquisition and tracking for underwater optical communications

NASA Astrophysics Data System (ADS)

Williams, Andrew J.; Laycock, Leslie L.; Griffith, Michael S.; McCarthy, Andrew G.; Rowe, Duncan P.

2017-10-01

There is a growing requirement to transfer large volumes of data between underwater platforms. As seawater is transmissive in the visible band, underwater optical communications is an active area of interest since it offers the potential for power efficient, covert and high bandwidth datalinks at short to medium ranges. Short range systems have been successfully demonstrated using sources with low directionality. To realise higher data rates and/or longer ranges, the use of more efficient directional beams is required; by necessity, these must be sufficiently aligned to achieve the required link margin. For mobile platforms, the acquisition and tracking of each node is therefore critical in order to establish and maintain an optical datalink. This paper describes work undertaken to demonstrate acquisition and tracking in a 3D underwater environment. A range of optical sources, beam steering technologies, and tracking sensors have been assessed for suitability. A novel scanning strategy exploiting variable beam divergence was developed to provide robust acquisition whilst minimising acquisition time. A prototype system was assembled and demonstrated in a large water tank. This utilised custom quadrant detectors based on Silicon PhotoMultiplier (SiPM) arrays for fine tracking, and a Wide Field of View (WFoV) sCMOS camera for link acquisition. Fluidic lenses provided dynamic control of beam divergence, and AC modulation/filtering enabled background rejection. The system successfully demonstrated robust optical acquisition and tracking between two nodes with only nanowatt received optical powers. The acquisition time was shown to be dependent on the initial conditions and the transmitted optical power.

Optophysiological Approach to Resolve Neuronal Action Potentials with High Spatial and Temporal Resolution in Cultured Neurons

PubMed Central

Pagès, Stéphane; Côté, Daniel; De Koninck, Paul

2011-01-01

Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm). Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs) have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser-scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (>10% of fluorescence change for 100 mV depolarization) and time response (sub millisecond) of the dye allows the robust detection of action potentials (APs) even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive, and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms) resolution and high spatial (μm) resolution. PMID:22016723

High-order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico-cortical pathways.

PubMed

Kunori, Nobuo; Takashima, Ichiro

2016-12-01

The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher-order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb-evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb-related sensory inputs would be transmitted to the RFA from the CFA via the cortico-cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher-order motor cortex in primates. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Use of a vessel sealant device for cystic duct ligation in the dog.

PubMed

Marvel, Sarah; Monnet, Eric

2014-11-01

To compare a vessel sealant device to hemostatic clips for cystic duct ligation in a canine cadaveric model. Experimental. Hepatobiliary systems were collected from normal dogs. A microtip pressure transducer was inserted into the common bile duct and a 20-24 g intravenous catheter was placed in a hepatic duct. The cystic duct was ligated with 1 of 3 techniques: vessel sealant device (VSD), 10 mm medium Endoclips™, or 10 mm large Endoclips™ with 6 specimens in each group. Methylene blue was infused until failure, which was recorded as seal/clip failure or retrograde movement of methylene blue into the liver. Mean failure pressure of the medium endoclip group was significantly lower than the large endoclip group (P = .014). There was no difference between the failure pressure of the VSD group and the medium and large endoclip groups (P = .097, P = .34, respectively). Failure by leakage at the cut surface of the cystic duct occurred in 2 specimens in the medium endoclip group while all others failed by retrograde flow of the methylene blue through the hepatic ducts. The vessel sealant device appears comparable to large endoclips for closure of the cystic duct in an acute cadaveric model, while medium endoclips may not fully compress or span the diameter of a cystic duct in large breed dogs and leak at lower pressures. © Copyright 2014 by The American College of Veterinary Surgeons.

Prenatal diagnosis of two fetuses with deletions of 8p23.1, critical region for congenital diaphragmatic hernia and heart defects.

PubMed

Keitges, Elisabeth A; Pasion, Romela; Burnside, Rachel D; Mason, Carla; Gonzalez-Ruiz, Antonio; Dunn, Teresa; Masiello, Meredith; Gebbia, Joseph A; Fernandez, Carlos O; Risheg, Hiba

2013-07-01

Microdeletions of 8p23.1 are mediated by low copy repeats and can cause congenital diaphragmatic hernia (CDH) and cardiac defects. Within this region, point mutations of the GATA4 gene have been shown to cause cardiac defects. However, the cause of CDH in these deletions has been difficult to determine due to the paucity of mutations that result in CDH, the lack of smaller deletions to refine the region and the reduced penetrance of CDH in these large deletions. Mice deficient for one copy of the Gata4 gene have been described with CDH and heart defects suggesting mutations in Gata4 can cause the phenotype in mice. We report on the SNP microarray analysis on two fetuses with deletions of 8p23.1. The first had CDH and a ventricular septal defect (VSD) on ultrasonography and a family history of a maternal VSD. Microarray analysis detected a 127-kb deletion which included the GATA4 and NEIL2 genes which was inherited from the mother. The second fetus had an incomplete atrioventricular canal defect on ultrasonography. Microarray analysis showed a 315-kb deletion that included seven genes, GATA4, NEIL2, FDFT1, CTSB, DEFB136, DEFB135, and DEFB134. These results suggest that haploinsufficiency of the two genes in common within 8p23.1; GATA4 and NEIL2 can cause CDH and cardiac defects in humans. Copyright © 2013 Wiley Periodicals, Inc.

Myocardial Oxidative Stress in Infants Undergoing Cardiac Surgery.

PubMed

Sznycer-Taub, Nathaniel; Mackie, Stewart; Peng, Yun-Wen; Donohue, Janet; Yu, Sunkyung; Aiyagari, Ranjit; Charpie, John

2016-04-01

Cardiac surgery for congenital heart disease often necessitates a period of myocardial ischemia during cardiopulmonary bypass and cardioplegic arrest, followed by reperfusion after aortic cross-clamp removal. In experimental models, myocardial ischemia-reperfusion is associated with significant oxidative stress and ventricular dysfunction. A prospective observational study was conducted in infants (<1 year) who underwent elective surgical repair of a ventricular septal defect (VSD) or tetralogy of Fallot (TOF). Blood samples were drawn following anesthetic induction (baseline) and directly from the coronary sinus at 1, 3, 5, and 10 min following aortic cross-clamp removal. Samples were analyzed for oxidant stress using assays for thiobarbituric acid-reactive substances, protein carbonyl, 8-isoprostane, and total antioxidant capacity. For each subject, raw assay data were normalized to individual baseline samples and expressed as fold-change from baseline. Results were compared using a one-sample t test with Bonferroni correction for multiple comparisons. Sixteen patients (ten with TOF and six with VSD) were enrolled in the study, and there were no major postoperative complications observed. For the entire cohort, there was an immediate, rapid increase in myocardial oxidative stress that was sustained for 10 min following aortic cross-clamp removal in all biomarker assays (all P < 0.01), except total antioxidant capacity. Infant cardiac surgery is associated with a rapid, robust, and time-dependent increase in myocardial oxidant stress as measured from the coronary sinus in vivo. Future studies with larger enrollment are necessary to assess any association between myocardial oxidative stress and early postoperative outcomes.

A New Coated Nitinol Occluder for Transcatheter Closure of Ventricular Septal Defects in a Canine Model

PubMed Central

Zhou, Yong; Chen, Feng; Huang, Xinmiao; Zhao, Xianxian; Wu, Hong; Bai, Yuan; Qin, Yongwen

2013-01-01

Aims. This study evaluated feasibility and safety of implanting the polyester-coated nitinol ventricular septal defect occluder (pcVSDO) in the canine model. Methods and Results. VSD models were successfully established by transseptal ventricular septal puncture via the right jugular vein in 15 out of 18 canines. Two types of VSDOs were implanted, either with pcVSDOs (n = 8) as the new type occluder group or with the commercial ventricular septal defect occluders (VSDOs, n = 7, Shanghai Sharp Memory Alloy Co. Ltd.) as the control group. Sheath size was 10 French (10 Fr) in two groups. Then the general state of the canines was observed after implantation. ECG and TTE were performed, respectively, at 7, 30, 90 days of follow-up. The canines were sacrificed at these time points for pathological and scanning electron microscopy examination. The devices were successfully implanted in all 15 canines and were retrievable and repositionable. There was no thrombus formation on the device or occurrence of complete heart block. The pcVSDO surface implanted at day 7 was already covered with neotissue by gross examination, and it completed endothelialization at day 30, while the commercial VSDO was covered with the neotissue in 30th day and the complete endothelialization in 90th day. Conclusion. The study shows that pcVSDO is feasible and safe to close canine VSD model and has good biocompatibility and shorter time of endothelialization. PMID:24066289

The Molecular Basis of Polyunsaturated Fatty Acid Interactions with the Shaker Voltage-Gated Potassium Channel

PubMed Central

Yazdi, Samira; Stein, Matthias; Elinder, Fredrik; Andersson, Magnus; Lindahl, Erik

2016-01-01

Voltage-gated potassium (KV) channels are membrane proteins that respond to changes in membrane potential by enabling K+ ion flux across the membrane. Polyunsaturated fatty acids (PUFAs) induce channel opening by modulating the voltage-sensitivity, which can provide effective treatment against refractory epilepsy by means of a ketogenic diet. While PUFAs have been reported to influence the gating mechanism by electrostatic interactions to the voltage-sensor domain (VSD), the exact PUFA-protein interactions are still elusive. In this study, we report on the interactions between the Shaker KV channel in open and closed states and a PUFA-enriched lipid bilayer using microsecond molecular dynamics simulations. We determined a putative PUFA binding site in the open state of the channel located at the protein-lipid interface in the vicinity of the extracellular halves of the S3 and S4 helices of the VSD. In particular, the lipophilic PUFA tail covered a wide range of non-specific hydrophobic interactions in the hydrophobic central core of the protein-lipid interface, while the carboxylic head group displayed more specific interactions to polar/charged residues at the extracellular regions of the S3 and S4 helices, encompassing the S3-S4 linker. Moreover, by studying the interactions between saturated fatty acids (SFA) and the Shaker KV channel, our study confirmed an increased conformational flexibility in the polyunsaturated carbon tails compared to saturated carbon chains, which may explain the specificity of PUFA action on channel proteins. PMID:26751683

Molecular transistors based on BDT-type molecular bridges.

PubMed

Wheeler, W D; Dahnovsky, Yu

2008-10-21

In this work we study the effect of electron correlations in molecular transistors with molecular bridges based on 1,4-benzene-dithiol (BDT) and 2-nitro-1,4-benzene-dithiol (nitro-BDT) by using ab initio electron propagator calculations. We find that there is no gate field effect for the BDT based transistor in accordance with the experimental data. After verifying the computational method on the BDT molecule, we consider a transistor with a nitro-BDT molecular bridge. From the electron propagator calculations, we predict strong negative differential resistance at small positive and negative values of source-drain voltages. The explanation of the peak and the minimum in the current is given in terms of the molecular orbital picture and switch-on (-off) properties due to the voltage dependencies of the Dyson poles (ionization potentials). When the current is off, the electronic states on both electrodes are populated resulting in the vanishing tunneling probability due to the Pauli principle. Besides the minimum and the maximum in the I-V characteristics, we find a strong gate field effect in the conductance where the peak at V(sd) = 0.15 eV and E(g) = 4x10(-3) a.u. switches to the minimum at E(g) = -4x10(-3) a.u. A similar behavior is discovered at the negative V(sd). Such a feature can be used for fast current modulation by changing the polarity of a gate field.

A massive haemothorax as an unusual complication of infective endocarditis caused by Streptococcus sanguinis.

PubMed

Kim, Kyoung Jin; Lee, Kang Won; Choi, Ju Hee; Sohn, Jang Wook; Kim, Min Ja; Yoon, Young Kyung

2016-08-01

Infective endocarditis involving the tricuspid valve is an uncommon condition, and a consequent haemothorax associated with pulmonary embolism is extremely rare. Particularly, there are no guidelines for the management of this complication. We describe a rare case of pulmonary embolism and infarction followed by a haemothorax due to infective endocarditis of the tricuspid valve caused by Streptococcus sanguinis. A 25-year-old man with a ventricular septal defect (VSD) presented with fever. On physical examination, his body temperature was 38.8 °C, and a grade III holosystolic murmur was heard. A chest X-ray did not reveal any specific findings. A transoesophageal echocardiogram showed a perimembranous VSD and echogenic material attached to the tricuspid valve. All blood samples drawn from three different sites yielded growth of pan-susceptible S. sanguinis in culture bottles. On day 12 of hospitalization, the patient complained of pleuritic chest pain without fever. Physical examination revealed reduced breathing sounds and dullness in the lower left thorax. On his chest computed tomography scan, pleural effusion with focal infarction and pulmonary embolism were noted on the left lower lung. Thoracentesis indicated the presence of a haemothorax. Our case was successfully treated using antibiotic therapy alone with adjunctive chest tube insertion, rather than with anticoagulation therapy for pulmonary embolism or cardiac surgery. When treating infective endocarditis caused by S. sanguinis, clinicians should include haemothorax in the differential diagnosis of patients complaining of sudden chest pain.

The NASA Langley Research Center's Unmanned Aerial System Surrogate Research Aircraft

NASA Technical Reports Server (NTRS)

Howell, Charles T., III; Jessup, Artie; Jones, Frank; Joyce, Claude; Sugden, Paul; Verstynen, Harry; Mielnik, John

2010-01-01

Research is needed to determine what procedures, aircraft sensors and other systems will be required to allow Unmanned Aerial Systems (UAS) to safely operate with manned aircraft in the National Airspace System (NAS). The NASA Langley Research Center has transformed a Cirrus Design SR22 general aviation (GA) aircraft into a UAS Surrogate research aircraft to serve as a platform for UAS systems research, development, flight testing and evaluation. The aircraft is manned with a Safety Pilot and systems operator that allows for flight operations almost anywhere in the NAS without the need for a Federal Aviation Administration (FAA) Certificate of Authorization (COA). The UAS Surrogate can be controlled from a modular, transportable ground station like a true UAS. The UAS Surrogate is able to file and fly in the NAS with normal traffic and is a better platform for real world UAS research and development than existing vehicles flying in restricted ranges or other sterilized airspace. The Cirrus Design SR22 aircraft is a small, singleengine, four-place, composite-construction aircraft that NASA Langley acquired to support NASA flight-research programs like the Small Aircraft Transportation System (SATS) Project. Systems were installed to support flight test research and data gathering. These systems include: separate research power; multi-function flat-panel displays; research computers; research air data and inertial state sensors; video recording; data acquisition; data-link; S-band video and data telemetry; Common Airborne Instrumentation System (CAIS); Automatic Dependent Surveillance-Broadcast (ADS-B); instrumented surfaces and controls; and a systems operator work station. The transformation of the SR22 to a UAS Surrogate was accomplished in phases. The first phase was to modify the existing autopilot to accept external commands from a research computer that was connected by redundant data-link radios to a ground control station. An electro-mechanical auto-throttle was added in the next phase to provide ground station control of airspeed. Additional phases are in progress to add waypoint navigation and long range satellite voice and data communications. Potential areas for UAS Surrogate research include the development, flight test and evaluation of sensors to aid in the process of air traffic detect-sense-and-avoid. These sensors could be evaluated in real-time and compared with onboard human evaluation pilots. This paper describes the systems and design considerations that were incorporated in the development of the UAS Surrogate along with details of development problems encountered and the corresponding solutions.

AN overview of the FLYSAFE datalink solution for the exchange of weather information: supporting aircrew decision making processes.

NASA Astrophysics Data System (ADS)

Mirza, A.; Drouin, A.

2009-09-01

FLYSAFE is an Integrated Project of the 6th framework of the European Commission with the aim to improve flight safety through the development of an avionics solution the Next Generation Integrated Surveillance System (NGISS), which is supported by a ground based network of Weather Information Management Systems (WIMS) and access points in the form of the Ground Weather Processor (GWP). The NGISS provides information to the flight crew on the three major external hazards for aviation: weather, air traffic and terrain. The NGISS has the capability of displaying data about all three hazards on a single display screen, facilitating rapid appreciation of the situation by the flight crew. Weather Information Management Systems (WIMS) were developed to provide the NGISS and the flight crew with weather related information on in-flight icing, thunderstorms and clear-air turbulence. These products are generated on the ground from observations and model forecasts. WIMS will supply relevant information on three different scales: global, regional and local (over airport Terminal Manoeuvring Area). The Ground Weather Processor is a client-server architecture that utilises open source components, which include a geospatial database and web feature services. The GWP stores Weather Objects generated by the WIMS. An aviation user can retrieve on-demand all Weather Objects that intersect the volume of space that is of interest to them. The Weather Objects are fused with in-situ observation data and can be used by the flight management system to propose a route to avoid the hazard. In addition they can be used to display the current hazardous weather to the Flight Crew thereby raising their awareness. Within the FLYSAFE program, around 120 hours of flight trials were performed during February 2008 and August 2008. Two aircraft were involved each with separate objectives: - to assess FLYSAFE's innovative solutions for the data-link, on-board data-fusion and data-display and data-updates during flight; - to evaluate the new weather information management systems (in-flight icing and thunderstorms) using in-situ measurements recorded on-board the test aircraft. In this presentation we will focus on the data link solution to uplink the Weather Objects to the NGISS. As part of the solution, a brief description is given on how grid data created by the WIMS are transformed to Weather Objects; which describe the weather hazard and are formatted using the Geospatial Mark-up Language.

Weather Information System

NASA Technical Reports Server (NTRS)

1995-01-01

WxLink is an aviation weather system based on advanced airborne sensors, precise positioning available from the satellite-based Global Positioning System, cockpit graphics and a low-cost datalink. It is a two-way system that uplinks weather information to the aircraft and downlinks automatic pilot reports of weather conditions aloft. Manufactured by ARNAV Systems, Inc., the original technology came from Langley Research Center's cockpit weather information system, CWIN (Cockpit Weather INformation). The system creates radar maps of storms, lightning and reports of surface observations, offering improved safety, better weather monitoring and substantial fuel savings.

Electronic Derivative Classifier/Reviewing Official

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, Joshua C; McDuffie, Gregory P; Light, Ken L

2017-02-17

The electronic Derivative Classifier, Reviewing Official (eDC/RO) is a web based document management and routing system that reduces security risks and increases workflow efficiencies. The system automates the upload, notification review request, and document status tracking of documents for classification review on a secure server. It supports a variety of document formats (i.e., pdf, doc, docx, xls, xlsx, xlsm, ppt, pptx, vsd, vsdx and txt), and allows for the dynamic placement of classification markings such as the classification level, category and caveats on the document, in addition to a document footer and digital signature.

A study on aircraft map display location and orientation. [effects of map display location on manual piloting performance

NASA Technical Reports Server (NTRS)

Baty, D. L.; Wempe, T. E.; Huff, E. M.

1973-01-01

Six airline pilots participated in a fixed-base simulator study to determine the effects of two Horizontal Situation Display (HSD/map) panel locations relative to the Vertical Situation Display (VSD), and of three map orientations on manual piloting performance. Pilot comments and opinions were formally obtained. Significant performance differences were found between wind conditions, and among pilots, but not between map locations and orientations. The results also illustrate the potential tracking accuracy of such a display. Recommendations concerning display location and map orientation are made.

Development and evaluation of a profile negotiation process for integrating aircraft and air traffic control automation

NASA Technical Reports Server (NTRS)

Green, Steven M.; Denbraven, Wim; Williams, David H.

1993-01-01

The development and evaluation of the profile negotiation process (PNP), an interactive process between an aircraft and air traffic control (ATC) that integrates airborne and ground-based automation capabilities to determine conflict-free trajectories that are as close to an aircraft's preference as possible, are described. The PNP was evaluated in a real-time simulation experiment conducted jointly by NASA's Ames and Langley Research Centers. The Ames Center/TRACON Automation System (CTAS) was used to support the ATC environment, and the Langley Transport Systems Research Vehicle (TSRV) piloted cab was used to simulate a 4D Flight Management System (FMS) capable aircraft. Both systems were connected in real time by way of voice and data lines; digital datalink communications capability was developed and evaluated as a means of supporting the air/ground exchange of trajectory data. The controllers were able to consistently and effectively negotiate nominally conflict-free vertical profiles with the 4D-equipped aircraft. The actual profiles flown were substantially closer to the aircraft's preference than would have been possible without the PNP. However, there was a strong consensus among the pilots and controllers that the level of automation of the PNP should be increased to make the process more transparent. The experiment demonstrated the importance of an aircraft's ability to accurately execute a negotiated profile as well as the need for digital datalink to support advanced air/ground data communications. The concept of trajectory space is proposed as a comprehensive approach for coupling the processes of trajectory planning and tracking to allow maximum pilot discretion in meeting ATC constraints.

Risk factors for Burkitt lymphoma: a nested case-control study in the UK Clinical Practice Research Datalink.

PubMed

Karimi, Parisa; Birmann, Brenda M; Anderson, Lesley A; McShane, Charlene M; Gadalla, Shahinaz M; Sampson, Joshua N; Mbulaiteye, Sam M

2018-04-20

Burkitt lymphoma (BL) occurs as three subtypes: endemic BL, immunosuppression-related BL and sporadic BL. Descriptive studies of BL age-specific incidence patterns have suggested multimodal peaks near 10, 40 and 70 years of age, but the risk factors for BL at different ages are unknown. We investigated risk factors for BL in the United Kingdom among 156 BL cases and 608 matched BL-free controls identified in the Clinical Practice Research Datalink (CPRD) between 1992 and 2016. Associations with pre-diagnostic body mass index, cigarette smoking, alcohol consumption, hepatitis, Epstein-Barr virus (EBV), human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), malaria, allergic and autoimmune conditions, and prednisone use were evaluated. Overall, we identified inverse associations between smoking and BL risk, and positive associations between prior EBV infection, HIV/AIDS and prescription or use of prednisone with BL risk. In age-group stratified analyses, BL was associated with malaria exposure (vs. no exposure, odds ratio [OR] 8·00, 95% confidence interval [CI] 1·46-43·7) among those aged 20-59 years old and with hepatitis infection (vs. no infection, OR 3·41, 95% CI 1·01-11·5) among those aged 60+ years old. The effects of EBV, malaria, HIV/AIDS, prednisone and hepatitis on BL remained significant in mutually-adjusted age-group-specific analyses. No risk factors were associated with childhood BL. We report novel associations for BL in non-endemic settings. © 2018 John Wiley & Sons Ltd.

Evaluation of methods to estimate missing days' supply within pharmacy data of the Clinical Practice Research Datalink (CPRD) and The Health Improvement Network (THIN).

PubMed

Lum, Kirsten J; Newcomb, Craig W; Roy, Jason A; Carbonari, Dena M; Saine, M Elle; Cardillo, Serena; Bhullar, Harshvinder; Gallagher, Arlene M; Lo Re, Vincent

2017-01-01

The extent to which days' supply data are missing in pharmacoepidemiologic databases and effective methods for estimation is unknown. We determined the percentage of missing days' supply on prescription and patient levels for oral anti-diabetic drugs (OADs) and evaluated three methods for estimating days' supply within the Clinical Practice Research Datalink (CPRD) and The Health Improvement Network (THIN). We estimated the percentage of OAD prescriptions and patients with missing days' supply in each database from 2009 to 2013. Within a random sample of prescriptions with known days' supply, we measured the accuracy of three methods to estimate missing days' supply by imputing the following: (1) 28 days' supply, (2) mode number of tablets/day by drug strength and number of tablets/prescription, and (3) number of tablets/day via a machine learning algorithm. We determined incidence rates (IRs) of acute myocardial infarction (AMI) using each method to evaluate the impact on ascertainment of exposure time and outcomes. Days' supply was missing for 24 % of OAD prescriptions in CPRD and 33 % in THIN (affecting 48 and 57 % of patients, respectively). Methods 2 and 3 were very accurate in estimating days' supply for OADs prescribed at a consistent number of tablets/day. Method 3 was more accurate for OADs prescribed at varying number of tablets/day. IRs of AMI were similar across methods for most OADs. Missing days' supply is a substantial problem in both databases. Method 2 is easy and very accurate for most OADs and results in IRs comparable to those from method 3.

Modelling Conditions and Health Care Processes in Electronic Health Records: An Application to Severe Mental Illness with the Clinical Practice Research Datalink.

PubMed

Olier, Ivan; Springate, David A; Ashcroft, Darren M; Doran, Tim; Reeves, David; Planner, Claire; Reilly, Siobhan; Kontopantelis, Evangelos

2016-01-01

The use of Electronic Health Records databases for medical research has become mainstream. In the UK, increasing use of Primary Care Databases is largely driven by almost complete computerisation and uniform standards within the National Health Service. Electronic Health Records research often begins with the development of a list of clinical codes with which to identify cases with a specific condition. We present a methodology and accompanying Stata and R commands (pcdsearch/Rpcdsearch) to help researchers in this task. We present severe mental illness as an example. We used the Clinical Practice Research Datalink, a UK Primary Care Database in which clinical information is largely organised using Read codes, a hierarchical clinical coding system. Pcdsearch is used to identify potentially relevant clinical codes and/or product codes from word-stubs and code-stubs suggested by clinicians. The returned code-lists are reviewed and codes relevant to the condition of interest are selected. The final code-list is then used to identify patients. We identified 270 Read codes linked to SMI and used them to identify cases in the database. We observed that our approach identified cases that would have been missed with a simpler approach using SMI registers defined within the UK Quality and Outcomes Framework. We described a framework for researchers of Electronic Health Records databases, for identifying patients with a particular condition or matching certain clinical criteria. The method is invariant to coding system or database and can be used with SNOMED CT, ICD or other medical classification code-lists.

Voltage-sensitive-dye imaging of microstimulation-evoked neural activity through intracortical horizontal and callosal connections in cat visual cortex.

PubMed

Suzurikawa, Jun; Tani, Toshiki; Nakao, Masayuki; Tanaka, Shigeru; Takahashi, Hirokazu

2009-12-01

Recently, intrinsic signal optical imaging has been widely used as a routine procedure for visualizing cortical functional maps. We do not, however, have a well-established imaging method for visualizing cortical functional connectivity indicating spatio-temporal patterns of activity propagation in the cerebral cortex. In the present study, we developed a novel experimental setup for investigating the propagation of neural activities combining the intracortical microstimulation (ICMS) technique with voltage sensitive dye (VSD) imaging, and demonstrated the feasibility of this setup applying to the measurement of time-dependent intra- and inter-hemispheric spread of ICMS-evoked excitation in the cat visual cortices, areas 17 and 18. A microelectrode array for the ICMS was inserted with a specially designed easy-to-detach electrode holder around the 17/18 transition zones (TZs), where the left and right hemispheres were interconnected via the corpus callosum. The microelectrode array was stably anchored in agarose without any holder, which enabled us to visualize evoked activities even in the vicinity of penetration sites as well as in a wide recording region that covered a part of both hemispheres. The VSD imaging could successfully visualize ICMS-evoked excitation and subsequent propagation in the visual cortices contralateral as well as ipsilateral to the ICMS. Using the orientation maps as positional references, we showed that the activity propagation patterns were consistent with previously reported anatomical patterns of intracortical and interhemispheric connections. This finding indicates that our experimental system can serve for the investigation of cortical functional connectivity.

Exploring energy loss by vector flow mapping in children with ventricular septal defect: Pathophysiologic significance.

PubMed

Honda, Takashi; Itatani, Keiichi; Takanashi, Manabu; Kitagawa, Atsushi; Ando, Hisashi; Kimura, Sumito; Oka, Norihiko; Miyaji, Kagami; Ishii, Masahiro

2017-10-01

Vector flow mapping is a novel echocardiographic flow visualization method, and it has enabled us to quantitatively evaluate the energy loss in the left ventricle (intraventricular energy loss). Although intraventricular energy loss is assumed to be a part of left ventricular workload itself, it is unclear what this parameter actually represents. The aim of the present study was to elucidate the characteristics of intraventricular energy loss. We enrolled 26 consecutive children with ventricular septal defect (VSD). On echocardiography vector flow mapping, intraventricular energy loss was measured in the apical 3-chamber view. We measured peak energy loss and averaged energy loss in the diastolic and systolic phases, and subsequently compared these parameters with catheterization parameters and serum brain natrium peptide (BNP) level. Diastolic, peak, and systolic energy loss were strongly and positively correlated with right ventricular systolic pressure (r=0.76, 0.68, and 0.56, p<0.0001, = 0.0001, and 0.0029, respectively) and right ventricular end diastolic pressure (r=0.55, 0.49, and 0.49, p=0.0038, 0.0120, and 0.0111, respectively). In addition, diastolic, peak, and systolic energy loss were significantly correlated with BNP (r=0.75, 0.69 and 0.49, p<0.0001, < 0.0001, and=0.0116, respectively). In children with VSD, elevated right ventricular pressure is one of the factors that increase energy loss in the left ventricle. The results of the present study encourage further studies in other study populations to elucidate the characteristics of intraventricular energy loss for its possible clinical application. Copyright © 2017 Elsevier B.V. All rights reserved.

N-Acetylcysteine prevents congenital heart defects induced by pregestational diabetes

PubMed Central

2014-01-01

Background Pregestational diabetes is a major risk factor of congenital heart defects (CHDs). Glutathione is depleted and reactive oxygen species (ROS) production is elevated in diabetes. In the present study, we aimed to examine whether treatment with N-acetylcysteine (NAC), which increases glutathione synthesis and inhibits ROS production, prevents CHDs induced by pregestational diabetes. Methods Female mice were treated with streptozotocin (STZ) to induce pregestational diabetes prior to breeding with normal males to produce offspring. Some diabetic mice were treated with N-acetylcysteine (NAC) in drinking water from E0.5 to the end of gestation or harvesting of the embryos. CHDs were identified by histology. ROS levels, cell proliferation and gene expression in the fetal heart were analyzed. Results Our data show that pregestational diabetes resulted in CHDs in 58% of the offspring, including ventricular septal defect (VSD), atrial septal defect (ASD), atrioventricular septal defects (AVSD), transposition of great arteries (TGA), double outlet right ventricle (DORV) and tetralogy of Fallot (TOF). Treatment with NAC in drinking water in pregestational diabetic mice completely eliminated the incidence of AVSD, TGA, TOF and significantly diminished the incidence of ASD and VSD. Furthermore, pregestational diabetes increased ROS, impaired cell proliferation, and altered Gata4, Gata5 and Vegf-a expression in the fetal heart of diabetic offspring, which were all prevented by NAC treatment. Conclusions Treatment with NAC increases GSH levels, decreases ROS levels in the fetal heart and prevents the development of CHDs in the offspring of pregestational diabetes. Our study suggests that NAC may have therapeutic potential in the prevention of CHDs induced by pregestational diabetes. PMID:24533448

Retrospective review of congenital heart disease in 976 dogs.

PubMed

Oliveira, P; Domenech, O; Silva, J; Vannini, S; Bussadori, R; Bussadori, C

2011-01-01

Knowledge of epidemiology is important for recognition of cardiovascular malformations. Review the incidence of congenital heart defects in dogs in Italy and assess breed and sex predispositions. Nine hundred and seventy-six dogs diagnosed with congenital heart disease (CHD) of 4,480 dogs presented to Clinica Veterinaria Gran Sasso for cardiovascular examination from 1997 to 2010. A retrospective analysis of medical records regarding signalment, history, clinical examination, radiography, electrocardiography, echocardiography, angiography, and postmortem examination was performed. Breed and sex predisposition were assessed with the odds ratio test. CHD was observed in 21.7% of cases. A total of 1,132 defects were observed with single defects in 832 cases (85%), 2 concurrent defects in 132 cases (14%), and 3 concurrent defects in 12 cases (1%). The most common defects were pulmonic stenosis (PS; 32.1%), subaortic stenosis (SAS; 21.3%), and patent ductus arteriosus (20.9%), followed by ventricular septal defect (VSD; 7.5%), valvular aortic stenosis (AS; 5.7%), and tricuspid dysplasia (3.1%). SAS, PS, and VSD frequently were associated with other defects. Several breed and sex predispositions were identified. The results of this study are in accordance with previous studies, with slight differences. The breed and sex predilections identified may be of value for the diagnosis and screening of CHD in dogs. Additionally, the relatively high percentage of concurrent heart defects emphasizes the importance of accurate and complete examinations for identification. Because these data are from a cardiology referral center, a bias may exist. Copyright © 2011 by the American College of Veterinary Internal Medicine.

[Pulsatile total cavopulmonary shunt for hypoplastic right heart syndrome with abnormal systemic venous return--a case report].

PubMed

Oiwa, H; Kawauchi, M; Chikada, M; Yagyu, K; Kotsuka, Y; Furuse, A

1995-01-01

A pulsatile total cavopulmonary shunt was successfully performed on a 5-year-old girl with hypoplastic right heart syndrome associated with abnormal systemic venous return; at the same time, modified mitral valve replacement was performed for mitral regurgitation. The right atrium, tricuspid valve and right ventricle were all extremely dimunitive. The diameter of the tricuspid valve was 50% of normal and the volume of the right ventricle was 8.6% of normal. In addition, there were severe subpumonary stenosis, a restrictive ventricular septal defect (VSD) and an atrial septal defect (ASD). The bilateral superior venae cavae (SVCs) and the hepatic vein drained to the left atrium, and the inferior vena cava was infrahepatically interrupted with a hemiazygos connection to the left superior vena cava. At the operation, each SVC was anastomosed end-to-side to each branch of the pulmonary artery (PA). The restrictive ventricular septal defect and stenotic subpulmonary lesion were left. The diameter of the ASD was reduced from 12 mm to 7 mm. The main PA was neither divided nor banded. The pulsatile blood flow from the left heart to the PA was regurated by a native restrictive VSD and stenotic subpulmonary lesion, and that from the right heart via the ASD was limited by reducing the size of the ASD. These described anatomic arrangements produced adequate antegrade pulsatile flow in the PA, which might prevent the development of pulmonary arteriovenous fistulae and, besides permit transfer of drainage of the hepatic vein from the left to the right atrium via the ASD in future.

Streptococcus dysgalactiae subsp. dysgalactiae isolated from milk of the bovine udder as emerging pathogens: In vitro and in vivo infection of human cells and zebrafish as biological models.

