Sick sinus syndrome

MedlinePlus

... the heart (atria). This area is the heart's pacemaker. It may be called the sinoatrial node, sinus ... do so. You may need a permanent implanted pacemaker if your symptoms are related to bradycardia (slow ...

Expression and distribution of voltage-gated ion channels in ferret sinoatrial node.

PubMed

Brahmajothi, Mulugu V; Morales, Michael J; Campbell, Donald L; Steenbergen, Charles; Strauss, Harold C

2010-10-01

Spontaneous diastolic depolarization in the sinoatrial (SA) node enables it to serve as pacemaker of the heart. The variable cell morphology within the SA node predicts that ion channel expression would be heterogeneous and different from that in the atrium. To evaluate ion channel heterogeneity within the SA node, we used fluorescent in situ hybridization to examine ion channel expression in the ferret SA node region and atrial appendage. SA nodal cells were distinguished from surrounding cardiac myocytes by expression of the slow (SA node) and cardiac (surrounding tissue) forms of troponin I. Nerve cells in the sections were identified by detection of GAP-43 and cytoskeletal middle neurofilament. Transcript expression was characterized for the 4 hyperpolarization-activated cation channels, 6 voltage-gated Na(+) channels, 3 voltage-gated Ca(2+) channels, 24 voltage-gated K(+) channel α-subunits, and 3 ancillary subunits. To ensure that transcript expression was representative of protein expression, immunofluorescence was used to verify localization patterns of voltage-dependent K(+) channels. Colocalizations were performed to observe any preferential patterns. Some overlapping and nonoverlapping binding patterns were observed. Measurement of different cation channel transcripts showed heterogeneous expression with many different patterns of expression, attesting to the complexity of electrical activity in the SA node. This study provides insight into the possible role ion channel heterogeneity plays in SA node pacemaker activity.

Tachycardia | Fast Heart Rate

MedlinePlus

... sinoatrial (SA) node --- the heart's natural pacemaker. A series of early beats in the atria speeds up the heart rate. The rapid heartbeat does not allow enough time for the heart to fill before it contracts ...

Effects of hemicholinium and bretylium on the release of autonomic transmitters in the isolated sino-atrial node

PubMed Central

Appel, W. C.; Vincenzi, F. F.

1970-01-01

1. In the isolated, spontaneously beating, sino-atrial node of the rabbit selective electrical excitation of intranodal autonomic nerve fibres results in a biphasic chronotropic response. This chronotropic response (negative followed by positive chronotropism) is due to the release of the autonomic transmitters (acetylcholine and noradrenaline, respectively) from intranodal nerve fibres. 2. In the presence of 2 × 10-4 g/ml hemicholinium, the negative chronotropic (cholinergic) response is abolished while the positive chronotropic (adrenergic) response is unaltered. 3. In the presence of 5 × 10-6 g/ml bretylium, the positive chronotropic response is abolished while the negative chronotropic response is little affected. 4. After blockade of the negative chronotropic response by hemicholinium, bretylium abolishes the remaining positive chronotropic response. The effect of bretylium is not altered in the presence of hemicholinium. 5. Considering currently accepted mechanisms of action for hemicholinium and bretylium, the results of these experiments do not lend support to the cholinergic link hypothesis of adrenergic neuro-effector transmission. PMID:5492897

Effects of hemicholinium and bretylium on the release of autonomic transmitters in the isolated sino-atrial node.

PubMed

Appel, W C; Vincenzi, F F

1970-10-01

1. In the isolated, spontaneously beating, sino-atrial node of the rabbit selective electrical excitation of intranodal autonomic nerve fibres results in a biphasic chronotropic response. This chronotropic response (negative followed by positive chronotropism) is due to the release of the autonomic transmitters (acetylcholine and noradrenaline, respectively) from intranodal nerve fibres.2. In the presence of 2 x 10(-4) g/ml hemicholinium, the negative chronotropic (cholinergic) response is abolished while the positive chronotropic (adrenergic) response is unaltered.3. In the presence of 5 x 10(-6) g/ml bretylium, the positive chronotropic response is abolished while the negative chronotropic response is little affected.4. After blockade of the negative chronotropic response by hemicholinium, bretylium abolishes the remaining positive chronotropic response. The effect of bretylium is not altered in the presence of hemicholinium.5. Considering currently accepted mechanisms of action for hemicholinium and bretylium, the results of these experiments do not lend support to the cholinergic link hypothesis of adrenergic neuro-effector transmission.

Oxidized CaMKII causes cardiac sinus node dysfunction in mice

PubMed Central

Swaminathan, Paari Dominic; Purohit, Anil; Soni, Siddarth; Voigt, Niels; Singh, Madhu V.; Glukhov, Alexey V.; Gao, Zhan; He, B. Julie; Luczak, Elizabeth D.; Joiner, Mei-ling A.; Kutschke, William; Yang, Jinying; Donahue, J. Kevin; Weiss, Robert M.; Grumbach, Isabella M.; Ogawa, Masahiro; Chen, Peng-Sheng; Efimov, Igor; Dobrev, Dobromir; Mohler, Peter J.; Hund, Thomas J.; Anderson, Mark E.

2011-01-01

Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress. Here, we show that oxidized calmodulin kinase II (ox-CaMKII) is a biomarker for SND in patients and dogs and a disease determinant in mice. In wild-type mice, Ang II infusion caused sinoatrial nodal (SAN) cell oxidation by activating NADPH oxidase, leading to increased ox-CaMKII, SAN cell apoptosis, and SND. p47–/– mice lacking functional NADPH oxidase and mice with myocardial or SAN-targeted CaMKII inhibition were highly resistant to SAN apoptosis and SND, suggesting that ox-CaMKII–triggered SAN cell death contributed to SND. We developed a computational model of the sinoatrial node that showed that a loss of SAN cells below a critical threshold caused SND by preventing normal impulse formation and propagation. These data provide novel molecular and mechanistic information to understand SND and suggest that targeted CaMKII inhibition may be useful for preventing SND in high-risk patients. PMID:21785215

Inhibitory effects of sevoflurane on pacemaking activity of sinoatrial node cells in guinea-pig heart

PubMed Central

Kojima, Akiko; Kitagawa, Hirotoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Nosaka, Shuichi

2012-01-01

BACKGROUND AND PURPOSE The volatile anaesthetic sevoflurane affects heart rate in clinical settings. The present study investigated the effect of sevoflurane on sinoatrial (SA) node automaticity and its underlying ionic mechanisms. EXPERIMENTAL APPROACH Spontaneous action potentials and four ionic currents fundamental for pacemaking, namely, the hyperpolarization-activated cation current (If), T-type and L-type Ca2+ currents (ICa,T and ICa,L, respectively), and slowly activating delayed rectifier K+ current (IKs), were recorded in isolated guinea-pig SA node cells using perforated and conventional whole-cell patch-clamp techniques. Heart rate in guinea-pigs was recorded ex vivo in Langendorff mode and in vivo during sevoflurane inhalation. KEY RESULTS In isolated SA node cells, sevoflurane (0.12–0.71 mM) reduced the firing rate of spontaneous action potentials and its electrical basis, diastolic depolarization rate, in a qualitatively similar concentration-dependent manner. Sevoflurane (0.44 mM) reduced spontaneous firing rate by approximately 25% and decreased If, ICa,T, ICa,L and IKs by 14.4, 31.3, 30.3 and 37.1%, respectively, without significantly affecting voltage dependence of current activation. The negative chronotropic effect of sevoflurane was partly reproduced by a computer simulation of SA node cell electrophysiology. Sevoflurane reduced heart rate in Langendorff-perfused hearts, but not in vivo during sevoflurane inhalation in guinea-pigs. CONCLUSIONS AND IMPLICATIONS Sevoflurane at clinically relevant concentrations slowed diastolic depolarization and thereby reduced pacemaking activity in SA node cells, at least partly due to its inhibitory effect on If, ICa,T and ICa,L. These findings provide an important electrophysiological basis of alterations in heart rate during sevoflurane anaesthesia in clinical settings. PMID:22356456

TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling.

PubMed

Zhong, Hongbin; Wang, Tingjun; Lian, Guili; Xu, Changsheng; Wang, Huajun; Xie, Liangdi

2018-03-06

Sinoatrial node fibrosis is involved in the pathogenesis of sinus sick syndrome (SSS). Transient receptor potential (TRP) subfamily M member 7 (TRPM7) is implicated in cardiac fibrosis. However, the mechanisms underlying the regulation of sinoatrial node (SAN) fibrosis in SSS by TRPM7 remain unknown. The aim of this study was to investigate the role of angiotensin II (Ang II)/TRPM7/Smad pathway in the SAN fibrosis in rats with SSS. The rat SSS model was established with sodium hydroxide pinpoint pressing permeation. Forty-eight rats were randomly divided into six groups: normal control (ctrl), sham operation (sham), postoperative 1-, 2-, 3-, and 4-week SSS, respectively. The tissue explant culture method was used to culture cardiac fibroblasts (CFs) from rat SAN tissues. TRPM7 siRNA or encoding plasmids were used to knock down or overexpress TRPM7. Collagen (Col) distribution in SAN and atria was assessed using PASM-Masson staining. Ang II, Col I, and Col III levels in serum and tissues or in CFs were determined by ELISA. TRPM7, smad2 and p-smad2 levels were evaluated by real-time PCR, and/or western blot and immunohistochemistry. SAN and atria in rats of the SSS groups had more fibers and higher levels of Ang II, Col I and III than the sham rats. Similar findings were obtained for TRPM7 and pSmad2 expression. In vitro, Ang II promoted CFs collagen synthesis in a dose-dependent manner, and potentiated TRPM7 and p-Smad2 expression. TRPM7 depletion inhibited Ang II-induced p-Smad2 expression and collagen synthesis in CFs, whereas increased TRPM7 expression did the opposite. SAN fibrosis is regulated by the Ang II/TRPM7/Smad pathway in SSS, indicating that TRPM7 is a potential target for SAN fibrosis therapy in SSS.

Expression of key ion channels in the rat cardiac conduction system by laser capture microdissection and quantitative real-time PCR.

PubMed

Ou, Yan; Niu, Xiao-lin; Ren, Fu-xian

2010-09-01

The objective of this study was to investigate the molecular basis of the inferior nodal extension (INE) in the atrioventricular junctional area that accounts for arrhythmias. The INE was separated from the adult rat heart by laser capture microdissection. The mRNA expression of ion channels was detected by quantitative real-time PCR. Hierarchical clustering was used to demonstrate clustering of expression of genes in sections. The mRNA expression of HCN4, Ca(v)3.1 and Ca(v)3.2 was high in the INE, atrioventricular node and sino-atrial node, and that of Ca(v)3.2 high in Purkinje fibres. Although the expression of HCN1 and Ca(v)1.3 was low in the rat heart, it was relatively higher in the INE, atrioventricular node and sino-atrial node than in right atrial and right ventricular (working) myocytes. Both HCN2 and Ca(v)1.2 were expressed at higher levels in working myocytes than in nodal tissues and in the INE. Hierarchical clustering analysis demonstrated that the expression of the HCN and calcium channels in INE was similar to that in the slow-response automatic cells and different from that in working myocytes and Purkinje fibres. The expression of HCN and calcium channels in the INE of the adult rat heart is similar to that of slow-response automatic cells and provides a substrate for automatic phase 4 depolarization in cells.

Ion Channels in the Heart

PubMed Central

Bartos, Daniel C.; Grandi, Eleonora; Ripplinger, Crystal M.

2015-01-01

Optimal cardiac function depends on proper timing of excitation and contraction in various regions of the heart, as well as on appropriate heart rate. This is accomplished via specialized electrical properties of various components of the system, including the sinoatrial node, atria, atrioventricular node, His-Purkinje system, and ventricles. Here we review the major regionally-determined electrical properties of these cardiac regions and present the available data regarding the molecular and ionic bases of regional cardiac function and dysfunction. Understanding these differences is of fundamental importance for the investigation of arrhythmia mechanisms and pharmacotherapy. PMID:26140724

Caffeine depression of spontaneous activity in rabbit sino-atrial node cells.

PubMed

Satoh, H

1993-05-01

1. Effects of caffeine on the action potentials and the membrane currents in spontaneously beating rabbit sino-atrial (SA) node cells were examined using a two-microelectrode technique. 2. Cumulative administrations of caffeine (1-10 mM) caused a negative chronotropic effect in a concentration-dependent manner, which was not modified by atropine (0.1 microM). At 10 mM, caffeine increased the amplitude and prolonged the duration of action potentials significantly; the other parameters were unaffected. 3. In 3 of 16 preparations, caffeine (5 mM) elicited arrhythmia. At high Ca2+ (8.1 mM), caffeine (5 mM) increased the incidence of arrhythmia. 4. Caffeine (0.5-10 mM) enhanced the slow inward current, but at 10 mM decreased the enhanced peak current by 5 mM. The hyperpolarization-activated inward current was also enhanced by caffeine, but 10 mM caffeine decreased the current peak as compared with that at 5 mM. In addition, caffeine inhibited the delayed rectifying outward current in a concentration-dependent manner, accompanied by a depressed activation curve without any shift in the half-maximum activation voltage. 5. Caffeine elevated the cytoplasmic Ca2+ level in the SA node cells loaded with Ca(2+)-sensitive fluorescent dye (fura-2). 6. These results suggest that caffeine enhances and/or inhibits the ionic currents and elicits arrhythmia due to the induction of cellular calcium overload.

Klotho protein lowered in senile patients with brady sinus arrhythmia.

PubMed

Wang, Ying; Yang, Wei; Zheng, Ernv; Zhang, Wei; Su, Xianming

2015-01-01

To explore the correlationship between brady sinus arrhythmia and the levels of serum klotho protein in aged. 104 patients over 75 years old with brady sinus arrhythmia (experiment group) were enrolled, including 34 cases of sinus arrest, 43 cases of sinus bradycardia and 25 cases of atrioventricular block. 109 patients over 75 years old without brady sinus arrhymia were chosen as control group. All subjects were monitored by Holter. The levels of serum klotho protein were detected and compared among three groups. The correlation between the frequency of sinus arrest and the levels of serum klotho protein was analyzed simultaneously. The levels of serum klotho protein in experiment group were lower than that in control group (P<0.01); the sinus arrest frequency was negatively correlated with the levels of serum klotho protien. The levels of serum klotho protein in patients with sinus arrest were lower than that with sinus bradycardia and atrioventricularblock (P<0.05). But there was no significant difference between sinus bradycardia group and atrioventricular block group. The levels of serum klotho protein may reflect the function of sinoatrial node and could be used as an index to estimate the function of sinoatrial node.

Klotho protein lowered in senile patients with brady sinus arrhythmia

PubMed Central

Wang, Ying; Yang, Wei; Zheng, Ernv; Zhang, Wei; Su, Xianming

2015-01-01

Objective: To explore the correlationship between brady sinus arrhythmia and the levels of serum klotho protein in aged. Methods: 104 patients over 75 years old with brady sinus arrhythmia (experiment group) were enrolled, including 34 cases of sinus arrest, 43 cases of sinus bradycardia and 25 cases of atrioventricular block. 109 patients over 75 years old without brady sinus arrhymia were chosen as control group. All subjects were monitored by Holter. The levels of serum klotho protein were detected and compared among three groups. The correlation between the frequency of sinus arrest and the levels of serum klotho protein was analyzed simultaneously. Results: The levels of serum klotho protein in experiment group were lower than that in control group (P<0.01); the sinus arrest frequency was negatively correlated with the levels of serum klotho protien. The levels of serum klotho protein in patients with sinus arrest were lower than that with sinus bradycardia and atrioventricularblock (P<0.05). But there was no significant difference between sinus bradycardia group and atrioventricular block group. Conclusion: The levels of serum klotho protein may reflect the function of sinoatrial node and could be used as an index to estimate the function of sinoatrial node. PMID:26550342

Role of sinoatrial node architecture in maintaining a balanced source-sink relationship and synchronous cardiac pacemaking

PubMed Central

Unudurthi, Sathya D.; Wolf, Roseanne M.; Hund, Thomas J.

2014-01-01

Normal heart rhythm (sinus rhythm) depends on regular activity of the sinoatrial node (SAN), a heterogeneous collection of specialized myocytes in the right atrium. SAN cells, in general, possess a unique electrophysiological profile that promotes spontaneous electrical activity (automaticity). However, while automaticity is required for normal pacemaking, it is not necessarily sufficient. Less appreciated is the importance of the elaborate structure of the SAN complex for proper pacemaker function. Here, we review the important structural features of the SAN with a focus on how these elements help manage a precarious balance between electrical charge generated by the SAN (“source”) and the charge needed to excite the surrounding atrial tissue (“sink”). We also discuss how compromised “source-sink” balance due, for example to fibrosis, may promote SAN dysfunction, characterized by slow and/or asynchronous pacemaker activity and even failure, in the setting of cardiovascular disease (e.g., heart failure, atrial fibrillation). Finally, we discuss implications of the “source-sink” balance in the SAN complex for cell and gene therapies aimed at creating a biological pacemaker as replacement or bridge to conventional electronic pacemakers. PMID:25505419

Long-Term Effects of Atrial Ganglionated Plexi Ablation on Function and Structure of Sinoatrial and Atrioventricular Node in Canine.

PubMed

Zhang, Ming; Wang, Ximin; Xie, Xinxing; Wang, Zhongsu; Liu, Xiaoyan; Guan, Juan; Wang, Weizong; Li, Zhan; Wang, Jiangrong; Gao, Mei; Hou, Yinglong

2015-10-01

Long-term effects of ganglionated plexi (GP) ablation on sinoatrial node (SAN) and atrioventricular node (AVN) remain unclear. This study is to investigate the long-term effects of ablation of cardiac anterior right GP (ARGP) and inferior right GP (IRGP) on function and structure of SAN and AVN in canine. Thirty-two dogs were randomly divided into an operated group (n = 24) and sham-operated group (n = 8). ARGP and IRGP were ablated in operated group which was randomly divided into three subgroups according to the period of evaluation after operation (1 month, 6 months, 12 months). The functional and histological characteristics of SAN and AVN, as well as the expression of connexin (Cx) 43 and Cx 45 in SAN and AVN, were evaluated before and after ablation. Resting heart rate was increased and AVN effective refractory period was prolonged and sinus node recovery time (SNRT) and corrected SNRT were shortened immediately after ablation. These changes were reverted to preablation level after 1 month. At 1 month, ventricular rate during atrial fibrillation was slowed, atria-His intervals were prolonged, and Cx43 and Cx45 expression in SAN and AVN were downregulated. At 6 months, all changes were reverted to preablation level. The histological characteristics of SAN and AVN did not change. Ablation of ARGP and IRGP has short-term effects on function and structure of SAN and AVN rather than long-term effects, which suggests that ablation of ARGP and IRGP is safe. Atrioventricular conduction dysfunction after ablation may be related to downregulated Cx43 and Cx45 expression in AVN. © 2015 Wiley Periodicals, Inc.

Next-generation pacemakers: from small devices to biological pacemakers.

PubMed

Cingolani, Eugenio; Goldhaber, Joshua I; Marbán, Eduardo

2018-03-01

Electrogenesis in the heart begins in the sinoatrial node and proceeds down the conduction system to originate the heartbeat. Conduction system disorders lead to slow heart rates that are insufficient to support the circulation, necessitating implantation of electronic pacemakers. The typical electronic pacemaker consists of a subcutaneous generator and battery module attached to one or more endocardial leads. New leadless pacemakers can be implanted directly into the right ventricular apex, providing single-chamber pacing without a subcutaneous generator. Modern pacemakers are generally reliable, and their programmability provides options for different pacing modes tailored to specific clinical needs. Advances in device technology will probably include alternative energy sources and dual-chamber leadless pacing in the not-too-distant future. Although effective, current electronic devices have limitations related to lead or generator malfunction, lack of autonomic responsiveness, undesirable interactions with strong magnetic fields, and device-related infections. Biological pacemakers, generated by somatic gene transfer, cell fusion, or cell transplantation, provide an alternative to electronic devices. Somatic reprogramming strategies, which involve transfer of genes encoding transcription factors to transform working myocardium into a surrogate sinoatrial node, are furthest along in the translational pipeline. Even as electronic pacemakers become smaller and less invasive, biological pacemakers might expand the therapeutic armamentarium for conduction system disorders.

Effects of Nicotinamide Adenine Dinucleotide (NAD(+)) and Diadenosine Tetraphosphate (Ap4A) on Electrical Activity of Working and Pacemaker Atrial Myocardium in Guinea Pigs.

PubMed

Pustovit, K B; Abramochkin, D V

2016-04-01

Effects of nucleotide polyphosphate compounds (nicotinamide adenine dinucleotide, NAD(+); diadenosine tetraphosphate, Ap4A) on the confi guration of action potentials were studied in isolated preparations of guinea pig sinoatrial node and right atrial appendage (auricle). In the working myocardium, NAD(+) and Ap4A in concentrations of 10(-5) and 10(-4) M had no effect on resting potential, but significantly reduced the duration of action potentials; the most pronounced decrease was found at 25% repolarization. In the primary pacemaker of the sinoatrial node, both concentrations of NAD(+) and Ap4A induced hyperpolarization and reduction in the rate of slow diastolic depolarization, but significant slowing of the sinus rhythm was produced by these substances only in the concentration of 10(-4) M. Moreover, AP shortening and marked acceleration of AP upstroke were observed in the pacemaker myocardium after application of polyphosphates. Comparative analysis of the effects of NAD(+) and Ap4A in the working and pacemaker myocardium drove us to a hypothesis on inhibitory effects of these substances on L-type calcium current accompanied by stimulation of one or several potassium currents, which induce enhancement of repolarization and hyperpolarization of membranes probably mediated by the activation of purine receptors.

β1-Adrenergic blocker bisoprolol reverses down-regulated ion channels in sinoatrial node of heart failure rats.

PubMed

Du, Yuan; Zhang, Junbo; Xi, Yutao; Wu, Geru; Han, Ke; Huang, Xin; Ma, Aiqun; Wang, Tingzhong

2016-06-01

Bisoprolol, an antagonist of β1-adrenergic receptors, is effective in reducing the morbidity and mortality in patients with heart failure (HF). It has been found that HF is accompanied with dysfunction of the sinoatrial node (SAN). However, whether bisoprolol reverses the decreased SAN function in HF and how the relevant ion channels in SAN change were relatively less studied. SAN function and messenger RNA (mRNA) expression of sodium channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits were assessed in sham-operated rats, abdominal arterio-venous shunt (volume overload)-induced HF rats, and bisoprolol- treated HF rats. SAN cells of rats were isolated by laser capture microdissection. Quantitative real-time PCR analysis was used to quantify mRNA expression of sodium channels and HCN channel subunits in SAN. Intrinsic heart rate declined and sinus node recovery time prolonged in HF rats, indicating the suppressed SAN function, which could be improved by bisoprolol treatment. Nav1.1, Nav1.6, and HCN4 mRNA expressions were reduced in SAN in HF rats compared with that in control rats. Treatment with bisoprolol could reverse both the SAN function and the Nav1.1, Nav1.6, and HCN4 mRNA expression partially. These data indicated that bisoprolol is effective in HF treatment partially due to improved SAN function by reversing the down-regulation of sodium channels (Nav1.1 and Nav1.6) and HCN channel (HCN4) subunits in SAN in failing hearts.

Beat-to-Beat Variation in Periodicity of Local Calcium Releases Contributes to Intrinsic Variations of Spontaneous Cycle Length in Isolated Single Sinoatrial Node Cells

PubMed Central

Monfredi, Oliver; Maltseva, Larissa A.; Spurgeon, Harold A.; Boyett, Mark R.; Lakatta, Edward G.; Maltsev, Victor A.

2013-01-01

Spontaneous, submembrane local Ca2+ releases (LCRs) generated by the sarcoplasmic reticulum in sinoatrial nodal cells, the cells of the primary cardiac pacemaker, activate inward Na+/Ca2+-exchange current to accelerate the diastolic depolarization rate, and therefore to impact on cycle length. Since LCRs are generated by Ca2+ release channel (i.e. ryanodine receptor) openings, they exhibit a degree of stochastic behavior, manifested as notable cycle-to-cycle variations in the time of their occurrence. Aim The present study tested whether variation in LCR periodicity contributes to intrinsic (beat-to-beat) cycle length variability in single sinoatrial nodal cells. Methods We imaged single rabbit sinoatrial nodal cells using a 2D-camera to capture LCRs over the entire cell, and, in selected cells, simultaneously measured action potentials by perforated patch clamp. Results LCRs begin to occur on the descending part of the action potential-induced whole-cell Ca2+ transient, at about the time of the maximum diastolic potential. Shortly after the maximum diastolic potential (mean 54±7.7 ms, n = 14), the ensemble of waxing LCR activity converts the decay of the global Ca2+ transient into a rise, resulting in a late, whole-cell diastolic Ca2+ elevation, accompanied by a notable acceleration in diastolic depolarization rate. On average, cells (n = 9) generate 13.2±3.7 LCRs per cycle (mean±SEM), varying in size (7.1±4.2 µm) and duration (44.2±27.1 ms), with both size and duration being greater for later-occurring LCRs. While the timing of each LCR occurrence also varies, the LCR period (i.e. the time from the preceding Ca2+ transient peak to an LCR’s subsequent occurrence) averaged for all LCRs in a given cycle closely predicts the time of occurrence of the next action potential, i.e. the cycle length. Conclusion Intrinsic cycle length variability in single sinoatrial nodal cells is linked to beat-to-beat variations in the average period of individual LCRs each cycle. PMID:23826247

Comprehensive multilevel in vivo and in vitro analysis of heart rate fluctuations in mice by ECG telemetry and electrophysiology.

PubMed

Fenske, Stefanie; Pröbstle, Rasmus; Auer, Franziska; Hassan, Sami; Marks, Vanessa; Pauza, Danius H; Biel, Martin; Wahl-Schott, Christian

2016-01-01

The normal heartbeat slightly fluctuates around a mean value; this phenomenon is called physiological heart rate variability (HRV). It is well known that altered HRV is a risk factor for sudden cardiac death. The availability of genetic mouse models makes it possible to experimentally dissect the mechanism of pathological changes in HRV and its relation to sudden cardiac death. Here we provide a protocol that allows for a comprehensive multilevel analysis of heart rate (HR) fluctuations. The protocol comprises a set of techniques that include in vivo telemetry and in vitro electrophysiology of intact sinoatrial network preparations or isolated single sinoatrial node (SAN) cells. In vitro preparations can be completed within a few hours, with data acquisition within 1 d. In vivo telemetric ECG requires 1 h for surgery and several weeks for data acquisition and analysis. This protocol is of interest to researchers investigating cardiovascular physiology and the pathophysiology of sudden cardiac death.

Development of the cardiac pacemaker

PubMed Central

Liang, Xingqun; Evans, Sylvia M.

2017-01-01

The sinoatrial node (SAN) is the dominant pacemaker of the heart. Abnormalities in SAN formation and function can cause sinus arrhythmia, including sick sinus syndrome and sudden death. A better understanding of genes and signaling pathways that regulate SAN development and function is essential to develop more effective treatment to sinus arrhythmia, including biological pacemakers. In this review, we briefly summarize the key processes of SAN morphogenesis during development, and focus on the transcriptional network that drives SAN development. PMID:27770149

[Changes of heart electrophysiological parameters after destruction of epicardial subplexuses that innervate sinoatrial node].

PubMed

Kulboka, Arūnas; Veikutis, Vincentas; Pauza, Dainius Haroldas; Lekas, Raimundas

2003-01-01

The aims of present study were to verify the topography of the intracardiac nerve subplexuses (INS) by using electrophysiological methods, its relations with sinoatrial (SA) node function and to investigate possibility of selective surgical SA node denervation. Fifteen mongrel dogs of either sex weighing 8 to 15 kg were used for electrophysiological studies. Both cervical vagosympathetic trunks were isolated and crushed by tight ligatures. Nervus subplexuses destructions were performed by cryocoagulation in three zones located around the right superior vena cava: ventral, lateral and dorsal. The sinus rhythm, SA node function recovery time, AV node conductivity, AV node and atrial effective refractory period were measured. Five experiments in each of three zones were performed. Experimental data show that destruction of the epicardial nerves has different effect on electrophysiological parameters. After destruction of the anterior zone of the right atrium the sinus rhythm decreased on an average by 11.6%; SA node function recovery time prolonged by 7.2%; AV node conductivity decreased by 13.1%; AV node effective refractory period prolonged by 12.9% and atrial effective refractory period, by 10.9 %. Measurements of electrophysiological parameters after intravenous injection of atropine sulphate show that sinus rhythm decreased on an average by 23.4%; SA node function recovery time increased by 9.1%; the conductivity of AV node decreased by 10.2%; AV node effective refractory period prolonged by 15.4% and atrial effective refractory period, by 13.2%. After destruction of the intracardiac nerves of the lateral zone, the sinus rhythm decreased by 15.7%; SA node function recovery time increased by 16.3%; AV node conductivity decreased by 8.3%; AV node effective refractory period and atrial effective refractory period prolonged by 11.9% and 10.0%, respectively. After the atropine sulphate intravenous injection, the sinus rhythm decreased on an average by 7.1%, SA node function recovery time prolonged by 7.1%, AV conductivity decreased by 9.1%, AV node effective refractory period increased by 12.4%, and atrial effective refractory period prolonged by 12.5%. After destruction of the nerves in the dorsal zone the changes of electrophysiological parameters were opposite to those obtained after destruction of the nerve tracts in the anterior or lateral zones: the sinus rhythm increased on an average by 4.3%; SA node function recovery time shortened by 8.8%; AV conductivity increased by 9.7%; AV node and atrial effective refractory period decreased by 12.3% and 12.1%, respectively. After intravenous atropine sulphate infusion, sinus rhythm decreased on an average by 8.3%; SA node function recovery time prolonged by 9.6%; AV node conductivity decreased by 5%; AV node and atrial effective refractory period prolonged by 4.2% and 5.2%, respectively. The average changes of electrophysiological parameters before and after INS destruction shows that cryocoagulation of ventral and lateral zones eliminates the effects of sympathetic tone to SA and AV nodal activity. Cryocoagulation of dorsal zone eliminates the effects of nervus vagus to both nodal structures. These findings shows the possibility alter or correct SA node function by making selective surgical SA node denervation.

Carvedilol analog modulates both basal and stimulated sinoatrial node automaticity.

PubMed

Shinohara, Tetsuji; Kim, Daehyeok; Joung, Boyoung; Maruyama, Mitsunori; Vembaiyan, Kannan; Back, Thomas G; Wayne Chen, S R; Chen, Peng-Sheng; Lin, Shien-Fong

2014-05-01

The membrane voltage clock and calcium (Ca(2+)) clock jointly regulate sinoatrial node (SAN) automaticity. VK-II-36 is a novel carvedilol analog that suppresses sarcoplasmic reticulum (SR) Ca(2+) release but does not block the β-receptor. The effect of VK-II-36 on SAN function remains unclear. The purpose of this study was to evaluate whether VK-II-36 can influence SAN automaticity by inhibiting the Ca(2+) clock. We simultaneously mapped intracellular Ca(2+) and membrane potential in 24 isolated canine right atriums using previously described criteria of the timing of late diastolic intracellular Ca elevation (LDCAE) relative to the action potential upstroke to detect the Ca(2+) clock. Pharmacological interventions with isoproterenol (ISO), ryanodine, caffeine, and VK-II-36 were performed after baseline recordings. VK-II-36 caused sinus rate downregulation and reduced LDCAE in the pacemaking site under basal conditions (P < 0.01). ISO induced an upward shift of the pacemaking site in SAN and augmented LDCAE in the pacemaking site. ISO also significantly and dose-dependently increased the sinus rate. The treatment of VK-II-36 (30 μmol/l) abolished both the ISO-induced shift of the pacemaking site and augmentation of LDCAE (P < 0.01), and it suppressed the ISO-induced increase in sinus rate (P = 0.02). Our results suggest that the sinus rate may be partly controlled by the Ca(2+) clock via SR Ca(2+) release during β-adrenergic stimulation.

Carvedilol Analogue Modulates both Basal and Stimulated Sinoatrial Node Automaticity

PubMed Central

Shinohara, Tetsuji; Kim, Daehyeok; Joung, Boyoung; Maruyama, Mitsunori; Vembaiyan, Kannan; Back, Thomas G.; Chen, S.R. Wayne; Chen, Peng-Sheng; Lin, Shien-Fong

2013-01-01

Background The membrane voltage clock and calcium (Ca2+) clock jointly regulate sinoatrial node (SAN) automaticity. VK-II-36 is a novel carvedilol analog that suppress sarcoplasmic reticulum (SR) Ca2+ release but does not block β-receptor. The effect of VK-II-36 on SAN function remains unclear. The purpose of this study was to evaluate whether VK-II-36 can influence SAN automaticity through inhibiting the Ca2+ clock. Methods and Results We simultaneously mapped intracellular Ca2+ and membrane potential in 24 isolated canine right atriums, using previously described criteria of the timing of late diastolic intracellular Ca elevation (LDCAE) relative to the action potential upstroke to detect the Ca2+ clock. Pharmacological intervention with isoproterenol (ISO), ryanodine, caffeine, and VK-II-36 were performed after baseline recordings. VK-II-36 caused sinus rate downregulation and reduced LDCAE in the pacemaking site under basal condition (P<0.01). ISO induced an upward shift of the pacemaking site in SAN and augmented LDCAE in pacemaking site. ISO also significantly and dose-dependently increased the sinus rate. The treatment of VK-II-36 (30 μmol/L) abolished both the ISO-induced shift of pacemaking site and augmentation of LDCAE (P<0.01), and suppressed the ISO-induced increase in sinus rate (P=0.02). Conclusions Our results suggest that sinus rate may be partly controlled by Ca2+ clock via SR Ca2+ release during β-adrenergic stimulation. PMID:23836067

Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

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

Weinberger, Florian, E-mail: f.weinberger@uke.de; Mehrkens, Dennis, E-mail: dennis.mehrkens@uk-koeln.de; Starbatty, Jutta, E-mail: starbatty@uke.uni-hamburg.de

Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activitymore » and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.« less

If and SR Ca2+ release both contribute to pacemaker activity in canine sinoatrial node cells

PubMed Central

Gao, Zhan; Chen, Biyi; Joiner, Mei-ling A.; Wu, Yuejin; Guan, Xiaoqun; Koval, Olha M.; Chaudhary, Ashok K.; Cunha, Shane R.; Mohler, Peter J.; Martins, James B.; Song, Long-Sheng; Anderson, Mark E.

2010-01-01

Increasing evidence suggests that cardiac pacemaking is the result of two sinoatrial node (SAN) cell mechanisms: a ‘voltage clock’ and a Ca2+ dependent process, or ‘Ca2+ clock.’ The voltage clock initiates action potentials (APs) by SAN cell membrane potential depolarization from inward currents, of which the pacemaker current (If) is thought to be particularly important. A Ca2+ dependent process triggers APs when sarcoplasmic reticulum (SR) Ca2+ release activates inward current carried by the forward mode of the electrogenic Na+/Ca2+ exchanger (NCX). However, these mechanisms have mostly been defined in rodents or rabbits, but are unexplored in single SAN cells from larger animals. Here, we used patch-clamp and confocal microscope techniques to explore the roles of the voltage and Ca2+ clock mechanisms in canine SAN pacemaker cells. We found that ZD7288, a selective If antagonist, significantly reduced basal automaticity and induced irregular, arrhythmia-like activity in canine SAN cells. In addition, ZD7288 impaired but did not eliminate the SAN cell rate acceleration by isoproterenol. In contrast, ryanodine significantly reduced the SAN cell acceleration by isoproterenol, while ryanodine reduction of basal automaticity was modest (∼14%) and did not reach statistical significance. Importantly, pretreatment with ryanodine eliminated SR Ca2+ release, but did not affect basal or isoproterenol-enhanced If. Taken together, these results indicate that voltage and Ca2+ dependent automaticity mechanisms coexist in canine SAN cells, and suggest If and SR Ca2+ release cooperate to determine baseline and catecholamine-dependent automaticity in isolated dog SAN cells. PMID:20380837

Model for the respiratory modulation of the heart beat-to-beat time interval series

NASA Astrophysics Data System (ADS)

Capurro, Alberto; Diambra, Luis; Malta, C. P.

2005-09-01

In this study we present a model for the respiratory modulation of the heart beat-to-beat interval series. The model consists of a set of differential equations used to simulate the membrane potential of a single rabbit sinoatrial node cell, excited with a periodic input signal with added correlated noise. This signal, which simulates the input from the autonomous nervous system to the sinoatrial node, was included in the pacemaker equations as a modulation of the iNaK current pump and the potassium current iK. We focus at modeling the heart beat-to-beat time interval series from normal subjects during meditation of the Kundalini Yoga and Chi techniques. The analysis of the experimental data indicates that while the embedding of pre-meditation and control cases have a roughly circular shape, it acquires a polygonal shape during meditation, triangular for the Kundalini Yoga data and quadrangular in the case of Chi data. The model was used to assess the waveshape of the respiratory signals needed to reproduce the trajectory of the experimental data in the phase space. The embedding of the Chi data could be reproduced using a periodic signal obtained by smoothing a square wave. In the case of Kundalini Yoga data, the embedding was reproduced with a periodic signal obtained by smoothing a triangular wave having a rising branch of longer duration than the decreasing branch. Our study provides an estimation of the respiratory signal using only the heart beat-to-beat time interval series.

Knockdown of cardiac Kir3.1 gene with siRNA can improve bradycardia in an experimental sinus bradycardia rat model.

PubMed

Li, Yang; Fu, Xiaodan; Zhang, Zhi; Yu, Bo

2017-05-01

The objective of this study was to explore whether the inhibition of potassium inwardly rectifying channel (Kir3.1) with short interfering RNA (siRNA) can improve bradycardia in an experimental sinus bradycardia rat model. 54 Sprague Dawley (SD) rats were randomly divided into three groups: experimental group, control group, and sham group. Sinus bradycardia model was established in SD rats through chemical ablation of sinoatrial (SA) node with 20% formaldehyde. Variations of Kir3.1 expression at mRNA and protein level were examined with qPCR and Western blotting. Electrocardiograms (ECG) of rats at 3 days and 1, 2, 3, and 4 weeks after chemical ablation and lentivirus injection were recorded and differences were compared among the three groups. The differences among multiple groups were analyzed by one-way analysis of variance (ANOVA). It was found through RT-PCR and Western blot that the mRNA and protein levels of Kir3.1 at sinoatrial node areas were decreased by 42 ± 7% and 31 ± 7% in comparison with control group, respectively (P < 0.05 in both comparisons) after 4 weeks of chemical ablation/injection. Whole-cell patch clamp data showed that the lentiviral construct could significantly inhibit the potassium current of a muscarinic acetylcholine-sensitive K + channel, I KACh . ECG data showed that the heart rate of experimental group increased after 3 days of chemical ablation/injection and lasted for at least 4 weeks after the chemical ablation/injection (heart rate increased 15.4 ± 3.8% in comparison with control group, P < 0.05). Inhibition of Kir3.1 could rescue sinus bradycardia induced by chemical ablation of SA node with 20% formaldehyde at least partly through inhibiting I KACh channel.

Radiotherapy as a cause of complete atrioventricular block in Hodgkin's disease. An electrophysiological-pathological correlation

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

Cohen, S.I.; Bharati, S.; Glass, J.

1981-04-01

A 20-year-old man contracted Hodgkin's disease and was treated with mantle radiotherapy. Heart block developed 11 years later. Electrocardiograms revealed predominant atrioventricular (AV) block and occasional AV conduction. Intracardiac electrograms demonstrated that the site of AV block was above the level of the His bundle. A permanent transvenous pacemaker was implanted. Seven months later the patient died of complications from cryptococcal meningitis. Pathological study of the heart revealed marked arteriosclerosis with fibrosis of the epicardium, myocardium, and endocardium. Examination of the conduction system revealed extensive arteriolosclerosis of the sinoatrial node and its approaches. In addition, there was marked fibrosis ofmore » the approaches to the AV node, the AV bundle, and both bundle branches. There was no evidence of Hodgkin's disease. This case documents the rare occurrence of AV block due to tissue destruction by radiotherapy. There was a good correlation between block proximal to the His bundle recording site and fibrosis of the approaches to the AV node.« less

Radiotherapy as a cause of complete atrioventricular block in Hodgkin's disease: an electrophysiological-pathological correlation

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

Cohen, S.I.; Bharati, S.; Glass, J.

1981-04-01

A 20-year-old man contracted Hodgkin's disease and was treated with mantle radiotherapy. Heart block developed 11 years later. Electrocardiograms revealed predominant atrioventricular (AV) block and occasional AV conduction. Intracardiac electrograms demonstrated that the site of AV block was above the level of the His bundle. A permanent transvenous pacemaker was implanted. Seven months later the patient died of complications from cryptococcal meningitis. Pathological study of the heart revealed marked arteriosclerosis with fibrosis of the epicardium, myocardium, and endocardium. Examination of the conduction system revealed extensive arteriolosclerosis of the sinoatrial node and its approaches. In addition, there was marked fibrosis ofmore » the approaches to the AV node, the AV bundle, and both bundle branches. There was no evidence of Hodgkin's disease. This case documents the rare occurrence of AV block due to tissue destruction by radiotherapy. There was a good correlation between block proximal to the His bundle recording site and fibrosis of the approaches to the AV node.« less

Increasing T-type calcium channel activity by β-adrenergic stimulation contributes to β-adrenergic regulation of heart rates.

PubMed

Li, Yingxin; Zhang, Xiaoxiao; Zhang, Chen; Zhang, Xiaoying; Li, Ying; Qi, Zhao; Szeto, Christopher; Tang, Mingxin; Peng, Yizhi; Molkentin, Jeffery D; Houser, Steven R; Xie, Mingxing; Chen, Xiongwen

2018-04-01

Cav3.1 T-type Ca 2+ channel current (I Ca-T ) contributes to heart rate genesis but is not known to contribute to heart rate regulation by the sympathetic/β-adrenergic system (SAS). We show that the loss of Cav3.1 makes the beating rates of the heart in vivo and perfused hearts ex vivo, as well as sinoatrial node cells, less sensitive to β-adrenergic stimulation; it also renders less conduction acceleration through the atrioventricular node by β-adrenergic stimulation. Increasing Cav3.1 in cardiomyocytes has the opposite effects. I Ca-T in sinoatrial nodal cells can be upregulated by β-adrenergic stimulation. The results of the present study add a new contribution to heart rate regulation by the SAS system and provide potential new mechanisms for the dysregulation of heart rate and conduction by the SAS in the heart. T-type Ca 2+ channel can be a target for heart disease treatments that aim to slow down the heart rate ABSTRACT: Cav3.1 (α 1G ) T-type Ca 2+ channel (TTCC) is expressed in mouse sinoatrial node cells (SANCs) and atrioventricular (AV) nodal cells and contributes to heart rate (HR) genesis and AV conduction. However, its role in HR regulation and AV conduction acceleration by the β-adrenergic system (SAS) is unclear. In the present study, L- (I Ca-L ) and T-type (I Ca-T ) Ca 2+ currents were recorded in SANCs from Cav3.1 transgenic (TG) and knockout (KO), and control mice. I Ca-T was absent in KO SANCs but enhanced in TG SANCs. In anaesthetized animals, different doses of isoproterenol (ISO) were infused via the jugular vein and the HR was recorded. The EC 50 of the HR response to ISO was lower in TG mice but higher in KO mice, and the maximal percentage of HR increase by ISO was greater in TG mice but less in KO mice. In Langendorff-perfused hearts, ISO increased HR and shortened PR intervals to a greater extent in TG but to a less extent in KO hearts. KO SANCs had significantly slower spontaneous beating rates than control SANCs before and after ISO; TG SANCs had similar basal beating rates as control SANCs probably as a result of decreased I Ca-L but a greater response to ISO than control SANCs. I Ca-T in SANCs was significantly increased by ISO. I Ca-T upregulation by β-adrenergic stimulation contributes to HR and conduction regulation by the SAS. TTCC can be a target for slowing the HR. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

A comparison of the chronotropic and dromotropic actions between adenosine triphosphate and edrophonium in patients undergoing coronary artery bypass graft surgery.

PubMed

Watanabe, Seiji; Kono, Yasuo; Oishi-Tobinaga, Yoko; Yamada, Shin-ichi; Hara, Masato; Kano, Tatsuhiko

2002-10-01

To compare the effects of the stimulation of adenosine receptors and acetylcholine receptors in the cardiac conduction system in patients with ischemic heart disease. Prospective. University hospital. Patients scheduled for coronary artery bypass graft surgery (n = 37). The patients were divided into 3 groups: control group (n = 9), adenosine triphosphate (ATP) group (n = 12), and edrophonium group (n = 16). ATP (10 mg) or edrophonium (0.25 mg/kg) followed by saline or the same amount of saline was injected through a central venous catheter. ATP induced atrioventricular block in 10 of 12 patients (83%). The ATP injection produced a more prominent prolongation in the PQ duration (P-R interval) (139%) than in the P-P interval (105%) at the last beat before the development of atrioventricular block. The prolongation in the P-P interval (11%, average 85 msec) and PQ duration during atrioventricular block disappeared immediately after the restoration of atrioventricular conduction. After edrophonium, the maximal prolongation in P-P (118%, p < 0.01) and PQ (120%, p < 0.01) intervals was the same. P-P interval remained prolonged (p < 0.01) after PQ interval returned to baseline. Neither ATP nor edrophonium affected the QRS duration. These findings suggest that ATP predominantly inhibited atrioventricular conduction rather than the firing rate of sinoatrial nodes, and edrophonium inhibited both proportionally even with prolonged inhibitory action on the sinoatrial nodes. An injection of ATP is needed only when a transient cardiac standstill is requested, such as in endovascular grafting surgery. Edrophonium may be used to slow heart rate during coronary artery bypass graft surgery. Copyright 2002, Elsevier Science (USA). All rights reserved.

Remodeling of cardiac cholinergic innervation and control of heart rate in mice with streptozotocin-induced diabetes.

PubMed

Mabe, Abigail M; Hoover, Donald B

2011-07-05

Cardiac autonomic neuropathy is a frequent complication of diabetes and often presents as impaired cholinergic regulation of heart rate. Some have assumed that diabetics have degeneration of cardiac cholinergic nerves, but basic knowledge on this topic is lacking. Accordingly, our goal was to evaluate the structure and function of cardiac cholinergic neurons and nerves in C57BL/6 mice with streptozotocin-induced diabetes. Electrocardiograms were obtained weekly from conscious control and diabetic mice for 16 weeks. Resting heart rate decreased in diabetic mice, but intrinsic heart rate was unchanged. Power spectral analysis of electrocardiograms revealed decreased high frequency and increased low frequency power in diabetic mice, suggesting a relative reduction of parasympathetic tone. Negative chronotropic responses to right vagal nerve stimulation were blunted in 16-week diabetic mice, but postjunctional sensitivity of isolated atria to muscarinic agonists was unchanged. Immunohistochemical analysis of hearts from diabetic and control mice showed no difference in abundance of cholinergic neurons, but cholinergic nerve density was increased at the sinoatrial node of diabetic mice (16 weeks: 14.9±1.2% area for diabetics versus 8.9±0.8% area for control, P<0.01). We conclude that disruption of cholinergic function in diabetic mice cannot be attributed to a loss of cardiac cholinergic neurons and nerve fibers or altered cholinergic sensitivity of the atria. Instead, decreased responses to vagal stimulation might be caused by a defect of preganglionic cholinergic neurons and/or ganglionic neurotransmission. The increased density of cholinergic nerves observed at the sinoatrial node of diabetic mice might be a compensatory response. Copyright © 2011 Elsevier B.V. All rights reserved.

Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1

PubMed Central

Glukhov, Alexey V.; Kalyanasundaram, Anuradha; Lou, Qing; Hage, Lori T.; Hansen, Brian J.; Belevych, Andriy E.; Mohler, Peter J.; Knollmann, Björn C.; Periasamy, Muthu; Györke, Sandor; Fedorov, Vadim V.

2015-01-01

Aims Loss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study the sinoatrial node (SAN) dysfunction due to loss of CASQ2. Methods and results In vivo electrocardiogram (ECG) monitoring, in vitro high-resolution optical mapping, confocal imaging of intracellular Ca2+ cycling, and 3D atrial immunohistology were performed in wild-type (WT) and Casq2 null (Casq2−/−) mice. Casq2−/− mice exhibited bradycardia, SAN conduction abnormalities, and beat-to-beat heart rate variability due to enhanced atrial ectopic activity both at baseline and with autonomic stimulation. Loss of CASQ2 increased fibrosis within the pacemaker complex, depressed primary SAN activity, and conduction, but enhanced atrial ectopic activity and atrial fibrillation (AF) associated with macro- and micro-reentry during autonomic stimulation. In SAN myocytes, CASQ2 deficiency induced perturbations in intracellular Ca2+ cycling, including abnormal Ca2+ release, periods of significantly elevated diastolic Ca2+ levels leading to pauses and unstable pacemaker rate. Importantly, Ca2+ cycling dysfunction occurred not only at the SAN cellular level but was also globally manifested as an increased delay between action potential (AP) and Ca2+ transient upstrokes throughout the atrial pacemaker complex. Conclusions Loss of CASQ2 causes abnormal sarcoplasmic reticulum Ca2+ release and selective interstitial fibrosis in the atrial pacemaker complex, which disrupt SAN pacemaking but enhance latent pacemaker activity, create conduction abnormalities and increase susceptibility to AF. These functional and extensive structural alterations could contribute to SAN dysfunction as well as AF in CPVT patients. PMID:24216388

Repeated arterial occlusion, delta-opioid receptor (DOR) plasticity and vagal transmission within the sinoatrial node of the anesthetized dog.

PubMed

Deo, Shekhar H; Barlow, Matthew A; Gonzalez, Leticia; Yoshishige, Darice; Caffrey, James L

2009-01-01

Brief interruptions in coronary blood flow precondition the heart, engage delta-opioid receptor (DOR) mechanisms and reduce the damage that typically accompanies subsequent longer coronary occlusions. Repeated short occlusions of the sinoatrial (SA) node artery progressively raised nodal methionine-enkephalin-arginine-phenylalanine (MEAP) and improved vagal transmission during subsequent long occlusions in anesthetized dogs. The DOR type-1 (DOR-1) antagonist, BNTX reversed the vagotonic effect. Higher doses of enkephalin interrupted vagal transmission through a DOR-2 mechanism. The current study tested whether the preconditioning (PC) protocol, the later occlusion or a combination of both was required for the vagotonic effect. The study also tested whether evolving vagotonic effects included withdrawal of competing DOR-2 vagolytic influences. Vagal transmission progressively improved during successive SA nodal artery occlusions. The vagotonic effect was absent in sham animals and after DOR-1 blockade. After completing the PC protocol, exogenously applied vagolytic doses of MEAP reduced vagal transmission under both normal and occluded conditions. The magnitude of these DOR-2 vagolytic effects was small compared to controls and repeated MEAP challenges rapidly eroded vagolytic responses further. Prior DOR-1 blockade did not alter the PC mediated, progressive loss of DOR-2 vagolytic responses. In conclusion, DOR-1 vagotonic responses evolved from signals earlier in the PC protocol and erosion of competing DOR-2 vagolytic responses may have contributed to an unmasking of vagotonic responses. The data support the hypothesis that PC and DOR-2 stimulation promote DOR trafficking, and down regulation of the vagolytic DOR-2 phenotype in favor of the vagotonic DOR-1 phenotype. DOR-1 blockade may accelerate the process by sequestering newly emerging receptors.

A Parametric Computational Model of the Action Potential of Pacemaker Cells.

PubMed

Ai, Weiwei; Patel, Nitish D; Roop, Partha S; Malik, Avinash; Andalam, Sidharta; Yip, Eugene; Allen, Nathan; Trew, Mark L

2018-01-01

A flexible, efficient, and verifiable pacemaker cell model is essential to the design of real-time virtual hearts that can be used for closed-loop validation of cardiac devices. A new parametric model of pacemaker action potential is developed to address this need. The action potential phases are modeled using hybrid automaton with one piecewise-linear continuous variable. The model can capture rate-dependent dynamics, such as action potential duration restitution, conduction velocity restitution, and overdrive suppression by incorporating nonlinear update functions. Simulated dynamics of the model compared well with previous models and clinical data. The results show that the parametric model can reproduce the electrophysiological dynamics of a variety of pacemaker cells, such as sinoatrial node, atrioventricular node, and the His-Purkinje system, under varying cardiac conditions. This is an important contribution toward closed-loop validation of cardiac devices using real-time heart models.

Cross-correlation of heartbeat and respiration rhythms

NASA Astrophysics Data System (ADS)

Capurro, A.; Malta, C. P.; Diambra, L.; Contreras, P.; Migliaro, E. R.

2005-10-01

The cross-correlation function between respiration and heart beat interval series shows that during metronomized breathing the heart beat follows the respiration more closely than during spontaneous breathing. We reproduced the heart beat interval modulations during metronomized breathing using a biophysical model of the sinoatrial node excited by an input signal formed by the recorded respiration. In the case of spontaneous breathing, a good agreement with the experimental data was obtained only by using an input signal formed by the sum of the recorded respiration and a realization of correlated noise. Metronomized breathing refers to the situation where a subject breathes following the rhythm of a metronome.

A case of atrial tachycardia treated with ivabradine as bridge to ablation.

PubMed

Meles, Ester; Carbone, Claudio; Maggiolini, Stefano; Moretti, Paolo; DE Carlini, Caterina C; Gentile, Gaetano; Gnecchi-Ruscone, Tomaso

2015-05-01

Ivabradine is indicated in cardiac failure and ischemia to reduce sinus rate by inhibition of the pacemaker I(f) current in sinoatrial node. We report a case of an 18-year-old woman with left atrial tachyarrhythmia resistant to several antiarrhythmic drugs and to electric cardioversion who responded only to ivabradine, which significantly reduced heart rate without abolishing the arrhythmia itself. An ectopic focus in the ostium of left pulmonary veins was found and the patient was successfully ablated. We suggest that ivabradine might be therefore useful in the treatment of supraventricular tachyarrhythmias due to an enhanced automaticity. © 2015 Wiley Periodicals, Inc.

Computational analysis of the human sinus node action potential: model development and effects of mutations

PubMed Central

Fabbri, Alan; Fantini, Matteo; Wilders, Ronald

2017-01-01

Key points We constructed a comprehensive mathematical model of the spontaneous electrical activity of a human sinoatrial node (SAN) pacemaker cell, starting from the recent Severi–DiFrancesco model of rabbit SAN cells.Our model is based on electrophysiological data from isolated human SAN pacemaker cells and closely matches the action potentials and calcium transient that were recorded experimentally.Simulated ion channelopathies explain the clinically observed changes in heart rate in corresponding mutation carriers, providing an independent qualitative validation of the model.The model shows that the modulatory role of the ‘funny current’ (I f) in the pacing rate of human SAN pacemaker cells is highly similar to that of rabbit SAN cells, despite its considerably lower amplitude.The model may prove useful in the design of experiments and the development of heart‐rate modulating drugs. Abstract The sinoatrial node (SAN) is the normal pacemaker of the mammalian heart.  Over several decades, a large amount of data on the ionic mechanisms underlying the spontaneous electrical activity of SAN pacemaker cells has been obtained, mostly in experiments on single cells isolated from rabbit SAN. This wealth of data has allowed the development of mathematical models of the electrical activity of rabbit SAN pacemaker cells. The present study aimed to construct a comprehensive model of the electrical activity of a human SAN pacemaker cell using recently obtained electrophysiological data from human SAN pacemaker cells.  We based our model on the recent Severi–DiFrancesco model of a rabbit SAN pacemaker cell. The action potential and calcium transient of the resulting model are close to the experimentally recorded values. The model has a much smaller ‘funny current’ (I f) than do rabbit cells, although its modulatory role is highly similar. Changes in pacing rate upon the implementation of mutations associated with sinus node dysfunction agree with the clinical observations. This agreement holds for both loss‐of‐function and gain‐of‐function mutations in the HCN4, SCN5A and KCNQ1 genes, underlying ion channelopathies in I f, fast sodium current and slow delayed rectifier potassium current, respectively. We conclude that our human SAN cell model can be a useful tool in the design of experiments and the development of drugs that aim to modulate heart rate. PMID:28185290

Activity of cholinesterases of blood and heart in rats of different sex and age during muscular loads and hypokinesia

NASA Technical Reports Server (NTRS)

Rozanova, V. D.; Antonova, G. A.

1979-01-01

The activity of acetylcholinesterase (Ache) and butyrilcholinesterase (Bche) in the blood and the heart of 3 and 13 month old control male rats is considerably lower than in female rats. In 25 month old rats, no sex differences in the Ache and Bche were revealed in the heart. In 3 and 13 month old male and female rats, under conditions of muscular exercises, the Ache and Bche activity is lower, and in hypokinetic male rats -- higher than that in respective control animals. In all the rats, irrespective of sex, age, and motor conditions, Ache and Bche activity tended to decrease from the sinoatrial node to the heart apex.

The natriuretic peptides BNP and CNP increase heart rate and electrical conduction by stimulating ionic currents in the sinoatrial node and atrial myocardium following activation of guanylyl cyclase-linked natriuretic peptide receptors.

PubMed

Springer, Jeremy; Azer, John; Hua, Rui; Robbins, Courtney; Adamczyk, Andrew; McBoyle, Sarah; Bissell, Mary Beth; Rose, Robert A

2012-05-01

Natriuretic peptides (NPs) are best known for their ability to regulate blood vessel tone and kidney function whereas their electrophysiological effects on the heart are less clear. Here, we measured the effects of BNP and CNP on sinoatrial node (SAN) and atrial electrophysiology in isolated hearts as well as isolated SAN and right atrial myocytes from mice. BNP and CNP dose-dependently increased heart rate and conduction through the heart as indicated by reductions in R-R interval, P wave duration and P-R interval on ECGs. In conjunction with these ECG changes BNP and CNP (100 nM) increased spontaneous action potential frequency in isolated SAN myocytes by increasing L-type Ca(2+) current (I(Ca,L)) and the hyperpolarization-activated current (I(f)). BNP had no effect on right atrial myocyte APs in basal conditions; however, in the presence of isoproterenol (10nM), BNP increased atrial AP duration and I(Ca,L). Quantitative gene expression and immunocytochemistry data show that all three NP receptors (NPR-A, NPR-B and NPR-C) are expressed in the SAN and atrium. The effects of BNP and CNP on SAN and right atrial myocytes were maintained in mutant mice lacking functional NPR-C receptors and blocked by the NPR-A antagonist A71915 indicating that BNP and CNP function through their guanylyl cyclase-linked receptors. Our data also show that the effects of BNP and CNP are completely absent in the presence of the phosphodiesterase 3 inhibitor milrinone. Based on these data we conclude that NPs can increase heart rate and electrical conduction by activating the guanylyl cyclase-linked NPR-A and NPR-B receptors and inhibiting PDE3 activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Late arrhythmias in the operated interatrial communication. Analysis of sinus node function and the conduction pathways by His bundle electrocardiography].

PubMed

Ramírez, A; Gil, M; Martínez Ríos, M A; Cárdenas, M; Pliego, J; Zamora, C; Mata, L A

1982-01-01

Four hundred patients with atrial septal defect treated surgically were reviewed. Thirty five (8.7%) developed arrhytmias post-surgery which persisted for over a year. Sinus bradycardia was found in 10 patients, nodal rhythm in 21, and atrial fibrilation and flutter in 4 patients. Thirty five per cent of the patients with late arrhythmias developed related symptomatology. In 14 patients the function of the sinus node was studied with electrical stimulation of the atrium and with His registry. The interatrial conduction time, AV node and His Purkinje were analized employing various stimulation frequencies. All the cases studied had normal intra-atrial conduction; the response of the atrio-ventricular node to increasing frequencies was normal, an the intraventricular conduction remained constant. In 8 patients (52%), alterations of the sinus node were found; these consisted of prolonged post-stimulation pauses, Wenckebach's type sinoatrial block and suppression of sinus automatism employing vagal procedures or through electrical stimulation. A patient with severe bradycardia detected by dynamic electrocardiography had to be treated with a permanent pacemaker. We confirm that these arrhytmias are not produced by lesions of the internodal tracts, and that an alteration of the sinus node is frequent without a concomitant lesion of the intraventricular pathway. The lesion to the nutrient artery could be due to trauma and/or surgically induced. The response to anticholinergic drugs was good. Prolonged observation of these patients could increase the morbility of these arrythmias and raise doubts of the surgical indications in cases with moderate hemodynamic repercussion.