PubMed

Alves-Barroco, Cinthia; Roma-Rodrigues, Catarina; Raposo, Luís R; Brás, Catarina; Diniz, Mário; Caço, João; Costa, Pedro M; Santos-Sanches, Ilda; Fernandes, Alexandra R

2018-03-25

Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) is a major cause of bovine mastitis and has been regarded as an animal-restricted pathogen, although rare infections have been described in humans. Previous studies revealed the presence of virulence genes encoded by phages of the human pathogen Group A Streptococcus pyogenes (GAS) in SDSD isolated from the milk of bovine udder with mastitis. The isolates SDSD VSD5 and VSD13 could adhere and internalize human primary keratinocyte cells, suggesting a possible human infection potential of bovine isolates. In this work, the in vitro and in vivo potential of SDSD to internalize/adhere human cells of the respiratory track and zebrafish as biological models was evaluated. Our results showed that, in vitro, bovine SDSD strains could interact and internalize human respiratory cell lines and that this internalization was dependent on an active transport mechanism and that, in vivo, SDSD are able to cause invasive infections producing zebrafish morbidity and mortality. The infectious potential of these isolates showed to be isolate-specific and appeared to be independent of the presence or absence of GAS phage-encoded virulence genes. Although the infection ability of the bovine SDSD strains was not as strong as the human pathogenic S. pyogenes in the zebrafish model, results suggested that these SDSD isolates are able to interact with human cells and infect zebrafish, a vertebrate infectious model, emerging as pathogens with zoonotic capability. © 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

An investigation of air transportation technology at the Massachusetts Institute of Technology, 1990-1991

NASA Technical Reports Server (NTRS)

Simpson, Robert W.

1991-01-01

Brief summaries are given of research activities at the Massachusetts Institute of Technology (MIT) under the sponsorship of the FAA/NASA Joint University Program. Topics covered include hazard assessment and cockpit presentation issues for microburst alerting systems; the situational awareness effect of automated air traffic control (ATC) datalink clearance amendments; a graphical simulation system for adaptive, automated approach spacing; an expert system for temporal planning with application to runway configuration management; deterministic multi-zone ice accretion modeling; alert generation and cockpit presentation for an integrated microburst alerting system; and passive infrared ice detection for helicopter applications.

A graphical workstation based part-task flight simulator for preliminary rapid evaluation of advanced displays

NASA Technical Reports Server (NTRS)

Wanke, Craig; Kuchar, James; Hahn, Edward; Pritchett, A.; Hansman, R. John

1994-01-01

Advances in avionics and display technology are significantly changing the cockpit environment in current transport aircraft. The MIT Aeronautical Systems Lab (ASL) developed a part-task flight simulator specifically to study the effects of these new technologies on flight crew situational awareness and performance. The simulator is based on a commercially-available graphics workstation, and can be rapidly reconfigured to meet the varying demands of experimental studies. The simulator was successfully used to evaluate graphical microbursts alerting displays, electronic instrument approach plates, terrain awareness and alerting displays, and ATC routing amendment delivery through digital datalinks.

[One-stage operation for pelvis and acetabular fractures combined with Morel-Lavallée injury by internal fixation associated with vacuum sealing drainage].

PubMed

Wei, Dan; Wang, Yue; Yuan, Jiabin; Tang, Xiaoming; Zhang, Bin; Lu, Bing; Tan, Bo

2014-01-01

To investigate the methods and effectiveness of one-stage operation for pelvis and acetabular fractures combined with Morel-Lavallée injury by internal fixation associated with vacuum sealing drainage (VSD). Between June 2008 and October 2012, 15 cases of pelvis and acetabular fractures combined with Morel-Lavallée injury were treated. There were 5 males and 10 females, aged from 18 to 67 years (mean, 36.8 years). Fractures were caused by traffic accident in 11 cases and crashing injury of heavy object in 4 cases. The time from injury to hospitalization was 3 hours to 9 days (mean, 5.4 days). Morel-Lavallée injury located in the above posterior superior iliac spine in 4 cases, greater trochanter in 7 cases, and anterior proximal thigh in 4 cases. In 10 cases complicated by pelvic fracture, there were 1 case of anteroposterior compression type, 3 cases of lateral compression type, 5 cases of vertical shear type, and 1 case of compound injury type; in 5 cases complicated by acetabular fracture, there were 1 case of transverse fracture, 1 case of posterior wall and posterior column fracture, 1 case of transverse acetabulum plus posterior wall fracture, and 2 cases of both columns fracture. Open reduction and internal fixation were used to treat pelvic and acetabular fractures, and VSD to treat Morel-Lavallée injury. When the drainage volume was less than 20 mL/d, interrupted wound suture or free skin grafting was performed. The hospitalization time was 16-31 days (mean, 20.8 days). Thirteen cases were followed up 4-16 months (mean, 7.8 months). The healing time of Morel-Lavallée injury was 16-36 days after operation (mean, 21.3 days). All the wounds had primary healing, and no infection occurred. The X-ray films showed that all fractures healed, with a mean healing time of 13.6 weeks (range, 11-18 weeks). At 6.5 months after operation, according to Majeed function scoring system in 8 cases of pelvic fracture, the results were excellent in 5 cases, good in 2 cases, and fair in 1 case; according to Harris hip scoring in 4 cases of acetabular fracture, the results were excellent in 2 cases, good in 1 case, and fair in 1 case. To pelvis-acetabular fractures combined with Morel-Lavallée injury, internal fixation treatment for fracture and VSD for Morel-Lavallée injury not only can cure merge Morel-Lavallée injury effectively, but also can guarantee the operation timing and incision safty of the pelvis-acetabular fractures.

Use of demographic and pharmacy data to identify patients included within both the Clinical Practice Research Datalink (CPRD) and The Health Improvement Network (THIN).

PubMed

Carbonari, Dena M; Saine, M Elle; Newcomb, Craig W; Blak, Betina; Roy, Jason A; Haynes, Kevin; Wood, Jennifer; Gallagher, Arlene M; Bhullar, Harshvinder; Cardillo, Serena; Hennessy, Sean; Strom, Brian L; Lo Re, Vincent

2015-09-01

Pharmacoepidemiology researchers often utilize data from two UK electronic medical record databases, the Clinical Practice Research Datalink (CPRD) and The Health Improvement Network (THIN), and may choose to combine the two in an effort to increase sample size. To minimize duplication of data, previous studies examined the practice-level overlap between these databases. However, the proportion of overlapping patients remains unknown. We developed a method using demographic and pharmacy variables to identify patients included in both CPRD and THIN, and applied this method to measure the proportion of overlapping patients who initiated the oral anti-diabetic drug saxagliptin. We conducted a cross-sectional study among patients initiating saxagliptin in CPRD and THIN between October 2009 and September 2012. Within both databases, we identified patients: (i) ≥18 years, (ii) newly prescribed saxagliptin, and (iii) with ≥180 days enrollment prior to saxagliptin initiation. Demographic data (birth year, sex, patient registration date, family number, and marital status) and prescriptions (including dates) for the first two oral anti-diabetic drugs prescribed within the study period were used to identify matching patients. Among 4202 CPRD and 3641 THIN patients initiating saxagliptin, 2574 overlapping patients (61% of CPRD saxagliptin initiators; 71% of THIN saxagliptin initiators) were identified. Among these patients, 2474 patients (96%) perfectly matched on all demographic and prescription data. Within each database, over 60% of patients initiating saxagliptin were included within both CPRD and THIN. Combined demographic and prescription data can be used to identify patients included in both CPRD and THIN. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluating the validity of clinical codes to identify cataract and glaucoma in the UK Clinical Practice Research Datalink.

PubMed

Kang, Elizabeth M; Pinheiro, Simone P; Hammad, Tarek A; Abou-Ali, Adel

2015-01-01

The aim of this study is to determine (i) the positive predictive value (PPV) of an algorithm using clinical codes to identify incident glaucoma and cataract events in the Clinical Practice Research Datalink (CPRD) and (ii) the ability to capture the correct timing of these clinical events. A total of 21,339 and 5349 potential cataract and glaucoma cases, respectively, were identified in CPRD between 1 January 1990 and 31 December 2010. Questionnaires were sent to the general practitioners (GP) of 1169 (5.5%) cataract and 1163 (21.7%) glaucoma cases for validation. GPs were asked to verify the diagnosis and the timing of the diagnosis and to provide other supporting information. A total of 986 (84.3%) valid cataract questionnaires and 863 (74.2%) glaucoma questionnaires were completed. 92.1% and 92.4% of these used information beyond EMR to verify the diagnosis. Cataract and glaucoma diagnoses were confirmed in the large majority of the cases. The PPV (95% CI) of the cataract and glaucoma Read code algorithm were 92.0% (90.3-93.7%) and 84.1% (81.7-86.6%), respectively. However, timing of diagnosis was incorrect for a substantial proportion of the cases (20.3% and 32.8% of the cataract and glaucoma cases, respectively) among whom 30.4% and 49.2% had discrepancies in diagnosis timing greater than 1 year. High PPV suggests that the algorithms based on the clinical Read codes are sufficient to identify the cataract and glaucoma cases in CPRD. However, these codes alone may not be able to accurately identify the timing of the diagnosis of these eye disorders. Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Representativeness and optimal use of body mass index (BMI) in the UK Clinical Practice Research Datalink (CPRD)

PubMed Central

Bhaskaran, Krishnan; Forbes, Harriet J; Douglas, Ian; Leon, David A; Smeeth, Liam

2013-01-01

Objectives To assess the completeness and representativeness of body mass index (BMI) data in the Clinical Practice Research Datalink (CPRD), and determine an optimal strategy for their use. Design Descriptive study. Setting Electronic healthcare records from primary care. Participants A million patient random sample from the UK CPRD primary care database, aged ≥16 years. Primary and secondary outcome measures BMI completeness in CPRD was evaluated by age, sex and calendar period. CPRD-based summary BMI statistics for each calendar year (2003–2010) were age-standardised and sex-standardised and compared with equivalent statistics from the Health Survey for England (HSE). Results BMI completeness increased over calendar time from 37% in 1990–1994 to 77% in 2005–2011, was higher among females and increased with age. When BMI at specific time points was assigned based on the most recent record, calendar–year-specific mean BMI statistics underestimated equivalent HSE statistics by 0.75–1.1 kg/m2. Restriction to those with a recent (≤3 years) BMI resulted in mean BMI estimates closer to HSE (≤0.28 kg/m2 underestimation), but excluded up to 47% of patients. An alternative strategy of imputing up-to-date BMI based on modelled changes in BMI over time since the last available record also led to mean BMI estimates that were close to HSE (≤0.37 kg/m2 underestimation). Conclusions Completeness of BMI in CPRD increased over time and varied by age and sex. At a given point in time, a large proportion of the most recent BMIs are unlikely to reflect current BMI; consequent BMI misclassification might be reduced by employing model-based imputation of current BMI. PMID:24038008

Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD)

PubMed Central

Quint, Jennifer K; Müllerova, Hana; DiSantostefano, Rachael L; Forbes, Harriet; Eaton, Susan; Hurst, John R; Davis, Kourtney; Smeeth, Liam

2014-01-01

Objectives The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database. Setting 951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard. Primary outcome measure The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed. Results 951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5–92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7–94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2–44.4%). Conclusions Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. PMID:25056980

The impact of persistence with bisphosphonates on health resource utilization and fracture risk in the UK: a study of patient records from the UK Clinical Practice Research Datalink.

PubMed

Ferguson, Samara; Feudjo Tepie, Maurille; Taylor, Andrew; Roddam, Andrew; Critchlow, Cathy; Iqbal, Mazhar; Spangler, Leslie; Bayly, Jonathan

2016-02-01

Clinical trial data suggest that patients who have received bisphosphonates continue to benefit from them after discontinuation. However, data from real-world clinical practice are inconclusive. We assessed the impact of persistence and discontinuation on health resource utilization (HRU) and fracture rate in women who were prescribed oral bisphosphonates. The study used data from the UK Clinical Practice Research Datalink. Women aged 50 years or older with a first prescription of oral bisphosphonate therapy between January 2000 and December 2007 were included. Multivariate modelling compared rate ratios for fracture and HRU between patients who had discontinued medication (shorter persistence group) and patients who took their medication for longer (longer persistence group). The interactions of elapsed time (measured as 6-month intervals) with HRU and with fracture rate for all patients within paired groups were also assessed. Overall, 36 320 patients were included. Pairwise comparisons showed that HRU and fracture rates were lower in longer persistence groups than in shorter persistence groups. Analysis by 6-month interval showed that, across all patients in persistence group pairs, HRU significantly increased for each additional 6 months elapsed; trends towards increased risk of fracture were also seen. In contrast to results from clinical trials, in this patient population the protective effect of oral bisphosphonates after discontinuation was not sufficient to reduce HRU and fracture rates to the levels that would be seen if patients had continued on therapy. Reducing the rate of treatment discontinuation may decrease the burden that osteoporosis places on both patients and health care systems. © 2015 AMGEN Inc. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

Data Relay Board with Protocol for High-Speed, Free-Space Optical Communications

NASA Technical Reports Server (NTRS)

Wright, Malcolm; Clare, Loren; Gould, Gary; Pedyash, Maxim

2004-01-01

In a free-space optical communication system, the mitigation of transient outages through the incorporation of error-control methods is of particular concern, the outages being caused by scintillation fades and obscurants. The focus of this innovative technology is the development of a data relay system for a reliable high-data-rate free-spacebased optical-transport network. The data relay boards will establish the link, maintain synchronous connection, group the data into frames, and provide for automatic retransmission (ARQ) of lost or erred frames. A certain Quality of Service (QoS) can then be ensured, compatible with the required data rate. The protocol to be used by the data relay system is based on the draft CCSDS standard data-link protocol Proximity-1, selected by orbiters to multiple lander assets in the Mars network, for example. In addition to providing data-link protocol capabilities for the free-space optical link and buffering the data, the data relay system will interface directly with user applications over Gigabit Ethernet and/or with highspeed storage resources via Fibre Channel. The hardware implementation is built on a network-processor-based architecture. This technology combines the power of a hardware switch capable of data switching and packet routing at Gbps rates, with the flexibility of a software- driven processor that can host highly adaptive and reconfigurable protocols used, for example, in wireless local-area networks (LANs). The system will be implemented in a modular multi-board fashion. The main hardware elements of the data relay system are the new data relay board developed by Rockwell Scientific, a COTS Gigabit Ethernet board for user interface, and a COTS Fibre Channel board that connects to local storage. The boards reside in a cPCI back plane, and can be housed in a VME-type enclosure.

Cancer recording in patients with and without type 2 diabetes in the Clinical Practice Research Datalink primary care data and linked hospital admission data: a cohort study.

PubMed

Williams, Rachael; van Staa, Tjeerd-Pieter; Gallagher, Arlene M; Hammad, Tarek; Leufkens, Hubert G M; de Vries, Frank

2018-05-26

Conflicting results from studies using electronic health records to evaluate the associations between type 2 diabetes and cancer fuel concerns regarding potential biases. This study aimed to describe completeness of cancer recording in UK primary care data linked to hospital admissions records. Patients aged 40+ years with insulin or oral antidiabetic prescriptions in Clinical Practice Research Datalink (CPRD) primary care without type 1 diabetes were matched by age, sex and general practitioner practice to non-diabetics. Those eligible for linkage to Hospital Episode Statistics Admitted Patient Care (HES APC), and with follow-up during April 1997-December 2006 were included. Cancer recording and date of first record of cancer were compared. Characteristics of patients with cancer most likely to have the diagnosis recorded only in a single data source were assessed. Relative rates of cancer estimated from the two datasets were compared. 53 585 patients with type 2 diabetes matched to 47 435 patients without diabetes were included. Of all cancers (excluding non-melanoma skin cancer) recorded in CPRD, 83% were recorded in HES APC. 94% of cases in HES APC were recorded in CPRD. Concordance was lower when restricted to same-site cancer records, and was negatively associated with increasing age. Relative rates for cancer were similar in both datasets. Good concordance in cancer recording was found between CPRD and HES APC among type 2 diabetics and matched controls. Linked data may reduce misclassification and increase case ascertainment when analysis focuses on site-specific cancers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An algorithm to identify rheumatoid arthritis in primary care: a Clinical Practice Research Datalink study

PubMed Central

Muller, Sara; Hider, Samantha L; Raza, Karim; Stack, Rebecca J; Hayward, Richard A; Mallen, Christian D

2015-01-01

Objective Rheumatoid arthritis (RA) is a multisystem, inflammatory disorder associated with increased levels of morbidity and mortality. While much research into the condition is conducted in the secondary care setting, routinely collected primary care databases provide an important source of research data. This study aimed to update an algorithm to define RA that was previously developed and validated in the General Practice Research Database (GPRD). Methods The original algorithm consisted of two criteria. Individuals meeting at least one were considered to have RA. Criterion 1: ≥1 RA Read code and a disease modifying antirheumatic drug (DMARD) without an alternative indication. Criterion 2: ≥2 RA Read codes, with at least one ‘strong’ code and no alternative diagnoses. Lists of codes for consultations and prescriptions were obtained from the authors of the original algorithm where these were available, or compiled based on the original description and clinical knowledge. 4161 people with a first Read code for RA between 1 January 2010 and 31 December 2012 were selected from the Clinical Practice Research Datalink (CPRD, successor to the GPRD), and the criteria applied. Results Code lists were updated for the introduction of new Read codes and biological DMARDs. 3577/4161 (86%) of people met the updated algorithm for RA, compared to 61% in the original development study. 62.8% of people fulfilled both Criterion 1 and Criterion 2. Conclusions Those wishing to define RA in the CPRD, should consider using this updated algorithm, rather than a single RA code, if they wish to identify only those who are most likely to have RA. PMID:26700281

Can commonly prescribed drugs be repurposed for the prevention or treatment of Alzheimer's and other neurodegenerative diseases? Protocol for an observational cohort study in the UK Clinical Practice Research Datalink.

PubMed

Walker, Venexia M; Davies, Neil M; Jones, Tim; Kehoe, Patrick G; Martin, Richard M

2016-12-13

Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis. Our research will focus on drugs used for the treatment of hypertension, hypercholesterolaemia and type 2 diabetes, all of which have previously been identified as potentially cerebroprotective and have variable levels of preclinical evidence that suggest they may have beneficial effects for various aspects of dementia pathology. We will conduct a hypothesis testing observational cohort study using data from the Clinical Practice Research Datalink (CPRD). Our analysis will consider four statistical methods, which have different approaches for modelling confounding. These are multivariable adjusted Cox regression; propensity matched regression; instrumental variable analysis and marginal structural models. We will also use an intention-to-treat analysis, whereby we will define all exposures based on the first prescription observed in the database so that the target parameter is comparable to that estimated by a randomised controlled trial. This protocol has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will publish the results of the study as open-access peer-reviewed publications and disseminate findings through national and international conferences as are appropriate. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Which Patients with Giant Cell Arteritis Will Develop Cardiovascular or Cerebrovascular Disease? A Clinical Practice Research Datalink Study.

PubMed

Robson, Joanna C; Kiran, Amit; Maskell, Joe; Hutchings, Andrew; Arden, Nigel; Dasgupta, Bhaskar; Hamilton, William; Emin, Akan; Culliford, David; Luqmani, Raashid

2016-06-01

To evaluate the risk of cerebrovascular disease and cardiovascular disease (CVD) in patients with giant cell arteritis (GCA), and to identify predictors. The UK Clinical Practice Research Datalink 1991-2010 was used for a parallel cohort study of 5827 patients with GCA and 37,090 age-, sex-, and location-matched controls. A multivariable competing risk model (non-cerebrovascular/CV-related death as the competing risk) determined the relative risk [subhazard ratio (SHR)] between patients with GCA compared with background controls for cerebrovascular disease, CVD, or either. Each cohort (GCA and controls) was then analyzed individually using the same multivariable model, with age and sex now present, to identify predictors of CVD or cerebrovascular disease. Patients with GCA, compared with controls, had an increased risk SHR (95% CI) of cerebrovascular disease (1.45, 1.31-1.60), CVD (1.49, 1.37-1.62), or either (1.47, 1.37-1.57). In the GCA cohort, predictors of "cerebrovascular disease or CVD" included increasing age, > 80 years versus < 65 years (1.98, 1.62-2.42), male sex (1.20, 1.05-1.38), and socioeconomic status, most deprived quintile versus least deprived (1.34, 1.01-1.78). These predictors were also present within the non-GCA cohort. Patients with GCA are more likely to develop cerebrovascular disease or CVD than age-, sex-, and location-matched controls. In common with the non-GCA cohort, patients who are older, male, and from the most deprived compared with least deprived areas have a higher risk of cerebrovascular disease or CVD. Further work is needed to understand how this risk may be mediated by specific behavioral, social, and economic factors.

Understanding flucloxacillin prescribing trends and treatment non-response in UK primary care: a Clinical Practice Research Datalink (CPRD) study

PubMed Central

Francis, Nick A.; Hood, Kerenza; Lyons, Ronan; Butler, Christopher C.

2016-01-01

Objectives The volume of prescribed antibiotics is associated with antimicrobial resistance and, unlike most other antibiotic classes, flucloxacillin prescribing has increased. We aimed to describe UK primary care flucloxacillin prescribing and factors associated with subsequent antibiotic prescribing as a proxy for non-response. Patients and methods Clinical Practice Research Datalink patients with acute prescriptions for oral flucloxacillin between January 2004 and December 2013, prescription details, associated Read codes and patient demographics were identified. Monthly prescribing rates were plotted and logistic regression identified factors associated with having a subsequent antibiotic prescription within 28 days. Results 3 031 179 acute prescriptions for 1 667 431 patients were included. Average monthly prescription rates increased from 4.74 prescriptions per 1000 patient-months in 2004 to 5.74 (increase of 21.1%) in 2013. The highest prescribing rates and the largest increases in rates were seen in older adults (70+ years), but the overall increase in prescribing was not accounted for by an ageing population. Prescribing 500 mg tablets/capsules rather than 250 mg became more common. Children were frequently prescribed low doses and small volumes (5 day course) and prescribing declined for children, including for impetigo. Only 4.2% of new prescriptions involved co-prescription of another antibiotic. Age (<5 and ≥60 years), diagnosis of ‘cellulitis or abscess’ or no associated code, and 500 mg dose were associated with a subsequent antibiotic prescription, which occurred after 17.6% of first prescriptions. Conclusions There is a need to understand better the reasons for increased prescribing of flucloxacillin in primary care, optimal dosing (and the need to co-prescribe other antibiotics) and the reasons why one in five patients are prescribed a further antibiotic within 4 weeks. PMID:27090629

Modelling Conditions and Health Care Processes in Electronic Health Records: An Application to Severe Mental Illness with the Clinical Practice Research Datalink

PubMed Central

Olier, Ivan; Springate, David A.; Ashcroft, Darren M.; Doran, Tim; Reeves, David; Planner, Claire; Reilly, Siobhan; Kontopantelis, Evangelos

2016-01-01

Background The use of Electronic Health Records databases for medical research has become mainstream. In the UK, increasing use of Primary Care Databases is largely driven by almost complete computerisation and uniform standards within the National Health Service. Electronic Health Records research often begins with the development of a list of clinical codes with which to identify cases with a specific condition. We present a methodology and accompanying Stata and R commands (pcdsearch/Rpcdsearch) to help researchers in this task. We present severe mental illness as an example. Methods We used the Clinical Practice Research Datalink, a UK Primary Care Database in which clinical information is largely organised using Read codes, a hierarchical clinical coding system. Pcdsearch is used to identify potentially relevant clinical codes and/or product codes from word-stubs and code-stubs suggested by clinicians. The returned code-lists are reviewed and codes relevant to the condition of interest are selected. The final code-list is then used to identify patients. Results We identified 270 Read codes linked to SMI and used them to identify cases in the database. We observed that our approach identified cases that would have been missed with a simpler approach using SMI registers defined within the UK Quality and Outcomes Framework. Conclusion We described a framework for researchers of Electronic Health Records databases, for identifying patients with a particular condition or matching certain clinical criteria. The method is invariant to coding system or database and can be used with SNOMED CT, ICD or other medical classification code-lists. PMID:26918439

Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink

PubMed Central

Langham, Julia; Bhaskaran, Krishnan; Brauer, Ruth; Smeeth, Liam

2013-01-01

Objective To measure the association between orlistat and acute liver injury. Design Self controlled case series study. Setting Population based primary care setting, United Kingdom. Participants 94 695 patients receiving orlistat and registered in the UK Clinical Practice Research Datalink and linked with Hospital Episode Statistics data between 1999 and 2011. Main outcome measure Relative incidence of acute liver injury comparing periods when patients were receiving orlistat with periods of non-usage. Results Among 94 695 patients who received orlistat, 988 cases of acute liver injury were identified, with 335 confirmed as definite cases and 653 as probable cases. For all cases an increased incidence of liver injury was detected during the 90 day period before orlistat was first started, with an incidence rate ratio of 1.50 (95% confidence interval 1.10 to 2.06). The incidence remained raised during the first 30 days of treatment (2.21, 1.43 to 3.42), before returning to baseline levels with prolonged treatment. When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of liver injury was not increased (1.02, 0.67 to 1.56). An analysis restricted to definite cases showed no evidence of an increased risk of liver injury during treatment. Conclusion The incidence of acute liver injury was higher in the periods both immediately before and immediately after the start of orlistat treatment. This suggests that the observed increased risks of liver injury linked to the start of treatment may reflect changes in health status associated with the decision to begin treatment rather than any causal effect of the drug. PMID:23585064

The management of acne vulgaris in primary care: a cohort study of consulting and prescribing patterns using the Clinical Practice Research Datalink.

PubMed

Francis, N A; Entwistle, K; Santer, M; Layton, A M; Eady, E A; Butler, C C

2017-01-01

Effective management of acne vulgaris in primary care involves support (usually provided over a number of consultations) and prescription of effective treatments. However, consulting and prescribing patterns for acne in primary care are not well described. To describe the rate of primary-care consultations and follow-up consultations; prescribing patterns, including overall use of acne-related medications (ARMs); and initial and follow-up prescription for acne vulgaris in the U.K. U.K. primary-care acne consultations and prescriptions for ARMs were identified in the Clinical Practice Research Datalink. Annual consultation rates (between 2004 and 2013) by age and sex, new consultations and consultations in the subsequent year were calculated, along with prescribing trends - during a new consultation and over the subsequent 90 days and year - using the number of registered patients as the denominator. Two-thirds (66·1%) of patients who had a new acne consultation had no further acne consultations in the subsequent year. Overall 26·7%, 24·9%, and 23·6% and 2·8% of patients were prescribed no ARM, an oral antibiotic, a topical antibiotic or an oral plus topical antibiotic, respectively, during a new acne consultation. In total 60·1% and 38·6% of patients prescribed an ARM received no further ARM prescriptions in the following 90 days and 1 year, respectively, despite most prescriptions being for 2 months or less. Prescribing rates for lymecycline and topical combined clindamycin and benzoyl peroxide increased substantially between 2004 and 2013. There were no important changes in consultation rates between 2004 and 2013. These data suggest that patients with acne are receiving a suboptimal initial choice of ARMs, longitudinal care and prescribing. © 2016 British Association of Dermatologists.

Validation of suicide and self-harm records in the Clinical Practice Research Datalink

PubMed Central

Thomas, Kyla H; Davies, Neil; Metcalfe, Chris; Windmeijer, Frank; Martin, Richard M; Gunnell, David

2013-01-01

Aims The UK Clinical Practice Research Datalink (CPRD) is increasingly being used to investigate suicide-related adverse drug reactions. No studies have comprehensively validated the recording of suicide and nonfatal self-harm in the CPRD. We validated general practitioners' recording of these outcomes using linked Office for National Statistics (ONS) mortality and Hospital Episode Statistics (HES) admission data. Methods We identified cases of suicide and self-harm recorded using appropriate Read codes in the CPRD between 1998 and 2010 in patients aged ≥15 years. Suicides were defined as patients with Read codes for suicide recorded within 95 days of their death. International Classification of Diseases codes were used to identify suicides/hospital admissions for self-harm in the linked ONS and HES data sets. We compared CPRD-derived cases/incidence of suicide and self-harm with those identified from linked ONS mortality and HES data, national suicide incidence rates and published self-harm incidence data. Results Only 26.1% (n = 590) of the ‘true’ (ONS-confirmed) suicides were identified using Read codes. Furthermore, only 55.5% of Read code-identified suicides were confirmed as suicide by the ONS data. Of the HES-identified cases of self-harm, 68.4% were identified in the CPRD using Read codes. The CPRD self-harm rates based on Read codes had similar age and sex distributions to rates observed in self-harm hospital registers, although rates were underestimated in all age groups. Conclusions The CPRD recording of suicide using Read codes is unreliable, with significant inaccuracy (over- and under-reporting). Future CPRD suicide studies should use linked ONS mortality data. The under-reporting of self-harm appears to be less marked. PMID:23216533

Point-of-care cluster randomized trial in stroke secondary prevention using electronic health records.

PubMed

Dregan, Alex; van Staa, Tjeerd P; McDermott, Lisa; McCann, Gerard; Ashworth, Mark; Charlton, Judith; Wolfe, Charles D A; Rudd, Anthony; Yardley, Lucy; Gulliford, Martin C; Trial Steering Committee

2014-07-01

The aim of this study was to evaluate whether the remote introduction of electronic decision support tools into family practices improves risk factor control after first stroke. This study also aimed to develop methods to implement cluster randomized trials in stroke using electronic health records. Family practices were recruited from the UK Clinical Practice Research Datalink and allocated to intervention and control trial arms by minimization. Remotely installed, electronic decision support tools promoted intensified secondary prevention for 12 months with last measure of systolic blood pressure as the primary outcome. Outcome data from electronic health records were analyzed using marginal models. There were 106 Clinical Practice Research Datalink family practices allocated (intervention, 53; control, 53), with 11 391 (control, 5516; intervention, 5875) participants with acute stroke ever diagnosed. Participants at trial practices had similar characteristics as 47,887 patients with stroke at nontrial practices. During the intervention period, blood pressure values were recorded in the electronic health records for 90% and cholesterol values for 84% of participants. After intervention, the latest mean systolic blood pressure was 131.7 (SD, 16.8) mm Hg in the control trial arm and 131.4 (16.7) mm Hg in the intervention trial arm, and adjusted mean difference was -0.56 mm Hg (95% confidence interval, -1.38 to 0.26; P=0.183). The financial cost of the trial was approximately US $22 per participant, or US $2400 per family practice allocated. Large pragmatic intervention studies may be implemented at low cost by using electronic health records. The intervention used in this trial was not found to be effective, and further research is needed to develop more effective intervention strategies. http://www.controlled-trials.com. Current Controlled Trials identifier: ISRCTN35701810. © 2014 American Heart Association, Inc.

Can commonly prescribed drugs be repurposed for the prevention or treatment of Alzheimer's and other neurodegenerative diseases? Protocol for an observational cohort study in the UK Clinical Practice Research Datalink

PubMed Central

Davies, Neil M; Jones, Tim; Kehoe, Patrick G; Martin, Richard M

2016-01-01

Introduction Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis. Our research will focus on drugs used for the treatment of hypertension, hypercholesterolaemia and type 2 diabetes, all of which have previously been identified as potentially cerebroprotective and have variable levels of preclinical evidence that suggest they may have beneficial effects for various aspects of dementia pathology. Methods and analysis We will conduct a hypothesis testing observational cohort study using data from the Clinical Practice Research Datalink (CPRD). Our analysis will consider four statistical methods, which have different approaches for modelling confounding. These are multivariable adjusted Cox regression; propensity matched regression; instrumental variable analysis and marginal structural models. We will also use an intention-to-treat analysis, whereby we will define all exposures based on the first prescription observed in the database so that the target parameter is comparable to that estimated by a randomised controlled trial. Ethics and dissemination This protocol has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will publish the results of the study as open-access peer-reviewed publications and disseminate findings through national and international conferences as are appropriate. PMID:27965247

Convection Weather Detection by General Aviation Pilots with Convectional and Data-Linked Graphical Weather Information Sources

NASA Technical Reports Server (NTRS)

Chamberlain, James P.; Latorella, Kara A.

2001-01-01

This study compares how well general aviation (GA) pilots detect convective weather in flight with different weather information sources. A flight test was conducted in which GA pilot test subjects were given different in-flight weather information cues and flown toward convective weather of moderate or greater intensity. The test subjects were not actually flying the aircraft, but were given pilot tasks representative of the workload and position awareness requirements of the en route portion of a cross country GA flight. On each flight, one test subject received weather cues typical of a flight in visual meteorological conditions (VMC), another received cues typical of flight in instrument meteorological conditions (IMC), and a third received cues typical of flight in IMC but augmented with a graphical weather information system (GWIS). The GWIS provided the subject with near real time data-linked weather products, including a weather radar mosaic superimposed on a moving map with a symbol depicting the aircraft's present position and direction of track. At several points during each flight, the test subjects completed short questionnaires which included items addressing their weather situation awareness and flight decisions. In particular, test subjects were asked to identify the location of the nearest convective cells. After the point of nearest approach to convective weather, the test subjects were asked to draw the location of convective weather on an aeronautical chart, along with the aircraft's present position. This paper reports preliminary results on how accurately test subjects provided with these different weather sources could identify the nearest cell of moderate or greater intensity along their route of flight. Additional flight tests are currently being conducted to complete the data set.

Birth Defects in Infants Born to Employees of a Microelectronics and Business Machine Manufacturing Facility

PubMed Central

Silver, Sharon R.; Pinkerton, Lynne E.; Rocheleau, Carissa M.; Deddens, James A.; Michalski, Adrian M.; Van Zutphen, Alissa R.

2017-01-01

Background Concerns about solvent releases from a microelectronics/business machine manufacturing facility in upstate New York led to interest in the health of former workers, including this investigation of birth defects in children of male and female employees. Methods Children born 1983 to 2001 to facility employees were enumerated and matched to New York State’s Congenital Malformations Registry. Reported structural birth defects were compared with numbers expected from state rates (excluding New York City), generating standardized prevalence ratios (SPRs). Exposure assessors classified employees as ever/never potentially exposed at the facility to metals, chlorinated hydrocarbons, and other hydrocarbons during windows critical to organogenesis (female workers) or spermatogenesis (male workers). Among workers, adjusted prevalence ratios were generated to evaluate associations between potential exposures and specific birth defects. Results External comparisons for structural defects were at expectation for infants of male workers (SPR = 1.01; 95% confidence interval [CI], 0.77–1.29; n = 60) and lower for births to female workers (SPR = 0.84; 95% CI, 0.50–1.33; n = 18). Among full-term infants of male workers, ventricular septal defects (VSDs) were somewhat elevated compared with the general population (SPR = 1.58; 95% CI, 0.99–2.39; n = 22). Within the cohort, potential paternal metal exposure was associated with increased VSD risk (adjusted prevalence ratio = 2.70; 95% CI, = 1.09–6.67; n = 7). Conclusion While overall SPRs were near expectation, paternal exposure to metals (primarily lead) appeared to be associated with increased VSD risk in infants. Take-home of occupational exposures, nonoccupational exposures, and chance could not be ruled out as causes. Case numbers for many defects were small, limiting assessment of the role of occupational exposures. PMID:27224896

Lipid-protein nanodiscs for cell-free production of integral membrane proteins in a soluble and folded state: comparison with detergent micelles, bicelles and liposomes.