Distribution of the muscarinic K+ channel proteins Kir3.1 and Kir3.4 in the ventricle, atrium, and sinoatrial node of heart.

PubMed

Dobrzynski, H; Marples, D D; Musa, H; Yamanushi, T T; Henderson, Z; Takagishi, Y; Honjo, H; Kodama, I; Boyett, M R

2001-10-01

The functionally important effects on the heart of ACh released from vagal nerves are principally mediated by the muscarinic K+ channel. The aim of this study was to determine the abundance and cellular location of the muscarinic K+ channel subunits Kir3.1 and Kir3.4 in different regions of heart. Western blotting showed a very low abundance of Kir3.1 in rat ventricle, although Kir3.1 was undetectable in guinea pig and ferret ventricle. Although immunofluorescence on tissue sections showed no labeling of Kir3.1 in rat, guinea pig, and ferret ventricle and Kir3.4 in rat ventricle, immunofluorescence on single ventricular cells from rat showed labeling in t-tubules of both Kir3.1 and Kir3.4. Kir3.1 was abundant in the atrium of the three species, as shown by Western blotting and immunofluorescence, and Kir3.4 was abundant in the atrium of rat, as shown by immunofluorescence. Immunofluorescence showed Kir3.1 expression in SA node from the three species and Kir3.4 expression in the SA node from rat. The muscarinic K+ channel is activated by ACh via the m2 muscarinic receptor and, in atrium and SA node from ferret, Kir3.1 labeling was co-localized with m2 muscarinic receptor labeling throughout the outer cell membrane.

Model for the heart beat-to-beat time series during meditation

NASA Astrophysics Data System (ADS)

Capurro, A.; Diambra, L.; Malta, C. P.

2003-09-01

We present a model for the respiratory modulation of the heart beat-to-beat interval series. The model consists of a pacemaker, that simulates the membrane potential of the sinoatrial node, modulated by a periodic input signal plus correlated noise that simulates the respiratory input. The model was used to assess the waveshape of the respiratory signals needed to reproduce in the phase space the trajectory of experimental heart beat-to-beat interval data. The data sets were recorded during meditation practices of the Chi and Kundalini Yoga techniques. Our study indicates that in the first case the respiratory signal has the shape of a smoothed square wave, and in the second case it has the shape of a smoothed triangular wave.

Electrophysiological heterogeneity of pacemaker cells in the rabbit intercaval region, including the SA node: insights from recording multiple ion currents in each cell.

PubMed

Monfredi, Oliver; Tsutsui, Kenta; Ziman, Bruce; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A

2018-03-01

Cardiac pacemaker cells, including cells of the sinoatrial node, are heterogeneous in size, morphology, and electrophysiological characteristics. The exact extent to which these cells differ electrophysiologically is unclear yet is critical to understanding their functioning. We examined major ionic currents in individual intercaval pacemaker cells (IPCs) sampled from the paracristal, intercaval region (including the sinoatrial node) that were spontaneously beating after enzymatic isolation from rabbit hearts. The beating rate was measured at baseline and after inhibition of the Ca 2+ pump with cyclopiazonic acid. Thereafter, in each cell, we consecutively measured the density of funny current ( I f ), delayed rectifier K + current ( I K ) (a surrogate of repolarization capacity), and L-type Ca 2+ current ( I Ca,L ) using whole cell patch clamp . The ionic current densities varied to a greater extent than previously appreciated, with some IPCs demonstrating very small or zero I f . The density of none of the currents was correlated with cell size, while I Ca,L and I f densities were related to baseline beating rates. I f density was correlated with I K density but not with that of I Ca,L . Inhibition of Ca 2+ cycling had a greater beating rate slowing effect in IPCs with lower I f densities. Our numerical model simulation indicated that 1) IPCs with small (or zero) I f or small I Ca,L can operate via a major contribution of Ca 2+ clock, 2) I f -Ca 2+ -clock interplay could be important for robust pacemaking function, and 3) coupled I f - I K function could regulate maximum diastolic potential. Thus, we have demonstrated marked electrophysiological heterogeneity of IPCs. This heterogeneity is manifested in basal beating rate and response to interference of Ca 2+ cycling, which is linked to I f . NEW & NOTEWORTHY In the present study, a hitherto unrecognized range of heterogeneity of ion currents in pacemaker cells from the intercaval region is demonstrated. Relationships between basal beating rate and L-type Ca 2+ current and funny current ( I f ) density are uncovered, along with a positive relationship between I f and delayed rectifier K + current. Links are shown between the response to Ca 2+ cycling blockade and I f density.

Myristoylated peptides potentiate the funny current (If) in sinoatrial myocytes

PubMed Central

Liao, Zhandi; St Clair, Joshua R; Larson, Eric D

2011-01-01

The funny current, If, in sinoatrial myocytes is thought to contribute to the sympathetic fight-or-flight increase in heart rate. If is produced by hyperpolarization-activated cyclic nucleotide sensitive-4 (HCN4) channels, and it is widely believed that sympathetic regulation of If occurs via direct binding of cAMP to HCN4, independent of phosphorylation. However, we have recently shown that Protein Kinase A (PKA) activity is required for sympathetic regulation of If, and that PKA can directly phosphorylate HCN4.1 In the present study, we examined the effects of a myristoylated PKA inhibitory peptide (myr-PKI) on If in mouse sinoatrial myocytes. We found that myr-PKI and another myristoylated peptide potently and specifically potentiated If via a mechanism that did not involve PKA inhibition and that was independent of the peptide sequence, Protein Kinase C or phosphatidylinositol-4,5-bisphosphate. The off-target activation of If by myristoylated peptides limits their usefulness for studies of pacemaker mechanisms in sinoatrial myocytes. PMID:21150293

Cardiac Resynchronization Therapy and phase resetting of the sinoatrial node: A conjecture

NASA Astrophysics Data System (ADS)

Cantini, Federico; Varanini, Maurizio; Macerata, Alberto; Piacenti, Marcello; Morales, Maria-Aurora; Balocchi, Rita

2007-03-01

Congestive heart failure is a severe chronic disease often associated with disorders that alter the mechanisms of excitation-contraction coupling that may result in an asynchronous left ventricular motion which may further impair the ability of the failing heart to eject blood. In recent years a therapeutic approach to resynchronize the ventricles (cardiac resynchronization therapy, CRT) has been performed through the use of a pacemaker device able to provide atrial-based biventricular stimulation. Atrial lead senses the spontaneous occurrence of cells depolarization and sends the information to the generator which, in turn, after a settled delay [atrioventricular (AV) delay], sends electrical impulses to both ventricles to stimulate their synchronous contraction. Recent studies performed on heart rate behavior of chronically implanted patients at different epochs after implantation have shown that CRT can lead to sustained overall improvement of heart function with a reduction in morbidity and mortality. At this moment, however, there are no studies about CRT effects on spontaneous heart activity of chronically implanted patients. We performed an experimental study in which the electrocardiographic signal of five subjects under chronic CRT was recorded during the activity of the pacemaker programmed at different AV delays and under spontaneous cardiac activity after pacemaker deactivation. The different behavior of heart rate variability during pacemaker activity and after pacemaker deactivation suggested the hypothesis of a phase resetting mechanism induced by the pacemaker stimulus on the sinoatrial (SA) node, a phenomenon already known in literature for aggregate of cardiac cells, but still unexplored in vivo. The constraints imposed by the nature of our study (in vivo tests) made it impossible to plan an experiment to prove our hypothesis directly. We therefore considered the best attainable result would be to prove the accordance of our data to the conjecture through the use of models and physical considerations. We first used the data of literature on far-field effects of cardiac defibrillators to prove that the pacemaker impulses delivered to the two ventricles were able to induce modifications in membrane voltage at the level of the SA node. To simulate a phase resetting mechanism of the SA node, we used a Van der Pol modified model to allow the possibility of changing the refractory period and the firing frequency of the cells separately. With appropriate parameters of the model we reproduced phase response curves that can account for our experimental data. Furthermore, the simulated curves closely resemble the functional form proposed in literature for perturbed aggregate of cardiac cells. Despite the small sample of subjects investigated and the limited number of ECG recordings at different AV delays, we think we have proved the plausibility of the proposed conjecture.

Upregulation of adenosine A1 receptors facilitates sinoatrial node dysfunction in chronic canine heart failure by exacerbating nodal conduction abnormalities revealed by novel dual-sided intramural optical mapping.

PubMed

Lou, Qing; Hansen, Brian J; Fedorenko, Olga; Csepe, Thomas A; Kalyanasundaram, Anuradha; Li, Ning; Hage, Lori T; Glukhov, Alexey V; Billman, George E; Weiss, Raul; Mohler, Peter J; Györke, Sándor; Biesiadecki, Brandon J; Carnes, Cynthia A; Fedorov, Vadim V

2014-07-22

Although sinoatrial node (SAN) dysfunction is a hallmark of human heart failure (HF), the underlying mechanisms remain poorly understood. We aimed to examine the role of adenosine in SAN dysfunction and tachy-brady arrhythmias in chronic HF. We applied multiple approaches to characterize SAN structure, SAN function, and adenosine A1 receptor expression in control (n=17) and 4-month tachypacing-induced chronic HF (n=18) dogs. Novel intramural optical mapping of coronary-perfused right atrial preparations revealed that adenosine (10 μmol/L) markedly prolonged postpacing SAN conduction time in HF by 206 ± 99 milliseconds (versus 66 ± 21 milliseconds in controls; P=0.02). Adenosine induced SAN intranodal conduction block or microreentry in 6 of 8 dogs with HF versus 0 of 7 controls (P=0.007). Adenosine-induced SAN conduction abnormalities and automaticity depression caused postpacing atrial pauses in HF versus control dogs (17.1 ± 28.9 versus 1.5 ± 1.3 seconds; P<0.001). Furthermore, 10 μmol/L adenosine shortened atrial repolarization and led to pacing-induced atrial fibrillation in 6 of 7 HF versus 0 of 7 control dogs (P=0.002). Adenosine-induced SAN dysfunction and atrial fibrillation were abolished or prevented by adenosine A1 receptor antagonists (50 μmol/L theophylline/1 μmol/L 8-cyclopentyl-1,3-dipropylxanthine). Adenosine A1 receptor protein expression was significantly upregulated during HF in the SAN (by 47 ± 19%) and surrounding atrial myocardium (by 90 ± 40%). Interstitial fibrosis was significantly increased within the SAN in HF versus control dogs (38 ± 4% versus 23 ± 4%; P<0.001). In chronic HF, adenosine A1 receptor upregulation in SAN pacemaker and atrial cardiomyocytes may increase cardiac sensitivity to adenosine. This effect may exacerbate conduction abnormalities in the structurally impaired SAN, leading to SAN dysfunction, and potentiate atrial repolarization shortening, thereby facilitating atrial fibrillation. Atrial fibrillation may further depress SAN function and lead to tachy-brady arrhythmias in HF. © 2014 American Heart Association, Inc.

Prevalence and predictors of low voltage zones in the left atrium in patients with atrial fibrillation.

PubMed

Huo, Yan; Gaspar, Thomas; Pohl, Matthias; Sitzy, Judith; Richter, Utz; Neudeck, Sebastian; Mayer, Julia; Kronborg, Mads Brix; Piorkowski, Christopher

2017-06-10

To describe the extent and distribution of low voltage zones (LVZ) in a large cohort of patients undergoing ablation for paroxysmal and persistent atrial fibrillation (AF), and to explore baseline predictors of LVZ in these patients. Consecutive patients who underwent a bipolar voltage map guided AF ablation, were enrolled. Voltage maps were conducted for each patient using 3-dimensional electroanatomical mapping system and LVZ were defined as areas of bipolar voltage < 0.5 mV. A total of 539 patients (309 male, age 65 ± 10 years) were included. Low voltage zones was present in 58 out of 292 patients with paroxysmal and 134 out of 247 persistent AF (P < 0.001). The area of LVZ was larger in patients with persistent as compare to paroxysmal AF, 5 cm2 (IQR 3-18.6) vs. 12.1 cm2 (IQR 3.6-28.5), P = 0.026, respectively. In the multivariate analysis age (OR 1.07, 95%CI 1.05-1.10, P < 0.001), female gender (OR 2.18, 95%CI 1.38-3.43, P = 0.001), sinoatrial node dysfunction (OR 3.90, 95%CI 1.24-12.21, P = 0.020), larger surface area of left atrium pr. cm2 (OR 1.01, 95%CI 1.00-1.02, P = 0.016), and persistent AF (OR 5.03, 95%CI 3.20-7.90, P<0.001) were associated with presence of LVZ. In a large cohort of patients undergoing ablation for AF, the prevalence of LVZ was higher and LVZ areas larger in patients with persistent as compared with paroxysmal AF. The most frequent localization of LVZ was anterior wall, septum and posterior wall. Presence of LVZ was associated with higher age, female gender, larger LA surface area, and sinoatrial node dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Modulation of voltage- and Ca2+-dependent gating of CaV1.3 L-type calcium channels by alternative splicing of a C-terminal regulatory domain.

PubMed

Singh, Anamika; Gebhart, Mathias; Fritsch, Reinhard; Sinnegger-Brauns, Martina J; Poggiani, Chiara; Hoda, Jean-Charles; Engel, Jutta; Romanin, Christoph; Striessnig, Jörg; Koschak, Alexandra

2008-07-25

Low voltage activation of Ca(V)1.3 L-type Ca(2+) channels controls excitability in sensory cells and central neurons as well as sinoatrial node pacemaking. Ca(V)1.3-mediated pacemaking determines neuronal vulnerability of dopaminergic striatal neurons affected in Parkinson disease. We have previously found that in Ca(V)1.4 L-type Ca(2+) channels, activation, voltage, and calcium-dependent inactivation are controlled by an intrinsic distal C-terminal modulator. Because alternative splicing in the Ca(V)1.3 alpha1 subunit C terminus gives rise to a long (Ca(V)1.3(42)) and a short form (Ca(V)1.3(42A)), we investigated if a C-terminal modulatory mechanism also controls Ca(V)1.3 gating. The biophysical properties of both splice variants were compared after heterologous expression together with beta3 and alpha2delta1 subunits in HEK-293 cells. Activation of calcium current through Ca(V)1.3(42A) channels was more pronounced at negative voltages, and inactivation was faster because of enhanced calcium-dependent inactivation. By investigating several Ca(V)1.3 channel truncations, we restricted the modulator activity to the last 116 amino acids of the C terminus. The resulting Ca(V)1.3(DeltaC116) channels showed gating properties similar to Ca(V)1.3(42A) that were reverted by co-expression of the corresponding C-terminal peptide C(116). Fluorescence resonance energy transfer experiments confirmed an intramolecular protein interaction in the C terminus of Ca(V)1.3 channels that also modulates calmodulin binding. These experiments revealed a novel mechanism of channel modulation enabling cells to tightly control Ca(V)1.3 channel activity by alternative splicing. The absence of the C-terminal modulator in short splice forms facilitates Ca(V)1.3 channel activation at lower voltages expected to favor Ca(V)1.3 activity at threshold voltages as required for modulation of neuronal firing behavior and sinoatrial node pacemaking.

Sinoatrial block complicating legionnaire's disease.

PubMed

Medarov, B; Tongia, S; Rossoff, L

2003-11-01

A 59 year old woman presented with acute onset of fever, chills, diaphoresis, vague chest discomfort, and was found to be hypotensive and tachypnoeic. An electrocardiogram demonstrated sinoatrial block with a junctional rhythm between 50 and 80 beats/min. All cultures were negative and imaging studies unrevealing. Her urine tested positive for Legionella pneumophila antigen serotype 1 and she improved with antibiotic therapy.

Sodium Hydroxide Pinpoint Pressing Permeation Method for the Animal Modeling of Sick Sinus Syndrome.

PubMed

Geng, Naizhi; Jiang, Ning; Peng, Cailiang; Wang, Huaiping; Zhang, Shuoxin; Chen, Tianyu; Liu, Lixia; Wu, Yaping; Liu, Dandan

2015-01-01

Sodium hydroxide pinpoint pressing permeation (SHPPP) was investigated in order to build a rat model of sick sinus syndrome (SSS), which is easy to operate and control the degree of damage, with fewer complications and applicable for large and small animals.Thirty healthy Wistar rats (15 males and 15 females, weighing 250-350 g) were randomly divided into 3 groups, namely a formaldehyde thoracotomy wet compressing group (FTWC), formaldehyde pinpoint pressing permeation group (FPPP) group, and SHPPP group. The number of surviving rats, heart rate (HR), sinoatrial node recovery time (SNRT), corrected SNRT (CSNRT), and sinoatrial conduction time (SACT) were recorded 3 days, one week, and two weeks after modeling.The achievement ratio of modeling was 10% in the FTWC group, 40% in the FPPP group, and 70% in the SHPPP group, and the differences were statistically significant (χ(2) = 7.250, P = 0.007). Meanwhile, the HR was reduced by about 37% in these 3 groups 3 days after modeling, while the reduction was maintained only in SHPPP (P > 0.05) and the HR was re-elevated in the FTWC and FPPP groups 2 weeks after modeling (P < 0.05). Additionally, the SNRT, cS-NRT, and SACT were significantly prolonged compared with pre-modeling in all 3 groups (P < 0.01).SHPPP was the best method with which to build an SSS model with stable and lasting low HR and high success rate of modeling, which might be helpful for further studies on the SSS mechanisms and drugs.

Review of the If selective channel inhibitor ivabradine in the treatment of chronic stable angina.

PubMed

Prasad, Usha K; Gray, David; Purcell, Henry

2009-02-01

Coronary heart disease is the major cause of morbidity and mortality in industrialized countries, and its prevalence is predicted to grow as the population ages. Current drugs for chronic stable angina (such as beta-blockers, calcium-channel blockers, long- and short-acting nitrates, and potassium-channel activators) are often effective, either as monotherapy or in combination, but side effects and contraindications may limit their use. The "I(f)" (for "funny") channel, discovered in 1979, is expressed mainly in the membrane of pacemaker cells present in the sinus node, the atrioventricular node, the ventricular conduction pathways, and ventricular myocytes. By determining the slope of diastolic depolarization, which in turn controls action potential frequency, it is a key determinant of heart rate and so provides a new therapeutic target for controlling angina symptoms. A new antiangina drug, ivabradine, has been developed and licensed for clinical use. It exclusively reduces the heart rate by selectively blocking the I(f) channel of the sino-atrial node. As clinical trials have shown it to be remarkably well-tolerated, ivabradine offers an alternative for patients who cannot take, or are intolerant of, beta blockade. This review provides an insight into this new agent, its historical background, mechanism of action, and pathophysiologic basis, and provides up-to-date evidence-based information on its optimum use in stable angina.

Effect of interconnection between cervical vagus trunk, epicardial fat pad on sinus node function, and atrial fibrillation.

PubMed

Zhou, Qina; Zhang, Ling; Wang, Kun; Xu, Xiaoxia; Ji, Meng; Zhang, Feng; Wang, Hongli; Hou, Yuemei

2014-03-01

The epicardial fat pad (FP) integrates the autonomic innervation between the extrinsic and intrinsic cardiac autonomic nervous system and affects atrial electrophysiology and pathophysiology. Eighteen dogs were divided into two groups: sequential ablation of sinoatrial node FP (SAN-FP) and atrioventricular node FP (AVN-FP). Sinus rate (SR), atrial fibrillation (AF) inducibility, and effective refractory period (ERP) changes during electrical stimulation of the vagus trunk were detected before and after ablation. In the SAN-FP group, the SR slowing, increasing AF inducibility, and ERP shortening that induced by vagus trunk stimulation were significantly attenuated by isolated SAN-FP ablation, compared with the same group prior to ablation (all P < 0.05). Subsequent AVN-FP ablation following SAN-FP ablation almost cannot produce further attenuation during vagus trunk stimulation, compared with isolated SAN-FP ablation (P > 0.05). In the AVN-FP group, SR slowing, increasing AF inducibility, and ERP shortening that induced by vagus trunk stimulation were completely eliminated by isolated AVN-FP ablation, compared with the same group prior to ablation (all P < 0.05). Subsequent SAN-FP ablation following AVN-FP ablation produced no further attenuation, compared with isolated AVN-FP ablation (P > 0.05). A neural pathway from the cervical vagus trunk to the sinus node and atrium runs through the SAN-FP, but eventually converges at the AVN-FP and also suggested that the AVN-FP serves as an "integration center" for the SAN-FP to modulate sinus node function. The AVN-FP may play a more critical role in the initiation and maintenance of AF. ©2013 First Affilated Hospital of Xingiang Medical University Pacing and Clinical Electrophysiology ©2013 Wiley Periodicals, Inc.

Microwave effects on isolated chick embryo hearts

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

Caddemi, A.; Tamburello, C.C.; Zanforlin, L.

1986-01-01

This study was designed to examine the effects of microwaves on the electric activity of hearts as a means of elucidating interactive mechanisms of nonionizing radiation with cardiac tissue. Experiments were performed on isolated hearts of 9-12-day-old chick embryos placed in small petri dishes. Oxygenated isotonic Ringer's solution at 37 degrees C permitted heart survival. Samples were irradiated at 2.45 GHz with a power density of 3 mW/cm2. The heart signal was detected with a glass micropipet inserted into the sinoatrial node and examined by means of a Berg-Fourier analyzer. Pulsed microwaves caused the locking of the heartbeat to themore » modulation frequency, whereas continuous wave irradiation might have induced slight bradycardia. Pulsed fields induced stimulation or regularization of the heartbeat in arrhythmia, fibrillation, or arrest of the heart.« less

Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

PubMed Central

Guo, Tianruo; Al Abed, Amr; Lovell, Nigel H.; Dokos, Socrates

2013-01-01

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation. PMID:23710254

Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?

PubMed Central

Li, RA

2012-01-01

Normal rhythms originate in the sino-atrial node, a specialized cardiac tissue consisting of only a few thousands of pacemaker cells. Malfunction of pacemaker cells due to diseases or aging leads to rhythm generation disorders (for example, bradycardias and sick-sinus syndrome (SSS)), which often necessitate the implantation of electronic pacemakers. Although effective, electronic devices are associated with such shortcomings as limited battery life, permanent implantation of leads, lead dislodging, the lack of autonomic responses and so on. Here, various gene- and cell-based approaches, with a particular emphasis placed on the use of pluripotent stem cells and the hyperpolarization-activated cyclic nucleotide-gated-encoded pacemaker gene family, that have been pursued in the past decade to reconstruct bio-artificial pacemakers as alternatives will be discussed in relation to the basic biological insights and translational regenerative potential. PMID:22673497

Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned?

PubMed

Li, R A

2012-06-01

Normal rhythms originate in the sino-atrial node, a specialized cardiac tissue consisting of only a few thousands of nodal pacemaker cells. Malfunction of pacemaker cells due to diseases or aging leads to rhythm generation disorders (for example, bradycardias and sick-sinus syndrome (SSS)), which often necessitate the implantation of electronic pacemakers. Although effective, electronic devices are associated with such shortcomings as limited battery life, permanent implantation of leads, lead dislodging, the lack of autonomic responses and so on. Here, various gene- and cell-based approaches, with a particular emphasis placed on the use of pluripotent stem cells and the hyperpolarization-activated cyclic nucleotide-gated-encoded pacemaker gene family, that have been pursued in the past decade to reconstruct bio-artificial pacemakers as alternatives will be discussed in relation to the basic biological insights and translational regenerative potential.

Exercise training-induced bradycardia: evidence for enhanced parasympathetic regulation without changes in intrinsic sinoatrial node function.

PubMed

Billman, George E; Cagnoli, Kristen L; Csepe, Thomas; Li, Ning; Wright, Patrick; Mohler, Peter J; Fedorov, Vadim V

2015-06-01

The mechanisms responsible for exercise-induced reductions in baseline heart rate (HR), known as training bradycardia, remain controversial. Therefore, changes in cardiac autonomic regulation and intrinsic sinoatrial nodal (SAN) rate were evaluated using dogs randomly assigned to either a 10- to 12-wk exercise training (Ex, n = 15) or an equivalent sedentary period (Sed, n = 10). Intrinsic HR was revealed by combined autonomic nervous system (ANS) blockade (propranolol + atropine, iv) before and after completion of the study. At the end of the study, SAN function was further evaluated by examining the SAN recovery time (SNRT) following rapid atrial pacing and the response to adenosine in anesthetized animals. As expected, both the response to submaximal exercise and baseline HR significantly (P < 0.01) decreased, and heart rate variability (HRV; e.g., high-frequency R-R interval variability) significantly (P < 0.01) increased in the Ex group but did not change in the Sed group. Atropine also induced significantly (P < 0.01) greater reductions in HRV in the Ex group compared with the Sed group; propranolol elicited similar HR and HRV changes in both groups. In contrast, neither intrinsic HR (Ex before, 141.2 ± 6.7; Ex after, 146.0 ± 8.0 vs. Sed before, 143.3 ± 11.1; Sed after, 141.0 ± 11.3 beats per minute), the response to adenosine, corrected SNRT, nor atrial fibrosis and atrial fibrillation inducibility differed in the Ex group vs. the Sed group. These data suggest that in a large-animal model, training bradycardia results from an enhanced cardiac parasympathetic regulation and not from changes in intrinsic properties of the SAN. Copyright © 2015 the American Physiological Society.

The effects of the new antiarrhythmic E 047/1 on postoperative ischemia-induced arrhythmias in dogs.

PubMed

Kulier, A H; Novalija, E; Hogan, Q; Vicenzi, M N; Woehlck, H J; Bajic, J; Atlee, J L; Bosnjak, Z J

1999-12-01

Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens. Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.

Dilated cardiomyopathy and sinoatrial dysfunction in an Estrela mountain dog.

PubMed

Lobo, Luis; Pinheiro-Vieira, António; Gomes, João L; Canada, Nuno; Ribeiro, Lenio; Costa, Paulo D; Oliveira, Pedro; Bussadori, Claudio

2012-01-01

A 1 yr old male Estrela mountain dog was evaluated as a part of a screening program for dilated cardiomyopathy. The dog came from a family with a history of dilated cardiomyopathy but was asymptomatic. Occult dilated cardiomyopathy and sino-atrial dysfunction were diagnosed based on echocardiography and electrocardiography. These two disorders may be associated given that related dogs have been diagnosed with the same disorders. The dog has remained asymptomatic for 4 years following initial evaluation.

Inhibition of spontaneous activity of rabbit atrioventricular node cells by KB-R7943 and inhibitors of sarcoplasmic reticulum Ca2+ ATPase

PubMed Central

Cheng, Hongwei; Smith, Godfrey L.; Hancox, Jules C.; Orchard, Clive H.

2011-01-01

The atrioventricular node (AVN) can act as a subsidiary cardiac pacemaker if the sinoatrial node fails. In this study, we investigated the effects of the Na–Ca exchange (NCX) inhibitor KB-R7943, and inhibition of the sarcoplasmic reticulum calcium ATPase (SERCA), using thapsigargin or cyclopiazonic acid (CPA), on spontaneous action potentials (APs) and [Ca2+]i transients from cells isolated from the rabbit AVN. Spontaneous [Ca2+]i transients were monitored from undialysed AVN cells at 37 °C using Fluo-4. In separate experiments, spontaneous APs and ionic currents were recorded using the whole-cell patch clamp technique. Rapid application of 5 μM KB-R7943 slowed or stopped spontaneous APs and [Ca2+]i transients. However, in voltage clamp experiments in addition to blocking NCX current (INCX) KB-R7943 partially inhibited L-type calcium current (ICa,L). Rapid reduction of external [Na+] also abolished spontaneous activity. Inhibition of SERCA (using 2.5 μM thapsigargin or 30 μM CPA) also slowed or stopped spontaneous APs and [Ca2+]i transients. Our findings are consistent with the hypothesis that sarcoplasmic reticulum (SR) Ca2+ release influences spontaneous activity in AVN cells, and that this occurs via [Ca2+]i-activated INCX; however, the inhibitory action of KB-R7943 on ICa,L means that care is required in the interpretation of data obtained using this compound. PMID:21163524

Cardiac rhythm and pacemaking abnormalities in patients affected by endemic pemphigus in Colombia may be the result of deposition of autoantibodies, complement, fibrinogen, and other molecules.

PubMed

Abreu Velez, Ana Maria; Howard, Michael S; Velazquez-Velez, Jorge Enrique

2018-05-01

We previously showed that one-third of patients affected by endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF), display autoreactivity to the heart. The purpose of this study was to investigate rhythm disturbances with the presence of autoantibodies and correlate them with ECG changes in these patients. We performed a study comparing 30 patients and 30 controls from the endemic area, matched by demographics, including age, sex, weight, work activities, and comorbidities. ECG as well as direct and indirect immunofluorescence, immunohistochemistry, and confocal microscopic studies focusing on cardiac node abnormalities were performed. Autopsies of 7 patients also were reviewed. The main ECG abnormalities seen in the El Bagre-EPF patients were sinus bradycardia (in one-half), followed by left bundle branch block, left posterior fascicular block, and left anterior fascicular block compared with the controls. One-third of the patients displayed polyclonal autoantibodies against the sinoatrial and/or AV nodes and the His bundle correlating with rhythm anomalies and delays in the cardiac conduction system (P <.01). The patient antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), and myocardium-enriched zonula occludens-1-associated protein (MYZAP; Progen Biotechnik) (P <.01). One-third of the patients affected by El Bagre-EPF have rhythm abnormalities that slow the conduction of impulses in cardiac nodes and the cardiac conduction system. These abnormalities likely occur as a result of deposition of autoantibodies, complement, and other inflammatory molecules. We show for the first time that MYZAP is present in cardiac nodes. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Effects of acetylcholine and noradrenalin on action potentials of isolated rabbit sinoatrial and atrial myocytes.

PubMed

Verkerk, Arie O; Geuzebroek, Guillaume S C; Veldkamp, Marieke W; Wilders, Ronald

2012-01-01

The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1-1000 nM, while a clear-cut frequency dependence in the range of 1-4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins.

Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

PubMed Central

Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

2012-01-01

The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins. PMID:22754533

Computer algorithms for automated detection and analysis of local Ca2+ releases in spontaneously beating cardiac pacemaker cells

PubMed Central

Kim, Mary S.; Tsutsui, Kenta; Stern, Michael D.; Lakatta, Edward G.; Maltsev, Victor A.

2017-01-01

Local Ca2+ Releases (LCRs) are crucial events involved in cardiac pacemaker cell function. However, specific algorithms for automatic LCR detection and analysis have not been developed in live, spontaneously beating pacemaker cells. In the present study we measured LCRs using a high-speed 2D-camera in spontaneously contracting sinoatrial (SA) node cells isolated from rabbit and guinea pig and developed a new algorithm capable of detecting and analyzing the LCRs spatially in two-dimensions, and in time. Our algorithm tracks points along the midline of the contracting cell. It uses these points as a coordinate system for affine transform, producing a transformed image series where the cell does not contract. Action potential-induced Ca2+ transients and LCRs were thereafter isolated from recording noise by applying a series of spatial filters. The LCR birth and death events were detected by a differential (frame-to-frame) sensitivity algorithm applied to each pixel (cell location). An LCR was detected when its signal changes sufficiently quickly within a sufficiently large area. The LCR is considered to have died when its amplitude decays substantially, or when it merges into the rising whole cell Ca2+ transient. Ultimately, our algorithm provides major LCR parameters such as period, signal mass, duration, and propagation path area. As the LCRs propagate within live cells, the algorithm identifies splitting and merging behaviors, indicating the importance of locally propagating Ca2+-induced-Ca2+-release for the fate of LCRs and for generating a powerful ensemble Ca2+ signal. Thus, our new computer algorithms eliminate motion artifacts and detect 2D local spatiotemporal events from recording noise and global signals. While the algorithms were developed to detect LCRs in sinoatrial nodal cells, they have the potential to be used in other applications in biophysics and cell physiology, for example, to detect Ca2+ wavelets (abortive waves), sparks and embers in muscle cells and Ca2+ puffs and syntillas in neurons. PMID:28683095

Electrophysiological effects of FK664, a new cardiotonic agent, on preparations from guinea pig ventricle and from rabbit sino-atrial node.

PubMed

Kodama, I; Anno, T; Sudo, Y; Satake, N; Shibata, S

1989-05-01

Effects of the cardiotonic agent FK664, 6-(3, 4-dimethoxy-phenyl)-1-ethyl-4-mesitylimino-3-methyl-3,4-dihydro-2 (1H)-pyrimidone, on isolated guinea pig ventricular muscles and rabbit sinus node pacemaker cells were studied using micro-electrode techniques. In ventricular muscles driven at 0.5-1.0 Hz, FK664 above 3 mumol.litre-1 caused an increase in contractile force and a shortening of time to peak tension. This positive inotropic effect of FK664 was accompanied by a slight elevation of the early plateau phase of the action potential, while other action potential variables were unaffected. The change in contractile force induced by FK664 was abolished in a low Ca2+ medium (0.12 mmol.litre-1) or by treatment with ryanodine (2 mumol.litre-1), whereas it was relatively well preserved in the preparations pretreated with nefedipine (1 mumol.litre-1). The slow action potentials induced by isoprenaline (0.3 mumol.litre-1) in high K+ medium (30 mmol.litre-1) and the slow inward current measured by single sucrose gap voltage clamp at a holding potential of -40 mV were unaffected by FK664. In sinus node pacemaker cells, FK664 (1-10 mumol.litre-1) caused a dose dependent acceleration of phase 4 depolarisation and a shortening of spontaneous firing cycle length. This positive chronotropic effect of FK664 was markedly inhibited in a low Ca2+ medium (0.3 mmol.litre-1). These findings suggest that FK664 has positive inotropic and chronotropic effects on the heart, due to an enhancement of transsarcolemmal calcium influx through the low threshold, dihydropyridine insensitive Ca2+ channel population.

Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection

PubMed Central

Rimmbach, Christian; Jung, Julia J.; David, Robert

2015-01-01

Treatment of the “sick sinus syndrome” is based on artificial pacemakers. These bear hazards such as battery failure and infections. Moreover, they lack hormone responsiveness and the overall procedure is cost-intensive. “Biological pacemakers” generated from PSCs may become an alternative, yet the typical content of pacemaker cells in Embryoid Bodies (EBs) is extremely low. The described protocol combines “forward programming” of murine PSCs via the sinus node inducer TBX3 with Myh6-promoter based antibiotic selection. This yields cardiomyocyte aggregates consistent of >80% physiologically functional pacemaker cells. These “induced-sinoatrial-bodies” (“iSABs”) are spontaneously contracting at yet unreached frequencies (400-500 bpm) corresponding to nodal cells isolated from mouse hearts and are able to pace murine myocardium ex vivo. Using the described protocol highly pure sinus nodal single cells can be generated which e.g. can be used for in vitro drug testing. Furthermore, the iSABs generated according to this protocol may become a crucial step towards heart tissue engineering. PMID:25742394

Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block

PubMed Central

Hu, Yu-Feng; Dawkins, James Frederick; Cho, Hee Cheol; Marbán, Eduardo; Cingolani, Eugenio

2016-01-01

Somatic reprogramming by reexpression of the embryonic transcription factor T-box 18 (TBX18) converts cardiomyocytes into pacemaker cells. We hypothesized that this could be a viable therapeutic avenue for pacemaker-dependent patients afflicted with device-related complications, and therefore tested whether adenoviral TBX18 gene transfer could create biological pacemaker activity in vivo in a large-animal model of complete heart block. Biological pacemaker activity, originating from the intramyocardial injection site, was evident in TBX18-transduced animals starting at day 2 and persisted for the duration of the study (14 days) with minimal backup electronic pacemaker use. Relative to controls transduced with a reporter gene, TBX18-transduced animals exhibited enhanced autonomic responses and physiologically superior chronotropic support of physical activity. Induced sinoatrial node cells could be identified by their distinctive morphology at the site of injection in TBX18-transduced animals, but not in controls. No local or systemic safety concerns arose. Thus, minimally invasive TBX18 gene transfer creates physiologically relevant pacemaker activity in complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically relevant disease model. PMID:25031269

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

PubMed Central

Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard

2016-01-01

The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca2+-activated K+ channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity. PMID:26725737

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels.

PubMed

Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard

2016-01-01

The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca(2+)-activated K(+) channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

Nonlinear physics of electrical wave propagation in the heart: a review

NASA Astrophysics Data System (ADS)

Alonso, Sergio; Bär, Markus; Echebarria, Blas

2016-09-01

The beating of the heart is a synchronized contraction of muscle cells (myocytes) that is triggered by a periodic sequence of electrical waves (action potentials) originating in the sino-atrial node and propagating over the atria and the ventricles. Cardiac arrhythmias like atrial and ventricular fibrillation (AF,VF) or ventricular tachycardia (VT) are caused by disruptions and instabilities of these electrical excitations, that lead to the emergence of rotating waves (VT) and turbulent wave patterns (AF,VF). Numerous simulation and experimental studies during the last 20 years have addressed these topics. In this review we focus on the nonlinear dynamics of wave propagation in the heart with an emphasis on the theory of pulses, spirals and scroll waves and their instabilities in excitable media with applications to cardiac modeling. After an introduction into electrophysiological models for action potential propagation, the modeling and analysis of spatiotemporal alternans, spiral and scroll meandering, spiral breakup and scroll wave instabilities like negative line tension and sproing are reviewed in depth and discussed with emphasis on their impact for cardiac arrhythmias.

Role of ivabradine and heart rate lowering in chronic heart failure: guideline update.

PubMed

Chow, Sheryl L; Page, Robert Lee; Depre, Christophe

2018-06-14

This review summarizes the current management of heart failure (HF) in patients with reduced ejection fraction and the potential role of heart rate lowering agents in select populations, as recommended in the updated guidelines. Areas covered: PubMed was searched for studies that evaluated the role of heart rate lowering or ivabradine in HF management. Expert commentary: Targeting heart rate may offer benefit when added to renin-angiotensin aldosterone antagonists, and beta-blockers. Ivabradine is a heart rate lowering agent that acts on the funny current (I f ) in the sinoatrial node, thereby reducing heart rate without directly affecting cardiac contraction and relaxation. Clinical data from a phase 3 trial demonstrated that ivabradine reduced the composite endpoint of cardiovascular death or hospital admission for worsening systolic HF, while maintaining an acceptable safety profile in patients receiving standard of care therapy. These data, in addition to more recently published guidelines, suggest ivabradine as a promising new treatment option for lowering heart rate after optimizing standard therapy in select patients with chronic HF.

Genetic loci associated with heart rate variability and their effects on cardiac disease risk

PubMed Central

Nolte, Ilja M.; Munoz, M. Loretto; Tragante, Vinicius; Amare, Azmeraw T.; Jansen, Rick; Vaez, Ahmad; von der Heyde, Benedikt; Avery, Christy L.; Bis, Joshua C.; Dierckx, Bram; van Dongen, Jenny; Gogarten, Stephanie M.; Goyette, Philippe; Hernesniemi, Jussi; Huikari, Ville; Hwang, Shih-Jen; Jaju, Deepali; Kerr, Kathleen F.; Kluttig, Alexander; Krijthe, Bouwe P.; Kumar, Jitender; van der Laan, Sander W.; Lyytikäinen, Leo-Pekka; Maihofer, Adam X.; Minassian, Arpi; van der Most, Peter J.; Müller-Nurasyid, Martina; Nivard, Michel; Salvi, Erika; Stewart, James D.; Thayer, Julian F.; Verweij, Niek; Wong, Andrew; Zabaneh, Delilah; Zafarmand, Mohammad H.; Abdellaoui, Abdel; Albarwani, Sulayma; Albert, Christine; Alonso, Alvaro; Ashar, Foram; Auvinen, Juha; Axelsson, Tomas; Baker, Dewleen G.; de Bakker, Paul I. W.; Barcella, Matteo; Bayoumi, Riad; Bieringa, Rob J.; Boomsma, Dorret; Boucher, Gabrielle; Britton, Annie R.; Christophersen, Ingrid; Dietrich, Andrea; Ehret, George B.; Ellinor, Patrick T.; Eskola, Markku; Felix, Janine F.; Floras, John S.; Franco, Oscar H.; Friberg, Peter; Gademan, Maaike G. J.; Geyer, Mark A.; Giedraitis, Vilmantas; Hartman, Catharina A.; Hemerich, Daiane; Hofman, Albert; Hottenga, Jouke-Jan; Huikuri, Heikki; Hutri-Kähönen, Nina; Jouven, Xavier; Junttila, Juhani; Juonala, Markus; Kiviniemi, Antti M.; Kors, Jan A.; Kumari, Meena; Kuznetsova, Tatiana; Laurie, Cathy C.; Lefrandt, Joop D.; Li, Yong; Li, Yun; Liao, Duanping; Limacher, Marian C.; Lin, Henry J.; Lindgren, Cecilia M.; Lubitz, Steven A.; Mahajan, Anubha; McKnight, Barbara; zu Schwabedissen, Henriette Meyer; Milaneschi, Yuri; Mononen, Nina; Morris, Andrew P.; Nalls, Mike A.; Navis, Gerjan; Neijts, Melanie; Nikus, Kjell; North, Kari E.; O'Connor, Daniel T.; Ormel, Johan; Perz, Siegfried; Peters, Annette; Psaty, Bruce M.; Raitakari, Olli T.; Risbrough, Victoria B.; Sinner, Moritz F.; Siscovick, David; Smit, Johannes H.; Smith, Nicholas L.; Soliman, Elsayed Z.; Sotoodehnia, Nona; Staessen, Jan A.; Stein, Phyllis K.; Stilp, Adrienne M.; Stolarz-Skrzypek, Katarzyna; Strauch, Konstantin; Sundström, Johan; Swenne, Cees A.; Syvänen, Ann-Christine; Tardif, Jean-Claude; Taylor, Kent D.; Teumer, Alexander; Thornton, Timothy A.; Tinker, Lesley E.; Uitterlinden, André G.; van Setten, Jessica; Voss, Andreas; Waldenberger, Melanie; Wilhelmsen, Kirk C.; Willemsen, Gonneke; Wong, Quenna; Zhang, Zhu-Ming; Zonderman, Alan B.; Cusi, Daniele; Evans, Michele K.; Greiser, Halina K.; van der Harst, Pim; Hassan, Mohammad; Ingelsson, Erik; Järvelin, Marjo-Riitta; Kääb, Stefan; Kähönen, Mika; Kivimaki, Mika; Kooperberg, Charles; Kuh, Diana; Lehtimäki, Terho; Lind, Lars; Nievergelt, Caroline M.; O'Donnell, Chris J.; Oldehinkel, Albertine J.; Penninx, Brenda; Reiner, Alexander P.; Riese, Harriëtte; van Roon, Arie M.; Rioux, John D.; Rotter, Jerome I.; Sofer, Tamar; Stricker, Bruno H.; Tiemeier, Henning; Vrijkotte, Tanja G. M.; Asselbergs, Folkert W.; Brundel, Bianca J. J. M.; Heckbert, Susan R.; Whitsel, Eric A.; den Hoed, Marcel; Snieder, Harold; de Geus, Eco J. C.

2017-01-01

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (−0.74

Inhibition of sarcoplasmic reticulum Ca(2+)-ATPase decreases atrioventricular node-paced heart rate in rabbits.

PubMed

Cheng, Hongwei; Smith, Godfrey L; Orchard, Clive H; Hancox, Jules C; Burton, Francis L

2012-10-01

Recent data indicate that Ca(2+) cycling in isolated atrioventricular node (AVN) cells contributes to setting spontaneous rate. The aim of the present study was to extend this observation to the intact AVN in situ, by evaluating the effects of inhibiting sarcoplasmic reticulum Ca(2+) uptake with cyclopiazonic acid (CPA) on intact AVN spontaneous activity and its response to isoprenaline. A model of the AVN-paced heart was produced to investigate intact AVN automaticity, by surgical ablation of the sino-atrial node (SAN) in the rabbit Langendorff-perfused heart. Electrograms were recorded from a site close to the AVN (triangle of Koch), an atrial site above the AVN, the left atrium and right ventricle, enabling AVN pacing of the preparation to be confirmed. Before SAN ablation, the heart rate was 166.8 ± 5.4 beats min(-1). Ablation of the SAN was clearly indicated by a sudden and significant decrease of heart rate to 108.6 ± 9.6 beats min(-1) (P < 0.01, n = 10). Isoprenaline (100 nm) increased AVN rate to 187.8 ± 12.0 beats min(-1) after 1 min of application (P < 0.01, n = 10). Cyclopiazonic acid (10 and 30 μm) decreased AVN rate to 81.6 ± 4.8 (n = 9) and 77.4 ± 6.0 beats min(-1) (n = 7), respectively [P < 0.05, 10 or 30 μm CPA versus control (n = 10)] and also reduced the AVN rate increase in response to isoprenaline from 78.8 ± 10.0 to 46.8 ± 6.8 and 26.7 ± 5.3%, respectively (P < 0.01). These inhibitory effects of CPA on the intact AVN rate and its response to isoprenaline indicate that Ca(2+) cycling is important to the intact AVN spontaneous activity and its acceleration during sympathetic stimulation.

Acute desensitization of acetylcholine and endothelin-1 activated inward rectifier K+ current in myocytes from the cardiac atrioventricular node.

PubMed

Choisy, Stéphanie C M; James, Andrew F; Hancox, Jules C

2012-07-06

The atrioventricular node (AVN) is a vital component of the pacemaker-conduction system of the heart, co-ordinating conduction of electrical excitation from cardiac atria to ventricles and acting as a secondary pacemaker. The electrical behaviour of the AVN is modulated by vagal activity via activation of muscarinic potassium current, IKACh. However, it is not yet known if this response exhibits 'fade' or desensitization in the AVN, as established for the heart's primary pacemaker--the sinoatrial node. In this study, acute activation of IKACh in rabbit single AVN cells was investigated using whole-cell patch clamp at 37 °C. 0.1-1 μM acetylcholine (ACh) rapidly activated a robust IKACh in AVN myocytes during a descending voltage-ramp protocol. This response was inhibited by tertiapin-Q (TQ; 300 nM) and by the M2 muscarinic ACh receptor antagonist AFDX-116 (1 μM). During sustained ACh exposure the elicited IKACh exhibited bi-exponential fade (τf of 2.0 s and τs 76.9 s at -120 mV; 1 μM ACh). 10 nM ET-1 elicited a current similar to IKACh, which faded with a mono-exponential time-course (τ of 52.6 s at -120 mV). When ET-1 was applied following ACh, the ET-1 activated response was greatly attenuated, demonstrating that ACh could desensitize the response to ET-1. For neither ACh nor ET-1 was the rate of current fade dependent upon the initial response magnitude, which is inconsistent with K+ flux mediated changes in electrochemical driving force as the underlying mechanism. Collectively, these findings demonstrate that TQ sensitive inwardly rectifying K+ current in cardiac AVN cells, elicited by M2 muscarinic receptor or ET-1 receptor activation, exhibits fade due to rapid desensitization. Copyright © 2012 Elsevier Inc. All rights reserved.

Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart.

PubMed

Herrmann, Stefan; Layh, Beate; Ludwig, Andreas

2011-12-01

HCN pacemaker channels (I(f) channels) are believed to contribute to important functions in the heart; thus these channels became an attractive target for generating transgenic mouse mutants to elucidate their role in physiological and pathophysiological cardiac conditions. A full understanding of cardiac I(f) and the interpretation of studies using HCN mouse mutants require detailed information about the expression profile of the individual HCN subunits. Here we investigate the cardiac expression pattern of the HCN isoforms at the mRNA as well as at the protein level. The specificity of antibodies used was strictly confirmed by the use of HCN1, HCN2 and HCN4 knockout animals. We find a low, but highly differential HCN expression profile outside the cardiac conduction pathway including left and right atria and ventricles. Additionally HCN distribution was investigated in tissue slices of the sinoatrial node, the atrioventricular node, the bundle of His and the bundle branches. The conduction system was marked by acetylcholine esterase staining. HCN4 was confirmed as the predominant isoform of the primary pacemaker followed by a distinct expression of HCN1. In contrast HCN2 shows only a confined expression to individual pacemaker cells. Immunolabeling of the AV-node reveals also a pronounced specificity for HCN1 and HCN4. Compared to the SN and AVN we found a low but selective expression of HCN4 as the only isoform in the atrioventricular bundle. However in the bundle branches HCN1, HCN4 and also HCN2 show a prominent and selective expression pattern. Our results display a characteristic distribution of individual HCN isoforms in several cardiac compartments and reveal that beside HCN4, HCN1 represents the isoform which is selectively expressed in most parts of the conduction system suggesting a substantial contribution of HCN1 to pacemaking. 2011 Elsevier Ltd. All rights reserved.

Maximum heart rate in brown trout (Salmo trutta fario) is not limited by firing rate of pacemaker cells.

PubMed

Haverinen, Jaakko; Abramochkin, Denis V; Kamkin, Andre; Vornanen, Matti

2017-02-01

Temperature-induced changes in cardiac output (Q̇) in fish are largely dependent on thermal modulation of heart rate (f H ), and at high temperatures Q̇ collapses due to heat-dependent depression of f H This study tests the hypothesis that firing rate of sinoatrial pacemaker cells sets the upper thermal limit of f H in vivo. To this end, temperature dependence of action potential (AP) frequency of enzymatically isolated pacemaker cells (pacemaker rate, f PM ), spontaneous beating rate of isolated sinoatrial preparations (f SA ), and in vivo f H of the cold-acclimated (4°C) brown trout (Salmo trutta fario) were compared under acute thermal challenges. With rising temperature, f PM steadily increased because of the acceleration of diastolic depolarization and shortening of AP duration up to the break point temperature (T BP ) of 24.0 ± 0.37°C, at which point the electrical activity abruptly ceased. The maximum f PM at T BP was much higher [193 ± 21.0 beats per minute (bpm)] than the peak f SA (94.3 ± 6.0 bpm at 24.1°C) or peak f H (76.7 ± 2.4 at 15.7 ± 0.82°C) (P < 0.05). These findings strongly suggest that the frequency generator of the sinoatrial pacemaker cells does not limit f H at high temperatures in the brown trout in vivo. Copyright © 2017 the American Physiological Society.

Zebrafish heart as a model to study the integrative autonomic control of pacemaker function

PubMed Central

Stoyek, Matthew R.; Quinn, T. Alexander; Croll, Roger P.

2016-01-01

The cardiac pacemaker sets the heart's primary rate, with pacemaker discharge controlled by the autonomic nervous system through intracardiac ganglia. A fundamental issue in understanding the relationship between neural activity and cardiac chronotropy is the identification of neuronal populations that control pacemaker cells. To date, most studies of neurocardiac control have been done in mammalian species, where neurons are embedded in and distributed throughout the heart, so they are largely inaccessible for whole-organ, integrative studies. Here, we establish the isolated, innervated zebrafish heart as a novel alternative model for studies of autonomic control of heart rate. Stimulation of individual cardiac vagosympathetic nerve trunks evoked bradycardia (parasympathetic activation) and tachycardia (sympathetic activation). Simultaneous stimulation of both vagosympathetic nerve trunks evoked a summative effect. Effects of nerve stimulation were mimicked by direct application of cholinergic and adrenergic agents. Optical mapping of electrical activity confirmed the sinoatrial region as the site of origin of normal pacemaker activity and identified a secondary pacemaker in the atrioventricular region. Strong vagosympathetic nerve stimulation resulted in a shift in the origin of initial excitation from the sinoatrial pacemaker to the atrioventricular pacemaker. Putative pacemaker cells in the sinoatrial and atrioventricular regions expressed adrenergic β2 and cholinergic muscarinic type 2 receptors. Collectively, we have demonstrated that the zebrafish heart contains the accepted hallmarks of vertebrate cardiac control, establishing this preparation as a viable model for studies of integrative physiological control of cardiac function by intracardiac neurons. PMID:27342878

Tachycardia-bradycardia syndrome: Electrophysiological mechanisms and future therapeutic approaches (Review)

PubMed Central

Tse, Gary; Liu, Tong; Li, Ka Hou Christien; Laxton, Victoria; Wong, Andy On-Tik; Chan, Yin Wah Fiona; Keung, Wendy; Chan, Camie W.Y.; Li, Ronald A.

2017-01-01

Sick sinus syndrome (SSS) encompasses a group of disorders whereby the heart is unable to perform its pacemaker function, due to genetic and acquired causes. Tachycardia-bradycardia syndrome (TBS) is a complication of SSS characterized by alternating tachycardia and bradycardia. Techniques such as genetic screening and molecular diagnostics together with the use of pre-clinical models have elucidated the electrophysiological mechanisms of this condition. Dysfunction of ion channels responsible for initiation or conduction of cardiac action potentials may underlie both bradycardia and tachycardia; bradycardia can also increase the risk of tachycardia, and vice versa. The mainstay treatment option for SSS is pacemaker implantation, an effective approach, but has disadvantages such as infection, limited battery life, dislodgement of leads and catheters to be permanently implanted in situ. Alternatives to electronic pacemakers are gene-based bio-artificial sinoatrial node and cell-based bio-artificial pacemakers, which are promising techniques whose long-term safety and efficacy need to be established. The aim of this article is to review the different ion channels involved in TBS, examine the three-way relationship between ion channel dysfunction, tachycardia and bradycardia in TBS and to consider its current and future therapies. PMID:28204831

Tachycardia-bradycardia syndrome: Electrophysiological mechanisms and future therapeutic approaches (Review).

PubMed

Tse, Gary; Liu, Tong; Li, Ka Hou Christien; Laxton, Victoria; Wong, Andy On-Tik; Chan, Yin Wah Fiona; Keung, Wendy; Chan, Camie W Y; Li, Ronald A

2017-03-01

Sick sinus syndrome (SSS) encompasses a group of disorders whereby the heart is unable to perform its pacemaker function, due to genetic and acquired causes. Tachycardia‑bradycardia syndrome (TBS) is a complication of SSS characterized by alternating tachycardia and bradycardia. Techniques such as genetic screening and molecular diagnostics together with the use of pre-clinical models have elucidated the electrophysiological mechanisms of this condition. Dysfunction of ion channels responsible for initiation or conduction of cardiac action potentials may underlie both bradycardia and tachycardia; bradycardia can also increase the risk of tachycardia, and vice versa. The mainstay treatment option for SSS is pacemaker implantation, an effective approach, but has disadvantages such as infection, limited battery life, dislodgement of leads and catheters to be permanently implanted in situ. Alternatives to electronic pacemakers are gene‑based bio‑artificial sinoatrial node and cell‑based bio‑artificial pacemakers, which are promising techniques whose long-term safety and efficacy need to be established. The aim of this article is to review the different ion channels involved in TBS, examine the three‑way relationship between ion channel dysfunction, tachycardia and bradycardia in TBS and to consider its current and future therapies.

Reduced intrinsic heart rate is associated with reduced arrhythmic susceptibility in guinea-pig heart.

PubMed

Osadchii, Oleg E

2014-12-01

In the clinical setting, patients with slower resting heart rate are less prone to cardiovascular death compared with those with elevated heart rate. However, electrophysiological adaptations associated with reduced cardiac rhythm have not been thoroughly explored. In this study, relationships between intrinsic heart rate and arrhythmic susceptibility were examined by assessments of action potential duration (APD) rate adaptation and inducibility of repolarization alternans in sinoatrial node (SAN)-driven and atrioventricular (AV)-blocked guinea-pig hearts perfused with Langendorff apparatus. Electrocardiograms, epicardial monophasic action potentials, and effective refractory periods (ERP) were assessed in normokalemic and hypokalemic conditions. Slower basal heart rate in AV-blocked hearts was associated with prolonged ventricular repolarization during spontaneous beating, and with attenuated APD shortening at increased cardiac activation rates during dynamic pacing, when compared with SAN-driven hearts. During hypokalemic perfusion, the inducibility of repolarization alternans and tachyarrhythmia by rapid pacing was found to be lower in AV-blocked hearts. This difference was ascribed to prolonged ERP in the setting of reduced basal heart rate, which prevented ventricular capture at critically short pacing intervals required to induce arrhythmia. Reduced basal heart rate is associated with electrophysiological changes that prevent electrical instability upon an abrupt cardiac acceleration.

Accelerating sino-atrium computer simulations with graphic processing units.

PubMed

Zhang, Hong; Xiao, Zheng; Lin, Shien-fong

2015-01-01

Sino-atrial node cells (SANCs) play a significant role in rhythmic firing. To investigate their role in arrhythmia and interactions with the atrium, computer simulations based on cellular dynamic mathematical models are generally used. However, the large-scale computation usually makes research difficult, given the limited computational power of Central Processing Units (CPUs). In this paper, an accelerating approach with Graphic Processing Units (GPUs) is proposed in a simulation consisting of the SAN tissue and the adjoining atrium. By using the operator splitting method, the computational task was made parallel. Three parallelization strategies were then put forward. The strategy with the shortest running time was further optimized by considering block size, data transfer and partition. The results showed that for a simulation with 500 SANCs and 30 atrial cells, the execution time taken by the non-optimized program decreased 62% with respect to a serial program running on CPU. The execution time decreased by 80% after the program was optimized. The larger the tissue was, the more significant the acceleration became. The results demonstrated the effectiveness of the proposed GPU-accelerating methods and their promising applications in more complicated biological simulations.

New Medications for Heart Failure

PubMed Central

Gordin, Jonathan S.; Fonarow, Gregg C.

2016-01-01

Heart failure is common and results in substantial morbidity and mortality. Current guideline-based therapies for heart failure with reduced ejection fraction, including beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and aldosterone antagonists aim to interrupt deleterious neurohormonal pathways and have shown significant success in reducing morbidity and mortality associated with heart failure. Continued efforts to further improve outcomes in patients with heart failure with reduced ejection fraction have led to the first new-in-class medications approved for heart failure since 2005, ivabradine and sacubitril/valsartan. Ivabradine targets the If channels in the sinoatrial node of the heart, decreasing heart rate. Sacubitril/valsartan combines a neprilysin inhibitor that increases levels of beneficial vasodilatory peptides with an angiotensin receptor antagonist. On a background of previously approved, guideline-directed medical therapies for heart failure, these medications have shown improved clinical outcomes ranging from decreased hospitalizations in a select group of patients to a reduction in all-cause mortality across all pre-specified subgroups. In this review, we will discuss the previously established guideline-directed medical therapies for heart failure with reduced ejection fraction, the translational research that led to the development of these new therapies, and the results from the major clinical trials of ivabradine and sacubitril/valsartan. PMID:27038558

Diadenosine pentaphosphate affects electrical activity in guinea pig atrium via activation of potassium acetylcholine-dependent inward rectifier.

PubMed

Abramochkin, Denis V; Karimova, Viktoria M; Filatova, Tatiana S; Kamkin, Andre

2017-07-01

Diadenosine pentaphosphate (Ap5A) belongs to the family of diadenosine polyphosphates, endogenously produced compounds that affect vascular tone and cardiac performance when released from platelets. The previous findings indicate that Ap5A shortens action potentials (APs) in rat myocardium via activation of purine P2 receptors. The present study demonstrates alternative mechanism of Ap5A electrophysiological effects found in guinea pig myocardium. Ap5A (10 -4  M) shortens APs in guinea pig working atrial myocardium and slows down pacemaker activity in the sinoatrial node. P1 receptors antagonist DPCPX (10 -7  M) or selective GIRK channels blocker tertiapin (10 -6  M) completely abolished all Ap5A effects, while P2 blocker PPADS (10 -4  M) was ineffective. Patch-clamp experiments revealed potassium inward rectifier current activated by Ap5A in guinea pig atrial myocytes. The current was abolished by DPCPX or tertiapin and therefore was considered as potassium acetylcholine-dependent inward rectifier (I KACh ). Thus, unlike rat, in guinea pig atrium Ap5A produces activation of P1 receptors and subsequent opening of KACh channels leading to negative effects on cardiac electrical activity.

Identification of nodal tissue in the living heart using rapid scanning fiber-optics confocal microscopy and extracellular fluorophores.

PubMed

Huang, Chao; Kaza, Aditya K; Hitchcock, Robert W; Sachse, Frank B

2013-09-01

Risks associated with pediatric reconstructive heart surgery include injury of the sinoatrial node (SAN) and atrioventricular node (AVN), requiring cardiac rhythm management using implantable pacemakers. These injuries are the result of difficulties in identifying nodal tissues intraoperatively. Here we describe an approach based on confocal microscopy and extracellular fluorophores to quantify tissue microstructure and identify nodal tissue. Using conventional 3-dimensional confocal microscopy we investigated the microstructural arrangement of SAN, AVN, and atrial working myocardium (AWM) in fixed rat heart. AWM exhibited a regular striated arrangement of the extracellular space. In contrast, SAN and AVN had an irregular, reticulated arrangement. AWM, SAN, and AVN tissues were beneath a thin surface layer of tissue that did not obstruct confocal microscopic imaging. Subsequently, we imaged tissues in living rat hearts with real-time fiber-optics confocal microscopy. Fiber-optics confocal microscopy images resembled images acquired with conventional confocal microscopy. We investigated spatial regularity of tissue microstructure from Fourier analysis and second-order image moments. Fourier analysis of fiber-optics confocal microscopy images showed that the spatial regularity of AWM was greater than that of nodal tissues (37.5 ± 5.0% versus 24.3 ± 3.9% for SAN and 23.8 ± 3.7% for AVN; P<0.05). Similar differences of spatial regularities were revealed from second-order image moments (50.0 ± 7.3% for AWM versus 29.3 ± 6.7% for SAN and 27.3 ± 5.5% for AVN; P<0.05). The study demonstrates feasibility of identifying nodal tissue in living heart using extracellular fluorophores and fiber-optics confocal microscopy. Application of the approach in pediatric reconstructive heart surgery may reduce risks of injuring nodal tissues.

An updated computational model of rabbit sinoatrial action potential to investigate the mechanisms of heart rate modulation

PubMed Central

Severi, Stefano; Fantini, Matteo; Charawi, Lara A; DiFrancesco, Dario

2012-01-01

The cellular basis of cardiac pacemaking is still debated. Reliable computational models of the sinoatrial node (SAN) action potential (AP) may help gain a deeper understanding of the phenomenon. Recently, novel models incorporating detailed Ca2+-handling dynamics have been proposed, but they fail to reproduce a number of experimental data, and more specifically effects of ‘funny’ (If) current modifications. We therefore developed a SAN AP model, based on available experimental data, in an attempt to reproduce physiological and pharmacological heart rate modulation. Cell compartmentalization and intracellular Ca2+-handling mechanisms were formulated as in the Maltsev–Lakatta model, focusing on Ca2+-cycling processes. Membrane current equations were revised on the basis of published experimental data. Modifications of the formulation of currents/pumps/exchangers to simulate If blockers, autonomic modulators and Ca2+-dependent mechanisms (ivabradine, caesium, acetylcholine, isoprenaline, BAPTA) were derived from experimental data. The model generates AP waveforms typical of rabbit SAN cells, whose parameters fall within the experimental ranges: 352 ms cycle length, 80 mV AP amplitude, −58 mV maximum diastolic potential (MDP), 108 ms APD50, and 7.1 V s−1 maximum upstroke velocity. Rate modulation by If-blocking drugs agrees with experimental findings: 20% and 22% caesium-induced (5 mm) and ivabradine-induced (3 μm) rate reductions, respectively, due to changes in diastolic depolarization (DD) slope, with no changes in either MDP or take-off potential (TOP). The model consistently reproduces the effects of autonomic modulation: 20% rate decrease with 10 nm acetylcholine and 28% increase with 1 μm isoprenaline, again entirely due to increase in the DD slope, with no changes in either MDP or TOP. Model testing of BAPTA effects showed slowing of rate, −26%, without cessation of beating. Our up-to-date model describes satisfactorily experimental data concerning autonomic stimulation, funny-channel blockade and inhibition of the Ca2+-related system by BAPTA, making it a useful tool for further investigation. Simulation results suggest that a detailed description of the intracellular Ca2+ fluxes is fully compatible with the observation that If is a major component of pacemaking and rate modulation. PMID:22711956

Intracardiac Origin of Heart Rate Variability, Pacemaker Funny Current and their Possible Association with Critical Illness

PubMed Central

Papaioannou, Vasilios E; Verkerk, Arie O; Amin, Ahmed S; de Bakker, Jaques MT

2013-01-01

Heart rate variability (HRV) is an indirect estimator of autonomic modulation of heart rate and is considered a risk marker in critical illness, particularly in heart failure and severe sepsis. A reduced HRV has been found in critically ill patients and has been associated with neuro-autonomic uncoupling or decreased baroreflex sensitivity. However, results from human and animal experimental studies indicate that intracardiac mechanisms might also be responsible for interbeat fluctuations. These studies have demonstrated that different membrane channel proteins and especially the so-called ‘funny’ current (If), an hyperpolarization-activated, inward current that drives diastolic depolarization resulting in spontaneous activity in cardiac pacemaker cells, are altered during critical illness. Furthermore, membrane channels kinetics seem to have significant impact upon HRV, whose early decrease might reflect a cellular metabolic stress. In this review article we present research findings regarding intracardiac origin of HRV, at the cellular level and in both isolated sinoatrial node and whole ex vivo heart preparations. In addition, we will review results from various experimental studies that support the interrelation between If and HRV during endotoxemia. We suggest that reduced HRV during sepsis could also be associated with altered pacemaker cell membrane properties, due to ionic current remodeling. PMID:22920474

Characterization of QT and RR interval series during acute myocardial ischemia by means of recurrence quantification analysis.

PubMed

Peng, Yi; Sun, Zhongwei

2011-01-01

This study is aimed to investigate the nonlinear dynamic properties of the fluctuations in ventricular repolarization, heart rate and their correlation during acute myocardial ischemia. From 13 ECG records in long-term ST-T database, 170 ischemic episodes were selected with the duration of 34 s to 23 min 18 s, and two 5-min episodes immediately before and after each ischemic episode as non-ischemic ones for comparison. QT interval (QTI) and RR interval (RRI) were extracted and the ectopic beats were removed. Recurrence quantification analysis (RQA) was performed on QTI and RRI series, respectively, and cross recurrence quantification analysis (CRQA) on paired normalized QTI and RRI series. Wilcoxon signed-rank test was used for statistical analysis. Results revealed that the RQA indexes for QTI and HRI series had the same changing trend during ischemia with more significantly changed indexes in QTI series. In the CRQA, indexes related to the vertical and horizontal structures in recurrence plot significantly increased, representing decreased dependency of QTI on RRI. Both QTI and RRI series showed reduced complexity during ischemia with higher sensitivity in ventricular repolarization. The weakened coupling between QTI and RRI suggests the decreased influence of sinoatrial node on QTI modulation during ischemia.

The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction - baseline characteristics of the study population.

PubMed

Ferrari, R; Ford, I; Fox, K; Steg, P G; Tendera, M

2008-01-01

Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients. (c) 2007 S. Karger AG, Basel

Functional Characterization of Cnidarian HCN Channels Points to an Early Evolution of Ih.

PubMed

Baker, Emma C; Layden, Michael J; van Rossum, Damian B; Kamel, Bishoy; Medina, Monica; Simpson, Eboni; Jegla, Timothy

2015-01-01

HCN channels play a unique role in bilaterian physiology as the only hyperpolarization-gated cation channels. Their voltage-gating is regulated by cyclic nucleotides and phosphatidylinositol 4,5-bisphosphate (PIP2). Activation of HCN channels provides the depolarizing current in response to hyperpolarization that is critical for intrinsic rhythmicity in neurons and the sinoatrial node. Additionally, HCN channels regulate dendritic excitability in a wide variety of neurons. Little is known about the early functional evolution of HCN channels, but the presence of HCN sequences in basal metazoan phyla and choanoflagellates, a protozoan sister group to the metazoans, indicate that the gene family predates metazoan emergence. We functionally characterized two HCN channel orthologs from Nematostella vectensis (Cnidaria, Anthozoa) to determine which properties of HCN channels were established prior to the emergence of bilaterians. We find Nematostella HCN channels share all the major functional features of bilaterian HCNs, including reversed voltage-dependence, activation by cAMP and PIP2, and block by extracellular Cs+. Thus bilaterian-like HCN channels were already present in the common parahoxozoan ancestor of bilaterians and cnidarians, at a time when the functional diversity of voltage-gated K+ channels was rapidly expanding. NvHCN1 and NvHCN2 are expressed broadly in planulae and in both the endoderm and ectoderm of juvenile polyps.

Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology

PubMed Central

Roncaglia, Paola; Howe, Douglas G.; Laulederkind, Stanley J.F.; Khodiyar, Varsha K.; Berardini, Tanya Z.; Tweedie, Susan; Foulger, Rebecca E.; Osumi-Sutherland, David; Campbell, Nancy H.; Huntley, Rachael P.; Talmud, Philippa J.; Blake, Judith A.; Breckenridge, Ross; Riley, Paul R.; Lambiase, Pier D.; Elliott, Perry M.; Clapp, Lucie; Tinker, Andrew; Hill, David P.

2018-01-01

Background: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. Methods and Results: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. Conclusions: We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. PMID:29440116

Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.

PubMed

Lin, Honghuang; van Setten, Jessica; Smith, Albert V; Bihlmeyer, Nathan A; Warren, Helen R; Brody, Jennifer A; Radmanesh, Farid; Hall, Leanne; Grarup, Niels; Müller-Nurasyid, Martina; Boutin, Thibaud; Verweij, Niek; Lin, Henry J; Li-Gao, Ruifang; van den Berg, Marten E; Marten, Jonathan; Weiss, Stefan; Prins, Bram P; Haessler, Jeffrey; Lyytikäinen, Leo-Pekka; Mei, Hao; Harris, Tamara B; Launer, Lenore J; Li, Man; Alonso, Alvaro; Soliman, Elsayed Z; Connell, John M; Huang, Paul L; Weng, Lu-Chen; Jameson, Heather S; Hucker, William; Hanley, Alan; Tucker, Nathan R; Chen, Yii-Der Ida; Bis, Joshua C; Rice, Kenneth M; Sitlani, Colleen M; Kors, Jan A; Xie, Zhijun; Wen, Chengping; Magnani, Jared W; Nelson, Christopher P; Kanters, Jørgen K; Sinner, Moritz F; Strauch, Konstantin; Peters, Annette; Waldenberger, Melanie; Meitinger, Thomas; Bork-Jensen, Jette; Pedersen, Oluf; Linneberg, Allan; Rudan, Igor; de Boer, Rudolf A; van der Meer, Peter; Yao, Jie; Guo, Xiuqing; Taylor, Kent D; Sotoodehnia, Nona; Rotter, Jerome I; Mook-Kanamori, Dennis O; Trompet, Stella; Rivadeneira, Fernando; Uitterlinden, André; Eijgelsheim, Mark; Padmanabhan, Sandosh; Smith, Blair H; Völzke, Henry; Felix, Stephan B; Homuth, Georg; Völker, Uwe; Mangino, Massimo; Spector, Timothy D; Bots, Michiel L; Perez, Marco; Kähönen, Mika; Raitakari, Olli T; Gudnason, Vilmundur; Arking, Dan E; Munroe, Patricia B; Psaty, Bruce M; van Duijn, Cornelia M; Benjamin, Emelia J; Rosand, Jonathan; Samani, Nilesh J; Hansen, Torben; Kääb, Stefan; Polasek, Ozren; van der Harst, Pim; Heckbert, Susan R; Jukema, J Wouter; Stricker, Bruno H; Hayward, Caroline; Dörr, Marcus; Jamshidi, Yalda; Asselbergs, Folkert W; Kooperberg, Charles; Lehtimäki, Terho; Wilson, James G; Ellinor, Patrick T; Lubitz, Steven A; Isaacs, Aaron

2018-05-01

Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability. We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval. We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction ( P <1.2×10 -6 ), including 11 novel loci that have not been reported previously. Many of these loci are involved in heart morphogenesis. In gene-based analysis, we found that multiple rare variants at MYH6 ( P =5.9×10 -11 ) and SCN5A ( P =1.1×10 -7 ) were associated with PR interval. SCN5A locus also was implicated in the common variant analysis, whereas MYH6 was a novel locus. We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health. © 2018 American Heart Association, Inc.

Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology.

PubMed

Lovering, Ruth C; Roncaglia, Paola; Howe, Douglas G; Laulederkind, Stanley J F; Khodiyar, Varsha K; Berardini, Tanya Z; Tweedie, Susan; Foulger, Rebecca E; Osumi-Sutherland, David; Campbell, Nancy H; Huntley, Rachael P; Talmud, Philippa J; Blake, Judith A; Breckenridge, Ross; Riley, Paul R; Lambiase, Pier D; Elliott, Perry M; Clapp, Lucie; Tinker, Andrew; Hill, David P

2018-02-01

A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. © 2018 The Authors.

RGS6, but not RGS4, is the dominant regulator of G protein signaling (RGS) modulator of the parasympathetic regulation of mouse heart rate.

PubMed

Wydeven, Nicole; Posokhova, Ekaterina; Xia, Zhilian; Martemyanov, Kirill A; Wickman, Kevin

2014-01-24

Parasympathetic activity decreases heart rate (HR) by inhibiting pacemaker cells in the sinoatrial node (SAN). Dysregulation of parasympathetic influence has been linked to sinus node dysfunction and arrhythmia. RGS (regulator of G protein signaling) proteins are negative modulators of the parasympathetic regulation of HR and the prototypical M2 muscarinic receptor (M2R)-dependent signaling pathway in the SAN that involves the muscarinic-gated atrial K(+) channel IKACh. Both RGS4 and RGS6-Gβ5 have been implicated in these processes. Here, we used Rgs4(-/-), Rgs6(-/-), and Rgs4(-/-):Rgs6(-/-) mice to compare the relative influence of RGS4 and RGS6 on parasympathetic regulation of HR and M2R-IKACh-dependent signaling in the SAN. In retrogradely perfused hearts, ablation of RGS6, but not RGS4, correlated with decreased resting HR, increased heart rate variability, and enhanced sensitivity to the negative chronotropic effects of the muscarinic agonist carbachol. Similarly, loss of RGS6, but not RGS4, correlated with enhanced sensitivity of the M2R-IKACh signaling pathway in SAN cells to carbachol and a significant slowing of M2R-IKACh deactivation rate. Surprisingly, concurrent genetic ablation of RGS4 partially rescued some deficits observed in Rgs6(-/-) mice. These findings, together with those from an acute pharmacologic approach in SAN cells from Rgs6(-/-) and Gβ5(-/-) mice, suggest that the partial rescue of phenotypes in Rgs4(-/-):Rgs6(-/-) mice is attributable to another R7 RGS protein whose influence on M2R-IKACh signaling is masked by RGS4. Thus, RGS6-Gβ5, but not RGS4, is the primary RGS modulator of parasympathetic HR regulation and SAN M2R-IKACh signaling in mice.

RyR2R420Q catecholaminergic polymorphic ventricular tachycardia mutation induces bradycardia by disturbing the coupled clock pacemaker mechanism

PubMed Central

Wang, Yue Yi; Mesirca, Pietro; Marqués-Sulé, Elena; Villejoubert, Olivier; D’Ocon, Pilar; Ruiz, Cristina; Domingo, Diana; Zorio, Esther; Mangoni, Matteo E.; Benitah, Jean-Pierre; Gómez, Ana María

2017-01-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal genetic arrhythmia that manifests syncope or sudden death in children and young adults under stress conditions. CPVT patients often present bradycardia and sino-atrial node (SAN) dysfunction. However, the mechanism remains unclear. We analyzed SAN function in two CPVT families and in a novel knock-in (KI) mouse model carrying the RyR2R420Q mutation. Humans and KI mice presented slower resting heart rate. Accordingly, the rate of spontaneous intracellular Ca2+ ([Ca2+]i) transients was slower in KI mouse SAN preparations than in WT, without any significant alteration in the “funny” current (If ). The L-type Ca2+ current was reduced in KI SAN cells in a [Ca2+]i-dependent way, suggesting that bradycardia was due to disrupted crosstalk between the “voltage” and “Ca2+” clock, and the mechanisms of pacemaking was induced by aberrant spontaneous RyR2- dependent Ca2+ release. This finding was consistent with a higher Ca2+ leak during diastolic periods produced by long-lasting Ca2+ sparks in KI SAN cells. Our results uncover a mechanism for the CPVT-causing RyR2 N-terminal mutation R420Q, and they highlight the fact that enhancing the Ca2+ clock may slow the heart rhythm by disturbing the coupling between Ca2+ and voltage clocks. PMID:28422759

Ablation of RIC8A function in mouse neurons leads to a severe neuromuscular phenotype and postnatal death.

PubMed

Ruisu, Katrin; Kask, Keiu; Meier, Riho; Saare, Merly; Raid, Raivo; Veraksitš, Alar; Karis, Alar; Tõnissoo, Tambet; Pooga, Margus

2013-01-01

Resistance to inhibitors of cholinesterase 8 (RIC8) is a guanine nucleotide exchange factor required for the intracellular regulation of G protein signalling. RIC8 activates different Gα subunits via non-canonical pathway, thereby amplifying and prolonging the G protein mediated signal. In order to circumvent the embryonic lethality associated with the absence of RIC8A and to study its role in the nervous system, we constructed Ric8a conditional knockout mice using Cre/loxP technology. Introduction of a synapsin I promoter driven Cre transgenic mouse strain (SynCre) into the floxed Ric8a (Ric8a (F/F) ) background ablated RIC8A function in most differentiated neuron populations. Mutant SynCre (+/-) Ric8 (lacZ/F) mice were born at expected Mendelian ratio, but they died in early postnatal age (P4-P6). The mutants exhibited major developmental defects, like growth retardation and muscular weakness, impaired coordination and balance, muscular spasms and abnormal heart beat. Histological analysis revealed that the deficiency of RIC8A in neurons caused skeletal muscle atrophy and heart muscle hypoplasia, in addition, the sinoatrial node was misplaced and its size reduced. However, we did not observe gross morphological changes in brains of SynCre (+/-) Ric8a (lacZ/F) mutants. Our results demonstrate that in mice the activity of RIC8A in neurons is essential for survival and its deficiency causes a severe neuromuscular phenotype.

Ablation of RIC8A Function in Mouse Neurons Leads to a Severe Neuromuscular Phenotype and Postnatal Death

PubMed Central

Ruisu, Katrin; Kask, Keiu; Meier, Riho; Saare, Merly; Raid, Raivo; Veraksitš, Alar; Karis, Alar; Tõnissoo, Tambet; Pooga, Margus

2013-01-01

Resistance to inhibitors of cholinesterase 8 (RIC8) is a guanine nucleotide exchange factor required for the intracellular regulation of G protein signalling. RIC8 activates different Gα subunits via non-canonical pathway, thereby amplifying and prolonging the G protein mediated signal. In order to circumvent the embryonic lethality associated with the absence of RIC8A and to study its role in the nervous system, we constructed Ric8a conditional knockout mice using Cre/loxP technology. Introduction of a synapsin I promoter driven Cre transgenic mouse strain (SynCre) into the floxed Ric8a (Ric8a F/F) background ablated RIC8A function in most differentiated neuron populations. Mutant SynCre +/- Ric8 lacZ/F mice were born at expected Mendelian ratio, but they died in early postnatal age (P4-P6). The mutants exhibited major developmental defects, like growth retardation and muscular weakness, impaired coordination and balance, muscular spasms and abnormal heart beat. Histological analysis revealed that the deficiency of RIC8A in neurons caused skeletal muscle atrophy and heart muscle hypoplasia, in addition, the sinoatrial node was misplaced and its size reduced. However, we did not observe gross morphological changes in brains of SynCre +/- Ric8a lacZ/F mutants. Our results demonstrate that in mice the activity of RIC8A in neurons is essential for survival and its deficiency causes a severe neuromuscular phenotype. PMID:23977396

Calcium dynamics in cardiac excitatory and non-excitatory cells and the role of gap junction.

PubMed

Das, Phonindra Nath; Mehrotra, Parul; Mishra, Aseem; Bairagi, Nandadulal; Chatterjee, Samrat

2017-07-01

Calcium ions aid in the generation of action potential in myocytes and are responsible for the excitation-contraction coupling of heart. The heart muscle has specialized patches of cells, called excitatory cells (EC) such as the Sino-atrial node cells capable of auto-generation of action potential and cells which receive signals from the excitatory cells, called non-excitatory cells (NEC) such as cells of the ventricular and auricular walls. In order to understand cardiac calcium homeostasis, it is, therefore, important to study the calcium dynamics taking into account both types of cardiac cells. Here we have developed a model to capture the calcium dynamics in excitatory and non-excitatory cells taking into consideration the gap junction mediated calcium ion transfer from excitatory cell to non-excitatory cell. Our study revealed that the gap junctional coupling between excitatory and non-excitatory cells plays important role in the calcium dynamics. It is observed that any reduction in the functioning of gap junction may result in abnormal calcium oscillations in NEC, even when the calcium dynamics is normal in EC cell. Sensitivity of gap junction is observed to be independent of the pacing rate and hence a careful monitoring is required to maintain normal cardiomyocyte condition. It also highlights that sarcoplasmic reticulum may not be always able to control the amount of cytoplasmic calcium under the condition of calcium overload. Copyright © 2017 Elsevier Inc. All rights reserved.

Murine Electrophysiological Models of Cardiac Arrhythmogenesis

PubMed Central

2016-01-01

Cardiac arrhythmias can follow disruption of the normal cellular electrophysiological processes underlying excitable activity and their tissue propagation as coherent wavefronts from the primary sinoatrial node pacemaker, through the atria, conducting structures and ventricular myocardium. These physiological events are driven by interacting, voltage-dependent, processes of activation, inactivation, and recovery in the ion channels present in cardiomyocyte membranes. Generation and conduction of these events are further modulated by intracellular Ca2+ homeostasis, and metabolic and structural change. This review describes experimental studies on murine models for known clinical arrhythmic conditions in which these mechanisms were modified by genetic, physiological, or pharmacological manipulation. These exemplars yielded molecular, physiological, and structural phenotypes often directly translatable to their corresponding clinical conditions, which could be investigated at the molecular, cellular, tissue, organ, and whole animal levels. Arrhythmogenesis could be explored during normal pacing activity, regular stimulation, following imposed extra-stimuli, or during progressively incremented steady pacing frequencies. Arrhythmic substrate was identified with temporal and spatial functional heterogeneities predisposing to reentrant excitation phenomena. These could arise from abnormalities in cardiac pacing function, tissue electrical connectivity, and cellular excitation and recovery. Triggering events during or following recovery from action potential excitation could thereby lead to sustained arrhythmia. These surface membrane processes were modified by alterations in cellular Ca2+ homeostasis and energetics, as well as cellular and tissue structural change. Study of murine systems thus offers major insights into both our understanding of normal cardiac activity and its propagation, and their relationship to mechanisms generating clinical arrhythmias. PMID:27974512

Essential Role of the m2R-RGS6-IKACh Pathway in Controlling Intrinsic Heart Rate Variability

PubMed Central

Posokhova, Ekaterina; Ng, David; Opel, Aaisha; Masuho, Ikuo; Tinker, Andrew; Biesecker, Leslie G.; Wickman, Kevin; Martemyanov, Kirill A.

2013-01-01

Normal heart function requires generation of a regular rhythm by sinoatrial pacemaker cells and the alteration of this spontaneous heart rate by the autonomic input to match physiological demand. However, the molecular mechanisms that ensure consistent periodicity of cardiac contractions and fine tuning of this process by autonomic system are not completely understood. Here we examined the contribution of the m2R-IKACh intracellular signaling pathway, which mediates the negative chronotropic effect of parasympathetic stimulation, to the regulation of the cardiac pacemaking rhythm. Using isolated heart preparations and single-cell recordings we show that the m2R-IKACh signaling pathway controls the excitability and firing pattern of the sinoatrial cardiomyocytes and determines variability of cardiac rhythm in a manner independent from the autonomic input. Ablation of the major regulator of this pathway, Rgs6, in mice results in irregular cardiac rhythmicity and increases susceptibility to atrial fibrillation. We further identify several human subjects with variants in the RGS6 gene and show that the loss of function in RGS6 correlates with increased heart rate variability. These findings identify the essential role of the m2R-IKACh signaling pathway in the regulation of cardiac sinus rhythm and implicate RGS6 in arrhythmia pathogenesis. PMID:24204714

Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and Genetic Evidence for Direct S1P3 Regulation of Mouse Cardiac Conduction.

PubMed

Sanna, M Germana; Vincent, Kevin P; Repetto, Emanuela; Nguyen, Nhan; Brown, Steven J; Abgaryan, Lusine; Riley, Sean W; Leaf, Nora B; Cahalan, Stuart M; Kiosses, William B; Kohno, Yasushi; Brown, Joan Heller; McCulloch, Andrew D; Rosen, Hugh; Gonzalez-Cabrera, Pedro J

2016-01-01

The molecular pharmacology of the G protein-coupled receptors for sphingosine 1-phosphate (S1P) provides important insight into established and new therapeutic targets. A new, potent bitopic S1P3 antagonist, SPM-354, with in vivo activity, has been used, together with S1P3-knockin and S1P3-knockout mice to define the spatial and functional properties of S1P3 in regulating cardiac conduction. We show that S1P3 is a key direct regulator of cardiac rhythm both in vivo and in isolated perfused hearts. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in vivo and S1P in isolated hearts induced a spectrum of cardiac effects, ranging from sinus bradycardia to complete heart block, as measured by a surface electrocardiogram in anesthetized mice and in volume-conducted Langendorff preparations. The agonist effects on complete heart block are absent in S1P3-knockout mice and are reversed in wild-type mice with SPM-354, as characterized and described here. Homologous knockin of S1P3-mCherry is fully functional pharmacologically and is strongly expressed by immunohistochemistry confocal microscopy in Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 4 (HCN4)-positive atrioventricular node and His-Purkinje fibers, with relative less expression in the HCN4-positive sinoatrial node. In Langendorff studies, at constant pressure, SPM-354 restored sinus rhythm in S1P-induced complete heart block and fully reversed S1P-mediated bradycardia. S1P3 distribution and function in the mouse ventricular cardiac conduction system suggest a direct mechanism for heart block risk that should be further studied in humans. A richer understanding of receptor and ligand usage in the pacemaker cells of the cardiac system is likely to be useful in understanding ventricular conduction in health, disease, and pharmacology. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Ca(2+)/calmodulin-activated phosphodiesterase 1A is highly expressed in rabbit cardiac sinoatrial nodal cells and regulates pacemaker function.

PubMed

Lukyanenko, Yevgeniya O; Younes, Antoine; Lyashkov, Alexey E; Tarasov, Kirill V; Riordon, Daniel R; Lee, Joonho; Sirenko, Syevda G; Kobrinsky, Evgeny; Ziman, Bruce; Tarasova, Yelena S; Juhaszova, Magdalena; Sollott, Steven J; Graham, David R; Lakatta, Edward G

2016-09-01

Constitutive Ca(2+)/calmodulin (CaM)-activation of adenylyl cyclases (ACs) types 1 and 8 in sinoatrial nodal cells (SANC) generates cAMP within lipid-raft-rich microdomains to initiate cAMP-protein kinase A (PKA) signaling, that regulates basal state rhythmic action potential firing of these cells. Mounting evidence in other cell types points to a balance between Ca(2+)-activated counteracting enzymes, ACs and phosphodiesterases (PDEs) within these cells. We hypothesized that the expression and activity of Ca(2+)/CaM-activated PDE Type 1A is higher in SANC than in other cardiac cell types. We found that PDE1A protein expression was 5-fold higher in sinoatrial nodal tissue than in left ventricle, and its mRNA expression was 12-fold greater in the corresponding isolated cells. PDE1 activity (nimodipine-sensitive) accounted for 39% of the total PDE activity in SANC lysates, compared to only 4% in left ventricular cardiomyocytes (LVC). Additionally, total PDE activity in SANC lysates was lowest (10%) in lipid-raft-rich and highest (76%) in lipid-raft-poor fractions (equilibrium sedimentation on a sucrose density gradient). In intact cells PDE1A immunolabeling was not localized to the cell surface membrane (structured illumination microscopy imaging), but located approximately within about 150nm inside of immunolabeling of hyperpolarization-activated cyclic nucleotide-gated potassium channels (HCN4), which reside within lipid-raft-rich microenvironments. In permeabilized SANC, in which surface membrane ion channels are not functional, nimodipine increased spontaneous SR Ca(2+) cycling. PDE1A mRNA silencing in HL-1 cells increased the spontaneous beating rate, reduced the cAMP, and increased cGMP levels in response to IBMX, a broad spectrum PDE inhibitor (detected via fluorescence resonance energy transfer microscopy). We conclude that signaling via cAMP generated by Ca(2+)/CaM-activated AC in SANC lipid raft domains is limited by cAMP degradation by Ca(2+)/CaM-activated PDE1A in non-lipid raft domains. This suggests that local gradients of [Ca(2+)]-CaM or different AC and PDE1A affinity regulate both cAMP production and its degradation, and this balance determines the intensity of Ca(2+)-AC-cAMP-PKA signaling that drives SANC pacemaker function. Copyright © 2016. Published by Elsevier Ltd.

Electrophysiological properties of prion-positive cardiac progenitors derived from murine embryonic stem cells.

PubMed

Fujii, Hiroshi; Ikeuchi, Yu; Kurata, Yasutaka; Ikeda, Nobuhito; Bahrudin, Udin; Li, Peili; Nakayama, Yuji; Endo, Ryo; Hasegawa, Akira; Morikawa, Kumi; Miake, Junichiro; Yoshida, Akio; Hidaka, Kyoko; Morisaki, Takayuki; Ninomiya, Haruaki; Shirayoshi, Yasuaki; Yamamoto, Kazuhiro; Hisatome, Ichiro

2012-01-01

The prion protein (PrP) has been reported to serve as a surface maker for isolation of cardiomyogenic progenitors from murine embryonic stem (ES) cells. Although PrP-positive cells exhibited automaticity, their electrophysiological characteristics remain unresolved. The aim of the present study was therefore to investigate the electrophysiological properties of PrP-positive cells in comparison with those of HCN4p-or Nkx2.5-positive cells. Differentiation of AB1, HCN5p-EGFP and hcgp7 ES cells into cardiac progenitors was induced by embryoid body (EB) formation. EBs were dissociated and cells expressing PrP, HCN4-EGFP and/or Nkx2.5-GFP were collected via flow cytometry. Sorted cells were subjected to reverse transcriptase-polymerase chain reaction, immunostaining and patch-clamp experiments. PrP-positive cells expressed mRNA of undifferentiation markers, first and second heart field markers, and cardiac-specific genes and ion channels, indicating their commitment to cardiomyogenic progenitors. PrP-positive cells with automaticity showed positive and negative chronotropic responses to isoproterenol and carbamylcholine, respectively. Hyperpolarization-activated cation current (I(f)) was barely detectable, whereas Na(+) and L-type Ca(2+) channel currents were frequently observed. Their spontaneous activity was slowed by inhibition of sarcoplasmic reticulum Ca(2+) uptake and release but not by blocking I(f). The maximum diastolic potential of their spontaneous firings was more depolarized than that of Nkx2.5-GFP-positive cells. PrP-positive cells contained cardiac progenitors that separated from the lineage of sinoatrial node cells. PrP can be used as a marker to enrich nascent cardiac progenitors.

Effect of antihypertensive drug therapy on short-term heart rate variability in newly diagnosed essential hypertension.

PubMed

Pavithran, Purushothaman; Prakash, E Sankaranarayanan; Dutta, Tarun K; Madanmohan, Trakroo

2010-02-01

1. Abnormalities of cardiac autonomic regulation are a potential mechanism for morbidity despite blood pressure (BP) lowering in hypertension. Analysis of short-term (5 min) heart rate variability (HRV) provides a non-invasive probe of autonomic regulation of sino-atrial (SA) node automaticity. 2. We hypothesized that antihypertensive drug therapy would be associated with an increase in 5 min overall HRV, along with a decrease in blood pressure (BP), at 8 weeks follow up in subjects with newly diagnosed, never-treated essential hypertension. 3. One hundred and fifty patients (84 men and 66 women; mean (+/-SD) age 48 +/- 10 years) with newly diagnosed essential hypertension were divided to five groups of 30 patients each to receive one of the following antihypertensive drugs (or drug combinations): 5 mg/day amlodipine; 50 mg/day atenolol; 5 mg/day enalapril; 25 mg/day hydrochlorothiazide; or a combination of 5 mg/day amlodipine and 50 mg/day atenolol. 4. The only significant change in HRV indices was an increase in total variability of RR intervals and an increase in high-frequency (HF) RR interval spectral power in the amlodipine + atenolol-treated group (P < 0.05). 5. The results indicate that there is a dissociation between changes in short-term HRV and mean RR interval and BP lowering in patients with newly diagnosed hypertension. 6. We interpret the increase in HF RR interval spectral power in the amlodipine + atenolol-treated group as being due to an increase in vagal modulation of RR intervals and/or diminution in sympathetic restraint of respiratory sinus arrhythmia.

G-protein mediated gating of inward-rectifier K+ channels.

PubMed

Mark, M D; Herlitze, S

2000-10-01

G-protein regulated inward-rectifier potassium channels (GIRK) are part of a superfamily of inward-rectifier K+ channels which includes seven family members. To date four GIRK subunits, designated GIRK1-4 (also designated Kir3.1-4), have been identified in mammals, and GIRK5 has been found in Xenopus oocytes. GIRK channels exist in vivo both as homotetramers and heterotetramers. In contrast to the other mammalian GIRK family members, GIRK1 can not form functional channels by itself and has to assemble with GIRK2, 3 or 4. As the name implies, GIRK channels are modulated by G-proteins; they are also modulated by phosphatidylinositol 4,5-bisphosphate, intracellular sodium, ethanol and mechanical stretch. Recently a family of GTPase activating proteins known as regulators of G-protein signaling were shown to be the missing link for the fast deactivation kinetics of GIRK channels in native cells, which contrast with the slow kinetics observed in heterologously expressed channels. GIRK1, 2 and 3 are highly abundant in brain, while GIRK4 has limited distribution. Here, GIRK1/2 seems to be the predominant heterotetramer. In general, neuronal GIRK channels are involved in the regulation of the excitability of neurons and may contribute to the resting potential. Interestingly, only the GIRK1 and 4 subunits are distributed in the atrial and sinoatrial node cells of the heart and are involved in the regulation of cardiac rate. Our main objective of this review is to assess the current understanding of the G-protein modulation of GIRK channels and their physiological importance in mammals.

Structural and functional cardiac cholinergic deficits in adult neurturin knockout mice.

PubMed

Mabe, Abigail M; Hoover, Donald B

2009-04-01

Previous work provided indirect evidence that the neurotrophic factor neurturin (NRTN) is required for normal cholinergic innervation of the heart. This study used nrtn knockout (KO) and wild-type (WT) mice to determine the effect of nrtn deletion on cardiac cholinergic innervation and function in the adult heart. Immunohistochemistry, confocal microscopy, and quantitative image analysis were used to directly evaluate intrinsic cardiac neuronal development. Atrial acetylcholine (ACh) levels were determined as an indirect index of cholinergic innervation. Cholinergic function was evaluated by measuring negative chronotropic responses to right vagal nerve stimulation in anaesthetized mice and responses of isolated atria to muscarinic agonists. KO hearts contained only 35% the normal number of cholinergic neurons, and the residual cholinergic neurons were 15% smaller than in WT. Cholinergic nerve density at the sinoatrial node was reduced by 87% in KOs, but noradrenergic nerve density was unaffected. Atrial ACh levels were substantially lower in KO mice (0.013 +/- 0.004 vs. 0.050 +/- 0.011 pmol/microg protein; P < 0.02) as expected from cholinergic neuron and nerve fibre deficits. Maximum bradycardia evoked by vagal stimulation was reduced in KO mice (38 +/- 6% vs. 69 +/- 3% decrease at 20 Hz; P < 0.001), and chronotropic responses took longer to develop and fade. In contrast to these deficits, isolated atria from KO mice had normal post-junctional sensitivity to carbachol and bethanechol. These findings demonstrate that NRTN is essential for normal cardiac cholinergic innervation and cholinergic control of heart rate. The presence of residual cardiac cholinergic neurons and vagal bradycardia in KO mice suggests that additional neurotrophic factors may influence this system.

High resolution heart rate variability analysis in patients with angina pectoris during coronary artery bypass graft surgery

NASA Astrophysics Data System (ADS)

Mironov, V. A.; Mironova, T. F.; Kuvatov, V. A.; Nokhrina, O. Yu.; Kuvatova, E. V.

2017-12-01

The purpose of the study is approbation of the capabilities of high-resolution rhythmocardiography (RCG) for the determination of the actual cardiovascular status of operated patients with angina pectoris during coronary artery bypass graft surgery (CABGS) for myocardial revascularization. The research was done by means of a KAP-RK-02-Mikor hardware-software complex with a monitor record and the time- and frequency-domain analyses of heart rate variability (HRV). Monitor records were made at each stage of CABGS in 123 patients. As a result, HRV manifested itself as a fairly adequate and promising method for the determination of the cardiovascular status during CABGS. In addition, the data of the HRV study during CABGS testify to the capability of RCG to determine the high risk of life-threatening cardioarrhythmias before and during operation, to different changes in sinoatrial heart node (SN) dysregulation, and contain the HRV symptoms of a high death risk before, during and after shunting. The loss of the peripheral autonomic sympathetic and parasympathetic control in SN in the form of the autonomic cardioneuropathy syndrome is a predictor of the complications related to CABGS. The obtained data on RCG monitoring of HRV recording are suggestive of wide prospects of the high-resolution RCG method to be used in cardiac surgery as a whole. The actual multivariant dysregulations of SN pacemaker activity testify to its adequacy to the pathophysiology of each period of the cardiac operation, according to the initial ischemic damages and localization of cardiosurgical manipulations during CABGS.

Mechanism underlying impaired cardiac pacemaking rhythm during ischemia: A simulation study

NASA Astrophysics Data System (ADS)

Bai, Xiangyun; Wang, Kuanquan; Yuan, Yongfeng; Li, Qince; Dobrzynski, Halina; Boyett, Mark R.; Hancox, Jules C.; Zhang, Henggui

2017-09-01

Ischemia in the heart impairs function of the cardiac pacemaker, the sinoatrial node (SAN). However, the ionic mechanisms underlying the ischemia-induced dysfunction of the SAN remain elusive. In order to investigate the ionic mechanisms by which ischemia causes SAN dysfunction, action potential models of rabbit SAN and atrial cells were modified to incorporate extant experimental data of ischemia-induced changes to membrane ion channels and intracellular ion homeostasis. The cell models were incorporated into an anatomically detailed 2D model of the intact SAN-atrium. Using the multi-scale models, the functional impact of ischemia-induced electrical alterations on cardiac pacemaking action potentials (APs) and their conduction was investigated. The effects of vagal tone activity on the regulation of cardiac pacemaker activity in control and ischemic conditions were also investigated. The simulation results showed that at the cellular level ischemia slowed the SAN pacemaking rate, which was mainly attributable to the altered Na+-Ca2+ exchange current and the ATP-sensitive potassium current. In the 2D SAN-atrium tissue model, ischemia slowed down both the pacemaking rate and the conduction velocity of APs into the surrounding atrial tissue. Simulated vagal nerve activity, including the actions of acetylcholine in the model, amplified the effects of ischemia, leading to possible SAN arrest and/or conduction exit block, which are major features of the sick sinus syndrome. In conclusion, this study provides novel insights into understanding the mechanisms by which ischemia alters SAN function, identifying specific conductances as contributors to bradycardia and conduction block.

Ivabradine prolongs phase 3 of cardiac repolarization and blocks the hERG1 (KCNH2) current over a concentration-range overlapping with that required to block HCN4.

PubMed

Lees-Miller, James P; Guo, Jiqing; Wang, Yibo; Perissinotti, Laura L; Noskov, Sergei Y; Duff, Henry J

2015-08-01

In Europe, ivabradine has recently been approved to treat patients with angina who have intolerance to beta blockers and/or heart failure. Ivabradine is considered to act specifically on the sinoatrial node by inhibiting the If current (the funny current) to slow automaticity. However, in vitro studies show that ivabradine prolongs phase 3 repolarization in ventricular tissue. No episodes of Torsades de Pointes have been reported in randomized clinical studies. The objective of this study is to assess whether ivabradine blocked the hERG1 current. In the present study we discovered that ivabradine prolongs action potential and blocks the hERG current over a range of concentrations overlapping with those required to block HCN4. Ivabradine produced tonic, rather than use-dependent block. The mutation Y652A significantly suppressed pharmacologic block of hERG by ivabradine. Disruption of C-type inactivation also suppressed block of hERG1 by ivabradine. Molecular docking and molecular dynamics simulations indicate that ivabradine may access the inner cavity of the hERG1 via a lipophilic route and has a well-defined binding site in the closed state of the channel. Structural organization of the binding pockets for ivabradine is discussed. Ivabradine blocks hERG and prolongs action potential duration. Our study is potentially important because it indicates the need for active post marketing surveillance of ivabradine. Importantly, proarrhythmia of a number of other drugs has only been discovered during post marketing surveillance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of a right atrial subsidiary pacemaker and acceleration of the pacing rate by HCN over-expression.

PubMed

Morris, Gwilym M; D'Souza, Alicia; Dobrzynski, Halina; Lei, Ming; Choudhury, Moinuddin; Billeter, Rudi; Kryukova, Yelena; Robinson, Richard B; Kingston, Paul A; Boyett, Mark R

2013-10-01

Although the right atrium (RA contains subsidiary atrial pacemaker (SAP) tissue that can take over from the sinoatrial node (SAN) in sick sinus syndrome (SSS), SAP tissue is bradycardic. Little is known about SAP tissue and one aim of the study was to characterize ion channel expression to obtain insight into SAP pacemaker mechanisms. A second aim was to determine whether HCN over-expression (a 'biopacemaker'-like strategy) can accelerate the pacemaker rate producing a pacemaker that is similar in nature to the SAN. SAP tissue was isolated from the rat and the leading pacemaker site was characterized. Cell size at the leading pacemaker site in the SAP was smaller than in the RA and comparable to that in the SAN. mRNA levels showed the SAP to be similar to, but distinct from, the SAN. For example, in the SAN and SAP, expression of Tbx3 and HCN1 was higher and Nav1.5 and Cx43 lower than in the RA. Organ-cultured SAP tissue beat spontaneously, but at a slower rate than the SAN. Adenovirus-mediated gene transfer of HCN2 and the chimeric protein HCN212 significantly increased the pacemaker rate of the SAP close to that of the native SAN, but HCN4 was ineffective. SAP tissue near the inferior vena cava is bradycardic, but shares characteristics with the SAN. Pacing can be accelerated by the over-expression of HCN2 or HCN212. This provides proof of concept for the use of SAP tissue as a substrate for biopacemaking in the treatment of SSS.

Ivabradine: Current and Future Treatment of Heart Failure.

PubMed

Thorup, Lene; Simonsen, Ulf; Grimm, Daniela; Hedegaard, Elise R

2017-08-01

In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT 1 ) antagonists, β-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT 1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm. Here, we review the evidence regarding the use of ivabradine for lowering HR in HF. Ivabradine is a blocker of an I funny current (I(f)) channel and causes rate-dependent inhibition of the pacemaker activity in the sinoatrial node. In clinical trials of HFrEF, treatment with ivabradine seems to improve clinical outcome, for example improved ejection fraction (EF) and less readmission for hospital, but the effect appears most pronounced in patients with HRs above 70 bpm, while the effect on cardiovascular death appears less consistent. The adverse effects of ivabradine include bradycardia, atrial fibrillation and visual disturbances, but ivabradine avoids the negative inotrope effects observed with β-adrenoceptor antagonists. In conclusion, in patients with stable HFrEF with EF<35% and HR above 70 bpm, ivabradine improves the outcome and might be a first choice of therapy, if beta-adrenoceptor antagonists are not tolerated. Further studies must show whether that can be extended to HF patients with preserved EF. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Reversible autonomic dysfunction in hyperthyroid patients affects gastric myoelectrical activity and emptying.

PubMed

Barczyński, M; Thor, P

2001-08-01

The autonomic nervous system (ANS) function in hyperthyroidism has been so far investigated mainly from the cardiovascular point of view. The aim of this study is to show that the ANS dysfunction in hyperthyroidism is also expressed in gastric myoelectrical activity disturbances and gastric emptying disorders and to search for a correlation between the severity of clinical manifestation and free thyroid hormone levels and the degree of the ANS dysfunction. The analyzed group included 50 recently diagnosed patients with hyperthyroidism who were examined twice: before and after 3 months of thyrostatic treatment. Results were compared with those of a sex-, age- and BMI-matched control group of 50 healthy volunteers. The study included: heart rate variability analysis in time and frequency domain, at rest and during a deep-breathing test, surface electrogastrography in preprandial and postprandial periods measured simultaneously with the ultrasound assessment of gastric emptying time by Bolondi method. In patients with hyperthyroidism in comparison with the control group, the following significant differences were observed: a sharp reduction of the high-frequency component and a decrease of heart rate variability, a high incidence of dysrhythmia with dominant bradyarrhythmia, and a delay of gastric emptying. The degree of disorders related to the degree of clinical manifestation of hyperthyroidism's symptoms and free triiodothyronine serum concentration both. All the disorders were functional and disappeared in a stable euthyroidism. To conclude, the ANS dysfunction in hyperthyroidism results not only in withdrawal of vagal inhibitory effect on sinoatrial node, but in impaired mutual neuro-hormonal regulation (decrease of vagal influence) of gastric myoelectrical activity followed by delay of gastric emptying.

Intracellular Calcium Dynamics and the Acceleration of Sinus Rhythm by β-Adrenergic Stimulation

PubMed Central

Joung, Boyoung; Tang, Liang; Maruyama, Mitsunori; Han, Seongwook; Chen, Zhenhui; Stucky, Marcelle; Jones, Larry R.; Fishbein, Michael C.; Weiss, James N.; Chen, Peng-Sheng; Lin, Shien-Fong

2009-01-01

Background Recent evidence indicates that membrane voltage and Ca2+ clocks jointly regulate sinoatrial node (SAN) automaticity. Here we test the hypothesis that sinus rate acceleration by β-adrenergic stimulation involves synergistic interactions between these clock mechanisms. Methods and Results We simultaneously mapped intracellular calcium (Cai) and membrane potential (Vm) in 25 isolated canine right atrium (RA), using previously described criteria of the timing of late diastolic Cai elevation (LDCAE) relative to the action potential (AP) upstroke to detect the Ca2+ clock. Before isoproterenol, the earliest pacemaking site occurred in the inferior SAN, and LDCAE was observed in only 4/25 preparations. Isoproterenol (1 μmol/L) increased sinus rate and shifted pacemaking site to superior SAN, concomitant with the appearance of LDCAE preceding the AP upstroke by 98 ± 31 ms. Caffeine had similar effects, while SR Ca2+ depletion with ryanodine and thapsigargin prevented isoproterenol-induced LDCAE and blunted sinus rate acceleration. Cai transient relaxation time during ISO was shorter in superior SAN (124 ± 34 ms) than inferior SAN (138 ± 24 ms, p = 0.01) or RA (164 ± 33 ms, p = 0.001), and was associated with a lower SR Ca2+ ATPase pump to phospholamban protein ratio in SAN than in RA. If current blockade with ZD 7288 modestly blunted, but did not prevent LDCAE or sinus rate acceleration by isoproterenol. Conclusions Acceleration of the Ca2+ clock in the superior SAN plays an important role in sinus acceleration during β-adrenergic stimulation, interacting synergistically with the voltage clock to increase sinus rate. PMID:19188501

Chronic orthostatic intolerance: a disorder with discordant cardiac and vascular sympathetic control

NASA Technical Reports Server (NTRS)

Furlan, R.; Jacob, G.; Snell, M.; Robertson, D.; Porta, A.; Harris, P.; Mosqueda-Garcia, R.

1998-01-01

BACKGROUND: Chronic orthostatic intolerance (COI) is a debilitating autonomic condition in young adults. Its neurohumoral and hemodynamic profiles suggest possible alterations of postural sympathetic function and of baroreflex control of heart rate (HR). METHODS AND RESULTS: In 16 COI patients and 16 healthy volunteers, intra-arterial blood pressure (BP), ECG, central venous pressure (CVP), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during 75 degrees tilt. Spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided indices of sympathovagal modulation of the sinoatrial node (ratio of low-frequency to high-frequency components, LF/HF) and of sympathetic vasomotor control (LFSAP). Baroreflex mechanisms were assessed (1) by the slope of the regression line obtained from changes of RR interval and MSNA evoked by pharmacologically induced alterations in BP and (2) by the index alpha, obtained from cross-spectral analysis of RR and SAP variabilities. At rest, HR, MSNA, LF/HF, and LFSAP were higher in COI patients, whereas BP and CVP were similar in the two groups. During tilt, BP did not change and CVP fell by the same extent in the 2 groups; the increase of HR and LF/HF was more pronounced in COI patients. Conversely, the increase of MSNA was lower in COI than in control subjects. Baroreflex sensitivity was similar in COI and control subjects at rest; tilt reduced alpha similarly in both groups. CONCLUSIONS: COI is characterized by an overall enhancement of noradrenergic tone at rest and by a blunted postganglionic sympathetic response to standing, with a compensatory cardiac sympathetic overactivity. Baroreflex mechanisms maintain their functional responsiveness. These data suggest that in COI, the functional distribution of central sympathetic tone to the heart and vasculature is abnormal.

I(f) inhibition in cardiovascular diseases.

PubMed

Thollon, Catherine; Vilaine, Jean-Paul

2010-01-01

Heart rate (HR) is determined by the pacemaker activity of cells from the sinoatrial node (SAN), located in the right atria. Spontaneous electrical activity of SAN cells results from a diastolic depolarization (DD). Despite controversy in the exact contribution of funny current (I(f)) in pacemaking, it is a major contributor of DD. I(f) is an inward Na(+)/K(+) current, activated upon hyperpolarization and directly modulated by cyclic adenosine monophosphate. The f-proteins are hyperpolarization-activated cyclic nucleotide-gated channels, HCN4 being the main isoform of SAN. Ivabradine (IVA) decreases DD and inhibits I(f) in a use-dependent manner. Under normal conditions IVA selectively reduces HR and limits exercise-induced tachycardia, in animals and young volunteers. Reduction in HR with IVA both decreases myocardial oxygen consumption and increases its supply due to prolongation of diastolic perfusion time. In animal models and in human with coronary artery disease (CAD), IVA has anti-anginal and anti-ischemic efficacy, equipotent to classical treatments, β-blockers, or calcium channel blockers. As expected from its selectivity for I(f), the drug is safe and well tolerated with minor visual side effects. As a consequence, IVA is the first inhibitor of I(f) approved for the treatment of stable angina. Available clinical data indicate that IVA could improve the management of stable angina in all patients including those treated with β-blockers. As chronic elevation of resting HR is an independent predictor of mortality, pure HR reduction by inhibition of I(f) could, beyond the control of anti-anginal symptoms, improve the prognosis of CAD and heart failure; this therapeutic potential is currently under evaluation with IVA. Copyright © 2010 Elsevier Inc. All rights reserved.

Heart Rate Reduction With Ivabradine Protects Against Left Ventricular Remodeling by Attenuating Infarct Expansion and Preserving Remote-Zone Contractile Function and Synchrony in a Mouse Model of Reperfused Myocardial Infarction.

PubMed

O'Connor, Daniel M; Smith, Robert S; Piras, Bryan A; Beyers, Ronald J; Lin, Dan; Hossack, John A; French, Brent A

2016-04-22

Ivabradine selectively inhibits the pacemaker current of the sinoatrial node, slowing heart rate. Few studies have examined the effects of ivabradine on the mechanical properties of the heart after reperfused myocardial infarction (MI). Advances in ultrasound speckle-tracking allow strain analyses to be performed in small-animal models, enabling the assessment of regional mechanical function. After 1 hour of coronary occlusion followed by reperfusion, mice received 10 mg/kg per day of ivabradine dissolved in drinking water (n=10), or were treated as infarcted controls (n=9). Three-dimensional high-frequency echocardiography was performed at baseline and at days 2, 7, 14, and 28 post-MI. Speckle-tracking software was used to calculate intramural longitudinal myocardial strain (Ell) and strain rate. Standard deviation time to peak radial strain (SD Tpeak Err) and temporal uniformity of strain were calculated from short-axis cines acquired in the left ventricular remote zone. Ivabradine reduced heart rate by 8% to 16% over the course of 28 days compared to controls (P<0.001). On day 28 post-MI, the ivabradine group was found to have significantly smaller end-systolic volumes, greater ejection fraction, reduced wall thinning, and greater peak Ell and Ell rate in the remote zone, as well as globally. Temporal uniformity of strain and SD Tpeak Err were significantly smaller in the ivabradine-treated group by day 28 (P<0.05). High-frequency ultrasound speckle-tracking demonstrated decreased left ventricular remodeling and dyssynchrony, as well as improved mechanical performance in remote myocardium after heart rate reduction with ivabradine. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

[Morphological and electrophysiological changes of the heart atria in necropsy patients with atrial fibrillation - a pilot study].

PubMed

Matějková, Adéla; Steiner, Ivo

2014-01-01

Atrial fibrillation (AF), the most common supraventricular tachycardia, has a morphological base, so called remodelation of atrial myocardium, with its abnormal conduction pattern as a consequence. The remodelation regards electrical, contractile, and structural properties. In this pilot study we attempted to find relations between the myocardial morphological (scarring, amyloidosis, left atrial enlargement) and electrophysiological (ECG characteristics of the P-wave) changes in patients with AF. We examined 40 hearts of necropsy patients - 20 with a history of AF and 20 with no history of AF. Grossly, the heart weight and the size of the left atrium (LA) were evaluated. Histologically, 7 standard sites from the atria were examined. In each specimen, the degree of myocardial scarring and of deposition of isolated atrial amyloid (IAA) were assessed. We failed to show any significant difference in the P-wave pattern between patients with and without AF. Morphologically, however, there were several differences - the patients with AF had significantly heavier hearts, larger left atria, more severely scarred myocardium of the LA and the atrial septum, and more severe deposition of IAA in both atria in comparison to the control group of patients with sinus rhythm. The left atrial distribution of both fibrosis and amyloidosis was irregular. In patients with AF the former was most pronounced in the LA ceiling while the latter in the LA anterior wall. The entire series showed more marked amyloidosis in the left than in the right atrium. An interesting finding was the universal absence of IAA in the sinoatrial node. The knowledge of distribution of atrial myocardial structural changes could be utilized by pathologists in taking specimens for histology and also by cardiologists in targeting the radiofrequency ablation therapy.

Electrophysiological effects of desflurane in children with Wolff-Parkinson-White syndrome: a randomized crossover study.

PubMed

Hino, H; Oda, Y; Yoshida, Y; Suzuki, T; Shimada, M; Nishikawa, K

2018-02-01

We hypothesized that, compared with propofol, desflurane prolongs the antegrade accessory pathway effective refractory period (APERP) in children undergoing radiofrequency catheter ablation for Wolff-Parkinson-White (WPW) syndrome. In this randomized crossover study, children aged 4.1-16.1 years undergoing radiofrequency catheter ablation for WPW syndrome were randomly divided into four groups according to the concentration of desflurane and anesthetics used in the first and the second electrophysiological studies (EPS). After induction of general anesthesia with propofol and tracheal intubation, they received one of the following regimens: 0.5 minimum alveolar concentration (MAC) desflurane (first EPS) and propofol (second EPS) (Des0.5-Prop group, n = 8); propofol (first EPS) and 0.5 MAC desflurane (second EPS) (Prop-Des0.5 group, n = 9); 1 MAC desflurane (first EPS) and propofol (second EPS) (Des1.0-Prop group, n = 10); propofol (first EPS) and 1 MAC desflurane (second EPS) (Prop-Des1.0 group, n = 9). Radiofrequency catheter ablation was performed upon completion of EPS. Sample size was determined to detect a difference in the APERP. Desflurane at 1.0 MAC significantly prolonged the APERP compared with propofol, but did not affect the sinoatrial conduction time, atrio-His interval or atrioventricular node effective refractory period. Supraventricular tachycardia was induced in all children receiving propofol, but not induced in 1 and 4 children receiving 0.5 MAC and 1.0 MAC desflurane, respectively. Desflurane enhances the refractoriness and may block the electrical conduction of the atrioventricular accessory pathway, and is therefore not suitable for use in children undergoing radiofrequency catheter ablation for WPW syndrome. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Double valvular insufficiency in a Burmese python (Python molurus bivittatus, Linnaeus, 1758) suffering from concomitant bacterial pneumonia.

PubMed

Schilliger, Lionel; Tréhiou-Sechi, Emilie; Petit, Amandine M P; Misbach, Charlotte; Chetboul, Valérie

2010-12-01

Ultrasonography, and, to a lesser extent, echocardiography are now well-established, noninvasive, and painless diagnostic tools in herpetologic medicine. Various cardiac lesions have been previously described in reptiles, but valvulopathy is rarely documented in these animals and, consequently, is poorly understood. In this report, sinoatrial and atrioventricular insufficiencies were diagnosed in a 5-yr-old captive dyspneic Burmese python (Python molurus bivittatus) on the basis of echocardiographic and Doppler examination. This case report is the first to document Doppler assessment of valvular regurgitations in a reptile.

[Auricular arrhythmia in Steinert's myotonia. Apropos of a case with a familial study].

PubMed

Chagnon, A; Vidal, M E

1983-02-24

A case of bradycardia-tachycardia syndrome leading to the late discovery of Steinert syndrome is reported. There is a discrepancy between the frequency of the main features of the bradycardia-tachycardia syndrome (sinoatrial block and atrial flutter in our observation) usually reported in Steinert disease and the fact that no case similar to ours seems to have yet been reported; this suggests definite underrating. Insertion of a pacemaker should avoid sudden death from a conduction disturbance. The heart should be carefully monitored in patients with myotonic dystrophy; conversely, this diagnosis should be considered in the etiologic diagnosis of myocardiopathies.

Development of cardiac parasympathetic neurons, glial cells, and regional cholinergic innervation of the mouse heart.

PubMed

Fregoso, S P; Hoover, D B

2012-09-27

Very little is known about the development of cardiac parasympathetic ganglia and cholinergic innervation of the mouse heart. Accordingly, we evaluated the growth of cholinergic neurons and nerve fibers in mouse hearts from embryonic day 18.5 (E18.5) through postnatal day 21(P21). Cholinergic perikarya and varicose nerve fibers were identified in paraffin sections immunostained for the vesicular acetylcholine transporter (VAChT). Satellite cells and Schwann cells in adjacent sections were identified by immunostaining for S100β calcium binding protein (S100) and brain-fatty acid binding protein (B-FABP). We found that cardiac ganglia had formed in close association to the atria and cholinergic innervation of the atrioventricular junction had already begun by E18.5. However, most cholinergic innervation of the heart, including the sinoatrial node, developed postnatally (P0.5-P21) along with a doubling of the cross-sectional area of cholinergic perikarya. Satellite cells were present throughout neonatal cardiac ganglia and expressed primarily B-FABP. As they became more mature at P21, satellite cells stained strongly for both B-FABP and S100. Satellite cells appeared to surround most cardiac parasympathetic neurons, even in neonatal hearts. Mature Schwann cells, identified by morphology and strong staining for S100, were already present at E18.5 in atrial regions that receive cholinergic innervation at later developmental times. The abundance and distribution of S100-positive Schwann cells increased postnatally along with nerve density. While S100 staining of cardiac Schwann cells was maintained in P21 and older mice, Schwann cells did not show B-FABP staining at these times. Parallel development of satellite cells and cholinergic perikarya in the cardiac ganglia and the increase in abundance of Schwann cells and varicose cholinergic nerve fibers in the atria suggest that neuronal-glial interactions could be important for development of the parasympathetic nervous system in the heart. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

An experimental ovine Theileriosis: The effect of Theileria lestoquardi infection on cardiovascular system in sheep.

PubMed

Yaghfoori, Saeed; Razmi, Gholam Reza; Mohri, Mehrdad; Razavizadeh, Ali Reza Taghavi; Movassaghi, Ahmad Reza

2016-09-01

The malignant ovine theileriosis is caused by Theileria lestoquardi, which is highly pathogenic in sheep. Theileriosis involves different organs in ruminants, but the effect of the disease on the cardiovascular system is unclear. To understand the pathogenesis of T. lestoquardi on the cardiovascular system, Baluchi breed sheep were infected with the mentioned parasite by releasing unfed adults of Hyalomma anatolicum anatolicum, which were infected with T. lestoquardi. The infected sheep were clinically examined on days 0, 2, 5, 7, 10, 12, 14, 17, and 21, and the blood samples were collected for biochemical parameters measurement. At termination of the experiment, the infected sheep were euthanized and pathological examinations of heart tissue were conducted. During experimental infection of sheep with T. lestoquardi, activities of cardiac troponin I (cTnI), lactate dehydrogenase, and aspartate aminotransferase, were significantly increased (P˂0.05), while a conspicuous decrease (P˂0.05) was observed in creatine phosphokinase activities. Alterations made in biochemical factors almost coincided with the presence of piroplasm in the blood and schizont in lymph nodes. Maximum and minimum of parasitemia in the sheep stood between 3.3% and 0.28%, respectively. In addition, electrocardiography revealed sinus tachycardia, sinus arrhythmia, sino-atrial block and ST-elevation, atrial premature beat, and alteration in QRS and in T waves' amplitude. Heart histopathological examination showed hyperemia, infiltration of mononuclear inflammatory cells into interstitial tissue, endocarditis, and focal necrosis of cardiac muscle cells. In addition, in one of the sheep, definite occurrence of infarction was observed. The results indicate that T. lestoquardi infection has devastating pathological impacts on the cardiovascular system of sheep. Furthermore, measurement of the cTnI amount is a useful biochemical factor for diagnosis and for better understanding of the severity and progression of the disease and its effects on cardiac tissue. Copyright © 2016 Elsevier B.V. All rights reserved.