PubMed

Lyukmanova, E N; Shenkarev, Z O; Khabibullina, N F; Kopeina, G S; Shulepko, M A; Paramonov, A S; Mineev, K S; Tikhonov, R V; Shingarova, L N; Petrovskaya, L E; Dolgikh, D A; Arseniev, A S; Kirpichnikov, M P

2012-03-01

Production of integral membrane proteins (IMPs) in a folded state is a key prerequisite for their functional and structural studies. In cell-free (CF) expression systems membrane mimicking components could be added to the reaction mixture that promotes IMP production in a soluble form. Here lipid-protein nanodiscs (LPNs) of different lipid compositions (DMPC, DMPG, POPC, POPC/DOPG) have been compared with classical membrane mimicking media such as detergent micelles, lipid/detergent bicelles and liposomes by their ability to support CF synthesis of IMPs in a folded and soluble state. Three model membrane proteins of different topology were used: homodimeric transmembrane (TM) domain of human receptor tyrosine kinase ErbB3 (TM-ErbB3, 1TM); voltage-sensing domain of K(+) channel KvAP (VSD, 4TM); and bacteriorhodopsin from Exiguobacterium sibiricum (ESR, 7TM). Structural and/or functional properties of the synthesized proteins were analyzed. LPNs significantly enhanced synthesis of the IMPs in a soluble form regardless of the lipid composition. A partial disintegration of LPNs composed of unsaturated lipids was observed upon co-translational IMP incorporation. Contrary to detergents the nanodiscs resulted in the synthesis of ~80% active ESR and promoted correct folding of the TM-ErbB3. None of the tested membrane mimetics supported CF synthesis of correctly folded VSD, and the protocol of the domain refolding was developed. The use of LPNs appears to be the most promising approach to CF production of IMPs in a folded state. NMR analysis of (15)N-Ile-TM-ErbB3 co-translationally incorporated into LPNs shows the great prospects of this membrane mimetics for structural studies of IMPs produced by CF systems. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular characterization and virus neutralization patterns of severe, non-epizootic forms of feline calicivirus infections resembling virulent systemic disease in cats in Switzerland and in Liechtenstein.

PubMed

Willi, Barbara; Spiri, Andrea M; Meli, Marina L; Samman, Ayman; Hoffmann, Karolin; Sydler, Titus; Cattori, Valentino; Graf, Felix; Diserens, Kevin A; Padrutt, Isabelle; Nesina, Stefanie; Berger, Alice; Ruetten, Maja; Riond, Barbara; Hosie, Margaret J; Hofmann-Lehmann, Regina

2016-01-15

Feline calicivirus (FCV) infections are associated with oral ulceration, chronic stomatitis and a limping syndrome. Epizootic outbreaks of virulent systemic disease (VSD) have been reported in the USA and Europe. Here, the molecular characterization and neutralization patterns of FCV isolates from cases of severe, non-epizootic infection associated with skin ulceration and edema are presented. Samples from eleven symptomatic cats, four in-contact cats and 27 cats with no contact with symptomatic cats were collected and tested for FCV, feline herpesvirus-1 (FHV-1), feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). Phylogenetic analyses based on the capsid (VP1) gene of FCV and virus neutralization with antisera raised against four FCV vaccine strains were performed. Nine kittens and two adult cats in two shelters and two veterinary clinics in four geographically distinct locations in Switzerland and Liechtenstein were affected. The cats showed fever, tongue and skin ulceration, head and paw edema, and occasionally jaundice, generalized edema and dyspnea. All symptomatic cats tested FCV-positive but were negative for FHV-1, FeLV and FIV, with the exception of one FIV-positive kitten. All kittens of one litter and both adult cats died. The disease did not spread to cats in the environment. Cats in the environment displayed phylogenetically distinct, but related, FCV strains. Virus neutralization patterns suggested that some cases might have been potentially prevented by vaccination with the optimal vaccine strain. In conclusion, clinicians should be aware of severe, non-epizootic forms of FCV infections with initial clinical presentations similar to VSD. Copyright © 2015 Elsevier B.V. All rights reserved.

Screening for AMPA receptor auxiliary subunit specific modulators

PubMed Central

Azumaya, Caleigh M.; Days, Emily L.; Vinson, Paige N.; Stauffer, Shaun; Sulikowski, Gary; Weaver, C. David; Nakagawa, Terunaga

2017-01-01

AMPA receptors (AMPAR) are ligand gated ion channels critical for synaptic transmission and plasticity. Their dysfunction is implicated in a variety of psychiatric and neurological diseases ranging from major depressive disorder to amyotrophic lateral sclerosis. Attempting to potentiate or depress AMPAR activity is an inherently difficult balancing act between effective treatments and debilitating side effects. A newly explored strategy to target subsets of AMPARs in the central nervous system is to identify compounds that affect specific AMPAR-auxiliary subunit complexes. This exploits diverse spatio-temporal expression patterns of known AMPAR auxiliary subunits, providing means for designing brain region-selective compounds. Here we report a high-throughput screening-based pipeline that can identify compounds that are selective for GluA2-CNIH3 and GluA2-stargazin complexes. These compounds will help us build upon the growing library of AMPAR-auxiliary subunit specific inhibitors, which have thus far all been targeted to TARP γ-8. We used a cell-based assay combined with a voltage-sensitive dye (VSD) to identify changes in glutamate-gated cation flow across the membranes of HEK cells co-expressing GluA2 and an auxiliary subunit. We then used a calcium flux assay to further validate hits picked from the VSD assay. VU0612951 and VU0627849 are candidate compounds from the initial screen that were identified as negative and positive allosteric modulators (NAM and PAM), respectively. They both have lower IC50/EC50s on complexes containing stargazin and CNIH3 than GSG1L or the AMPAR alone. We have also identified a candidate compound, VU0539491, that has NAM activity in GluA2(R)-CNIH3 and GluA2(Q) complexes and PAM activity in GluA2(Q)-GSG1L complexes. PMID:28358902

Tetralogy of Fallot and aortic root dilation: a long-term outlook.

PubMed

Nagy, Christian D; Alejo, Diane E; Corretti, Mary C; Ravekes, William J; Crosson, Jane E; Spevak, Philip J; Ringel, Richard; Carson, Kathryn A; Khalil, Sara; Dietz, Harry C; Cameron, Duke E; Vricella, Luca A; Traill, Thomas A; Holmes, Kathryn W

2013-04-01

Dilation of the sinus of Valsalva (SoV) has been increasingly observed after repaired tetralogy of Fallot (TOF). We estimate the prevalence of SoV dilation in adults with repaired TOF and analyze possible factors related to aortic disease. Adults with TOF [n = 109, median age 33.2 years (range 18.1 to 69.5)] evaluated at Johns Hopkins Hospital from 2001 to 2009 were reviewed in an observational retrospective cohort study. Median follow-up was 27.3 (range 0.1-48.8) years. SoV dilation was defined as >95 % confidence interval adjusted for age and body surface area (z-score > 2). The prevalence of SoV dilation was 51 % compared with that of a normal population with a mean z-score of 2.03. Maximal aortic diameters were ≥ 4 cm in 39 % (42 of 109), ≥ 4.5 cm in 21 % (23 of 109), ≥ 5 cm in 8 % (9 of 109), and ≥ 5.5 cm in 2 % (2 of 109). There was no aortic dissection or death due contributable to aortic disease. Aortic valve replacement was performed in 1.8 % and aortic root or ascending aorta (AA) replacement surgery in 2.8 % of patients. By multivariate logistic regression analysis, aortic regurgitation (AR) [odds ratio (OR) = 3.09, p = 0.005], residual ventricular septal defect (VSD) (OR = 4.14, p < 0.02), and TOF with pulmonary atresia (TOF/PA) (OR = 6.75, p = 0.03) were associated with increased odds of dilated aortic root. SoV dilation after TOF repair is common and persists with aging. AR, residual VSD, and TOF/PA are associated with increased odds of dilation. AA evaluation beyond the SoV is important. Indexed values are imperative to avoid bias on the basis of age and body surface area.

Early pregnancy exposure to antihistamines and risk of congenital heart defects: results of two case-control studies.

PubMed

Smedts, Huberdina P M; de Jonge, Linda; Bandola, Sarah J G; Baardman, Marlies E; Bakker, Marian K; Stricker, Bruno H C; Steegers-Theunissen, Régine P M

2014-09-01

We aimed to study the association between use of antihistamines in early pregnancy and congenital heart defects (CHD) in the offspring. Two case-control studies. HAVEN study, Erasmus MC, University Medical Centre, Rotterdam, and Eurocat Northern Netherlands (NNL), University Medical Center Groningen, Groningen, the Netherlands. We studied 361 children with CHD and 410 controls without congenital malformations from the HAVEN study and replicated the analyses in 445 children with CHD and 530 controls from the Eurocat NNL registry. Information about antihistamine use in early pregnancy and potential confounders was obtained from questionnaires postpartum. We calculated the association between antihistamines and CHD risk by multivariable logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (CI). In the HAVEN study, 25 of 771 mothers used antihistamines that were associated with an increased CHD risk (OR 3.0, 95% CI 1.2-7.3), particularly atrioventricular septal defects (AVSD) (OR 5.1, 95 % CI 1.3-20.5) and perimembranous ventricular septal defects (pVSD) (OR 5.1, 95% CI 1.8-14.4). Mothers with severe nausea who did not use antihistamines had a reduced risk (OR 0.7, 95% CI 0.5-0.98), whereas nauseous mothers using antihistamines showed an almost fivefold increased risk of pVSD (OR 4.8, 95% CI 1.1-21.8). The association between antihistamines and AVSD was confirmed in the Eurocat cohort (OR 3.5, 95% CI 1.4-8.7), but we could not replicate the association with overall CHD risk. We found a positive association between antihistamine use in early pregnancy and CHD risk, particularly AVSD, which seemed to be independent of nausea/vomiting.

Surgical Interventions for Atrioventricular Septal Defect Subtypes: The Pediatric Heart Network Experience

PubMed Central

Kaza, Aditya K.; Colan, Steven D.; Jaggers, James; Lu, Minmin; Atz, Andrew M.; Sleeper, Lynn A.; McCrindle, Brian W.; Lambert, Linda M.; Margossian, Renee; Lacro, Ronald V.; Richmond, Marc E.; Natarajan, Shobha; Minich, L. LuAnn

2012-01-01

Background The influence of atrioventricular septal defect (AVSD) subtype on outcomes after repair is poorly understood. Methods Demographic, procedural, and outcome data were obtained 1 and 6 months after AVSD repair in an observational study conducted at 7 North American centers. Results The 215 AVSD patients were subtyped as 60 partial, 27 transitional, 120 complete, and 8 with canal-type VSD. Preoperatively, transitional patients had the highest prevalence of moderate or severe left atrioventricular valve regurgitation (LAVVR, p = 0.01). At repair, complete AVSD and canal-type VSD patients, both with the highest prevalence of trisomy 21 (p < 0.001), were younger (p < 0.001), had lower weight-for-age z scores (p = 0.005), and had more associated cardiac defects (p < 0.001). Annuloplasty was similar among subtypes (p = 0.91), with longer duration of ventilation and hospitalization for complete AVSD (p < 0.001). Independent predictors of moderate or severe LAVVR at the 6-month follow-up were older log(age) at repair (p = 0.02) but not annuloplasty, subtype, or center (p > 0.4). Weight-for-age z scores improved in all subtypes at the 6-month follow-up, and improvement was similar among subtypes (p = 0.17). Conclusions AVSD subtype was significantly associated with patient characteristics and clinical status before repair and influenced age at repair. Significant postoperative LAVVR is the most common sequela, with a similar prevalence across centers 6 months after the intervention. Annuloplasty failed to decrease the postoperative prevalence of moderate or severe LAVVR at 6 months. After accounting for age at repair, AVSD subtype was not associated with postoperative LAVVR severity or growth failure at 6 months. Further investigation is needed to determine if interventional strategies specific to AVSD subtype improve surgical outcomes. PMID:21872212

Micro-computed Tomography Provides High Accuracy Congenital Heart Disease Diagnosis in Neonatal and Fetal Mice

PubMed Central

Kim, Andrew J.; Francis, Richard; Liu, Xiaoqin; Devine, William A.; Ramirez, Ricardo; Anderton, Shane J.; Wong, Li Yin; Faruque, Fahim; Gabriel, George C.; Leatherbury, Linda; Tobita, Kimimasa; Lo, Cecilia W.

2013-01-01

Background Mice are well suited for modeling human congenital heart defects (CHD), given their four-chamber cardiac anatomy. However, mice with CHD invariably die prenatally/neonatally, causing CHD phenotypes to be missed. Therefore, we investigated the efficacy of noninvasive micro-computed tomography (micro-CT) to screen for CHD in stillborn/fetal mice. These studies were carried out using chemically mutagenized mice expected to be enriched for birth defects including CHD. Methods and Results Stillborn/fetal mice obtained from the breeding of N-ethyl-N-nitrosourea (ENU) mutagenized mice were formalin-fixed and stained with iodine, then micro-CT scanned. Those diagnosed with CHD and some CHD-negative pups were necropsied. A subset of these were further analyzed by histopathology to confirm the CHD/no-CHD diagnosis. Micro-CT scanning of 2105 fetal/newborn mice revealed an abundance of ventricular septal defects (VSD) (n=307). Overall, we observed an accuracy of 89.8% for VSD diagnosis. Outflow tract anomalies identified by micro-CT included double outlet right ventricle (n=36), transposition of the great arteries (n=14), and persistent truncus arteriosus (n=3). These were diagnosed with a 97.4% accuracy. Aortic arch anomalies also were readily detected with an overall 99.6% accuracy. This included right aortic arch (n=28) and coarctation/interrupted aortic arch (n=12). Also detected by micro-CT were atrioventricular septal defects (n=22), tricuspid hypoplasia/atresia (n=13), and coronary artery fistulas (n=16). They yielded accuracies of 98.9%, 100%, and 97.8% respectively. Conclusions Contrast enhanced micro-CT imaging in neonatal/fetal mice can reliably detect a wide spectrum of CHD. We conclude micro-CT imaging can be used for routine rapid assessments of structural heart defects in fetal/newborn mice. PMID:23759365

Long-Term Follow-Up Study of Temporary Tricuspid Valve Detachment as Approach to VSD Repair without Consequent Tricuspid Dysfunction.

PubMed

Lucchese, Gianluca; Rossetti, Lucia; Faggian, Giuseppe; Luciani, Giovanni B

2016-10-01

Temporary tricuspid valve detachment improves the operative view of certain congenital ventricular septal defects (VSDs), but its long-term effects on tricuspid valve function are still debated. From 2002 through 2012, we performed a prospective study of 68 children (mean age, 1.28 ± 1.01 yr) who underwent transatrial closure of VSDs following temporary tricuspid valve detachment. Sixty patients had conoventricular and 8 had mid-muscular VSDs. All were in sinus rhythm. Seventeen patients had systemic pulmonary artery pressures. Preoperative echocardiograms showed trivial-to-mild tricuspid regurgitation in 62 patients and tricuspid dysplasia with severe regurgitation in 6 patients. Patients were clinically and echocardiographically monitored at 30 postoperative days, 3 months, 6 months, every 6 months thereafter for the first 2 years, and then once a year. No in-hospital or late death was observed at the median follow-up evaluation of 5.9 years. Mean intensive care unit and hospital stays were 1.6 ± 1.1 and 7.3 ± 2.7 days, respectively. Residual small VSDs occurred in 3 patients, and temporary atrioventricular block in one. After VSD repair, 62 patients (91%) had trivial or mild tricuspid regurgitation, and 6 moderate. Five of these last had severe tricuspid regurgitation preoperatively and had undergone additional tricuspid valve repair during the procedure. The grade of residual tricuspid regurgitation remained stable postoperatively, and no tricuspid stenosis was documented. All patients were in New York Heart Association class I at follow-up. Temporary tricuspid valve detachment is a simple and useful method for a complete visualization of certain VSDs without incurring substantial tricuspid dysfunction.

Long-Term Follow-Up Study of Temporary Tricuspid Valve Detachment as Approach to VSD Repair without Consequent Tricuspid Dysfunction

PubMed Central

Rossetti, Lucia; Faggian, Giuseppe; Luciani, Giovanni B.

2016-01-01

Temporary tricuspid valve detachment improves the operative view of certain congenital ventricular septal defects (VSDs), but its long-term effects on tricuspid valve function are still debated. From 2002 through 2012, we performed a prospective study of 68 children (mean age, 1.28 ± 1.01 yr) who underwent transatrial closure of VSDs following temporary tricuspid valve detachment. Sixty patients had conoventricular and 8 had mid-muscular VSDs. All were in sinus rhythm. Seventeen patients had systemic pulmonary artery pressures. Preoperative echocardiograms showed trivial-to-mild tricuspid regurgitation in 62 patients and tricuspid dysplasia with severe regurgitation in 6 patients. Patients were clinically and echocardiographically monitored at 30 postoperative days, 3 months, 6 months, every 6 months thereafter for the first 2 years, and then once a year. No in-hospital or late death was observed at the median follow-up evaluation of 5.9 years. Mean intensive care unit and hospital stays were 1.6 ± 1.1 and 7.3 ± 2.7 days, respectively. Residual small VSDs occurred in 3 patients, and temporary atrioventricular block in one. After VSD repair, 62 patients (91%) had trivial or mild tricuspid regurgitation, and 6 moderate. Five of these last had severe tricuspid regurgitation preoperatively and had undergone additional tricuspid valve repair during the procedure. The grade of residual tricuspid regurgitation remained stable postoperatively, and no tricuspid stenosis was documented. All patients were in New York Heart Association class I at follow-up. Temporary tricuspid valve detachment is a simple and useful method for a complete visualization of certain VSDs without incurring substantial tricuspid dysfunction. PMID:27777518

Comparison of Forced ENSO-Like Hydrological Expressions in Simulations of the Preindustrial and Mid-Holocene

NASA Technical Reports Server (NTRS)

Lewis, Sophie C.; LeGrande, Allegra N.; Schmidt, Gavin A.; Kelley, Maxwell

2014-01-01

Using the water isotope- and vapor source distribution (VSD) tracer-enabled Goddard Institute for Space Studies ModelE-R, we examine changing El Nino-Southern Oscillation (ENSO)-like expressions in the hydrological cycle in a suite of model experiments. We apply strong surface temperature anomalies associated with composite observed El Nino and La Nina events as surface boundary conditions to preindustrial and mid-Holocene model experiments in order to investigate ENSO-like expressions in the hydrological cycle under varying boundary conditions. We find distinct simulated hydrological anomalies associated with El Nino-like ("ENSOWARM") and La Nina-like ("ENSOCOOL") conditions, and the region-specific VSD tracers show hydrological differences across the Pacific basin between El Nino-like and La Nina-like events. The application of ENSOCOOL forcings does not produce climatological anomalies that represent the equal but opposite impacts of the ENSOWARM experiment, as the isotopic anomalies associated with ENSOWARM conditions are generally stronger than with ENSOCOOL and the spatial patterns of change distinct. Also, when the same ENSO-like surface temperature anomalies are imposed on the mid-Holocene, the hydrological response is muted, relative to the preindustrial. Mid-Holocene changes in moisture sources to the analyzed regions across the Pacific reveal potentially complex relationships between ENSO-like conditions and boundary conditions. Given the complex impacts of ENSO-like conditions on various aspects of the hydrological cycle, we suggest that proxy record insights into paleo-ENSO variability are most likely to be robust when synthesized from a network of many spatially diverse archives, which can account for the potential nonstationarity of ENSO teleconnections under different boundary conditions.

A graphical workstation based part-task flight simulator for preliminary rapid evaluation of advanced displays

NASA Technical Reports Server (NTRS)

Wanke, Craig; Kuchar, James; Hahn, Edward; Pritchett, Amy; Hansman, R. J.

1992-01-01

Advances in avionics and display technology are significantly changing the cockpit environment in current transport aircraft. The MIT Aeronautical Systems Lab (ASL) has developed a part-task flight simulator specifically to study the effects of these new technologies on flight crew situational awareness and performance. The simulator is based on a commercially-available graphics workstation, and can be rapidly reconfigured to meet the varying demands of experimental studies. The simulator has been successfully used to evaluate graphical microburst alerting displays, electronic instrument approach plates, terrain awareness and alerting displays, and ATC routing amendment delivery through digital datalinks.

LinkWinds: An Approach to Visual Data Analysis

NASA Technical Reports Server (NTRS)

Jacobson, Allan S.

1992-01-01

The Linked Windows Interactive Data System (LinkWinds) is a prototype visual data exploration and analysis system resulting from a NASA/JPL program of research into graphical methods for rapidly accessing, displaying and analyzing large multivariate multidisciplinary datasets. It is an integrated multi-application execution environment allowing the dynamic interconnection of multiple windows containing visual displays and/or controls through a data-linking paradigm. This paradigm, which results in a system much like a graphical spreadsheet, is not only a powerful method for organizing large amounts of data for analysis, but provides a highly intuitive, easy to learn user interface on top of the traditional graphical user interface.

US Navy Littoral Combat Ship (LCS) Capabilities, Risks, Possible Missions, and Modules to Support Future USMC Operating Concepts

DTIC Science & Technology

2011-07-29

squad Armament: M60 7 .62mm machine gun , MK19 40mm, M2 .50 caL machine gun 61 "Spartan Scout Unmanned Surface Vehicle (USV)," Defense Industry...1) RQ-8B Fire Scout helicopter (VTUAV) a) EO/IR/LD sensor and datalink relay 2) MH-60R/S helicopters a) GAU 16/19 machine gun b) AGM-114 Hellfire...60Rhelicopter car1ies the a .50 caliber OAU 16/A machine gun , a crew-served, recoil operated, belt-fed, air cooled, percussion fired weapon, with a rate of fire

Off-pump repair of a post-infarct ventricular septal defect: the 'Hamburger procedure'

PubMed Central

Barker, Thomas A; Ng, Alexander; Morgan, Ian S

2006-01-01

We report a novel off-pump technique for the surgical closure of post-infarct ventricular septal defects (VSDs). The case report describes the peri-operative management of a 76 year old lady who underwent the 'Hamburger procedure' for closure of her apical VSD. Refractory cardiogenic shock meant that traditional patch repairs requiring cardiopulmonary bypass would be poorly tolerated. We show that echocardiography guided off-pump posterior-anterior septal plication is a safe, effective method for closing post-infarct VSDs in unstable patients. More experience is required to ascertain whether this technique will become an accepted alternative to patch repairs. PMID:16722552

The off-label use of the Amplatzer muscular VSD occluder for large patent ductus arteriosus: a case report and review.

PubMed

Cubeddu, Roberto J; Babin, Ivan; Inglessis, Ignacio

2014-07-01

A percutaneous approach to the closure of patent ductus arteriosus (PDA) is the preferred procedure in the majority of cases. However, there is little experience with percutaneous closure of unusually large PDA. We report the case of a 28-year-old female with moderate left ventricular dilation and pulmonary hypertension resulting from a large 16 mm PDA. Percutaneous closure was successfully performed using an off-label Amplatzer muscular ventricular septal defect occluder after intravascular ultrasound assessment. Technical challenges, including accurate assessment of defect size and device selection are exemplified along with a comprehensive overview of the available literature.

SISSY: An example of a multi-threaded, networked, object-oriented databased application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scipioni, B.; Liu, D.; Song, T.

1993-05-01

The Systems Integration Support SYstem (SISSY) is presented and its capabilities and techniques are discussed. It is fully automated data collection and analysis system supporting the SSCL`s systems analysis activities as they relate to the Physics Detector and Simulation Facility (PDSF). SISSY itself is a paradigm of effective computing on the PDSF. It uses home-grown code (C++), network programming (RPC, SNMP), relational (SYBASE) and object-oriented (ObjectStore) DBMSs, UNIX operating system services (IRIX threads, cron, system utilities, shells scripts, etc.), and third party software applications (NetCentral Station, Wingz, DataLink) all of which act together as a single application to monitor andmore » analyze the PDSF.« less

A prototype home robot with an ambient facial interface to improve drug compliance.

PubMed

Takacs, Barnabas; Hanak, David

2008-01-01

We have developed a prototype home robot to improve drug compliance. The robot is a small mobile device, capable of autonomous behaviour, as well as remotely controlled operation via a wireless datalink. The robot is capable of face detection and also has a display screen to provide facial feedback to help motivate patients and thus increase their level of compliance. An RFID reader can identify tags attached to different objects, such as bottles, for fluid intake monitoring. A tablet dispenser allows drug compliance monitoring. Despite some limitations, experience with the prototype suggests that simple and low-cost robots may soon become feasible for care of people living alone or in isolation.

Signal detection of adverse events with imperfect confirmation rates in vaccine safety studies using self-controlled case series design.

PubMed

Xu, Stanley; Newcomer, Sophia; Nelson, Jennifer; Qian, Lei; McClure, David; Pan, Yi; Zeng, Chan; Glanz, Jason

2014-05-01

The Vaccine Safety Datalink project captures electronic health record data including vaccinations and medically attended adverse events on 8.8 million enrollees annually from participating managed care organizations in the United States. While the automated vaccination data are generally of high quality, a presumptive adverse event based on diagnosis codes in automated health care data may not be true (misclassification). Consequently, analyses using automated health care data can generate false positive results, where an association between the vaccine and outcome is incorrectly identified, as well as false negative findings, where a true association or signal is missed. We developed novel conditional Poisson regression models and fixed effects models that accommodate misclassification of adverse event outcome for self-controlled case series design. We conducted simulation studies to evaluate their performance in signal detection in vaccine safety hypotheses generating (screening) studies. We also reanalyzed four previously identified signals in a recent vaccine safety study using the newly proposed models. Our simulation studies demonstrated that (i) outcome misclassification resulted in both false positive and false negative signals in screening studies; (ii) the newly proposed models reduced both the rates of false positive and false negative signals. In reanalyses of four previously identified signals using the novel statistical models, the incidence rate ratio estimates and statistical significances were similar to those using conventional models and including only medical record review confirmed cases. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Critically Underdeveloped Left Heart Morphology Associated with Prematurity and Low Birth Weight: Conditional Staged Rehabilitation Towards Biventricular Repair and Time-Related Growth of Left Heart Structures.

PubMed

Ahmad, Fareed; Mangano, Robert; Shore, Shirah; Polimenakos, Anastasios

2017-10-01

This is a case report of premature low birth weight infant with hypoplasia of left heart structures and a large malaligned VSD who underwent successful staged approach of biventricular repair. We obtained qualitative and quantitative echocardiographic, MRI, and conventional catheterization data to support stepwise strategy towards LV rehabilitation to sustain adequate cardiac output. A thorough and intense follow-up has shown significant growth of left heart structures and favorable clinical status following staged biventricular repair. Our data indicate usefulness of qualitative and quantitative advanced complimentary multi-imaging modalities in predicting the postnatal growth potential of critically underdeveloped left heart structures.

In search of a consensus model of the resting state of a voltage-sensing domain.

PubMed

Vargas, Ernesto; Bezanilla, Francisco; Roux, Benoît

2011-12-08

Voltage-sensing domains (VSDs) undergo conformational changes in response to the membrane potential and are the critical structural modules responsible for the activation of voltage-gated channels. Structural information about the key conformational states underlying voltage activation is currently incomplete. Through the use of experimentally determined residue-residue interactions as structural constraints, we determine and refine a model of the Kv channel VSD in the resting conformation. The resulting structural model is in broad agreement with results that originate from various labs using different techniques, indicating the emergence of a consensus for the structural basis of voltage sensing. Copyright © 2011 Elsevier Inc. All rights reserved.

Pattern of risks of rheumatoid arthritis among patients using statins: A cohort study with the clinical practice research datalink.

PubMed

de Jong, Hilda J I; Cohen Tervaert, Jan Willem; Lalmohamed, Arief; de Vries, Frank; Vandebriel, Rob J; van Loveren, Henk; Klungel, Olaf H; van Staa, Tjeerd P

2018-01-01

We examined the association between statin use and the risk of rheumatoid arthritis (RA), with special focus on describing the patterns of risks of RA during statin exposure in a large population-based cohort in the United Kingdom. In the Clinical Practice Research Datalink, patients aged ≥40 years with at least one prescription of statins (1995-2009) were selected, and matched by age (+/-5 years), sex, practice and date of first prescription of statins to non-users. The follow-up period of statin use was divided into periods of current, recent and past exposure, with patients moving between these three exposure categories over time. Time-dependent Cox models were used to derive hazard ratios (HRs) of RA, adjusted for disease history and previous drug use. The study population included 1,023,240 patients, of whom 511,620 were statin users. No associations were found between RA and current (HRadj,1.06;99%CI:0.88-1.27) or past statin users (HRadj,1.18;99%CI:0.88-1.57). However, in patients who currently used statins, hazard rates were increased shortly after the first prescription of statins and then gradually decreased to baseline level. The risk of developing RA was increased in recent statin users, as compared to non-users (HRadj,1.39;99%CI:1.01-1.90). The risk of RA is substantially increased in the first year after the start of statins and then diminishes to baseline level. These findings may suggest that statins might accelerate disease onset in patients susceptible to develop RA, but in other patients, statins are probably safe and well tolerated, even after prolonged use. Alternatively, we cannot rule out that confounding by cardiovascular risk factors and ascertainment bias may have influenced the findings.

Pattern of risks of rheumatoid arthritis among patients using statins: A cohort study with the clinical practice research datalink

PubMed Central

de Jong, Hilda J. I.; Cohen Tervaert, Jan Willem; Lalmohamed, Arief; de Vries, Frank; Vandebriel, Rob J.; van Loveren, Henk; van Staa, Tjeerd P.

2018-01-01

We examined the association between statin use and the risk of rheumatoid arthritis (RA), with special focus on describing the patterns of risks of RA during statin exposure in a large population-based cohort in the United Kingdom. In the Clinical Practice Research Datalink, patients aged ≥40 years with at least one prescription of statins (1995–2009) were selected, and matched by age (+/-5 years), sex, practice and date of first prescription of statins to non-users. The follow-up period of statin use was divided into periods of current, recent and past exposure, with patients moving between these three exposure categories over time. Time-dependent Cox models were used to derive hazard ratios (HRs) of RA, adjusted for disease history and previous drug use. The study population included 1,023,240 patients, of whom 511,620 were statin users. No associations were found between RA and current (HRadj,1.06;99%CI:0.88–1.27) or past statin users (HRadj,1.18;99%CI:0.88–1.57). However, in patients who currently used statins, hazard rates were increased shortly after the first prescription of statins and then gradually decreased to baseline level. The risk of developing RA was increased in recent statin users, as compared to non-users (HRadj,1.39;99%CI:1.01–1.90). The risk of RA is substantially increased in the first year after the start of statins and then diminishes to baseline level. These findings may suggest that statins might accelerate disease onset in patients susceptible to develop RA, but in other patients, statins are probably safe and well tolerated, even after prolonged use. Alternatively, we cannot rule out that confounding by cardiovascular risk factors and ascertainment bias may have influenced the findings. PMID:29474418

Prevalence, incidence, indication, and choice of antidepressants in patients with and without chronic kidney disease: a matched cohort study in UK Clinical Practice Research Datalink.

PubMed

Iwagami, Masao; Tomlinson, Laurie A; Mansfield, Kathryn E; McDonald, Helen I; Smeeth, Liam; Nitsch, Dorothea

2017-07-01

People with chronic kidney disease (CKD) have an increased prevalence of depression, anxiety, and neuropathic pain. We examined prevalence, incidence, indication for, and choice of antidepressants among patients with and without CKD. Using the UK Clinical Practice Research Datalink, we identified patients with CKD (two measurements of estimated glomerular filtration rate < 60 mL/min/1.73m 2 for ≥3 months) between April 2004 and March 2014. We compared those with CKD to a general population cohort without CKD (matched on age, sex, general practice, and calendar time [index date]). We identified any antidepressant prescribing in the six months prior to index date (prevalence), the first prescription after index date among non-prevalent users (incidence), and recorded diagnoses (indication). We compared antidepressant choice between patients with and without CKD among patients with a diagnosis of depression. There were 242 349 matched patients (median age 76 [interquartile range 70-82], male 39.3%) with and without CKD. Prevalence of antidepressant prescribing was 16.3 and 11.9%, and incidence was 57.2 and 42.4/1000 person-years, in patients with and without CKD, respectively. After adjusting for confounders, CKD remained associated with higher prevalence and incidence of antidepressant prescription. Regardless of CKD status, selective serotonin reuptake inhibitors were predominantly prescribed for depression or anxiety, while tricyclic antidepressants were prescribed for neuropathic pain or other reasons. Antidepressant choice was similar in depressed patients with and without CKD. The rate of antidepressant prescribing was nearly one and a half times higher among people with CKD than in the general population. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Health care resource use by patients before and after a diagnosis of chronic fatigue syndrome (CFS/ME): a clinical practice research datalink study.

PubMed

Collin, Simon M; Bakken, Inger J; Nazareth, Irwin; Crawley, Esther; White, Peter D

2017-05-05

Our aim was to investigate patterns of health care resource use by patients before and after a diagnosis of CFS/ME, as recorded by Clinical Practice Research Datalink (CPRD) GP practices in the UK. We used a case-control study design in which patients who had a first recorded diagnosis of CFS/ME during the period 01/01/2001 to 31/12/2013 were matched 1:1 with controls by age, sex, and GP practice. We compared rates of GP consultations, diagnostic tests, prescriptions, referrals, and symptoms between the two groups from 15 years (in adults) or 10 years (in children) before diagnosis to 10 years after diagnosis. Data were available for 6710 adult and 916 child (age <18 years) matched case-control pairs. Rates of GP consultations, diagnostic tests, prescriptions, referrals, and symptoms spiked dramatically in the year when a CFS/ME diagnosis was recorded. GP consultation rates were 50% higher in adult cases compared to controls 11-15 years before diagnosis (rate ratio (RR) 1.49 (95% CI 1.46, 1.52)) and 56% higher 6-10 years after diagnosis (RR 1.56 (1.54, 1.57)). In children, consultation rates in cases were 45% higher 6-10 years before diagnosis (RR 1.45 (1.40, 1.51)) and 62% higher 6-10 years after diagnosis (RR 1.62 (1.54, 1.70)). For adults and children, rates of tests, prescriptions, referrals, and symptoms were higher in cases compared to controls for up to 10 years before and after diagnosis. Adults and children with CFS/ME have greater health care needs than the rest of the population for at least ten years before their diagnosis, and these higher levels of health care resource use continue for at least ten years after diagnosis.