Multivariate assessment of the central-cardiorespiratory network structure in neuropathological disease.

PubMed

Schulz, Steffen; Haueisen, Jens; Bär, Karl-Juergen; Voss, Andreas

2018-06-22

The new interdisciplinary field of network physiology is getting more and more into the focus of interest in medicine. The autonomic nervous system (ANS) dysfunction is well described in schizophrenia (SZO). However, the linear and nonlinear coupling between the ANS and central nervous system (CNS) is only partly addressed until now. This coupling can be assumed as a feedback-feedforward network, reacting with flexible and adaptive responses to internal and external factors. Approach: For the first time, in this study, we investigated linear and nonlinear short-term central-cardiorespiratory couplings of 17 patients suffering from paranoid schizophrenia (SZO) in comparison to 17 age-gender matched healthy subjects (CON) analyzing heart rate (HR), respiration (RESP) and the power of frontal EEG activity (PEEG). The objective is to determine how the different regulatory aspects of the CNS-ANS compose the central-cardiorespiratory network (CCRN). To quantify these couplings within the CCRN the normalized short time partial directed coherence (NSTPDC) and the new multivariate high-resolution joint symbolic dynamics (mHRJSD) were applied. Main results: We found that the CCRN in SZO is characterized as a bidirectional one, with stronger central driving mechanisms (PEEG→HR) towards HR regulation than vice versa, and with stronger respiratory influence (RESP→PEEG) on central activity than vice versa. This suggests that the central-cardiorespiratory process (closed-loop) is mainly focusing on adapting the HR via the sinoatrial node than focusing on respiratory regulation. On the other side, the feedback-loop from ANS to CNS is strongly dominated via respiratory activity. Significance: We could demonstrate a considerably significantly different central-cardiorespiratory network structure in schizophrenia with strong central influence on the cardiac system and a strong respiratory influence on the central nervous system. Moreover, this study provides a more in-depth understanding of the interplay of the central and autonomic regulatory network in healthy subjects and schizophrenic patients. . © 2018 Institute of Physics and Engineering in Medicine.

Organization of the sympathetic innervation of the forelimb resistance vessels in the cat.

PubMed

Backman, S B; Stein, R D; Polosa, C

1999-02-01

Detailed information on the outflow pathway of sympathetic vasoconstrictor fibers to the upper extremity is lacking. We studied the organization of the sympathetic innervation of the forelimb resistance vessels and of the sinoatrial (SA) node in the decerebrated, artificially respirated cat. The distal portion of sectioned individual rami T1-8 and the sympathetic chain immediately caudal to T8 on the right side were electrically stimulated while the right forelimb perfusion pressure (forelimb perfused at constant flow) and heart rate were recorded. Increases in perfusion pressure were evoked by stimulation of T2-8 (maximal response T7: 55 +/- 2.3 mm Hg). Responses were still evoked by stimulation of the sympathetic chain immediately caudal to T8 (44 +/- 15 mm Hg). Increases in heart rate were evoked by the stimulation of more rostral rami (T1-5; maximal response T3: 55.2 +/- 8 bpm). These vasoconstrictor and cardioacceleratory responses were blocked by the cholinergic antagonists hexamethonium and scopolamine. Sectioning of the vertebral nerve and the T1 ramus abolished the vasoconstrictor response. Stimulation of the vertebral nerve and of the proximal portion of the sectioned T1 ramus increased perfusion pressure (69 +/- 9 and 34 +/- 14 mm Hg, respectively), which was unaffected by ganglionic cholinergic block. These data suggest that forelimb resistance vessel control is subserved by sympathetic preganglionic neurons located mainly in the middle to caudal thoracic spinal segments. Some of the postganglionic axons subserving vasomotor function course through the T1 ramus, in addition to the vertebral nerve. Forelimb vasculature is controlled by sympathetic preganglionic neurons located in middle to caudal thoracic spinal segments and by postganglionic axons carried in the T1 ramus and vertebral nerve. This helps to provide the anatomical substrate of interruption of sympathetic outflow to the upper extremity produced by major conduction anesthesia of the stellate ganglion or spinal cord.

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential

PubMed Central

Capel, Rebecca A.; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R.; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J.; Terrar, Derek A.; Burton, Rebecca-Ann B.

2015-01-01

Background Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. Objectives The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. Methods We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the “funny” current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1–30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). Results In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. Conclusions We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. PMID:26025323

Assessment of the clinical cardiac drug-drug interaction associated with the combination of hepatitis C virus nucleotide inhibitors and amiodarone in guinea pigs and rhesus monkeys.

PubMed

Regan, Christopher P; Morissette, Pierre; Regan, Hillary K; Travis, Jeffery J; Gerenser, Pamela; Wen, Jianzhong; Fitzgerald, Kevin; Gruver, Shaun; DeGeorge, Joseph J; Sannajust, Frederick J

2016-11-01

In 2015, European and U.S. health agencies issued warning letters in response to 9 reported clinical cases of severe bradycardia/bradyarrhythmia in hepatitis C virus (HCV)-infected patients treated with sofosbuvir (SOF) in combination with other direct acting antivirals (DAAs) and the antiarrhythmic drug, amiodarone (AMIO). We utilized preclinical in vivo models to better understand this cardiac effect, the potential pharmacological mechanism(s), and to identify a clinically translatable model to assess the drug-drug interaction (DDI) cardiac risk of current and future HCV inhibitors. An anesthetized guinea pig model was used to elicit a SOF+AMIO-dependent bradycardia. Detailed cardiac electrophysiological studies in this species revealed SOF+AMIO-dependent selective nodal dysfunction, with initial, larger effects on the sinoatrial node. Further studies in conscious, rhesus monkeys revealed an emergent bradycardia and bradyarrhythmia in 3 of 4 monkeys administered SOF+AMIO, effects not observed with either agent alone. Morever, bradycardia and bradyarrhythmia were not observed in rhesus monkeys when intravenous infusion of MK-3682 was completed after AMIO pretreatment. These are the first preclinical in vivo experiments reported to replicate the severe clinical SOF+AMIO cardiac DDI and provide potential in vivo mechanism of action. As such, these data provide a preclinical risk assessment paradigm, including a clinically relevant nonhuman primate model, with which to better understand cardiovascular DDI risk for this therapeutic class. Furthermore, these studies suggest that not all HCV DAAs and, in particular, not all HCV nonstructural protein 5B inhibitors may exhibit this cardiac DDI with amiodarone. Given the selective in vivo cardiac electrophysiological effect, these data enable targeted cellular/molecular mechanistic studies to more precisely identify cell types, receptors, and/or ion channels responsible for the clinical DDI. (Hepatology 2016;64:1430-1441). © 2016 by the American Association for the Study of Liver Diseases.

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.

PubMed

Capel, Rebecca A; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J; Terrar, Derek A; Burton, Rebecca-Ann B

2015-10-01

Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the "funny" current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1-30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Advances in the management of heart failure: the role of ivabradine

PubMed Central

Müller-Werdan, Ursula; Stöckl, Georg; Werdan, Karl

2016-01-01

A high resting heart rate (≥70–75 b.p.m.) is a risk factor for patients with heart failure (HF) with reduced ejection fraction (EF), probably in the sense of accelerated atherosclerosis, with an increased morbidity and mortality. Beta-blockers not only reduce heart rate but also have negative inotropic and blood pressure-lowering effects, and therefore, in many patients, they cannot be given in the recommended dose. Ivabradine specifically inhibits the pacemaker current (funny current, If) of the sinoatrial node cells, resulting in therapeutic heart rate lowering without any negative inotropic and blood pressure-lowering effect. According to the European Society of Cardiology guidelines, ivabradine should be considered to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients with a reduced left ventricular EF ≤35% and sinus rhythm ≥70 b.p.m. despite treatment with an evidence-based dose of beta-blocker or a dose below the recommended dose (recommendation class “IIa” = weight of evidence/opinion is in favor of usefulness/efficacy: “should be considered”; level of evidence “B” = data derived from a single randomized clinical trial or large nonrandomized studies). Using a heart rate cutoff of ≥ 75 b.p.m., as licensed by the European Medicines Agency, treatment with ivabradine 5–7.5 mg b.i.d. reduces cardiovascular mortality by 17%, HF mortality by 39% and HF hospitalization rate by 30%. A high resting heart rate is not only a risk factor in HF with reduced EF but also at least a risk marker in HF with preserved EF, in acute HF and also in special forms of HF. In this review, we discuss the proven role of ivabradine in the validated indication “HF with reduced EF” together with interesting preliminary findings, and the potential role of ivabradine in further, specific forms of HF. PMID:27895488

Ca2+-regulated-cAMP/PKA signaling in cardiac pacemaker cells links ATP supply to demand.

PubMed

Yaniv, Yael; Juhaszova, Magdalena; Lyashkov, Alexey E; Spurgeon, Harold A; Sollott, Steven J; Lakatta, Edward G

2011-11-01

In sinoatrial node cells (SANC), Ca(2+) activates adenylate cyclase (AC) to generate a high basal level of cAMP-mediated/protein kinase A (PKA)-dependent phosphorylation of Ca(2+) cycling proteins. These result in spontaneous sarcoplasmic-reticulum (SR) generated rhythmic Ca(2+) oscillations during diastolic depolarization, that not only trigger the surface membrane to generate rhythmic action potentials (APs), but, in a feed-forward manner, also activate AC/PKA signaling. ATP is consumed to pump Ca(2+) to the SR, to produce cAMP, to support contraction and to maintain cell ionic homeostasis. Since feedback mechanisms link ATP-demand to ATP production, we hypothesized that (1) both basal ATP supply and demand in SANC would be Ca(2+)-cAMP/PKA dependent; and (2) due to its feed-forward nature, a decrease in flux through the Ca(2+)-cAMP/PKA signaling axis will reduce the basal ATP production rate. O(2) consumption in spontaneous beating SANC was comparable to ventricular myocytes (VM) stimulated at 3 Hz. Graded reduction of basal Ca(2+)-cAMP/PKA signaling to reduce ATP demand in rabbit SANC produced graded ATP depletion (r(2)=0.96), and reduced O(2) consumption and flavoprotein fluorescence. Neither inhibition of glycolysis, selectively blocking contraction nor specific inhibition of mitochondrial Ca(2+) flux reduced the ATP level. Feed-forward basal Ca(2+)-cAMP/PKA signaling both consumes ATP to drive spontaneous APs in SANC and is tightly linked to mitochondrial ATP production. Interfering with Ca(2+)-cAMP/PKA signaling not only slows the firing rate and reduces ATP consumption, but also appears to reduce ATP production so that ATP levels fall. This distinctly differs from VM, which lack this feed-forward basal cAMP/PKA signaling, and in which ATP level remains constant when the demand changes. Published by Elsevier Ltd.

Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials.

PubMed

Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J

2014-01-01

The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models-of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells-to investigate the relative effects of reducing two important voltage-gated Ca currents-the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action.

Computational modeling of inhibition of voltage-gated Ca channels: identification of different effects on uterine and cardiac action potentials

PubMed Central

Tong, Wing-Chiu; Ghouri, Iffath; Taggart, Michael J.

2014-01-01

The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs). Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models—of uterine smooth muscle cells (USMC), cardiac sinoatrial node cells (SAN), and ventricular cells—to investigate the relative effects of reducing two important voltage-gated Ca currents—the L-type (ICaL) and T-type (ICaT) Ca currents. Reduction of ICaL (10%) alone, or ICaT (40%) alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine specificity of action. PMID:25360118

A New Algorithm to Diagnose Atrial Ectopic Origin from Multi Lead ECG Systems - Insights from 3D Virtual Human Atria and Torso

PubMed Central

Alday, Erick A. Perez; Colman, Michael A.; Langley, Philip; Butters, Timothy D.; Higham, Jonathan; Workman, Antony J.; Hancox, Jules C.; Zhang, Henggui

2015-01-01

Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms. PMID:25611350

Role of the P-wave high frequency energy and duration as noninvasive cardiovascular predictors of paroxysmal atrial fibrillation.

PubMed

Alcaraz, Raúl; Martínez, Arturo; Rieta, José J

2015-04-01

A normal cardiac activation starts in the sinoatrial node and then spreads throughout the atrial myocardium, thus defining the P-wave of the electrocardiogram. However, when the onset of paroxysmal atrial fibrillation (PAF) approximates, a highly disturbed electrical activity occurs within the atria, thus provoking fragmented and eventually longer P-waves. Although this altered atrial conduction has been successfully quantified just before PAF onset from the signal-averaged P-wave spectral analysis, its evolution during the hours preceding the arrhythmia has not been assessed yet. This work focuses on quantifying the P-wave spectral content variability over the 2h preceding PAF onset with the aim of anticipating as much as possible the arrhythmic episode envision. For that purpose, the time course of several metrics estimating absolute energy and ratios of high- to low-frequency power in different bands between 20 and 200Hz has been computed from the P-wave autoregressive spectral estimation. All the analyzed metrics showed an increasing variability trend as PAF onset approximated, providing the P-wave high-frequency energy (between 80 and 150Hz) a diagnostic accuracy around 80% to discern between healthy subjects, patients far from PAF and patients less than 1h close to a PAF episode. This discriminant power was similar to that provided by the most classical time-domain approach, i.e., the P-wave duration. Furthermore, the linear combination of both metrics improved the diagnostic accuracy up to 88.07%, thus constituting a reliable noninvasive harbinger of PAF onset with a reasonable anticipation. The information provided by this methodology could be very useful in clinical practice either to optimize the antiarrhythmic treatment in patients at high-risk of PAF onset and to limit drug administration in low risk patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Spaceflight Activates Protein Kinase C Alpha Signaling and Modifies the Developmental Stage of Human Neonatal Cardiovascular Progenitor Cells.

PubMed

Baio, Jonathan; Martinez, Aida F; Bailey, Leonard; Hasaniya, Nahidh; Pecaut, Michael J; Kearns-Jonker, Mary

2018-02-12

Spaceflight impacts cardiovascular function in astronauts; however, its impact on cardiac development and the stem cells that form the basis for cardiac repair is unknown. Accordingly, further research is needed to uncover the potential relevance of such changes to human health. Using simulated microgravity (SMG) generated by two-dimensional clinorotation and culture aboard the International Space Station (ISS), we assessed the effects of mechanical unloading on human neonatal cardiovascular progenitor cell (CPC) developmental properties and signaling. Following 6-7 days of SMG and 12 days of ISS culture, we analyzed changes in gene expression. Both environments induced the expression of genes that are typically associated with an earlier state of cardiovascular development. To understand the mechanism by which such changes occurred, we assessed the expression of mechanosensitive small RhoGTPases in SMG-cultured CPCs and observed decreased levels of RHOA and CDC42. Given the effect of these molecules on intracellular calcium levels, we evaluated changes in noncanonical Wnt/calcium signaling. After 6-7 days under SMG, CPCs exhibited elevated levels of WNT5A and PRKCA. Similarly, ISS-cultured CPCs exhibited elevated levels of calcium handling and signaling genes, which corresponded to protein kinase C alpha (PKCα), a calcium-dependent protein kinase, activation after 30 days. Akt was activated, whereas phosphorylated extracellular signal-regulated kinase levels were unchanged. To explore the effect of calcium induction in neonatal CPCs, we activated PKCα using hWnt5a treatment on Earth. Subsequently, early cardiovascular developmental marker levels were elevated. Transcripts induced by SMG and hWnt5a-treatment are expressed within the sinoatrial node, which may represent embryonic myocardium maintained in its primitive state. Calcium signaling is sensitive to mechanical unloading and directs CPC developmental properties. Further research both in space and on Earth may help refine the use of CPCs in stem cell-based therapies and highlight the molecular events of development.

Subtype-specific differentiation of cardiac pacemaker cell clusters from human induced pluripotent stem cells.

PubMed

Schweizer, Patrick A; Darche, Fabrice F; Ullrich, Nina D; Geschwill, Pascal; Greber, Boris; Rivinius, Rasmus; Seyler, Claudia; Müller-Decker, Karin; Draguhn, Andreas; Utikal, Jochen; Koenen, Michael; Katus, Hugo A; Thomas, Dierk

2017-10-16

Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties. hiPSC were differentiated into spontaneously beating clusters by co-culturing with visceral endoderm-like cells in a serum-free medium. Subsequent culturing in a specified fetal bovine serum (FBS)-enriched cell medium produced a pacemaker-type phenotype that was studied in detail using quantitative real-time polymerase chain reaction (qRT-PCR), immunocytochemistry, and patch-clamp electrophysiology. Further investigations comprised pharmacological stimulations and co-culturing with neonatal cardiomyocytes. hiPSC co-cultured in a serum-free medium with the visceral endoderm-like cell line END-2 produced spontaneously beating clusters after 10-12 days of culture. The pacemaker-specific genes HCN4, TBX3, and TBX18 were abundantly expressed at this early developmental stage, while levels of sarcomeric gene products remained low. We observed that working-type cardiomyogenic differentiation can be suppressed by transfer of early clusters into a FBS-enriched cell medium immediately after beating onset. After 6 weeks under these conditions, sinoatrial node (SAN) hallmark genes remained at high levels, while working-type myocardial transcripts (NKX2.5, TBX5) were low. Clusters were characterized by regular activity and robust beating rates (70-90 beats/min) and were triggered by spontaneous Ca 2+ transients recapitulating calcium clock properties of genuine pacemaker cells. They were responsive to adrenergic/cholinergic stimulation and able to pace neonatal rat ventricular myocytes in co-culture experiments. Action potential (AP) measurements of cells individualized from clusters exhibited nodal-type (63.4%) and atrial-type (36.6%) AP morphologies, while ventricular AP configurations were not observed. We provide a novel culture media-based, transgene-free approach for targeted generation of hiPSC-derived pacemaker-type cells that grow in clusters and offer the potential for disease modeling, drug testing, and individualized cell-based replacement therapy of the SAN.

3D virtual human atria: A computational platform for studying clinical atrial fibrillation

PubMed Central

Aslanidi, Oleg V; Colman, Michael A; Stott, Jonathan; Dobrzynski, Halina; Boyett, Mark R; Holden, Arun V; Zhang, Henggui

2011-01-01

Despite a vast amount of experimental and clinical data on the underlying ionic, cellular and tissue substrates, the mechanisms of common atrial arrhythmias (such as atrial fibrillation, AF) arising from the functional interactions at the whole atria level remain unclear. Computational modelling provides a quantitative framework for integrating such multi-scale data and understanding the arrhythmogenic behaviour that emerges from the collective spatio-temporal dynamics in all parts of the heart. In this study, we have developed a multi-scale hierarchy of biophysically detailed computational models for the human atria – 3D virtual human atria. Primarily, diffusion tensor MRI reconstruction of the tissue geometry and fibre orientation in the human sinoatrial node (SAN) and surrounding atrial muscle was integrated into the 3D model of the whole atria dissected from the Visible Human dataset. The anatomical models were combined with the heterogeneous atrial action potential (AP) models, and used to simulate the AP conduction in the human atria under various conditions: SAN pacemaking and atrial activation in the normal rhythm, break-down of regular AP wave-fronts during rapid atrial pacing, and the genesis of multiple re-entrant wavelets characteristic of AF. Contributions of different properties of the tissue to the mechanisms of the normal rhythm and AF arrhythmogenesis are investigated and discussed. The 3D model of the atria itself was incorporated into the torso model to simulate the body surface ECG patterns in the normal and arrhythmic conditions. Therefore, a state-of-the-art computational platform has been developed, which can be used for studying multi-scale electrical phenomena during atrial conduction and arrhythmogenesis. Results of such simulations can be directly compared with experimental electrophysiological and endocardial mapping data, as well as clinical ECG recordings. More importantly, the virtual human atria can provide validated means for directly dissecting 3D excitation propagation processes within the atrial walls from an in vivo whole heart, which are beyond the current technical capabilities of experimental or clinical set-ups. PMID:21762716

Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells.

PubMed

Sirenko, Syevda G; Yang, Dongmei; Maltseva, Larissa A; Kim, Mary S; Lakatta, Edward G; Maltsev, Victor A

2017-01-01

Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed "calcium clock"), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca2+ transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled-clock system regulation of APCL is a general, species-independent, mechanism of pacemaker cell normal automaticity. Lack of LCRs in prior studies is likely explained by technical issues, as individual LCRs are small stochastic events occurring mainly near the cell border.

Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells

PubMed Central

Sirenko, Syevda G.; Yang, Dongmei; Maltseva, Larissa A.; Kim, Mary S.; Lakatta, Edward G.

2017-01-01

Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed “calcium clock”), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca2+ transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled-clock system regulation of APCL is a general, species-independent, mechanism of pacemaker cell normal automaticity. Lack of LCRs in prior studies is likely explained by technical issues, as individual LCRs are small stochastic events occurring mainly near the cell border. PMID:28945810

Small functional If current in sinoatrial pacemaker cells of the brown trout (Salmo trutta fario) heart despite strong expression of HCN channel transcripts.

PubMed

Hassinen, Minna; Haverinen, Jaakko; Vornanen, Matti

2017-12-01

Funny current ( I f ), formed by hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels), is supposed to be crucial for the membrane clock regulating the cardiac pacemaker mechanism. We examined the presence and activity of HCN channels in the brown trout ( Salmo trutta fario ) sinoatrial (SA) pacemaker cells and their putative role in heart rate ( f H ) regulation. Six HCN transcripts (HCN1, HCN2a, HCN2ba, HCN2bb, HCN3, and HCN4) were expressed in the brown trout heart. The total HCN transcript abundance was 4.0 and 4.9 times higher in SA pacemaker tissue than in atrium and ventricle, respectively. In the SA pacemaker, HCN3 and HCN4 were the main isoforms representing 35.8 ± 2.7 and 25.0 ± 1.5%, respectively, of the total HCN transcripts. Only a small I f with a mean current density of -1.2 ± 0.37 pA/pF at -140 mV was found in 4 pacemaker cells out of 16 spontaneously beating cells examined, despite the optimization of recording conditions for I f activity. I f was not found in any of the 24 atrial myocytes and 21 ventricular myocytes examined. HCN4 coexpressed with the MinK-related peptide 1 (MiRP1) β-subunit in CHO cells generated large I f currents. In contrast, HCN3 (+MiRP1) failed to produce I f in the same expression system. Cs + (2 mM), which blocked 84 ± 12% of the native I f , reversibly reduced f H 19.2 ± 3.6% of the excised multicellular pacemaker tissue from 53 ± 5 to 44 ± 5 beats/min ( P < 0.05). However, this effect was probably due to the reduction of I Kr , which was also inhibited (63.5 ± 4.6%) by Cs + These results strongly suggest that f H regulation in the brown trout heart is largely independent on I f . Copyright © 2017 the American Physiological Society.

Drug insight: If inhibitors as specific heart-rate-reducing agents.

PubMed

Borer, Jeffrey S

2004-12-01

Heart rate is determined primarily by spontaneously repeating net inward current carried by sodium ions and potassium ions through hyperpolarization-activated cyclic-nucleotide-gated channels. Within the heart, these channels are found most abundantly in sinoatrial cardiomyocytes. The channels open in response to membrane hyperpolarization, modulated by local cAMP concentrations. They permit activation of the I(f) current, which can be blocked specifically by molecules characterized by linked benzazepinone and benzocyclobutane rings, and which are devoid of effects on cardiac conduction, inotropy or peripheral vascular tone. The resulting heart-rate reduction has been effective in angina prevention in clinical trials involving 4,000 patients, using the prototype I(f) inhibitor, ivabradine. No serious adverse events have been attributed to the treatment; the most prominent side-effect is dose-related, always reversible and often transient visual symptoms that seldom result in voluntary drug discontinuation.

Surgical treatment for ectopic atrial tachycardia.

PubMed

Graffigna, A; Vigano, M; Pagani, F; Salerno, G

1992-08-01

Atrial tachycardia is an infrequent but potentially dangerous arrhythmia which often determines cardiac enlargement. Surgical ablation of the arrhythmia is effective and safe, provided a careful atrial mapping is performed and the surgical technique is tailored to the individual focus location. Eight patients underwent surgical ablation of ectopic atrial tachycardia between 1977 and 1990. Different techniques were adopted for each patient according to the anatomical location of the focus and possibly associated arrhythmias. Whenever possible, a closed heart procedure was chosen. In 1 patient a double focal origin was found and treated by separate procedures. In 1 patient with ostium secundum atrial septal defect and atrial flutter, surgical isolation of the right appendage and the ectopic focus was performed. In all patients ectopic atrial tachycardia was ablated with maintenance of the sinoatrial and atrioventricular nodal function as well as internodal conduction. In follow-up up to December 1991, no recurrency was recorded.

Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells

PubMed Central

Jung, Julia Jeannine; Husse, Britta; Rimmbach, Christian; Krebs, Stefan; Stieber, Juliane; Steinhoff, Gustav; Dendorfer, Andreas; Franz, Wolfgang-Michael; David, Robert

2014-01-01

Summary Therapeutic approaches for “sick sinus syndrome” rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via “biological pacemakers” derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300–400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro. PMID:24936448

C-terminal modulatory domain controls coupling of voltage-sensing to pore opening in Cav1.3 L-type Ca(2+) channels.

PubMed

Lieb, Andreas; Ortner, Nadine; Striessnig, Jörg

2014-04-01

Activity of voltage-gated Cav1.3 L-type Ca(2+) channels is required for proper hearing as well as sinoatrial node and brain function. This critically depends on their negative activation voltage range, which is further fine-tuned by alternative splicing. Shorter variants miss a C-terminal regulatory domain (CTM), which allows them to activate at even more negative potentials than C-terminally long-splice variants. It is at present unclear whether this is due to an increased voltage sensitivity of the Cav1.3 voltage-sensing domain, or an enhanced coupling of voltage-sensor conformational changes to the subsequent opening of the activation gate. We studied the voltage-dependence of voltage-sensor charge movement (QON-V) and of current activation (ICa-V) of the long (Cav1.3L) and a short Cav1.3 splice variant (Cav1.342A) expressed in tsA-201 cells using whole cell patch-clamp. Charge movement (QON) of Cav1.3L displayed a much steeper voltage-dependence and a more negative half-maximal activation voltage than Cav1.2 and Cav3.1. However, a significantly higher fraction of the total charge had to move for activation of Cav1.3 half-maximal conductance (Cav1.3: 68%; Cav1.2: 52%; Cav3.1: 22%). This indicated a weaker coupling of Cav1.3 voltage-sensor charge movement to pore opening. However, the coupling efficiency was strengthened in the absence of the CTM in Cav1.342A, thereby shifting ICa-V by 7.2 mV to potentials that were more negative without changing QON-V. We independently show that the presence of intracellular organic cations (such as n-methyl-D-glucamine) induces a pronounced negative shift of QON-V and a more negative activation of ICa-V of all three channels. These findings illustrate that the voltage sensors of Cav1.3 channels respond more sensitively to depolarization than those of Cav1.2 or Cav3.1. Weak coupling of voltage sensing to pore opening is enhanced in the absence of the CTM, allowing short Cav1.342A splice variants to activate at lower voltages without affecting QON-V. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

[Autonomic contribution to the blood pressure and heart rate variability changes in early experimental hyperthyroidism].

PubMed

Safa-Tisseront, V; Ponchon, P; Blanc, J; Elghozi, J L

1998-08-01

A great deal of uncertainty persists regarding the exact nature of the interaction between autonomic nervous activity and thyroid hormones in the control of heart rate (HR) and blood pressure (BP). Thyrotoxicosis was produced by a daily intraperitoneal (i.p.) injection of L-thyroxine (0.5 mg/kg body wt in 1 ml of 5 mM NaOH for 5 days). Control rats received i.p. daily injections of the thyroxine solvant. Autonomic blockers were administered intravenously: atropine (0.5 mg/kg), atenolol (1 mg/kg), atenolol + atropine or prazosin (1 mg/kg). Eight animals were studied in each group. Thyroxine treatment was sufficient to induce a significant degree of tachycardia (423 +/- 6 vs 353 +/- 4 bpm; p < 0.001, unpaired Student's tests), systolic BP elevation (142 +/- 3 vs 127 +/- 2 mmHg; p < 0.001), pulse pressure increase (51 +/- 2 vs 41 +/- 2 mmHg, p < 0.01), cardiac hypertrophy (1.165 +/- 0.017 vs 1.006 +/- 0.012 g, p < 0.001), weight loss (-21 +/- 2 g; p < 0.001) and hyperthermia (37.8 +/- 0.1 vs 37.0 +/- 0.1 degrees C, p < 0.001). The intrinsic HR observed after double blockade (atenolol + atropine) was markedly increased after treatment with thyroxine (497 +/- 16 vs 373 +/- 10 bpm, p < 0.05). Vagal tone (difference between HR obtained after atenolol and intrinsic HR) was positively linearly related to intrinsic HR (r = 0.84; p < 0.01). Atenolol neither modified HR nor BP variability in rats with hyperthyrodism. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of BP variability (analyses on 102.4 sec segments, modulus 1.10 +/- 0.07 vs 1.41 +/- 0.06 mmHg; p < 0.01). Prazosin was without effect on this 0.4 Hz component in these animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in experimental hyperthyroidism. Increased intrinsic HR resulting from the direct effect of thyroid hormone on the sinoatrial node is the main determinant of a tachycardia leading to a subsequent rise in cardiac output. The resulting BP elevation could reflexly induce a vagal activation and a sympathetic (vascular and cardiac) inhibition.

3D virtual human atria: A computational platform for studying clinical atrial fibrillation.

PubMed

Aslanidi, Oleg V; Colman, Michael A; Stott, Jonathan; Dobrzynski, Halina; Boyett, Mark R; Holden, Arun V; Zhang, Henggui

2011-10-01

Despite a vast amount of experimental and clinical data on the underlying ionic, cellular and tissue substrates, the mechanisms of common atrial arrhythmias (such as atrial fibrillation, AF) arising from the functional interactions at the whole atria level remain unclear. Computational modelling provides a quantitative framework for integrating such multi-scale data and understanding the arrhythmogenic behaviour that emerges from the collective spatio-temporal dynamics in all parts of the heart. In this study, we have developed a multi-scale hierarchy of biophysically detailed computational models for the human atria--the 3D virtual human atria. Primarily, diffusion tensor MRI reconstruction of the tissue geometry and fibre orientation in the human sinoatrial node (SAN) and surrounding atrial muscle was integrated into the 3D model of the whole atria dissected from the Visible Human dataset. The anatomical models were combined with the heterogeneous atrial action potential (AP) models, and used to simulate the AP conduction in the human atria under various conditions: SAN pacemaking and atrial activation in the normal rhythm, break-down of regular AP wave-fronts during rapid atrial pacing, and the genesis of multiple re-entrant wavelets characteristic of AF. Contributions of different properties of the tissue to mechanisms of the normal rhythm and arrhythmogenesis were investigated. Primarily, the simulations showed that tissue heterogeneity caused the break-down of the normal AP wave-fronts at rapid pacing rates, which initiated a pair of re-entrant spiral waves; and tissue anisotropy resulted in a further break-down of the spiral waves into multiple meandering wavelets characteristic of AF. The 3D virtual atria model itself was incorporated into the torso model to simulate the body surface ECG patterns in the normal and arrhythmic conditions. Therefore, a state-of-the-art computational platform has been developed, which can be used for studying multi-scale electrical phenomena during atrial conduction and AF arrhythmogenesis. Results of such simulations can be directly compared with electrophysiological and endocardial mapping data, as well as clinical ECG recordings. The virtual human atria can provide in-depth insights into 3D excitation propagation processes within atrial walls of a whole heart in vivo, which is beyond the current technical capabilities of experimental or clinical set-ups. Copyright © 2011 Elsevier Ltd. All rights reserved.

Heart Rate Fragmentation: A Symbolic Dynamical Approach.

PubMed

Costa, Madalena D; Davis, Roger B; Goldberger, Ary L

2017-01-01

Background: We recently introduced the concept of heart rate fragmentation along with a set of metrics for its quantification. The term was coined to refer to an increase in the percentage of changes in heart rate acceleration sign, a dynamical marker of a type of anomalous variability. The effort was motivated by the observation that fragmentation, which is consistent with the breakdown of the neuroautonomic-electrophysiologic control system of the sino-atrial node, could confound traditional short-term analysis of heart rate variability. Objective: The objectives of this study were to: (1) introduce a symbolic dynamical approach to the problem of quantifying heart rate fragmentation; (2) evaluate how the distribution of the different dynamical patterns ("words") varied with the participants' age in a group of healthy subjects and patients with coronary artery disease (CAD); and (3) quantify the differences in the fragmentation patterns between the two sample populations. Methods: The symbolic dynamical method employed here was based on a ternary map of the increment NN interval time series and on the analysis of the relative frequency of symbolic sequences (words) with a pre-defined set of features. We analyzed annotated, open-access Holter databases of healthy subjects and patients with CAD, provided by the University of Rochester Telemetric and Holter ECG Warehouse (THEW). Results: The degree of fragmentation was significantly higher in older individuals than in their younger counterparts. However, the fragmentation patterns were different in the two sample populations. In healthy subjects, older age was significantly associated with a higher percentage of transitions from acceleration/deceleration to zero acceleration and vice versa (termed "soft" inflection points). In patients with CAD, older age was also significantly associated with higher percentages of frank reversals in heart rate acceleration (transitions from acceleration to deceleration and vice versa , termed "hard" inflection points). Compared to healthy subjects, patients with CAD had significantly higher percentages of soft and hard inflection points, an increased percentage of words with a high degree of fragmentation and a decreased percentage of words with a lower degree of fragmentation. Conclusion: The symbolic dynamical method employed here was useful to probe the newly recognized property of heart rate fragmentation. The findings from these cross-sectional studies confirm that CAD and older age are associated with higher levels of heart rate fragmentation. Furthermore, fragmentation with healthy aging appears to be phenotypically different from fragmentation in the context of CAD.

The sedative and analgesic effects of detomidine-butorphanol and detomidine alone in donkeys.

PubMed

Joubert, K E; Briggs, P; Gerber, D; Gottschalk, R G

1999-09-01

Butorphanol and detomidine constitute an effective combination for sedation and analgesia in horses. This trial was undertaken to assess the effectiveness of this combination in donkeys. The detomidine and butorphanol were given intravenously one after the other. A dose of 10 microg/kg of detomidine and 25 microg/kg of butorphanol was used. Sedation is easily extended by additional doses of butorphanol. The average dose of detomidine was 11.24 microg/kg and that of butorphanol was 28.0 microg/kg. Four donkeys in the detomidine group required additional sedation and analgesia. Detomidine alone did not totally eliminate coronary band pain. Heart rates dropped significantly in the first minute after the injection of the combination. One donkey developed an atrioventricular block, while another developed a sino-atrial block. Four donkeys developed a Cheyne-Stokes respiratory pattern. The combination of detomidine and butorphanol is an effective combination for sedation and analgesia of donkeys for standing procedures.

Synergistic nonuniform shortening of atrial refractory period induced by autonomic stimulation.

PubMed

Takei, M; Furukawa, Y; Narita, M; Ren, L M; Karasawa, Y; Murakami, M; Chiba, S

1991-12-01

We investigated the nonuniform effects of autonomic nerve stimulation of the effective refractory period (ERP) of the right atrium in the anesthetized dog. Stimulation of the discrete intracardiac sympathetic nerves to the sinoatrial (SA) nodal region uniformly shortened ERPs at three sites in the right atrium after administration of atropine. Right ansa subclavia (RS) stimulation similarly shortened ERPs in the absence of atropine. Stimulation of the discrete intracardiac parasympathetic nerves to the SA nodal region (SAP stimulation) shortened ERPs of the right atrium in a nonuniform manner. Simultaneous RS and SAP stimulation additively shortened ERPs at each site and decreased sinus rate much more than SAP stimulation alone. Shortening of ERP induced by SAP stimulation was greater than that induced by RS stimulation at similar absolute changes in heart rate. These results suggest that simultaneous activation of sympathetic and parasympathetic nerves nonuniformly shortens the ERP in the right atrium as the algebraic sum of the individual responses to each stimulation. However, parasympathetics exert the principal neural control over atrial ERP.

Systems and methods for optimal power flow on a radial network

DOEpatents

Low, Steven H.; Peng, Qiuyu

2018-04-24

Node controllers and power distribution networks in accordance with embodiments of the invention enable distributed power control. One embodiment includes a node controller including a distributed power control application; a plurality of node operating parameters describing the operating parameter of a node and a set of at least one node selected from the group consisting of an ancestor node and at least one child node; wherein send node operating parameters to nodes in the set of at least one node; receive operating parameters from the nodes in the set of at least one node; calculate a plurality of updated node operating parameters using an iterative process to determine the updated node operating parameters using the node operating parameters that describe the operating parameters of the node and the set of at least one node, where the iterative process involves evaluation of a closed form solution; and adjust node operating parameters.

Sentinel nodes identified by computed tomography-lymphography accurately stage the axilla in patients with breast cancer

PubMed Central

2013-01-01

Background Sentinel node biopsy often results in the identification and removal of multiple nodes as sentinel nodes, although most of these nodes could be non-sentinel nodes. This study investigated whether computed tomography-lymphography (CT-LG) can distinguish sentinel nodes from non-sentinel nodes and whether sentinel nodes identified by CT-LG can accurately stage the axilla in patients with breast cancer. Methods This study included 184 patients with breast cancer and clinically negative nodes. Contrast agent was injected interstitially. The location of sentinel nodes was marked on the skin surface using a CT laser light navigator system. Lymph nodes located just under the marks were first removed as sentinel nodes. Then, all dyed nodes or all hot nodes were removed. Results The mean number of sentinel nodes identified by CT-LG was significantly lower than that of dyed and/or hot nodes removed (1.1 vs 1.8, p <0.0001). Twenty-three (12.5%) patients had ≥2 sentinel nodes identified by CT-LG removed, whereas 94 (51.1%) of patients had ≥2 dyed and/or hot nodes removed (p <0.0001). Pathological evaluation demonstrated that 47 (25.5%) of 184 patients had metastasis to at least one node. All 47 patients demonstrated metastases to at least one of the sentinel nodes identified by CT-LG. Conclusions CT-LG can distinguish sentinel nodes from non-sentinel nodes, and sentinel nodes identified by CT-LG can accurately stage the axilla in patients with breast cancer. Successful identification of sentinel nodes using CT-LG may facilitate image-based diagnosis of metastasis, possibly leading to the omission of sentinel node biopsy. PMID:24321242

Broadcasting a message in a parallel computer

DOEpatents

Archer, Charles J; Faraj, Ahmad A

2013-04-16

Methods, systems, and products are disclosed for broadcasting a message in a parallel computer that includes: transmitting, by the logical root to all of the nodes directly connected to the logical root, a message; and for each node except the logical root: receiving the message; if that node is the physical root, then transmitting the message to all of the child nodes except the child node from which the message was received; if that node received the message from a parent node and if that node is not a leaf node, then transmitting the message to all of the child nodes; and if that node received the message from a child node and if that node is not the physical root, then transmitting the message to all of the child nodes except the child node from which the message was received and transmitting the message to the parent node.

Broadcasting a message in a parallel computer

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

None

Methods, systems, and products are disclosed for broadcasting a message in a parallel computer that includes: transmitting, by the logical root to all of the nodes directly connected to the logical root, a message; and for each node except the logical root: receiving the message; if that node is the physical root, then transmitting the message to all of the child nodes except the child node from which the message was received; if that node received the message from a parent node and if that node is not a leaf node, then transmitting the message to all of the childmore » nodes; and if that node received the message from a child node and if that node is not the physical root, then transmitting the message to all of the child nodes except the child node from which the message was received and transmitting the message to the parent node.« less

Dynamically reassigning a connected node to a block of compute nodes for re-launching a failed job

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

Budnik, Thomas A; Knudson, Brant L; Megerian, Mark G

Methods, systems, and products for dynamically reassigning a connected node to a block of compute nodes for re-launching a failed job that include: identifying that a job failed to execute on the block of compute nodes because connectivity failed between a compute node assigned as at least one of the connected nodes for the block of compute nodes and its supporting I/O node; and re-launching the job, including selecting an alternative connected node that is actively coupled for data communications with an active I/O node; and assigning the alternative connected node as the connected node for the block of computemore » nodes running the re-launched job.« less

Identifying messaging completion in a parallel computer by checking for change in message received and transmitted count at each node

DOEpatents

Archer, Charles J [Rochester, MN; Hardwick, Camesha R [Fayetteville, NC; McCarthy, Patrick J [Rochester, MN; Wallenfelt, Brian P [Eden Prairie, MN

2009-06-23

Methods, parallel computers, and products are provided for identifying messaging completion on a parallel computer. The parallel computer includes a plurality of compute nodes, the compute nodes coupled for data communications by at least two independent data communications networks including a binary tree data communications network optimal for collective operations that organizes the nodes as a tree and a torus data communications network optimal for point to point operations that organizes the nodes as a torus. Embodiments include reading all counters at each node of the torus data communications network; calculating at each node a current node value in dependence upon the values read from the counters at each node; and determining for all nodes whether the current node value for each node is the same as a previously calculated node value for each node. If the current node is the same as the previously calculated node value for all nodes of the torus data communications network, embodiments include determining that messaging is complete and if the current node is not the same as the previously calculated node value for all nodes of the torus data communications network, embodiments include determining that messaging is currently incomplete.

Fault tolerant hypercube computer system architecture

NASA Technical Reports Server (NTRS)

Madan, Herb S. (Inventor); Chow, Edward (Inventor)

1989-01-01

A fault-tolerant multiprocessor computer system of the hypercube type comprising a hierarchy of computers of like kind which can be functionally substituted for one another as necessary is disclosed. Communication between the working nodes is via one communications network while communications between the working nodes and watch dog nodes and load balancing nodes higher in the structure is via another communications network separate from the first. A typical branch of the hierarchy reporting to a master node or host computer comprises, a plurality of first computing nodes; a first network of message conducting paths for interconnecting the first computing nodes as a hypercube. The first network provides a path for message transfer between the first computing nodes; a first watch dog node; and a second network of message connecting paths for connecting the first computing nodes to the first watch dog node independent from the first network, the second network provides an independent path for test message and reconfiguration affecting transfers between the first computing nodes and the first switch watch dog node. There is additionally, a plurality of second computing nodes; a third network of message conducting paths for interconnecting the second computing nodes as a hypercube. The third network provides a path for message transfer between the second computing nodes; a fourth network of message conducting paths for connecting the second computing nodes to the first watch dog node independent from the third network. The fourth network provides an independent path for test message and reconfiguration affecting transfers between the second computing nodes and the first watch dog node; and a first multiplexer disposed between the first watch dog node and the second and fourth networks for allowing the first watch dog node to selectively communicate with individual ones of the computing nodes through the second and fourth networks; as well as, a second watch dog node operably connected to the first multiplexer whereby the second watch dog node can selectively communicate with individual ones of the computing nodes through the second and fourth networks. The branch is completed by a first load balancing node; and a second multiplexer connected between the first load balancing node and the first and second watch dog nodes, allowing the first load balancing node to selectively communicate with the first and second watch dog nodes.

The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice.

PubMed

Baggio, Laurie L; Ussher, John R; McLean, Brent A; Cao, Xiemin; Kabir, M Golam; Mulvihill, Erin E; Mighiu, Alexandra S; Zhang, Hangjun; Ludwig, Andreas; Seeley, Randy J; Heximer, Scott P; Drucker, Daniel J

2017-11-01

Glucagon-like peptide-1 (GLP-1) is secreted from enteroendocrine cells and exerts a broad number of metabolic actions through activation of a single GLP-1 receptor (GLP-1R). The cardiovascular actions of GLP-1 have garnered increasing attention as GLP-1R agonists are used to treat human subjects with diabetes and obesity that may be at increased risk for development of heart disease. Here we studied mechanisms linking GLP-1R activation to control of heart rate (HR) in mice. The actions of GLP-1R agonists were examined on the control of HR in wild type mice (WT) and in mice with cardiomyocyte-selective disruption of the GLP-1R (Glp1r CM-/- ). Complimentary studies examined the effects of GLP-1R agonists in mice co-administered propranolol or atropine. The direct effects of GLP-1R agonism on HR and ventricular developed pressure were examined in isolated perfused mouse hearts ex vivo, and atrial depolarization was quantified in mouse hearts following direct application of liraglutide to perfused atrial preparations ex vivo. Doses of liraglutide and lixisenatide that were equipotent for acute glucose control rapidly increased HR in WT and Glp1r CM-/- mice in vivo. The actions of liraglutide to increase HR were more sustained relative to lixisenatide, and diminished in Glp1r CM-/- mice. The acute chronotropic actions of GLP-1R agonists were attenuated by propranolol but not atropine. Neither native GLP-1 nor lixisenatide increased HR or developed pressure in perfused hearts ex vivo. Moreover, liraglutide had no direct effect on sinoatrial node firing rate in mouse atrial preparations ex vivo. Despite co-localization of HCN4 and GLP-1R in primate hearts, HCN4-directed Cre expression did not attenuate levels of Glp1r mRNA transcripts, but did reduce atrial Gcgr expression in the mouse heart. GLP-1R agonists increase HR through multiple mechanisms, including regulation of autonomic nervous system function, and activation of the atrial GLP-1R. Surprisingly, the isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.

PubMed

Fox, Kim; Ford, Ian; Steg, P Gabriel; Tendera, Michal; Ferrari, Roberto

2008-09-06

Ivabradine specifically inhibits the I(f) current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction. Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507. Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016). Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.

Scheduling applications for execution on a plurality of compute nodes of a parallel computer to manage temperature of the nodes during execution

DOEpatents

Archer, Charles J; Blocksome, Michael A; Peters, Amanda E; Ratterman, Joseph D; Smith, Brian E

2012-10-16

Methods, apparatus, and products are disclosed for scheduling applications for execution on a plurality of compute nodes of a parallel computer to manage temperature of the plurality of compute nodes during execution that include: identifying one or more applications for execution on the plurality of compute nodes; creating a plurality of physically discontiguous node partitions in dependence upon temperature characteristics for the compute nodes and a physical topology for the compute nodes, each discontiguous node partition specifying a collection of physically adjacent compute nodes; and assigning, for each application, that application to one or more of the discontiguous node partitions for execution on the compute nodes specified by the assigned discontiguous node partitions.

Aggregating job exit statuses of a plurality of compute nodes executing a parallel application

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

Aho, Michael E.; Attinella, John E.; Gooding, Thomas M.

Aggregating job exit statuses of a plurality of compute nodes executing a parallel application, including: identifying a subset of compute nodes in the parallel computer to execute the parallel application; selecting one compute node in the subset of compute nodes in the parallel computer as a job leader compute node; initiating execution of the parallel application on the subset of compute nodes; receiving an exit status from each compute node in the subset of compute nodes, where the exit status for each compute node includes information describing execution of some portion of the parallel application by the compute node; aggregatingmore » each exit status from each compute node in the subset of compute nodes; and sending an aggregated exit status for the subset of compute nodes in the parallel computer.« less

Distributing an executable job load file to compute nodes in a parallel computer

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

Gooding, Thomas M.

Distributing an executable job load file to compute nodes in a parallel computer, the parallel computer comprising a plurality of compute nodes, including: determining, by a compute node in the parallel computer, whether the compute node is participating in a job; determining, by the compute node in the parallel computer, whether a descendant compute node is participating in the job; responsive to determining that the compute node is participating in the job or that the descendant compute node is participating in the job, communicating, by the compute node to a parent compute node, an identification of a data communications linkmore » over which the compute node receives data from the parent compute node; constructing a class route for the job, wherein the class route identifies all compute nodes participating in the job; and broadcasting the executable load file for the job along the class route for the job.« less

Reconfigureable network node

DOEpatents

Vanderveen, Keith B [Tracy, CA; Talbot, Edward B [Livermore, CA; Mayer, Laurence E [Davis, CA

2008-04-08

Nodes in a network having a plurality of nodes establish communication links with other nodes using available transmission media, as the ability to establish such links becomes available and desirable. The nodes predict when existing communications links will fail, become overloaded or otherwise degrade network effectiveness and act to establish substitute or additional links before the node's ability to communicate with the other nodes on the network is adversely affected. A node stores network topology information and programmed link establishment rules and criteria. The node evaluates characteristics that predict existing links with other nodes becoming unavailable or degraded. The node then determines whether it can form a communication link with a substitute node, in order to maintain connectivity with the network. When changing its communication links, a node broadcasts that information to the network. Other nodes update their stored topology information and consider the updated topology when establishing new communications links for themselves.

Protocol for multiple node network

NASA Technical Reports Server (NTRS)

Kirkham, Harold (Inventor)

1995-01-01

The invention is a multiple interconnected network of intelligent message-repeating remote nodes which employs an antibody recognition message termination process performed by all remote nodes and a remote node polling process performed by other nodes which are master units controlling remote nodes in respective zones of the network assigned to respective master nodes. Each remote node repeats only those messages originated in the local zone, to provide isolation among the master nodes.

Protocol for multiple node network

NASA Technical Reports Server (NTRS)

Kirkham, Harold (Inventor)

1994-01-01

The invention is a multiple interconnected network of intelligent message-repeating remote nodes which employs an antibody recognition message termination process performed by all remote nodes and a remote node polling process performed by other nodes which are master units controlling remote nodes in respective zones of the network assigned to respective master nodes. Each remote node repeats only those messages originated in the local zone, to provide isolation among the master nodes.

In vivo and ex vivo sentinel node mapping does not identify the same lymph nodes in colon cancer.

PubMed

Andersen, Helene Schou; Bennedsen, Astrid Louise Bjørn; Burgdorf, Stefan Kobbelgaard; Eriksen, Jens Ravn; Eiholm, Susanne; Toxværd, Anders; Riis, Lene Buhl; Rosenberg, Jacob; Gögenur, Ismail

2017-07-01

Identification of lymph nodes and pathological analysis is crucial for the correct staging of colon cancer. Lymph nodes that drain directly from the tumor area are called "sentinel nodes" and are believed to be the first place for metastasis. The purpose of this study was to perform sentinel node mapping in vivo with indocyanine green and ex vivo with methylene blue in order to evaluate if the sentinel lymph nodes can be identified by both techniques. Patients with colon cancer UICC stage I-III were included from two institutions in Denmark from February 2015 to January 2016. In vivo sentinel node mapping with indocyanine green during laparoscopy and ex vivo sentinel node mapping with methylene blue were performed in all patients. Twenty-nine patients were included. The in vivo sentinel node mapping was successful in 19 cases, and ex vivo sentinel node mapping was successful in 13 cases. In seven cases, no sentinel nodes were identified. A total of 51 sentinel nodes were identified, only one of these where identified by both techniques (2.0%). In vivo sentinel node mapping identified 32 sentinel nodes, while 20 sentinel nodes were identified by ex vivo sentinel node mapping. Lymph node metastases were found in 10 patients, and only two had metastases in a sentinel node. Placing a deposit in relation to the tumor by indocyanine green in vivo or of methylene blue ex vivo could only identify sentinel lymph nodes in a small group of patients.

Node 3 Relocation Environmental Control and Life Support System Modification Kit Verification and Updated Status

NASA Technical Reports Server (NTRS)

Williams, David E.; Spector Lawrence N.

2010-01-01

Node 1 (Unity) flew to International Space Station (ISS) on Flight 2A. Node 1 was the first module of the United States On-Orbit Segment (USOS) launched to ISS. The Node 1 ISS Environmental Control and Life Support (ECLS) design featured limited ECLS capability. The main purpose of Node 1 was to provide internal storage by providing four stowage rack locations within the module and to allow docking of multiple modules and a truss segment to it. The ECLS subsystems inside Node 1 were routed through the element prior to launch to allow for easy integration of the attached future elements, particularly the Habitation Module which was planned to be located at the nadir docking port of Node 1. After Node I was on-orbit, the Program decided not to launch the Habitation Module and instead, to replace it with Node 3 (Tranquility). In 2007, the Program became concerned with a potential Russian docking port approach issue for the Russian FGB nadir docking port after Node 3 is attached to Node 1. To solve this concern the Program decided to relocate Node 3 from Node I nadir to Node 1 port. To support the movement of Node 3 the Program decided to build a modification kit for Node 1, an on-orbit feedthrough leak test device, and new vestibule jumpers to support the ECLS part of the relocation. This paper provides a design overview of the modification kit for Node 1, a summary of the Node 1 ECLS re-verification to support the Node 3 relocation from Node 1 nadir to Node 1 port, and a status of the ECLS modification kit installation into Node 1.

Method and apparatus for routing data in an inter-nodal communications lattice of a massively parallel computer system by routing through transporter nodes

DOEpatents

Archer, Charles Jens; Musselman, Roy Glenn; Peters, Amanda; Pinnow, Kurt Walter; Swartz, Brent Allen; Wallenfelt, Brian Paul

2010-11-16

A massively parallel computer system contains an inter-nodal communications network of node-to-node links. An automated routing strategy routes packets through one or more intermediate nodes of the network to reach a destination. Some packets are constrained to be routed through respective designated transporter nodes, the automated routing strategy determining a path from a respective source node to a respective transporter node, and from a respective transporter node to a respective destination node. Preferably, the source node chooses a routing policy from among multiple possible choices, and that policy is followed by all intermediate nodes. The use of transporter nodes allows greater flexibility in routing.

Compiling software for a hierarchical distributed processing system

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2013-12-31

Compiling software for a hierarchical distributed processing system including providing to one or more compiling nodes software to be compiled, wherein at least a portion of the software to be compiled is to be executed by one or more nodes; compiling, by the compiling node, the software; maintaining, by the compiling node, any compiled software to be executed on the compiling node; selecting, by the compiling node, one or more nodes in a next tier of the hierarchy of the distributed processing system in dependence upon whether any compiled software is for the selected node or the selected node's descendents; sending to the selected node only the compiled software to be executed by the selected node or selected node's descendent.

Synchronizing compute node time bases in a parallel computer

DOEpatents

Chen, Dong; Faraj, Daniel A; Gooding, Thomas M; Heidelberger, Philip

2015-01-27

Synchronizing time bases in a parallel computer that includes compute nodes organized for data communications in a tree network, where one compute node is designated as a root, and, for each compute node: calculating data transmission latency from the root to the compute node; configuring a thread as a pulse waiter; initializing a wakeup unit; and performing a local barrier operation; upon each node completing the local barrier operation, entering, by all compute nodes, a global barrier operation; upon all nodes entering the global barrier operation, sending, to all the compute nodes, a pulse signal; and for each compute node upon receiving the pulse signal: waking, by the wakeup unit, the pulse waiter; setting a time base for the compute node equal to the data transmission latency between the root node and the compute node; and exiting the global barrier operation.

Synchronizing compute node time bases in a parallel computer

DOEpatents

Chen, Dong; Faraj, Daniel A; Gooding, Thomas M; Heidelberger, Philip

2014-12-30

Synchronizing time bases in a parallel computer that includes compute nodes organized for data communications in a tree network, where one compute node is designated as a root, and, for each compute node: calculating data transmission latency from the root to the compute node; configuring a thread as a pulse waiter; initializing a wakeup unit; and performing a local barrier operation; upon each node completing the local barrier operation, entering, by all compute nodes, a global barrier operation; upon all nodes entering the global barrier operation, sending, to all the compute nodes, a pulse signal; and for each compute node upon receiving the pulse signal: waking, by the wakeup unit, the pulse waiter; setting a time base for the compute node equal to the data transmission latency between the root node and the compute node; and exiting the global barrier operation.

Distributed downhole drilling network

DOEpatents

Hall, David R.; Hall, Jr., H. Tracy; Fox, Joe; Pixton, David S.

2006-11-21

A high-speed downhole network providing real-time data from downhole components of a drilling strings includes a bottom-hole node interfacing to a bottom-hole assembly located proximate the bottom end of a drill string. A top-hole node is connected proximate the top end of the drill string. One or several intermediate nodes are located along the drill string between the bottom-hole node and the top-hole node. The intermediate nodes are configured to receive and transmit data packets transmitted between the bottom-hole node and the top-hole node. A communications link, integrated into the drill string, is used to operably connect the bottom-hole node, the intermediate nodes, and the top-hole node. In selected embodiments, a personal or other computer may be connected to the top-hole node, to analyze data received from the intermediate and bottom-hole nodes.

EXTENSIBLE DATABASE FRAMEWORK FOR MANAGEMENT OF UNSTRUCTURED AND SEMI-STRUCTURED DOCUMENTS

NASA Technical Reports Server (NTRS)

Gawdiak, Yuri O. (Inventor); La, Tracy T. (Inventor); Lin, Shu-Chun Y. (Inventor); Malof, David A. (Inventor); Tran, Khai Peter B. (Inventor)

2005-01-01

Method and system for querying a collection of Unstructured or semi-structured documents to identify presence of, and provide context and/or content for, keywords and/or keyphrases. The documents are analyzed and assigned a node structure, including an ordered sequence of mutually exclusive node segments or strings. Each node has an associated set of at least four, five or six attributes with node information and can represent a format marker or text, with the last node in any node segment usually being a text node. A keyword (or keyphrase) is specified. and the last node in each node segment is searched for a match with the keyword. When a match is found at a query node, or at a node determined with reference to a query node, the system displays the context andor the content of the query node.

Cholinergic modulation of activation sequence in the atrial myocardium of non-mammalian vertebrates.

PubMed

Abramochkin, Denis V; Kuzmin, Vladislav S; Sukhova, Galina S; Rosenshtraukh, Leonid V

2010-02-01

Cholinergic changes of electric activity were studied in isolated atrium preparations from fishes (cod and carp), amphibians (frog) and reptilians (lizard) using the microelectrode technique and high-resolution optical mapping. Perfusion of isolated atrium with acetylcholine (10(-6)-5.10(-5) M) caused gradual suppression of action potential generation and, eventually, completely blocked the excitation in a part of the preparation. Other regions of atrium, situated close to the sinoatrial and atrioventricular junctions, remained excitable. Such cholinergic suppression of electric activity was observed in the atrial myocardium of frog and in both fish species, but not in reptilians. Ba(2+) (10(-4) M), which blocks the acetylcholine-dependent potassium current (I(KACh)), prevented cholinergic reduction of action potential amplitude. In several preparations of frog atrium, cholinergic suppression of excitation coincided with episodes of atrial fibrillation. We conclude that the phenomenon of cholinergic suppression of electric activity is typical for atria of fishes and amphibians. It is likely to be caused by I(KACh) activation and may be important for initiation of atrial arrhythmias. 2009 Elsevier Inc. All rights reserved.

Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate

PubMed Central

Burkhard, Silja Barbara

2018-01-01

Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/β-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/β-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions. PMID:29400650

Node 3 Relocation Environmental Control and Life Support System Modification Kit Verification and Updated Status

NASA Technical Reports Server (NTRS)

Williams, David E.; Spector, Lawrence N.

2009-01-01

Node 1 (Unity) flew to International Space Station (ISS) on Flight 2A. Node 1 was the first module of the United States On-Orbit Segment (USOS) launched to ISS. The Node 1 ISS Environmental Control and Life Support (ECLS) design featured limited ECLS capability. The main purpose of Node 1 was to provide internal storage by providing four stowage rack locations within the module and to allow docking of multiple modules and a truss segment to it. The ECLS subsystems inside Node 1 were routed through the element prior to launch to allow for easy integration of the attached future elements, particularly the Habitation Module which was planned to be located at the nadir docking port of Node 1. After Node 1 was on-orbit, the Program decided not to launch the Habitation Module and instead, to replace it with Node 3 (Tranquility). In 2007, the Program became concerned with a potential Russian docking port approach issue for the Russian FGB nadir docking port after Node 3 is attached to Node 1. To solve this concern the Program decided to relocate Node 3 from Node 1 nadir to Node 1 port. To support the movement of Node 3 the Program decided to build a modification kit for Node 1, an on-orbit feedthrough leak test device, and new vestibule jumpers to support the ECLS part of the relocation. This paper provides a design overview of the modification kit, a summary of the Node 1 ECLS re-verification to support the Node 3 relocation from Node 1 nadir to Node 1 port, and a status of the ECLS modification kit installation into Node 1.

Weighted compactness function based label propagation algorithm for community detection

NASA Astrophysics Data System (ADS)

Zhang, Weitong; Zhang, Rui; Shang, Ronghua; Jiao, Licheng

2018-02-01

Community detection in complex networks, is to detect the community structure with the internal structure relatively compact and the external structure relatively sparse, according to the topological relationship among nodes in the network. In this paper, we propose a compactness function which combines the weight of nodes, and use it as the objective function to carry out the node label propagation. Firstly, according to the node degree, we find the sets of core nodes which have great influence on the network. The more the connections between the core nodes and the other nodes are, the larger the amount of the information these kernel nodes receive and transform. Then, according to the similarity of the nodes between the core nodes sets and the nodes degree, we assign weights to the nodes in the network. So the label of the nodes with great influence will be the priority in the label propagation process, which effectively improves the accuracy of the label propagation. The compactness function between nodes and communities in this paper is based on the nodes influence. It combines the connections between nodes and communities with the degree of the node belongs to its neighbor communities based on calculating the node weight. The function effectively uses the information of nodes and connections in the network. The experimental results show that the proposed algorithm can achieve good results in the artificial network and large-scale real networks compared with the 8 contrast algorithms.

Anatomy and nomenclature of murine lymph nodes: Descriptive study and nomenclatory standardization in BALB/cAnNCrl mice.

PubMed

Van den Broeck, Wim; Derore, Annie; Simoens, Paul

2006-05-30

Murine lymph nodes are intensively studied but often assigned incorrectly in scientific papers. In BALB/cAnNCrl mice, we characterized a total of 22 different lymph nodes. Peripheral nodes were situated in the head and neck region (mandibular, accessory mandibular, superficial parotid, cranial deep cervical nodes), and at the forelimb (proper axillary, accessory axillary nodes) and hindlimb (subiliac, sciatic, popliteal nodes). Intrathoracic lymph nodes included the cranial mediastinal, tracheobronchal and caudal mediastinal nodes. Abdominal lymph nodes were associated with the gastrointestinal tract (gastric, pancreaticoduodenal, jejunal, colic, caudal mesenteric nodes) or were located along the major intra-abdominal blood vessels (renal, lumbar aortic, lateral iliac, medial iliac and external iliac nodes). Comparative and nomenclative aspects of murine lymph nodes are discussed. The position of the lymph nodes of BALB/cAnNCrl mice is summarized and illustrated in an anatomical chart containing proposals for both an official nomenclature according to the Nomina Anatomica Veterinaria and English terms.

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

Gooding, Thomas M.

Distributing an executable job load file to compute nodes in a parallel computer, the parallel computer comprising a plurality of compute nodes, including: determining, by a compute node in the parallel computer, whether the compute node is participating in a job; determining, by the compute node in the parallel computer, whether a descendant compute node is participating in the job; responsive to determining that the compute node is participating in the job or that the descendant compute node is participating in the job, communicating, by the compute node to a parent compute node, an identification of a data communications linkmore » over which the compute node receives data from the parent compute node; constructing a class route for the job, wherein the class route identifies all compute nodes participating in the job; and broadcasting the executable load file for the job along the class route for the job.« less

Error recovery to enable error-free message transfer between nodes of a computer network

DOEpatents

Blumrich, Matthias A.; Coteus, Paul W.; Chen, Dong; Gara, Alan; Giampapa, Mark E.; Heidelberger, Philip; Hoenicke, Dirk; Takken, Todd; Steinmacher-Burow, Burkhard; Vranas, Pavlos M.

2016-01-26

An error-recovery method to enable error-free message transfer between nodes of a computer network. A first node of the network sends a packet to a second node of the network over a link between the nodes, and the first node keeps a copy of the packet on a sending end of the link until the first node receives acknowledgment from the second node that the packet was received without error. The second node tests the packet to determine if the packet is error free. If the packet is not error free, the second node sets a flag to mark the packet as corrupt. The second node returns acknowledgement to the first node specifying whether the packet was received with or without error. When the packet is received with error, the link is returned to a known state and the packet is sent again to the second node.

AISIM (Automated Interactive Simulation Modeling System) VAX Version Training Manual.

DTIC Science & Technology

1985-02-01

node to which the link is to run, a-nd-(3) a user-given name of the link. To pi’ace a link called " LINKI " from NODE1 to NODE2, type CON NODE1,NODE2...example, to eliminate the connection between NODEI and NODE2 type DELETE LINKI The result on the screen would be that the link named "LINK1" would...the user should now enter the command: DEFINE PATH,NODE2 ,NODE4, LINKI ,LINK4 not only would the path from NODE2 to NODE4 be established, but the path

[Correlation factors of lymph node metastasis in patients with clinical stage T1a non-small cell lung cancer].

PubMed

Ruochuan, Zang; Shugeng, Guo; Jie, He; Yousheng, Mao; Qi, Xue; Dali, Wang; Juwei, Mu; Jun, Zhao; Yonggang, Wang; Xiangyang, Liu; Fengwei, Tan; Gefei, Zhao; Qian, Zhang; Moyan, Zhang; Peng, Song

2015-04-01

To explore the relationship between the lymph node metastasis and clinicopathological features in patients with clinical stage T1a non-small cell lung cancer (NSCLC). Clinicopathological data of a total of 418 patients who underwent lobectomy and systematic lymph node dissection were retrospectively analyzed. Logistic regression was used to analyze the relationship between lymph node metastasis and clinicopathological features. Lymph node metastasis was observed in 25 patients. There were 122 patients who were diagnosed as ground glass opacity with no lymph node metastasis. 399 patients had subcarinal dissection, among them 7 patients were found to have lymph node metastasis. Univariate analysis showed that gender, smoking history, diameter of lymph node, ground glass opacity (GGO), differentiation of the tumor and tumor site were the factors affecting lymph node metastasis (all P < 0.05). Logistic regression analysis showed that diameter of lymph node, differentiation of the tumor and the site of lesion were independent risk factors for lymph node metastasis of NSCLC. Tumor in the left lung, poor differentiation, and diameter of lymph nodes ≥ 1 cm on the preoperative CT image are independent risk factors for lymph node metastasis of NSCLC, hence we should pay attention before surgery and systematic lymph node dissection should be done. For patients with poor differentiation and lymph nodes ≥ 1 cm, subcarinal lymph nodes dissection is recommended for the sake of higher possibility of lymph node metastasis. For patients with ground glass opacity ≤ 2 cm, the lymph node metastasis is extremely rare, therefore, selective lymph node dissection is reconmmended.

Node Self-Deployment Algorithm Based on an Uneven Cluster with Radius Adjusting for Underwater Sensor Networks

PubMed Central

Jiang, Peng; Xu, Yiming; Wu, Feng

2016-01-01

Existing move-restricted node self-deployment algorithms are based on a fixed node communication radius, evaluate the performance based on network coverage or the connectivity rate and do not consider the number of nodes near the sink node and the energy consumption distribution of the network topology, thereby degrading network reliability and the energy consumption balance. Therefore, we propose a distributed underwater node self-deployment algorithm. First, each node begins the uneven clustering based on the distance on the water surface. Each cluster head node selects its next-hop node to synchronously construct a connected path to the sink node. Second, the cluster head node adjusts its depth while maintaining the layout formed by the uneven clustering and then adjusts the positions of in-cluster nodes. The algorithm originally considers the network reliability and energy consumption balance during node deployment and considers the coverage redundancy rate of all positions that a node may reach during the node position adjustment. Simulation results show, compared to the connected dominating set (CDS) based depth computation algorithm, that the proposed algorithm can increase the number of the nodes near the sink node and improve network reliability while guaranteeing the network connectivity rate. Moreover, it can balance energy consumption during network operation, further improve network coverage rate and reduce energy consumption. PMID:26784193

High speed polling protocol for multiple node network

NASA Technical Reports Server (NTRS)

Kirkham, Harold (Inventor)

1995-01-01

The invention is a multiple interconnected network of intelligent message-repeating remote nodes which employs a remote node polling process performed by a master node by transmitting a polling message generically addressed to all remote nodes associated with the master node. Each remote node responds upon receipt of the generically addressed polling message by transmitting a poll-answering informational message and by relaying the polling message to other adjacent remote nodes.

Identifying failure in a tree network of a parallel computer

DOEpatents

Archer, Charles J.; Pinnow, Kurt W.; Wallenfelt, Brian P.

2010-08-24

Methods, parallel computers, and products are provided for identifying failure in a tree network of a parallel computer. The parallel computer includes one or more processing sets including an I/O node and a plurality of compute nodes. For each processing set embodiments include selecting a set of test compute nodes, the test compute nodes being a subset of the compute nodes of the processing set; measuring the performance of the I/O node of the processing set; measuring the performance of the selected set of test compute nodes; calculating a current test value in dependence upon the measured performance of the I/O node of the processing set, the measured performance of the set of test compute nodes, and a predetermined value for I/O node performance; and comparing the current test value with a predetermined tree performance threshold. If the current test value is below the predetermined tree performance threshold, embodiments include selecting another set of test compute nodes. If the current test value is not below the predetermined tree performance threshold, embodiments include selecting from the test compute nodes one or more potential problem nodes and testing individually potential problem nodes and links to potential problem nodes.

Value of peripheral nodes in controlling multilayer scale-free networks

NASA Astrophysics Data System (ADS)

Zhang, Yan; Garas, Antonios; Schweitzer, Frank

2016-01-01

We analyze the controllability of a two-layer network, where driver nodes can be chosen randomly only from one layer. Each layer contains a scale-free network with directed links and the node dynamics depends on the incoming links from other nodes. We combine the in-degree and out-degree values to assign an importance value w to each node, and distinguish between peripheral nodes with low w and central nodes with high w . Based on numerical simulations, we find that the controllable part of the network is larger when choosing low w nodes to connect the two layers. The control is as efficient when peripheral nodes are driver nodes as it is for the case of more central nodes. However, if we assume a cost to utilize nodes that is proportional to their overall degree, utilizing peripheral nodes to connect the two layers or to act as driver nodes is not only the most cost-efficient solution, it is also the one that performs best in controlling the two-layer network among the different interconnecting strategies we have tested.

Electronic Resources for Security Related Information, CIAC-2307 R.1

DTIC Science & Technology

1994-12-01

administrators NETwork - Statistics about the network NODEntry node1 <node2 <…>> - BITEARN NODES entry for the specified node(s) NODEntry node1 / abc */xyz...Just the “:xyz.” tag and all tags whose name starts with “ abc ” PATHs snode node1 <node2 <…>> - BITNET path between “snode” and the specified node(s...protect their data and sytems . The mention of vendors or product names does not imply criticism or endorsement by the National Institute of Standards

Performing process migration with allreduce operations

DOEpatents

Archer, Charles Jens; Peters, Amanda; Wallenfelt, Brian Paul

2010-12-14

Compute nodes perform allreduce operations that swap processes at nodes. A first allreduce operation generates a first result and uses a first process from a first compute node, a second process from a second compute node, and zeros from other compute nodes. The first compute node replaces the first process with the first result. A second allreduce operation generates a second result and uses the first result from the first compute node, the second process from the second compute node, and zeros from others. The second compute node replaces the second process with the second result, which is the first process. A third allreduce operation generates a third result and uses the first result from first compute node, the second result from the second compute node, and zeros from others. The first compute node replaces the first result with the third result, which is the second process.

System for solving diagnosis and hitting set problems

NASA Technical Reports Server (NTRS)

Vatan, Farrokh (Inventor); Fijany, Amir (Inventor)

2007-01-01

The diagnosis problem arises when a system's actual behavior contradicts the expected behavior, thereby exhibiting symptoms (a collection of conflict sets). System diagnosis is then the task of identifying faulty components that are responsible for anomalous behavior. To solve the diagnosis problem, the present invention describes a method for finding the minimal set of faulty components (minimal diagnosis set) that explain the conflict sets. The method includes acts of creating a matrix of the collection of conflict sets, and then creating nodes from the matrix such that each node is a node in a search tree. A determination is made as to whether each node is a leaf node or has any children nodes. If any given node has children nodes, then the node is split until all nodes are leaf nodes. Information gathered from the leaf nodes is used to determine the minimal diagnosis set.

Send-side matching of data communications messages

DOEpatents

Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

2014-07-01

Send-side matching of data communications messages includes a plurality of compute nodes organized for collective operations, including: issuing by a receiving node to source nodes a receive message that specifies receipt of a single message to be sent from any source node, the receive message including message matching information, a specification of a hardware-level mutual exclusion device, and an identification of a receive buffer; matching by two or more of the source nodes the receive message with pending send messages in the two or more source nodes; operating by one of the source nodes having a matching send message the mutual exclusion device, excluding messages from other source nodes with matching send messages and identifying to the receiving node the source node operating the mutual exclusion device; and sending to the receiving node from the source node operating the mutual exclusion device a matched pending message.

Send-side matching of data communications messages

DOEpatents

Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

2014-06-17

Send-side matching of data communications messages in a distributed computing system comprising a plurality of compute nodes, including: issuing by a receiving node to source nodes a receive message that specifies receipt of a single message to be sent from any source node, the receive message including message matching information, a specification of a hardware-level mutual exclusion device, and an identification of a receive buffer; matching by two or more of the source nodes the receive message with pending send messages in the two or more source nodes; operating by one of the source nodes having a matching send message the mutual exclusion device, excluding messages from other source nodes with matching send messages and identifying to the receiving node the source node operating the mutual exclusion device; and sending to the receiving node from the source node operating the mutual exclusion device a matched pending message.

Methods and apparatus using commutative error detection values for fault isolation in multiple node computers

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

Almasi, Gheorghe; Blumrich, Matthias Augustin; Chen, Dong

Methods and apparatus perform fault isolation in multiple node computing systems using commutative error detection values for--example, checksums--to identify and to isolate faulty nodes. When information associated with a reproducible portion of a computer program is injected into a network by a node, a commutative error detection value is calculated. At intervals, node fault detection apparatus associated with the multiple node computer system retrieve commutative error detection values associated with the node and stores them in memory. When the computer program is executed again by the multiple node computer system, new commutative error detection values are created and stored inmore » memory. The node fault detection apparatus identifies faulty nodes by comparing commutative error detection values associated with reproducible portions of the application program generated by a particular node from different runs of the application program. Differences in values indicate a possible faulty node.« less

Providing full point-to-point communications among compute nodes of an operational group in a global combining network of a parallel computer

DOEpatents

Archer, Charles J; Faraj, Ahmad A; Inglett, Todd A; Ratterman, Joseph D

2013-04-16

Methods, apparatus, and products are disclosed for providing full point-to-point communications among compute nodes of an operational group in a global combining network of a parallel computer, each compute node connected to each adjacent compute node in the global combining network through a link, that include: receiving a network packet in a compute node, the network packet specifying a destination compute node; selecting, in dependence upon the destination compute node, at least one of the links for the compute node along which to forward the network packet toward the destination compute node; and forwarding the network packet along the selected link to the adjacent compute node connected to the compute node through the selected link.

What Is a False Negative Sentinel Node Biopsy: Definition, Reasons and Ways to Minimize It?

PubMed

Kataria, Kamal; Srivastava, Anurag; Qaiser, Darakhshan

2016-10-01

Sentinel node biopsy helps in assessing the involvement of axillary lymph node without the morbidity of full axillary lymph node dissection, namely arm and shoulder pain, paraesthesia and lymphoedema. The various methods described in the literature identify the sentinel lymph nodes in approximately 96 % of cases and associated with a false negativity rate of 5 to 10 %. A false negative sentinel node is defined as the proportion of cases in whom sentinel node biopsy is reported as negative, but the rest of axillary lymph node(s) harbours cancer cells. The possible causes of a false negative sentinel lymph node may be because of blocked lymphatics either by cancer cells or following fibrosis of previous surgery/radiotherapy, and an alternative pathway opens draining the blue dye or isotope to another uninvolved node . The other reasons may be two lymphatic pathways for a tumour area, the one opening to a superficial node and the other in deep nodes. Sometimes, lymphatics do not relay into a node but traverse it going to a higher node. In some patients, the microscopic focus of metastasis inside a lymph node is so small-micrometastasis (i.e. between 0.2 and 2 mm) or isolated tumour cells (i.e. less than 0.2 mm) that is missed by the pathologist. The purpose of this review is to clear some fears lurking in the mind of most surgeons about the false negative sentinel lymph node (FNSLN).

Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

PubMed

van Rijk, Maartje C; Nieweg, Omgo E; Rutgers, Emiel J T; Oldenburg, Hester S A; Olmos, Renato Valdés; Hoefnagel, Cornelis A; Kroon, Bin B R

2006-04-01

Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

Method and apparatus for obtaining stack traceback data for multiple computing nodes of a massively parallel computer system

DOEpatents

Gooding, Thomas Michael; McCarthy, Patrick Joseph

2010-03-02

A data collector for a massively parallel computer system obtains call-return stack traceback data for multiple nodes by retrieving partial call-return stack traceback data from each node, grouping the nodes in subsets according to the partial traceback data, and obtaining further call-return stack traceback data from a representative node or nodes of each subset. Preferably, the partial data is a respective instruction address from each node, nodes having identical instruction address being grouped together in the same subset. Preferably, a single node of each subset is chosen and full stack traceback data is retrieved from the call-return stack within the chosen node.

[Incidence and influencing factors of distal external iliac lymph node metastasis in early cervical cancer].

PubMed

Yin, Yueju; Sheng, Xiugui; Li, Xinglan; Li, Dapeng; Han, Xiaoyun; Zhang, Xiaoling; Zhang, Tingting

2014-06-01

The distal external iliac lymph nodes are located along the external iliac artery between the deep circumflex iliac vein and the inguinal canal. Our study aimed to investigate the incidence of metastasis in distal external iliac lymph nodes and its association with clinicopathological factors in patients with early stage cervical cancer, and to determine the role of distal external iliac lymph nodes dissection in the surgery. Five hundred and twenty-four patients with early stage cervical cancer underwent radical hysterectomy and bilateral pelvic lymphadenectomy in the Shandong Province Cancer Hospital between June 1995 and December 2011, and their clinicopathological features were analyzed retrospectively. Of the 524 patients, 124 (23.7%) had pelvic lymph node metastasis. The metastasis rates were 16.2% (85 of 524 patients) in the obturator lymph nodes, 12.2% (64 of 524 patients) in the internal and external iliac lymph nodes, 2.9% (15 of 524 patients) in the common iliac lymph nodes, 2.1% (11 of 524 patients) in the distal external iliac lymph nodes, and 1.7% (9 of 524 patients) in the para-aortic nodes. The incidence of isolated positive distal external iliac lymph nodes was 0.2%. Univariate analysis showed that lymphovascular space invasion, pelvic lymph node metastases (excluding distal external iliac lymph nodes) were significantly associated with distal external iliac lymph node metastasis (P < 0.05). Logistic regression analysis showed that pelvic lymph node metastasis (excluding distal external iliac lymph nodes) was the independent risk factor for metastasis to distal external iliac lymph nodes. In early stage cervical cancer, distal external iliac lymph node metastasis is rare, especially in cases with stage IA or without pelvic lymph node metastasis. Less extensive pelvic lymphadenectomy may be considered in these patients in order to reduce operative complications and improve patients' quality of life. The deep circumflex iliac vein may be an appropriate landmark for the caudal limit of external iliac lymphadenectomy. However, if pelvic lymph node metastasis (excluding distal external iliac lymph nodes) is found by intraoperative rapid pathological diagnosis, systematic pelvic lymphadenectomy including removal of the distal external iliac lymph nodes should be performed in order to reduce the risk of distant metastasis.

Information-based self-organization of sensor nodes of a sensor network

DOEpatents

Ko, Teresa H [Castro Valley, CA; Berry, Nina M [Tracy, CA

2011-09-20

A sensor node detects a plurality of information-based events. The sensor node determines whether at least one other sensor node is an information neighbor of the sensor node based on at least a portion of the plurality of information-based events. The information neighbor has an overlapping field of view with the sensor node. The sensor node sends at least one communication to the at least one other sensor node that is an information neighbor of the sensor node in response to at least one information-based event of the plurality of information-based events.

Method and system for monitoring environmental conditions

DOEpatents

Kulesz, James J [Oak Ridge, TN; Lee, Ronald W [Oak Ridge, TN

2010-11-16

A system for detecting the occurrence of anomalies includes a plurality of spaced apart nodes, with each node having adjacent nodes, each of the nodes having one or more sensors associated with the node and capable of detecting anomalies, and each of the nodes having a controller connected to the sensors associated with the node. The system also includes communication links between adjacent nodes, whereby the nodes form a network. At least one software agent is capable of changing the operation of at least one of the controllers in response to the detection of an anomaly by a sensor.

Sentinel lymph node biopsy under fluorescent indocyanin green guidance: Initial experience.

PubMed

Aydoğan, Fatih; Arıkan, Akif Enes; Aytaç, Erman; Velidedeoğlu, Mehmet; Yılmaz, Mehmet Halit; Sager, Muhammet Sait; Çelik, Varol; Uras, Cihan

2016-01-01

Sentinel lymph node biopsy can be applied by using either blue dye or radionuclide method or both in breast cancer. Fluorescent imaging with indocyanine green is a new defined method. This study evaluates the applicability of sentinel lymph node biopsy via fluorescent indocyanine green. IC-VIEW (Pulsion Medical Systems AG, Munich, Germany) infrared visualization system was used for imaging. Two mL of indocyanine green was injected to visualize sentinel lymph nodes. After injection, subcutaneous lymphatics were traced and sentinel lymph nodes were found with simultaneous imaging. Sentinel lymph nodes were excised under fluorescent light guidance, and excised lymph nodes were examined histopathologically. Patients with sentinel lymph node metastases underwent axillary dissection. Four patients with sentinel lymph node biopsy due to breast cancer were included in the study. Sentinel lymph nodes were visualized with indocyanine green in all patients. The median number of excised sentinel lymph node was 2 (2-3). Two patients with lymph node metastasis underwent axillary dissection. No metastasis was detected in lymph nodes other than the sentinel nodes in patients with axillary dissection. There was no complication during and after the operation related to the method. According to our limited experience, sentinel lymph node biopsy under fluorescent indocyanine green guidance, which has an advantage of simultaneous visualization, is technically feasible.

All row, planar fault detection system

DOEpatents

Archer, Charles Jens; Pinnow, Kurt Walter; Ratterman, Joseph D; Smith, Brian Edward

2013-07-23

An apparatus, program product and method for detecting nodal faults may simultaneously cause designated nodes of a cell to communicate with all nodes adjacent to each of the designated nodes. Furthermore, all nodes along the axes of the designated nodes are made to communicate with their adjacent nodes, and the communications are analyzed to determine if a node or connection is faulty.

Node Redeployment Algorithm Based on Stratified Connected Tree for Underwater Sensor Networks

PubMed Central

Liu, Jun; Jiang, Peng; Wu, Feng; Yu, Shanen; Song, Chunyue

2016-01-01

During the underwater sensor networks (UWSNs) operation, node drift with water environment causes network topology changes. Periodic node location examination and adjustment are needed to maintain good network monitoring quality as long as possible. In this paper, a node redeployment algorithm based on stratified connected tree for UWSNs is proposed. At every network adjustment moment, self-examination and adjustment on node locations are performed firstly. If a node is outside the monitored space, it returns to the last location recorded in its memory along straight line. Later, the network topology is stratified into a connected tree that takes the sink node as the root node by broadcasting ready information level by level, which can improve the network connectivity rate. Finally, with synthetically considering network coverage and connectivity rates, and node movement distance, the sink node performs centralized optimization on locations of leaf nodes in the stratified connected tree. Simulation results show that the proposed redeployment algorithm can not only keep the number of nodes in the monitored space as much as possible and maintain good network coverage and connectivity rates during network operation, but also reduce node movement distance during node redeployment and prolong the network lifetime. PMID:28029124

Identifying a largest logical plane from a plurality of logical planes formed of compute nodes of a subcommunicator in a parallel computer

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

Davis, Kristan D.; Faraj, Daniel A.

In a parallel computer, a largest logical plane from a plurality of logical planes formed of compute nodes of a subcommunicator may be identified by: identifying, by each compute node of the subcommunicator, all logical planes that include the compute node; calculating, by each compute node for each identified logical plane that includes the compute node, an area of the identified logical plane; initiating, by a root node of the subcommunicator, a gather operation; receiving, by the root node from each compute node of the subcommunicator, each node's calculated areas as contribution data to the gather operation; and identifying, bymore » the root node in dependence upon the received calculated areas, a logical plane of the subcommunicator having the greatest area.« less

The posterior cervical lymph node in toxoplasmosis.

PubMed

Gray, G F; Kimball, A C; Kean, B H

1972-11-01

Posterior cervical node enlargement is characteristic of clinical toxoplasmosis in adults. Lymph node biopsies from 37 patients, who were tested for toxoplasmosis by serologic and isolation studies, were examined. A characteristic pattern of sinus histiocytosis was seen in 17 of 18 posterior cervical nodes and in only 1 of 4 lymph nodes from other sites from patients with toxoplasmosis. The characteristic pattern was not seen in posterior cervical nodes or in lymph nodes from other sites from patients with other diseases. Lymphoma obscured the characteristic changes of toxoplasmosis in the posterior cervical nodes and other nodes of 5 patients with these coexisting diseases. Organisms were seen in tissue sections in only 2 instances. T gondii was isolated from mice in 14 of 17 attempts using nodes from patients with toxoplasmosis, but from none of 8 attempts using nodes from patients with other diseases.

Providing full point-to-point communications among compute nodes of an operational group in a global combining network of a parallel computer

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

Archer, Charles J.; Faraj, Daniel A.; Inglett, Todd A.

Methods, apparatus, and products are disclosed for providing full point-to-point communications among compute nodes of an operational group in a global combining network of a parallel computer, each compute node connected to each adjacent compute node in the global combining network through a link, that include: receiving a network packet in a compute node, the network packet specifying a destination compute node; selecting, in dependence upon the destination compute node, at least one of the links for the compute node along which to forward the network packet toward the destination compute node; and forwarding the network packet along the selectedmore » link to the adjacent compute node connected to the compute node through the selected link.« less

Controlling data transfers from an origin compute node to a target compute node

DOEpatents

Archer, Charles J [Rochester, MN; Blocksome, Michael A [Rochester, MN; Ratterman, Joseph D [Rochester, MN; Smith, Brian E [Rochester, MN

2011-06-21

Methods, apparatus, and products are disclosed for controlling data transfers from an origin compute node to a target compute node that include: receiving, by an application messaging module on the target compute node, an indication of a data transfer from an origin compute node to the target compute node; and administering, by the application messaging module on the target compute node, the data transfer using one or more messaging primitives of a system messaging module in dependence upon the indication.

Method and system for source authentication in group communications

NASA Technical Reports Server (NTRS)

Roy-Chowdhury, Ayan (Inventor); Baras, John S. (Inventor)

2013-01-01

A method and system for authentication is provided. A central node for issuing certificates to a plurality of nodes associated with the central node in a network is also provided. The central node receives a first key from at least one node from among the plurality of nodes and generates a second key based on the received first key and generates a certificate for the at least one node. The generated certificate is transmitted to the at least one node.

Simplified intraoperative sentinel-node detection performed by the urologist accurately determines lymph-node stage in prostate cancer.

PubMed

Kjölhede, Henrik; Bratt, Ola; Gudjonsson, Sigurdur; Sundqvist, Pernilla; Liedberg, Fredrik

2015-04-01

The reference standard for lymph-node staging in prostate cancer is currently an extended pelvic lymph-node dissection (ePLND), which detects most, but not all, regional lymph-node metastases. As an alternative to ePLND, sentinel-node dissection with preoperative isotope injection and imaging has been reported. The objective was to determine whether intraoperative sentinel-node detection with a simplified protocol can accurately determine lymph-node stage in prostate cancer patients. Patients with biopsy-verified high-risk prostate cancer with tumour stage T2-3 were included in the study. All patients underwent both ePLND and sentinel-node detection. (99m)Tc-marked nanocolloid was injected peritumourally by the operating urologist after induction of anaesthesia just before surgery. Sentinel nodes were detected both in vivo and ex vivo intraoperatively using a gamma probe. Sentinel nodes and metastases and their locations were recorded. Sensitivity and specificity were calculated. At least one sentinel node was detected in 72 (87%) of the 83 patients. In 13 (18%) of these 72 patients sentinel nodes were detected outside the ePLND template. In six of these 13 patients, the Sentinel nodes from outside the template contained metastases, which proved to be the only metastases in two. For 12 patients the only metastatic deposit found was a micrometastasis (≤2 mm) in a sentinel node. In the 72 patients with detectable sentinel nodes, pathological analysis of the sentinel node correctly categorized 71 and ePLND 70 patients. This protocol yielded results comparable to the commonly used technique of sentinel-node detection, but with more cases of non-detection.

Repeat sentinel lymph node biopsy in patients with ipsilateral recurrent breast cancer after breast-conserving therapy and negative sentinel lymph node biopsy: a prospective study.

PubMed

Folli, Secondo; Falco, Giuseppe; Mingozzi, Matteo; Buggi, Federico; Curcio, Annalisa; Ferrari, Guglielmo; Taffurelli, Mario; Regolo, Lea; Nanni, Oriana

2016-04-01

Patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous breast conservative surgery with negative sentinel lymph node biopsy need a new axillary staging procedure. However, the best surgical option, i.e. repeat sentinel lymph node biopsy or axillary lymph node dissection, is still debated. Purpose of the study is to assess the performance of repeat sentinel lymph node biopsy. In a multicenter study, lymph node biopsy completed by back-up axillary lymph node dissection was undertaken for ipsilateral breast tumor recurrence or new ipsilateral primary tumor. Tracer uptake was used to identify and isolate the sentinel lymph node during surgery, and it was classified after staining with hematoxylin and eosin and monoclonal anti-cytokeratin antibodies. Aside from negative predictive value, overall accuracy and false-negative rate of repeat sentinel lymph node biopsy were assessed. A multicenter, prospective study was conducted performing 30 repeat sentinel lymph node biopsy completed by back-up axillary lymph node dissection for ipsilateral breast tumor recurrence or new ipsilateral primary tumor in patients formerly treated with previous breast conservative surgery and negative sentinel lymph node biopsy. Negative predictive value, overall accuracy and false-negative rate of repeat sentinel lymph node biopsy were assessed. Sentinel lymph nodes were mapped in 27 patients out of 30 (90%). Aberrant drainage pathways were observed in one patient (3.7%). Tracer uptake was sufficient to identify and isolate the sentinel lymph node during surgery in 23 cases (76.6%); the patients in whom lymphoscintigraphy failed or no sentinel lymph nodes could be isolated underwent axillary lymph node dissection. The negative predictive value was 95.2%, the accuracy was 95.6% and the false-negative rate was 33%. Repeat sentinel lymph node biopsy is feasible and accurate, with a high negative predictive value. Patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous breast conservative surgery and negative sentinel lymph node biopsy can be treated with repeat sentinel lymph node biopsy for the axillary staging and can be spared axillary dissection in case of absence of metastases. However, repeat sentinel lymph node biopsy may prove technically impracticable in about one quarter of cases and thus axillary lymph node dissection remains the only viable option in such instance.

Reducing power consumption while synchronizing a plurality of compute nodes during execution of a parallel application

DOEpatents

Archer, Charles J [Rochester, MN; Blocksome, Michael A [Rochester, MN; Peters, Amanda A [Rochester, MN; Ratterman, Joseph D [Rochester, MN; Smith, Brian E [Rochester, MN

2012-01-10

Methods, apparatus, and products are disclosed for reducing power consumption while synchronizing a plurality of compute nodes during execution of a parallel application that include: beginning, by each compute node, performance of a blocking operation specified by the parallel application, each compute node beginning the blocking operation asynchronously with respect to the other compute nodes; reducing, for each compute node, power to one or more hardware components of that compute node in response to that compute node beginning the performance of the blocking operation; and restoring, for each compute node, the power to the hardware components having power reduced in response to all of the compute nodes beginning the performance of the blocking operation.

Reducing power consumption while synchronizing a plurality of compute nodes during execution of a parallel application

DOEpatents

Archer, Charles J [Rochester, MN; Blocksome, Michael A [Rochester, MN; Peters, Amanda E [Cambridge, MA; Ratterman, Joseph D [Rochester, MN; Smith, Brian E [Rochester, MN

2012-04-17

Methods, apparatus, and products are disclosed for reducing power consumption while synchronizing a plurality of compute nodes during execution of a parallel application that include: beginning, by each compute node, performance of a blocking operation specified by the parallel application, each compute node beginning the blocking operation asynchronously with respect to the other compute nodes; reducing, for each compute node, power to one or more hardware components of that compute node in response to that compute node beginning the performance of the blocking operation; and restoring, for each compute node, the power to the hardware components having power reduced in response to all of the compute nodes beginning the performance of the blocking operation.

Sentinel Lymph Nodes for Breast Carcinoma: A Paradigm Shift.

PubMed

Maguire, Aoife; Brogi, Edi

2016-08-01

-Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. -To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. -Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. -The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin-stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non-sentinel lymph node involvement. This information is important to decide on further axillary treatment.

Network structures sustained by internal links and distributed lifetime of old nodes in stationary state of number of nodes

NASA Astrophysics Data System (ADS)

Ikeda, Nobutoshi

2017-12-01

In network models that take into account growth properties, deletion of old nodes has a serious impact on degree distributions, because old nodes tend to become hub nodes. In this study, we aim to provide a simple explanation for why hubs can exist even in conditions where the number of nodes is stationary due to the deletion of old nodes. We show that an exponential increase in the degree of nodes is a natural consequence of the balance between the deletion and addition of nodes as long as a preferential attachment mechanism holds. As a result, the largest degree is determined by the magnitude relationship between the time scale of the exponential growth of degrees and lifetime of old nodes. The degree distribution exhibits a power-law form ˜ k -γ with exponent γ = 1 when the lifetime of nodes is constant. However, various values of γ can be realized by introducing distributed lifetime of nodes.

Lymph node staging of oral and maxillofacial neoplasms in 31 dogs and cats.

PubMed

Herring, Erin S; Smith, Mark M; Robertson, John L

2002-09-01

A retrospective study was performed to report the histologic examination results of regional lymph nodes of dogs and cats with oral or maxillofacial neoplasms. Twenty-eight dogs and 3 cats were evaluated. Histologic examination results of standard and serial tissue sectioning of regional lymph nodes were recorded. When available, other clinical parameters including mandibular lymph node palpation, thoracic radiographs, and pre- and postoperative fine needle aspiration of lymph nodes were compared with the histologic results. Squamous cell carcinoma, fibrosarcoma, and melanoma were the most common neoplasms diagnosed in dogs. Squamous cell carcinoma and fibrosarcoma were diagnosed in cats. Of the palpably enlarged mandibular lymph nodes, 17.0% had metastatic disease histologically. Radiographically evident thoracic metastatic disease was present in 7.4% of cases. Preoperative cytologic evaluation of the mandibular lymph node based on fine needle aspiration concurred with the histologic results in 90.5% of lymph nodes examined. Postoperative cytologic evaluation of fine needle aspirates of regional lymph nodes concurred with the histologic results in 80.6% of lymph nodes examined. Only 54.5% of cases with metastatic disease to regional lymph nodes had metastasis that included the mandibular lymph node. Serial lymph node sectioning provided additional information or metastasis detection. Cytologic evaluation of the mandibular lymph node correlates positively with histology, however results may fail to indicate the presence of regional metastasis. Assessment of all regional lymph nodes in dogs and cats with oral or maxillofacial neoplasms will detect more metastatic disease than assessing the mandibular lymph node only.

The Posterior Cervical Lymph Node in Toxoplasmosis

PubMed Central

Gray, George F.; Kimball, Anne C.; Kean, B. H.

1972-01-01

Posterior cervical node enlargement is characteristic of clinical toxoplasmosis in adults. Lymph node biopsies from 37 patients, who were tested for toxoplasmosis by serologic and isolation studies, were examined. A characteristic pattern of sinus histiocytosis was seen in 17 of 18 posterior cervical nodes and in only 1 of 4 lymph nodes from other sites from patients with toxoplasmosis. The characteristic pattern was not seen in posterior cervical nodes or in lymph nodes from other sites from patients with other diseases. Lymphoma obscured the characteristic changes of toxoplasmosis in the posterior cervical nodes and other nodes of 5 patients with these coexisting diseases. Organisms were seen in tissue sections in only 2 instances. T gondii was isolated from mice in 14 of 17 attempts using nodes from patients with toxoplasmosis, but from none of 8 attempts using nodes from patients with other diseases. ImagesFig 3Fig 4Fig 1Fig 2 PMID:4634739

Performing an allreduce operation on a plurality of compute nodes of a parallel computer

DOEpatents

Faraj, Ahmad

2013-07-09

Methods, apparatus, and products are disclosed for performing an allreduce operation on a plurality of compute nodes of a parallel computer, each node including at least two processing cores, that include: establishing, for each node, a plurality of logical rings, each ring including a different set of at least one core on that node, each ring including the cores on at least two of the nodes; iteratively for each node: assigning each core of that node to one of the rings established for that node to which the core has not previously been assigned, and performing, for each ring for that node, a global allreduce operation using contribution data for the cores assigned to that ring or any global allreduce results from previous global allreduce operations, yielding current global allreduce results for each core; and performing, for each node, a local allreduce operation using the global allreduce results.

Performing an allreduce operation on a plurality of compute nodes of a parallel computer

DOEpatents

Faraj, Ahmad

2013-02-12

Methods, apparatus, and products are disclosed for performing an allreduce operation on a plurality of compute nodes of a parallel computer, each node including at least two processing cores, that include: performing, for each node, a local reduction operation using allreduce contribution data for the cores of that node, yielding, for each node, a local reduction result for one or more representative cores for that node; establishing one or more logical rings among the nodes, each logical ring including only one of the representative cores from each node; performing, for each logical ring, a global allreduce operation using the local reduction result for the representative cores included in that logical ring, yielding a global allreduce result for each representative core included in that logical ring; and performing, for each node, a local broadcast operation using the global allreduce results for each representative core on that node.

Locating hardware faults in a data communications network of a parallel computer

DOEpatents

Archer, Charles J.; Megerian, Mark G.; Ratterman, Joseph D.; Smith, Brian E.

2010-01-12

Hardware faults location in a data communications network of a parallel computer. Such a parallel computer includes a plurality of compute nodes and a data communications network that couples the compute nodes for data communications and organizes the compute node as a tree. Locating hardware faults includes identifying a next compute node as a parent node and a root of a parent test tree, identifying for each child compute node of the parent node a child test tree having the child compute node as root, running a same test suite on the parent test tree and each child test tree, and identifying the parent compute node as having a defective link connected from the parent compute node to a child compute node if the test suite fails on the parent test tree and succeeds on all the child test trees.

Determining collective barrier operation skew in a parallel computer

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

Faraj, Daniel A.

2015-11-24

Determining collective barrier operation skew in a parallel computer that includes a number of compute nodes organized into an operational group includes: for each of the nodes until each node has been selected as a delayed node: selecting one of the nodes as a delayed node; entering, by each node other than the delayed node, a collective barrier operation; entering, after a delay by the delayed node, the collective barrier operation; receiving an exit signal from a root of the collective barrier operation; and measuring, for the delayed node, a barrier completion time. The barrier operation skew is calculated by:more » identifying, from the compute nodes' barrier completion times, a maximum barrier completion time and a minimum barrier completion time and calculating the barrier operation skew as the difference of the maximum and the minimum barrier completion time.« less

Performing a scatterv operation on a hierarchical tree network optimized for collective operations

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

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D

Performing a scatterv operation on a hierarchical tree network optimized for collective operations including receiving, by the scatterv module installed on the node, from a nearest neighbor parent above the node a chunk of data having at least a portion of data for the node; maintaining, by the scatterv module installed on the node, the portion of the data for the node; determining, by the scatterv module installed on the node, whether any portions of the data are for a particular nearest neighbor child below the node or one or more other nodes below the particular nearest neighbor child; andmore » sending, by the scatterv module installed on the node, those portions of data to the nearest neighbor child if any portions of the data are for a particular nearest neighbor child below the node or one or more other nodes below the particular nearest neighbor child.« less

Determining collective barrier operation skew in a parallel computer

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

Faraj, Daniel A.

Determining collective barrier operation skew in a parallel computer that includes a number of compute nodes organized into an operational group includes: for each of the nodes until each node has been selected as a delayed node: selecting one of the nodes as a delayed node; entering, by each node other than the delayed node, a collective barrier operation; entering, after a delay by the delayed node, the collective barrier operation; receiving an exit signal from a root of the collective barrier operation; and measuring, for the delayed node, a barrier completion time. The barrier operation skew is calculated by:more » identifying, from the compute nodes' barrier completion times, a maximum barrier completion time and a minimum barrier completion time and calculating the barrier operation skew as the difference of the maximum and the minimum barrier completion time.« less

Cross-ontological analytics for alignment of different classification schemes

DOEpatents

Posse, Christian; Sanfilippo, Antonio P; Gopalan, Banu; Riensche, Roderick M; Baddeley, Robert L

2010-09-28

Quantification of the similarity between nodes in multiple electronic classification schemes is provided by automatically identifying relationships and similarities between nodes within and across the electronic classification schemes. Quantifying the similarity between a first node in a first electronic classification scheme and a second node in a second electronic classification scheme involves finding a third node in the first electronic classification scheme, wherein a first product value of an inter-scheme similarity value between the second and third nodes and an intra-scheme similarity value between the first and third nodes is a maximum. A fourth node in the second electronic classification scheme can be found, wherein a second product value of an inter-scheme similarity value between the first and fourth nodes and an intra-scheme similarity value between the second and fourth nodes is a maximum. The maximum between the first and second product values represents a measure of similarity between the first and second nodes.

Multi-directional fault detection system

DOEpatents

Archer, Charles Jens; Pinnow, Kurt Walter; Ratterman, Joseph D.; Smith, Brian Edward

2010-11-23

An apparatus, program product and method checks for nodal faults in a group of nodes comprising a center node and all adjacent nodes. The center node concurrently communicates with the immediately adjacent nodes in three dimensions. The communications are analyzed to determine a presence of a faulty node or connection.

Multi-directional fault detection system

DOEpatents

Archer, Charles Jens [Rochester, MN; Pinnow, Kurt Walter [Rochester, MN; Ratterman, Joseph D [Rochester, MN; Smith, Brian Edward [Rochester, MN

2009-03-17

An apparatus, program product and method checks for nodal faults in a group of nodes comprising a center node and all adjacent nodes. The center node concurrently communicates with the immediately adjacent nodes in three dimensions. The communications are analyzed to determine a presence of a faulty node or connection.

Multi-directional fault detection system

DOEpatents

Archer, Charles Jens; Pinnow, Kurt Walter; Ratterman, Joseph D.; Smith, Brian Edward

2010-06-29

An apparatus, program product and method checks for nodal faults in a group of nodes comprising a center node and all adjacent nodes. The center node concurrently communicates with the immediately adjacent nodes in three dimensions. The communications are analyzed to determine a presence of a faulty node or connection.

Flexible embedding of networks

NASA Astrophysics Data System (ADS)

Fernandez-Gracia, Juan; Buckee, Caroline; Onnela, Jukka-Pekka

We introduce a model for embedding one network into another, focusing on the case where network A is much bigger than network B. Nodes from network A are assigned to the nodes in network B using an algorithm where we control the extent of localization of node placement in network B using a single parameter. Starting from an unassigned node in network A, called the source node, we first map this node to a randomly chosen node in network B, called the target node. We then assign the neighbors of the source node to the neighborhood of the target node using a random walk based approach. To assign each neighbor of the source node to one of the nodes in network B, we perform a random walk starting from the target node with stopping probability α. We repeat this process until all nodes in network A have been mapped to the nodes of network B. The simplicity of the model allows us to calculate key quantities of interest in closed form. By varying the parameter α, we are able to produce embeddings from very local (α = 1) to very global (α --> 0). We show how our calculations fit the simulated results, and we apply the model to study how social networks are embedded in geography and how the neurons of C. Elegans are embedded in the surrounding volume.

Sentinel lymph node biopsy under fluorescent indocyanin green guidance: Initial experience

PubMed Central

Aydoğan, Fatih; Arıkan, Akif Enes; Aytaç, Erman; Velidedeoğlu, Mehmet; Yılmaz, Mehmet Halit; Sager, Muhammet Sait; Çelik, Varol; Uras, Cihan

2016-01-01

Objective: Sentinel lymph node biopsy can be applied by using either blue dye or radionuclide method or both in breast cancer. Fluorescent imaging with indocyanine green is a new defined method. This study evaluates the applicability of sentinel lymph node biopsy via fluorescent indocyanine green. Material and Methods: IC-VIEW (Pulsion Medical Systems AG, Munich, Germany) infrared visualization system was used for imaging. Two mL of indocyanine green was injected to visualize sentinel lymph nodes. After injection, subcutaneous lymphatics were traced and sentinel lymph nodes were found with simultaneous imaging. Sentinel lymph nodes were excised under fluorescent light guidance, and excised lymph nodes were examined histopathologically. Patients with sentinel lymph node metastases underwent axillary dissection. Results: Four patients with sentinel lymph node biopsy due to breast cancer were included in the study. Sentinel lymph nodes were visualized with indocyanine green in all patients. The median number of excised sentinel lymph node was 2 (2–3). Two patients with lymph node metastasis underwent axillary dissection. No metastasis was detected in lymph nodes other than the sentinel nodes in patients with axillary dissection. There was no complication during and after the operation related to the method. Conclusion: According to our limited experience, sentinel lymph node biopsy under fluorescent indocyanine green guidance, which has an advantage of simultaneous visualization, is technically feasible. PMID:26985159

Anatomic-histologic study of the floor of the mouth: the lingual lymph nodes.

PubMed

Ananian, Sargis G; Gvetadze, Shalva R; Ilkaev, Konstantin D; Mochalnikova, Valeria V; Zayratiants, Georgiy O; Mkhitarov, Vladimir A; Yang, Xin; Ciciashvili, Aleksandr M

2015-06-01

The lingual lymph nodes are inconstant nodes located within the fascial/intermuscular spaces of the floor of the mouth. Oral tongue squamous cell carcinoma has been reported to recur and metastasize in lingual lymph nodes with poor prognosis. Lingual lymph nodes are not currently included in basic tongue squamous cell carcinoma surgery. Twenty-one cadavers (7 males, 14 females) were studied, aged from 57 to 94 years (mean age 76.3 years). The gross specimen of the floor of the mouth was divided into blocks: A (median nodes), B, B' (parahyoid), C, C' (paraglandular). Serial histological microslides were cut and stained with hematoxylin-eosin. Frequency of lingual lymph nodes in each block and their microscopic features were assessed. The lingual lymph nodes in overall number of 7 were detected in 5 of the 21 cadavers (23.8%). The total incidence of lingual lymph node was 33.3% (7 nodes/21 cadavers). Block A failed to demonstrate any lymph nodes (0%); Blocks B, B'-2 nodes (9.5%) and 2 nodes (9.5%), respectively; Blocks C, C'-1 node (4.8%) and 2 nodes (9.5%), respectively. The mean lingual lymph node length was 4.1 mm (from 1.4 to 8.7 mm), the mean thickness was 2.8 mm (from 0.8 to 7.5 mm). Five cadavers (23.8%) revealed mucosa-associated lymphoid tissue. Atrophic changes appeared in 4 (57.1%) lingual lymph nodes. The presence of lymph node-bearing tissue in the floor of the mouth is demonstrated. In account of resection radicalism and better local control the fat tissue of the floor of the mouth should be removed in conjunction to glossectomy. Further anatomic and clinical research is required to establish the role of lingual lymph node in oral squamous cell carcinoma recurrence and metastasis. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Classification between Failed Nodes and Left Nodes in Mobile Asset Tracking Systems †

PubMed Central

Kim, Kwangsoo; Jin, Jae-Yeon; Jin, Seong-il

2016-01-01

Medical asset tracking systems track a medical device with a mobile node and determine its status as either in or out, because it can leave a monitoring area. Due to a failed node, this system may decide that a mobile asset is outside the area, even though it is within the area. In this paper, an efficient classification method is proposed to separate mobile nodes disconnected from a wireless sensor network between nodes with faults and a node that actually has left the monitoring region. The proposed scheme uses two trends extracted from the neighboring nodes of a disconnected mobile node. First is the trend in a series of the neighbor counts; the second is that of the ratios of the boundary nodes included in the neighbors. Based on such trends, the proposed method separates failed nodes from mobile nodes that are disconnected from a wireless sensor network without failures. The proposed method is evaluated using both real data generated from a medical asset tracking system and also using simulations with the network simulator (ns-2). The experimental results show that the proposed method correctly differentiates between failed nodes and nodes that are no longer in the monitoring region, including the cases that the conventional methods fail to detect. PMID:26901200

[Ambulatory surgical treatment for breast carcinoma].

PubMed

Barillari, P; Leuzzi, R; Bassiri-Gharb, A; D'Angelo, F; Aurello, P; Naticchioni, E

2001-02-01

The aim of the study is to demonstrate the feasibility and the oncologic effectiveness of quadrantectomy plus sentinel node biopsy performed under local anesthesia, and to demonstrate the economic and psychologic advantages. From October 1996 to March 2000, 71 patients affected with clinical T1 N0 breast cancer, underwent quadrantectomy or tumor resection plus sentinel node biopsy and clinically suspicion axillary nodes biopsy, under local anesthesia at the Casa di Cura "Villa Mafalda" in Rome. Twenty tumors were T1a, 26 T1b e 25 T1c. A mean of 2 sentinel nodes (range 1-4) and a mean of 8 axillary nodes were removed during the procedure. In 2 cases sentinel nodes were not identified. Intraoperative histologic examination showed metastatic sentinel nodes in 11 cases. An axillary node dissection was performed in all cases (>12 nodes) and no other metastatic nodes were found. In all patients clinically suspected nodes were removed. In two cases no evidence of metastasis was found in sentinel nodes, while histologic examination revealed in a patient micrometastasis in one node, and in another patient two metastatic nodes. Fifty-three patients rated the overall surgical, anesthetic and recovery experience as "very satisfactory", 13 "satisfactory" and 5 "unsatisfactory". Patients typically expressed their pleasure at the possibility to return home and stressed the ease of recovery.

Sentinel Lymph Nodes for Breast Carcinoma A Paradigm Shift

PubMed Central

Maguire, Aoife; Brogi, Edi

2016-01-01

Context Sentinel lymph node biopsy has been established as the new standard of care for axillary staging in most patients with invasive breast carcinoma. Historically, all patients with a positive sentinel lymph node biopsy result underwent axillary lymph node dissection. Recent trials show that axillary lymph node dissection can be safely omitted in women with clinically node negative, T1 or T2 invasive breast cancer treated with breast-conserving surgery and whole-breast radiotherapy. This change in practice also has implications on the pathologic examination and reporting of sentinel lymph nodes. Objective To review recent clinical and pathologic studies of sentinel lymph nodes and explore how these findings influence the pathologic evaluation of sentinel lymph nodes. Data Sources Sources were published articles from peer-reviewed journals in PubMed (US National Library of Medicine) and published guidelines from the American Joint Committee on Cancer, the Union for International Cancer Control, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. Conclusions The main goal of sentinel lymph node examination should be to detect all macrometastases (>2 mm). Grossly sectioning sentinel lymph nodes at 2-mm intervals and evaluation of one hematoxylin-eosin–stained section from each block is the preferred method of pathologic evaluation. Axillary lymph node dissection can be safely omitted in clinically node-negative patients with negative sentinel lymph nodes, as well as in a selected group of patients with limited sentinel lymph node involvement. The pathologic features of the primary carcinoma and its sentinel lymph node metastases contribute to estimate the extent of non–sentinel lymph node involvement. This information is important to decide on further axillary treatment. PMID:27472237

Radionavigated detection of sentinel nodes in breast carcinoma--first experiences of our department.

PubMed

Duchaj, B; Chvalny, P; Vesely, J; Makaiova, I; Durdik, S; Straka, V; Palaj, J; Procka, V; Aksamitova, K; Skraskova, S; Banki, P; Kovacova, S; Galbavy, S

2010-01-01

Biopsy and histological evaluation of sentinel lymphatic node limits the axillary node dissection only in cases of positive histological finding and decreases the occurrence of postoperative complications related to the axillary node dissection. We used radiotracer SentiScint, Medi-Radiopharma Ltd, Hungary and preoperatively administered blue dye--Blue Patenté V, Guebert, Aulnay-Sous-Bios, France. 11 (18%) patients were subdued to deep peritimorous application of radiotracer, 10 (16.4%) to sub/intradermal application over the lesions and n 40 (65.6%) patients the application was sub/intradermal and periareolar. The patients underwent an operation protocol of corresponding quadrantectomy, radionavigated blue-dye sentinel node biopsy and axillary dissection. From May 2006 to June 2008, we examined 61 patients with breast carcinoma. They underwent radionavigated and blue-dye sentinel node biopsy. We detected 57 (93.4%) sentinel nodes with preoperative scintigraphy, of which only 51 (83.6%) were detected peroperatively and underwent histological evaluation. In six (9.8%) cases, the "frozen cut" histology of the primary lesion had shown a benign lesion; hence no sentinel node biopsy or axillary disection was performed. 12 (19.7%) of 51 histologically evaluated sentinel nodes had metastatic invasion. We retrospectively compared the histological fund in sentinel and axillary nodes in patients with metastatic sentinel nodes. In 6 (16.6%) cases, the sentinel node was positive of metastatic invasion but axillary nodes were histologically negative, in 6 (16.6%) cases the sentinel node and axillary nodes were positive for metastatic invasion. We observed falsely negative findings in 3 (8.3%) patients with negative histological fund in the sentinel node, but positive axillary nodes (Tab. 3, Fig. 2, Ref. 11). Full Text (Free, PDF) www.bmj.sk.

The congestion control algorithm based on queue management of each node in mobile ad hoc networks

NASA Astrophysics Data System (ADS)

Wei, Yifei; Chang, Lin; Wang, Yali; Wang, Gaoping

2016-12-01

This paper proposes an active queue management mechanism, considering the node's own ability and its importance in the network to set the queue threshold. As the network load increases, local congestion of mobile ad hoc network may lead to network performance degradation, hot node's energy consumption increase even failure. If small energy nodes congested because of forwarding data packets, then when it is used as the source node will cause a lot of packet loss. This paper proposes an active queue management mechanism, considering the node's own ability and its importance in the network to set the queue threshold. Controlling nodes buffer queue in different levels of congestion area probability by adjusting the upper limits and lower limits, thus nodes can adjust responsibility of forwarding data packets according to their own situation. The proposed algorithm will slow down the send rate hop by hop along the data package transmission direction from congestion node to source node so that to prevent further congestion from the source node. The simulation results show that, the algorithm can better play the data forwarding ability of strong nodes, protect the weak nodes, can effectively alleviate the network congestion situation.

Pattern of node metastases in patients treated with radical cystectomy and extended or superextended pelvic lymph node dissection due to bladder cancer.

PubMed

Moschini, Marco; Arbelaez, Emilio; Cornelius, Julian; Mattei, Agostino; Shariat, Shahrokh F; Dell Oglio, Paolo; Zaffuto, Emanuele; Salonia, Andrea; Montorsi, Francesco; Briganti, Alberto; Colombo, Renzo; Gallina, Andrea

2018-06-01

Pelvic lymph node dissection (PLND) has a diagnostic and therapeutic role during radical cystectomy in bladder cancer patients. However, at the time, no prospective data supports the value of extended PLND in improving survival expectances. We sought to describe incidence and location of node metastases in patients treated with extended and superextended PLND. We evaluated 653 contemporary patients with clinically nonmetastatic high risk nonmuscle invasive or muscle-invasive bladder cancer treated with radical cystectomy and extended or superextended PLND without neoadjuvant chemotherapy at a single tertiary referral center between 1990 and 2013. Limited PLND is defined as the removal of obturator and internal iliac nodes. Standard included also the external iliac nodes. Extended includes also common and presacral nodes. Finally, superextended PLND includes all the nodes removed along the inferior mesenteric artery. We evaluated incidence of pathologically node metastases. Logistic regression analyses evaluate preoperative and pathologic characteristics to the risk of harboring node metastases in the extended and superextended template. Overall, 191 (29.3%) patients were found with pathologically node confirmed metastases. Of these, 56 (29.3%) patients were found with a single node metastasis, while 135 (70.7%) had multiple node metastases. The vast majority of patients were found with node metastases standard template (n = 172, 26.3%), on the other hand 30 (4.6%) and 21 (3.2%) patients had node metastases in extended and superextended templates, respectively. However, of these only 2 patients were found without concomitant lymph node metastases in the limited or standard templates. On multivariable analyses, cN+ status (odds ratio = 4.40, P<0.001) and cT3-4 vs. cT1-2 (odds ratio = 2.25, P<0.001) were associated with an increased risk of harboring node metastases in the extended or superextended template. We found that the majority of patients harbored node disease in the limited or standard node dissection pattern. On the other hand, only a minority of patient were found with a disease in extended or superextended template without harboring a concomitant node disease in the limited pattern. Copyright © 2018 Elsevier Inc. All rights reserved.

Modular sensor network node

DOEpatents

Davis, Jesse Harper Zehring [Berkeley, CA; Stark, Jr., Douglas Paul; Kershaw, Christopher Patrick [Hayward, CA; Kyker, Ronald Dean [Livermore, CA

2008-06-10

A distributed wireless sensor network node is disclosed. The wireless sensor network node includes a plurality of sensor modules coupled to a system bus and configured to sense a parameter. The parameter may be an object, an event or any other parameter. The node collects data representative of the parameter. The node also includes a communication module coupled to the system bus and configured to allow the node to communicate with other nodes. The node also includes a processing module coupled to the system bus and adapted to receive the data from the sensor module and operable to analyze the data. The node also includes a power module connected to the system bus and operable to generate a regulated voltage.

Hybrid data storage system in an HPC exascale environment

DOEpatents

Bent, John M.; Faibish, Sorin; Gupta, Uday K.; Tzelnic, Percy; Ting, Dennis P. J.

2015-08-18

A computer-executable method, system, and computer program product for managing I/O requests from a compute node in communication with a data storage system, including a first burst buffer node and a second burst buffer node, the computer-executable method, system, and computer program product comprising striping data on the first burst buffer node and the second burst buffer node, wherein a first portion of the data is communicated to the first burst buffer node and a second portion of the data is communicated to the second burst buffer node, processing the first portion of the data at the first burst buffer node, and processing the second portion of the data at the second burst buffer node.

Clinicopathologic risk factors for right paraesophageal lymph node metastasis in patients with papillary thyroid carcinoma.

PubMed

Yu, Q A; Ma, D K; Liu, K P; Wang, P; Xie, C M; Wu, Y H; Dai, W J; Jiang, H C

2018-03-17

To investigate risk factors associated with right paraesophageal lymph node (RPELN) metastasis in patients with papillary thyroid carcinoma (PTC) and to determine the indications for right lymph node dissection. Clinicopathologic data from 829 patients (104 men and 725 women) with PTC, operated on by the same thyroid surgery team at the First Affiliated Hospital of Harbin Medical University from January 2013 to May 2017, were analyzed. Overall, 309 patients underwent total thyroidectomy with bilateral lymph node dissection, 488 underwent right thyroid lobe and isthmic resection with right central compartment lymph node dissection, and 32 underwent near-total thyroidectomy (ipsilateral thyroid lobectomy with contralateral near-total lobectomy) with bilateral lymph node dissection. The overall rate of central compartment lymph node metastasis was 43.5% (361/829), with right central compartment lymph node and RPELN metastasis rates of 35.5% (294/829) and 19.1% (158/829), respectively. Tumor size, number, invasion, and location, lymph node metastasis, right central compartment lymph node metastasis, and right lateral compartment lymph node metastasis were associated with RPELN in the univariate analysis, whereas age and sex were not. Multivariate analysis identified tumors with a diameter ≥ 1 cm, multiple tumors, tumors located in the right lobe, right central compartment lymph node metastasis, and right lateral compartment lymph node metastasis as independent risk factors for RPELN metastasis. Lymph node dissection, including RPELN dissection, should be performed for patients with PTC with a tumor diameter ≥ 1 cm, multiple tumors, right-lobe tumors, right central compartment lymph node metastasis, or suspected lateral compartment lymph node metastasis.

Using Link Disconnection Entropy Disorder to Detect Fast Moving Nodes in MANETs.