Lansoprazole use and tuberculosis incidence in the United Kingdom Clinical Practice Research Datalink: A population based cohort

PubMed Central

Yates, Tom A.; Tomlinson, Laurie A.; Bhaskaran, Krishnan; Langan, Sinead; Thomas, Sara; Smeeth, Liam

2017-01-01

Background Recent in vitro and animal studies have found the proton pump inhibitor (PPI) lansoprazole to be highly active against Mycobacterium tuberculosis. Omeprazole and pantoprazole have no activity. There is no evidence that, in clinical practice, lansoprazole can treat or prevent incident tuberculosis (TB) disease. Methods and findings We studied a cohort of new users of lansoprazole, omeprazole, or pantoprazole from the United Kingdom Clinical Practice Research Datalink to determine whether lansoprazole users have a lower incidence of TB disease than omeprazole or pantoprazole users. Negative control outcomes of myocardial infarction (MI) and herpes zoster were also studied. Multivariable Cox proportional hazards regression was used to adjust for potential confounding by a wide range of factors. We identified 527,364 lansoprazole initiators and 923,500 omeprazole or pantoprazole initiators. Lansoprazole users had a lower rate of TB disease (n = 86; 10.0 cases per 100,000 person years; 95% confidence interval 8.1–12.4) than omeprazole or pantoprazole users (n = 193; 15.3 cases per 100,000 person years; 95% confidence interval 13.3–17.7), with an adjusted hazard ratio (HR) of 0.68 (0.52–0.89). No association was found with MI (adjusted HR 1.04; 95% confidence interval 1.00–1.08) or herpes zoster (adjusted HR 1.03; 95% confidence interval 1.00–1.06). Limitations of this study are that we could not determine whether TB disease was due to reactivation of latent infection or a result of recent transmission, nor could we determine whether lansoprazole would have a beneficial effect if given to people presenting with TB disease. Conclusions In this study, use of the commonly prescribed and cheaply available PPI lansoprazole was associated with reduced incidence of TB disease. Given the serious problem of drug resistance and the adverse side effect profiles of many TB drugs, further investigation of lansoprazole as a potential antituberculosis agent is warranted. PMID:29161254

Creating a Realistic Weather Environment for Motion-Based Piloted Flight Simulation

NASA Technical Reports Server (NTRS)

Daniels, Taumi S.; Schaffner, Philip R.; Evans, Emory T.; Neece, Robert T.; Young, Steve D.

2012-01-01

A flight simulation environment is being enhanced to facilitate experiments that evaluate research prototypes of advanced onboard weather radar, hazard/integrity monitoring (HIM), and integrated alerting and notification (IAN) concepts in adverse weather conditions. The simulation environment uses weather data based on real weather events to support operational scenarios in a terminal area. A simulated atmospheric environment was realized by using numerical weather data sets. These were produced from the High-Resolution Rapid Refresh (HRRR) model hosted and run by the National Oceanic and Atmospheric Administration (NOAA). To align with the planned flight simulation experiment requirements, several HRRR data sets were acquired courtesy of NOAA. These data sets coincided with severe weather events at the Memphis International Airport (MEM) in Memphis, TN. In addition, representative flight tracks for approaches and departures at MEM were generated and used to develop and test simulations of (1) what onboard sensors such as the weather radar would observe; (2) what datalinks of weather information would provide; and (3) what atmospheric conditions the aircraft would experience (e.g. turbulence, winds, and icing). The simulation includes a weather radar display that provides weather and turbulence modes, derived from the modeled weather along the flight track. The radar capabilities and the pilots controls simulate current-generation commercial weather radar systems. Appropriate data-linked weather advisories (e.g., SIGMET) were derived from the HRRR weather models and provided to the pilot consistent with NextGen concepts of use for Aeronautical Information Service (AIS) and Meteorological (MET) data link products. The net result of this simulation development was the creation of an environment that supports investigations of new flight deck information systems, methods for incorporation of better weather information, and pilot interface and operational improvements for better aviation safety. This research is part of a larger effort at NASA to study the impact of the growing complexity of operations, information, and systems on crew decision-making and response effectiveness; and then to recommend methods for improving future designs.

Interval between onset of psoriasis and psoriatic arthritis comparing the UK Clinical Practice Research Datalink with a hospital-based cohort.

PubMed

Tillett, William; Charlton, Rachel; Nightingale, Alison; Snowball, Julia; Green, Amelia; Smith, Catherine; Shaddick, Gavin; McHugh, Neil

2017-12-01

To describe the time interval between the onset of psoriasis and PsA in the UK primary care setting and compare with a large, well-classified secondary care cohort. Patients with PsA and/or psoriasis were identified in the UK Clinical Practice Research Datalink (CPRD). The secondary care cohort comprised patients from the Bath PsA longitudinal observational cohort study. For incident PsA patients in the CPRD who also had a record of psoriasis, the time interval between PsA diagnosis and first psoriasis record was calculated. Comparisons were made with the time interval between diagnoses in the Bath cohort. There were 5272 eligible PsA patients in the CPRD and 815 in the Bath cohort. In both cohorts, the majority of patients (82.3 and 61.3%, respectively) had psoriasis before their PsA diagnosis or within the same calendar year (10.5 and 23.8%), with only a minority receiving their PsA diagnosis first (7.1 and 14.8%). Excluding those who presented with arthritis before psoriasis, the median time between diagnoses was 8 years [interquartile range (IQR) 2-15] in the CPRD and 7 years (IQR 0-20) in the Bath cohort. In the CPRD, 60.1 and 75.1% received their PsA diagnosis within 10 and 15 years of their psoriasis diagnosis, respectively; this was comparable with 57.2 and 67.7% in the Bath cohort. A similar distribution for the time interval between psoriasis and arthritis was observed in the CPRD and secondary care cohort. These data can inform screening strategies and support the validity of data from each cohort. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006.

PubMed

Abrams, Joseph Y; Weintraub, Eric S; Baggs, James M; McCarthy, Natalie L; Schonberger, Lawrence B; Lee, Grace M; Klein, Nicola P; Belongia, Edward A; Jackson, Michael L; Naleway, Allison L; Nordin, James D; Hambidge, Simon J; Belay, Ermias D

2015-01-03

Kawasaki disease is a childhood vascular disorder of unknown etiology. Concerns have been raised about vaccinations being a potential risk factor for Kawasaki disease. Data from the Vaccine Safety Datalink were collected on children aged 0-6 years at seven managed care organizations across the United States. Defining exposure as one of several time periods up to 42 days after vaccination, we conducted Poisson regressions controlling for age, sex, season, and managed care organization to determine if rates of physician-diagnosed and verified Kawasaki disease were elevated following vaccination compared to rates during all unexposed periods. We also performed case-crossover analyses to control for unmeasured confounding. A total of 1,721,186 children aged 0-6 years from seven managed care organizations were followed for a combined 4,417,766 person-years. The rate of verified Kawasaki disease was significantly lower during the 1-42 days after vaccination (rate ratio=0.50, 95% CL=0.27-0.92) and 8-42 days after vaccination (rate ratio=0.45, 95% CL=0.22-0.90) compared to rates during unexposed periods. Breaking down the analysis by vaccination category did not identify a subset of vaccines which was solely responsible for this association. The case-crossover analyses revealed that children with Kawasaki disease had lower rates of vaccination in the 42 days prior to symptom onset for both physician-diagnosed Kawasaki disease (rate ratio=0.79, 95% CL=0.64-0.97) and verified Kawasaki disease (rate ratio=0.38, 95% CL=0.20-0.75). Childhood vaccinations' studied did not increase the risk of Kawasaki disease; conversely, vaccination was associated with a transient decrease in Kawasaki disease incidence. Verifying and understanding this potential protective effect could yield clues to the underlying etiology of Kawasaki disease. Copyright © 2014. Published by Elsevier Ltd.

Ischaemic cardiac events and use of strontium ranelate in postmenopausal osteoporosis: a nested case-control study in the CPRD.

PubMed

Cooper, C; Fox, K M; Borer, J S

2014-02-01

We explored the cardiac safety of the osteoporosis treatment strontium ranelate in the UK Clinical Practice Research Datalink. While known cardiovascular risk factors like obesity and smoking were associated with increased cardiac risk, use of strontium ranelate was not associated with any increase in myocardial infarction or cardiovascular death. It has been suggested that strontium ranelate may increase risk for cardiac events in postmenopausal osteoporosis. We set out to explore the cardiac safety of strontium ranelate in the Clinical Practice Research Datalink (CPRD) and linked datasets. We performed a nested case-control study. Primary outcomes were first definite myocardial infarction, hospitalisation with myocardial infarction, and cardiovascular death. Cases and matched controls were nested in a cohort of women treated for osteoporosis. The association with exposure to strontium ranelate was analysed by multivariate conditional logistic regression. Of the 112,445 women with treated postmenopausal osteoporosis, 6,487 received strontium ranelate. Annual incidence rates for first definite myocardial infarction (1,352 cases), myocardial infarction with hospitalisation (1,465 cases), and cardiovascular death (3,619 cases) were 3.24, 6.13, and 14.66 per 1,000 patient-years, respectively. Obesity, smoking, and cardiovascular treatments were associated with significant increases in risk for cardiac events. Current or past use of strontium ranelate was not associated with increased risk for first definite myocardial infarction (odds ratio [OR] 1.05, 95 % confidence interval [CI] 0.68-1.61 and OR 1.12, 95 % CI 0.79-1.58, respectively), hospitalisation with myocardial infarction (OR 0.84, 95 % CI 0.54-1.30 and OR 1.17, 95 % CI 0.83-1.66), or cardiovascular death (OR 0.96, 95 % CI 0.76-1.21 and OR 1.16, 95 % CI 0.94-1.43) versus patients who had never used strontium ranelate. Analysis in the CPRD did not find evidence for a higher risk for cardiac events associated with the use of strontium ranelate in postmenopausal osteoporosis.

Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozolinš, Terence R.S., E-mail: ozolinst@queensu.ca; Weston, Andrea D.; Perretta, Anthony

Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GDmore » 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.« less

Congenital heart surgery: expected versus observed surgical performance according to the Aristotle complexity score.

PubMed

Photiadis, J; Sinzobahamvya, N; Arenz, C; Sata, S; Haun, C; Schindler, E; Asfour, B; Hraska, V

2011-08-01

The Aristotle score quantifies the complexity involved in congenital heart surgery. It defines surgical performance as complexity score times hospital survival. We studied how expected and observed surgical performance evolved over time. 2312 main procedures carried out between 2006 and 2010 were analyzed. The Aristotle basic score, corresponding hospital survival and related observed surgical performance were estimated. Expected survival was based on the mortality risks published by O'Brien and coauthors. Observed performance divided by expected performance was called the standardized ratio of performance. This should trend towards a figure above 100%. Survival rates and performance are given with 95% confidence intervals. The mean Aristotle basic score was 7.88 ± 2.68. 51 patients died: observed hospital survival was 97.8 % (97.1 %-98.3%). 115 deaths were anticipated: expected survival was 95.2% (93.5%-96.3%). Observed and expected surgical performance reached 7.71 (7.65-7.75) and 7.49 (7.37-7.59), respectively. Therefore the overall standardized ratio of performance was 102.94%. The ratio increased from 2006 (ratio = 101.60%) to 2009 (103.92%) and was 103.42% in 2010. Performance was high for the repair of congenital corrected transposition of the great arteries and ventricular septal defect (VSD) by atrial switch and Rastelli procedure, the Norwood procedure, repair of truncus arteriosus, aortic arch repair and VSD closure, and the Ross-Konno procedure, with corresponding standardized ratios of 123.30%, 116.83%, 112.99%, 110.86% and 110.38%, respectively. With a ratio of 82.87%, performance was low for repair of Ebstein's anomaly. The standardized ratio of surgical performance integrates three factors into a single value: procedure complexity, postoperative observed survival, and comparison with expected survival. It constitutes an excellent instrument for quality monitoring of congenital heart surgery programs over time. It allows an accurate comparison of surgical performance across institutions with different case mixes. © Georg Thieme Verlag KG Stuttgart · New York.

Trends in 30-day mortality rate and case mix for paediatric cardiac surgery in the UK between 2000 and 2010.

PubMed

Brown, Katherine L; Crowe, Sonya; Franklin, Rodney; McLean, Andrew; Cunningham, David; Barron, David; Tsang, Victor; Pagel, Christina; Utley, Martin

2015-01-01

To explore changes over time in the 30-day mortality rate for paediatric cardiac surgery and to understand the role of attendant changes in the case mix. Included were: all mandatory submissions to the National Institute of Cardiovascular Outcomes Research (NICOR) relating to UK cardiac surgery in patients aged <16 years. The χ(2) test for trend was used to retrospectively analyse the proportion of surgical episodes ending in 30-day mortality and with various case mix indicators, in 10 consecutive time periods, from 2000 to 2010. Comparisons were made between two 5-year eras of: 30-day mortality, period prevalence and mean age for 30 groups of specific operations. 30-day mortality for an episode of surgical management. Our analysis includes 36 641 surgical episodes with an increase from 2283 episodes in 2000 to 3939 in 2009 (p<0.01). The raw national 30-day mortality rate fell over the period of review from 4.3% (95% CI 3.5% to 5.1%) in 2000 to 2.6% (95% CI 2.2% to 3.0%) in 2009/2010 (p<0.01). The case mix became more complex in terms of the percentage of patients <2.5 kg (p=0.05), with functionally univentricular hearts (p<0.01) and higher risk diagnoses (p<0.01). In the later time era, there was significant improvement in 30-day mortality for arterial switch with ventricular septal defect (VSD) repair, patent ductus arteriosus ligation, Fontan-type operation, tetralogy of Fallot and VSD repair, and the mean age of patients fell for a range of operations performed in infancy. The raw 30-day mortality rate for paediatric cardiac surgery fell over a decade despite a rise in the national case mix complexity, and compares well with international benchmarks. Definitive repair is now more likely at a younger age for selected infants with congenital heart defects.

Direct radiative forcing of urban aerosols over Pretoria (25.75°S, 28.28°E) using AERONET Sunphotometer data: first scientific results and environmental impact.

PubMed

Adesina, Ayodele Joseph; Kumar, Kanike Raghavendra; Sivakumar, Venkataraman; Griffith, Derek

2014-12-01

The present study uses the data collected from Cimel Sunphotometer of Aerosol Robotic Network (AERONET) for the period from January to December, 2012 over an urban site, Pretoria (PTR; 25.75°S, 28.28°E, 1449 m above sea level), South Africa. We found that monthly mean aerosol optical depth (AOD, τ(a)) exhibits two maxima that occurred in summer (February) and winter (August) having values of 0.36 ± 0.19 and 0.25 ± 0.14, respectively, high-to-moderate values in spring and thereafter, decreases from autumn with a minima in early winter (June) 0.12 ± 0.07. The Angstrom exponents (α440-870) likewise, have its peak in summer (January) 1.70 ± 0.21 and lowest in early winter (June) 1.38 ± 0.26, while the columnar water vapor (CWV) followed AOD pattern with high values (summer) at the beginning of the year (February, 2.10 ± 0.37 cm) and low values (winter) in the middle of the year (July, 0.66 ± 0.21 cm). The volume size distribution (VSD) in the fine-mode is higher in the summer and spring seasons, whereas in the coarse mode the VSD is higher in the winter and lower in the summer due to the hygroscopic growth of aerosol particles. The single scattering albedo (SSA) ranged from 0.85 to 0.96 at 440 nm over PTR for the entire study period. The averaged aerosol radiative forcing (ARF) computed using SBDART model at the top of the atmosphere (TOA) was -8.78 ± 3.1 W/m², while at the surface it was -25.69 ± 8.1 W/m² leading to an atmospheric forcing of +16.91 ± 6.8 W/m², indicating significant heating of the atmosphere with a mean of 0.47K/day. Copyright © 2014. Published by Elsevier B.V.

Surgical treatment of interrupted aortic arch associated with ventricular septal defect and patent ductus arteriosus in patients over one year of age.

PubMed

Li, Zhiqiang; Li, Bin; Fan, Xiangming; Su, Junwu; Zhang, Jing; He, Yan; Liu, Yinglong

2014-01-01

Interrupted aortic arch (IAA) is a rare congenital anomaly affecting 1.5% of infants with congenital heart disease. Neonatal repair of IAA is required to avoid irreversible pulmonary vascular lesion. However, in China, patients with IAA associated with ventricular septal defect (VSD) and patent ductus arteriosus (PDA) over one year of age are common. So we investigated the outcome of surgical treatment of IAA with VSD and PDA in patients over one year of age. From January 2009 to December 2012, 19 patients with IAA have undergone complete single-stage repair. The patients' mean age was 4.4 years, ranging 1 to 15 years; and their mean weight was 12.8 kg, ranging 4.2 to 36.0 kg. Fifteen IAA were type A, four were type B. Preoperative cardiac catheterization data were available from all patients. Mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were measured. The measurements of postoperative pulmonary artery pressure were taken in the operating room at the end of the case. All patients underwent echocardiographic examinations before discharged from the hospital. In addition, cardiac catheterization and echocardiographic examinations were performed during follow-up. Selective brain perfusion through the innominate artery during aortic arch reconstruction was used in all patients. Mean follow-up was (1.6±0.8) years. There were two hospital deaths (2/19, 11%). One patient died of pulmonary hypertension crisis, and another died of postoperative low cardiac output. Five cases had other main postoperative complications but no postoperative neurologic complications. Seventeen survivors were followed up, and there were no late deaths or reoperation. Mean cross-clamp duration was (85±22) minutes and selective brain perfusion duration was (34±11) minutes. Two patients required delayed sternal closure at two days postoperatively. Intensive care unit and hospital stays were (9±8) days and (47±24) days, respectively. Pressure gradients across the anastomosis at most recent follow up were less than 22 mmHg. mPAP regressed significantly from preoperative (62.1±8.1) mmHg to postoperative (37.3±11.3) mmHg (P < 0.001) and (24.2±6.0) mmHg at six months after discharged from the hospital (P < 0.001). The pulmonary vascular resistance also regressed significantly from preoperative (1 501.4±335.7) dyn×s×cm(-5) to (485.0±215.1) dyn×s×cm(-5) at six months after discharged from the hospital (P < 0.001). The majority of the seventeen patients (89%) were in New York Heart Association (NYHA) class I, and 11% remained in NYHA class II. Single-stage repair of patients with IAA, VSD and PDA over one year of age can have good surgical results and functional outcomes. Assessment and treatment of pulmonary artery pressure pre-operatively and postoperatively was crucial. mPAP and pulmonary vascular resistance may have regress significantly compared to preoperative values.

Technical concept of the UK Tornado stand-off reconnaissance system

NASA Astrophysics Data System (ADS)

Dyer, Gavin R.

1996-11-01

The operational limitations exposed during the Gulf War have led to the formulation of a requirement for anew generation of tactical reconnaissance pod for the Royal Air Force Tornado aircraft. The pod will contain a high resolution Electro-Optical sensor capable of day and night-time operations, digital recording of the imagery for airborne replay and ground exploitation, and a data-link for real time/near real time imagery transmission. The program requirement includes a deployable ground exploitation system to provide a comprehensive independent capability. The interoperability of the air and ground segments with other systems is addressed through NATO standardization agreements. This system will provide the Tornado with a highly flexible stand-off imaging system for day/night operations from a range of altitudes.

Variations in "Party Line" Information Importance Between Pilots of Difference Characteristics

NASA Technical Reports Server (NTRS)

Pritchett, Amy R.; Hansman, R. John

1995-01-01

The introduction of digital datalink communications into the air traffic control (ATC) system may cause a reduction of the situation awareness of flight crews due to the reduction of 'Party Line' Information (PLI) that can be overheard on the shared voice frequencies. A survey was distributed to determine current PLI use by pilots from different geographic regions, operational groups, experience levels, and aircraft equipage. Pilots indicated highest perceived importance for PLI during the phases of flight nearest the airport and lowest importance during cruise. Several specific traffic and weather information elements were identified as particularly important; traffic and weather information was also cited by pilots as information required for global situation awareness. Some variations in responses were found between pilots from different operational types.

Data processing for the DMSP microwave radiometer system

NASA Technical Reports Server (NTRS)

Rigone, J. L.; Stogryn, A. P.

1977-01-01

A software program was developed and tested to process microwave radiometry data to be acquired by the microwave sensor (SSM/T) on the Defense Meteorological Satellite Program spacecraft. The SSM/T 7-channel microwave radiometer and systems data will be data-linked to Air Force Global Weather Central (AFGWC) where they will be merged with ephemeris data prior to product processing for use in the AFGWC upper air data base (UADB). The overall system utilizes an integrated design to provide atmospheric temperature soundings for global applications. The fully automated processing at AFGWC was accomplished by four related computer processor programs to produce compatible UADB soundings, evaluate system performance, and update the a priori developed inversion matrices. Tests with simulated data produced results significantly better than climatology.

Preliminary analysis of pilot ratings of 'part line' information importance

NASA Technical Reports Server (NTRS)

Pritchett, Amy; Hansman, R. John

1993-01-01

With the introduction of digital datalink communications into the Air Traffic Control (ATC) system, there is concern over the potential loss of situational awareness by flight crews due to the reduction in the 'Party Line Information' (PLI). This information is available to the pilot by overhearing communications between ATC and other aircraft. A survey was distributed to determine current PLI use by several pilot operational groups, experience levels and geographic regions. The survey identified numerous important elements. PLI was rated the highest for operations near or on approach to the airport. Several significant variations were found between pilots from different operational groups and experience levels. Traffic and weather information were the most frequently cited as information required to obtain global situation awareness.

PhotoMEA: an opto-electronic biosensor for monitoring in vitro neuronal network activity.

PubMed

Ghezzi, Diego; Pedrocchi, Alessandra; Menegon, Andrea; Mantero, Sara; Valtorta, Flavia; Ferrigno, Giancarlo

2007-02-01

PhotoMEA is a biosensor useful for the analysis of an in vitro neuronal network, fully based on optical methods. Its function is based on the stimulation of neurons with caged glutamate and the recording of neuronal activity by Voltage-Sensitive fluorescent Dyes (VSD). The main advantage is that it will be possible to stimulate even at sub-single neuron level and to record with high resolution the activity of the entire network in the culture. A large-scale view of neuronal intercommunications offers a unique opportunity for testing the ability of drugs to affect neuronal properties as well as alterations in the behaviour of the entire network. The concept and a prototype for validation is described here in detail.

Cardiac Injury After All-Terrain Vehicle Accidents in 2 Children and a Review of the Literature.

PubMed

Ngo, Kimberly D; Pian, Phillip; Hanfland, Robert; Nichols, Christopher S; Merritt, Glenn R; Campbell, David; Ing, Richard J

2016-07-01

All-terrain vehicle (ATV) accidents leading to severe morbidity and mortality are common. At our institution, 2 children presented within weeks of each other after ATV accidents. Both children required cardiac valve surgery. The surgical management of these 2 children is discussed, and the literature is reviewed. On initial patient presentation, the diagnosis of a ruptured cardiac valve or ventricular septal defect (VSD) associated with these types of accidents is often delayed. We propose that patients presenting with evidence of high-energy blunt thoracic trauma after an ATV accident should undergo an electrocardiogram, cardiac enzyme assessment, and cardiac echocardiogram as part of the initial work-up to rule out significant myocardial injury.

Using administrative medical claims data to supplement state disease registry systems for reporting zoonotic infections.

PubMed

Jones, Stephen G; Coulter, Steven; Conner, William

2013-01-01

To determine what, if any, opportunity exists in using administrative medical claims data for supplemental reporting to the state infectious disease registry system. Cases of five tick-borne (Lyme disease (LD), babesiosis, ehrlichiosis, Rocky Mountain spotted fever (RMSF), tularemia) and two mosquito-borne diseases (West Nile virus, La Crosse viral encephalitis) reported to the Tennessee Department of Health during 2000-2009 were selected for study. Similarly, medically diagnosed cases from a Tennessee-based managed care organization (MCO) claims data warehouse were extracted for the same time period. MCO and Tennessee Department of Health incidence rates were compared using a complete randomized block design within a general linear mixed model to measure potential supplemental reporting opportunity. MCO LD incidence was 7.7 times higher (p<0.001) than that reported to the state, possibly indicating significant under-reporting (∼196 unreported cases per year). MCO data also suggest about 33 cases of RMSF go unreported each year in Tennessee (p<0.001). Three cases of babesiosis were discovered using claims data, a significant finding as this disease was only recently confirmed in Tennessee. Data sharing between MCOs and health departments for vaccine information already exists (eg, the Vaccine Safety Datalink Rapid Cycle Analysis project). There may be a significant opportunity in Tennessee to supplement the current passive infectious disease reporting system with administrative claims data, particularly for LD and RMSF. There are limitations with administrative claims data, but health plans may help bridge data gaps and support the federal administration's vision of combining public and private data into one source.

Multisensor Equipped Uav/ugv for Automated Exploration

NASA Astrophysics Data System (ADS)

Batzdorfer, S.; Bobbe, M.; Becker, M.; Harms, H.; Bestmann, U.

2017-08-01

The usage of unmanned systems for exploring disaster scenarios has become more and more important in recent times as a supporting system for action forces. These systems have to offer a well-balanced relationship between the quality of support and additional workload. Therefore within the joint research project ANKommEn - german acronym for Automated Navigation and Communication for Exploration - a system for exploration of disaster scenarios is build-up using multiple UAV und UGV controlled via a central ground station. The ground station serves as user interface for defining missions and tasks conducted by the unmanned systems, equipped with different environmental sensors like cameras - RGB as well as IR - or LiDAR. Depending on the exploration task results, in form of pictures, 2D stitched orthophoto or LiDAR point clouds will be transmitted via datalinks and displayed online at the ground station or will be processed in short-term after a mission, e.g. 3D photogrammetry. For mission planning and its execution, UAV/UGV monitoring and georeferencing of environmental sensor data, reliable positioning and attitude information is required. This is gathered using an integrated GNSS/IMU positioning system. In order to increase availability of positioning information in GNSS challenging scenarios, a GNSS-Multiconstellation based approach is used, amongst others. The present paper focuses on the overall system design including the ground station and sensor setups on the UAVs and UGVs, the underlying positioning techniques as well as 2D and 3D exploration based on a RGB camera mounted on board the UAV and its evaluation based on real world field tests.

Blue Guardian: open architecture intelligence, surveillance, and reconnaissance (ISR) demonstrations

NASA Astrophysics Data System (ADS)

Shirey, Russell G.; Borntrager, Luke A.; Soine, Andrew T.; Green, David M.

2017-04-01

The Air Force Research Laboratory (AFRL) - Sensors Directorate has developed the Blue Guardian program to demonstrate advanced sensing technology utilizing open architectures in operationally relevant environments. Blue Guardian has adopted the core concepts and principles of the Air Force Rapid Capabilities Office (AFRCO) Open Mission Systems (OMS) initiative to implement an open Intelligence, Surveillance and Reconnaissance (ISR) platform architecture. Using this new OMS standard provides a business case to reduce cost and program schedules for industry and the Department of Defense (DoD). Blue Guardian is an early adopting program of OMS and provides much needed science and technology improvements, development, testing, and implementation of OMS for ISR purposes. This paper presents results and lessons learned under the Blue Guardian Project Shepherd program which conducted Multi-INT operational demonstrations in the Joint Interagency Task Force - South (JIATF-S) and USSOUTHCOM area of operations in early 2016. Further, on-going research is discussed to enhance Blue Guardian Multi-INT ISR capabilities to support additional mission sets and platforms, including unmanned operations over line of sight (LOS) and beyond line of sight (BLOS) datalinks. An implementation of additional OMS message sets and services to support off-platform sensor command and control using OMS/UCI data structures and dissemination of sensor product data/metadata is explored. Lastly, the Blue Guardian team is working with the AgilePod program to use OMS in a full Government Data Rights Pod to rapidly swap these sensors to different aircraft. The union of the AgilePod (which uses SOSA compliant standards) and OMS technologies under Blue Guardian programs is discussed.

Digital Avionics

NASA Technical Reports Server (NTRS)

Koelbl, Terry G.; Ponchak, Denise; Lamarche, Teresa

2002-01-01

The field of digital avionics experienced another year of important advances in civil aviation, military systems, and space applications. As a result of the events of 9/11/2001, NASA has pursued activities to apply its aerospace technologies toward improved aviation security. Both NASA Glenn Research Center and Langley Research Center have performed flight research demonstrations using advanced datalink concepts to transmit live pictures from inside a jetliner, and to downlink the contents of the plane's 'black box' recorder in real time. The U.S. Navy and General Electric demonstrated survivable engine control (SEC) algorithms during engine ground tests at the Weapons Survivability Laboratory at China Lake. The scientists at Boeing Satellite Systems advanced the field of stellar inertial technology with the development of a new method for positioning optical star trackers on satellites.

Flightdeck and air traffic control collaboration evaluation (FACE): evaluating aviation communication in the laboratory and field.

PubMed

Sharples, Sarah; Stedmon, Alex; Cox, Gemma; Nicholls, Alistair; Shuttleworth, Tracey; Wilson, John

2007-07-01

The challenge to anticipate the human factors impact of introducing new technologies into a safety critical environment can be addressed in a number of ways. This paper presents a research programme that utilised both laboratory- and field-based assessments to examine the way in which datalink and freeflight may affect the communication and collaboration between pilots, air traffic controllers, and other actors and artefacts in the flightdeck-air traffic control (ATC) joint cognitive system. An overview of the results from these studies is presented, and guidance is provided as to the likely situations in which this new technology is most likely to be successfully applied. In addition, the methodological approach of combining results from field and laboratory data is discussed.

Hemolysis induced by PMIVSD occluder.

PubMed

Rao, D Sheshagiri; Barik, Ramachandra; Siva Prasad, Akula

2016-09-01

Hemolysis related to occluder, prosthetic valve, and prosthetic ring used for mitral valve annuloplasty are not very unusual. However, hemolysis related to transcathetor closure of post-myocardial infarction ventricular septal defect (PMIVSD) is infrequent. A close follow-up for spontaneous resolution with or without blood transfusion has been reported in a few cases. Occasionally, surgical retrieval is unavoidable or lifelong blood transfusion is required if surgery cannot be done because of higher risk. In this illustration, we have showed a close follow-up of a case of hemolysis induced by atrial septal occluder used for VSD closure after myocardial infarction. Despite successful device closure of PMIVSD which is difficult, a close watch is needed for complications like residual leak, device embolization, and hemolysis. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Fast calcium and voltage-sensitive dye imaging in enteric neurones reveal calcium peaks associated with single action potential discharge.

PubMed

Michel, K; Michaelis, M; Mazzuoli, G; Mueller, K; Vanden Berghe, P; Schemann, M

2011-12-15

Slow changes in [Ca(2+)](i) reflect increased neuronal activity. Our study demonstrates that single-trial fast [Ca(2+)](i) imaging (≥200 Hz sampling rate) revealed peaks each of which are associated with single spike discharge recorded by consecutive voltage-sensitive dye (VSD) imaging in enteric neurones and nerve fibres. Fast [Ca(2+)](i) imaging also revealed subthreshold fast excitatory postsynaptic potentials. Nicotine-evoked [Ca(2+)](i) peaks were reduced by -conotoxin and blocked by ruthenium red or tetrodotoxin. Fast [Ca(2+)](i) imaging can be used to directly record single action potentials in enteric neurones. [Ca(2+)](i) peaks required opening of voltage-gated sodium and calcium channels as well as Ca(2+) release from intracellular stores.

Diagnosis and treatment of chlamydia and gonorrhoea in general practice in England 2000–2011: a population-based study using data from the UK Clinical Practice Research Datalink

PubMed Central

Wetten, Sally; Mohammed, Hamish; Yung, Mandy; Mercer, Catherine H; Cassell, Jackie A; Hughes, Gwenda

2015-01-01

Objectives To determine the relative contribution of general practices (GPs) to the diagnosis of chlamydia and gonorrhoea in England and whether treatment complied with national guidelines. Design Analysis of longitudinal electronic health records in the Clinical Practice Research Datalink (CPRD) and national sexually transmitted infection (STI) surveillance databases, England, 2000–2011. Setting GPs, and community and specialist STI services. Participants Patients diagnosed with chlamydia (n=1 386 169) and gonorrhoea (n=232 720) at CPRD GPs, and community and specialist STI Services from 2000–2011. Main outcome measures Numbers and rates of chlamydia and gonorrhoea diagnoses; percentages of patients diagnosed by GPs relative to other services; percentage of GP patients treated and antimicrobials used; percentage of GP patients referred. Results The diagnosis rate (95% CI) per 100 000 population of chlamydia in GP increased from 22.8 (22.4–23.2) in 2000 to 29.3 (28.8–29.7) in 2011 (p<0.001), while the proportion treated increased from 59.5% to 78.4% (p=0.001). Over 90% were prescribed a recommended antimicrobial. Over the same period, the diagnosis rate (95% CI) per 100 000 population of gonorrhoea in GP ranged between 3.2 (3–3.3) and 2.4 (2.2–2.5; p=0.607), and the proportion treated ranged between 32.7% and 53.6% (p=0.262). Despite being discontinued as a recommended therapy for gonorrhoea in 2005, ciprofloxacin accounted for 42% of prescriptions in 2007 and 20% in 2011. Over the study period, GPs diagnosed between 9% and 16% of chlamydia cases and between 6% and 9% of gonorrhoea cases in England. Conclusions GP makes an important contribution to the diagnosis and treatment of bacterial STIs in England. While most patients diagnosed with chlamydia were managed appropriately, many of those treated for gonorrhoea received antimicrobials no longer recommended for use. Given the global threat of antimicrobial resistance, GPs should remain abreast of national treatment guidelines and alert to treatment failure in their patients. PMID:26022269

Nutritional recovery after cardiac surgery in children with congenital heart disease.

PubMed

Oyarzún, I; Claveria, C; Larios, G; Le Roy, C

2018-02-01

Malnutrition is common in children with congenital heart disease (CHD). Medical treatment and surgical interventions contribute improving the nutritional status of these children. To describe nutritional recovery in children with CHD and associated factors after surgery. Longitudinal study. 46 Children under 18 years old admitted for CHD surgery between April 2015 and April 2016 were recruited. The following CHD were included: Ventricular septal defect (VSD), Atrial septal defect (ASD), Hypoplastic left heart syndrome (HLHS), Tetralogy of Fallot (TOF), and Transposition of great arteries (dTGA). Children with genetic syndromes and other diseases that could compromise nutritional status were excluded. We obtained demographic, CHD, nasogastric tube use (NGT), nutritional evaluation, and weight and height data at the time of admission and one, three and six months after surgery and. Z-score to assess anthropometric measu res were calculated according to WHO standards. Median age was 8 months (IQR: 3,26), 24 (52%) male, 6 (13%) preterm and 12 (26,1%) small for gestational age (SGA). CHD diagnosis were: 9 (19,6%) VSD, 8 (17,4%) ASD, 12 (26,1%) HLHS, 9 (19,6%) TOF and 8 (17,4%) dTGA. The mean weight-for-heigth-BMI-for-age-z-score (W/H-BMI/AZ) was 0,6 ± 1,5 SD, (28.3% of undernutri tion). The mean heigth-for-age-z-score (H/AZ) was -0,86 ± 1.3sd (21.7% of short stature). We found differences between each CHD and age, use of NGT and been under nutritional follow-up. There was an improvement between H/AZ at admission and 3rd month (p = 0,02), and W/H-BMI/AZ at 3th (p = 0,046) and 6th month (p = 0,001). Use of NGT decreased from admission to 6th month (19 vs 3) (p = 0,0016). We found correlation between admission W/H-BMI/AZ and nutritional recovery (r = -0,7; p < 0,001). There is a high prevalence of prematurity, SGA, undernutrition and short stature use of with weight recovery but not in heigth after cardio-surgery.