PubMed

Alvarez, Carlos F; Palafox, Luis E; Aguilar, Leocundo; Sanchez, Mauricio A; Martinez, Luis G

2016-01-01

Mobile ad-hoc networks (MANETs) are dynamic by nature; this dynamism comes from node mobility, traffic congestion, and other transmission conditions. Metrics to evaluate the effects of those conditions shine a light on node's behavior in an ad-hoc network, helping to identify the node or nodes with better conditions of connection. In this paper, we propose a relative index to evaluate a single node reliability, based on the link disconnection entropy disorder using neighboring nodes as reference. Link disconnection entropy disorder is best used to identify fast moving nodes or nodes with unstable communications, this without the need of specialized sensors such as GPS. Several scenarios were studied to verify the index, measuring the effects of Speed and traffic density on the link disconnection entropy disorder. Packet delivery ratio is associated to the metric detecting a strong relationship, enabling the use of the link disconnection entropy disorder to evaluate the stability of a node to communicate with other nodes. To expand the utilization of the link entropy disorder, we identified nodes with higher speeds in network simulations just by using the link entropy disorder.

An Optimized Hidden Node Detection Paradigm for Improving the Coverage and Network Efficiency in Wireless Multimedia Sensor Networks.

PubMed

Alanazi, Adwan; Elleithy, Khaled

2016-09-07

Successful transmission of online multimedia streams in wireless multimedia sensor networks (WMSNs) is a big challenge due to their limited bandwidth and power resources. The existing WSN protocols are not completely appropriate for multimedia communication. The effectiveness of WMSNs varies, and it depends on the correct location of its sensor nodes in the field. Thus, maximizing the multimedia coverage is the most important issue in the delivery of multimedia contents. The nodes in WMSNs are either static or mobile. Thus, the node connections change continuously due to the mobility in wireless multimedia communication that causes an additional energy consumption, and synchronization loss between neighboring nodes. In this paper, we introduce an Optimized Hidden Node Detection (OHND) paradigm. The OHND consists of three phases: hidden node detection, message exchange, and location detection. These three phases aim to maximize the multimedia node coverage, and improve energy efficiency, hidden node detection capacity, and packet delivery ratio. OHND helps multimedia sensor nodes to compute the directional coverage. Furthermore, an OHND is used to maintain a continuous node- continuous neighbor discovery process in order to handle the mobility of the nodes. We implement our proposed algorithms by using a network simulator (NS2). The simulation results demonstrate that nodes are capable of maintaining direct coverage and detecting hidden nodes in order to maximize coverage and multimedia node mobility. To evaluate the performance of our proposed algorithms, we compared our results with other known approaches.

Numeric pathologic lymph node classification shows prognostic superiority to topographic pN classification in esophageal squamous cell carcinoma.

PubMed

Sugawara, Kotaro; Yamashita, Hiroharu; Uemura, Yukari; Mitsui, Takashi; Yagi, Koichi; Nishida, Masato; Aikou, Susumu; Mori, Kazuhiko; Nomura, Sachiyo; Seto, Yasuyuki

2017-10-01

The current eighth tumor node metastasis lymph node category pathologic lymph node staging system for esophageal squamous cell carcinoma is based solely on the number of metastatic nodes and does not consider anatomic distribution. We aimed to assess the prognostic capability of the eighth tumor node metastasis pathologic lymph node staging system (numeric-based) compared with the 11th Japan Esophageal Society (topography-based) pathologic lymph node staging system in patients with esophageal squamous cell carcinoma. We retrospectively reviewed the clinical records of 289 patients with esophageal squamous cell carcinoma who underwent esophagectomy with extended lymph node dissection during the period from January 2006 through June 2016. We compared discrimination abilities for overall survival, recurrence-free survival, and cancer-specific survival between these 2 staging systems using C-statistics. The median number of dissected and metastatic nodes was 61 (25% to 75% quartile range, 45 to 79) and 1 (25% to 75% quartile range, 0 to 3), respectively. The eighth tumor node metastasis pathologic lymph node staging system had a greater ability to accurately determine overall survival (C-statistics: tumor node metastasis classification, 0.69, 95% confidence interval, 0.62-0.76; Japan Esophageal Society classification; 0.65, 95% confidence interval, 0.58-0.71; P = .014) and cancer-specific survival (C-statistics: tumor node metastasis classification, 0.78, 95% confidence interval, 0.70-0.87; Japan Esophageal Society classification; 0.72, 95% confidence interval, 0.64-0.80; P = .018). Rates of total recurrence rose as the eighth tumor node metastasis pathologic lymph node stage increased, while stratification of patients according to the topography-based node classification system was not feasible. Numeric nodal staging is an essential tool for stratifying the oncologic outcomes of patients with esophageal squamous cell carcinoma even in the cohort in which adequate numbers of lymph nodes were harvested. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic value of total number of lymph nodes retrieved differs between left-sided colon cancer and right-sided colon cancer in stage III patients with colon cancer.

PubMed

Yang, Lin; Xiong, Zhenchong; Xie, Qiankun; He, Wenzhuo; Liu, Shousheng; Kong, Pengfei; Jiang, Chang; Guo, Guifang; Xia, Liangping

2018-05-11

The consensus is that a minimum of 12 lymph nodes should be analyzed at colectomy for colon cancer. However, right colon cancer and left colon cancer have different characteristics, and this threshold value for total number of lymph nodes retrieved may not be universally applicable. The data of 63,243 patients with colon cancer treated between 2004 and 2012 were retrieved from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Multivariate Cox regression analysis was used to determine the predictive value of total number of lymph nodes for survival after adjusting for lymph nodes ratio. The predictive value in left-sided colon cancer and right-sided colon cancer was compared. The optimal total number of lymph nodes cutoff value for prediction of overall survival was identified using the online tool Cutoff Finder. Survival of patients with high total number of lymph nodes (≥12) and low total number of lymph nodes (< 12) was compared by Kaplan-Meier analysis. After stratifying by lymph nodes ratio status, total number of lymph nodes≥12 remained an independent predictor of survival in the whole cohort and in right-sided colon cancer, but not in left-sided colon cancer. The optimal cutoff value for total number of lymph nodes was determined to be 11. Low total number of lymph nodes (< 11) was associated with significantly poorer survival after adjusting for lymph nodes ratio in all subgroups except in the subgroup with high lymph nodes ratio (0.5-1.0). Previous reports of the prognostic significance of total number of lymph nodes on node-positive colon cancer were confounded by lymph nodes ratio. The 12-node standard for total number of lymph nodes may not be equally applicable in right-sided colon cancer and left-sided colon cancer.

Localization of antigen-specific lymphocytes following lymph node challenge.

PubMed Central

Liu, H; Splitter, G A

1986-01-01

The effect of subcutaneous injections of Brucella abortus strain 19 antigen on the specific localization of autologous lymphocytes in the regional nodes of calves was analysed by fluorescent labelling and flow cytometry. Both in vitro and in vivo FITC labelling of lymphocytes indicated the preferential migration of lymphocytes from a previously challenged lymph node to a recently challenged lymph node. However, lymphocytes from a lymph node challenged with B. abortus failed to localize preferentially in a lymph node challenged with a control antigen, Listeria monocytogenes. Lymph node cells, enriched for T lymphocytes and isolated from primary stimulated or secondary challenged B. abortus lymph nodes, could proliferate when cultured with autologous antigen-pulsed macrophages. The kinetics of [3H]thymidine incorporation in lymphocytes from secondarily challenged lymph nodes occurred earlier and to a greater extent when compared with lymphocytes from primary challenged lymph nodes. Our data show that the accumulation of B. abortus-specific lymphocytes in secondarily challenged lymph nodes is increased by the presence of the specific antigen. Images Figure 4 PMID:2426183

Providing nearest neighbor point-to-point communications among compute nodes of an operational group in a global combining network of a parallel computer

DOEpatents

Archer, Charles J.; Faraj, Ahmad A.; Inglett, Todd A.; Ratterman, Joseph D.

2012-10-23

Methods, apparatus, and products are disclosed for providing nearest neighbor point-to-point communications among compute nodes of an operational group in a global combining network of a parallel computer, each compute node connected to each adjacent compute node in the global combining network through a link, that include: identifying each link in the global combining network for each compute node of the operational group; designating one of a plurality of point-to-point class routing identifiers for each link such that no compute node in the operational group is connected to two adjacent compute nodes in the operational group with links designated for the same class routing identifiers; and configuring each compute node of the operational group for point-to-point communications with each adjacent compute node in the global combining network through the link between that compute node and that adjacent compute node using that link's designated class routing identifier.

Factors affecting sentinel lymph node metastasis in Turkish breast cancer patients: Predictive value of Ki-67 and the size of lymph node.

PubMed

Ozemir, I A; Orhun, K; Eren, T; Baysal, H; Sagiroglu, J; Leblebici, M; Ceyran, A B; Alimoglu, O

We aimed to analyze the factors that affect the axillary lymph node involvement in Turkish breast cancer patients with clinically non-palpable axillary lymph node. Sentinel lymph node biopsy is the gold standard technique to evaluate the axillary lymph node status that directly influences the prognosis and the treatment options in breast cancer. Breast cancer patients without axillary lymph node involvement in clinic examination were enrolled the study. Patients were categorized into the two groups according to existence of axillary lymph node metastasis or not. Demographic, histopathological and clinical data of patients were revealed retrospectively. One-hundred and eighty-seven patients were analyzed and 101 of patients fulfilled the criteria and were included the study. Metastatic lymph node was detected in 38 (37.6 %) patients (Group 1), and was negative in 63 (62.4 %) patients (Group 2). Sentinel lymph node metastasis were statistically significant higher in patients with Ki-67 ≥ 14 % than patients with Ki-67 < 14 % (51.9 % vs 22.4 %; p < 0.01). Likewise, the mean size of the sentinel lymph node was statistically significant higher in Group 1 compared to Group 2 (p < 0.01). Ki-67 proliferation index and sentinel lymph node size may provide a higher prediction about the sentinel lymph node involvement in patients with clinically negative axillary lymph nodes (Tab. 3, Fig. 1, Ref. 31).

Early diagnosis of lymph node metastasis: Importance of intranodal pressures.

PubMed

Miura, Yoshinobu; Mikada, Mamoru; Ouchi, Tomoki; Horie, Sachiko; Takeda, Kazu; Yamaki, Teppei; Sakamoto, Maya; Mori, Shiro; Kodama, Tetsuya

2016-03-01

Regional lymph node status is an important prognostic indicator of tumor aggressiveness. However, early diagnosis of metastasis using intranodal pressure, at a stage when lymph node size has not changed significantly, has not been investigated. Here, we use an MXH10/Mo-lpr/lpr mouse model of lymph node metastasis to show that intranodal pressure increases in both the subiliac lymph node and proper axillary lymph node, which are connected by lymphatic vessels, when tumor cells are injected into the subiliac lymph node to induce metastasis to the proper axillary lymph node. We found that intranodal pressure in the subiliac lymph node increased at the stage when metastasis was detected by in vivo bioluminescence, but when proper axillary lymph node volume (measured by high-frequency ultrasound imaging) had not increased significantly. Intravenously injected liposomes, encapsulating indocyanine green, were detected in solid tumors by in vivo bioluminescence, but not in the proper axillary lymph node. Basic blood vessel and lymphatic channel structures were maintained in the proper axillary lymph node, although sinus histiocytosis was detected. These results show that intranodal pressure in the proper axillary lymph node increases at early stages when metastatic tumor cells have not fully proliferated. Intranodal pressure may be a useful parameter for facilitating early diagnosis of lymph node metastasis. © 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Configuring compute nodes of a parallel computer in an operational group into a plurality of independent non-overlapping collective networks

DOEpatents

Archer, Charles J.; Inglett, Todd A.; Ratterman, Joseph D.; Smith, Brian E.

2010-03-02

Methods, apparatus, and products are disclosed for configuring compute nodes of a parallel computer in an operational group into a plurality of independent non-overlapping collective networks, the compute nodes in the operational group connected together for data communications through a global combining network, that include: partitioning the compute nodes in the operational group into a plurality of non-overlapping subgroups; designating one compute node from each of the non-overlapping subgroups as a master node; and assigning, to the compute nodes in each of the non-overlapping subgroups, class routing instructions that organize the compute nodes in that non-overlapping subgroup as a collective network such that the master node is a physical root.

Indocyanine Green Guided Pelvic Lymph Node Dissection: An Efficient Technique to Classify the Lymph Node Status of Patients with Prostate Cancer Who Underwent Radical Prostatectomy.

PubMed

Ramírez-Backhaus, Miguel; Mira Moreno, Alejandra; Gómez Ferrer, Alvaro; Calatrava Fons, Ana; Casanova, Juan; Solsona Narbón, Eduardo; Ortiz Rodríguez, Isabel María; Rubio Briones, José

2016-11-01

We evaluated the effectiveness of indocyanine green guided pelvic lymph node dissection for the optimal staging of prostate cancer and analyzed whether the technique could replace extended pelvic lymph node dissection. A solution of 25 mg indocyanine green in 5 ml sterile water was transperineally injected. Pelvic lymph node dissection was started with the indocyanine green stained nodes followed by extended pelvic lymph node dissection. Primary outcome measures were sensitivity, specificity, predictive value and likelihood ratio of a negative test of indocyanine green guided pelvic lymph node dissection. A total of 84 patients with a median age of 63.55 years and a median prostate specific antigen of 8.48 ng/ml were included in the study. Of these patients 60.7% had intermediate risk disease and 25% had high or very high risk disease. A median of 7 indocyanine green stained nodes per patient was detected (range 2 to 18) with a median of 22 nodes excised during extended pelvic lymph node dissection. Lymph node metastasis was identified in 25 patients, 23 of whom had disease properly classified by indocyanine green guided pelvic lymph node dissection. The most frequent location of indocyanine green stained nodes was the proximal internal iliac artery followed by the fossa of Marcille. The negative predictive value was 96.7% and the likelihood ratio of a negative test was 8%. Overall 1,856 nodes were removed and 603 were stained indocyanine green. Pathological examination revealed 82 metastatic nodes, of which 60% were indocyanine green stained. The negative predictive value was 97.4% but the likelihood ratio of a negative test was 58.5%. Indocyanine green guided pelvic lymph node dissection correctly staged 97% of cases. However, according to our data it cannot replace extended pelvic lymph node dissection. Nevertheless, its high negative predictive value could allow us to avoid extended pelvic lymph node dissection if we had an accurate intraoperative lymph fluorescent analysis. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Adaptive Connectivity Restoration from Node Failure(s) in Wireless Sensor Networks

PubMed Central

Wang, Huaiyuan; Ding, Xu; Huang, Cheng; Wu, Xiaobei

2016-01-01

Recently, there is a growing interest in the applications of wireless sensor networks (WSNs). A set of sensor nodes is deployed in order to collectively survey an area of interest and/or perform specific surveillance tasks in some of the applications, such as battlefield reconnaissance. Due to the harsh deployment environments and limited energy supply, nodes may fail, which impacts the connectivity of the whole network. Since a single node failure (cut-vertex) will destroy the connectivity and divide the network into disjoint blocks, most of the existing studies focus on the problem of single node failure. However, the failure of multiple nodes would be a disaster to the whole network and must be repaired effectively. Only few studies are proposed to handle the problem of multiple cut-vertex failures, which is a special case of multiple node failures. Therefore, this paper proposes a comprehensive solution to address the problems of node failure (single and multiple). Collaborative Single Node Failure Restoration algorithm (CSFR) is presented to solve the problem of single node failure only with cooperative communication, but CSFR-M, which is the extension of CSFR, handles the single node failure problem more effectively with node motion. Moreover, Collaborative Connectivity Restoration Algorithm (CCRA) is proposed on the basis of cooperative communication and node maneuverability to restore network connectivity after multiple nodes fail. CSFR-M and CCRA are reactive methods that initiate the connectivity restoration after detecting the node failure(s). In order to further minimize the energy dissipation, CCRA opts to simplify the recovery process by gridding. Moreover, the distance that an individual node needs to travel during recovery is reduced by choosing the nearest suitable candidates. Finally, extensive simulations validate the performance of CSFR, CSFR-M and CCRA. PMID:27690030

Scalable Node Monitoring

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

Drotar, Alexander P.; Quinn, Erin E.; Sutherland, Landon D.

2012-07-30

Project description is: (1) Build a high performance computer; and (2) Create a tool to monitor node applications in Component Based Tool Framework (CBTF) using code from Lightweight Data Metric Service (LDMS). The importance of this project is that: (1) there is a need a scalable, parallel tool to monitor nodes on clusters; and (2) New LDMS plugins need to be able to be easily added to tool. CBTF stands for Component Based Tool Framework. It's scalable and adjusts to different topologies automatically. It uses MRNet (Multicast/Reduction Network) mechanism for information transport. CBTF is flexible and general enough to bemore » used for any tool that needs to do a task on many nodes. Its components are reusable and 'EASILY' added to a new tool. There are three levels of CBTF: (1) frontend node - interacts with users; (2) filter nodes - filters or concatenates information from backend nodes; and (3) backend nodes - where the actual work of the tool is done. LDMS stands for lightweight data metric servies. It's a tool used for monitoring nodes. Ltool is the name of the tool we derived from LDMS. It's dynamically linked and includes the following components: Vmstat, Meminfo, Procinterrupts and more. It works by: Ltool command is run on the frontend node; Ltool collects information from the backend nodes; backend nodes send information to the filter nodes; and filter nodes concatenate information and send to a database on the front end node. Ltool is a useful tool when it comes to monitoring nodes on a cluster because the overhead involved with running the tool is not particularly high and it will automatically scale to any size cluster.« less

FDG-PET/CT lymph node staging after neoadjuvant chemotherapy in patients with adenocarcinoma of the esophageal-gastric junction.

PubMed

Fencl, Pavel; Belohlavek, Otakar; Harustiak, Tomas; Zemanova, Milada

2016-11-01

The aim of the analysis was to assess the accuracy of various FDG-PET/CT parameters in staging lymph nodes after neoadjuvant chemotherapy. In this prospective study, 74 patients with adenocarcinoma of the esophageal-gastric junction were examined by FDG-PET/CT in the course of their neoadjuvant chemotherapy given before surgical treatment. Data from the final FDG-PET/CT examinations were compared with the histology from the surgical specimens (gold standard). The accuracy was calculated for four FDG-PET/CT parameters: (1) hypermetabolic nodes, (2) large nodes, (3) large-and-medium large nodes, and (4) hypermetabolic or large nodes. In 74 patients, a total of 1540 lymph nodes were obtained by surgery, and these were grouped into 287 regions according to topographic origin. Five hundred and two nodes were imaged by FDG-PET/CT and were grouped into these same regions for comparison. In the analysis, (1) hypermetabolic nodes, (2) large nodes, (3) large-and-medium large nodes, and (4) hypermetabolic or large nodes identified metastases in particular regions with sensitivities of 11.6%, 2.9%, 21.7%, and 13.0%, respectively; specificity was 98.6%, 94.5%, 74.8%, and 93.6%, respectively. The best accuracy of 77.7% reached the parameter of hypermetabolic nodes. Accuracy decreased to 62.0% when also smaller nodes (medium-large) were taken for the parameter of metastases. FDG-PET/CT proved low sensitivity and high specificity. Low sensitivity was based on low detection rate (32.6%) when compared nodes imaged by FDG-PET/CT to nodes found by surgery, and in inability to detect micrometastases. Sensitivity increased when also medium-large LNs were taken for positive, but specificity and accuracy decreased.

Distribution of finger nodes and their association with underlying radiographic features of osteoarthritis.

PubMed

Rees, Frances; Doherty, Sally; Hui, Michelle; Maciewicz, Rose; Muir, Kenneth; Zhang, Weiya; Doherty, Michael

2012-04-01

To determine the distribution of clinically palpable hand interphalangeal (IP) nodes at each finger and thumb joint in a population with nodes, the influence of left or right hand dominance and sex on the development of nodes, and the association between nodes and underlying radiographic features of osteoarthritis (OA). We performed a cross-sectional analysis of participants in the Genetics of Osteoarthritis and Lifestyle (GOAL) study who had ≥1 Heberden's nodes or Bouchard's nodes on clinical examination. Frequencies (%) of nodes were described for each IP joint in the hand. Associations between nodes and underlying radiographic OA were shown with odds ratios (ORs) and 95% confidence intervals. A logistic regression model was used to adjust for the following confounding factors: age, sex, body mass index, left or right hand dominance, hand trauma, occupation with heavy manual activity, and participation in sports. Of the 3,170 GOAL participants, 1,939 had ≥1 nodes (mean age 68 years, 54% women). The distal IP joints of the index finger were the most frequently affected, followed by the thumb IP joint. Nodes were more common in dominant hands and women. There was a significant association between nodes and underlying radiographic OA (OR range 2.26-21.23). This association was stronger for joint space narrowing than for osteophytes. A dose-response relationship was found between clinical severity of Heberden's nodes and underlying radiographic change. Our study supports the positive association between nodes and radiographic OA, especially narrowing, and the influence of sex and left or right hand dominance on development of nodes. In this age group, presence of nodes may be taken as an indication of underlying small joint OA. Copyright © 2012 by the American College of Rheumatology.

Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

PubMed

Carrera, D; de la Flor, M; Galera, J; Amillano, K; Gomez, M; Izquierdo, V; Aguilar, E; López, S; Martínez, M; Martínez, S; Serra, J M; Pérez, M; Martin, L

2016-01-01

The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Longitudinal 3.0T MRI analysis of changes in lymph node volume and apparent diffusion coefficient in an experimental animal model of metastatic and hyperplastic lymph nodes.

PubMed

Klerkx, Wenche M; Geldof, Albert A; Heintz, A Peter; van Diest, Paul J; Visser, Fredy; Mali, Willem P; Veldhuis, Wouter B

2011-05-01

To perform a longitudinal analysis of changes in lymph node volume and apparent diffusion coefficient (ADC) in healthy, metastatic, and hyperplastic lymph nodes. Three groups of four female Copenhagen rats were studied. Metastasis was induced by injecting cells with a high metastatic potential in their left hind footpad. Reactive nodes were induced by injecting Complete Freund Adjuvant (CFA). Imaging was performed at baseline and at 2, 5, 8, 11, and 14 days after tumor cell injection. Finally, lymph nodes were examined histopathologically. The model was highly efficient in inducing lymphadenopathy: subcutaneous cell or CFA inoculation resulted in ipsilateral metastatic or reactive popliteal lymph nodes in all rats. Metastatic nodal volumes increased exponentially from 5-7 mm(3) at baseline to 25 mm(3) at day 14, while the control node remained 5 mm(3). The hyperplastic nodes showed a rapid volume increase reaching a plateau at day 6. The ADC of metastatic nodes significantly decreased (range 13%-32%), but this decrease was also seen in reactive nodes. Metastatic and hyperplastic lymph nodes differed in terms of enlargement patterns and ADC changes. Enlarged reactive or malignant nodes could not be differentiated based on their ADC values. Copyright © 2011 Wiley-Liss, Inc.

Glide dislocation nucleation from dislocation nodes at semi-coherent {111} Cu–Ni interfaces

DOE PAGES

Shao, Shuai; Wang, Jian; Beyerlein, Irene J.; ...

2015-07-23

Using atomistic simulations and dislocation theory on a model system of semi-coherent {1 1 1} interfaces, we show that misfit dislocation nodes adopt multiple atomic arrangements corresponding to the creation and redistribution of excess volume at the nodes. We identified four distinctive node structures: volume-smeared nodes with (i) spiral or (ii) straight dislocation patterns, and volume-condensed nodes with (iii) triangular or (iv) hexagonal dislocation patterns. Volume-smeared nodes contain interfacial dislocations lying in the Cu–Ni interface but volume-condensed nodes contain two sets of interfacial dislocations in the two adjacent interfaces and jogs across the atomic layer between the two adjacent interfaces.more » Finally, under biaxial tension/compression applied parallel to the interface, we show that the nucleation of lattice dislocations is preferred at the nodes and is correlated with the reduction of excess volume at the nodes.« less

Implementing asyncronous collective operations in a multi-node processing system

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

Chen, Dong; Eisley, Noel A.; Heidelberger, Philip

A method, system, and computer program product are disclosed for implementing an asynchronous collective operation in a multi-node data processing system. In one embodiment, the method comprises sending data to a plurality of nodes in the data processing system, broadcasting a remote get to the plurality of nodes, and using this remote get to implement asynchronous collective operations on the data by the plurality of nodes. In one embodiment, each of the nodes performs only one task in the asynchronous operations, and each nodes sets up a base address table with an entry for a base address of a memorymore » buffer associated with said each node. In another embodiment, each of the nodes performs a plurality of tasks in said collective operations, and each task of each node sets up a base address table with an entry for a base address of a memory buffer associated with the task.« less

Self-pacing direct memory access data transfer operations for compute nodes in a parallel computer

DOEpatents

Blocksome, Michael A

2015-02-17

Methods, apparatus, and products are disclosed for self-pacing DMA data transfer operations for nodes in a parallel computer that include: transferring, by an origin DMA on an origin node, a RTS message to a target node, the RTS message specifying an message on the origin node for transfer to the target node; receiving, in an origin injection FIFO for the origin DMA from a target DMA on the target node in response to transferring the RTS message, a target RGET descriptor followed by a DMA transfer operation descriptor, the DMA descriptor for transmitting a message portion to the target node, the target RGET descriptor specifying an origin RGET descriptor on the origin node that specifies an additional DMA descriptor for transmitting an additional message portion to the target node; processing, by the origin DMA, the target RGET descriptor; and processing, by the origin DMA, the DMA transfer operation descriptor.

Constructing a logical, regular axis topology from an irregular topology

DOEpatents

Faraj, Daniel A.

2014-07-22

Constructing a logical regular topology from an irregular topology including, for each axial dimension and recursively, for each compute node in a subcommunicator until returning to a first node: adding to a logical line of the axial dimension a neighbor specified in a nearest neighbor list; calling the added compute node; determining, by the called node, whether any neighbor in the node's nearest neighbor list is available to add to the logical line; if a neighbor in the called compute node's nearest neighbor list is available to add to the logical line, adding, by the called compute node to the logical line, any neighbor in the called compute node's nearest neighbor list for the axial dimension not already added to the logical line; and, if no neighbor in the called compute node's nearest neighbor list is available to add to the logical line, returning to the calling compute node.

Constructing a logical, regular axis topology from an irregular topology

DOEpatents

Faraj, Daniel A.

2014-07-01

Constructing a logical regular topology from an irregular topology including, for each axial dimension and recursively, for each compute node in a subcommunicator until returning to a first node: adding to a logical line of the axial dimension a neighbor specified in a nearest neighbor list; calling the added compute node; determining, by the called node, whether any neighbor in the node's nearest neighbor list is available to add to the logical line; if a neighbor in the called compute node's nearest neighbor list is available to add to the logical line, adding, by the called compute node to the logical line, any neighbor in the called compute node's nearest neighbor list for the axial dimension not already added to the logical line; and, if no neighbor in the called compute node's nearest neighbor list is available to add to the logical line, returning to the calling compute node.

Laboratory for Computer Science Progress Report 16, 1 July 1978 - 30 June 1979,

DTIC Science & Technology

1980-08-01

name strongly distinguishes the XLMS node from ordinary nameless semantic network nodes. The name of a node has two parts: the " genus ", itself a node...and the "specializer", a node or an atomic symbol. The genus and specializer of a node are almost always semantically meaningful, though their...meaning is almost never suppliec by XLMS, but rather by some system built on top of XLMS. The genus of a node almost always plays a crucial role in its

High speed polling protocol for multiple node network with sequential flooding of a polling message and a poll-answering message

NASA Technical Reports Server (NTRS)

Marvit, Maclen (Inventor); Kirkham, Harold (Inventor)

1995-01-01

The invention is a multiple interconnected network of intelligent message-repeating remote nodes which employs a remote node polling process performed by a master node by transmitting a polling message generically addressed to all remote nodes associated with the master node. Each remote node responds upon receipt of the generically addressed polling message by sequentially flooding the network with a poll-answering informational message and with the polling message.

Anatomical classification of breast sentinel lymph nodes using computed tomography-lymphography.

PubMed

Fujita, Tamaki; Miura, Hiroyuki; Seino, Hiroko; Ono, Shuichi; Nishi, Takashi; Nishimura, Akimasa; Hakamada, Kenichi; Aoki, Masahiko

2018-05-03

To evaluate the anatomical classification and location of breast sentinel lymph nodes, preoperative computed tomography-lymphography examinations were retrospectively reviewed for sentinel lymph nodes in 464 cases clinically diagnosed with node-negative breast cancer between July 2007 and June 2016. Anatomical classification was performed based on the numbers of lymphatic routes and sentinel lymph nodes, the flow direction of lymphatic routes, and the location of sentinel lymph nodes. Of the 464 cases reviewed, anatomical classification could be performed in 434 (93.5 %). The largest number of cases showed single route/single sentinel lymph node (n = 296, 68.2 %), followed by multiple routes/multiple sentinel lymph nodes (n = 59, 13.6 %), single route/multiple sentinel lymph nodes (n = 53, 12.2 %), and multiple routes/single sentinel lymph node (n = 26, 6.0 %). Classification based on the flow direction of lymphatic routes showed that 429 cases (98.8 %) had outward flow on the superficial fascia toward axillary lymph nodes, whereas classification based on the height of sentinel lymph nodes showed that 323 cases (74.4 %) belonged to the upper pectoral group of axillary lymph nodes. There was wide variation in the number of lymphatic routes and their branching patterns and in the number, location, and direction of flow of sentinel lymph nodes. It is clinically very important to preoperatively understand the anatomical morphology of lymphatic routes and sentinel lymph nodes for optimal treatment of breast cancer, and computed tomography-lymphography is suitable for this purpose.

Intraoperative sentinel node identification in early stage cervical cancer using a combination of radiolabeled albumin injection and isosulfan blue dye injection.

PubMed

Martínez-Palones, José M; Gil-Moreno, Antonio; Pérez-Benavente, María A; Roca, Isabel; Xercavins, Jordi

2004-03-01

We investigated the feasibility of sentinel lymph node identification using radioisotopic lymphatic mapping with technetium-99m-labeled human serum albumin and isosulfan blue dye injection in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. Between September 2000 and October 2002, 25 patients with cervical cancer FIGO stage I (n=24) or stage II (n=1) underwent sentinel lymph node detection with preoperative lymphoscintigraphy (technetium-99m colloid albumin injection around the tumor) and intraoperative lymphatic mapping with blue dye and a handheld or laparoscopic gamma probe. Complete pelvic or paraaortic lymphadenectomy was performed in all cases by open surgery or laparoscopic surgery. In 23 evaluable patients, a total of 51 sentinel lymph nodes were detected by lymphoscintigraphy (mean 2.21 nodes per patient). Intraoperatively, 61 sentinel lymph nodes were identified, with a mean of 2.52 nodes per patient by gamma probe and a mean of 1.94 nodes per patient after isosulfan blue injection. Forty percent of sentinel nodes were found in the interiliac region and 25% in the external iliac area. Microscopic nodal metastases (four nodes) were confirmed in 12% of cases. All these lymph nodes were previously detected as sentinel lymph nodes. The remaining 419 nodes after pelvic lymphadenectomy were histologically negative. Sentinel lymph node identification with technetium-99m-labeled nanocolloid combined with blue dye injection is feasible and showed a 100% negative predictive value, and potentially identified women in whom lymph node dissection can be avoided.

phylo-node: A molecular phylogenetic toolkit using Node.js.

PubMed

O'Halloran, Damien M

2017-01-01

Node.js is an open-source and cross-platform environment that provides a JavaScript codebase for back-end server-side applications. JavaScript has been used to develop very fast and user-friendly front-end tools for bioinformatic and phylogenetic analyses. However, no such toolkits are available using Node.js to conduct comprehensive molecular phylogenetic analysis. To address this problem, I have developed, phylo-node, which was developed using Node.js and provides a stable and scalable toolkit that allows the user to perform diverse molecular and phylogenetic tasks. phylo-node can execute the analysis and process the resulting outputs from a suite of software options that provides tools for read processing and genome alignment, sequence retrieval, multiple sequence alignment, primer design, evolutionary modeling, and phylogeny reconstruction. Furthermore, phylo-node enables the user to deploy server dependent applications, and also provides simple integration and interoperation with other Node modules and languages using Node inheritance patterns, and a customized piping module to support the production of diverse pipelines. phylo-node is open-source and freely available to all users without sign-up or login requirements. All source code and user guidelines are openly available at the GitHub repository: https://github.com/dohalloran/phylo-node.

A dual-modal magnetic nanoparticle probe for preoperative and intraoperative mapping of sentinel lymph nodes by magnetic resonance and near infrared fluorescence imaging

PubMed Central

Zhou, Zhengyang; Chen, Hongwei; Lipowska, Malgorzata; Wang, Liya; Yu, Qiqi; Yang, Xiaofeng; Tiwari, Diana; Yang, Lily; Mao, Hui

2016-01-01

The ability to reliably detect sentinel lymph nodes for sentinel lymph node biopsy and lymphadenectomy is important in clinical management of patients with metastatic cancers. However, the traditional sentinel lymph node mapping with visible dyes is limited by the penetration depth of light and fast clearance of the dyes. On the other hand, sentinel lymph node mapping with radionucleotide technique has intrinsically low spatial resolution and does not provide anatomic details in the sentinel lymph node mapping procedure. This work reports the development of a dual modality imaging probe with magnetic resonance and near infrared imaging capabilities for sentinel lymph node mapping using magnetic iron oxide nanoparticles (10 nm core size) conjugated with a near infrared molecule with emission at 830 nm. Accumulation of magnetic iron oxide nanoparticles in sentinel lymph nodes leads to strong T2 weighted magnetic resonance imaging contrast that can be potentially used for preoperative localization of sentinel lymph nodes, while conjugated near infrared molecules provide optical imaging tracking of lymph nodes with a high signal to background ratio. The new magnetic nanoparticle based dual imaging probe exhibits a significant longer lymph node retention time. Near infrared signals from nanoparticle conjugated near infrared dyes last up to 60 min in sentinel lymph node compared to that of 25 min for the free near infrared dyes in a mouse model. Furthermore, axillary lymph nodes, in addition to sentinel lymph nodes, can be also visualized with this probe, given its slow clearance and sufficient sensitivity. Therefore, this new dual modality imaging probe with the tissue penetration and sensitive detection of sentinel lymph nodes can be applied for preoperative survey of lymph nodes with magnetic resonance imaging and allows intraoperative sentinel lymph node mapping using near infrared optical devices. PMID:23812946

Identifying logical planes formed of compute nodes of a subcommunicator in a parallel computer

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

Davis, Kristan D.; Faraj, Daniel

In a parallel computer, a plurality of logical planes formed of compute nodes of a subcommunicator may be identified by: for each compute node of the subcommunicator and for a number of dimensions beginning with a first dimension: establishing, by a plane building node, in a positive direction of the first dimension, all logical planes that include the plane building node and compute nodes of the subcommunicator in a positive direction of a second dimension, where the second dimension is orthogonal to the first dimension; and establishing, by the plane building node, in a negative direction of the first dimension,more » all logical planes that include the plane building node and compute nodes of the subcommunicator in the positive direction of the second dimension.« less

Improved Survival in Male Melanoma Patients in the Era of Sentinel Node Biopsy.

PubMed

Koskivuo, I; Vihinen, P; Mäki, M; Talve, L; Vahlberg, T; Suominen, E

2017-03-01

Sentinel node biopsy is a standard method for nodal staging in patients with clinically localized cutaneous melanoma, but the survival advantage of sentinel node biopsy remains unsolved. The aim of this case-control study was to investigate the survival benefit of sentinel node biopsy. A total of 305 prospective melanoma patients undergoing sentinel node biopsy were compared with 616 retrospective control patients with clinically localized melanoma whom have not undergone sentinel node biopsy. Survival differences were calculated with the median follow-up time of 71 months in sentinel node biopsy patients and 74 months in control patients. Analyses were calculated overall and separately in males and females. Overall, there were no differences in relapse-free survival or cancer-specific survival between sentinel node biopsy patients and control patients. Male sentinel node biopsy patients had significantly higher relapse-free survival ( P = 0.021) and cancer-specific survival ( P = 0.024) than control patients. In females, no differences were found. Cancer-specific survival rates at 5 years were 87.8% in sentinel node biopsy patients and 85.2% in controls overall with 88.3% in male sentinel node biopsy patients and 80.6% in male controls and 87.3% in female sentinel node biopsy patients and 89.8% in female controls. Sentinel node biopsy did not improve survival in melanoma patients overall. While females had no differences in survival, males had significantly improved relapse-free survival and cancer-specific survival following sentinel node biopsy.

An Optimized Hidden Node Detection Paradigm for Improving the Coverage and Network Efficiency in Wireless Multimedia Sensor Networks

PubMed Central

Alanazi, Adwan; Elleithy, Khaled

2016-01-01

Successful transmission of online multimedia streams in wireless multimedia sensor networks (WMSNs) is a big challenge due to their limited bandwidth and power resources. The existing WSN protocols are not completely appropriate for multimedia communication. The effectiveness of WMSNs varies, and it depends on the correct location of its sensor nodes in the field. Thus, maximizing the multimedia coverage is the most important issue in the delivery of multimedia contents. The nodes in WMSNs are either static or mobile. Thus, the node connections change continuously due to the mobility in wireless multimedia communication that causes an additional energy consumption, and synchronization loss between neighboring nodes. In this paper, we introduce an Optimized Hidden Node Detection (OHND) paradigm. The OHND consists of three phases: hidden node detection, message exchange, and location detection. These three phases aim to maximize the multimedia node coverage, and improve energy efficiency, hidden node detection capacity, and packet delivery ratio. OHND helps multimedia sensor nodes to compute the directional coverage. Furthermore, an OHND is used to maintain a continuous node– continuous neighbor discovery process in order to handle the mobility of the nodes. We implement our proposed algorithms by using a network simulator (NS2). The simulation results demonstrate that nodes are capable of maintaining direct coverage and detecting hidden nodes in order to maximize coverage and multimedia node mobility. To evaluate the performance of our proposed algorithms, we compared our results with other known approaches. PMID:27618048

Frequency of an accessory popliteal efferent lymphatic pathway in dogs.

PubMed

Mayer, Monique N; Sweet, Katherine A; Patsikas, Michael N; Sukut, Sally L; Waldner, Cheryl L

2018-05-01

Staging and therapeutic planning for dogs with malignant disease in the popliteal lymph node are based on the expected patterns of lymphatic drainage from the lymph node. The medial iliac lymph nodes are known to receive efferent lymph from the popliteal lymph node; however, an accessory popliteal efferent pathway with direct connection to the sacral lymph nodes has also been less frequently reported. The primary objective of this prospective, anatomic study was to describe the frequency of various patterns of lymphatic drainage of the popliteal lymph node. With informed client consent, 50 adult dogs with no known disease of the lymphatic system underwent computed tomographic lymphography after ultrasound-guided, percutaneous injection of 350 mg/ml iohexol into a popliteal lymph node. In all 50 dogs, the popliteal lymph node drained directly to the ipsilateral medial iliac lymph node through multiple lymphatic vessels that coursed along the medial thigh. In 26% (13/50) of dogs, efferent vessels also drained from the popliteal lymph node directly to the internal iliac and/or sacral lymph nodes, coursing laterally through the gluteal region and passing over the dorsal aspect of the pelvis. Lymphatic connections between the right and left medial iliac and right and left internal iliac lymph nodes were found. Based on our findings, the internal iliac and sacral lymph nodes should be considered when staging or planning therapy for dogs with malignant disease in the popliteal lymph node. © 2018 American College of Veterinary Radiology.

Renal lymph nodes for tumor staging: appraisal of 871 nephrectomies with examination of hilar fat.

PubMed

Mehta, Vikas; Mudaliar, Kumaran; Ghai, Ritu; Quek, Marcus L; Milner, John; Flanigan, Robert C; Picken, Maria M

2013-11-01

Despite decades of research, the role of lymphadenectomy in the management of renal cell carcinoma (RCC) is still not clearly defined. Before the implementation of targeted therapies, lymph node metastases were considered to be a portent of markedly decreased survival, regardless of the tumor stage. However, the role of lymphadenectomy and the relative benefit of retroperitoneal lymph node dissection in the context of modern adjunctive therapies have not been conclusively addressed in the clinical literature. The current pathologic literature does not offer clear recommendations with regard to the minimum number of lymph nodes that should be examined in order to accurately stage the pN in renal cell carcinoma. Although gross examination of the hilar fat to assess the nodal status is performed routinely, it has not yet been determined whether this approach is adequate. To evaluate the status of lymph nodes and their rate of identification in the pathologic examination of nephrectomy specimens in adult renal malignancies. We reviewed the operative and pathology reports of 871 patients with renal malignancies treated by nephrectomy. All tumors were classified according to the seventh edition of the Tumor-Nodes-Metastasis classification. Patients were divided into 3 groups: Nx, no lymph nodes recovered; N0, negative; and N1, with positive lymph nodes. Grossly visible lymph nodes were submitted separately; as per grossing protocol, hilar fatty tissue was submitted for microscopic examination. We evaluated the factors that affected the number of lymph nodes identified and the variables that allowed the prediction of nodal involvement. Lymph nodes were recovered in 333 of 871 patients (38%): hilar in 125 patients, nonhilar in 137 patients, and hilar and nonhilar in 71 patients. Patients with positive lymph nodes (n = 87) were younger, had larger primary tumors, and had lymph nodes of average size, as well as a higher pT stage, nuclear grade, and rate of metastases. Metastases were seen only in grossly identified lymph nodes (65% hilar, 16% nonhilar); all microscopic nodes were negative. Even with the microscopic examination of fat, hilar lymph nodes were recovered in only 22.5% of patients. A nonhilar route of node metastasis was suspected in 40 patients. Only grossly identifiable lymph nodes, both hilar and nonhilar, were positive for metastases. Although microscopic examination of the hilar fat increased the number of lymph nodes recovered, the identification rate of these nodes was low (22.5%), and such microscopic nodes were invariably negative. Hence, microscopic examination of the hilar fat may be unnecessary.

Impact of affected lymph nodes on long-term outcome after surgical therapy of alveolar echinococcosis.

PubMed

Hillenbrand, Andreas; Beck, Annika; Kratzer, Wolfgang; Graeter, Tilmann; Barth, Thomas F E; Schmidberger, Julian; Möller, Peter; Henne-Bruns, Doris; Gruener, Beate

2018-06-16

Alveolar echinococcosis (AE) is a life-threatening helminthic disease. In humans, AE mostly affects the liver; the regional hepatic lymph nodes may be involved, indicating dissemination of AE from the liver. To achieve complete removal of the disease, enlarged hepatic lymph nodes may be resected during surgical treatment. We evaluated the frequency of affected lymph nodes by conventional microscopic and immunohistochemical analyses including detection of small particles of Echinococcus multilocularis (spem). Furthermore, we analyzed the association of resection of enlarged and affected lymph nodes with long-term outcome after surgical therapy of patients who underwent surgery with curative intent. We identified 43 patients who underwent hepatic surgery with curative intent with lymph node resection for AE. We analyzed the cohort for the manifestation of the parasite in the resected lymph nodes by conventional histology and by immunohistochemistry and compared these data with the further course of AE. Microscopically infected lymph nodes (laminar layer visible) were found in 7 out of these 43 patients (16%). In more than three quarters (25/32) of all specimens investigated, lymph nodes showed spems when stained with antibody against Em2G11, a monoclonal antibody specific for the Em2 antigen of the Echinococcus multilocularis metacestode. Most frequently, lymph nodes were resected due to enlargement. The median size of microscopically affected lymph nodes was 2 cm (range, 1.2 to 2.5 cm), the median size of immunohistochemically and non-affected lymph nodes was 1.3 cm each (range, "small" to 2.3 or 2.5 cm, respectively). Median follow-up was 8 years for all patients, 5 years for patients with lymph node resection, and 4 years for patients with infested lymph nodes. Overall, recurrent disease was seen in ten patients (10/109; 9%) after a median period of 1.5 years (range, 4 months to 4 years). None of the seven patients with conventionally microscopically affected lymph nodes suffered from recurrent disease. One patient with negative resected nodes and one patient with spems showed recurrent disease after 4 and 35 months, respectively. Lymph node involvement in AE is frequent, particularly when evaluated by immunohistochemical examination of lymph nodes with the monoclonal antibody Em2G11. Affected lymph nodes tend to be larger in size. Lymph node involvement is not associated with recurrent disease and therefore warrants further analysis of the biological significance of lymph node involvement.

Implementation of Multiple Host Nodes in Wireless Sensing Node Network System for Landslide Monitoring

NASA Astrophysics Data System (ADS)

Abas, Faizulsalihin bin; Takayama, Shigeru

2015-02-01

This paper proposes multiple host nodes in Wireless Sensing Node Network System (WSNNS) for landslide monitoring. As landslide disasters damage monitoring system easily, one major demand in landslide monitoring is the flexibility and robustness of the system to evaluate the current situation in the monitored area. For various reasons WSNNS can provide an important contribution to reach that aim. In this system, acceleration sensors and GPS are deployed in sensing nodes. Location information by GPS, enable the system to estimate network topology and enable the system to perceive the location in emergency by monitoring the node mode. Acceleration sensors deployment, capacitate this system to detect slow mass movement that can lead to landslide occurrence. Once deployed, sensing nodes self-organize into an autonomous wireless ad hoc network. The measurement parameter data from sensing nodes is transmitted to Host System via host node and "Cloud" System. The implementation of multiple host nodes in Local Sensing Node Network System (LSNNS), improve risk- management of the WSNNS for real-time monitoring of landslide disaster.

A Simulation Program with Latency Exploitation and Node Tearing.

DTIC Science & Technology

1985-02-01

translation table JUNODE is constructed to give the relation between the user-defined node set and the node set used in the pro- gram. The ground node...90, 0, 45 and 80, then, user’s node renumbered node JUNODE table 0(ground) 1 nodplc(IUNODE+1)=O 10 2 ( +2)=10 45 3 ( +3)=45 80 4 ( +4)=80 90 5 ( +5

Contrast-enhanced ultrasound mapping of sentinel lymph nodes in oral tongue cancer-a pilot study.

PubMed

Gvetadze, Shalva R; Xiong, Ping; Lv, Mingming; Li, Jun; Hu, Jingzhou; Ilkaev, Konstantin D; Yang, Xin; Sun, Jian

2017-03-01

To assess the usefulness of contrast-enhanced ultrasound (CEUS) with peritumoral injection of microbubble contrast agent for detecting the sentinel lymph nodes for oral tongue carcinoma. The study was carried out on 12 patients with T1-2cN0 oral tongue cancer. A radical resection of the primary disease was planned; a modified radical supraomohyoid neck dissection was reserved for patients with larger lesions (T2, n = 8). The treatment plan and execution were not influenced by sentinel node mapping outcome. The Sonovue ™ contrast agent (Bracco Imaging, Milan, Italy) was utilized. After detection, the position and radiologic features of the sentinel nodes were recorded. The identification rate of the sentinel nodes was 91.7%; one patient failed to demonstrate any enhanced areas. A total of 15 sentinel nodes were found in the rest of the 11 cases, with a mean of 1.4 nodes for each patient. The sentinel nodes were localized in: Level IA-1 (6.7%) node; Level IB-11 (73.3%) nodes; Level IIA-3 (20.0%) nodes. No contrast-related adverse effects were observed. For oral tongue tumours, CEUS is a feasible and potentially widely available approach of sentinel node mapping. Further clinical research is required to establish the position of CEUS detection of the sentinel nodes in oral cavity cancers.

Cloud computing method for dynamically scaling a process across physical machine boundaries

DOEpatents

Gillen, Robert E.; Patton, Robert M.; Potok, Thomas E.; Rojas, Carlos C.

2014-09-02

A cloud computing platform includes first device having a graph or tree structure with a node which receives data. The data is processed by the node or communicated to a child node for processing. A first node in the graph or tree structure determines the reconfiguration of a portion of the graph or tree structure on a second device. The reconfiguration may include moving a second node and some or all of its descendant nodes. The second and descendant nodes may be copied to the second device.

Characterization of gut microbiota profiles by disease activity in patients with Crohn's disease using data mining analysis of terminal restriction fragment length polymorphisms.

PubMed

Andoh, Akira; Kobayashi, Toshio; Kuzuoka, Hiroyuki; Tsujikawa, Tomoyuki; Suzuki, Yasuo; Hirai, Fumihito; Matsui, Toshiyuki; Nakamura, Shiro; Matsumoto, Takayuki; Fujiyama, Yoshihide

2014-05-01

The gut microbiota plays a significant role in the pathogenesis of Crohn's disease (CD). In this study, we analyzed the disease activity and associated fecal microbiota profiles in 160 CD patients and 121 healthy individuals. Fecal samples from the CD patients were collected during three different clinical phases, the active (n=66), remission-achieved (n=51) and remission-maintained (n=43) phases. Terminal restriction fragment length polymorphism (T-RFLP) and data mining analysis using the Classification and Regression Tree (C&RT) approach were performed. Data mining provided a decision tree that clearly identified the various subject groups (nodes). The majority of the healthy individuals were divided into Node-5 and Node-8. Healthy subjects comprised 99% of Node-5 (91 of 92) and 84% of Node-8 (21 of 25 subjects). Node-3 was characterized by CD (136 of 160 CD subjects) and was divided into Node-6 and Node-7. Node-6 (n=103) was characterized by subjects in the active phase (n=48; 46%) and remission-achieved phase (n=39; 38%) and Node-7 was characterized by the remission-maintained phase (21 of 37 subjects; 57%). Finally, Node-6 was divided into Node-9 and Node-10. Node-9 (n=78) was characterized by subjects in the active phase (n=43; 55%) and Node-10 (n=25) was characterized by subjects in the remission-maintained phase (n=16; 64%). Differences in the gut microbiota associated with disease activity of CD patients were identified. Thus, data mining analysis appears to be an ideal tool for the characterization of the gut microbiota in inflammatory bowel disease.

Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma.

PubMed

Mantel, Hendrik T J; Wiggers, Jim K; Verheij, Joanne; Doff, Jan J; Sieders, Egbert; van Gulik, Thomas M; Gouw, Annette S H; Porte, Robert J

2015-12-01

Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of this study was to assess the effect on survival of immunohistochemically detected lymph node micrometastases in patients with node-negative (pN0) hilar cholangiocarcinoma on routine histology. Between 1990 and 2010, a total of 146 patients underwent curative-intent resection of hilar cholangiocarcinoma with regional lymphadenectomy at two university medical centers in the Netherlands. Ninety-one patients (62 %) without lymph node metastases at routine histology were included. Micrometastases were identified by multiple sectioning of all lymph nodes and additional immunostaining with an antibody against cytokeratin 19 (K19). The association with overall survival was assessed in univariable and multivariable analysis. Median follow-up was 48 months. Micrometastases were identified in 16 (5 %) of 324 lymph nodes, corresponding to 11 (12 %) of 91 patients. There were no differences in clinical variables between K19 lymph node-positive and -negative patients. Five-year survival rates in patients with lymph node micrometastases were significantly lower compared to patients without micrometastases (27 vs. 54 %, P = 0.01). Multivariable analysis confirmed micrometastases as an independent prognostic factor for survival (adjusted Hazard ratio 2.4, P = 0.02). Lymph node micrometastases are associated with worse survival after resection of hilar cholangiocarcinoma. Immunohistochemical detection of lymph node micrometastases leads to better staging of patients who were initially diagnosed with node-negative (pN0) hilar cholangiocarcinoma on routine histology.

RTOG GU Radiation Oncology Specialists Reach Consensus on Pelvic Lymph Node Volumes for High-Risk Prostate Cancer

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

Lawton, Colleen A.F.; Michalski, Jeff; El-Naqa, Issam

2009-06-01

Purpose: Radiation therapy to the pelvic lymph nodes in high-risk prostate cancer is required on several Radiation Therapy Oncology Group (RTOG) clinical trials. Based on a prior lymph node contouring project, we have shown significant disagreement in the definition of pelvic lymph node volumes among genitourinary radiation oncology specialists involved in developing and executing current RTOG trials. Materials and Methods: A consensus meeting was held on October 3, 2007, to reach agreement on pelvic lymph node volumes. Data were presented to address the lymph node drainage of the prostate. Extensive discussion ensued to develop clinical target volume (CTV) pelvic lymphmore » node consensus. Results: Consensus was obtained resulting in computed tomography image-based pelvic lymph node CTVs. Based on this consensus, the pelvic lymph node volumes to be irradiated include: distal common iliac, presacral lymph nodes (S{sub 1}-S{sub 3}), external iliac lymph nodes, internal iliac lymph nodes, and obturator lymph nodes. Lymph node CTVs include the vessels (artery and vein) and a 7-mm radial margin being careful to 'carve out' bowel, bladder, bone, and muscle. Volumes begin at the L5/S1 interspace and end at the superior aspect of the pubic bone. Consensus on dose-volume histogram constraints for OARs was also attained. Conclusions: Consensus on pelvic lymph node CTVs for radiation therapy to address high-risk prostate cancer was attained and is available as web-based computed tomography images as well as a descriptive format through the RTOG. This will allow for uniformity in evaluating the benefit and risk of such treatment.« less

Prognostic Significance of the Location of Lymph Node Metastases in Patients With Adenocarcinoma of the Distal Esophagus or Gastroesophageal Junction.

PubMed

Anderegg, Maarten C J; Lagarde, Sjoerd M; Jagadesham, Vamshi P; Gisbertz, Suzanne S; Immanuel, Arul; Meijer, Sybren L; Hulshof, Maarten C C M; Bergman, Jacques J G H M; van Laarhoven, Hanneke W M; Griffin, S Michael; van Berge Henegouwen, Mark I

2016-11-01

To identify the prognostic significance of the location of lymph node metastases in patients with esophageal or gastroesophageal junction (GEJ) adenocarcinoma treated with neoadjuvant therapy followed by esophagectomy. Detection of lymph node metastases in the upper mediastinum and around the celiac trunk after neoadjuvant therapy and resection does not alter the TNM classification of esophageal carcinoma. The impact of these distant lymph node metastases on survival remains unclear. Between March 2003 and September 2013, 479 consecutive patients with adenocarcinoma of the distal esophagus or GEJ who underwent transthoracic esophagectomy with en bloc 2-field lymphadenectomy after neoadjuvant therapy were included, and survival was analyzed according to the location of positive lymph nodes in the resection specimen. Two hundred fifty-three patients had nodal metastases in the resection specimen. Of these patients, 92 patients had metastases in locoregional nodes, 114 patients in truncal nodes, 21 patients in the proximal field of the chest, and 26 patients had both positive truncal and proximal field nodes. Median disease-free survival was 170 months in the absence of nodal metastases, 35 months for metastases limited to locoregional nodes, 16 months for positive truncal nodes, 15 months for positive nodes in the proximal field, and 8 months for nodal metastases in both truncal and the proximal field. On multivariate analysis, location of lymph node metastases was independently associated with survival. Location of lymph node metastases is an independent predictor for survival. Relatively distant lymph node metastases along the celiac axis and/or the proximal field have a negative impact on survival. Location of lymph node metastases should therefore be considered in future staging systems of esophageal and GEJ adenocarcinoma.

Sentinel Node Detection in Head and Neck Malignancies: Innovations in Radioguided Surgery

PubMed Central

Vermeeren, L.; Klop, W. M. C.; van den Brekel, M. W. M.; Balm, A. J. M.; Nieweg, O. E.; Valdés Olmos, R. A.

2009-01-01

Sentinel node mapping is becoming a routine procedure for staging of various malignancies, because it can determine lymph node status more precisely. Due to anatomical problems, localizing sentinel nodes in the head and neck region on the basis of conventional images can be difficult. New diagnostic tools can provide better visualization of sentinel nodes. In an attempt to keep up with possible scientific progress, this article reviews new and innovative tools for sentinel node localization in this specific area. The overview comprises a short introduction of the sentinel node procedure as well as indications in the head and neck region. Then the results of SPECT/CT for sentinel node detection are described. Finally, a portable gamma camera to enable intraoperative real-time imaging with improved sentinel node detection is described. PMID:20016804

Multiple node remote messaging

DOEpatents

Blumrich, Matthias A.; Chen, Dong; Gara, Alan G.; Giampapa, Mark E.; Heidelberger, Philip; Ohmacht, Martin; Salapura, Valentina; Steinmacher-Burow, Burkhard; Vranas, Pavlos

2010-08-31

A method for passing remote messages in a parallel computer system formed as a network of interconnected compute nodes includes that a first compute node (A) sends a single remote message to a remote second compute node (B) in order to control the remote second compute node (B) to send at least one remote message. The method includes various steps including controlling a DMA engine at first compute node (A) to prepare the single remote message to include a first message descriptor and at least one remote message descriptor for controlling the remote second compute node (B) to send at least one remote message, including putting the first message descriptor into an injection FIFO at the first compute node (A) and sending the single remote message and the at least one remote message descriptor to the second compute node (B).

System and method for merging clusters of wireless nodes in a wireless network

DOEpatents

Budampati, Ramakrishna S [Maple Grove, MN; Gonia, Patrick S [Maplewood, MN; Kolavennu, Soumitri N [Blaine, MN; Mahasenan, Arun V [Kerala, IN

2012-05-29

A system includes a first cluster having multiple first wireless nodes. One first node is configured to act as a first cluster master, and other first nodes are configured to receive time synchronization information provided by the first cluster master. The system also includes a second cluster having one or more second wireless nodes. One second node is configured to act as a second cluster master, and any other second nodes configured to receive time synchronization information provided by the second cluster master. The system further includes a manager configured to merge the clusters into a combined cluster. One of the nodes is configured to act as a single cluster master for the combined cluster, and the other nodes are configured to receive time synchronization information provided by the single cluster master.

Deadlock-free class routes for collective communications embedded in a multi-dimensional torus network

DOEpatents

Chen, Dong; Eisley, Noel A.; Steinmacher-Burow, Burkhard; Heidelberger, Philip

2013-01-29

A computer implemented method and a system for routing data packets in a multi-dimensional computer network. The method comprises routing a data packet among nodes along one dimension towards a root node, each node having input and output communication links, said root node not having any outgoing uplinks, and determining at each node if the data packet has reached a predefined coordinate for the dimension or an edge of the subrectangle for the dimension, and if the data packet has reached the predefined coordinate for the dimension or the edge of the subrectangle for the dimension, determining if the data packet has reached the root node, and if the data packet has not reached the root node, routing the data packet among nodes along another dimension towards the root node.

Network of dedicated processors for finding lowest-cost map path

NASA Technical Reports Server (NTRS)

Eberhardt, Silvio P. (Inventor)

1991-01-01

A method and associated apparatus are disclosed for finding the lowest cost path of several variable paths. The paths are comprised of a plurality of linked cost-incurring areas existing between an origin point and a destination point. The method comprises the steps of connecting a purality of nodes together in the manner of the cost-incurring areas; programming each node to have a cost associated therewith corresponding to one of the cost-incurring areas; injecting a signal into one of the nodes representing the origin point; propagating the signal through the plurality of nodes from inputs to outputs; reducing the signal in magnitude at each node as a function of the respective cost of the node; and, starting at one of the nodes representing the destination point and following a path having the least reduction in magnitude of the signal from node to node back to one of the nodes representing the origin point whereby the lowest cost path from the origin point to the destination point is found.

Patterns of regional head and neck lymph node metastasis in primary conjunctival malignant melanoma

PubMed Central

Lim, M; Tatla, T; Hersh, D; Hungerford, J

2006-01-01

Objective To correlate patterns of regional lymph node metastasis with the site of origin in primary conjunctival malignant melanoma. Design Retrospective analysis (1990–2003) of clinical data. Setting Two London tertiary referral centres. Participants 12 patients presenting with regional metastases after failed local treatment for conjunctival malignant melanoma. Results 6 cases predominantly involving the temporal conjunctiva metastasised to the pre‐auricular lymph nodes. Two cases predominantly involving the nasal conjunctiva metastasised to the submandibular nodes. Of the two cases with purely multifocal disease, one metastasised to the pre‐auricular nodes and another to both submandibular and parotid nodes. One primary conjunctival malignant melanoma had its origin in temporal conjunctiva but metastasised to submandibular nodes, and another case originating from nasal conjunctiva metastasised to pre‐auricular nodes. Conclusions Temporal conjunctival melanotic lesions tend to metastasise clinically to pre‐auricular lymph nodes and nasal conjunctival melanotic lesions metastasise to the submandibular lymph nodes. Patterns appear consistent with laboratory‐based anatomically mapped lymphatic drainage basins of the conjunctiva. PMID:16928703

Ultrasonography of the medial iliac lymph nodes in the dog.