Neonatal right ventricle to pulmonary connection as a palliative procedure for pulmonary atresia with ventricular septal defect or severe tetralogy of Fallot.

PubMed

Gerelli, Sébastien; van Steenberghe, Mathieu; Murtuza, Bari; Bojan, Mirela; Harding, Ekoué Diana; Bonnet, Damien; Vouhé, Pascal R; Raisky, Olivier

2014-02-01

Right ventricle to pulmonary artery connection (RVPA connection) without prosthetic material has been our ideal strategy to palliate pulmonary atresia with ventricular septal defect (VSD) or severe tetralogy of Fallot for the last decade. We speculate that RVPA connection ensures adequate postoperative haemodynamics for symptomatic neonates and promotes pulmonary artery rehabilitation. The present study was undertaken to assess the outcome of this strategy. Between 2000 and 2010, among 107 patients who benefited from an RVPA connection, 57 were neonates. Forty-eight of these underwent autologous tissue reconstruction, 5 using left atrial appendage. Median weight was 2.9 kg (range 1.8-4.4). Median Nakata index was 100 mm2/m2 (range 17-185 mm2/m2); 12% had major aortopulmonary collaterals. All patients were reviewed retrospectively. End-points were death or complete repair; reintervention for restrictive pulmonary blood flow was considered as failure. At follow-up, we evaluated reintervention after complete repair, and quality of life. There were 2 early deaths (RV hypoplasia and RV failure) and 3 late sudden deaths (range 3-6 months). Pulmonary blood flow required to be increased in 8 patients: 4 underwent shunt after a median delay of 1 month; RVPA connection enlargement was needed in 3; 1 patient had percutaneous angioplasty. Finally, 47 patients (81%) had a complete repair, of which 70% were performed without prosthetic material at a median age of 7 months (range 2-53), with a median Nakata index of 221 mm2/m2 (range 102-891). One patient died early and 1 was a failure with opening of the VSD after intracardiac repair. At last follow-up, 4 patients were still awaiting repair, with 1 late death and 5 who had required reintervention after intracardiac repair; there were 3 conduit replacements and 2 balloon dilatation patch enlargements. The neonatal RVPA connection approach (i) provides an acceptable survival rate with a satisfactory haemodynamic adaptation, (ii) facilitates rehabilitation of PAs and (iii) avoids the use of prosthetic graft at correction.

Nonsensing residues in S3-S4 linker's C terminus affect the voltage sensor set point in K+ channels.

PubMed

Carvalho-de-Souza, Joao L; Bezanilla, Francisco

2018-02-05

Voltage sensitivity in ion channels is a function of highly conserved arginine residues in their voltage-sensing domains (VSDs), but this conservation does not explain the diversity in voltage dependence among different K + channels. Here we study the non-voltage-sensing residues 353 to 361 in Shaker K + channels and find that residues 358 and 361 strongly modulate the voltage dependence of the channel. We mutate these two residues into all possible remaining amino acids (AAs) and obtain Q-V and G-V curves. We introduced the nonconducting W434F mutation to record sensing currents in all mutants except L361R, which requires K + depletion because it is affected by W434F. By fitting Q-Vs with a sequential three-state model for two voltage dependence-related parameters ( V 0 , the voltage-dependent transition from the resting to intermediate state and V 1 , from the latter to the active state) and G-Vs with a two-state model for the voltage dependence of the pore domain parameter ( V 1/2 ), Spearman's coefficients denoting variable relationships with hydrophobicity, available area, length, width, and volume of the AAs in 358 and 361 positions could be calculated. We find that mutations in residue 358 shift Q-Vs and G-Vs along the voltage axis by affecting V 0 , V 1 , and V 1/2 according to the hydrophobicity of the AA. Mutations in residue 361 also shift both curves, but V 0 is affected by the hydrophobicity of the AA in position 361, whereas V 1 and V 1/2 are affected by size-related AA indices. Small-to-tiny AAs have opposite effects on V 1 and V 1/2 in position 358 compared with 361. We hypothesize possible coordination points in the protein that residues 358 and 361 would temporarily and differently interact with in an intermediate state of VSD activation. Our data contribute to the accumulating knowledge of voltage-dependent ion channel activation by adding functional information about the effects of so-called non-voltage-sensing residues on VSD dynamics. © 2018 Carvalho-de-Souza and Bezanilla.

Vascular Streak Dieback of cacao in Southeast Asia and Melanesia: in planta detection of the pathogen and a new taxonomy.

PubMed

Samuels, Gary J; Ismaiel, Adnan; Rosmana, Ade; Junaid, Muhammad; Guest, David; McMahon, Peter; Keane, Philip; Purwantara, Agus; Lambert, Smilja; Rodriguez-Carres, Marianela; Cubeta, Marc A

2012-01-01

Vascular Streak Dieback (VSD) disease of cacao (Theobroma cacao) in Southeast Asia and Melanesia is caused by a basidiomycete (Ceratobasidiales) fungus Oncobasidium theobromae (syn. =Thanatephorus theobromae). The most characteristic symptoms of the disease are green-spotted leaf chlorosis or, commonly since about 2004, necrotic blotches, followed by senescence of leaves beginning on the second or third flush behind the shoot apex, and blackening of infected xylem in the vascular traces at the leaf scars resulting from the abscission of infected leaves. Eventually the shoot apex is killed and infected branches die. In susceptible cacao the fungus may grow through the xylem down into the main stem and kill a mature cacao tree. Infections in the stem of young plants prior to the formation of the first 3-4 lateral branches usually kill the plant. Basidiospores released from corticioid basidiomata developed on leaf scars or along cracks in the main vein of infected leaves infect young leaves. The pathogen commonly infects cacao but there are rare reports from avocado. As both crops are introduced to the region, the pathogen is suspected to occur asymptomatically in native vegetation. The pathogen is readily isolated but cultures cannot be maintained. In this study, DNA was extracted from pure cultures of O. theobromae obtained from infected cacao plants sampled from Indonesia. The internal transcribed spacer region (ITS), consisting of ITS1, 5.8S ribosomal RNA and ITS2, and a portion of nuclear large subunit (LSU) were sequenced. Phylogenetic analysis of ITS sequences placed O. theobromae sister to Ceratobasidium anastomosis groups AG-A, AG-Bo, and AG-K with high posterior probability. Therefore the new combination Ceratobasidium theobromae is proposed. A PCR-based protocol was developed to detect and identify C. theobromae in plant tissue of cacao enabling early detection of the pathogen in plants. A second species of Ceratobasidium, Ceratobasidium ramicola, identified through ITS sequence analysis, was isolated from VSD-affected cacao plants in Java, and is widespread in diseased cacao collected from Indonesia. Published by Elsevier Ltd.

Prototype Conflict Alerting Logic for Free Flight

NASA Technical Reports Server (NTRS)

Yang, Lee C.; Kuchar, James K.

1997-01-01

This paper discusses the development of a prototype alerting system for a conceptual Free Flight environment. The concept assumes that datalink between aircraft is available and that conflicts are primarily resolved on the flight deck. Four alert stages are generated depending on the likelihood of a conflict. If the conflict is not resolved by the flight crews, Air Traffic Control is notified to take over separation authority. The alerting logic is based on probabilistic analysis through modeling of aircraft sensor and trajectory uncertainties. Monte Carlo simulations were used over a range of encounter situations to determine conflict probability. The four alert stages were then defined based on probability of conflict and on the number of avoidance maneuvers available to the flight crew. Preliminary results from numerical evaluations and from a piloted simulator study at NASA Ames Research Center are summarized.

Aeronautical-Satellite-Assisted Process Being Developed for Information Exchange Through Network Technologies (Aero-SAPIENT)

NASA Technical Reports Server (NTRS)

Zernic, Michael J.

2001-01-01

Communications technologies are being developed to address safety issues during aviation travel. Some of these technologies enable the aircraft to be in constant bidirectional communications with necessary systems, people, and other aircraft that are not currently in place today. Networking technologies, wireless datalinks, and advanced avionics techniques are areas of particular importance that the NASA Glenn Research Center has contributed. Glenn, in conjunction with the NASA Ames Research Center, NASA Dryden Flight Research Center, and NASA Langley Research Center, is investigating methods and applications that would utilize these communications technologies. In mid-June 2000, the flight readiness of the network and communications technologies were demonstrated via a simulated aircraft. A van simulating an aircraft was equipped with advanced phased-array antennas (Advanced Communications/Air Traffic Management (AC/ATM) Advanced Air Transportation Technologies (AATT) project) that used commercial Ku-band satellite communications to connect Glenn, Dryden, and Ames in a combined system ground test. This test simulated air-ground bidirectional transport of real-time digital audio, text, and video data via a hybrid network configuration that demonstrated the flight readiness of the network and communications technologies. Specifically, a Controller Pilot Data Link Communications application was used with other applications to demonstrate a multiprotocol capability via Internet-protocol encapsulated ATN (Aeronautical Telecommunications Network) data packets. The significance of this combined ground test is its contribution to the Aero Information Technology Base Program Level I milestone (Software Technology investment area) of a real-time data link for the National Airspace System. The objective of this milestone was to address multiprotocol technology applicable for real-time data links between aircraft, a satellite, and the ground as well as the ability to distribute flight data with multilevel priorities among several sites.

Radial tunnel diodes based on InP/InGaAs core-shell nanowires

NASA Astrophysics Data System (ADS)

Tizno, Ofogh; Ganjipour, Bahram; Heurlin, Magnus; Thelander, Claes; Borgström, Magnus T.; Samuelson, Lars

2017-03-01

We report on the fabrication and characterization of radial tunnel diodes based on InP(n+)/InGaAs(p+) core-shell nanowires, where the effect of Zn-dopant precursor flow on the electrical properties of the devices is evaluated. Selective and local etching of the InGaAs shell is employed to access the nanowire core in the contact process. Devices with an n+-p doping profile show normal diode rectification, whereas n+-p+ junctions exhibit typical tunnel diode characteristics with peak-to-valley current ratios up to 14 at room temperature and 100 at 4.2 K. A maximum peak current density of 28 A/cm2 and a reverse current density of 7.3 kA/cm2 at VSD = -0.5 V are extracted at room temperature after normalization with the effective junction area.

The impact of interface design during an initial high-technology AAC experience: a collective case study of people with aphasia.

PubMed

Dietz, Aimee; Weissling, Kristy; Griffith, Julie; McKelvey, Miechelle; Macke, Devan

2014-12-01

The purpose of this collective case study was to describe the communication behaviors of five people with chronic aphasia when they retold personal narratives to an unfamiliar communication partner using four variants of a visual scene display (VSD) interface. The results revealed that spoken language comprised roughly 70% of expressive modality units; variable patterns of use for other modalities emerged. Although inconsistent across participants, several people with aphasia experienced no trouble sources during the retells using VSDs with personally relevant photographs and text boxes. Overall, participants perceived the personally relevant photographs and the text as helpful during the retells. These patterns may serve as a springboard for future experimental investigations regarding how interface design influences the communicative and linguistic performance of people with aphasia.

[Closure of wide patent ductus arteriosus using a fenestrated muscular VSD occluder device in a pediatric patient with Down syndrome and pulmonary hypertension].

PubMed

Güvenç, Osman; Saygı, Murat; Demir, İbrahim Halil; Ödemiş, Ender

2017-06-01

Patients with wide patent ductus arteriosus and significant pulmonary hypertension not treated in time constitute a significant problem for cardiologists. For these patients, tests that could aid in decision-making for further planning include reversibility and balloon occlusion tests performed in the catheterization laboratory. Devices developed for the closure of ductus as well as different devices with off-label use may be employed in patients scheduled for transcatheter occlusion. When result of reversibility test is borderline positive, the use of fenestrated device may be applicable for selected patients. Presently described is case of a 10-year-old patient with Down syndrome who had a wide ductus and systemic pulmonary hypertension. Transcatheter closure procedure was performed with off-label use of a fenestrated muscular ventricular septal defect occluder device.

[A study of the process by which a school-age child adapted to body image changes following open-heart surgery].

PubMed

Lin, Heng-Ching; Tsai, Jia-Ling

2006-10-01

This case report attempts to explore the adaptive process of body image changes in school-age children suffering from congenital ventricular septal defect (VSD) following open-heart surgery. After establishing trust relationship, we applied atraumatic care, projective communication techniques, interviews, behavioral observation, storytelling and play in our interaction with that child. We found the child experienced "body image disturbance" after open-heart surgery and underwent a four stage adaptive process as follows: (1) Impact (questioning, perception of punishment for wrongdoing, loss, anger); (2) Retreat (denial, anxiety, withdrawal, escaping social contact, inferiority); (3) Acknowledgment (cognitive change, active participation, future-oriented concerns); and (4) Reconstruction (positive self-image, reconstructing body image). Nursing intervention provided the case with more opportunities for sensory feedback and positive reinforcement and also assisted the patient to adopt a positive view of the situation and then to reconstruct and realize the meaning of such surgery. We reinforced the social supporting system to promote self-confidence, self-esteem, and self-value. The child finally accepted the wounds resulting from the operation as a symbol of "bravery"; a breakthrough likely to help in the child's re-entrance to school and normalization of life. Study findings both enhanced pediatric nurse understanding of the adaptive process involved in body image change and provided knowledge essential to designing flexible-option nursing interventions tailored to meet the demands of different adaptation stages. Obviously, such a caring model designed to meet the differing needs of different body image changes has the potential to benefit of body image integration greatly and can provide the pediatric nursing framework in the future.

Satellite Broadcast of Graphical Weather Data Flight Tested

NASA Technical Reports Server (NTRS)

Mallasch, Paul G.

2000-01-01

NASA Glenn Research Center at Lewis Field's aviation Weather Information Communications (WINCOMM) and NASA Langley Research Center's Aviation Weather Information (AWIN) programs collaborated in a flight test and evaluation of a worldwide weather data-link capability using satellites. This successful flight testing moves NASA closer to its goal of developing advanced communications and information technologies to enable high-quality and timely dissemination of aviation weather information to all relevant users on the aviation information network. Recognized as a major contributing factor in aviation accidents and incidents, weather contributes directly or indirectly to nearly 80 percent of fatal general aviation (small private aircraft) accidents. In 1997, the Aeronautics Safety Investment Strategy Team s weather team produced a prioritized list of investment areas under weather accident prevention. Weather data dissemination is the most critical and highest ranked priority on the list. NASA's Aviation Safety Program founded the Aviation Weather Information initiative to focus efforts on significantly reducing the number of weather-related aviation fatalities. Access to accurate and timely weather data could contribute to a major reduction of weather-related incidents and accidents. However, a cost-effective solution has eluded most general aviation pilots because of the high cost of onboard weather radar equipment. Rockwell Collins, through a contract with NASA and in cooperation with WorldSpace Corporation, successfully completed ground and flight testing of a receiver and antenna in Johannesburg, South Africa. This NASA/Rockwell Collins project is an evaluation of worldwide weather data-link capability using transmissions from the Satellite Digital Audio Radio Services (S DARS) AfriStar satellite. Owned and operated by WorldSpace, AfriStar is a geostationary satellite that broadcasts commercial digital audio services to stationary and mobile platforms. S DARS satellites are the most powerful communications satellites produced to date, allowing users to receive signals using simple, low-cost patch antennas instead of more expensive, beam-steered antenna arrays. Engineers connected an inexpensive, commercially available radio receiver to a laptop computer and an antenna designed and built by Rockwell Collins, enabling them to receive WorldSpace signals from the AfriStar satellite during flight tests. WorldSpace broadcast their composite color graphical weather data files, which were multiplexed with normal audio streams, to the flat patch antenna mounted on a single-engine aircraft. The aircraft was equipped with a modified commercial S-DARS receiver, a Global Positioning Satellite (GPS) receiver, and a laptop computer with color display. Continuous data reception occurred during normal aircraft maneuvers performed throughout takeoff, cruise, and landing operations. In addition, engineers monitored receiver power levels during steep turns and banks. In most instances, the receiver was able to maintain acceptable power levels during all phases of flight and to obtain weather data with little or with the successful completion of ground and flight testing of a receiver and antenna in Johannesburg, South Africa, the team has started to prepare for experiments using highspeed aircraft in areas of the world with limited access to timely weather data. NASA plans to provide a more advanced antenna design and consultation support. This successful test of real-time aviation-related weather data is a positive step toward solving communications-specific issues associated with the dissemination of weather data directly to the cockpit.

A Distributed Simulation Facility to Support Human Factors Research in Advanced Air Transportation Technology

NASA Technical Reports Server (NTRS)

Amonlirdviman, Keith; Farley, Todd C.; Hansman, R. John, Jr.; Ladik, John F.; Sherer, Dana Z.

1998-01-01

A distributed real-time simulation of the civil air traffic environment developed to support human factors research in advanced air transportation technology is presented. The distributed environment is based on a custom simulation architecture designed for simplicity and flexibility in human experiments. Standard Internet protocols are used to create the distributed environment, linking all advanced cockpit simulator, all Air Traffic Control simulator, and a pseudo-aircraft control and simulation management station. The pseudo-aircraft control station also functions as a scenario design tool for coordinating human factors experiments. This station incorporates a pseudo-pilot interface designed to reduce workload for human operators piloting multiple aircraft simultaneously in real time. The application of this distributed simulation facility to support a study of the effect of shared information (via air-ground datalink) on pilot/controller shared situation awareness and re-route negotiation is also presented.

Predicting Operator Execution Times Using CogTool

NASA Technical Reports Server (NTRS)

Santiago-Espada, Yamira; Latorella, Kara A.

2013-01-01

Researchers and developers of NextGen systems can use predictive human performance modeling tools as an initial approach to obtain skilled user performance times analytically, before system testing with users. This paper describes the CogTool models for a two pilot crew executing two different types of a datalink clearance acceptance tasks, and on two different simulation platforms. The CogTool time estimates for accepting and executing Required Time of Arrival and Interval Management clearances were compared to empirical data observed in video tapes and registered in simulation files. Results indicate no statistically significant difference between empirical data and the CogTool predictions. A population comparison test found no significant differences between the CogTool estimates and the empirical execution times for any of the four test conditions. We discuss modeling caveats and considerations for applying CogTool to crew performance modeling in advanced cockpit environments.

A Wireless Monitoring Sub-nA Resolution Test Platform for Nanostructure Sensors

PubMed Central

Jang, Chi Woong; Byun, Young Tae; Lee, Taikjin; Woo, Deok Ha; Lee, Seok; Jhon, Young Min

2013-01-01

We have constructed a wireless monitoring test platform with a sub-nA resolution signal amplification/processing circuit (SAPC) and a wireless communication network to test the real-time remote monitoring of the signals from carbon nanotube (CNT) sensors. The operation characteristics of the CNT sensors can also be measured by the ISD-VSD curve with the SAPC. The SAPC signals are transmitted to a personal computer by Bluetooth communication and the signals from the computer are transmitted to smart phones by Wi-Fi communication, in such a way that the signals from the sensors can be remotely monitored through a web browser. Successful remote monitoring of signals from a CNT sensor was achieved with the wireless monitoring test platform for detection of 0.15% methanol vapor with 0.5 nA resolution and 7 Hz sampling rate. PMID:23783735

Computed tomography and magnetic resonance imaging of multiple focal nodular hyperplasias of the liver with congenital absence of the portal vein in a Chinese girl: case report and review of the literature.

PubMed

Zhang, Kun; Wang, Qingjun; Wang, Haiyi; Ye, Huiyi; Guo, Aitao; Duan, Weidong

2014-11-26

Patients with congenital absence of the portal vein (CAPV) often suffer from additional medical complications such as hepatic tumors and cardiac malformations. Congenital absence of the portal vein (CAPV) is a rare malformation. We present a case of a 16-year-old Chinese girl with CAPV with multiple pathology-proven hepatic focal nodular hyperplasias (FNHs) and ventricular septal defect (VSD). The CT and MRI features of this case are described, and previously reported cases are reviewed. CAPV is a rare congenital anomaly and in such patients, clarifying the site of portosystemic shunts, liver disease, and other anomalies is critical for appropriate treatment selection and accurate prognosis determination. Close follow-up, including laboratory testing and radiologic imaging, is recommended for all CAPV patients.

Priming with real motion biases visual cortical response to bistable apparent motion

PubMed Central

Zhang, Qing-fang; Wen, Yunqing; Zhang, Deng; She, Liang; Wu, Jian-young; Dan, Yang; Poo, Mu-ming

2012-01-01

Apparent motion quartet is an ambiguous stimulus that elicits bistable perception, with the perceived motion alternating between two orthogonal paths. In human psychophysical experiments, the probability of perceiving motion in each path is greatly enhanced by a brief exposure to real motion along that path. To examine the neural mechanism underlying this priming effect, we used voltage-sensitive dye (VSD) imaging to measure the spatiotemporal activity in the primary visual cortex (V1) of awake mice. We found that a brief real motion stimulus transiently biased the cortical response to subsequent apparent motion toward the spatiotemporal pattern representing the real motion. Furthermore, intracellular recording from V1 neurons in anesthetized mice showed a similar increase in subthreshold depolarization in the neurons representing the path of real motion. Such short-term plasticity in early visual circuits may contribute to the priming effect in bistable visual perception. PMID:23188797

Surgery of a cyanotic heart defect in an 11-year-old boy with thrombocytopenic thrombocytopathy and severe anemia due to a GATA-1 defect: hemostatic therapy.

PubMed

Hoefer, J; Streif, W; Kilo, J; Grimm, M; Berger, G; Velik-Salchner, C

2012-10-01

A child was admitted to our hospital for repair of a ventricular septal defect (VSD) characterized by a predominantly right-to-left shunt and a severe stenosis of the right ventricular outflow tract (Tetralogy of Fallot). Severe congenital anemia (hemoglobin 72 g/L), thrombocytopenia (42×G/L) and profound platelet dysfunction led a stem cell defect to be suspected. X-linked thrombocytopenia (GATA-1 mutation) was diagnosed. GATA-1 defect may complicate medical interventions due to excessive bleeding and partial or complete bone marrow failure. Maintaining a platelet count of 100 G/L and a maximal clot firmness (EXTEM-MCF) >50 mm allowed repair of the congenital heart defect without bleeding or hematological complications. Anemia and thrombocytopenia persisted after cardiac surgery, while the spontaneous bleeding tendency improved. © Georg Thieme Verlag KG Stuttgart · New York.

Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution.

PubMed

Shen, Huaizong; Zhou, Qiang; Pan, Xiaojing; Li, Zhangqiang; Wu, Jianping; Yan, Nieng

2017-03-03

Voltage-gated sodium (Na v ) channels are responsible for the initiation and propagation of action potentials. They are associated with a variety of channelopathies and are targeted by multiple pharmaceutical drugs and natural toxins. Here, we report the cryogenic electron microscopy structure of a putative Na v channel from American cockroach (designated Na v PaS) at 3.8 angstrom resolution. The voltage-sensing domains (VSDs) of the four repeats exhibit distinct conformations. The entrance to the asymmetric selectivity filter vestibule is guarded by heavily glycosylated and disulfide bond-stabilized extracellular loops. On the cytoplasmic side, a conserved amino-terminal domain is placed below VSD I , and a carboxy-terminal domain binds to the III-IV linker. The structure of Na v PaS establishes an important foundation for understanding function and disease mechanism of Na v and related voltage-gated calcium channels. Copyright © 2017, American Association for the Advancement of Science.

Epidemiology of fractures in the United Kingdom 1988-2012: Variation with age, sex, geography, ethnicity and socioeconomic status.

PubMed

Curtis, Elizabeth M; van der Velde, Robert; Moon, Rebecca J; van den Bergh, Joop P W; Geusens, Piet; de Vries, Frank; van Staa, Tjeerd P; Cooper, Cyrus; Harvey, Nicholas C

2016-06-01

Rates of fracture worldwide are changing. Using the Clinical Practice Research Datalink (CPRD), age, and gender, geographical, ethnic and socioeconomic trends in fracture rates across the United Kingdom were studied over a 24-year period 1988-2012. Previously observed patterns in fracture incidence by age and fracture site were evident. New data on the influence of geographic location, ethnic group and socioeconomic status were obtained. With secular changes in age- and sex-specific fracture incidence observed in many populations, and global shifts towards an elderly demography, it is vital for health care planners to have an accurate understanding of fracture incidence nationally. We aimed to present up to date fracture incidence data in the UK, stratified by age, sex, geographic location, ethnicity and socioeconomic status. The Clinical Practice Research Datalink (CPRD) contains anonymised electronic health records for approximately 6.9% of the UK population. Information comes from General Practitioners, and covers 11.3 million people from 674 practices across the UK, demonstrated to be representative of the national population. The study population consisted of all permanently registered individuals aged ≥18years. Validated data on fracture incidence were obtained from their medical records, as was information on socioeconomic deprivation, ethnicity and geographic location. Age- and sex-specific fracture incidence rates were calculated. Fracture incidence rates by age and sex were comparable to those documented in previous studies and demonstrated a bimodal distribution. Substantial geographic heterogeneity in age- and sex adjusted fracture incidence was observed, with rates in Scotland almost 50% greater than those in London and South East England. Lowest rates of fracture were observed in black individuals of both sexes; rates of fragility fracture in white women were 4.7 times greater than in black women. Strong associations between deprivation and fracture risk were observed in hip fracture in men, with a relative risk of 1.3 (95% CI 1.21-1.41) in Index of Multiple Deprivation category 5 (representing the most deprived) compared to category 1. This study presents robust estimates of fracture incidence across the UK, which will aid decisions regarding allocation of healthcare provision to populations of greatest need. It will also assist the implementation and design of strategies to reduce fracture incidence and its personal and financial impact on individuals and health services. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnosis and treatment of chlamydia and gonorrhoea in general practice in England 2000-2011: a population-based study using data from the UK Clinical Practice Research Datalink.

PubMed

Wetten, Sally; Mohammed, Hamish; Yung, Mandy; Mercer, Catherine H; Cassell, Jackie A; Hughes, Gwenda

2015-04-22

To determine the relative contribution of general practices (GPs) to the diagnosis of chlamydia and gonorrhoea in England and whether treatment complied with national guidelines. Analysis of longitudinal electronic health records in the Clinical Practice Research Datalink (CPRD) and national sexually transmitted infection (STI) surveillance databases, England, 2000-2011. GPs, and community and specialist STI services. Patients diagnosed with chlamydia (n=1,386,169) and gonorrhoea (n=232,720) at CPRD GPs, and community and specialist STI Services from 2000-2011. Numbers and rates of chlamydia and gonorrhoea diagnoses; percentages of patients diagnosed by GPs relative to other services; percentage of GP patients treated and antimicrobials used; percentage of GP patients referred. The diagnosis rate (95% CI) per 100,000 population of chlamydia in GP increased from 22.8 (22.4-23.2) in 2000 to 29.3 (28.8-29.7) in 2011 (p<0.001), while the proportion treated increased from 59.5% to 78.4% (p=0.001). Over 90% were prescribed a recommended antimicrobial. Over the same period, the diagnosis rate (95% CI) per 100,000 population of gonorrhoea in GP ranged between 3.2 (3-3.3) and 2.4 (2.2-2.5; p=0.607), and the proportion treated ranged between 32.7% and 53.6% (p=0.262). Despite being discontinued as a recommended therapy for gonorrhoea in 2005, ciprofloxacin accounted for 42% of prescriptions in 2007 and 20% in 2011. Over the study period, GPs diagnosed between 9% and 16% of chlamydia cases and between 6% and 9% of gonorrhoea cases in England. GP makes an important contribution to the diagnosis and treatment of bacterial STIs in England. While most patients diagnosed with chlamydia were managed appropriately, many of those treated for gonorrhoea received antimicrobials no longer recommended for use. Given the global threat of antimicrobial resistance, GPs should remain abreast of national treatment guidelines and alert to treatment failure in their patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Do pre-diagnosis primary care consultation patterns explain deprivation-specific differences in net survival among women with breast cancer? An examination of individually-linked data from the UK West Midlands cancer registry, national screening programme and Clinical Practice Research Datalink.

PubMed

Morris, M; Woods, L M; Bhaskaran, K; Rachet, B

2017-02-23

In England and Wales breast cancer survival is higher among more affluent women. Our aim was to investigate the potential of pre-diagnostic factors for explaining deprivation-related differences in survival. Individually-linked data from women aged 50-70 in the West Midlands region of England, diagnosed with breast cancer 1989-2006 and continuously eligible for screening, was retrieved from the cancer registry, screening service and Clinical Practice Research Datalink. Follow-up was to the end of July 2012. Deprivation was measured at small area level, based on the quintiles of the income domain of the English indices of deprivation. Consultation rates per woman per week, time from last breast-related GP consultation to diagnosis, and from diagnosis to first surgery were calculated. We estimated net survival using the non-parametric Pohar-Perme estimator. The rate of primary care consultations was similar during the 18 months prior to diagnosis in each deprivation group for breast and non-breast symptoms. Survival was lower for more deprived women from 4 years after diagnosis. Lower net survival was associated with more advanced extent of disease and being non-screen-detected. There was a persistent trend of lower net survival for more deprived women, irrespective of the woman's obesity, alcohol, smoking or comorbidity status. There was no significant variation in time from last breast symptom to diagnosis by deprivation. However, women in more deprived categories experienced significantly longer periods between cancer diagnosis and first surgery (mean = 21.5 vs. 28.4 days, p = 0.03). Those whose surgery occurred more than 12 weeks following their cancer diagnosis had substantially lower net survival. Our data suggest that although more deprived women with breast cancer display lifestyle factors associated with poorer outcomes, their consultation frequency, comorbidities and the breast cancer symptoms they present with are similar. We found weak evidence of extended times to surgical treatment among most deprived women who were not screen-detected but who presented with symptoms in primary care, which suggests that treatment delay may play a role. Further investigation of interrelationships between these variables within a larger dataset is warranted.

Computing danger zones for provably safe closely spaced parallel approaches: Theory and experiment

NASA Astrophysics Data System (ADS)

Teo, Rodney

In poor visibility, paired approaches to airports with closely spaced parallel runways are not permitted, thus halving the arrival rate. With Global Positioning System technology, datalinks and cockpit displays, this could be averted. One important problem is ensuring safety during a blundered approach by one aircraft. This is on-going research. A danger zone around the blunderer is required. If the correct danger zone could be calculated, then it would be possible to get 100% of clear-day capacity in poor-visibility days even on 750 foot runways. The danger zones vary significantly (during an approach) and calculating them in real time would be very significant. Approximations (e.g. outer bounds) are not good enough. This thesis presents a way to calculate these danger zones in real time for a very broad class of blunder trajectories. The approach in this thesis differs from others in that it guarantees safety for any possible blunder trajectory as long as the speeds and turn rates of the blunder are within certain bounds. In addition, the approach considers all emergency evasive maneuvers whose speeds and turn rates are within certain bounds about a nominal emergency evasive maneuver. For all combinations of these blunder and evasive maneuver trajectories, it guarantees that the evasive maneuver is safe. For more than 1 million simulation runs, the algorithm shows a 100% rate of Successful Alerts and a 0% rate of Collisions Given an Alert. As an experimental testbed, two 10-ft wingspan fully autonomous unmanned aerial vehicles and a ground station are developed together with J. S. Jang. The development includes the design and flight testing of automatic controllers. The testbed is used to demonstrate the algorithm implementation through an autonomous closely spaced parallel approach, with one aircraft programmed to blunder. The other aircraft responds according to the result of the algorithm on board it and evades autonomously when required. This experimental demonstration is successfully conducted, showing the implementation of the algorithm, in particular, demonstrating that it can run in real time. Finally; with the necessary sensors and datalink, and the appropriate procedures in place, the algorithm developed in this thesis will enable 100% of clear-day capacity in poor-visibility days even on 750 foot runways.

The incidence and healthcare costs of persistent postoperative pain following lumbar spine surgery in the UK: a cohort study using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES)

PubMed Central

Samnaliev, Mihail; Kuo, Tzu-Chun; Ni Choitir, Caitriona; Tierney, Travis S; Cumming, David; Manca, Andrea; Taylor, Rod S; Eldabe, Sam

2017-01-01

Objective To characterise incidence and healthcare costs associated with persistent postoperative pain (PPP) following lumbar surgery. Design Retrospective, population-based cohort study. Setting Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Participants Population-based cohort of 10 216 adults who underwent lumbar surgery in England from 1997/1998 through 2011/2012 and had at least 1 year of presurgery data and 2 years of postoperative follow-up data in the linked CPRD–HES. Primary and secondary outcomes measures Incidence and total healthcare costs over 2, 5 and 10 years attributable to persistent PPP following initial lumbar surgery. Results The rate of individuals undergoing lumbar surgery in the CPRD–HES linked data doubled over the 15-year study period, fiscal years 1997/1998 to 2011/2012, from 2.5 to 4.9 per 10 000 adults. Over the most recent 5-year period (2007/2008 to 2011/2012), on average 20.8% (95% CI 19.7% to 21.9%) of lumbar surgery patients met criteria for PPP. Rates of healthcare usage were significantly higher for patients with PPP across all types of care. Over 2 years following initial spine surgery, the mean cost difference between patients with and without PPP was £5383 (95% CI £4872 to £5916). Over 5 and 10 years following initial spine surgery, the mean cost difference between patients with and without PPP increased to £10 195 (95% CI £8726 to £11 669) and £14 318 (95% CI £8386 to £19 771), respectively. Extrapolated to the UK population, we estimate that nearly 5000 adults experience PPP after spine surgery annually, with each new cohort costing the UK National Health Service in excess of £70 million over the first 10 years alone. Conclusions Persistent pain affects more than one-in-five lumbar surgery patients and accounts for substantial long-term healthcare costs. There is a need for formal, evidence-based guidelines for a coherent, coordinated management strategy for patients with continuing pain after lumbar surgery. PMID:28893756

Trends in the incidence of chronic fatigue syndrome and fibromyalgia in the UK, 2001-2013: a Clinical Practice Research Datalink study.