PubMed

Llabrés-Díaz, Francisco J

2004-01-01

Sixty-one medial iliac lymph nodes of 38 different dogs (eight with adenocarcinoma of the apocrine glands of the anal sac, 13 with multicentric lymphoma, six with multicentric lymphoma but in clinical remission, and 11 control dogs) were evaluated to assess the ability of ultrasound to identify and interrogate these lymph nodes across the different groups and to differentiate these groups using different sonographic parameters. Ultrasound proved to be useful to assess canine medial iliac lymph nodes. An increase in size or number of detected lymph nodes or finding rounder or heterogeneous lymph nodes could differentiate lymph nodes of dogs of the control group from lymph nodes of dogs with lymphoma or an adenocarcinoma of the apocrine glands of the anal sac. Subcategories of malignancy could not be differentiated. More studies need to be performed, both with patients with reactive lymph nodes and also focusing on other canine superficial lymph nodes, before generalizing the results of this study to other areas or diseases.

Node Self-Deployment Algorithm Based on Pigeon Swarm Optimization for Underwater Wireless Sensor Networks

PubMed Central

Yu, Shanen; Xu, Yiming; Jiang, Peng; Wu, Feng; Xu, Huan

2017-01-01

At present, free-to-move node self-deployment algorithms aim at event coverage and cannot improve network coverage under the premise of considering network connectivity, network reliability and network deployment energy consumption. Thus, this study proposes pigeon-based self-deployment algorithm (PSA) for underwater wireless sensor networks to overcome the limitations of these existing algorithms. In PSA, the sink node first finds its one-hop nodes and maximizes the network coverage in its one-hop region. The one-hop nodes subsequently divide the network into layers and cluster in each layer. Each cluster head node constructs a connected path to the sink node to guarantee network connectivity. Finally, the cluster head node regards the ratio of the movement distance of the node to the change in the coverage redundancy ratio as the target function and employs pigeon swarm optimization to determine the positions of the nodes. Simulation results show that PSA improves both network connectivity and network reliability, decreases network deployment energy consumption, and increases network coverage. PMID:28338615

Innovative research of AD HOC network mobility model

NASA Astrophysics Data System (ADS)

Chen, Xin

2017-08-01

It is difficult for researchers of AD HOC network to conduct actual deployment during experimental stage as the network topology is changeable and location of nodes is unfixed. Thus simulation still remains the main research method of the network. Mobility model is an important component of AD HOC network simulation. It is used to describe the movement pattern of nodes in AD HOC network (including location and velocity, etc.) and decides the movement trail of nodes, playing as the abstraction of the movement modes of nodes. Therefore, mobility model which simulates node movement is an important foundation for simulation research. In AD HOC network research, mobility model shall reflect the movement law of nodes as truly as possible. In this paper, node generally refers to the wireless equipment people carry. The main research contents include how nodes avoid obstacles during movement process and the impacts of obstacles on the mutual relation among nodes, based on which a Node Self Avoiding Obstacle, i.e. NASO model is established in AD HOC network.

Method for designing gas tag compositions

DOEpatents

Gross, Kenny C.

1995-01-01

For use in the manufacture of gas tags such as employed in a nuclear reactor gas tagging failure detection system, a method for designing gas tagging compositions utilizes an analytical approach wherein the final composition of a first canister of tag gas as measured by a mass spectrometer is designated as node #1. Lattice locations of tag nodes in multi-dimensional space are then used in calculating the compositions of a node #2 and each subsequent node so as to maximize the distance of each node from any combination of tag components which might be indistinguishable from another tag composition in a reactor fuel assembly. Alternatively, the measured compositions of tag gas numbers 1 and 2 may be used to fix the locations of nodes 1 and 2, with the locations of nodes 3-N then calculated for optimum tag gas composition. A single sphere defining the lattice locations of the tag nodes may be used to define approximately 20 tag nodes, while concentric spheres can extend the number of tag nodes to several hundred.

Administering truncated receive functions in a parallel messaging interface

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2014-12-09

Administering truncated receive functions in a parallel messaging interface (`PMI`) of a parallel computer comprising a plurality of compute nodes coupled for data communications through the PMI and through a data communications network, including: sending, through the PMI on a source compute node, a quantity of data from the source compute node to a destination compute node; specifying, by an application on the destination compute node, a portion of the quantity of data to be received by the application on the destination compute node and a portion of the quantity of data to be discarded; receiving, by the PMI on the destination compute node, all of the quantity of data; providing, by the PMI on the destination compute node to the application on the destination compute node, only the portion of the quantity of data to be received by the application; and discarding, by the PMI on the destination compute node, the portion of the quantity of data to be discarded.

Global tree network for computing structures enabling global processing operations

DOEpatents

Blumrich; Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E.; Heidelberger, Philip; Hoenicke, Dirk; Steinmacher-Burow, Burkhard D.; Takken, Todd E.; Vranas, Pavlos M.

2010-01-19

A system and method for enabling high-speed, low-latency global tree network communications among processing nodes interconnected according to a tree network structure. The global tree network enables collective reduction operations to be performed during parallel algorithm operations executing in a computer structure having a plurality of the interconnected processing nodes. Router devices are included that interconnect the nodes of the tree via links to facilitate performance of low-latency global processing operations at nodes of the virtual tree and sub-tree structures. The global operations performed include one or more of: broadcast operations downstream from a root node to leaf nodes of a virtual tree, reduction operations upstream from leaf nodes to the root node in the virtual tree, and point-to-point message passing from any node to the root node. The global tree network is configurable to provide global barrier and interrupt functionality in asynchronous or synchronized manner, and, is physically and logically partitionable.

An Eccentricity Based Data Routing Protocol with Uniform Node Distribution in 3D WSN.

PubMed

Hosen, A S M Sanwar; Cho, Gi Hwan; Ra, In-Ho

2017-09-16

Due to nonuniform node distribution, the energy consumption of nodes are imbalanced in clustering-based wireless sensor networks (WSNs). It might have more impact when nodes are deployed in a three-dimensional (3D) environment. In this regard, we propose the eccentricity based data routing (EDR) protocol in a 3D WSN with uniform node distribution. It includes network partitions called 3D subspaces/clusters of equal member nodes, an energy-efficient routing centroid (RC) nodes election and data routing algorithm. The RC nodes election conducts in a quasi-static nature until a certain period unlike the periodic cluster heads election of typical clustering-based routing. It not only reduces the energy consumption of nodes during the election phase, but also in intra-communication. At the same time, the routing algorithm selects a forwarding node in such a way that balances the energy consumption among RC nodes and reduces the number of hops towards the sink. The simulation results validate and ensure the performance supremacy of the EDR protocol compared to existing protocols in terms of various metrics such as steady state and network lifetime in particular. Meanwhile, the results show the EDR is more robust in uniform node distribution compared to nonuniform.

Energy Efficient and Stable Weight Based Clustering for Mobile Ad Hoc Networks

NASA Astrophysics Data System (ADS)

Bouk, Safdar H.; Sasase, Iwao

Recently several weighted clustering algorithms have been proposed, however, to the best of our knowledge; there is none that propagates weights to other nodes without weight message for leader election, normalizes node parameters and considers neighboring node parameters to calculate node weights. In this paper, we propose an Energy Efficient and Stable Weight Based Clustering (EE-SWBC) algorithm that elects cluster heads without sending any additional weight message. It propagates node parameters to its neighbors through neighbor discovery message (HELLO Message) and stores these parameters in neighborhood list. Each node normalizes parameters and efficiently calculates its own weight and the weights of neighboring nodes from that neighborhood table using Grey Decision Method (GDM). GDM finds the ideal solution (best node parameters in neighborhood list) and calculates node weights in comparison to the ideal solution. The node(s) with maximum weight (parameters closer to the ideal solution) are elected as cluster heads. In result, EE-SWBC fairly selects potential nodes with parameters closer to ideal solution with less overhead. Different performance metrics of EE-SWBC and Distributed Weighted Clustering Algorithm (DWCA) are compared through simulations. The simulation results show that EE-SWBC maintains fewer average numbers of stable clusters with minimum overhead, less energy consumption and fewer changes in cluster structure within network compared to DWCA.

An Eccentricity Based Data Routing Protocol with Uniform Node Distribution in 3D WSN

PubMed Central

Hosen, A. S. M. Sanwar; Cho, Gi Hwan; Ra, In-Ho

2017-01-01

Due to nonuniform node distribution, the energy consumption of nodes are imbalanced in clustering-based wireless sensor networks (WSNs). It might have more impact when nodes are deployed in a three-dimensional (3D) environment. In this regard, we propose the eccentricity based data routing (EDR) protocol in a 3D WSN with uniform node distribution. It includes network partitions called 3D subspaces/clusters of equal member nodes, an energy-efficient routing centroid (RC) nodes election and data routing algorithm. The RC nodes election conducts in a quasi-static nature until a certain period unlike the periodic cluster heads election of typical clustering-based routing. It not only reduces the energy consumption of nodes during the election phase, but also in intra-communication. At the same time, the routing algorithm selects a forwarding node in such a way that balances the energy consumption among RC nodes and reduces the number of hops towards the sink. The simulation results validate and ensure the performance supremacy of the EDR protocol compared to existing protocols in terms of various metrics such as steady state and network lifetime in particular. Meanwhile, the results show the EDR is more robust in uniform node distribution compared to nonuniform. PMID:28926958

Decline in Frozen Section Diagnosis for Axillary Sentinel Lymph Nodes as a Result of the American College of Surgeons Oncology Group Z0011 Trial.

PubMed

Bishop, Julie Anne; Sun, Jihong; Ajkay, Nicolas; Sanders, Mary Ann G

2016-08-01

-Results of the American College of Surgeons Oncology Group Z0011 trial showed that patients with early-stage breast cancer and limited sentinel node metastasis treated with breast conservation and systemic therapy did not benefit from axillary lymph node dissection. Subsequently, most pathology departments have likely seen a decrease in frozen section diagnosis of sentinel lymph nodes. -To determine the effect of the Z0011 trial on pathology practice and to examine the utility of intraoperative sentinel lymph node evaluation for this subset of patients. -Pathology reports from cases of primary breast cancer that met Z0011 clinical criteria and were initially treated with lumpectomy and sentinel lymph node biopsy from 2009 to 2015 were collected. Clinicopathologic data were recorded. -Sentinel lymph node biopsies sent for frozen section diagnosis occurred in 22 of 22 cases (100%) in 2009 and 15 of 22 cases (68%) in 2010 during the pre-Z0011 years, and in 3 of 151 cases (2%) collected in 2011 through 2015, considered to be post-Z0011 years. Of the 151 post-Z0011 cases, 28 (19%) had sentinel lymph nodes with metastasis, and 147 (97%) were spared axillary lymph node dissection. -Following Z0011, intraoperative sentinel lymph node evaluation has significantly decreased at our institution. Prior to surgery, all patients had clinically node-negative disease. After sentinel lymph node evaluation, 97% (147 of 151) of the patients were spared axillary lymph node dissection. Therefore, routine frozen section diagnosis for sentinel lymph node biopsies can be avoided in these patients.

Modified methylene blue injection improves lymph node harvest in rectal cancer.

PubMed

Liu, Jianpei; Huang, Pinjie; Zheng, Zongheng; Chen, Tufeng; Wei, Hongbo

2017-04-01

The presence of nodal metastases in rectal cancer plays an important role in accurate staging and prognosis, which depends on adequate lymph node harvest. The aim of this prospective study is to investigate the feasibility and survival benefit of improving lymph node harvest by a modified method with methylene blue injection in rectal cancer specimens. One hundred and thirty-one patients with rectal cancer were randomly assigned to the control group in which lymph nodes were harvested by palpation and sight, or to the methylene blue group using a modified method of injection into the superior rectal artery with methylene blue. Analysis of clinicopathologic records, including a long-term follow-up, was performed. In the methylene blue group, 678 lymph nodes were harvested by simple palpation and sight. Methylene blue injection added 853 lymph nodes to the total harvest as well as 32 additional metastatic lymph nodes, causing a shift to node-positive stage in four patients. The average number of lymph nodes harvested was 11.7 ± 3.4 in the control group and 23.2 ± 4.7 in the methylene blue group, respectively. The harvest of small lymph nodes (<5 mm) and the average number of metastatic nodes were both significantly higher in the methylene blue group. The modified method of injection with methylene blue had no impact on overall survival. The modified method with methylene blue injection improved lymph node harvest in rectal cancer, especially small node and metastatic node retrieval, which provided more accurate staging. However, it was not associated with overall survival. © 2014 Royal Australasian College of Surgeons.

Isolated perifacial lymph node metastasis in oral squamous cell carcinoma with clinically node-negative neck.

PubMed

Agarwal, Sangeet Kumar; Arora, Sowrabh Kumar; Kumar, Gopal; Sarin, Deepak

2016-10-01

The incidence of occult perifacial nodal disease in oral cavity squamous cell carcinoma is not well reported. The purpose of this study was to evaluate the incidence of isolated perifacial lymph node metastasis in patients with oral squamous cell carcinoma with a clinically node-negative neck. The study will shed light on current controversies and will provide valuable clinical and pathological information in the practice of routine comprehensive removal of these lymph node pads in selective neck dissection in the node-negative neck. Prospective analysis. This study was started in August 2011 when intraoperatively we routinely separated the lymph node levels from the main specimen for evaluation of the metastatic rate to different lymph node levels in 231 patients of oral squamous cell cancer with a clinically node-negative neck. The current study demonstrated that 19 (8.22%) out of 231 patients showed ipsilateral isolated perifacial lymph node involvement. The incidence of isolated perifacial nodes did not differ significantly between the oral tongue (7.14%) and buccal mucosa (7.75%). Incidence was statistically significant in cases with lower age group (<45 years), advanced T stage, and higher depth of tumor invasion. Isolated perifacial node metastasis is high in oral squamous cell carcinoma with a clinically node-negative neck. The incidence of isolated perifacial involvement is high in cases of buccal mucosal and tongue cancers. A meticulous dissection of the perifacial nodes seems prudent when treating the neck in oral cavity squamous cell carcinoma. 4 Laryngoscope, 126:2252-2256, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Efficacy of Sentinel Lymph Node Biopsy in Detecting Axillary Metastasis in Breast Cancer Using Methylene Blue.

PubMed

Nandu, Vipul V; Chaudhari, Milind S

2017-06-01

Breast cancer is the leading malignancy and the second leading cause of cancer-related deaths. Axillary lymph node status is a very important prognostic factor in breast cancer patients; nodal evaluation is therefore a critical part of breast cancer management. Axillary lymph node dissection results in significant morbidity. Sentinel lymph node biopsy (SLNB) is being used in many centers to stage the axilla in planning axillary dissection management of patients and hence plays an important part in reducing morbidity among patients with carcinoma breast. The objectives of this paper is to study the (1) efficacy of sentinel lymph node biopsy in detecting axillary metastasis, (2) location of sentinel lymph node in the axilla, (3) rate of involvement of sentinel lymph nodes, and (4) incidence of skip metastasis. Thirty-five patients with breast cancer with clinically node-negative axilla were selected for the study. Methylene blue dye was injected intralesional and perilesional 20 min prior to surgery. All patients underwent modified radical mastectomy with sentinel lymph node biopsy and axillary dissection and after pathological examination diagnostic statics, namely sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were computed. Sentinel lymph node was identified in all of these patients. Sixty percent patients had pathologically positive lymph nodes in the axilla. 90.48% patients of these had sentinel lymph nodes positive for malignant cells. Incidence of skip metastasis is 9.52%. 88.57% patients had sentinel lymph node mapped to level I lymph nodes. Sensitivity of SLNB is 90.48%, specificity is 85.71%, PPV of is 90.48%, NPV is 85.71%, and accuracy is 88.57%. Sentinel lymph node biopsy is an effective method of staging the axilla and deciding on axillary clearance in patients of carcinoma breast. Unnecessary axillary dissection and associated complications can be prevented in most of patients due to sentinel lymph node biopsy.

Occult lymph node metastasis and risk of regional recurrence in papillary thyroid cancer after bilateral prophylactic central neck dissection: A multi-institutional study.

PubMed

Lee, Young Chan; Na, Se Young; Park, Gi Cheol; Han, Ju Hyun; Kim, Seung Woo; Eun, Young Gyu

2017-02-01

The impact of occult lymph node metastasis on regional recurrence after prophylactic central neck dissection for preoperative, nodal-negative papillary thyroid cancer is controversial. We investigated risk factors for regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Analysis was according to clinicopathologic characteristics and occult lymph node metastasis patterns. This multicenter study enrolled 211 consecutive patients who underwent total thyroidectomy with bilateral prophylactic central neck dissection for papillary thyroid cancer without evidence of central lymph node metastasis on preoperative imaging. Clinicopathologic features and central lymph node metastasis patterns were analyzed for predicting regional recurrence. Multivariate Cox regression analysis was used to identify independent factors for recurrence. Median follow-up time was 43 months (24-95 months). Ten patients (4.7%) showed regional lymph node recurrence. The estimated 5-year, regional recurrence-free survival was 95.2%. Tumor size ≥1 cm, central lymph node metastasis, lymph node ratio, and prelaryngeal lymph node metastasis were associated with regional recurrence in univariate analysis (P < .05). In multivariate analysis, a lymph node ratio ≥ 0.26 was a significant risk factor for regional lymph node recurrence (odds ratio = 11.63, P = .003). Lymph node ratio ≥ 0.26 was an independent predictor of worse recurrence-free survival on Cox regression analysis (hazard ratio = 11.49, P = .002). Although no significant association was observed between the presence of occult lymph node metastasis and regional recurrence, lymph node ratio ≥ 0.26 was an independent predictor of regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Copyright © 2016 Elsevier Inc. All rights reserved.

Cell proliferation in mammalian gastrulation: the ventral node and notochord are relatively quiescent.

PubMed

Bellomo, D; Lander, A; Harragan, I; Brown, N A

1996-04-01

During gastrulation, the node of the mammalian embryo appears to be an organising centre, homologous to Hensen's node in the chick and the dorsal lip of the amphibian blastopore. In addition, the node serves as a precursor population for the head process, notochord and foregut endoderm. We have studied node architecture and cell morphology by electron microscopy, and cell proliferation using bromodeoxyuridine incorporation and mitotic counts. The dorsal (ectodermal) and ventral (endodermal) components of the node are two distinct populations, separated by a basement membrane. The ventral node, contiguous with the head process, is characterised by a relatively low proliferation rate, with only approximately 10% of cells incorporating BrdU over 4 hr, compared to > 95% in surrounding mesodermal and ectodermal tissues. This is the case from the beginning of node formation, at the no-allantoic-bud stage, until the 7 somite stage, and is not compatible with the idea that the ventral node is a stem cell population. The dorsal node is highly proliferative, its rate of division being indistinguishable from the neurectoderm, with which it is contiguous. In the ventral node, two regions can be recognised: cells in the "pit" are columnar and all monociliated; around them lies a "crown" of cells arranged radially in a horseshoe shape and less often ciliated. Node derivatives share common features with the ventral node; the head process and the notochord are relatively quiescent; and some head process cells are also monociliated. Node and head process monocilia are immotile and appear to be associated with non-proliferation. We suggest that the ventral node contains all the properties of the organiser, while the dorsal node is indistinct from the surrounding epiblast. The cranial end of the foregut pouch, the thyroid diverticulum, and the promyocardium of early somite stage embryos are also areas of low cell division. All the described regions of relative quiescence are sites of expression of members of the TGF beta family, which may be involved in maintaining non-proliferation.

Penile Cancer: Contemporary Lymph Node Management.

PubMed

O'Brien, Jonathan S; Perera, Marlon; Manning, Todd; Bozin, Mike; Cabarkapa, Sonja; Chen, Emily; Lawrentschuk, Nathan

2017-06-01

In penile cancer, the optimal diagnostics and management of metastatic lymph nodes are not clear. Advances in minimally invasive staging, including dynamic sentinel lymph node biopsy, have widened the diagnostic repertoire of the urologist. We aimed to provide an objective update of the recent trends in the management of penile squamous cell carcinoma, and inguinal and pelvic lymph node metastases. We systematically reviewed several medical databases, including the Web of Science® (with MEDLINE®), Embase® and Cochrane databases, according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines. The search terms used were penile cancer, lymph node, sentinel node, minimally invasive, surgery and outcomes, alone and in combination. Articles pertaining to the management of lymph nodes in penile cancer were reviewed, including original research, reviews and clinical guidelines published between 1980 and 2016. Accurate and minimally invasive lymph node staging is of the utmost importance in the surgical management of penile squamous cell carcinoma. In patients with clinically node negative disease, a growing body of evidence supports the use of sentinel lymph node biopsies. Dynamic sentinel lymph node biopsy exposes the patient to minimal risk, and results in superior sensitivity and specificity profiles compared to alternate nodal staging techniques. In the presence of locoregional disease, improvements in inguinal or pelvic lymphadenectomy have reduced morbidity and improved oncologic outcomes. A multimodal approach of chemotherapy and surgery has demonstrated a survival benefit for patients with advanced disease. Recent developments in lymph node management have occurred in penile cancer, such as minimally invasive lymph node diagnosis and intervention strategies. These advances have been met with a degree of controversy in the contemporary literature. Current data suggest that dynamic sentinel lymph node biopsy provides excellent sensitivity and specificity for detecting lymph node metastases. More robust long-term data on multicenter patient cohorts are required to determine the optimal management of lymph nodes in penile cancer. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Paging memory from random access memory to backing storage in a parallel computer

DOEpatents

Archer, Charles J; Blocksome, Michael A; Inglett, Todd A; Ratterman, Joseph D; Smith, Brian E

2013-05-21

Paging memory from random access memory (`RAM`) to backing storage in a parallel computer that includes a plurality of compute nodes, including: executing a data processing application on a virtual machine operating system in a virtual machine on a first compute node; providing, by a second compute node, backing storage for the contents of RAM on the first compute node; and swapping, by the virtual machine operating system in the virtual machine on the first compute node, a page of memory from RAM on the first compute node to the backing storage on the second compute node.

Method and apparatus for offloading compute resources to a flash co-processing appliance

DOEpatents

Tzelnic, Percy; Faibish, Sorin; Gupta, Uday K.; Bent, John; Grider, Gary Alan; Chen, Hsing -bung

2015-10-13

Solid-State Drive (SSD) burst buffer nodes are interposed into a parallel supercomputing cluster to enable fast burst checkpoint of cluster memory to or from nearby interconnected solid-state storage with asynchronous migration between the burst buffer nodes and slower more distant disk storage. The SSD nodes also perform tasks offloaded from the compute nodes or associated with the checkpoint data. For example, the data for the next job is preloaded in the SSD node and very fast uploaded to the respective compute node just before the next job starts. During a job, the SSD nodes perform fast visualization and statistical analysis upon the checkpoint data. The SSD nodes can also perform data reduction and encryption of the checkpoint data.

Pacing a data transfer operation between compute nodes on a parallel computer

DOEpatents

Blocksome, Michael A [Rochester, MN

2011-09-13

Methods, systems, and products are disclosed for pacing a data transfer between compute nodes on a parallel computer that include: transferring, by an origin compute node, a chunk of an application message to a target compute node; sending, by the origin compute node, a pacing request to a target direct memory access (`DMA`) engine on the target compute node using a remote get DMA operation; determining, by the origin compute node, whether a pacing response to the pacing request has been received from the target DMA engine; and transferring, by the origin compute node, a next chunk of the application message if the pacing response to the pacing request has been received from the target DMA engine.

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

Davis, Kristan D.; Faraj, Daniel A.

In a parallel computer, a plurality of logical planes formed of compute nodes of a subcommunicator may be identified by: for each compute node of the subcommunicator and for a number of dimensions beginning with a first dimension: establishing, by a plane building node, in a positive direction of the first dimension, all logical planes that include the plane building node and compute nodes of the subcommunicator in a positive direction of a second dimension, where the second dimension is orthogonal to the first dimension; and establishing, by the plane building node, in a negative direction of the first dimension,more » all logical planes that include the plane building node and compute nodes of the subcommunicator in the positive direction of the second dimension.« less

Three faces of node importance in network epidemiology: Exact results for small graphs

NASA Astrophysics Data System (ADS)

Holme, Petter

2017-12-01

We investigate three aspects of the importance of nodes with respect to susceptible-infectious-removed (SIR) disease dynamics: influence maximization (the expected outbreak size given a set of seed nodes), the effect of vaccination (how much deleting nodes would reduce the expected outbreak size), and sentinel surveillance (how early an outbreak could be detected with sensors at a set of nodes). We calculate the exact expressions of these quantities, as functions of the SIR parameters, for all connected graphs of three to seven nodes. We obtain the smallest graphs where the optimal node sets are not overlapping. We find that (i) node separation is more important than centrality for more than one active node, (ii) vaccination and influence maximization are the most different aspects of importance, and (iii) the three aspects are more similar when the infection rate is low.

Executing scatter operation to parallel computer nodes by repeatedly broadcasting content of send buffer partition corresponding to each node upon bitwise OR operation

DOEpatents

Archer, Charles J [Rochester, MN; Ratterman, Joseph D [Rochester, MN

2009-11-06

Executing a scatter operation on a parallel computer includes: configuring a send buffer on a logical root, the send buffer having positions, each position corresponding to a ranked node in an operational group of compute nodes and for storing contents scattered to that ranked node; and repeatedly for each position in the send buffer: broadcasting, by the logical root to each of the other compute nodes on a global combining network, the contents of the current position of the send buffer using a bitwise OR operation, determining, by each compute node, whether the current position in the send buffer corresponds with the rank of that compute node, if the current position corresponds with the rank, receiving the contents and storing the contents in a reception buffer of that compute node, and if the current position does not correspond with the rank, discarding the contents.

Regional lymph node staging in breast cancer: the increasing role of imaging and ultrasound-guided axillary lymph node fine needle aspiration.

PubMed

Mainiero, Martha B

2010-09-01

The status of axillary lymph nodes is a key prognostic indicator in patients with breast cancer and helps guide patient management. Sentinel lymph node biopsy is increasingly being used as a less morbid alternative to axillary lymph node dissection. However, when sentinel lymph node biopsy is positive, axillary dissection is typically performed for complete staging and local control. Axillary ultrasound and ultrasound-guided fine needle aspiration (USFNA) are useful for detecting axillary nodal metastasis preoperatively and can spare patients sentinel node biopsy, because those with positive cytology on USFNA can proceed directly to axillary dissection or neoadjuvant chemotherapy. Internal mammary nodes are not routinely evaluated, but when the appearance of these nodes is abnormal on imaging, further treatment or metastatic evaluation may be necessary. Copyright © 2010 Elsevier Inc. All rights reserved.

Link failure detection in a parallel computer

DOEpatents

Archer, Charles J.; Blocksome, Michael A.; Megerian, Mark G.; Smith, Brian E.

2010-11-09

Methods, apparatus, and products are disclosed for link failure detection in a parallel computer including compute nodes connected in a rectangular mesh network, each pair of adjacent compute nodes in the rectangular mesh network connected together using a pair of links, that includes: assigning each compute node to either a first group or a second group such that adjacent compute nodes in the rectangular mesh network are assigned to different groups; sending, by each of the compute nodes assigned to the first group, a first test message to each adjacent compute node assigned to the second group; determining, by each of the compute nodes assigned to the second group, whether the first test message was received from each adjacent compute node assigned to the first group; and notifying a user, by each of the compute nodes assigned to the second group, whether the first test message was received.

Routing Based on Length of Time of Available Connection

NASA Technical Reports Server (NTRS)

Anandappan, Thanga (Inventor); Roy, Aloke (Inventor); Malve, Sharath Babu (Inventor); Toth, Louis T. (Inventor)

2016-01-01

In an embodiment, a method of routing packets at a first node in an ad-hoc network is provided. The method includes receiving, at the first node, a plurality of route-alive messages corresponding to a destination, each of the plurality of route-alive messages including a route time indicating a length of time in which a communicative connection is available between the second node that sent the respective route-alive message and the destination. The method also includes determining an updated route time for each second node. The updated route time corresponds to a length of time in which a communication connection is available between the first node and the destination through the respective second node. A second node is selected for sending a packet to based on the updated route time for each of the second nodes, wherein a node having a longer updated route time is given higher priority for selection.

Analysis of complex network performance and heuristic node removal strategies

NASA Astrophysics Data System (ADS)

Jahanpour, Ehsan; Chen, Xin

2013-12-01

Removing important nodes from complex networks is a great challenge in fighting against criminal organizations and preventing disease outbreaks. Six network performance metrics, including four new metrics, are applied to quantify networks' diffusion speed, diffusion scale, homogeneity, and diameter. In order to efficiently identify nodes whose removal maximally destroys a network, i.e., minimizes network performance, ten structured heuristic node removal strategies are designed using different node centrality metrics including degree, betweenness, reciprocal closeness, complement-derived closeness, and eigenvector centrality. These strategies are applied to remove nodes from the September 11, 2001 hijackers' network, and their performance are compared to that of a random strategy, which removes randomly selected nodes, and the locally optimal solution (LOS), which removes nodes to minimize network performance at each step. The computational complexity of the 11 strategies and LOS is also analyzed. Results show that the node removal strategies using degree and betweenness centralities are more efficient than other strategies.

Distributed Transforms for Efficient Data Gathering in Sensor Networks

NASA Technical Reports Server (NTRS)

Ortega, Antonio (Inventor); Shen, Godwin (Inventor); Narang, Sunil K. (Inventor); Perez-Trufero, Javier (Inventor)

2014-01-01

Devices, systems, and techniques for data collecting network such as wireless sensors are disclosed. A described technique includes detecting one or more remote nodes included in the wireless sensor network using a local power level that controls a radio range of the local node. The technique includes transmitting a local outdegree. The local outdegree can be based on a quantity of the one or more remote nodes. The technique includes receiving one or more remote outdegrees from the one or more remote nodes. The technique includes determining a local node type of the local node based on detecting a node type of the one or more remote nodes, using the one or more remote outdegrees, and using the local outdegree. The technique includes adjusting characteristics, including an energy usage characteristic and a data compression characteristic, of the wireless sensor network by selectively modifying the local power level and selectively changing the local node type.

The role of CEUS in characterization of superficial lymph nodes: a single center prospective study

PubMed Central

de Stefano, Giorgio; Scognamiglio, Umberto; Di Martino, Filomena; Parrella, Roberto; Scarano, Francesco; Signoriello, Giuseppe; Farella, Nunzia

2016-01-01

Accurate lymph node characterization is important in a large number of clinical settings. We evaluated the usefulness of Contrast Enhanced Ultrasound (CEUS) in distinguishing between benign and malignant lymph nodes compared with conventional ultrasonography in the differential diagnosis of superficial lymphadenopathy. We present our experience for 111 patients enrolled in a single center. 111 superficial lymph nodes were selected and only 1 lymph node per patient underwent CEUS. A definitive diagnosis for all lymph nodes was obtained by ultrasonographically guided biopsy and/or excision biopsy. The size of the lymph nodes, the site (neck, axilla, inguinal region) being easily accessible for biopsy, and the US and color Doppler US characteristics guided us in selecting the nodes to be evaluated by CEUS. In our study we identified different enhancement patterns in benign and malignant lymph nodes, with a high degree of diagnostic accuracy for superficial lymphadenopathy in comparison with conventional US. PMID:27191746

Using Link Disconnection Entropy Disorder to Detect Fast Moving Nodes in MANETs

PubMed Central

Palafox, Luis E.; Aguilar, Leocundo; Sanchez, Mauricio A.; Martinez, Luis G.

2016-01-01

Mobile ad-hoc networks (MANETs) are dynamic by nature; this dynamism comes from node mobility, traffic congestion, and other transmission conditions. Metrics to evaluate the effects of those conditions shine a light on node’s behavior in an ad-hoc network, helping to identify the node or nodes with better conditions of connection. In this paper, we propose a relative index to evaluate a single node reliability, based on the link disconnection entropy disorder using neighboring nodes as reference. Link disconnection entropy disorder is best used to identify fast moving nodes or nodes with unstable communications, this without the need of specialized sensors such as GPS. Several scenarios were studied to verify the index, measuring the effects of Speed and traffic density on the link disconnection entropy disorder. Packet delivery ratio is associated to the metric detecting a strong relationship, enabling the use of the link disconnection entropy disorder to evaluate the stability of a node to communicate with other nodes. To expand the utilization of the link entropy disorder, we identified nodes with higher speeds in network simulations just by using the link entropy disorder. PMID:27219671

[Injection of methylene blue into inferior mesenteric artery improves lymph node harvest in rectal cancer after neoadjuvant chemotherapy].

PubMed

Liu, Jianpei; Huang, Pinjie; Huang, Jianglong; Chen, Tufeng; Wei, Hongbo

2015-06-09

To confirm the feasibility of improving lymph node harvest by injecting methylene blue into inferior mesenteric artery in rectal cancer after neoadjuvant therapy. Forty two ex vivo specimens were collected from rectal cancer patients with neoadjuvant therapy and radical operation at our hospital. Traditional method with palpation and injection of methylene blue into inferior mesenteric artery were employed. The data of lymph node harvest were analyzed by paired t and chi-square tests. The average number of detected lymph node in traditional method and methylene blue groups were 6.1 ± 4.3 and 15.2 ± 6.4 respectively (P<0.001). The proportions of lymph nodes <5 mm were 14.1% and 46.7% in traditional method and methylene blue groups respectively (P<0.001). And the injection of methylene blue added 13 extra metastatic lymph nodes and caused a shift to node-positive stage (P=0.89). Neoadjuvant therapy decrease lymph node retrieval in rectal cancer. Injecting methylene blue into inferior mesenteric artery improves lymph node harvest especially for small nodes and helps to acquire more metastatic nodes for accurate pathological staging.

Uncovering hidden nodes in complex networks in the presence of noise

PubMed Central

Su, Ri-Qi; Lai, Ying-Cheng; Wang, Xiao; Do, Younghae

2014-01-01

Ascertaining the existence of hidden objects in a complex system, objects that cannot be observed from the external world, not only is curiosity-driven but also has significant practical applications. Generally, uncovering a hidden node in a complex network requires successful identification of its neighboring nodes, but a challenge is to differentiate its effects from those of noise. We develop a completely data-driven, compressive-sensing based method to address this issue by utilizing complex weighted networks with continuous-time oscillatory or discrete-time evolutionary-game dynamics. For any node, compressive sensing enables accurate reconstruction of the dynamical equations and coupling functions, provided that time series from this node and all its neighbors are available. For a neighboring node of the hidden node, this condition cannot be met, resulting in abnormally large prediction errors that, counterintuitively, can be used to infer the existence of the hidden node. Based on the principle of differential signal, we demonstrate that, when strong noise is present, insofar as at least two neighboring nodes of the hidden node are subject to weak background noise only, unequivocal identification of the hidden node can be achieved. PMID:24487720

FoxP3 and indoleamine 2,3-dioxygenase immunoreactivity in sentinel nodes from melanoma patients.

PubMed

Ryan, Marisa; Crow, Jennifer; Kahmke, Russel; Fisher, Samuel R; Su, Zuowei; Lee, Walter T

2014-01-01

1) Assess FoxP3/indoleamine 2,3-dioxygenase immunoreactivity in head and neck melanoma sentinel lymph nodes and 2) correlate FoxP3/indoleamine 2,3-dioxygenase with sentinel lymph node metastasis and clinical recurrence. Retrospective cohort study. Patients with sentinel lymph node biopsy for head and neck melanoma between 2004 and 2011 were identified. FoxP3/indoleamine 2,3-dioxygenase prevalence and intensity were determined from the nodes. Poor outcome was defined as local, regional or distant recurrence. The overall immunoreactivity score was correlated with clinical recurrence and sentinel lymph node metastasis using the chi-square test for trend. Fifty-six sentinel lymph nodes were reviewed, with 47 negative and 9 positive for melanoma. Patients with poor outcomes had a statistically significant trend for higher immunoreactivity scores (p=0.03). Positive nodes compared to negative nodes also had a statistically significant trend for higher immunoreactivity scores (p=0.03). Among the negative nodes, there was a statistically significant trend for a poor outcome with higher immunoreactivity scores (p=0.02). FoxP3/indoleamine 2,3-dioxygenase immunoreactivity correlates with sentinel lymph node positivity and poor outcome. Even in negative nodes, higher immunoreactivity correlated with poor outcome. Therefore higher immunoreactivity may portend a worse prognosis even without metastasis in the sentinel lymph node. This could identify a subset of patients that may benefit from future trials and treatment for melanoma through Treg and IDO suppression. Published by Elsevier Inc.

Identifying Node Role in Social Network Based on Multiple Indicators

PubMed Central

Huang, Shaobin; Lv, Tianyang; Zhang, Xizhe; Yang, Yange; Zheng, Weimin; Wen, Chao

2014-01-01

It is a classic topic of social network analysis to evaluate the importance of nodes and identify the node that takes on the role of core or bridge in a network. Because a single indicator is not sufficient to analyze multiple characteristics of a node, it is a natural solution to apply multiple indicators that should be selected carefully. An intuitive idea is to select some indicators with weak correlations to efficiently assess different characteristics of a node. However, this paper shows that it is much better to select the indicators with strong correlations. Because indicator correlation is based on the statistical analysis of a large number of nodes, the particularity of an important node will be outlined if its indicator relationship doesn't comply with the statistical correlation. Therefore, the paper selects the multiple indicators including degree, ego-betweenness centrality and eigenvector centrality to evaluate the importance and the role of a node. The importance of a node is equal to the normalized sum of its three indicators. A candidate for core or bridge is selected from the great degree nodes or the nodes with great ego-betweenness centrality respectively. Then, the role of a candidate is determined according to the difference between its indicators' relationship with the statistical correlation of the overall network. Based on 18 real networks and 3 kinds of model networks, the experimental results show that the proposed methods perform quite well in evaluating the importance of nodes and in identifying the node role. PMID:25089823

Sentinel node localization in oral cavity and oropharynx squamous cell cancer.

PubMed

Taylor, R J; Wahl, R L; Sharma, P K; Bradford, C R; Terrell, J E; Teknos, T N; Heard, E M; Wolf, G T; Chepeha, D B

2001-08-01

To evaluate the feasibility and predictive ability of the sentinel node localization technique for patients with squamous cell carcinoma of the oral cavity or oropharynx and clinically negative necks. Prospective, efficacy study comparing the histopathologic status of the sentinel node with that of the remaining neck dissection specimen. Tertiary referral center. Patients with T1 or T2 disease and clinically negative necks were eligible for the study. Nine previously untreated patients with oral cavity or oropharyngeal squamous cell carcinoma were enrolled in the study. Unfiltered technetium Tc 99m sulfur colloid injections of the primary tumor and lymphoscintigraphy were performed on the day before surgery. Intraoperatively, the sentinel node(s) was localized with a gamma probe and removed after tumor resection and before neck dissection. The primary outcome was the negative predictive value of the histopathologic status of the sentinel node for predicting cervical metastases. Sentinel nodes were identified in 9 previously untreated patients. In 5 patients, there were no positive nodes. In 4 patients, the sentinel nodes were the only histopathologically positive nodes. In previously untreated patients, the sentinel node technique had a negative predictive value of 100% for cervical metastasis. Our preliminary investigation shows that sentinel node localization is technically feasible in head and neck surgery and is predictive of cervical metastasis. The sentinel node technique has the potential to decrease the number of neck dissections performed in clinically negative necks, thus reducing the associated morbidity for patients in this group.

MAdCAM-1 expressing sacral lymph node in the lymphotoxin beta-deficient mouse provides a site for immune generation following vaginal herpes simplex virus-2 infection.

PubMed

Soderberg, Kelly A; Linehan, Melissa M; Ruddle, Nancy H; Iwasaki, Akiko

2004-08-01

The members of the lymphotoxin (LT) family of molecules play a critical role in lymphoid organogenesis. Whereas LT alpha-deficient mice lack all lymph nodes and Peyer's patches, mice deficient in LT beta retain mesenteric lymph nodes and cervical lymph nodes, suggesting that an LT beta-independent pathway exists for the generation of mucosal lymph nodes. In this study, we describe the presence of a lymph node in LT beta-deficient mice responsible for draining the genital mucosa. In the majority of LT beta-deficient mice, a lymph node was found near the iliac artery, slightly misplaced from the site of the sacral lymph node in wild-type mice. The sacral lymph node of the LT beta-deficient mice, as well as that of the wild-type mice, expressed the mucosal addressin cell adhesion molecule-1 similar to the mesenteric lymph node. Following intravaginal infection with HSV type 2, activated dendritic cells capable of stimulating a Th1 response were found in this sacral lymph node. Furthermore, normal HSV-2-specific IgG responses were generated in the LT beta-deficient mice following intravaginal HSV-2 infection even in the absence of the spleen. Therefore, an LT beta-independent pathway exists for the development of a lymph node associated with the genital mucosa, and such a lymph node serves to generate potent immune responses against viral challenge.

Immune response in melanoma: an in-depth analysis of the primary tumor and corresponding sentinel lymph node

PubMed Central

Ma, Michelle W.; Medicherla, Ratna C.; Qian, Meng; de Miera, Eleazar Vega-Saenz; Friedman, Erica B.; Berman, Russell S.; Shapiro, Richard L.; Pavlick, Anna C.; Ott, Patrick A.; Bhardwaj, Nina; Shao, Yongzhao; Osman, Iman; Darvishian, Farbod

2013-01-01

The sentinel lymph node is the initial site of metastasis. Down-regulation of anti-tumor immunity plays a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T-cells (Foxp3+) and dendritic cells (conventional: CD11c+, mature: CD86+) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunologic primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared to those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T-cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathologic variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Anti-tumor immunity was down-regulated in the positive sentinel lymph node with an increase in regulatory T-cells compared to the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared to the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T-cell expression improved the discriminative power of a recurrence risk assessment model using clinical stage. Primary tumor regression was associated with prolonged disease-free (P=0.025) and melanoma-specific (P=0.014) survival. Our results support an assessment of local immune profiles in both the primary tumor and sentinel lymph node to help guide therapeutic decisions. PMID:22425909

Computational lymphatic node models in pediatric and adult hybrid phantoms for radiation dosimetry

NASA Astrophysics Data System (ADS)

Lee, Choonsik; Lamart, Stephanie; Moroz, Brian E.

2013-03-01

We developed models of lymphatic nodes for six pediatric and two adult hybrid computational phantoms to calculate the lymphatic node dose estimates from external and internal radiation exposures. We derived the number of lymphatic nodes from the recommendations in International Commission on Radiological Protection (ICRP) Publications 23 and 89 at 16 cluster locations for the lymphatic nodes: extrathoracic, cervical, thoracic (upper and lower), breast (left and right), mesentery (left and right), axillary (left and right), cubital (left and right), inguinal (left and right) and popliteal (left and right), for different ages (newborn, 1-, 5-, 10-, 15-year-old and adult). We modeled each lymphatic node within the voxel format of the hybrid phantoms by assuming that all nodes have identical size derived from published data except narrow cluster sites. The lymph nodes were generated by the following algorithm: (1) selection of the lymph node site among the 16 cluster sites; (2) random sampling of the location of the lymph node within a spherical space centered at the chosen cluster site; (3) creation of the sphere or ovoid of tissue representing the node based on lymphatic node characteristics defined in ICRP Publications 23 and 89. We created lymph nodes until the pre-defined number of lymphatic nodes at the selected cluster site was reached. This algorithm was applied to pediatric (newborn, 1-, 5-and 10-year-old male, and 15-year-old males) and adult male and female ICRP-compliant hybrid phantoms after voxelization. To assess the performance of our models for internal dosimetry, we calculated dose conversion coefficients, called S values, for selected organs and tissues with Iodine-131 distributed in six lymphatic node cluster sites using MCNPX2.6, a well validated Monte Carlo radiation transport code. Our analysis of the calculations indicates that the S values were significantly affected by the location of the lymph node clusters and that the values increased for smaller phantoms due to the shorter inter-organ distances compared to the bigger phantoms. By testing sensitivity of S values to random sampling and voxel resolution, we confirmed that the lymph node model is reasonably stable and consistent for different random samplings and voxel resolutions.

Use of calcium channel blockers in hypertrophic cardiomyopathy.

PubMed

Lorell, B H

1985-02-22

Recent studies in patients with either obstructive or nonobstructive hypertrophic cardiomyopathy have suggested that increased resistance to diastolic filling of the stiff left ventricle may be an important mechanism contributing to symptoms. These observations have led to exploration of the effects of calcium channel blockers on systolic and diastolic function in patients with hypertrophic cardiomyopathy. Acute hemodynamic studies using verapamil and nifedipine have shown that these agents tend to cause: (1) a slight fall in systemic arterial pressure and reflex increase in heart rate; (2) a reduction in left ventricular outflow gradient in most but not all patients; and (3) variable effect on left-side heart filling pressures. In contrast to beta-adrenergic blockers, these hemodynamic effects are not associated with depression of systolic function, but appear to be related to improved left ventricular distensibility. Clinical trials have suggested that long-term administration of verapamil in patients with hypertrophic cardiomyopathy promotes improvement in symptomatic status and exercise tolerance in many but not all patients; similar results have been reported in preliminary studies using nifedipine. Potential major adverse effects include depression of sinoatrial activity and atrioventricular conduction with verapamil, and marked hypotension and, rarely, pulmonary edema with both verapamil and nifedipine.

International Registry for Patients With Castleman Disease

ClinicalTrials.gov

2017-07-12

Castleman Disease; Castleman's Disease; Giant Lymph Node Hyperplasia; Angiofollicular Lymph Hyperplasia; Angiofollicular Lymph Node Hyperplasia; Angiofollicular Lymphoid Hyperplasia; GLNH; Hyperplasia, Giant Lymph Node; Lymph Node Hyperplasia, Giant

Long-term prognoses and outcomes of axillary lymph node recurrence in 2,578 sentinel lymph node-negative patients for whom axillary lymph node dissection was omitted: results from one Japanese hospital.

PubMed

Ogiya, Akiko; Kimura, Kiyomi; Nakashima, Eri; Sakai, Takehiko; Miyagi, Yumi; Iijima, Kotaro; Morizono, Hidetomo; Makita, Masujiro; Horii, Rie; Akiyama, Futoshi; Iwase, Takuji

2016-03-01

Axillary dissection omission for sentinel lymph node-negative patients has been a practice at Cancer Institute Hospital, Japanese Foundation for Cancer Research since 2003. We examined the long-term results of omission of axillary dissection in sentinel lymph node-negative patients treated at our hospital, as well as their axillary lymph node recurrence characteristics and outcomes. Our study included 2,578 patients with cTis or T1-T3N0M0 primary breast cancer for whom dissection was omitted because they were sentinel lymph node negative. The median observation period was 75 months. In sentinel lymph node-negative patients for whom dissection was omitted, the rates of axillary lymph node recurrence, distant recurrence, and breast cancer mortality were 0.9, 2, and 1 %, respectively. Eighteen patients underwent additional dissection if axillary lymph node recurrence was observed at the first recurrence. Four triple-negative (TN) patients experienced distant recurrence after additional dissection. All four patients were administered anticancer agents after axillary lymph node recurrence and experienced recurrence within 1 year of additional dissection. The axillary lymph node recurrence rate was 0.8 % for luminal and 4.5 % for TN subtypes. The long-term prognoses of patients for whom dissection was omitted owing to negative sentinel lymph node metastases were similar to those reported previously-low recurrence and mortality rates. The frequency of axillary lymph node recurrence and the post-recurrence outcome differed between luminal and TN cases, with recurrence being more frequent in patients with the TN subtype. TN patients also had poorer prognoses, even after receiving additional dissection and anticancer agents after recurrence.

Outcome following sentinel lymph node biopsy-guided decisions in breast cancer patients with conversion from positive to negative axillary lymph nodes after neoadjuvant chemotherapy.

PubMed

Kang, Young-Joon; Han, Wonshik; Park, Soojin; You, Ji Young; Yi, Ha Woo; Park, Sungmin; Nam, Sanggeun; Kim, Joo Heung; Yun, Keong Won; Kim, Hee Jeong; Ahn, Sei Hyun; Park, Seho; Lee, Jeong Eon; Lee, Eun Sook; Noh, Dong-Young; Lee, Jong Won

2017-11-01

Many breast cancer patients with positive axillary lymph nodes achieve complete node remission after neoadjuvant chemotherapy. The usefulness of sentinel lymph node biopsy in this situation is uncertain. This study evaluated the outcomes of sentinel biopsy-guided decisions in patients who had conversion of axillary nodes from clinically positive to negative following neoadjuvant chemotherapy. We reviewed the records of 1247 patients from five hospitals in Korea who had breast cancer with clinically axillary lymph node-positive status and negative conversion after neoadjuvant chemotherapy, between 2005 and 2012. Patients who underwent axillary operations with sentinel biopsy-guided decisions (Group A) were compared with patients who underwent complete axillary lymph node dissection without sentinel lymph node biopsy (Group B). Axillary node recurrence and distant recurrence-free survival were compared. There were 428 cases in Group A and 819 in Group B. Kaplan-Meier analysis showed that recurrence-free survivals were not significantly different between Groups A and B (4-year axillary recurrence-free survival: 97.8 vs. 99.0%; p = 0.148). Multivariate analysis also indicated the two groups had no significant difference in axillary and distant recurrence-free survival. For breast cancer patients who had clinical conversion of axillary lymph nodes from positive to negative following neoadjuvant chemotherapy, sentinel biopsy-guided axillary surgery, and axillary lymph node dissection without sentinel lymph node biopsy had similar rates of recurrence. Thus, sentinel biopsy-guided axillary operation in breast cancer patients who have clinically axillary lymph node positive to negative conversion following neoadjuvant chemotherapy is a useful strategy.

Lymph node detection in IASLC-defined zones on PET/CT images

NASA Astrophysics Data System (ADS)

Song, Yihua; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Torigian, Drew A.

2016-03-01

Lymph node detection is challenging due to the low contrast between lymph nodes as well as surrounding soft tissues and the variation in nodal size and shape. In this paper, we propose several novel ideas which are combined into a system to operate on positron emission tomography/ computed tomography (PET/CT) images to detect abnormal thoracic nodes. First, our previous Automatic Anatomy Recognition (AAR) approach is modified where lymph node zones predominantly following International Association for the Study of Lung Cancer (IASLC) specifications are modeled as objects arranged in a hierarchy along with key anatomic anchor objects. This fuzzy anatomy model built from diagnostic CT images is then deployed on PET/CT images for automatically recognizing the zones. A novel globular filter (g-filter) to detect blob-like objects over a specified range of sizes is designed to detect the most likely locations and sizes of diseased nodes. Abnormal nodes within each automatically localized zone are subsequently detected via combined use of different items of information at various scales: lymph node zone model poses found at recognition indicating the geographic layout at the global level of node clusters, g-filter response which hones in on and carefully selects node-like globular objects at the node level, and CT and PET gray value but within only the most plausible nodal regions for node presence at the voxel level. The models are built from 25 diagnostic CT scans and refined for an object hierarchy based on a separate set of 20 diagnostic CT scans. Node detection is tested on an additional set of 20 PET/CT scans. Our preliminary results indicate node detection sensitivity and specificity at around 90% and 85%, respectively.

Subcarinal lymph node in upper lobe non-small cell lung cancer patients: is selective lymph node dissection valid?

PubMed

Aokage, Keiju; Yoshida, Junji; Ishii, Genichiro; Hishida, Tomoyuki; Nishimura, Mitsuyo; Nagai, Kanji

2010-11-01

Little is known about selective lymph node dissection in non-small cell lung cancer (NSCLC) patients. We sought to gain insight into subcarinal node involvement for its frequency and impact on outcome to evaluate whether it is valid to omit subcarinal lymph node dissection in upper lobe NSCLC patients. We reviewed node metastases distribution according to node region, tumor location, and histology among 1099 patients with upper lobe NSCLC. We paid special attention to subcarinal metastases patients without superior mediastinal node metastases, because their pathological stages would have been underdiagnosed if subcarinal node dissection had been omitted. We also assessed the outcome and the pattern of failure among subcarinal metastases patients. To identify subcarinal node involvement predictors, we analyzed 7 clinical factors. Subcarinal node metastases were found in 20 patients and were least frequent among squamous cell carcinoma patients (0.5%). Two of them were free from superior mediastinal metastases but died of the disease at 1 month and due to an unknown cause at 18 months, respectively. Seventeen of the 20 patients developed multi-site recurrence within 37 months. The 5-year survival rate of the 20 patients with subcarinal metastases was 9.0%, which was significantly lower than 32.0% of patients with only superior mediastinal metastases. Clinical diagnosis of node metastases was significantly predictive of subcarinal metastases. Subcarinal node metastases from upper lobe NSCLC were rare and predicted an extremely poor outcome. It appears valid to omit subcarinal node dissection in upper lobe NSCLC patients, especially in clinical N0 squamous cell carcinoma patients. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Lymph Node Yield as a Predictor of Survival in Pathologically Node Negative Oral Cavity Carcinoma.

PubMed

Lemieux, Aaron; Kedarisetty, Suraj; Raju, Sharat; Orosco, Ryan; Coffey, Charles

2016-03-01

Even after a pathologically node-negative (pN0) neck dissection for oral cavity squamous cell carcinoma (SCC), patients may develop regional recurrence. In this study, we (1) hypothesize that an increased number of lymph nodes removed (lymph node yield) in patients with pN0 oral SCC predicts improved survival and (2) explore predictors of survival in these patients using a multivariable model. Case series with chart review. Administrative database analysis. The SEER database was queried for patients diagnosed with all-stage oral cavity SCC between 1988 and 2009 who were determined to be pN0 after elective lymph node dissection. Demographic and treatment variables were extracted. The association of lymph node yield with 5-year all-cause survival was studied with multivariable survival analyses. A total of 4341 patients with pN0 oral SCC were included in this study. The 2 highest lymph node yield quartiles (representing >22 nodes removed) were found to be significant predictors of overall survival (22-35 nodes: hazard ratio [HR] = 0.854, P = .031; 36-98 nodes: HR = 0.827, P = .010). Each additional lymph node removed during neck dissection was associated with increased survival (HR = 0.995, P = .022). These data suggest that patients with oral SCC undergoing elective neck dissection may experience an overall survival benefit associated with greater lymph node yield. Mechanisms behind the demonstrated survival advantage are unknown. Larger nodal dissections may remove a greater burden of microscopic metastatic disease, diminishing the likelihood of recurrence. Lymph node yield may serve as an objective measure of the adequacy of lymphadenectomy. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Sentinel node biopsy in thin and thick melanoma.

PubMed

Mozzillo, Nicola; Pennacchioli, Elisabetta; Gandini, Sara; Caracò, Corrado; Crispo, Anna; Botti, Gerardo; Lastoria, Secondo; Barberis, Massimo; Verrecchia, Francesco; Testori, Alessandro

2013-08-01

Although sentinel node biopsy (SNB) has become standard of care in patients with melanoma, its use in patients with thin or thick melanomas remains a matter of debate. This was a retrospective analysis of patients with thin (≤1 mm) or thick (≥4 mm) melanomas who underwent SNB at two Italian centers between 1998 and 2011. The associations of clinicopathologic features with sentinel lymph node positive status and overall survival (OS) were analyzed. In 492 patients with thin melanoma, sentinel node was positive for metastatic melanoma in 24 (4.9 %) patients. No sentinel node positivity was detected in patients with primary tumor thickness <0.3 mm. Mitotic rate was the only factor significantly associated with sentinel node positivity (p = 0.0001). Five-year OS was 81 % for patients with positive sentinel node and 93 % for negative sentinel node (p = 0.001). In 298 patients with thick melanoma, 39 % of patients had positive sentinel lymph nodes (median Breslow thickness 5 mm). In patients with positive sentinel node, 93 % had mitotic rate >1/mm(2). Five-year OS was 49 % for patients with positive sentinel lymph nodes and 56 % for patients with negative sentinel nodes (p = 0.005). The rate of sentinel node positivity in patients with thin melanoma was 4.9 %. The only clinicopathologic factor related to node positivity was mitotic rate. Given its prognostic importance, SNB should be considered in such patients. SNB should also be the standard method for melanoma ≥4 mm, not only for staging, but also for guiding therapeutic decisions.

Impact of false-negative sentinel lymph node biopsy on survival in patients with cutaneous melanoma.

PubMed

Caracò, C; Marone, U; Celentano, E; Botti, G; Mozzillo, N

2007-09-01

Sentinel lymph node biopsy is widely accepted as standard care in melanoma despite lack of pertinent randomized trials results. A possible pitfall of this procedure is the inaccurate identification of the sentinel lymph node leading to biopsy and analysis of a nonsentinel node. Such a technical failure may yield a different prognosis. The purpose of this study is to analyze the incidence of false negativity and its impact on clinical outcome and to try to understand its causes. The Melanoma Data Base at National Cancer Institute of Naples was analyzed comparing results between false-negative and tumor-positive sentinel node patients focusing on overall survival and prognostic factors influencing the clinical outcome. One hundred fifty-one cases were diagnosed to be tumor-positive after sentinel lymph node biopsy and were subjected to complete lymph node dissection. Thirty-four (18.4%)patients with tumor-negative sentinel node subsequently developed lymph node metastases in the basin site of the sentinel procedure. With a median follow-up of 42.8 months the 5-year overall survival was 48.4% and 66.3% for false-negative and tumor-positive group respectively with significant statistical differences (P < .03). The sensitivity of sentinel lymph node biopsy was 81.6%, and a regional nodal basin recurrence after negative-sentinel node biopsy means a worse prognosis, compared with patients submitted to complete lymph node dissection after a positive sentinel biopsy. The evidence of higher number of tumor-positive nodes after delayed lymphadenectomy in false-negative group compared with tumor-positive sentinel node cases, confirmed the importance of an early staging of lymph nodal involvement. Further data will better clarify the role of prognostic factors to identify cases with a more aggressive biological behavior of the disease.

Potential role for carbon nanoparticles to guide central neck dissection in patients with papillary thyroid cancer.

PubMed

Yu, Wenbin; Cao, XiaoLi; Xu, Guihu; Song, Yuntao; Li, Guojun; Zheng, Hongliang; Zhang, Naisong

2016-09-01

The purpose of this study was to investigate the use and clinical utility of carbon nanoparticles as a lymph node tracer in the central neck lymph node dissection of patients with papillary thyroid cancer. One hundred forty consecutive patients were divided into a carbon nanoparticle group (n = 70) and a control group (n = 70). All patients underwent total or near-total thyroidectomy with bilateral central neck dissection. The carbon nanoparticle and control groups had different rates of metastatic lymph nodes (P = .017), total detected numbers of lymph nodes (P = .0001), total numbers of dissected lymph nodes <5 mm (P = .0001), and numbers of metastatic lymph nodes <5 mm (P = .0001). Of the 682 lymph nodes dissected in the carbon nanoparticle group, 579 (85%) were stained black, and of these, 147 (25%) were metastatic lymph nodes. There were 63 metastatic lymph nodes <5 mm among the black-stained metastatic lymph nodes, while there were 12 non-black-stained metastatic lymph nodes <5 mm. Of the total number of metastatic lymph nodes (n = 193), 147 (76%) were stained black. Moreover, pathologic results revealed that 5 accidental parathyroid resections occurred in the carbon nanoparticle group, compared with 14 in the control group (P = .046). Carbon nanoparticles might help to detect lymph nodes and increase the number of metastatic lymph nodes visualized and preserved. Therefore, use of carbon nanoparticles may reflect the metastatic condition of the central neck and have the potential to protect parathyroid glands. Copyright © 2016 Elsevier Inc. All rights reserved.

Mediastinal lymph node detection and station mapping on chest CT using spatial priors and random forest

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

Liu, Jiamin; Hoffman, Joanne; Zhao, Jocelyn

2016-07-15

Purpose: To develop an automated system for mediastinal lymph node detection and station mapping for chest CT. Methods: The contextual organs, trachea, lungs, and spine are first automatically identified to locate the region of interest (ROI) (mediastinum). The authors employ shape features derived from Hessian analysis, local object scale, and circular transformation that are computed per voxel in the ROI. Eight more anatomical structures are simultaneously segmented by multiatlas label fusion. Spatial priors are defined as the relative multidimensional distance vectors corresponding to each structure. Intensity, shape, and spatial prior features are integrated and parsed by a random forest classifiermore » for lymph node detection. The detected candidates are then segmented by the following curve evolution process. Texture features are computed on the segmented lymph nodes and a support vector machine committee is used for final classification. For lymph node station labeling, based on the segmentation results of the above anatomical structures, the textual definitions of mediastinal lymph node map according to the International Association for the Study of Lung Cancer are converted into patient-specific color-coded CT image, where the lymph node station can be automatically assigned for each detected node. Results: The chest CT volumes from 70 patients with 316 enlarged mediastinal lymph nodes are used for validation. For lymph node detection, their system achieves 88% sensitivity at eight false positives per patient. For lymph node station labeling, 84.5% of lymph nodes are correctly assigned to their stations. Conclusions: Multiple-channel shape, intensity, and spatial prior features aggregated by a random forest classifier improve mediastinal lymph node detection on chest CT. Using the location information of segmented anatomic structures from the multiatlas formulation enables accurate identification of lymph node stations.« less

A Distributed and Energy-Efficient Algorithm for Event K-Coverage in Underwater Sensor Networks.