PubMed

Collin, Simon M; Bakken, Inger J; Nazareth, Irwin; Crawley, Esther; White, Peter D

2017-06-01

Objective Trends in recorded diagnoses of chronic fatigue syndrome (CFS, also known as 'myalgic encephalomyelitis' (ME)) and fibromyalgia (FM) in the UK were last reported more than ten years ago, for the period 1990-2001. Our aim was to analyse trends in incident diagnoses of CFS/ME and FM for the period 2001-2013, and to investigate whether incidence might vary by index of multiple deprivation (IMD) score. Design Electronic health records cohort study. Setting NHS primary care practices in the UK. Participants Participants: Patients registered with general practices linked to the Clinical Practice Research Datalink (CPRD) primary care database from January 2001 to December 2013. Main outcome measure Incidence of CFS/ME, FM, post-viral fatigue syndrome (PVFS), and asthenia/debility. Results The overall annual incidence of recorded cases of CFS/ME was 14.8 (95% CI 14.5, 15.1) per 100,000 people. Overall annual incidence per 100,000 people for FM was 33.3 (32.8-33.8), for PVFS 12.2 (11.9, 12.5), and for asthenia/debility 7.0 (6.8, 7.2). Annual incidence rates for CFS/ME diagnoses decreased from 17.5 (16.1, 18.9) in 2001 to 12.6 (11.5, 13.8) in 2013 (annual percent change -2.8% (-3.6%, -2.0%)). Annual incidence rates for FM diagnoses decreased from 32.3 (30.4, 34.3) to 27.1 (25.5, 28.6) in 2007, then increased to 38.2 (36.3, 40.1) per 100,000 people in 2013. Overall annual incidence of recorded fatigue symptoms was 2246 (2242, 2250) per 100,000 people. Compared with the least deprived IMD quintile, incidence of CFS/ME in the most deprived quintile was 39% lower (incidence rate ratio (IRR) 0.61 (0.50, 0.75)), whereas rates of FM were 40% higher (IRR 1.40 (0.95, 2.06)). Conclusion These analyses suggest a gradual decline in recorded diagnoses of CFS/ME since 2001, and an increase in diagnoses of fibromyalgia, with opposing socioeconomic patterns of lower rates of CFS/ME diagnoses in the poorest areas compared with higher rates of FM diagnoses.

The incidence and healthcare costs of persistent postoperative pain following lumbar spine surgery in the UK: a cohort study using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES).

PubMed

Weir, Sharada; Samnaliev, Mihail; Kuo, Tzu-Chun; Ni Choitir, Caitriona; Tierney, Travis S; Cumming, David; Bruce, Julie; Manca, Andrea; Taylor, Rod S; Eldabe, Sam

2017-09-11

To characterise incidence and healthcare costs associated with persistent postoperative pain (PPP) following lumbar surgery. Retrospective, population-based cohort study. Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Population-based cohort of 10 216 adults who underwent lumbar surgery in England from 1997/1998 through 2011/2012 and had at least 1 year of presurgery data and 2 years of postoperative follow-up data in the linked CPRD-HES. Incidence and total healthcare costs over 2, 5 and 10 years attributable to persistent PPP following initial lumbar surgery. The rate of individuals undergoing lumbar surgery in the CPRD-HES linked data doubled over the 15-year study period, fiscal years 1997/1998 to 2011/2012, from 2.5 to 4.9 per 10 000 adults. Over the most recent 5-year period (2007/2008 to 2011/2012), on average 20.8% (95% CI 19.7% to 21.9%) of lumbar surgery patients met criteria for PPP. Rates of healthcare usage were significantly higher for patients with PPP across all types of care. Over 2 years following initial spine surgery, the mean cost difference between patients with and without PPP was £5383 (95% CI £4872 to £5916). Over 5 and 10 years following initial spine surgery, the mean cost difference between patients with and without PPP increased to £10 195 (95% CI £8726 to £11 669) and £14 318 (95% CI £8386 to £19 771), respectively. Extrapolated to the UK population, we estimate that nearly 5000 adults experience PPP after spine surgery annually, with each new cohort costing the UK National Health Service in excess of £70 million over the first 10 years alone. Persistent pain affects more than one-in-five lumbar surgery patients and accounts for substantial long-term healthcare costs. There is a need for formal, evidence-based guidelines for a coherent, coordinated management strategy for patients with continuing pain after lumbar surgery. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Understanding the health economic burden of patients with tuberous sclerosis complex (TSC) with epilepsy: a retrospective cohort study in the UK Clinical Practice Research Datalink (CPRD).

PubMed

Shepherd, Charles; Koepp, Matthias; Myland, Melissa; Patel, Keyur; Miglio, Cristiana; Siva, Vathani; Gray, Elizabeth; Neary, Maureen

2017-10-05

Epilepsy is highly prevalent in tuberous sclerosis complex (TSC), a multi-system genetic disorder. The clinical and economic burden of this condition is expected to be substantial due to treatment challenges, debilitating co-morbidities and the relationship between TSC-related manifestations. This study estimated healthcare resource utilisation (HCRU) and costs for patients with TSC with epilepsy (TSC+E) in the UK. Patients with TSC+E in the Clinical Practice Research Datalink (CPRD) linked to Hospital Episodes Statistics were identified from April 1997 to March 2012. Clinical data were extracted over the entire history, and costs were reported over the most recent 3-year period. HCRU was compared with a matched Comparator cohort, and the key cost drivers were identified by regression modelling. In total, 209 patients with TSC+E were identified, of which 40% recorded ≥2 other primary organ system manifestations and 42% had learning disability. Treatment with ≥2 concomitant antiepileptic drugs (AEDs) was prevalent (60%), potentially suggesting refractory epilepsy. Notwithstanding, many patients with TSC+E (12%) had no record of AED use in their entire history, which may indicate undertreatment for these patients.Brain surgery was recorded in 12% of patients. Routine electroencephalography and MRI were infrequently performed (30% of patients), yet general practitioner visits, hospitalisations and outpatient visits were more frequent in patients with TSC+E than the Comparator. This translated to threefold higher clinical costs (£14 335 vs £4448), which significantly increased with each additional primary manifestation (p<0.0001). Patients with TSC+E have increased HCRU compared with the general CPRD population, likely related to manifestations in several organ systems, substantial cognitive impairment and severe epilepsy, which is challenging to treat and may be intractable. Disease surveillance and testing appears to be inadequate with few treatments trialled.Multidisciplinary care in TSC clinics with specialist neurologist input may alleviate some of the morbidity of patients, but more innovative treatment and management options should be sought. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Association between cardiovascular events and sodium-containing effervescent, dispersible, and soluble drugs: nested case-control study

PubMed Central

George, Jacob; Majeed, Waseem; Mackenzie, Isla S; Wei, Li

2013-01-01

Objective To determine whether patients taking formulations of drugs that contain sodium have a higher incidence of cardiovascular events compared with patients on non-sodium formulations of the same drugs. Design Nested case-control study. Setting UK Primary Care Patients registered on the Clinical Practice Research Datalink (CPRD). Participants All patients aged 18 or over who were prescribed at least two prescriptions of sodium-containing formulations or matched standard formulations of the same drug between January 1987 and December 2010. Main outcome measures Composite primary outcome of incident non-fatal myocardial infarction, incident non-fatal stroke, or vascular death. We performed 1:1 incidence density sampling matched controls using the UK Clinical Practice Research Datalink (CPRD). For the secondary analyses, cases were patients with the individual components of the primary study composite endpoint of hypertension, incident heart failure, and all cause mortality. Results 1 292 337 patients were included in the study cohort. Mean follow-up time was 7.23 years. A total of 61 072 patients with an incident cardiovascular event were matched with controls. For the primary endpoint of incident non-fatal myocardial infarction, incident non-fatal stroke, or vascular death the adjusted odds ratio for exposure to sodium-containing drugs was 1.16 (95% confidence interval 1.12 to 1.21). The adjusted odds ratios for the secondary endpoints were 1.22 (1.16 to 1.29) for incident non-fatal stroke, 1.28 (1.23 to 1.33) for all cause mortality, 7.18 (6.74 to 7.65) for hypertension, 0.98 (0.93 to 1.04) for heart failure, 0.94 (0.88 to 1.00) for incident non-fatal myocardial infarction, and 0.70 (0.31 to 1.59) for vascular death. The median time from date of first prescription (that is, date of entry into cohort) to first event was 3.92 years. Conclusions Exposure to sodium-containing formulations of effervescent, dispersible, and soluble medicines was associated with significantly increased odds of adverse cardiovascular events compared with standard formulations of those same drugs. Sodium-containing formulations should be prescribed with caution only if the perceived benefits outweigh these risks. PMID:24284017

Guillain-Barré Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009–2011

PubMed Central

Greene, Sharon K.; Rett, Melisa D.; Vellozzi, Claudia; Li, Lingling; Kulldorff, Martin; Marcy, S. Michael; Daley, Matthew F.; Belongia, Edward A.; Baxter, Roger; Fireman, Bruce H.; Jackson, Michael L.; Omer, Saad B.; Nordin, James D.; Jin, Robert; Weintraub, Eric S.; Vijayadeva, Vinutha; Lee, Grace M.

2013-01-01

Background Guillain-Barré Syndrome (GBS) can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1) pandemic in the United States, monovalent inactivated influenza vaccine (MIV) availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited. Methods We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009–10 MIV, 2010–11 trivalent inactivated influenza vaccine (TIV), and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls. Results Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009–10 MIV recipients and 2.80 million 2010–11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009–10 MIV/2010–11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI), 0.59–3.99; risk difference = 0.93 per million doses, 95% CI, −0.71–5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60–16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49–26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior vaccination shorter than 6 weeks. Conclusions After adjusting for antecedent infections, we found no evidence for an elevated GBS risk following 2009–10 MIV/2010–11 TIV influenza vaccines. However, the association between GBS and antecedent infection was strongly elevated. PMID:23840621

Prenatal Diagnosis of Fetal Interrupted Aortic Arch Type A by Two-Dimensional Echocardiography and Four-Dimensional Echocardiography with B-Flow Imaging and Spatiotemporal Image Correlation.

PubMed

Zhang, Dongyu; Zhang, Ying; Ren, Weidong; Sun, Feifei; Guo, Yajun; Sun, Wei; Wang, Yu; Huang, Liping; Cai, Ailu

2016-01-01

Fetal interrupted aortic arch (IAA) is a rare cardiac anomaly and its prenatal diagnosis is challenging. The purpose of our report is to evaluate the use of two-dimensional echocardiography (2DE) and 4D echocardiography with B-flow imaging and spatiotemporal image correlation (4D BF-STIC) in detecting IAA type A (IAA-A). Twenty-three cases of confirmed IAA-A identified by fetal echocardiography were involved in the study. The fetal echocardiography image data were reviewed to analyze the ratio of right ventricle to left ventricle (RV/LV) diameter, the ratio of main pulmonary artery to ascending aorta (MPA/AAO) diameter, and the correlation of RV/LV diameter ratio and size of ventricular septal defect (VSD). 4D BF-STIC was performed in 21 fetuses using the sagittal view (4D BF-STIC-sagittal) and the four-chamber view (4D BF-STIC-4CV) as initial planes of view. An additional 183 normal fetuses were also included in our study. RV/LV and MPA/AAO ratios were calculated and compared with that of IAA-A fetuses. Fetal 2DE, 4D BF-STIC-sagittal, and 4D BF-STIC-4CV were used to visualize the aortic arch and its associated neck vessels. Six subgroups were evaluated according to gestational age. Fetal 2DE, 4D BF-STIC-sagittal, and 4D BF-STIC-4CV made the correct prenatal diagnosis of IAA-A in 19/23 (82.6%), 14/21 (66.7%), and 19/21 (90.5%) of patients, respectively. A significantly enlarged MPA combined with symmetric ventricles was found in the IAA-A fetuses, while the size of the VSD was negatively correlated with RV/LV ratio. 4D BF-STIC-sagittal and 4D BF-STIC-4CV were better than traditional 2D ultrasound in detecting the aortic arch and neck vessels between 17 and 28 gestational weeks and 29 to 40 gestational weeks in normal fetuses. It is demonstrated that IAA-A could be diagnosed by traditional fetal echocardiography, while 4D technique could better display the anatomic structure and the spatial relationships of the great arteries. Use of volume reconstruction may promote its clinical usage and help prenatal diagnosis. © 2015, Wiley Periodicals, Inc.

An internet-based bioinformatics toolkit for plant biosecurity diagnosis and surveillance of viruses and viroids.

PubMed

Barrero, Roberto A; Napier, Kathryn R; Cunnington, James; Liefting, Lia; Keenan, Sandi; Frampton, Rebekah A; Szabo, Tamas; Bulman, Simon; Hunter, Adam; Ward, Lisa; Whattam, Mark; Bellgard, Matthew I

2017-01-11

Detection and preventing entry of exotic viruses and viroids at the border is critical for protecting plant industries trade worldwide. Existing post entry quarantine screening protocols rely on time-consuming biological indicators and/or molecular assays that require knowledge of infecting viral pathogens. Plants have developed the ability to recognise and respond to viral infections through Dicer-like enzymes that cleave viral sequences into specific small RNA products. Many studies reported the use of a broad range of small RNAs encompassing the product sizes of several Dicer enzymes involved in distinct biological pathways. Here we optimise the assembly of viral sequences by using specific small RNA subsets. We sequenced the small RNA fractions of 21 plants held at quarantine glasshouse facilities in Australia and New Zealand. Benchmarking of several de novo assembler tools yielded SPAdes using a kmer of 19 to produce the best assembly outcomes. We also found that de novo assembly using 21-25 nt small RNAs can result in chimeric assemblies of viral sequences and plant host sequences. Such non-specific assemblies can be resolved by using 21-22 nt or 24 nt small RNAs subsets. Among the 21 selected samples, we identified contigs with sequence similarity to 18 viruses and 3 viroids in 13 samples. Most of the viruses were assembled using only 21-22 nt long virus-derived siRNAs (viRNAs), except for one Citrus endogenous pararetrovirus that was more efficiently assembled using 24 nt long viRNAs. All three viroids found in this study were fully assembled using either 21-22 nt or 24 nt viRNAs. Optimised analysis workflows were customised within the Yabi web-based analytical environment. We present a fully automated viral surveillance and diagnosis web-based bioinformatics toolkit that provides a flexible, user-friendly, robust and scalable interface for the discovery and diagnosis of viral pathogens. We have implemented an automated viral surveillance and diagnosis (VSD) bioinformatics toolkit that produces improved viruses and viroid sequence assemblies. The VSD toolkit provides several optimised and reusable workflows applicable to distinct viral pathogens. We envisage that this resource will facilitate the surveillance and diagnosis viral pathogens in plants, insects and invertebrates.

Selective cerebro-myocardial perfusion in complex congenital aortic arch pathology: a novel technique.

PubMed

De Rita, Fabrizio; Lucchese, Gianluca; Barozzi, Luca; Menon, Tiziano; Faggian, Giuseppe; Mazzucco, Alessandro; Luciani, Giovanni Battista

2011-11-01

Simultaneous cerebro-myocardial perfusion has been described in neonatal and infant arch surgery, suggesting a reduction in cardiac morbidity. Here reported is a novel technique for selective cerebral perfusion combined with controlled and independent myocardial perfusion during surgery for complex or recurrent aortic arch lesions. From April 2008 to April 2011, 10 patients with arch pathology underwent surgery (two hypoplastic left heart syndrome [HLHS], four recurrent arch obstruction, two aortic arch hypoplasia + ventricular septal defect [VSD], one single ventricle + transposition of the great arteries + arch hypoplasia, one interrupted aortic arch type B + VSD). Median age was 63 days (6 days-36 years) and median weight 4.0 kg (1.6-52). Via midline sternotomy, an arterial cannula (6 or 8 Fr for infants) was directly inserted into the innominate artery or through a polytetrafluoroethylene (PTFE) graft (for neonates <2.0 kg). A cardioplegia delivery system was inserted into the aortic root. Under moderate hypothermia, ascending and descending aorta were cross-clamped, and "beating heart and brain" aortic arch repair was performed. Arch repair was composed of patch augmentation in five, end-to-side anastomosis in three, and replacement in two patients. Average cardiopulmonary bypass time was 163 ± 68 min (71-310). In two patients only (one HLHS, one complex single ventricle), a period of cardiac arrest was required to complete intracardiac repair. In such cases, antegrade blood cardioplegia was delivered directly via the same catheter used for selective myocardial perfusion. Average time of splanchnic ischemia during cerebro-myocardial perfusion was 39 ± 18 min (17-69). Weaning from cardiopulmonary bypass was achieved without inotropic support in three and with low dose in seven patients. One patient required veno-arterial extracorporeal membrane oxygenation. Four patients, body weight <3.0 kg, needed delayed sternal closure. No neurologic dysfunction was noted. Renal function proved satisfactory in all, while liver function was adequate in all but one. The present experience suggests that selective and independent cerebro-myocardial perfusion is feasible in patients with complex or recurrent aortic arch disease, starting from premature newborn less than 2.0 kg of body weight to adults. The technique is as safe as previously reported methods of cerebro-myocardial perfusion and possibly more versatile. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

A Laboratory Glass-Cockpit Flight Simulator for Automation and Communications Research

NASA Technical Reports Server (NTRS)

Pisanich, Gregory M.; Heers, Susan T.; Shafto, Michael G. (Technical Monitor)

1995-01-01

A laboratory glass-cockpit flight simulator supporting research on advanced commercial flight deck and Air Traffic Control (ATC) automation and communication interfaces has been developed at the Aviation Operations Branch at the NASA Ames Research Center. This system provides independent and integrated flight and ATC simulator stations, party line voice and datalink communications, along with video and audio monitoring and recording capabilities. Over the last several years, it has been used to support the investigation of flight human factors research issues involving: communication modality; message content and length; graphical versus textual presentation of information, and human accountability for automation. This paper updates the status of this simulator, describing new functionality in the areas of flight management system, EICAS display, and electronic checklist integration. It also provides an overview of several experiments performed using this simulator, including their application areas and results. Finally future enhancements to its ATC (integration of CTAS software) and flight deck (full crew operations) functionality are described.

Neurodegeneration and mirror image agnosia.

PubMed

Chandra, Sadanandavalli Retnaswami; Issac, Thomas Gregor

2014-09-01

Normal Percept with abnormal meaning (Agnosias) has been described from nineteenth century onwards. Later literature became abundant with information on the spectrum of Prosopagnosias. However, selective difficulty in identifying reflected self images with relatively better cognitive functions leads to problems in differentiating it from non-organic psychosis. In the present study, we investigated patients with dementia who showed difficulty in identifying reflected self images while they were being tested for problems in gnosis with reference to identification of reflected objects, animals, relatives, and themselves and correlate with neuropsychological and radiological parameters. Five such patients were identified and tested with a 45 cm × 45 cm mirror kept at 30-cm distance straight ahead of them. Mirror image agnosia is seen in patients with moderate stage posterior dementias who showed neuropsychological and radiological evidence of right parietal dysfunction. Interpretation of reflected self images perception in real time probably involves distinct data-linking circuits in the right parietal lobe, which may get disrupted early in the course of the disease.

Neurodegeneration and Mirror Image Agnosia

PubMed Central

Chandra, Sadanandavalli Retnaswami; Issac, Thomas Gregor

2014-01-01

Background: Normal Percept with abnormal meaning (Agnosias) has been described from nineteenth century onwards. Later literature became abundant with information on the spectrum of Prosopagnosias. However, selective difficulty in identifying reflected self images with relatively better cognitive functions leads to problems in differentiating it from non-organic psychosis. Aim: In the present study, we investigated patients with dementia who showed difficulty in identifying reflected self images while they were being tested for problems in gnosis with reference to identification of reflected objects, animals, relatives, and themselves and correlate with neuropsychological and radiological parameters. Patients and Methods: Five such patients were identified and tested with a 45 cm × 45 cm mirror kept at 30-cm distance straight ahead of them. Results: Mirror image agnosia is seen in patients with moderate stage posterior dementias who showed neuropsychological and radiological evidence of right parietal dysfunction. Conclusion: Interpretation of reflected self images perception in real time probably involves distinct data-linking circuits in the right parietal lobe, which may get disrupted early in the course of the disease. PMID:25317393

Hazard evaluation and operational cockpit display of ground-measured windshear data

NASA Technical Reports Server (NTRS)

Wanke, Craig; Hansman, R. John, Jr.

1993-01-01

Low-altitude windshear is the leading weather-related cause of fatal aviation accidents in the U.S. Since 1964, there have been 26 accidents attributed to windshear resulting in over 500 fatalities. Low-altitude windshear can take several forms, including macroscopic forms such as cold-warm gustfronts down to the small, intense downdrafts known as microbursts. Microbursts are particularly dangerous and difficult to detect due to their small size, short duration, and occurrence under both heavy precipitation and virtually dry conditions. For these reasons, the real-time detection of windshear hazards is a very active field of research. Also, the advent of digital ground-to-air datalinks and electronic flight instrumentation opens up many options for implementation of windshear alerts in the terminal area environment. Study is required to determine the best content, format, timing, and cockpit presentation of windshear alerts in the modern ATC environment to best inform the flight crew without significantly increasing crew workload.

Software-Reconfigurable Processors for Spacecraft

NASA Technical Reports Server (NTRS)

Farrington, Allen; Gray, Andrew; Bell, Bryan; Stanton, Valerie; Chong, Yong; Peters, Kenneth; Lee, Clement; Srinivasan, Jeffrey

2005-01-01

A report presents an overview of an architecture for a software-reconfigurable network data processor for a spacecraft engaged in scientific exploration. When executed on suitable electronic hardware, the software performs the functions of a physical layer (in effect, acts as a software radio in that it performs modulation, demodulation, pulse-shaping, error correction, coding, and decoding), a data-link layer, a network layer, a transport layer, and application-layer processing of scientific data. The software-reconfigurable network processor is undergoing development to enable rapid prototyping and rapid implementation of communication, navigation, and scientific signal-processing functions; to provide a long-lived communication infrastructure; and to provide greatly improved scientific-instrumentation and scientific-data-processing functions by enabling science-driven in-flight reconfiguration of computing resources devoted to these functions. This development is an extension of terrestrial radio and network developments (e.g., in the cellular-telephone industry) implemented in software running on such hardware as field-programmable gate arrays, digital signal processors, traditional digital circuits, and mixed-signal application-specific integrated circuits (ASICs).

Transonic-supersonic high Reynolds number stability and control characteristics of a 0.015-scale (remotely controlled elevon) model 44-0 of the space shuttle orbiter tested in the VSD high speed wind tunnel (LA67)

NASA Technical Reports Server (NTRS)

1976-01-01

A detailed aerodynamic data base which can be used to substantiate the aerodynamic design data book for the current shuttle orbiter configuration was generated. Special attention was directed to definition of non-linear aerodynamic characteristics by taking data at small increments in the angle of attack, angle of sideslip, Mach number, and elevon position. Six-component aerodynamic force and moment and elevon position data were recorded over an angle-of-attack range from -2 deg to as high as 32 deg at angles of sideslip of 0 deg, 1 deg, and +2 deg. The test Mach numbers were 0.60, 0.80, 0.90, 1.2, 1.5, 2.0, 3.0, and 4.6. The effects of Reynolds number were investigated and covered a range from 5.0 to 16.0 million per foot.

Determination of wind tunnel constraint effects by a unified pressure signature method. Part 2: Application to jet-in-crossflow

NASA Technical Reports Server (NTRS)

Hackett, J. E.; Sampath, S.; Phillips, C. G.

1981-01-01

The development of an improved jet-in-crossflow model for estimating wind tunnel blockage and angle-of-attack interference is described. Experiments showed that the simpler existing models fall seriously short of representing far-field flows properly. A new, vortex-source-doublet (VSD) model was therefore developed which employs curved trajectories and experimentally-based singularity strengths. The new model is consistent with existing and new experimental data and it predicts tunnel wall (i.e. far-field) pressures properly. It is implemented as a preprocessor to the wall-pressure-signature-based tunnel interference predictor. The supporting experiments and theoretical studies revealed some new results. Comparative flow field measurements with 1-inch "free-air" and 3-inch impinging jets showed that vortex penetration into the flow, in diameters, was almost unaltered until 'hard' impingement occurred. In modeling impinging cases, a 'plume redirection' term was introduced which is apparently absent in previous models. The effects of this term were found to be very significant.

Supravalvar mitral ring with a parachute mitral valve and subcoarctation of the aorta in a child with hemodynamically significant VSD. A study of the morphology, echocardiographic diagnostics and surgical therapy.

PubMed

Mądry, Wojciech; Karolczak, Maciej A; Grabowski, Krzysztof

2017-09-01

The authors present a case of echocardiographic diagnosis of supravalvar mitral ring (a fibromembranous structure that arose from the atrial surface of the mitral leaflets) in a child with a parachute mitral valve, a ventricular septal defect, and mild narrowing of the aortic isthmus. The supravalvar mitral stenosis is a typical but very infrequently detected element of the complex of anatomical abnormalities located within the left heart and the proximal aorta, called the Shone's complex (syndrome). Diagnosing an additional, hemodynamically significant anatomic defect during echocardiography was possible thanks to the detection of marked mobility limitation of the ring-adjacent part of the mitral valve mural leaflet as well as of an atypical image of turbulence occurring during the inflow from the left atrium to the left ventricle. The early diagnosis made it possible to perform complete correction of this complex congenital defect within a single operation.

Successful living donor liver transplant in a child with Abernethy malformation with biliary atresia, ventricular septal defect and intrapulmonary shunting.

PubMed

Singhal, Ashish; Srivastava, Ajitabh; Goyal, Neerav; Vij, Vivek; Wadhawan, Manav; Bera, Motilal; Gupta, Subash

2009-12-01

Congenital portosystemic shunts are the anomalies in which the mesenteric venous drainage bypasses the liver and drains directly into the systemic circulation. This is a report of a rare case of LDLT in a four-yr old male child suffering with biliary atresia (post-failed Kasai procedure) associated with (i) a large congenital CEPSh from the spleno-mesentric confluence to the LHV, (ii) intrapulmonary shunts, (iii) perimembranous VSD. The left lobe graft was procured from the mother of the child. Recipient IVC and the shunt vessel were preserved during the hepatectomy, and the caval and shunt clamping were remarkably short while performing the HV and portal anastomosis. Post-operative course was uneventful; intrapulmonary shunts regressed within three months after transplantation and currently after 18 months following transplant child is doing well with normal liver functions. CEPSh has been extensively discussed and all the published cases of liver transplantation for CEPSh were reviewed.

Single-molecule fluorimetry and gating currents inspire an improved optical voltage indicator

PubMed Central

Treger, Jeremy S; Priest, Michael F; Bezanilla, Francisco

2015-01-01

Voltage-sensing domains (VSDs) underlie the movement of voltage-gated ion channels, as well as the voltage-sensitive fluorescent responses observed from a common class of genetically encoded voltage indicators (GEVIs). Despite the widespread use and potential utility of these GEVIs, the biophysical underpinnings of the relationship between VSD movement and fluorophore response remain unclear. We investigated the recently developed GEVI ArcLight, and its close variant Arclight', at both the single-molecule and macroscopic levels to better understand their characteristics and mechanisms of activity. These studies revealed a number of previously unobserved features of ArcLight's behavior, including millisecond-scale fluorescence fluctuations in single molecules as well as a previously unreported delay prior to macroscopic fluorescence onset. Finally, these mechanistic insights allowed us to improve the optical response of ArcLight to fast or repetitive pulses with the development of ArcLightning, a novel GEVI with improved kinetics. DOI: http://dx.doi.org/10.7554/eLife.10482.001 PMID:26599732

Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity.

PubMed

Rayaprolu, Vamseedhar; Royal, Perrine; Stengel, Karen; Sandoz, Guillaume; Kohout, Susy C

2018-05-07

Multimerization is a key characteristic of most voltage-sensing proteins. The main exception was thought to be the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP). In this study, we show that multimerization is also critical for Ci-VSP function. Using coimmunoprecipitation and single-molecule pull-down, we find that Ci-VSP stoichiometry is flexible. It exists as both monomers and dimers, with dimers favored at higher concentrations. We show strong dimerization via the voltage-sensing domain (VSD) and weak dimerization via the phosphatase domain. Using voltage-clamp fluorometry, we also find that VSDs cooperate to lower the voltage dependence of activation, thus favoring the activation of Ci-VSP. Finally, using activity assays, we find that dimerization alters Ci-VSP substrate specificity such that only dimeric Ci-VSP is able to dephosphorylate the 3-phosphate from PI(3,4,5)P 3 or PI(3,4)P 2 Our results indicate that dimerization plays a significant role in Ci-VSP function. © 2018 Rayaprolu et al.

Effect of desertification on productivity in a desert steppe.

PubMed

Tang, Zhuangsheng; An, Hui; Deng, Lei; Wang, Yingying; Zhu, Guangyu; Shangguan, Zhouping

2016-06-14

Desertification, one of the most severe types of land degradation in the world, is of great importance because it is occurring, to some degree, on approximately 40% of the global land area and is affecting more than 1 billion people. In this study, we used a space-for-time method to quantify the impact of five different desertification regimes (potential (PD), light (LD), moderate (MD), severe (SD), and very severe (VSD)) on a desert steppe ecosystem in northern China to examine the relationship between the productivity of the vegetation and soil properties and to determine the mechanism underlying the effects of desertification on productivity. Our results showed that the effects of desertification on TP (total phosphorus) and AP (available phosphorus) were not significant, and desertification decreased productivity in the desert steppe as a result of direct changes to soil physical properties, which can directly affect soil chemical properties. Therefore, intensive grassland management to improve soil quality may result in the long-term preservation of ecosystem functions and services.

Effect of desertification on productivity in a desert steppe

PubMed Central

Tang, Zhuangsheng; An, Hui; Deng, Lei; Wang, Yingying; Zhu, Guangyu; Shangguan, Zhouping

2016-01-01

Desertification, one of the most severe types of land degradation in the world, is of great importance because it is occurring, to some degree, on approximately 40% of the global land area and is affecting more than 1 billion people. In this study, we used a space-for-time method to quantify the impact of five different desertification regimes (potential (PD), light (LD), moderate (MD), severe (SD), and very severe (VSD)) on a desert steppe ecosystem in northern China to examine the relationship between the productivity of the vegetation and soil properties and to determine the mechanism underlying the effects of desertification on productivity. Our results showed that the effects of desertification on TP (total phosphorus) and AP (available phosphorus) were not significant, and desertification decreased productivity in the desert steppe as a result of direct changes to soil physical properties, which can directly affect soil chemical properties. Therefore, intensive grassland management to improve soil quality may result in the long-term preservation of ecosystem functions and services. PMID:27297202

Medium-term clinical outcomes following surgical repair for vaginal prolapse with tension-free mesh and vaginal support device.

PubMed

Sayer, T; Lim, J; Gauld, J M; Hinoul, P; Jones, P; Franco, N; Van Drie, D; Slack, M

2012-04-01

This study was designed to evaluate clinical outcomes ≥2 years following surgery with polypropylene mesh and vaginal support device (VSD) in women with vaginal prolapse, in a prospective, multi-center setting. Patients re-consented for this extended follow-up (n = 110), with anatomic evaluation using Pelvic Organ Prolapse Quantification (POP-Q) and validated questionnaires to assess pelvic symptoms and sexual function. Complications were recorded (safety set; n = 121). Median length of follow-up was 29 months (range 24-34 months). The primary anatomic success, defined as POP-Q 0-I, was 69.1%; however, in 84.5% of the cases, the leading vaginal edge was above the hymen. Pelvic symptoms and sexual function improved significantly from baseline (p < 0.01). Mesh exposure rate was 9.1%. Five percent reported stress urinary incontinence and 3.3% required further prolapse surgery. These results indicate this non-anchored mesh repair is a safe and effective treatment for women with symptomatic vaginal prolapse in the medium term.

Hip/femur fractures associated with the use of benzodiazepines (anxiolytics, hypnotics and related drugs): a methodological approach to assess consistencies across databases from the PROTECT-EU project.

PubMed

Requena, Gema; Huerta, Consuelo; Gardarsdottir, Helga; Logie, John; González-González, Rocío; Abbing-Karahagopian, Victoria; Miret, Montserrat; Schneider, Cornelia; Souverein, Patrick C; Webb, Dave; Afonso, Ana; Boudiaf, Nada; Martin, Elisa; Oliva, Belén; Alvarez, Arturo; De Groot, Mark C H; Bate, Andrew; Johansson, Saga; Schlienger, Raymond; Reynolds, Robert; Klungel, Olaf H; de Abajo, Francisco J

2016-03-01

Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies. To measure the risk of HFF among adult users of BZDs during 2001-2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A-D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated. Adjusted hazard ratios (Model C) were 1.34 (1.23-1.47) in BIFAP, 1.66 (1.54-1.78) in CPRD, and 2.22 (1.55-3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16-1.42) in BIFAP, 1.60 (1.49-1.72) in CPRD, and 1.48 (0.89-2.48) in Mondriaan in NCC studies. A short-term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs. Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs. Copyright © 2015 John Wiley & Sons, Ltd.

FLYSAFE, nowcasting of in flight icing supporting aircrew decision making process

NASA Astrophysics Data System (ADS)

Drouin, A.; Le Bot, C.

2009-09-01

FLYSAFE is an Integrated Project of the 6th framework of the European Commission with the aim to improve flight safety through the development of a Next Generation Integrated Surveillance System (NGISS). The NGISS provides information to the flight crew on the three major external hazards for aviation: weather, air traffic and terrain. The NGISS has the capability of displaying data about all three hazards on a single display screen, facilitating rapid pilot appreciation of the situation by the flight crew. Weather Information Management Systems (WIMS) were developed to provide the NGISS and the flight crew with weather related information on in-flight icing, thunderstorms, wake-vortex and clear-air turbulence. These products are generated on the ground from observations and model forecasts. WIMS supply relevant information on three different scales: global, regional and local (over airport Terminal Manoeuvring Area). Within the flysafe program, around 120 hours of flight trials were performed during February 2008 and August 2008. Two aircraft were involved each with separate objectives : - to assess FLYSAFE's innovative solutions for the data-link, on-board data fusion, data-display, and data-updates during flight; - to evaluate the new weather information management systems (in flight icing and thunderstorms) using in-situ measurements recorded on board the test aircraft. In this presentation we will focus on the in-flight icing nowcasting system developed at Météo France in the framework of FLYSAFE: the local ICE WIMS. The local ICE WIMS is based on data fusion. The most relevant information for icing detection is extracted from the numerical weather prediction model, the infra-red and visible satellite imagery and the ground weather radar reflectivities. After a presentation of the local ICE WIMS, we detail the evaluation of the local ICE WIMS performed using the winter and summer flight trial data.

Ikhana: A NASA UAS Supporting Long Duration Earth Science Missions

NASA Technical Reports Server (NTRS)

Cobleigh, Brent R.

2006-01-01

NASA's Ikhana unmanned aerial vehicle (UAV) is a General Atomics MQ-9 Predator-B modified to support the conduct of Earth science missions for the NASA Science Mission Directorate through partnerships, other government agencies and universities. Ikhana, a Native American word meaning 'intelligence', can carry over 2000 lbs of atmospheric and remote sensing instruments in the payload bay and external pods. The aircraft is capable of mission durations in excess of 24 hours at altitudes above 40,000 ft. Redundant flight control, avionics, power, and network systems increase the system reliability and allow easier access to public airspace. The aircraft is remotely piloted from a mobile ground control station (GCS) using both C-band line-of-sight and Ku-band over-the-horizon satellite datalinks. NASA's GCS has been modified to support on-site science monitoring, or the downlink data can be networked to remote sites. All ground support systems are designed to be deployable to support global Eart science investigations. On-board support capabilities include an instrumentation system and an Airborne Research Test System (ARTS). The ARTS can host research algorithms that will autonomously command and control on-board sensors, perform sensor health monitoring, conduct data analysis, and request changes to the flight plan to maximize data collection. The ARTS also has the ability to host algorithms that will autonomously control the aircraft trajectory based on sensor needs, (e.g. precision trajectory for repeat pass interferometry) or to optimize mission objectives (e.g. search for specific atmospheric conditions). Standard on-board networks will collect science data for recording and for inclusion in the aircraft's high bandwidth downlink. The Ikhana project will complete GCS development, science support systems integration, external pod integration and flight clearance, and operations crew training in early 2007. A large-area remote sensing mission is currently scheduled for the Summer 2007.

Validation of asthma recording in the Clinical Practice Research Datalink (CPRD)

PubMed Central

Morales, Daniel R; Mullerova, Hana; Smeeth, Liam; Douglas, Ian J; Quint, Jennifer K

2017-01-01

Objectives The optimal method of identifying people with asthma from electronic health records in primary care is not known. The aim of this study is to determine the positive predictive value (PPV) of different algorithms using clinical codes and prescription data to identify people with asthma in the United Kingdom Clinical Practice Research Datalink (CPRD). Methods 684 participants registered with a general practitioner (GP) practice contributing to CPRD between 1 December 2013 and 30 November 2015 were selected according to one of eight predefined potential asthma identification algorithms. A questionnaire was sent to the GPs to confirm asthma status and provide additional information to support an asthma diagnosis. Two study physicians independently reviewed and adjudicated the questionnaires and additional information to form a gold standard for asthma diagnosis. The PPV was calculated for each algorithm. Results 684 questionnaires were sent, of which 494 (72%) were returned and 475 (69%) were complete and analysed. All five algorithms including a specific Read code indicating asthma or non-specific Read code accompanied by additional conditions performed well. The PPV for asthma diagnosis using only a specific asthma code was 86.4% (95% CI 77.4% to 95.4%). Extra information on asthma medication prescription (PPV 83.3%), evidence of reversibility testing (PPV 86.0%) or a combination of all three selection criteria (PPV 86.4%) did not result in a higher PPV. The algorithm using non-specific asthma codes, information on reversibility testing and respiratory medication use scored highest (PPV 90.7%, 95% CI (82.8% to 98.7%), but had a much lower identifiable population. Algorithms based on asthma symptom codes had low PPVs (43.1% to 57.8%)%). Conclusions People with asthma can be accurately identified from UK primary care records using specific Read codes. The inclusion of spirometry or asthma medications in the algorithm did not clearly improve accuracy. Ethics and dissemination The protocol for this research was approved by the Independent Scientific Advisory Committee (ISAC) for MHRA Database Research (protocol number15_257) and the approved protocol was made available to the journal and reviewers during peer review. Generic ethical approval for observational research using the CPRD with approval from ISAC has been granted by a Health Research Authority Research Ethics Committee (East Midlands—Derby, REC reference number 05/MRE04/87). The results will be submitted for publication and will be disseminated through research conferences and peer-reviewed journals. PMID:28801439

Assessing the healthcare resource use associated with inappropriate prescribing of inhaled corticosteroids for people with chronic obstructive pulmonary disease (COPD) in GOLD groups A or B: an observational study using the Clinical Practice Research Datalink (CPRD).

PubMed

Chalmers, James D; Poole, Chris; Webster, Samantha; Tebboth, Abigail; Dickinson, Scott; Gayle, Alicia

2018-04-11

Recent recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) position inhaled corticosteroids (ICS) for use in chronic obstructive pulmonary disease (COPD) patients experiencing exacerbations (≥ 2 or ≥ 1 requiring hospitalisation); i.e. GOLD groups C and D. However, it is known that ICS is frequently prescribed for patients with less severe COPD. Potential drivers of inappropriate ICS use may be historical clinical guidance or a belief among physicians that intervening early with ICS would improve outcomes and reduce resource use. The objective of this study was to compare healthcare resource use in the UK for COPD patients in GOLD groups A and B (0 or 1 exacerbation not resulting in hospitalisation) who have either been prescribed an ICS-containing regimen or a non-ICS-containing regimen. Linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database were used. For the study period (1 July 2005 to 30 June 2015) a total 4009 patients met the inclusion criteria; 1745 receiving ICS-containing therapy and 2264 receiving non-ICS therapy. Treatment groups were propensity score-matched to account for potential confounders in the decision to prescribe ICS, leaving 1739 patients in both treatment arms. Resource use was assessed in terms of frequency of healthcare practitioner (HCP) interactions and rescue therapy prescribing. Treatment acquisition costs were not assessed. Results showed no benefit associated with the addition of ICS, with numerically higher all-cause HCP interactions (72,802 versus 69,136; adjusted relative rate: 1.07 [p = 0.061]) and rescue therapy prescriptions (24,063 versus 21,163; adjusted relative rate: 1.05 [p = 0.212]) for the ICS-containing group compared to the non-ICS group. Rate ratios favoured the non-ICS group for eight of nine outcomes assessed. Outcomes were similar for subgroup analyses surrounding potential influential parameters, including patients with poorer lung function (FEV 1  <  50% predicted), one prior exacerbation or elevated blood eosinophils. These data suggest that ICS use in GOLD A and B COPD patients is not associated with a benefit in terms of healthcare resource use compared to non-ICS bronchodilator-based therapy; using ICS according to GOLD recommendations may offer an opportunity for improving patient care and reducing resource use.

Does Angiotensin-Converting Enzyme Inhibitor and β-Blocker Use Reduce the Risk of Primary Liver Cancer? A Case-Control Study Using the U.K. Clinical Practice Research Datalink.

PubMed

Hagberg, Katrina Wilcox; Sahasrabuddhe, Vikrant V; McGlynn, Katherine A; Jick, Susan S

2016-02-01

It has been suggested that use of the antihypertensive drugs angiotensin-converting enzyme (ACE) inhibitors and β-blockers may decrease the risk of primary liver cancer; thus, the objective of this study was to evaluate whether use of ACE inhibitors and/or β-blockers is associated with a lower risk of liver cancer. Nested case-control study. United Kingdom Clinical Practice Research Datalink. We identified 490 cases with hypertension and a first-time (incident) diagnosis of primary liver cancer between 1988 and 2011. To account for an induction period, the index date was defined as the date of the first recorded liver cancer diagnosis minus 1 year. Controls were selected from patients with hypertension in the CPRD during the study period with a recorded diagnosis of hypertension who had no diagnosis of liver cancer and were free of any other cancer (except nonmelanoma skin cancer) before the index date; they were matched up to a 4:1 ratio to cases based on index date (same index date as that of their matched case), age (same year of birth), sex, general practice, and number of years of recorded history in the CPRD before the index date (1909 controls). Both cases and controls were required to have at least 2 years of recorded activity in the database before the index date. Exposure was defined as receipt of two or more prescriptions for ACE inhibitors and/or β-blockers before the index date; the reference group was nonuse (0-1 prescription) of ACE or β-blocker prescriptions before the index date. We also examined the effect of duration of use and, separately, the effect of individual drugs within each medication class on risk of liver cancer, and conducted analyses restricted to patients without liver disease or diabetes mellitus. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). No association was found between use of ACE inhibitors and/or β-blockers and the risk of liver cancer compared with nonuse (adjusted OR 1.14, 95% CI 0.85-1.55). No significant differences were noted in risk by duration of use or by individual drugs, or after restricting the analyses to patients without diabetes or liver disease. Use of ACE inhibitors and/or β-blockers was not associated with reduced risk of primary liver cancer compared with nonuse of these drugs in persons with hypertension. © 2016 Pharmacotherapy Publications, Inc.

Intraoperative three-dimensional transesophageal echocardiography for assessing the defect geometries of mitral prosthetic paravalvular leak during transcatheter closure.

PubMed

Wei, Jeng; Yin, Wei-Hsian; Lee, Yung-Tsai; Hsiung, Ming C; Tsai, Shen-Kou; Chuang, Yi Cheng; Ou, Ching-Huei; Chou, Yi-Pen

2015-03-01

Paravalvular leaks (PVLs) are a common complication of prosthetic valve replacement. Use of the transcatheter intervention technique is a suitable alternative in high-risk patients who may not tolerate repeat surgery. Common reasons for failure of this demanding intervention include poor imaging quality and unsuitable anatomy. The purpose of this study was to assess the usefulness and the incremental value of real-time three-dimensional (RT 3D) transesophageal echocardiography (TEE) over two-dimensional (2D) TEE findings in the evaluation of the geometry and track of mitral PVLs during transcatheter closure. Five patients with six mitral PVLs at high risk for repeat surgery underwent transcatheter leak closure. Intraoperative RT 3DTEE was used to assess the location, shape, number, and size of the defects. Transapical approaches were used in all cases with fluoroscopic and RT 3D TEE guidance of the wire and catheter, device positioning, and assessment of residual leak after the procedure. In all of the cases, defects with irregular crescent shapes and distorted tracks were clearly delineated by RT 3D TEE. This was compared to those results obtained through 2D TEE, which was unable to characterize the defects. Three cases showed small leaks, which were completely occluded with a patent ductus arteriosus (PDA) device in two cases, and a muscular ventricular septal defect (mVSD) occluder combined with coil devices in one case. One case involved a large leak and early device embolization of the muscular VSD occluder, which was removed surgically, and demonstrated a crescent-shaped defect. One patient had two releaks 2 months subsequent to the procedure due to two new extended leaks at the tails of the crescent-shaped defect. RT 3D TEE can clearly delineate the geometries of defects in their entirety, including shape, size, and location of the defect and track canal. It would also appear that RT 3D TEE is superior to 2D TEE in the process of guiding the wire through the difficult canal anatomy, facilitating the overall procedure. The small mitral PVLs can be completely occluded, but subsequent complications occurred with large defect closures because of embolization or releak. Therefore, transcatheter closure of PVLs seems to be an attractive alternative for these patients, but newer occluder designs that better conform to leak geometry will be required to improve outcomes. Copyright © 2014. Published by Elsevier Taiwan.

A flight investigation of simulated data-link communications during single-pilot IFR flight. Volume 2: Flight evaluations

NASA Technical Reports Server (NTRS)

Parker, J. F., Jr.; Duffy, J. W.

1982-01-01

Key problems in single pilot instrument flight operations are in the management of flight data and the processing of cockpit information during conditions of heavy workload. A flight data console was developed to allow simulation of a digital data link to replace the current voice communications stem used in air traffic control. This is a human factors evaluation of a data link communications system to determine how such a system might reduce cockpit workload, improve flight proficiency, and be accepted by general aviation pilots. The need for a voice channel as backup to a digital link is examined. The evaluations cover both airport terminal area operations and full mission instrument flight. Results show that general aviation pilots operate well with a digital data link communications system. The findings indicate that a data link system for pilot/ATC communications, with a backup voice channel, is well accepted by general aviation pilots and is considered to be safer, more efficient, and result in less workload than the current voice system.

NASA Aviation Safety Program Weather Accident Prevention/weather Information Communications (WINCOMM)

NASA Technical Reports Server (NTRS)

Feinberg, Arthur; Tauss, James; Chomos, Gerald (Technical Monitor)

2002-01-01

Weather is a contributing factor in approximately 25-30 percent of general aviation accidents. The lack of timely, accurate and usable weather information to the general aviation pilot in the cockpit to enhance pilot situational awareness and improve pilot judgment remains a major impediment to improving aviation safety. NASA Glenn Research Center commissioned this 120 day weather datalink market survey to assess the technologies, infrastructure, products, and services of commercial avionics systems being marketed to the general aviation community to address these longstanding safety concerns. A market survey of companies providing or proposing to provide graphical weather information to the general aviation cockpit was conducted. Fifteen commercial companies were surveyed. These systems are characterized and evaluated in this report by availability, end-user pricing/cost, system constraints/limits and technical specifications. An analysis of market survey results and an evaluation of product offerings were made. In addition, recommendations to NASA for additional research and technology development investment have been made as a result of this survey to accelerate deployment of cockpit weather information systems for enhancing aviation safety.

Trajectory Specification for Terminal Air Traffic: Pairwise Conflict Detection and Resolution

NASA Technical Reports Server (NTRS)

Paielli, Russell A.; Erzberger, Heinz

2017-01-01

Trajectory Specification is the explicit bounding and control of aircraft trajectories such that the position at any point in time is constrained to a precisely defined volume of space. The bounding space is defined by cross-track, along-track, and vertical tolerances relative to a reference trajectory that specifies position as a function of time. The tolerances are dynamic and will be based on the aircraft navigation capabilities and the current traffic situation. Assuming conformance, Trajectory Specification can guarantee safe separation for an arbitrary period of time even in the event of an air traffic control (ATC) system or datalink failure; hence it can help to achieve the high level of safety and reliability needed for ATC automation. It can also reduce the reliance on tactical backup systems during normal operation. This paper applies it to the terminal area around a major airport and presents algorithms and software for detecting and resolving conflicts. A representative set of pairwise conflicts was generated, and a fast-time simulation was run on them. All conflicts were successfully resolved in real time, demonstrating the computational feasibility of the concept.

Towards a real-time wide area motion imagery system

NASA Astrophysics Data System (ADS)

Young, R. I.; Foulkes, S. B.

2015-10-01

It is becoming increasingly important in both the defence and security domains to conduct persistent wide area surveillance (PWAS) of large populations of targets. Wide Area Motion Imagery (WAMI) is a key technique for achieving this wide area surveillance. The recent development of multi-million pixel sensors has provided sensors with wide field of view replete with sufficient resolution for detection and tracking of objects of interest to be achieved across these extended areas of interest. WAMI sensors simultaneously provide high spatial and temporal resolutions, giving extreme pixel counts over large geographical areas. The high temporal resolution is required to enable effective tracking of targets. The provision of wide area coverage with high frame rates generates data deluge issues; these are especially profound if the sensor is mounted on an airborne platform, with finite data-link bandwidth and processing power that is constrained by size, weight and power (SWAP) limitations. These issues manifest themselves either as bottlenecks in the transmission of the imagery off-board or as latency in the time taken to analyse the data due to limited computational processing power.

Evaluation of the navigation performance of shipboard-VTOL-landing guidance systems

NASA Technical Reports Server (NTRS)

Mcgee, L. A.; Paulk, C. H., Jr.; Steck, S. A.; Schmidt, S. F.; Merz, A. W.

1979-01-01

The objective of this study was to explore the performance of a VTOL aircraft landing approach navigation system that receives data (1) from either a microwave scanning beam (MSB) or a radar-transponder (R-T) landing guidance system, and (2) information data-linked from an aviation facility ship. State-of-the-art low-cost-aided inertial techniques and variable gain filters were used in the assumed navigation system. Compensation for ship motion was accomplished by a landing pad deviation vector concept that is a measure of the landing pad's deviation from its calm sea location. The results show that the landing guidance concepts were successful in meeting all of the current Navy navigation error specifications, provided that vector magnitude of the allowable error, rather than the error in each axis, is a permissible interpretation of acceptable performance. The success of these concepts, however, is strongly dependent on the distance measuring equipment bias. In addition, the 'best possible' closed-loop tracking performance achievable with the assumed point-mass VTOL aircraft guidance concept is demonstrated.

Statistical identification of stimulus-activated network nodes in multi-neuron voltage-sensitive dye optical recordings.

PubMed

Fathiazar, Elham; Anemuller, Jorn; Kretzberg, Jutta

2016-08-01

Voltage-Sensitive Dye (VSD) imaging is an optical imaging method that allows measuring the graded voltage changes of multiple neurons simultaneously. In neuroscience, this method is used to reveal networks of neurons involved in certain tasks. However, the recorded relative dye fluorescence changes are usually low and signals are superimposed by noise and artifacts. Therefore, establishing a reliable method to identify which cells are activated by specific stimulus conditions is the first step to identify functional networks. In this paper, we present a statistical method to identify stimulus-activated network nodes as cells, whose activities during sensory network stimulation differ significantly from the un-stimulated control condition. This method is demonstrated based on voltage-sensitive dye recordings from up to 100 neurons in a ganglion of the medicinal leech responding to tactile skin stimulation. Without relying on any prior physiological knowledge, the network nodes identified by our statistical analysis were found to match well with published cell types involved in tactile stimulus processing and to be consistent across stimulus conditions and preparations.

Vacuum sealing drainage therapy in the presence of an external fixation device

PubMed Central

Sun, Dahui; Ju, Weina; Wang, Tiejun; Yu, Tiecheng; Qi, Baochang

2016-01-01

Abstract Rationale: Vacuum sealing drainage (VSD) is widely utilized for treating traumatic wounds. Patient concerns: It is particularly difficult and time consuming to use in combination with an external fixator. Diagnoses: This is because the hardware or pins used for fixation interfere with maintaining a seal, resulting in poor adhesion and subsequent air leakage. Interventions: To resolve this problem, we have devised a new method for sealing the wound dressing, while maintaining the required vacuum.When using this technique, a rubber strip is wrapped around each pin in 3 circles outside the plastic drape, and then tightly tied. Outcomes: After completing this procedure, a vacuum is obtained, and any air leakage stops. We employed this technique to treat a cohort of patients in our department over a period of two years, and obtained good healing of soft tissue without air leakage, as well as good clinical outcomes. Lessons: We have observed that patients treated with this method experienced good clinical outcomes without air leakage, and we recommend its use in treating cases where an external fixation device is present. PMID:27861393

Probing α-3(10) transitions in a voltage-sensing S4 helix.

PubMed

Kubota, Tomoya; Lacroix, Jérôme J; Bezanilla, Francisco; Correa, Ana M

2014-09-02

The S4 helix of voltage sensor domains (VSDs) transfers its gating charges across the membrane electrical field in response to changes of the membrane potential. Recent studies suggest that this process may occur via the helical conversion of the entire S4 between α and 310 conformations. Here, using LRET and FRET, we tested this hypothesis by measuring dynamic changes in the transmembrane length of S4 from engineered VSDs expressed in Xenopus oocytes. Our results suggest that the native S4 from the Ciona intestinalis voltage-sensitive phosphatase (Ci-VSP) does not exhibit extended and long-lived 310 conformations and remains mostly α-helical. Although the S4 of NavAb displays a fully extended 310 conformation in x-ray structures, its transplantation in the Ci-VSP VSD scaffold yielded similar results as the native Ci-VSP S4. Taken together, our study does not support the presence of long-lived extended α-to-310 helical conversions of the S4 in Ci-VSP associated with voltage activation. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

[Medical transportation of Congolese children by the Foundation "Terre des hommes" Netherlands (1989--1998)].

PubMed

Cardorelle, A Mbika; Okoko, A R; Perez, A Cosio; Moyen, G

2004-01-01

We report the 10 year assessment of collaboration with the Foundation "Terre des hommes" concerning the medical transfer in the Netherlands of 41 children carrying pathologies which couldn't be treated or operated on in Brazzaville. The average age was 3 years and 6 months old (extremes: 2 months - 15 years). 33 non-cyanotic cardiopathies dominated by ventricular septal defect (VSD) (n = 10) and 11 cyanotic cardiopathies among them the tetralogy of Fallot (n = 5) were admitted. The other pathologies were respectively: osseous (n = 3), vesical (n = 2), pulmonary tumoral, ophthalmic in 1 case. The surgery consisted in a complete repair in 19 cases, palliative in 9 cases. Two children proved to be inoperable. Eight other extra-cardiac pathologies had a specific surgery for each case. The average stay in the Netherlands was 1 month 13 days (extremes: 1 - 12 months). The evolution was favourable for 35 children all pathologies included. Four deaths occurred in the Netherlands and 2 in Congo. The organization of the technology transfer would be probably a better choice in the future.

Heparan Sulfate Expression in the Neural Crest is Essential for Mouse Cardiogenesis

PubMed Central

Pan, Yi; Carbe, Christian; Pickhinke, Ute; Kupich, Sabine; Ohlig, Stefanie; Frye, Maike; Seelige, Ruth; Pallerla, Srinivas R.; Moon, Anne M.; Lawrence, Roger; Esko, Jeffrey D.; Zhang, Xin; Grobe, Kay

2015-01-01

Impaired heparan sulfate (HS) synthesis in vertebrate development causes complex malformations due to the functional disruption of multiple HS-binding growth factors and morphogens. Here, we report developmental heart defects in mice bearing a targeted disruption of the HS-generating enzyme GlcNAc N-Deacetylase/GlcN N-Sulfotransferase 1 (NDST1), including ventricular septal defects (VSD), persistent truncus arteriosus (PTA), double outlet right ventricle (DORV), and retroesophageal right subclavian artery (RERSC). These defects closely resemble cardiac anomalies observed in mice made deficient in the cardiogenic regulator fibroblast growth factor 8 (FGF8). Consistent with this, we show that HS-dependent FGF8/FGF-receptor2C assembly and FGF8-dependent ERK-phosphorylation are strongly reduced in NDST1−/− embryonic cells and tissues. Moreover, WNT1-Cre/LoxP-mediated conditional targeting of NDST function in neural crest cells (NCCs) revealed that their impaired HS-dependent development contributes strongly to the observed cardiac defects. These findings raise the possibility that defects in HS biosynthesis may contribute to congenital heart defects in humans that represent the most common type of birth defect. PMID:24200809

Emerging technologies in Si active photonics

NASA Astrophysics Data System (ADS)

Wang, Xiaoxin; Liu, Jifeng

2018-06-01

Silicon photonics for synergistic electronic–photonic integration has achieved remarkable progress in the past two decades. Active photonic devices, including lasers, modulators, and photodetectors, are the key challenges for Si photonics to meet the requirement of high bandwidth and low power consumption in photonic datalinks. Here we review recent efforts and progress in high-performance active photonic devices on Si, focusing on emerging technologies beyond conventional foundry-ready Si photonics devices. For emerging laser sources, we will discuss recent progress towards efficient monolithic Ge lasers, mid-infrared GeSn lasers, and high-performance InAs quantum dot lasers on Si for data center applications in the near future. We will then review novel modulator materials and devices beyond the free carrier plasma dispersion effect in Si, including GeSi and graphene electro-absorption modulators and plasmonic-organic electro-optical modulators, to achieve ultralow power and high speed modulation. Finally, we discuss emerging photodetectors beyond epitaxial Ge p–i–n photodiodes, including GeSn mid-infrared photodetectors, all-Si plasmonic Schottky infrared photodetectors, and Si quanta image sensors for non-avalanche, low noise single photon detection and photon counting. These emerging technologies, though still under development, could make a significant impact on the future of large-scale electronicSilicon photonics for synergistic electronic-photonic integration has achieved remarkable progress in the past two decades. Active photonic devices, including lasers, modulators, and photodetectors, are the key challenges for Si photonics to meet the requirement of high bandwidth and low power consumption in photonic datalinks. Here we review recent efforts and progress in high-performance active photonic devices on Si, focusing on emerging technologies beyond conventional foundry-ready Si photonics devices. For emerging laser sources, we will discuss recent progress towards efficient monolithic Ge lasers, mid-infrared GeSn lasers, and high-performance InAs quantum dot lasers on Si for data center applications in the near future. We will then review novel modulator materials and devices beyond the free carrier plasma dispersion effect in Si, including GeSi and graphene electro-absorption modulators and plasmonic-organic electro–optical modulators, to achieve ultralow power and high speed modulation. Finally, we discuss emerging photodetectors beyond epitaxial Ge p–i–n photodiodes, including GeSn mid-infrared photodetectors, all-Si plasmonic Schottky infrared photodetectors, and Si quanta image sensors for non-avalanche, low noise single photon detection and photon counting. These emerging technologies, though still under development, could make a significant impact on the future of large-scale electronic–photonic integration with performance inaccessible from conventional Si photonics technologies-photonic integration with performance inaccessible from conventional Si photonics technologies.

Early Dialysis and Adverse Outcomes After Hurricane Sandy.

PubMed

Lurie, Nicole; Finne, Kristen; Worrall, Chris; Jauregui, Maria; Thaweethai, Tanayott; Margolis, Gregg; Kelman, Jeffrey

2015-09-01

Hemodialysis patients have historically experienced diminished access to care and increased adverse outcomes after natural disasters. Although "early dialysis" in advance of a storm is promoted as a best practice, evidence for its effectiveness as a protective measure is lacking. Building on prior work, we examined the relationship between the receipt of dialysis ahead of schedule before the storm (also known as early dialysis) and adverse outcomes of patients with end-stage renal disease in the areas most affected by Hurricane Sandy. Retrospective cohort analysis, using claims data from the Centers for Medicare & Medicaid Services Datalink Project. Patients receiving long-term hemodialysis in New York City and the state of New Jersey, the areas most affected by Hurricane Sandy. Receipt of early dialysis compared to their usual treatment pattern in the week prior to the storm. Emergency department (ED) visits, hospitalizations, and 30-day mortality following the storm. Of 13,836 study patients, 8,256 (60%) received early dialysis. In unadjusted logistic regression models, patients who received early dialysis were found to have lower odds of ED visits (OR, 0.75; 95% CI, 0.63-0.89; P=0.001) and hospitalizations (OR, 0.77; 95% CI, 0.65-0.92; P=0.004) in the week of the storm and similar odds of 30-day mortality (OR, 0.80; 95% CI, 0.58-1.09; P=0.2). In adjusted multivariable logistic regression models, receipt of early dialysis was associated with lower odds of ED visits (OR, 0.80; 95% CI, 0.67-0.96; P=0.01) and hospitalizations (OR, 0.79; 95% CI, 0.66-0.94; P=0.01) in the week of the storm and 30-day mortality (OR, 0.72; 95% CI, 0.52-0.997; P=0.048). Inability to determine which patients were offered early dialysis and declined and whether important unmeasured patient characteristics are associated with receipt of early dialysis. Patients who received early dialysis had significantly lower odds of having an ED visit and hospitalization in the week of the storm and of dying within 30 days. Published by Elsevier Inc.

Creating an index to measure health state of depressed patients in automated healthcare databases: the methodology.

PubMed

François, Clément; Tanasescu, Adrian; Lamy, François-Xavier; Despiegel, Nicolas; Falissard, Bruno; Chalem, Ylana; Lançon, Christophe; Llorca, Pierre-Michel; Saragoussi, Delphine; Verpillat, Patrice; Wade, Alan G; Zighed, Djamel A

2017-01-01

Background and objective : Automated healthcare databases (AHDB) are an important data source for real life drug and healthcare use. In the filed of depression, lack of detailed clinical data requires the use of binary proxies with important limitations. The study objective was to create a Depressive Health State Index (DHSI) as a continuous health state measure for depressed patients using available data in an AHDB. Methods: The study was based on historical cohort design using the UK Clinical Practice Research Datalink (CPRD). Depressive episodes (depression diagnosis with an antidepressant prescription) were used to create the DHSI through 6 successive steps: (1) Defining study design; (2) Identifying constituent parameters; (3) Assigning relative weights to the parameters; (4) Ranking based on the presence of parameters; (5) Standardizing the rank of the DHSI; (6) Developing a regression model to derive the DHSI in any other sample. Results : The DHSI ranged from 0 (worst) to 100 (best health state) comprising 29 parameters. The proportion of depressive episodes with a remission proxy increased with DHSI quartiles. Conclusion : A continuous outcome for depressed patients treated by antidepressants was created in an AHDB using several different variables and allowed more granularity than currently used proxies.

PHY-DLL dialogue: cross-layer design for optical-wireless OFDM downlink transmission

NASA Astrophysics Data System (ADS)

Wang, Xuguo; Li, Lee

2005-11-01

The use of radio over fiber to provide radio access has a number of advantages including the ability to deploy small, low-cost remote antenna units and ease of upgrade. And due to the great potential for increasing the capacity and quality of service, the combination of Orthogonal Frequency Division Multiplexing (OFDM) modulation and the sub-carrier multiplexed optical transmission is one of the best solutions for the future millimeter-wave mobile communication. And this makes the optimum utility of valuable radio resources essential. This paper devises a cross-layer adaptive algorithm for optical-wireless OFDM system, which takes into consideration not only transmission power limitation in the physical layer, but also traffic scheduling and user fairness at the data-link layer. According to proportional fairness principle and water-pouring theorem, we put forward the complete description of this cross-layer adaptive downlink transmission 6-step algorithm. Simulation results show that the proposed cross-layer algorithm outperforms the mere physical layer adaptive algorithm markedly. The novel scheme is able to improve performance of the packet success rate per time chip and average packet delay, support added active users.

Definition and evaluation of the data-link layer of PACnet

NASA Astrophysics Data System (ADS)

Alsafadi, Yasser H.; Martinez, Ralph; Sanders, William H.

1991-07-01

PACnet is a 200-500 Mbps dual-ring fiber optic network designed to implement a picture archiving and communication system (PACS) in a hospital environment. The network consists of three channels: an image transfer channel, a command and control channel, and a real-time data channel. An initial network interface unit (NIU) design for PACnet consisted of a functional description of the protocols and NIU major components. In order to develop a demonstration prototype, additional definition of protocol algorithms of each channel is necessary. Using the International Standards Organization/Open Systems Interconnection (ISO/OSI) reference model as a guide, the definition of the data link layer is extended. This definition covers interface service specifications for the two constituent sublayers: logical link control (LLC) and medium access control (MAC). Furthermore, it describes procedures for data transfer, mechanisms of error detection and fault recovery. A performance evaluation study was then made to determine how the network performs under various application scenarios. The performance evaluation study was performed using stochastic activity networks, which can formally describe the network behavior. The results of the study demonstrate the feasibility of PACnet as an integrated image, data, and voice network for PACS.

Flight Crew Factors for CTAS/FMS Integration in the Terminal Area

NASA Technical Reports Server (NTRS)

Crane, Barry W.; Prevot, Thomas; Palmer, Everett A.; Shafto, M. (Technical Monitor)

2000-01-01

Center TRACON Automation System (CTAS)/Flight Management System (FMS) integration on the flightdeck implies flight crews flying coupled in highly automated FMS modes [i.e. Vertical Navigation (VNAV) and Lateral Navigation (LNAV)] from top of descent to the final approach phase of flight. Pilots may also have to make FMS route edits and respond to datalink clearances in the Terminal Radar Approach Control (TRACON) airspace. This full mission simulator study addresses how the introduction of these FMS descent procedures affect crew activities, workload, and performance. It also assesses crew acceptance of these procedures. Results indicate that the number of crew activities and workload ratings are significantly reduced below current day levels when FMS procedures can be flown uninterrupted, but that activity numbers increase significantly above current day levels and workload ratings return to current day levels when FMS procedures are interrupted by common ATC interventions and CTAS routing advisories. Crew performance showed some problems with speed control during FMS procedures. Crew acceptance of the FMS procedures and route modification requirements was generally high; a minority of crews expressed concerns about use of VNAV in the TRACON airspace. Suggestions for future study are discussed.

Supplementing electronic health records through sample collection and patient diaries: A study set within a primary care research database.

PubMed

Joseph, Rebecca M; Soames, Jamie; Wright, Mark; Sultana, Kirin; van Staa, Tjeerd P; Dixon, William G

2018-02-01

To describe a novel observational study that supplemented primary care electronic health record (EHR) data with sample collection and patient diaries. The study was set in primary care in England. A list of 3974 potentially eligible patients was compiled using data from the Clinical Practice Research Datalink. Interested general practices opted into the study then confirmed patient suitability and sent out postal invitations. Participants completed a drug-use diary and provided saliva samples to the research team to combine with EHR data. Of 252 practices contacted to participate, 66 (26%) mailed invitations to patients. Of the 3974 potentially eligible patients, 859 (22%) were at participating practices, and 526 (13%) were sent invitations. Of those invited, 117 (22%) consented to participate of whom 86 (74%) completed the study. We have confirmed the feasibility of supplementing EHR with data collected directly from patients. Although the present study successfully collected essential data from patients, it also underlined the requirement for improved engagement with both patients and general practitioners to support similar studies. © 2017 The Authors. Pharmacoepidemiology & Drug Safety published by John Wiley & Sons Ltd.

An observation tool to study air traffic control and flightdeck collaboration.

PubMed

Cox, Gemma; Sharples, Sarah; Stedmon, Alex; Wilson, John

2007-07-01

The complex systems of the flightdeck (FD) and the Air Traffic Control Centre (ATC) are characterised by numerous concurrently operating and interacting communication channels between people and between people and machines/computer systems. This paper describes work in support of investigating the impact of changes to technologies and responsibilities within this system with respect to human factors. It focuses primarily on the introduction of datalink (text-based communication rather than traditional radio communication) and the move towards freeflight (pilot-mediated air traffic control). Air traffic management investigations have outlined these specific changes as strategies to enable further increases in the volume of air traffic. A systems approach was taken and field studies were conducted. Small numbers of domain experts such as air traffic controllers (ATCOs) were involved in the field-based observations of how people interact with systems and each other. This paper summarises the overall research approach taken and then specifically reports on the field-based observations including the justification, development, and findings of the observation tool used. The observation tool examined information propagation through the air traffic control-flightdeck (ATC-FD) system, and resulted in models of possible information trajectories through the system.

A Perspective on NASA Ames Air Traffic Management Research

NASA Technical Reports Server (NTRS)

Schroeder, Jeffery A.

2012-01-01

This paper describes past and present air-traffic-management research at NASA Ames Research Center. The descriptions emerge from the perspective of a technical manager who supervised the majority of this research for the last four years. Past research contributions built a foundation for calculating accurate flight trajectories to enable efficient airspace management in time. That foundation led to two predominant research activities that continue to this day - one in automatically separating aircraft and the other in optimizing traffic flows. Today s national airspace uses many of the applications resulting from research at Ames. These applications include the nationwide deployment of the Traffic Management Advisor, new procedures enabling continuous descent arrivals, cooperation with industry to permit more direct flights to downstream way-points, a surface management system in use by two cargo carriers, and software to evaluate how well flights conform to national traffic management initiatives. The paper concludes with suggestions for prioritized research in the upcoming years. These priorities include: enabling more first-look operational evaluations, improving conflict detection and resolution for climbing or descending aircraft, and focusing additional attention on the underpinning safety critical items such as a reliable datalink.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farren-Chavez, D.M.; Guzman, E.R.; Peters, T.L.

A 32-year-old G{sub 3}P{sub 2002} Hispanic female presented at 14 weeks gestation for routine dating ultrasound. At that time ultrasonography revealed a septated cystic hygroma, omphalocele, bilateral talipes equinovarus, and hydrops. Amniocentesis was performed at 15 weeks and revealed a 46,XX,9p+ chromosome complement. The origin of the extra material on the terminal short arm of chromosome 9 could not be identified. Chromosome analysis was performed on the parents and the mother was found to carry the balanced translocation 46,XX,p(3;9)(q23;p13). Further analysis revealed that the fetus had inherited the derivative 9 chromosome. The fetus was therefore monosomic for 9p13-9pter and trisomicmore » for 3q23-3pter. The patient chose to continue the pregnancy. Serial ultrasonography later demonstrated a sloping forehead, small nose, micrognathia, ventriculomegaly, possible VSD, micropenis, hypospadias, cryptorchidism and post-axial polydactyly of the hands. The fetus was delivered prematurely at 31 weeks and survived one hour. Post-mortem examination confirmed the ultrasound findings and revealed additional stigmata consistent with both 9p monosomy and 3q trisomy. A review of the literature indicates no previous report of both syndromes concurrently.« less

Predicting acidification recovery at the Hubbard Brook Experimental Forest, New Hampshire: evaluation of four models.

PubMed

Tominaga, Koji; Aherne, Julian; Watmough, Shaun A; Alveteg, Mattias; Cosby, Bernard J; Driscoll, Charles T; Posch, Maximilian; Pourmokhtarian, Afshin

2010-12-01

The performance and prediction uncertainty (owing to parameter and structural uncertainties) of four dynamic watershed acidification models (MAGIC, PnET-BGC, SAFE, and VSD) were assessed by systematically applying them to data from the Hubbard Brook Experimental Forest (HBEF), New Hampshire, where long-term records of precipitation and stream chemistry were available. In order to facilitate systematic evaluation, Monte Carlo simulation was used to randomly generate common model input data sets (n = 10,000) from parameter distributions; input data were subsequently translated among models to retain consistency. The model simulations were objectively calibrated against observed data (streamwater: 1963-2004, soil: 1983). The ensemble of calibrated models was used to assess future response of soil and stream chemistry to reduced sulfur deposition at the HBEF. Although both hindcast (1850-1962) and forecast (2005-2100) predictions were qualitatively similar across the four models, the temporal pattern of key indicators of acidification recovery (stream acid neutralizing capacity and soil base saturation) differed substantially. The range in predictions resulted from differences in model structure and their associated posterior parameter distributions. These differences can be accommodated by employing multiple models (ensemble analysis) but have implications for individual model applications.

The participatory vulnerability scoping diagram - deliberative risk ranking for community water systems

USGS Publications Warehouse

Howe, Peter D.; Yarnal, Brent; Coletti, Alex; Wood, Nathan J.

2013-01-01

Natural hazards and climate change present growing challenges to community water system (CWS) managers, who are increasingly turning to vulnerability assessments to identify, prioritize, and adapt to risks. Effectively assessing CWS vulnerability requires information and participation from various sources, one of which is stakeholders. In this article, we present a deliberative risk-ranking methodology, the participatory vulnerability scoping diagram (P-VSD), which allows rapid assessment and integration of multiple stakeholder perspectives of vulnerability. This technique is based on methods of deliberative risk evaluation and the vulnerability scoping diagram. The goal of the methodology is to engage CWS managers and stakeholders collectively to provide qualitative contextual risk rankings as a first step in a vulnerability assessment. We conduct an initial assessment using a case study of CWS in two U.S. counties, sites with broadly similar exposures but differences in population, land use, and other social sensitivity factors. Results demonstrate that CWS managers and stakeholders in the two case study communities all share the belief that their CWS are vulnerable to hazards but differ in how this vulnerability manifests itself in terms of the exposure, sensitivity, and adaptive capacity of the system.

Complete trisomy 9 with unusual phenotypic associations: Dandy-Walker malformation, cleft lip and cleft palate, cardiovascular abnormalities.

PubMed

Tonni, Gabriele; Lituania, Mario; Chitayat, David; Bonasoni, Maria Paola; Keating, Sarah; Thompson, Megan; Shannon, Patrick

2014-12-01

Trisomy 9 is a rare chromosomal abnormality usually associated with first-trimester miscarriage; few fetuses survive until the second trimester. We report two new cases of complete trisomy 9 that both present unusual phenotypic associations, and we analyze the genetic pathway involved in this chromosomal abnormality. The first fetus investigated showed Dandy-Walker malformation, cleft lip, and cleft palate) at the second trimester scan. Cardiovascular abnormalities were characterized by a right-sided, U-shaped aortic arch associated with a ventricular septal defect (VSD). Symmetrical intrauterine growth restriction and multicystic dysplastic kidney disease were associated findings. The second fetus showed a dysmorphic face, bilateral cleft lip, hypoplastic corpus callosum, and a Dandy-Walker malformation. Postmortem examination revealed cardiovascular abnormalities such as persistent left superior vena cava draining into the coronary sinus, membranous ventricular septal defect, overriding aorta, pulmonary valve with two cusps and three sinuses, and the origin of the left subclavian artery distal to the junction of ductus arteriosus and aortic arch. Complete trisomy 9 may result in a wide spectrum of congenital abnormalities, and the presented case series contributes further details on the phenotype of this rare aneuploidy. Copyright © 2014. Published by Elsevier B.V.

Voltage-sensitive dye imaging of mouse neocortex during a whisker detection task

PubMed Central

Kyriakatos, Alexandros; Sadashivaiah, Vijay; Zhang, Yifei; Motta, Alessandro; Auffret, Matthieu; Petersen, Carl C. H.

2016-01-01

Abstract. Sensorimotor processing occurs in a highly distributed manner in the mammalian neocortex. The spatiotemporal dynamics of electrical activity in the dorsal mouse neocortex can be imaged using voltage-sensitive dyes (VSDs) with near-millisecond temporal resolution and ∼100-μm spatial resolution. Here, we trained mice to lick a water reward spout after a 1-ms deflection of the C2 whisker, and we imaged cortical dynamics during task execution with VSD RH1691. Responses to whisker deflection were highly dynamic and spatially highly distributed, exhibiting high variability from trial to trial in amplitude and spatiotemporal dynamics. We differentiated trials based on licking and whisking behavior. Hit trials, in which the mouse licked after the whisker stimulus, were accompanied by overall greater depolarization compared to miss trials, with the strongest hit versus miss differences being found in frontal cortex. Prestimulus whisking decreased behavioral performance by increasing the fraction of miss trials, and these miss trials had attenuated cortical sensorimotor responses. Our data suggest that the spatiotemporal dynamics of depolarization in mouse sensorimotor cortex evoked by a single brief whisker deflection are subject to important behavioral modulation during the execution of a simple, learned, goal-directed sensorimotor transformation. PMID:27921068

Comparative performance of a genetically-encoded voltage indicator and a blue voltage sensitive dye for large scale cortical voltage imaging

PubMed Central

Mutoh, Hiroki; Mishina, Yukiko; Gallero-Salas, Yasir; Knöpfel, Thomas

2015-01-01

Traditional small molecule voltage sensitive dye indicators have been a powerful tool for monitoring large scale dynamics of neuronal activities but have several limitations including the lack of cell class specific targeting, invasiveness and difficulties in conducting longitudinal studies. Recent advances in the development of genetically-encoded voltage indicators have successfully overcome these limitations. Genetically-encoded voltage indicators (GEVIs) provide sufficient sensitivity to map cortical representations of sensory information and spontaneous network activities across cortical areas and different brain states. In this study, we directly compared the performance of a prototypic GEVI, VSFP2.3, with that of a widely used small molecule voltage sensitive dye (VSD), RH1691, in terms of their ability to resolve mesoscopic scale cortical population responses. We used three synchronized CCD cameras to simultaneously record the dual emission ratiometric fluorescence signal from VSFP2.3 and RH1691 fluorescence. The results show that VSFP2.3 offers more stable and less invasive recording conditions, while the signal-to-noise level and the response dynamics to sensory inputs are comparable to RH1691 recordings. PMID:25964738

Voltage Sensing in Membranes: From Macroscopic Currents to Molecular Motions

PubMed Central

Freites, J. Alfredo; Tobias, Douglas J.

2015-01-01

Voltage-sensing domains (VSDs) are integral membrane protein units that sense changes in membrane electric potential, and through the resulting conformational changes, regulate a specific function. VSDs confer voltage-sensitivity to a large superfamily of membrane proteins that includes voltage-gated Na+, K+, Ca2+, and H+ selective channels, hyperpolarization-activated cyclic nucleotide-gated channels, and voltage-sensing phosphatases. VSDs consist of four transmembrane segments (termed S1 through S4). Their most salient structural feature is the highly conserved positions for charged residues in their sequences. S4 exhibits at least three conserved triplet repeats composed of one basic residue (mostly arginine) followed by two hydrophobic residues. These S4 basic side chains participate in a state-dependent internal salt-bridge network with at least four acidic residues in S1–S3. The signature of voltage-dependent activation in electrophysiology experiments is a transient current (termed gating or sensing current) upon a change in applied membrane potential as the basic side chains in S4 move across the membrane electric field. Thus, the unique structural features of the VSD architecture allow for competing requirements: maintaining a series of stable transmembrane conformations, while allowing charge motion, as briefly reviewed here. PMID:25972106

Structure of the Nav1.4-β1 Complex from Electric Eel.

PubMed

Yan, Zhen; Zhou, Qiang; Wang, Lin; Wu, Jianping; Zhao, Yanyu; Huang, Gaoxingyu; Peng, Wei; Shen, Huaizong; Lei, Jianlin; Yan, Nieng

2017-07-27

Voltage-gated sodium (Na v ) channels initiate and propagate action potentials. Here, we present the cryo-EM structure of EeNa v 1.4, the Na v channel from electric eel, in complex with the β1 subunit at 4.0 Å resolution. The immunoglobulin domain of β1 docks onto the extracellular L5 I and L6 IV loops of EeNa v 1.4 via extensive polar interactions, and the single transmembrane helix interacts with the third voltage-sensing domain (VSD III ). The VSDs exhibit "up" conformations, while the intracellular gate of the pore domain is kept open by a digitonin-like molecule. Structural comparison with closed Na v PaS shows that the outward transfer of gating charges is coupled to the iris-like pore domain dilation through intricate force transmissions involving multiple channel segments. The IFM fast inactivation motif on the III-IV linker is plugged into the corner enclosed by the outer S4-S5 and inner S6 segments in repeats III and IV, suggesting a potential allosteric blocking mechanism for fast inactivation. Copyright © 2017 Elsevier Inc. All rights reserved.

3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX): toxicological properties and risk assessment in drinking water.

PubMed

Hirose, A; Nishikawa, A; Kinae, N; Hasegawa, R

1999-01-01

MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone), one of the byproducts formed during the chlorine disinfection process of drinking water, shows strong mutagenic activity for Salmonella strains in the Ames test. In several countries, the contribution of MX to the total mutagenicity of drinking water is estimated to range from 7% to 67%. To assess the risk of MX for human health, we summarized the toxicological properties of MX and estimated the tolerable daily intake (TDI) or tolerable concentration in drinking water. MX is genotoxic in cultured mammalian cells and causes in vivo DNA damage in several tissues. MX is carcinogenic for rodents in addition to possessing skin and gastric promotion activities. From these toxicological profiles of MX, we estimated the virtual safety dose (VSD) for genotoxic action as 5 ng/kg/d and the TDI for non-genotoxic action of MX as 40 ng/kg/d. We assumed a tolerable MX concentration of 150 ng/L in drinking water. Because of the uncertainty about human genotoxicity, however, and the lack of information on reproductive or developmental toxicity, the estimated tolerable dose level may be provisional.

Protocol for Communication Networking for Formation Flying

NASA Technical Reports Server (NTRS)

Jennings, Esther; Okino, Clayton; Gao, Jay; Clare, Loren

2009-01-01

An application-layer protocol and a network architecture have been proposed for data communications among multiple autonomous spacecraft that are required to fly in a precise formation in order to perform scientific observations. The protocol could also be applied to other autonomous vehicles operating in formation, including robotic aircraft, robotic land vehicles, and robotic underwater vehicles. A group of spacecraft or other vehicles to which the protocol applies could be characterized as a precision-formation- flying (PFF) network, and each vehicle could be characterized as a node in the PFF network. In order to support precise formation flying, it would be necessary to establish a corresponding communication network, through which the vehicles could exchange position and orientation data and formation-control commands. The communication network must enable communication during early phases of a mission, when little positional knowledge is available. Particularly during early mission phases, the distances among vehicles may be so large that communication could be achieved only by relaying across multiple links. The large distances and need for omnidirectional coverage would limit communication links to operation at low bandwidth during these mission phases. Once the vehicles were in formation and distances were shorter, the communication network would be required to provide high-bandwidth, low-jitter service to support tight formation-control loops. The proposed protocol and architecture, intended to satisfy the aforementioned and other requirements, are based on a standard layered-reference-model concept. The proposed application protocol would be used in conjunction with conventional network, data-link, and physical-layer protocols. The proposed protocol includes the ubiquitous Institute of Electrical and Electronics Engineers (IEEE) 802.11 medium access control (MAC) protocol to be used in the datalink layer. In addition to its widespread and proven use in diverse local-area networks, this protocol offers both (1) a random- access mode needed for the early PFF deployment phase and (2) a time-bounded-services mode needed during PFF-maintenance operations. Switching between these two modes could be controlled by upper-layer entities using standard link-management mechanisms. Because the early deployment phase of a PFF mission can be expected to involve multihop relaying to achieve network connectivity (see figure), the proposed protocol includes the open shortest path first (OSPF) network protocol that is commonly used in the Internet. Each spacecraft in a PFF network would be in one of seven distinct states as the mission evolved from initial deployment, through coarse formation, and into precise formation. Reconfiguration of the formation to perform different scientific observations would also cause state changes among the network nodes. The application protocol provides for recognition and tracking of the seven states for each node and for protocol changes under specified conditions to adapt the network and satisfy communication requirements associated with the current PFF mission phase. Except during early deployment, when peer-to-peer random access discovery methods would be used, the application protocol provides for operation in a centralized manner.

Atrial flutter in grown-up congenital heart (GUCH) patients. Clinical characteristics of affected population.

PubMed

Li, W; Somerville, J

2000-09-15

To define occurrence, lesions and clinical characteristics of grown-up congenital heart (GUCH) patients who develop atrial flutter (AFL). All GUCH patients who presented as inpatients or outpatients with documented sustained AFL between 1996 and 1998 were studied prospectively. Retrospective review of case notes for basic data relating to underlying anomaly, prior surgery and age at onset of AFL, enquiry into events before the first attack. Clinical state was assessed by Ability Index before AFL and at last visit. Designated quaternary service for GUC in a tertiary referral centre. From October 1996 to April 1998, 100 consecutive patients (49 female) aged 17-77 (mean 35) years, who presented to the GUCH Unit at Royal Brompton Hospital with a sustained attack of AEL documented by a 12 lead electrocardiogram were studied. Four basic cardiac anomalies accounted for 75% patients: one ventricle (26), atrial septal defect (ASD) (19), transposition of great arteries (TGA) (17) and Tetralogy of Fallot (13). AFL occurred occasionally in small ventricular septal defect (VSD), congenital corrected TGA (CC-TGA), pulmonary stenosis and pulmonary atresia with or without VSD. 86/100 patients had undergone cardiac surgery: Fontan 19 (22%), reconstruction of right ventricular outflow tract 17 (20%), closure of ASD 15 (17%), Mustard for TGA 13 (15%), and other palliative surgery 22 (26%). AFL occurred in 'natural history' (unoperated) in 14 (14%) mostly in CC-TGA, ASD and Fallot. Age at first attack was 6-64 (mean 28) years with the first attack occurring at younger age after Mustard (22+/-7 years) and Fontan (24+/-7), than in un-operated ASD (46+/-13) and CCTGA (31+/-10). Haemodynamic abnormalities from anatomical causes were present in 62/74 (84%) patients who had undergone reparative surgery and included venous pathway obstruction, pulmonary regurgitation and pulmonary hypertension. Additional factors which could have precipitated AFL in prone patients were present in 63. New symptoms appeared in 96 patients with the first attack of AFL. Ability Index prior to onset in 90 patients who have been followed-up for more than 1 year since the first onset was 1 in 52, 2 in 31, 3 in 6 and 4 in 1 patients. At the last visit (mean time from the first onset 6.6+/-4.7 years), only 9 patients remained with Ability Index 1, 43 in 2, 20 in 3 and 18 in 4 despite return to sinus rhythm. One ventricle heart, ASD, transposition of great arteries and Tetrology of Fallot are the most common underlying anomalies in GUCH patients who develop AFL. It is less commonly seen in unoperated patients. When occurs AFL compromises patients' activities and deteriorates the clinical condition. Residual or developed haemodynamic abnormalities and precipitating factor are often present in this patients, hence full investigation and close follow up are necessary once AFL develops.

Health-related quality of life in paediatric patients with congenital heart defects: association with the type of heart defect and the surgical technique.

PubMed

Heusch, A; Kahl, H J; Hensel, K O; Calaminus, G

2017-11-01

The aim of the study was to investigate the impact of a number of surgical interventions for a various congenital cardiac defects (CHDs) on self-reported HRQoL. Patients who had received corrective surgery of several congenital heart defects (surgical VSD closure, Fallot, TGA after atrial or arterial switch or Fontan-type circulation for univentricular AV-connection) were interviewed in the office of their home peadiatric cardiologist. HRQoL in children along 7 dimensions was assessed using a standardised questionnaire (PEDQoL); information on the medical case history of each respondent was also collected. HRQoL was assessed in the questionnaire by asking about the frequency (never, rarely, often, always) of specific negative experiences; more frequent experiences indicate a lower quality of life. Frequency expressions were transformed into numerical values (25, 50, 75, 100%), and mean values for HRQoL were calculated for each patient and for each domain. Differences in HRQoL among patients with different types of interventions were analysed using the Mann-Whitney Test or the Kruskal-Wallis Test as appropriate; p values <0.05 were considered to indicate significant differences, while p values <0.1 were considered to indicate notable trends. Patients: 169 patients (60% male, 40% female) were part of the study. The mean age was 11.6 years; 50 patients had surgical VSD closure, 52 surgeries for Tetralogy of Fallot (22 transannular patch, 18 no transannular patch, 12 inaccurate description), 40 had complete transposition of the great arteries (28 atrial switch, 12 arterial switch), 22 had a Fontan-type procedure for univentricular AV-connection. HRQoL differed little among patients with different CHDs for the items "relation to friends," "interactions in the affected families", and "own body image". For other items, notable differences emerged: patients with univentricular hearts rated their physical capacity worse and showed a tendency towards negative ratings in other domains. On the other hand, patients after Fallot or TGA correction tended to rate their HRQoL in several domains as relatively high. Focusing on the mode of surgery for Fallot repair, respectively, TGA correction the only significant difference was found for "physical capacity" in TGA (atrial vs. arterial repair). Mustard patients tended to rate most items worse. Physical capacity was rated worst by patients with a Fontan circulation. Repeated surgery led to lower ratings for all domains except "physical capacity" and "body image". Different surgical techniques for CHD do not affect children's and adolescents' self-reported HRQoL to the extent that one would expect. This observation is in line with observations in groups of children with different chronic diseases. Specialised psychosocial support is necessary in order to maintain this positive self-evaluation and to ensure patients are able to lead autonomous personal and professional lives.

Health and Employment after Fifty (HEAF): a new prospective cohort study.

PubMed

Palmer, Keith T; Walker-Bone, Karen; Harris, E Clare; Linaker, Cathy; D'Angelo, Stefania; Sayer, Avan Aihie; Gale, Catharine R; Evandrou, Maria; van Staa, Tjeerd; Cooper, Cyrus; Coggon, David

2015-10-19

Demographic trends in developed countries have prompted governmental policies aimed at extending working lives. However, working beyond the traditional retirement age may not be feasible for those with major health problems of ageing, and depending on occupational and personal circumstances, might be either good or bad for health. To address these uncertainties, we have initiated a new longitudinal study. We recruited some 8000 adults aged 50-64 years from 24 British general practices contributing to the Clinical Practice Research Datalink (CPRD). Participants have completed questionnaires about their work and home circumstances at baseline, and will do so regularly over follow-up, initially for a 5-year period. With their permission, we will access their primary care health records via the CPRD. The inter-relation of changes in employment (with reasons) and changes in health (e.g., major new illnesses, new treatments, mortality) will be examined. CPRD linkage allows cost-effective frequent capture of detailed objective health data with which to examine the impact of health on work at older ages and of work on health. Findings will inform government policy and also the design of work for older people and the measures needed to support employment in later life, especially for those with health limitations.

Creating an index to measure health state of depressed patients in automated healthcare databases: the methodology

PubMed Central

François, Clément; Tanasescu, Adrian; Lamy, François-Xavier; Despiegel, Nicolas; Falissard, Bruno; Chalem, Ylana; Lançon, Christophe; Llorca, Pierre-Michel; Saragoussi, Delphine; Verpillat, Patrice; Wade, Alan G.; Zighed, Djamel A.

2017-01-01

ABSTRACT Background and objective: Automated healthcare databases (AHDB) are an important data source for real life drug and healthcare use. In the filed of depression, lack of detailed clinical data requires the use of binary proxies with important limitations. The study objective was to create a Depressive Health State Index (DHSI) as a continuous health state measure for depressed patients using available data in an AHDB. Methods: The study was based on historical cohort design using the UK Clinical Practice Research Datalink (CPRD). Depressive episodes (depression diagnosis with an antidepressant prescription) were used to create the DHSI through 6 successive steps: (1) Defining study design; (2) Identifying constituent parameters; (3) Assigning relative weights to the parameters; (4) Ranking based on the presence of parameters; (5) Standardizing the rank of the DHSI; (6) Developing a regression model to derive the DHSI in any other sample. Results: The DHSI ranged from 0 (worst) to 100 (best health state) comprising 29 parameters. The proportion of depressive episodes with a remission proxy increased with DHSI quartiles. Conclusion: A continuous outcome for depressed patients treated by antidepressants was created in an AHDB using several different variables and allowed more granularity than currently used proxies. PMID:29081921

High-spatial-resolution electron density measurement by Langmuir probe for multi-point observations using tiny spacecraft

NASA Astrophysics Data System (ADS)

Hoang, H.; Røed, K.; Bekkeng, T. A.; Trondsen, E.; Clausen, L. B. N.; Miloch, W. J.; Moen, J. I.

2017-11-01

A method for evaluating electron density using a single fixed-bias Langmuir probe is presented. The technique allows for high-spatio-temporal resolution electron density measurements, which can be effectively carried out by tiny spacecraft for multi-point observations in the ionosphere. The results are compared with the multi-needle Langmuir probe system, which is a scientific instrument developed at the University of Oslo comprising four fixed-bias cylindrical probes that allow small-scale plasma density structures to be characterized in the ionosphere. The technique proposed in this paper can comply with the requirements of future small-sized spacecraft, where the cost-effectiveness, limited space available on the craft, low power consumption and capacity for data-links need to be addressed. The first experimental results in both the plasma laboratory and space confirm the efficiency of the new approach. Moreover, detailed analyses on two challenging issues when deploying the DC Langmuir probe on a tiny spacecraft, which are the limited conductive area of the spacecraft and probe surface contamination, are presented in the paper. It is demonstrated that the limited conductive area, depending on applications, can either be of no concern for the experiment or can be resolved by mitigation methods. Surface contamination has a small impact on the performance of the developed probe.

Use of a Data-Linked Weather Information Display and Effects on Pilot Navigation Decision Making in a Piloted Simulation Study

NASA Technical Reports Server (NTRS)

Yuchnovicz, Daniel E.; Novacek, Paul F.; Burgess, Malcolm A.; Heck, Michael L.; Stokes, Alan F.

2001-01-01

This study provides recommendations to the FAA and to prospective manufacturers based on an exploration of the effects of data link weather displays upon pilot decision performance. An experiment was conducted with twenty-four current instrument rated pilots who were divided into two equal groups and presented with a challenging but realistic flight scenario involving weather containing significant embedded convective activity. All flights were flown in a full-mission simulation facility within instrument meteorological conditions. The inflight weather display depicted NexRad images, graphical METARs and textual METARs. The objective was to investigate the potential for misuse of a weather display, and incorporate recommendations for the design and use of these displays. The primary conclusion of the study found that the inflight weather display did not improve weather avoidance decision making. Some of the reasons to support this finding include: the pilot's inability to easily perceive their proximity to the storms, increased workload and difficulty in deciphering METAR textual data. The compelling nature of a graphical weather display caused many pilots to reduce their reliance on corroborating weather information from other sources. Minor changes to the weather display could improve the ability of a pilot to make better decisions on hazard avoidance.

Near field magnetic communications for helmet-mounted display applications

NASA Astrophysics Data System (ADS)

Field, Mark; Sailer, Alan

2005-05-01

Helmet-mounted displays need a data feed that is typically provided by a cable or RF wireless data link to an external computer. In defense applications these solutions are problematic: a cable gets in the way and restricts use and emergency egress, while an RF wireless link can be detected at some distance giving away position and is susceptible to jamming. What is required is an alternative wireless technology that is low power, extremely localized and difficult to detect or jam. Near field magnetic communications is one possible alternative to RF communications that may fulfill these needs. This technology uses a time varying magnetic field to carry information, and is only useable over small distances of order six feet. This is expected to have significant advantages for particular applications: notably power requirements and security compared with RF wireless links. The power stored in a magnetic field falls off as 1/r6, compared with 1/r2 for RF, which means that all the power is localized around the transmitter. By having a physically small communications region around each platform or user, a large bandwidth can be guaranteed by allowing the reuse of the frequency spectrum outside the immediate vicinity. It also confers security on the data-link, as the signal is undetectable beyond the short range of the system.

Knowledge-based processing for aircraft flight control

NASA Technical Reports Server (NTRS)

Painter, John H.

1991-01-01

The purpose is to develop algorithms and architectures for embedding artificial intelligence in aircraft guidance and control systems. With the approach adopted, AI-computing is used to create an outer guidance loop for driving the usual aircraft autopilot. That is, a symbolic processor monitors the operation and performance of the aircraft. Then, based on rules and other stored knowledge, commands are automatically formulated for driving the autopilot so as to accomplish desired flight operations. The focus is on developing a software system which can respond to linguistic instructions, input in a standard format, so as to formulate a sequence of simple commands to the autopilot. The instructions might be a fairly complex flight clearance, input either manually or by data-link. Emphasis is on a software system which responds much like a pilot would, employing not only precise computations, but, also, knowledge which is less precise, but more like common-sense. The approach is based on prior work to develop a generic 'shell' architecture for an AI-processor, which may be tailored to many applications by describing the application in appropriate processor data bases (libraries). Such descriptions include numerical models of the aircraft and flight control system, as well as symbolic (linguistic) descriptions of flight operations, rules, and tactics.

Defining the ATC Controller Interface for Data Link Clearances

NASA Technical Reports Server (NTRS)

Rankin, James

1998-01-01

The Controller Interface (CI) is the primary method for Air Traffic Controllers to communicate with aircraft via Controller-Pilot Data Link Communications (CPDLC). The controller, wearing a microphone/headset, aurally gives instructions to aircraft as he/she would with today's voice radio systems. The CI's voice recognition system converts the instructions to digitized messages that are formatted according to the RTCA DO-219 Operational Performance Standards for ATC Two-Way Data Link Communications. The DO-219 messages are transferred via RS-232 to the ATIDS system for uplink using a Mode-S datalink. Pilot acknowledgments of controller messages are downlinked to the ATIDS system and transferred to the Cl. A computer monitor is used to convey information to the controller. Aircraft data from the ARTS database are displayed on flight strips. The flight strips are electronic versions of the strips currently used in the ATC system. Outgoing controller messages cause the respective strip to change color to indicate an unacknowledged transmission. The message text is shown on the flight strips for reference. When the pilot acknowledges the message, the strip returns to its normal color. A map of the airport can also be displayed on the monitor. In addition to voice recognition, the controller can enter messages using the monitor's touch screen or by mouse/keyboard.

Method for detecting and avoiding flight hazards

NASA Astrophysics Data System (ADS)

von Viebahn, Harro; Schiefele, Jens

1997-06-01

Today's aircraft equipment comprise several independent warning and hazard avoidance systems like GPWS, TCAS or weather radar. It is the pilot's task to monitor all these systems and take the appropriate action in case of an emerging hazardous situation. The developed method for detecting and avoiding flight hazards combines all potential external threats for an aircraft into a single system. It is based on an aircraft surrounding airspace model consisting of discrete volume elements. For each element of the volume the threat probability is derived or computed from sensor output, databases, or information provided via datalink. The position of the own aircraft is predicted by utilizing a probability distribution. This approach ensures that all potential positions of the aircraft within the near future are considered while weighting the most likely flight path. A conflict detection algorithm initiates an alarm in case the threat probability exceeds a threshold. An escape manoeuvre is generated taking into account all potential hazards in the vicinity, not only the one which caused the alarm. The pilot gets a visual information about the type, the locating, and severeness o the threat. The algorithm was implemented and tested in a flight simulator environment. The current version comprises traffic, terrain and obstacle hazards avoidance functions. Its general formulation allows an easy integration of e.g. weather information or airspace restrictions.

Fusion of imaging and nonimaging data for surveillance aircraft

NASA Astrophysics Data System (ADS)

Shahbazian, Elisa; Gagnon, Langis; Duquet, Jean Remi; Macieszczak, Maciej; Valin, Pierre

1997-06-01

This paper describes a phased incremental integration approach for application of image analysis and data fusion technologies to provide automated intelligent target tracking and identification for airborne surveillance on board an Aurora Maritime Patrol Aircraft. The sensor suite of the Aurora consists of a radar, an identification friend or foe (IFF) system, an electronic support measures (ESM) system, a spotlight synthetic aperture radar (SSAR), a forward looking infra-red (FLIR) sensor and a link-11 tactical datalink system. Lockheed Martin Canada (LMCan) is developing a testbed, which will be used to analyze and evaluate approaches for combining the data provided by the existing sensors, which were initially not designed to feed a fusion system. Three concurrent research proof-of-concept activities provide techniques, algorithms and methodology into three sequential phases of integration of this testbed. These activities are: (1) analysis of the fusion architecture (track/contact/hybrid) most appropriate for the type of data available, (2) extraction and fusion of simple features from the imaging data into the fusion system performing automatic target identification, and (3) development of a unique software architecture which will permit integration and independent evolution, enhancement and optimization of various decision aid capabilities, such as multi-sensor data fusion (MSDF), situation and threat assessment (STA) and resource management (RM).

Contingency Management with Human Autonomy Teaming

NASA Technical Reports Server (NTRS)

Shively, Robert J.; Lachter, Joel B.

2018-01-01

Automation is playing an increasingly important role in many operations. It is often cheaper faster and more precise than human operators. However, automation is not perfect. There are many situations in which a human operator must step in. We refer to these instances as contingencies and the act of stepping in contingency management. Here we propose coupling Human Autonomy Teaming (HAT) with contingency management. We describe two aspects to HAT, bi-directional communication, and working agreements (or plays). Bi-directional communication like Crew Resource Management in traditional aviation, allows all parties to contribute to a decision. Working agreements specify roles and responsibilities. Importantly working agreements allow for the possibility of roles and responsibilities changing depending on environmental factors (e.g., situations the automation was not designed for, workload, risk, or trust). This allows for the automation to "automatically" become more autonomous as it becomes more trusted and/or it is updated to deal with a more complete set of possible situations. We present a concrete example using a prototype contingency management station one might find in a future airline operations center. Automation proposes reroutes for aircraft that encounter bad weather or are forced to divert for environmental or systems reasons. If specific conditions are met, these recommendations may be autonomously datalinked to the affected aircraft.

Implications of lower risk thresholds for statin treatment in primary prevention: analysis of CPRD and simulation modelling of annual cholesterol monitoring.

PubMed

McFadden, Emily; Stevens, Richard; Glasziou, Paul; Perera, Rafael

2015-01-01

To estimate numbers affected by a recent change in UK guidelines for statin use in primary prevention of cardiovascular disease. We modelled cholesterol ratio over time using a sample of 45,151 men (≥40years) and 36,168 women (≥55years) in 2006, without statin treatment or previous cardiovascular disease, from the Clinical Practice Research Datalink. Using simulation methods, we estimated numbers indicated for new statin treatment, if cholesterol was measured annually and used in the QRISK2 CVD risk calculator, using the previous 20% and newly recommended 10% thresholds. We estimate that 58% of men and 55% of women would be indicated for treatment by five years and 71% of men and 73% of women by ten years using the 20% threshold. Using the proposed threshold of 10%, 84% of men and 90% of women would be indicated for treatment by 5years and 92% of men and 98% of women by ten years. The proposed change of risk threshold from 20% to 10% would result in the substantial majority of those recommended for cholesterol testing being indicated for statin treatment. Implications depend on the value of statins in those at low to medium risk, and whether there are harms. Copyright © 2014. Published by Elsevier Inc.

Voltage-Gated Proton Channels: Molecular Biology, Physiology, and Pathophysiology of the HV Family

PubMed Central

2013-01-01

Voltage-gated proton channels (HV) are unique, in part because the ion they conduct is unique. HV channels are perfectly selective for protons and have a very small unitary conductance, both arguably manifestations of the extremely low H+ concentration in physiological solutions. They open with membrane depolarization, but their voltage dependence is strongly regulated by the pH gradient across the membrane (ΔpH), with the result that in most species they normally conduct only outward current. The HV channel protein is strikingly similar to the voltage-sensing domain (VSD, the first four membrane-spanning segments) of voltage-gated K+ and Na+ channels. In higher species, HV channels exist as dimers in which each protomer has its own conduction pathway, yet gating is cooperative. HV channels are phylogenetically diverse, distributed from humans to unicellular marine life, and perhaps even plants. Correspondingly, HV functions vary widely as well, from promoting calcification in coccolithophores and triggering bioluminescent flashes in dinoflagellates to facilitating killing bacteria, airway pH regulation, basophil histamine release, sperm maturation, and B lymphocyte responses in humans. Recent evidence that hHV1 may exacerbate breast cancer metastasis and cerebral damage from ischemic stroke highlights the rapidly expanding recognition of the clinical importance of hHV1. PMID:23589829