PubMed

Jiang, Peng; Xu, Yiming; Liu, Jun

2017-01-19

For event dynamic K-coverage algorithms, each management node selects its assistant node by using a greedy algorithm without considering the residual energy and situations in which a node is selected by several events. This approach affects network energy consumption and balance. Therefore, this study proposes a distributed and energy-efficient event K-coverage algorithm (DEEKA). After the network achieves 1-coverage, the nodes that detect the same event compete for the event management node with the number of candidate nodes and the average residual energy, as well as the distance to the event. Second, each management node estimates the probability of its neighbor nodes' being selected by the event it manages with the distance level, the residual energy level, and the number of dynamic coverage event of these nodes. Third, each management node establishes an optimization model that uses expectation energy consumption and the residual energy variance of its neighbor nodes and detects the performance of the events it manages as targets. Finally, each management node uses a constrained non-dominated sorting genetic algorithm (NSGA-II) to obtain the Pareto set of the model and the best strategy via technique for order preference by similarity to an ideal solution (TOPSIS). The algorithm first considers the effect of harsh underwater environments on information collection and transmission. It also considers the residual energy of a node and a situation in which the node is selected by several other events. Simulation results show that, unlike the on-demand variable sensing K-coverage algorithm, DEEKA balances and reduces network energy consumption, thereby prolonging the network's best service quality and lifetime.

Use of Indocyanine Green for Sentinel Lymph Node Biopsy: Case Series and Methods Comparison.

PubMed

McGregor, Andrew; Pavri, Sabrina N; Tsay, Cynthia; Kim, Samuel; Narayan, Deepak

2017-11-01

Sentinel lymph node biopsy is indicated for patients with biopsy-proven thickness melanoma greater than 1.0 mm. Use of lymphoscintigraphy along with vital blue dyes is the gold standard for identifying sentinel lymph nodes intraoperatively. Indocyanine green (ICG) has recently been used as a method of identifying sentinel lymph nodes. We herein describe a case series of patients who have successfully undergone ICG-assisted sentinel lymph node biopsy for melanoma. We compare 2 imaging systems that are used for ICG-assisted sentinel lymph node biopsy. Fourteen patients underwent ICG-assisted sentinel lymph node biopsy for melanoma using the SPY Elite system (Novadaq, Mississigua, Canada) and the Hamamatsu PDE-Neo probe system (Mitaka USA, Park City, Utah). We analyzed costs for 2 systems that utilize ICG for sentinel lymph node biopsies. Intraoperative use of ICG for sentinel lymph node biopsies was successful in correctly identifying sentinel lymph nodes. There was no difference between the Hamamatsu PDE-Neo probe and SPY Elite systems in the ability to detect sentinel lymph nodes; however, the former was associated with a lower operating cost and ease of use compared with the latter. ICG-assisted sentinel lymph biopsy using the SPY Elite or the Hamamatsu PDE-Neo probe systems for melanoma are comparable in terms of sentinel node detection. The Neo probe system delivers pertinent clinical data with the advantages of lower cost and ease of operation.

Surgical management of sentinel lymph node biopsy outside major nodal basin in patients with cutaneous melanoma.

PubMed

Caracò, Corrado; Marone, Ugo; Di Monta, Gianluca; Aloj, Luigi; Caracò, Corradina; Anniciello, Annamaria; Lastoria, Secondo; Botti, Gerardo; Mozzillo, Nicola

2014-01-01

To assess the incidence of nonmajor lymphatic basin sentinel nodes in patients with cutaneous melanoma in order to propose a correct nomenclature and inform appropriate surgical management. This was a retrospective review of 1,045 consecutive patients with cutaneous melanoma who underwent sentinel lymph node biopsy and dynamic lymphoscintigraphy to identify sentinel node site. Nonmajor drainage sites were classified as uncommon (located in a minor lymphatic basin along the lymphatic drainage to a major classical nodal basin) or interval (located anywhere along the lymphatics between the primary tumor site and the nearest lymphatic basin) sentinel nodes. Nonclassical sentinel nodes were identified in 32 patients (3.0 %). Uncommon sentinel nodes were identified in 3.2 % (n = 17) of trunk melanoma primary disease and in 1.5 % (n = 7) of upper and lower extremity sites. Interval sentinel nodes were identified in 1.3 % (n = 7) of trunk primary lesions, with none from upper and lower extremities melanomas. The incidence of tumor-positive sentinel nodes was 24.1 % (245 of 1,013) in classical sites and 12.5 % (4 of 32) in uncommon/interval sites. The definition of uncommon and interval sentinel nodes allows the identification of different lymphatic pathways and inform appropriate surgical treatment. Wider experience with uncommon/interval sentinel nodes will better clarify the clinical implications and surgical management to be adopted in the management of uncommon and interval sentinel node sites.

High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes.

PubMed

Walk, Elyse L; McLaughlin, Sarah L; Weed, Scott A

2015-07-25

High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal systems. HFUS has the ability to detect structures as small as 30 µm, a property that has been utilized for visualizing superficial lymph nodes in rodents in brightness (B)-mode. Combining power Doppler with B-mode imaging allows for measuring circulatory blood flow within lymph nodes and other organs. While HFUS has been utilized for lymph node imaging in a number of mouse  model systems, a detailed protocol describing HFUS imaging and characterization of the cervical lymph nodes in mice has not been reported. Here, we show that HFUS can be adapted to detect and characterize cervical lymph nodes in mice. Combined B-mode and power Doppler imaging can be used to detect increases in blood flow in immunologically-enlarged cervical nodes. We also describe the use of B-mode imaging to conduct fine needle biopsies of cervical lymph nodes to retrieve lymph tissue for histological  analysis. Finally, software-aided steps are described to calculate changes in lymph node volume and to visualize changes in lymph node morphology following image reconstruction. The ability to visually monitor changes in cervical lymph node biology over time provides a simple and powerful technique for the non-invasive monitoring of cervical lymph node alterations in preclinical mouse models of oral cavity disease.

A mathematical prediction model incorporating molecular subtype for risk of non-sentinel lymph node metastasis in sentinel lymph node-positive breast cancer patients: a retrospective analysis and nomogram development.

PubMed

Wang, Na-Na; Yang, Zheng-Jun; Wang, Xue; Chen, Li-Xuan; Zhao, Hong-Meng; Cao, Wen-Feng; Zhang, Bin

2018-04-25

Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017 at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025-2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111-23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714-3.892; P < 0.001), and the number of negative sentinel lymph nodes (OR = 0.686, 95% CI 0.575-0.817; P < 0.001) were independent statistically significant predictors of non-sentinel lymph node metastasis. Furthermore, luminal B (OR = 3.311, 95% CI 1.593-6.884; P = 0.001) and HER2 overexpression (OR = 4.308, 95% CI 1.097-16.912; P = 0.036) were independent and statistically significant predictor of non-sentinel lymph node metastasis versus luminal A. A regression model based on the results of multivariate analysis was established to predict the risk of non-sentinel lymph node metastasis, which had an AUC of 0.8188. The model was validated in the validation cohort and showed excellent diagnostic performance. The mathematical prediction model that incorporates five variables including breast cancer molecular subtype demonstrates excellent diagnostic performance in assessing the risk of non-sentinel lymph node metastasis in sentinel lymph node-positive patients. The prediction model could be of help surgeons in evaluating the risk of non-sentinel lymph node involvement for breast cancer patients; however, the model requires further validation in prospective studies.

Compression in wearable sensor nodes: impacts of node topology.

PubMed

Imtiaz, Syed Anas; Casson, Alexander J; Rodriguez-Villegas, Esther

2014-04-01

Wearable sensor nodes monitoring the human body must operate autonomously for very long periods of time. Online and low-power data compression embedded within the sensor node is therefore essential to minimize data storage/transmission overheads. This paper presents a low-power MSP430 compressive sensing implementation for providing such compression, focusing particularly on the impact of the sensor node architecture on the compression performance. Compression power performance is compared for four different sensor nodes incorporating different strategies for wireless transmission/on-sensor-node local storage of data. The results demonstrate that the compressive sensing used must be designed differently depending on the underlying node topology, and that the compression strategy should not be guided only by signal processing considerations. We also provide a practical overview of state-of-the-art sensor node topologies. Wireless transmission of data is often preferred as it offers increased flexibility during use, but in general at the cost of increased power consumption. We demonstrate that wireless sensor nodes can highly benefit from the use of compressive sensing and now can achieve power consumptions comparable to, or better than, the use of local memory.

Method for designing gas tag compositions

DOEpatents

Gross, K.C.

1995-04-11

For use in the manufacture of gas tags such as employed in a nuclear reactor gas tagging failure detection system, a method for designing gas tagging compositions utilizes an analytical approach wherein the final composition of a first canister of tag gas as measured by a mass spectrometer is designated as node No. 1. Lattice locations of tag nodes in multi-dimensional space are then used in calculating the compositions of a node No. 2 and each subsequent node so as to maximize the distance of each node from any combination of tag components which might be indistinguishable from another tag composition in a reactor fuel assembly. Alternatively, the measured compositions of tag gas numbers 1 and 2 may be used to fix the locations of nodes 1 and 2, with the locations of nodes 3-N then calculated for optimum tag gas composition. A single sphere defining the lattice locations of the tag nodes may be used to define approximately 20 tag nodes, while concentric spheres can extend the number of tag nodes to several hundred. 5 figures.

System and method for time synchronization in a wireless network

DOEpatents

Gonia, Patrick S.; Kolavennu, Soumitri N.; Mahasenan, Arun V.; Budampati, Ramakrishna S.

2010-03-30

A system includes multiple wireless nodes forming a cluster in a wireless network, where each wireless node is configured to communicate and exchange data wirelessly based on a clock. One of the wireless nodes is configured to operate as a cluster master. Each of the other wireless nodes is configured to (i) receive time synchronization information from a parent node, (ii) adjust its clock based on the received time synchronization information, and (iii) broadcast time synchronization information based on the time synchronization information received by that wireless node. The time synchronization information received by each of the other wireless nodes is based on time synchronization information provided by the cluster master so that the other wireless nodes substantially synchronize their clocks with the clock of the cluster master.

Broadcasting collective operation contributions throughout a parallel computer

DOEpatents

Faraj, Ahmad [Rochester, MN

2012-02-21

Methods, systems, and products are disclosed for broadcasting collective operation contributions throughout a parallel computer. The parallel computer includes a plurality of compute nodes connected together through a data communications network. Each compute node has a plurality of processors for use in collective parallel operations on the parallel computer. Broadcasting collective operation contributions throughout a parallel computer according to embodiments of the present invention includes: transmitting, by each processor on each compute node, that processor's collective operation contribution to the other processors on that compute node using intra-node communications; and transmitting on a designated network link, by each processor on each compute node according to a serial processor transmission sequence, that processor's collective operation contribution to the other processors on the other compute nodes using inter-node communications.

Shaper design in CMOS for high dynamic range

DOEpatents

De Geronimo, Gianluigi; Li, Shaorui

2015-06-30

An analog filter is presented that comprises a chain of filter stages, a feedback resistor for providing a negative feedback, and a feedback capacitor for providing a positive feedback. Each filter stage has an input node and an output node. The output node of a filter stage is connected to the input node of an immediately succeeding filter stage through a resistor. The feedback resistor has a first end connected to the output node of the last filter stage along the chain of filter stages, and a second end connected to the input node of a first preceding filter stage. The feedback capacitor has a first end connected to the output node of one of the chain of filter stages, and a second end connected to the input node of a second preceding filter stage.

History, present status and future of sentinel node biopsy in breast cancer. The Mary Béves Lecture.

PubMed

Mansel, R E; Khonji, N I; Clarke, D

2000-01-01

The word Sentinel' is defined in The Oxford English Dictionary as 'a guard, one who keeps watch or a sentry'. When translated to the concept of a tumour and its lymph node drainage, the sentinel node could be interpreted to mean the lymph node that guards or keeps watch over a tumour. The sentinel lymph node can thus be defined as the first lymph node that drains a primary tumour within the regional lymphatic basin of that tumour. We know that tumour progression in breast cancer often occurs in an orderly, progressive fashion. So in theory, if the sentinel node is tumour free then the rest of the nodes in the lymphatic basin should also be uninvolved by the tumour.

Parallel-aware, dedicated job co-scheduling within/across symmetric multiprocessing nodes

DOEpatents

Jones, Terry R.; Watson, Pythagoras C.; Tuel, William; Brenner, Larry; ,Caffrey, Patrick; Fier, Jeffrey

2010-10-05

In a parallel computing environment comprising a network of SMP nodes each having at least one processor, a parallel-aware co-scheduling method and system for improving the performance and scalability of a dedicated parallel job having synchronizing collective operations. The method and system uses a global co-scheduler and an operating system kernel dispatcher adapted to coordinate interfering system and daemon activities on a node and across nodes to promote intra-node and inter-node overlap of said interfering system and daemon activities as well as intra-node and inter-node overlap of said synchronizing collective operations. In this manner, the impact of random short-lived interruptions, such as timer-decrement processing and periodic daemon activity, on synchronizing collective operations is minimized on large processor-count SPMD bulk-synchronous programming styles.

Centrally managed unified shared virtual address space

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

Wilkes, John

Systems, apparatuses, and methods for managing a unified shared virtual address space. A host may execute system software and manage a plurality of nodes coupled to the host. The host may send work tasks to the nodes, and for each node, the host may externally manage the node's view of the system's virtual address space. Each node may have a central processing unit (CPU) style memory management unit (MMU) with an internal translation lookaside buffer (TLB). In one embodiment, the host may be coupled to a given node via an input/output memory management unit (IOMMU) interface, where the IOMMU frontendmore » interface shares the TLB with the given node's MMU. In another embodiment, the host may control the given node's view of virtual address space via memory-mapped control registers.« less

A prospective single-center study of sentinel lymph node detection in cervical carcinoma: is there a place in clinical practice?

PubMed

Devaja, Omer; Mehra, Gautam; Coutts, Michael; Montalto, Stephen Attard; Donaldson, John; Kodampur, Mallikarjun; Papadopoulos, Andreas John

2012-07-01

To establish the accuracy of sentinel lymph node (SLN) detection in early cervical cancer. Sentinel lymph node detection was performed prospectively over a 6-year period in 86 women undergoing surgery for cervical carcinoma by the combined method (Tc-99m and methylene blue dye). Further ultrastaging was performed on a subgroup of 26 patients who had benign SLNs on initial routine histological examination. The SLN was detected in 84 (97.7%) of 86 women by the combined method. Blue dye uptake was not seen in 8 women (90.7%). Sentinel lymph nodes were detected bilaterally in 63 women (73.3%), and the external iliac region was the most common anatomic location (48.8%). The median SLN count was 3 nodes (range, 1-7). Of the 84 women with sentinel node detection, 65 also underwent bilateral pelvic lymph node dissection, and in none of these cases was a benign SLN associated with a malignant non-SLN (100% negative predictive value). The median non-SLN count for all patients was 19 nodes (range, 8-35). Eighteen patients underwent removal of the SLN without bilateral pelvic lymph node dissection. Nine women (10.5%) had positive lymph nodes on final histology. One patient had bulky pelvic nodes on preoperative imaging and underwent removal of the negative bulky malignant lymph nodes and a benign SLN on the contralateral side. This latter case confirms the unreliability of the SLN method with bulky nodes. The remaining 8 patients had positive SLNs with negative nonsentinel lymph nodes. Fifty-nine SLNs from 26 patients, which were benign on initial routine histology, underwent ultrastaging, but no further disease was identified. Four patients (5%) relapsed after a median follow-up of 28 months (range, 8-80 months). Sentinel lymph node detection is an accurate and safe method in the assessment of nodal status in early cervical carcinoma.

The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer.

PubMed

Mikosiński, Sławomir; Pomorski, Lech; Oszukowska, Lidia; Makarewicz, Jacek; Adamczewski, Zbigniew; Sporny, Stanisław; Lewiński, Andrzej

2006-01-01

Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes. The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94-100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology. Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology. 1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes in patients with differentiated thyroid cancer.

Message propagation in the network based on node credibility

NASA Astrophysics Data System (ADS)

Nian, Fuzhong; Dang, Zhongkai

2018-04-01

In the propagation efficiency point of view, the node credibility is introduced in this paper. For the message receiver, the node would partially believe the message according to the credibility of the propagator. For a node, the credibility is variable. The more the true message spread, the higher the credibility, and vice versa, the credibility becomes smaller. Based on the idea, a new network was established with the node credibility. Finally, a comparing experiment between the fully trusted network and the network with the node credibility was implemented. The results indicate that the spread effect of messages is better in the network with the node credibility.

The broadcast classical-quantum capacity region of a two-phase bidirectional relaying channel

NASA Astrophysics Data System (ADS)

Boche, Holger; Cai, Minglai; Deppe, Christian

2015-10-01

We studied a three-node quantum network that enables bidirectional communication between two nodes with a half-duplex relay node for transmitting classical messages. A decode-and-forward protocol is used to perform the communication in two phases. In the first phase, the messages of two nodes are transmitted to the relay node. The capacity of the first phase is well known by previous works. In the second phase, the relay node broadcasts a re-encoded composition to the two nodes. We determine the capacity region of the broadcast phase. To the best of our knowledge, this is the first paper analyzing quantum bidirectional relay networks.

Swollen lymph nodes

MedlinePlus

... lymph nodes, including: Seizure medicines such as phenytoin Typhoid immunization Which lymph nodes are swollen depends on ... hard, irregular, or fixed in place. You have fever, night sweats, or unexplained weight loss. Any node ...

Lymph Node Size on Computed Tomography Images Is a Predictive Indicator for Lymph Node Metastasis in Patients with Colorectal Neuroendocrine Tumors.

PubMed

Tanaka, Toshiaki; Nozawa, Hiroaki; Kawai, Kazushige; Hata, Keisuke; Kiyomatsu, Tomomichi; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Murono, Koji; Watanabe, Toshiaki

2017-01-01

Colorectal neuroendocrine tumors (NET) are a rare manifestation of colorectal neoplasia, requiring for radical dissection of the regional lymph nodes along with colorectal resection similar to that required for colorectal cancer. However, thus far, no reports have described the ability of computed tomography (CT) to predict lymph node involvement. In this study, we revealed the prediction rate of lymph node metastasis using contrast-enhanced CT. A total of 21 patients with colorectal NET undergoing colorectal resection were recruited from January 2010 to June 2016. We compared the CT findings between samples with or without pathologically proven lymph node metastasis, in each field (pericolic/perirectal and intermediate nodes). Within the pericolic/perirectal field, any lymph node larger than 5 mm in the CT images was a predictive indicator of lymph node metastasis with a sensitivity, specificity, and area under ROC curve (AUC) of 66.7%, 87.5%, and 0.844, respectively. Within the intermediate field, any visible lymph node on the CT was a predictive indicator of lymph node metastasis with a sensitivity, specificity, and AUC of 100%, 76.4%, and 0.890, respectively. In addition, when we observed lymph nodes larger than 3 mm on the CT images, the sensitivity and specificity were 100% and 82.4%, respectively, with an AUC of 0.8971. CT images provide predictive information for lymph node metastasis with a high rate of accuracy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

BridgeRank: A novel fast centrality measure based on local structure of the network

NASA Astrophysics Data System (ADS)

Salavati, Chiman; Abdollahpouri, Alireza; Manbari, Zhaleh

2018-04-01

Ranking nodes in complex networks have become an important task in many application domains. In a complex network, influential nodes are those that have the most spreading ability. Thus, identifying influential nodes based on their spreading ability is a fundamental task in different applications such as viral marketing. One of the most important centrality measures to ranking nodes is closeness centrality which is efficient but suffers from high computational complexity O(n3) . This paper tries to improve closeness centrality by utilizing the local structure of nodes and presents a new ranking algorithm, called BridgeRank centrality. The proposed method computes local centrality value for each node. For this purpose, at first, communities are detected and the relationship between communities is completely ignored. Then, by applying a centrality in each community, only one best critical node from each community is extracted. Finally, the nodes are ranked based on computing the sum of the shortest path length of nodes to obtained critical nodes. We have also modified the proposed method by weighting the original BridgeRank and selecting several nodes from each community based on the density of that community. Our method can find the best nodes with high spread ability and low time complexity, which make it applicable to large-scale networks. To evaluate the performance of the proposed method, we use the SIR diffusion model. Finally, experiments on real and artificial networks show that our method is able to identify influential nodes so efficiently, and achieves better performance compared to other recent methods.

Predictors of sentinel lymph node metastases in breast cancer-radioactivity and Ki-67.

PubMed

Thangarajah, Fabinshy; Malter, Wolfram; Hamacher, Stefanie; Schmidt, Matthias; Krämer, Stefan; Mallmann, Peter; Kirn, Verena

2016-12-01

Since the introduction of the sentinel node technique for breast cancer in the 1990s patient's morbidity was reduced. Tracer uptake is known to be dependent from lymph node integrity and activity of macrophages. The aim of this study was to assess whether radioactivity of the tracer can predict sentinel lymph node metastases. Furthermore, a potential association with Ki-67 index was examined. Non-invasive prediction of lymph node metastases could lead to a further decrease of morbidity. We retrospectively analyzed patients with primary breast cancer who underwent surgery at the Department of Obstetrics and Gynecology in the University Hospital of Cologne between 2012 and 2013. Injection of radioactive tracer was done a day before surgery in the department of Nuclear Medicine. Clinical data and radioactivity of the sentinel node measured the day before and intraoperatively were abstracted from patient's files. Of 246 patients, 64 patients had at least one, five patients had two and one patient had three positive sentinel lymph nodes. Occurrence of sentinel lymph node metastases was not associated with preoperative tracer activity (p = 0,319), intraoperative tracer activity of first sentinel node (p = 0,086) or with loss of tracer activity until operation (p = 0,909). There was no correlation between preoperative Ki-67 index and occurrence of lymph node metastases (p = 0,403). In our cohort, there was no correlation between radioactivity and sentinel node metastases. Tracer uptake might not only be influenced by lymph node metastases and does not predict metastatic lymph node involvement. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vitro autoradiographic localization of angiotensin-converting enzyme in sarcoid lymph nodes

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

Allen, R.K.; Chai, S.Y.; Dunbar, M.S.

1986-09-01

Angiotensin-converting enzyme (ACE) was localized in sarcoid lymph nodes by an in vitro autoradiographic technique using a synthetic ACE inhibitor of high affinity, /sup 125/I-labelled 351A. The lymph nodes were from seven patients with active sarcoidosis who underwent mediastinoscopy and from six control subjects who had nodes resected at either mediastinoscopy or laparotomy. Angiotensin-converting enzyme was localized in the epithelioid cells of sarcoid granulomata in markedly increased amounts compared with control nodes, where it was restricted to vessels and some histiocytes. In sarcoid lymph nodes, there was little ACE present in lymphocytes or fibrous tissue. Sarcoid nodes with considerable fibrosismore » had much less intense ACE activity than the nonfibrotic nodes. The specific activity of ACE measured by an enzymatic assay in both the control and sarcoid lymph nodes closely reflected the ACE activity demonstrated by autoradiography. Sarcoid lymph nodes with fibrosis had an ACE specific activity of half that of nonfibrotic nodes (p less than 0.05). There was a 15-fold increase in specific ACE activity in sarcoid nodes (p less than 0.05) compared to normal. Serum ACE was significantly higher in those sarcoid patients whose lymph nodes were not fibrosed compared with those with fibrosis (p less than 0.01). This technique offers many advantages over the use of polyclonal antibodies. The 351A is a highly specific ACE inhibitor, chemically defined and in limitless supply. This method enables the quantitation of results, and autoradiographs may be stored indefinitely for later comparison.« less

An Algorithm for Timely Transmission of Solicitation Messages in RPL for Energy-Efficient Node Mobility.

PubMed

Park, Jihong; Kim, Ki-Hyung; Kim, Kangseok

2017-04-19

The IPv6 Routing Protocol for Low Power and Lossy Networks (RPL) was proposed for various applications of IPv6 low power wireless networks. While RPL supports various routing metrics and is designed to be suitable for wireless sensor network environments, it does not consider the mobility of nodes. Therefore, there is a need for a method that is energy efficient and that provides stable and reliable data transmission by considering the mobility of nodes in RPL networks. This paper proposes an algorithm to support node mobility in RPL in an energy-efficient manner and describes its operating principle based on different scenarios. The proposed algorithm supports the mobility of nodes by dynamically adjusting the transmission interval of the messages that request the route based on the speed and direction of the motion of mobile nodes, as well as the costs between neighboring nodes. The performance of the proposed algorithm and previous algorithms for supporting node mobility were examined experimentally. From the experiment, it was observed that the proposed algorithm requires fewer messages per unit time for selecting a new parent node following the movement of a mobile node. Since fewer messages are used to select a parent node, the energy consumption is also less than that of previous algorithms.

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience.

PubMed

Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R; Chagpar, Anees B; Killelea, Brigid K; Lannin, Donald R

2017-01-01

Background . Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods . Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results . At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion . Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient.

An Algorithm for Timely Transmission of Solicitation Messages in RPL for Energy-Efficient Node Mobility

PubMed Central

Park, Jihong; Kim, Ki-Hyung; Kim, Kangseok

2017-01-01

The IPv6 Routing Protocol for Low Power and Lossy Networks (RPL) was proposed for various applications of IPv6 low power wireless networks. While RPL supports various routing metrics and is designed to be suitable for wireless sensor network environments, it does not consider the mobility of nodes. Therefore, there is a need for a method that is energy efficient and that provides stable and reliable data transmission by considering the mobility of nodes in RPL networks. This paper proposes an algorithm to support node mobility in RPL in an energy-efficient manner and describes its operating principle based on different scenarios. The proposed algorithm supports the mobility of nodes by dynamically adjusting the transmission interval of the messages that request the route based on the speed and direction of the motion of mobile nodes, as well as the costs between neighboring nodes. The performance of the proposed algorithm and previous algorithms for supporting node mobility were examined experimentally. From the experiment, it was observed that the proposed algorithm requires fewer messages per unit time for selecting a new parent node following the movement of a mobile node. Since fewer messages are used to select a parent node, the energy consumption is also less than that of previous algorithms. PMID:28422084

The value of quantitative shear wave elastography in differentiating the cervical lymph nodes in patients with thyroid nodules.

PubMed

You, Jun; Chen, Juan; Xiang, Feixiang; Song, Yue; Khamis, Simai; Lu, Chengfa; Lv, Qing; Zhang, Yanrong; Xie, Mingxing

2018-04-01

This study aimed at evaluating the diagnostic performance of quantitative shear wave elastography (SWE) in differentiating metastatic cervical lymph nodes from benign nodes in patients with thyroid nodules. One hundred and forty-one cervical lymph nodes from 39 patients with thyroid nodules that were diagnosed as papillary thyroid cancer had been imaged with SWE. The shear elasticity modulus, which indicates the stiffness of the lymph nodes, was measured in terms of maximum shear elasticity modulus (maxSM), minimum shear elasticity modulus (minSM), mean shear elasticity modulus (meanSM), and standard deviation (SD) of the shear elasticity modulus. All the patients underwent thyroid surgery, 50 of the suspicious lymph nodes were resected, and 91 lymph nodes were followed up for 6 months. The maxSM value, minSM value, meanSM value, and SD value of the metastatic lymph nodes were significantly higher than those of the benign nodes. The area under the curve of the maxSM value, minSM value, meanSM value, and SD value were 0.918, 0.606, 0.865, and 0.915, respectively. SWE can differentiate metastasis from benign cervical lymph nodes in patients with thyroid nodules, and the maxSM, meanSM, and SD may be valuable quantitative indicators for characterizing cervical lymph nodes.

Sentinel lymph node detection in patients with endometrial cancer.

PubMed

Niikura, Hitoshi; Okamura, Chikako; Utsunomiya, Hiroki; Yoshinaga, Kosuke; Akahira, Junichi; Ito, Kiyoshi; Yaegashi, Nobuo

2004-02-01

The purpose of this study was to examine the feasibility of sentinel lymph node (SLN) detection in patients with endometrial cancer using preoperative lymphoscintigraphy and an intraoperative gamma probe. Between June 2001 and January 2003, 28 consecutive patients with endometrial cancer who were scheduled for total abdominal hysterectomy, bilateral salpingo-oophorectomy, total pelvic lymphadenectomy, and paraaortic lymphadenectomy at Tohoku University School of Medicine underwent sentinel lymph node detection. On the day before surgery, preoperative lymphoscintigraphy was performed by injection of 99m-Technetium ((99m)Tc)-labeled phytate into the endometrium during hysteroscopy. At the time of surgery, a gamma-detecting probe was used to locate radioactive lymph nodes. At least one sentinel node was detected in each of 23 of the 28 patients (82%). The mean number of sentinel nodes detected was 3.1 (range, 1-9). Sentinel nodes could be identified in 21 of 22 patients (95%) whose tumor did not invade more than halfway into the myometrium. Eighteen patients had radioactive nodes in the paraaortic area. Most patients had a sentinel node in one of the following three sites: paraaortic, external iliac, and obturator. The sensitivity and specificity for detecting lymph node metastases were both 100%. The combination of preoperative lymphoscintigraphy with intraoperative gamma probe detection may be useful in identifying sentinel nodes in early-stage endometrial cancer.

Concurrent hypercube system with improved message passing

NASA Technical Reports Server (NTRS)

Peterson, John C. (Inventor); Tuazon, Jesus O. (Inventor); Lieberman, Don (Inventor); Pniel, Moshe (Inventor)

1989-01-01

A network of microprocessors, or nodes, are interconnected in an n-dimensional cube having bidirectional communication links along the edges of the n-dimensional cube. Each node's processor network includes an I/O subprocessor dedicated to controlling communication of message packets along a bidirectional communication link with each end thereof terminating at an I/O controlled transceiver. Transmit data lines are directly connected from a local FIFO through each node's communication link transceiver. Status and control signals from the neighboring nodes are delivered over supervisory lines to inform the local node that the neighbor node's FIFO is empty and the bidirectional link between the two nodes is idle for data communication. A clocking line between neighbors, clocks a message into an empty FIFO at a neighbor's node and vica versa. Either neighbor may acquire control over the bidirectional communication link at any time, and thus each node has circuitry for checking whether or not the communication link is busy or idle, and whether or not the receive FIFO is empty. Likewise, each node can empty its own FIFO and in turn deliver a status signal to a neighboring node indicating that the local FIFO is empty. The system includes features of automatic message rerouting, block message transfer and automatic parity checking and generation.

An Autonomous Connectivity Restoration Algorithm Based on Finite State Machine for Wireless Sensor-Actor Networks.

PubMed

Zhang, Ying; Wang, Jun; Hao, Guan

2018-01-08

With the development of autonomous unmanned intelligent systems, such as the unmanned boats, unmanned planes and autonomous underwater vehicles, studies on Wireless Sensor-Actor Networks (WSANs) have attracted more attention. Network connectivity algorithms play an important role in data exchange, collaborative detection and information fusion. Due to the harsh application environment, abnormal nodes often appear, and the network connectivity will be prone to be lost. Network self-healing mechanisms have become critical for these systems. In order to decrease the movement overhead of the sensor-actor nodes, an autonomous connectivity restoration algorithm based on finite state machine is proposed. The idea is to identify whether a node is a critical node by using a finite state machine, and update the connected dominating set in a timely way. If an abnormal node is a critical node, the nearest non-critical node will be relocated to replace the abnormal node. In the case of multiple node abnormality, a regional network restoration algorithm is introduced. It is designed to reduce the overhead of node movements while restoration happens. Simulation results indicate the proposed algorithm has better performance on the total moving distance and the number of total relocated nodes compared with some other representative restoration algorithms.

An Autonomous Connectivity Restoration Algorithm Based on Finite State Machine for Wireless Sensor-Actor Networks

PubMed Central

Zhang, Ying; Wang, Jun; Hao, Guan

2018-01-01

With the development of autonomous unmanned intelligent systems, such as the unmanned boats, unmanned planes and autonomous underwater vehicles, studies on Wireless Sensor-Actor Networks (WSANs) have attracted more attention. Network connectivity algorithms play an important role in data exchange, collaborative detection and information fusion. Due to the harsh application environment, abnormal nodes often appear, and the network connectivity will be prone to be lost. Network self-healing mechanisms have become critical for these systems. In order to decrease the movement overhead of the sensor-actor nodes, an autonomous connectivity restoration algorithm based on finite state machine is proposed. The idea is to identify whether a node is a critical node by using a finite state machine, and update the connected dominating set in a timely way. If an abnormal node is a critical node, the nearest non-critical node will be relocated to replace the abnormal node. In the case of multiple node abnormality, a regional network restoration algorithm is introduced. It is designed to reduce the overhead of node movements while restoration happens. Simulation results indicate the proposed algorithm has better performance on the total moving distance and the number of total relocated nodes compared with some other representative restoration algorithms. PMID:29316702

Estimation of distributed Fermat-point location for wireless sensor networking.

PubMed

Huang, Po-Hsian; Chen, Jiann-Liang; Larosa, Yanuarius Teofilus; Chiang, Tsui-Lien

2011-01-01

This work presents a localization scheme for use in wireless sensor networks (WSNs) that is based on a proposed connectivity-based RF localization strategy called the distributed Fermat-point location estimation algorithm (DFPLE). DFPLE applies triangle area of location estimation formed by intersections of three neighboring beacon nodes. The Fermat point is determined as the shortest path from three vertices of the triangle. The area of estimated location then refined using Fermat point to achieve minimum error in estimating sensor nodes location. DFPLE solves problems of large errors and poor performance encountered by localization schemes that are based on a bounding box algorithm. Performance analysis of a 200-node development environment reveals that, when the number of sensor nodes is below 150, the mean error decreases rapidly as the node density increases, and when the number of sensor nodes exceeds 170, the mean error remains below 1% as the node density increases. Second, when the number of beacon nodes is less than 60, normal nodes lack sufficient beacon nodes to enable their locations to be estimated. However, the mean error changes slightly as the number of beacon nodes increases above 60. Simulation results revealed that the proposed algorithm for estimating sensor positions is more accurate than existing algorithms, and improves upon conventional bounding box strategies.

Data driven CAN node reliability assessment for manufacturing system

NASA Astrophysics Data System (ADS)

Zhang, Leiming; Yuan, Yong; Lei, Yong

2017-01-01

The reliability of the Controller Area Network(CAN) is critical to the performance and safety of the system. However, direct bus-off time assessment tools are lacking in practice due to inaccessibility of the node information and the complexity of the node interactions upon errors. In order to measure the mean time to bus-off(MTTB) of all the nodes, a novel data driven node bus-off time assessment method for CAN network is proposed by directly using network error information. First, the corresponding network error event sequence for each node is constructed using multiple-layer network error information. Then, the generalized zero inflated Poisson process(GZIP) model is established for each node based on the error event sequence. Finally, the stochastic model is constructed to predict the MTTB of the node. The accelerated case studies with different error injection rates are conducted on a laboratory network to demonstrate the proposed method, where the network errors are generated by a computer controlled error injection system. Experiment results show that the MTTB of nodes predicted by the proposed method agree well with observations in the case studies. The proposed data driven node time to bus-off assessment method for CAN networks can successfully predict the MTTB of nodes by directly using network error event data.

Information spreading in Delay Tolerant Networks based on nodes' behaviors

NASA Astrophysics Data System (ADS)

Wu, Yahui; Deng, Su; Huang, Hongbin

2014-07-01

Information spreading in DTNs (Delay Tolerant Networks) adopts a store-carry-forward method, and nodes receive the message from others directly. However, it is hard to judge whether the information is safe in this communication mode. In this case, a node may observe other nodes' behaviors. At present, there is no theoretical model to describe the varying rule of the nodes' trusting level. In addition, due to the uncertainty of the connectivity in DTN, a node is hard to get the global state of the network. Therefore, a rational model about the node's trusting level should be a function of the node's own observing result. For example, if a node finds k nodes carrying a message, it may trust the information with probability p(k). This paper does not explore the real distribution of p(k), but instead presents a unifying theoretical framework to evaluate the performance of the information spreading in above case. This framework is an extension of the traditional SI (susceptible-infected) model, and is useful when p(k) conforms to any distribution. Simulations based on both synthetic and real motion traces show the accuracy of the framework. Finally, we explore the impact of the nodes' behaviors based on certain special distributions through numerical results.

Extent of surgery for papillary thyroid cancer: preoperative imaging and role of prophylactic and therapeutic neck dissection.

PubMed

Cisco, Robin M; Shen, Wen T; Gosnell, Jessica E

2012-03-01

Papillary thyroid cancer (PTC) has an excellent prognosis, yet lymph node metastases are common. Most authors agree that central and/or lateral lymph node dissection should be undertaken in patients with abnormal lymph nodes detected on ultrasound, physical examination or intraoperative inspection. However the appropriate extent of prophylactic lymph node dissection for clinically node-negative patients remains the subject of controversy. There have been no randomized trials to date to offer guidance on this issue. The 2006 guidelines of the American Thyroid Association recommended consideration of prophylactic bilateral central lymph node dissection (CLND) for all patients undergoing thyroidectomy for PTC. However, the absence of compelling evidence for a benefit in terms of recurrence or survival, and the potential for increased morbidity, have led many, including our institution, to take an approach of selective central lymph node dissection. This approach is guided by the detection of abnormal lymph nodes on preoperative ultrasound, on physical examination, or during surgery. Postoperatively, ultrasound by an experienced ultrasonographer is the mainstay of evaluation for lymph node recurrence and is combined with monitoring of thyroglobulin and antithyroglobulin antibody levels. Reoperative lymph node dissection is typically undertaken upon detection and fine needle aspiration (FNA) of involved lymph nodes 0.8 cm or greater in size.

Towards understanding the behavior of physical systems using information theory

NASA Astrophysics Data System (ADS)

Quax, Rick; Apolloni, Andrea; Sloot, Peter M. A.

2013-09-01

One of the goals of complex network analysis is to identify the most influential nodes, i.e., the nodes that dictate the dynamics of other nodes. In the case of autonomous systems or transportation networks, highly connected hubs play a preeminent role in diffusing the flow of information and viruses; in contrast, in language evolution most linguistic norms come from the peripheral nodes who have only few contacts. Clearly a topological analysis of the interactions alone is not sufficient to identify the nodes that drive the state of the network. Here we show how information theory can be used to quantify how the dynamics of individual nodes propagate through a system. We interpret the state of a node as a storage of information about the state of other nodes, which is quantified in terms of Shannon information. This information is transferred through interactions and lost due to noise, and we calculate how far it can travel through a network. We apply this concept to a model of opinion formation in a complex social network to calculate the impact of each node by measuring how long its opinion is remembered by the network. Counter-intuitively we find that the dynamics of opinions are not determined by the hubs or peripheral nodes, but rather by nodes with an intermediate connectivity.

Lymph node clearance of plutonium from subcutaneous wounds in beagles

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

Dagle, G.E.

1973-08-01

The lymph node clearance of /sup 239/Pu O/sub 2/ administered as insoluble particles from subcutaneous implants was studied in adult beagles to simulate accidental contamination of hand wounds. External scintillation data were collected from the popliteal lymph nodes of each dog after 9.2 to 39.4 mu Ci of plutonium oxide was subcutaneously implanted into the left or right hind paws. The left hind paw was armputated 4 weeks after implantation to prevent continued deposition of plutonium oxide particles in the left popliteal lymph node. Groups of 3 dogs were sacrificed 4, 8, 16, and 32 weeks after plutonium implantation formore » histopathologic, electron microscopic, and radiochemical analysis of regional lymph nodes. An additional group of dogs received treatment with the chelating agent diethyenetriaminepentaacetic acid (DTPA). Plutonium rapidly accumulated in the popliteal lymph nodes after subcutaneous injection into the hind paw, and 1 to 10% of the implant dose was present in the popliteal lymph nodes at the time of necropsy. Histopathologic changes in the popliteal lymph nodes with plutonium particles were characterized primarily by reticular cell hyperplasia, increased numbers of macrophages, necrosis, and fibroplasia. Eventually, the plutonium particles became sequestered by scar tissue that often replaced the entire architecture of the lymph node. Light microscopic autoradiographs of the popliteal lymph nodes showed a time-related increase in number of alpha tracks per plutonium source. Electron microscopy showed that the plutonium particles were aggregated in phagolysosomes of macrophages. There was slight clearance of plutonium from the popliteal lymph nodes of dogs monitored for 32 weeks. The clearance of plutonium particles from the popliteal lymph nodes was associated with necrosis of macrophages. The external iliac lymph nodes contained fewer plutonium particles than the popliteal lymph nodes and histopathologic changes were less severe. The superficial inguinal lymph nodes of one dog contained appreciable amounts of plutonium. Treatment with diethylenetriaminepentaacetic acid (DTPA) did not have a measurable effect on the clearance of plutonium from the popliteal lymph nodes. (60 references) (auth)« less

The impact of superficial injections of radiocolloids and dynamic lymphoscintigraphy on sentinel node identification in oral cavity cancer: a same-day protocol.

PubMed

Tartaglione, Girolamo; Vigili, Maurizio G; Rahimi, Siavash; Celebrini, Alessandra; Pagan, Marco; Lauro, Luigi; Al-Nahhas, Adil; Rubello, Domenico

2008-04-01

To evaluate the role of dynamic lymphoscintigraphy with a same-day protocol for sentinel node biopsy in oral cavity cancer. Twenty-two consecutive patients affected by cT1-2N0 squamous cell carcinoma of the oral cavity were enrolled between September 2001 and November 2005. After a local anaesthetic (10% lidocaine spray), a dose of 30-50 MBq of Tc human serum albumin nanocolloid, in ml saline, was injected superficially (1-2 mm subendothelial injection) into four points around the lesion. Dynamic lymphoscintigraphy was acquired immediately (256x256 matrix, 5 min pre-set time, LEGP collimator) in lateral and anterior projections. The imaging was prolonged until the lymph nodes of at least two neck levels were visualized (time required min). About 3 h later (same-day protocol) the patients had a radioguided sentinel node biopsy. Elective neck dissection was performed in the first 13 patients; whereas the last nine patients had elective neck dissection only if the sentinel node was positive. Sentinel nodes were dissected into 1 mm thick block sections and studied by haematoxylin & eosin staining and immunohistochemistry (anticytokeratin antibody). The sentinel nodes were found on the 1st neck level in 13 cases, on the 2nd neck level in eight cases, and on the 3rd neck level in one case (100% sensitivity). The average number of sentinel nodes was 2.2 for each patient. The sentinel node was positive in eight patients (36%); with six of them having the sentinel node as the exclusive site of metastasis. No skip metastases were found in the 14 patients with negative sentinel node (100% specificity). Our preliminary data indicate that superficial injections of radiocolloid and dynamic lymphoscintigraphy provide a high success rate in sentinel node identification in oral cavity cancers. Dynamic lymphoscintigraphy helps in distinguishing sentinel node from second-tier lymph nodes. The same-day protocol is advisable in order to correctly identify the first sentinel node, avoiding multiple and unnecessary node biopsies, without reducing sensitivity.

Determining a bisection bandwidth for a multi-node data communications network

DOEpatents

Faraj, Ahmad A.

2010-01-26

Methods, systems, and products are disclosed for determining a bisection bandwidth for a multi-node data communications network that include: partitioning nodes in the network into a first sub-network and a second sub-network in dependence upon a topology of the network; sending, by each node in the first sub-network to a destination node in the second sub-network, a first message having a predetermined message size; receiving, by each node in the first sub-network from a source node in the second sub-network, a second message; measuring, by each node in the first sub-network, the elapsed communications time between the sending of the first message and the receiving of the second message; selecting the longest elapsed communications time; and calculating the bisection bandwidth for the network in dependence upon the number of the nodes in the first sub-network, the predetermined message size of the first test message, and the longest elapsed communications time.

Understanding the influence of all nodes in a network

PubMed Central

Lawyer, Glenn

2015-01-01

Centrality measures such as the degree, k-shell, or eigenvalue centrality can identify a network's most influential nodes, but are rarely usefully accurate in quantifying the spreading power of the vast majority of nodes which are not highly influential. The spreading power of all network nodes is better explained by considering, from a continuous-time epidemiological perspective, the distribution of the force of infection each node generates. The resulting metric, the expected force, accurately quantifies node spreading power under all primary epidemiological models across a wide range of archetypical human contact networks. When node power is low, influence is a function of neighbor degree. As power increases, a node's own degree becomes more important. The strength of this relationship is modulated by network structure, being more pronounced in narrow, dense networks typical of social networking and weakening in broader, looser association networks such as the Internet. The expected force can be computed independently for individual nodes, making it applicable for networks whose adjacency matrix is dynamic, not well specified, or overwhelmingly large. PMID:25727453

Sentinel lymph node mapping in melanoma with technetium-99m dextran.

PubMed

Neubauer, S; Mena, I; Iglesis, R; Schwartz, R; Acevedo, J C; Leon, A; Gomez, L

2001-06-01

The aim of this work is to evaluate the capability of Tc99m B Dextran as a lymphoscintigraphic agent in the detection of the sentinel node in skin lesions. Forty-one patients with melanomas (39) and Merkel cell tumors (2) had perilesional intradermal injection of Tc99m-Dextran 2 hours before surgery. Serial gamma camera images and a handheld gamma probe were used to direct sentinel node biopsy. In 39/41 patients, lymph channels and 52 sentinel nodes (one to three sentinel nodes/patient) could be visualized. In one patient, with a dorsal melanoma, no lymph channels or lymph nodes could be demonstrated on the images and only minimal radioactivity was found in the regional nodes with the probe. Another patient with a facial lesion failed to demonstrate lymph channels or nodes. No adverse reactions were observed. Tc99m-Dextran provided good definition of lymph channels and sentinel node localization, without the risks related to the use of potentially hazardous labeled materials of biological origin.

Performance Evaluation of AODV with Blackhole Attack

NASA Astrophysics Data System (ADS)

Dara, Karuna

2010-11-01

A Mobile Ad Hoc Network (MANET) is a temporary network set up by a wireless mobile computers moving arbitrary in the places that have no network infrastructure. These nodes maintain connectivity in a decentralized manner. Since the nodes communicate with each other, they cooperate by forwarding data packets to other nodes in the network. Thus the nodes find a path to the destination node using routing protocols. However, due to security vulnerabilities of the routing protocols, mobile ad-hoc networks are unprotected to attacks of the malicious nodes. One of these attacks is the Black Hole Attack against network integrity absorbing all data packets in the network. Since the data packets do not reach the destination node on account of this attack, data loss will occur. In this paper, we simulated the black hole attack in various mobile ad-hoc network scenarios using AODV routing protocol of MANET and have tried to find a effect if number of nodes are increased with increase in malicious nodes.

Distribution of prostate nodes: a PET/CT-derived anatomic atlas of prostate cancer patients before and after surgical treatment.

PubMed

Hegemann, Nina-Sophie; Wenter, Vera; Spath, Sonja; Kusumo, Nadia; Li, Minglun; Bartenstein, Peter; Fendler, Wolfgang P; Stief, Christian; Belka, Claus; Ganswindt, Ute

2016-03-11

In order to define adequate radiation portals in nodal positive prostate cancer a detailed knowledge of the anatomic lymph-node distribution is mandatory. We therefore systematically analyzed the localization of Choline PET/CT positive lymph nodes and compared it to the RTOG recommendation of pelvic CTV, as well as to previous work, the SPECT sentinel lymph node atlas. Thirty-two patients being mostly high risk patients with a PSA of 12.5 ng/ml (median) received PET/CT before any treatment. Eighty-seven patients received PET/CT for staging due to biochemical failure with a median PSA of 3.12 ng/ml. Each single PET-positive lymph node was manually contoured in a "virtual" patient dataset to achieve a 3-D visualization, resulting in an atlas of the cumulative PET positive lymph node distribution. Further the PET-positive lymph node location in each patient was assessed with regard to the existence of a potential geographic miss (i.e. PET-positive lymph nodes that would not have been treated adequately by the RTOG consensus on CTV definition of pelvic lymph nodes). Seventy-eight and 209 PET positive lymph nodes were detected in patients with no prior treatment and in postoperative patients, respectively. The most common sites of PET positive lymph nodes in patients with no prior treatment were external iliac (32.1 %), followed by common iliac (23.1 %) and para-aortic (19.2 %). In postoperative patients the most common sites of PET positive lymph nodes were common iliac (24.9 %), followed by external iliac (23.0 %) and para-aortic (20.1 %). In patients with no prior treatment there were 34 (43.6 %) and in postoperative patients there were 77 (36.8 %) of all detected lymph nodes that would not have been treated adequately using the RTOG CTV. We compared the distribution of lymph nodes gained by Choline PET/CT to the preexisting SPECT sentinel lymph node atlas and saw an overall good congruence. Choline PET/CT and SPECT sentinel lymph node atlas are comparable to each other. More than one-third of the PET positive lymph nodes in patients with no prior treatment and in postoperative patients would not have been treated adequately using the RTOG CTV. To reduce geographical miss, image based definition of an individual target volume is necessary.

Performing an allreduce operation on a plurality of compute nodes of a parallel computer

DOEpatents

Faraj, Ahmad [Rochester, MN

2012-04-17

Methods, apparatus, and products are disclosed for performing an allreduce operation on a plurality of compute nodes of a parallel computer. Each compute node includes at least two processing cores. Each processing core has contribution data for the allreduce operation. Performing an allreduce operation on a plurality of compute nodes of a parallel computer includes: establishing one or more logical rings among the compute nodes, each logical ring including at least one processing core from each compute node; performing, for each logical ring, a global allreduce operation using the contribution data for the processing cores included in that logical ring, yielding a global allreduce result for each processing core included in that logical ring; and performing, for each compute node, a local allreduce operation using the global allreduce results for each processing core on that compute node.

Wireless Sensor Node for Autonomous Monitoring and Alerts in Remote Environments

NASA Technical Reports Server (NTRS)

Panangadan, Anand V. (Inventor); Monacos, Steve P. (Inventor)

2015-01-01

A method, apparatus, system, and computer program products provides personal alert and tracking capabilities using one or more nodes. Each node includes radio transceiver chips operating at different frequency ranges, a power amplifier, sensors, a display, and embedded software. The chips enable the node to operate as either a mobile sensor node or a relay base station node while providing a long distance relay link between nodes. The power amplifier enables a line-of-sight communication between the one or more nodes. The sensors provide a GPS signal, temperature, and accelerometer information (used to trigger an alert condition). The embedded software captures and processes the sensor information, provides a multi-hop packet routing protocol to relay the sensor information to and receive alert information from a command center, and to display the alert information on the display.

Ultrasonography and fine needle aspirate cytology of the mesenteric lymph node in normal domestic ferrets (Mustela putorius furo).

PubMed

Paul-Murphy, J; O'Brien, R T; Spaeth, A; Sullivan, L; Dubielzig, R R

1999-01-01

The large mesenteric lymph node of 28 normal ferrets was imaged with ultrasound. The large node, located in the mid-abdomen at the root of the mesentery, was round to ovoid and uniformly hyperechoic. Mean ultrasonographic dimensions of the lymph node were 12.6 +/- 2.6 mm by 7.6 +/- 2.0 mm. Fine needle aspirates of 20 lymph nodes were obtained either using ultrasound guided free-hand techniques or at necropsy. The cytological descriptions were compared to histological descriptions of 13 lymph node core biopsies obtained during laparotomy or necropsy as well as 10 peripheral blood smear differentials. The large mesenteric lymph node of ferrets could be easily imaged and measured by ultrasound and evaluated by fine needle aspirate cytology. Normal lymph node cytology may include an eosinophilic infiltrate.

A new routing enhancement scheme based on node blocking state advertisement in wavelength-routed WDM networks

NASA Astrophysics Data System (ADS)

Hu, Peigang; Jin, Yaohui; Zhang, Chunlei; He, Hao; Hu, WeiSheng

2005-02-01

The increasing switching capacity brings the optical node with considerable complexity. Due to the limitation in cost and technology, an optical node is often designed with partial switching capability and partial resource sharing. It means that the node is of blocking to some extent, for example multi-granularity switching node, which in fact is a structure using pass wavelength to reduce the dimension of OXC, and partial sharing wavelength converter (WC) OXC. It is conceivable that these blocking nodes will have great effects on the problem of routing and wavelength assignment. Some previous works studied the blocking case, partial WC OXC, using complicated wavelength assignment algorithm. But the complexities of these schemes decide them to be not in practice in real networks. In this paper, we propose a new scheme based on the node blocking state advertisement to reduce the retry or rerouting probability and improve the efficiency of routing in the networks with blocking nodes. In the scheme, node blocking state are advertised to the other nodes in networks, which will be used for subsequent route calculation to find a path with lowest blocking probability. The performance of the scheme is evaluated using discrete event model in 14-node NSFNET, all the nodes of which employ a kind of partial sharing WC OXC structure. In the simulation, a simple First-Fit wavelength assignment algorithm is used. The simulation results demonstrate that the new scheme considerably reduces the retry or rerouting probability in routing process.

Feasibility of contrast-enhanced ultrasound-guided biopsy of sentinel lymph nodes in dogs.

PubMed

Gelb, Hylton R; Freeman, Lynetta J; Rohleder, Jacob J; Snyder, Paul W

2010-01-01

Our goal was to develop and validate a technique to identify the sentinel lymph nodes of the mammary glands of healthy dogs with contrast-enhanced ultrasound, and evaluate the feasibility of obtaining representative samples of a sentinel lymph node under ultrasound guidance using a new biopsy device. Three healthy intact female adult hounds were anesthetized and each received an injection of octafluoropropane-filled lipid microspheres and a separate subcutaneous injection of methylene blue dye around a mammary gland. Ultrasound was then used to follow the contrast agent through the lymphatic channel to the sentinel lymph node. Lymph node biopsy was performed under ultrasound guidance, followed by an excisional biopsy of the lymph nodes and a regional mastectomy procedure. Excised tissues were submitted for histopathologic examination and evaluated as to whether they were representative of the node. The ultrasound contrast agent was easily visualized with ultrasound leading up to the sentinel lymph nodes. Eight normal lymph nodes (two inguinal, one axillary in two dogs; two inguinal in one dog) were identified and biopsied. Lymphoid tissue was obtained from all biopsy specimens. Samples from four of eight lymph nodes contained both cortical and medullary lymphoid tissue. Contrast-enhanced ultrasound can be successfully used to image and guide minimally invasive biopsy of the normal sentinel lymph nodes draining the mammary glands in healthy dogs. Further work is needed to evaluate whether this technique may be applicable in patients with breast cancer or other conditions warranting evaluation of sentinel lymph nodes in animals.

Opinion formation driven by PageRank node influence on directed networks

NASA Astrophysics Data System (ADS)

Eom, Young-Ho; Shepelyansky, Dima L.

2015-10-01

We study a two states opinion formation model driven by PageRank node influence and report an extensive numerical study on how PageRank affects collective opinion formations in large-scale empirical directed networks. In our model the opinion of a node can be updated by the sum of its neighbor nodes' opinions weighted by the node influence of the neighbor nodes at each step. We consider PageRank probability and its sublinear power as node influence measures and investigate evolution of opinion under various conditions. First, we observe that all networks reach steady state opinion after a certain relaxation time. This time scale is decreasing with the heterogeneity of node influence in the networks. Second, we find that our model shows consensus and non-consensus behavior in steady state depending on types of networks: Web graph, citation network of physics articles, and LiveJournal social network show non-consensus behavior while Wikipedia article network shows consensus behavior. Third, we find that a more heterogeneous influence distribution leads to a more uniform opinion state in the cases of Web graph, Wikipedia, and Livejournal. However, the opposite behavior is observed in the citation network. Finally we identify that a small number of influential nodes can impose their own opinion on significant fraction of other nodes in all considered networks. Our study shows that the effects of heterogeneity of node influence on opinion formation can be significant and suggests further investigations on the interplay between node influence and collective opinion in networks.

Effective Social Relationship Measurement and Cluster Based Routing in Mobile Opportunistic Networks †

PubMed Central

Zeng, Feng; Zhao, Nan; Li, Wenjia

2017-01-01

In mobile opportunistic networks, the social relationship among nodes has an important impact on data transmission efficiency. Motivated by the strong share ability of “circles of friends” in communication networks such as Facebook, Twitter, Wechat and so on, we take a real-life example to show that social relationships among nodes consist of explicit and implicit parts. The explicit part comes from direct contact among nodes, and the implicit part can be measured through the “circles of friends”. We present the definitions of explicit and implicit social relationships between two nodes, adaptive weights of explicit and implicit parts are given according to the contact feature of nodes, and the distributed mechanism is designed to construct the “circles of friends” of nodes, which is used for the calculation of the implicit part of social relationship between nodes. Based on effective measurement of social relationships, we propose a social-based clustering and routing scheme, in which each node selects the nodes with close social relationships to form a local cluster, and the self-control method is used to keep all cluster members always having close relationships with each other. A cluster-based message forwarding mechanism is designed for opportunistic routing, in which each node only forwards the copy of the message to nodes with the destination node as a member of the local cluster. Simulation results show that the proposed social-based clustering and routing outperforms the other classic routing algorithms. PMID:28498309

Effective Social Relationship Measurement and Cluster Based Routing in Mobile Opportunistic Networks.

PubMed

Zeng, Feng; Zhao, Nan; Li, Wenjia

2017-05-12

In mobile opportunistic networks, the social relationship among nodes has an important impact on data transmission efficiency. Motivated by the strong share ability of "circles of friends" in communication networks such as Facebook, Twitter, Wechat and so on, we take a real-life example to show that social relationships among nodes consist of explicit and implicit parts. The explicit part comes from direct contact among nodes, and the implicit part can be measured through the "circles of friends". We present the definitions of explicit and implicit social relationships between two nodes, adaptive weights of explicit and implicit parts are given according to the contact feature of nodes, and the distributed mechanism is designed to construct the "circles of friends" of nodes, which is used for the calculation of the implicit part of social relationship between nodes. Based on effective measurement of social relationships, we propose a social-based clustering and routing scheme, in which each node selects the nodes with close social relationships to form a local cluster, and the self-control method is used to keep all cluster members always having close relationships with each other. A cluster-based message forwarding mechanism is designed for opportunistic routing, in which each node only forwards the copy of the message to nodes with the destination node as a member of the local cluster. Simulation results show that the proposed social-based clustering and routing outperforms the other classic routing algorithms.

Dual-modality imaging with 99mTc and fluorescent indocyanine green using surface-modified silica nanoparticles for biopsy of the sentinel lymph node: an animal study

PubMed Central

2013-01-01

Background We propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m (99mTc) and indocyanine green (ICG). Methods We conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with 99mTc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats. Results Scintigraphic images showed increased accumulation of 99mTc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes; mean, 0.001% ± 0.000%, p < 0.05). Transmission electron microscopy revealed that small black granules were localized to and dispersed within the cytoplasm of macrophages in the lymph nodes. Conclusion Although further studies are needed to determine the appropriate dose of the dual-imaging nanoparticle probe for effective sensitivity and safety, the results of this animal study revealed a novel method for improved node detection by a dual-modality approach for sentinel lymph node biopsy. PMID:23618132

International Space Station Node 1 is moved for leak test

NASA Technical Reports Server (NTRS)

1998-01-01

Node 1, the first element for the International Space Station, and attached Pressurized Mating Adapter-1 continue with prelaunch preparation activities at KSC's Space Station Processing Facility. Node 1 is a connecting passageway to the living and working areas of the space station. The node is being removed from the element rotation stand, or test stand, where it underwent an interim weight and center of gravity determination. (The final determination is planned to be performed prior to transporting Node 1 to the launch pad.) Now the node is being moved to the Shuttle payload transportation canister, where the doors will be closed for a two-week leak check. Node 1 is scheduled to fly on STS-88.

Suppressing epidemics on networks by exploiting observer nodes.

PubMed

Takaguchi, Taro; Hasegawa, Takehisa; Yoshida, Yuichi

2014-07-01

To control infection spreading on networks, we investigate the effect of observer nodes that recognize infection in a neighboring node and make the rest of the neighbor nodes immune. We numerically show that random placement of observer nodes works better on networks with clustering than on locally treelike networks, implying that our model is promising for realistic social networks. The efficiency of several heuristic schemes for observer placement is also examined for synthetic and empirical networks. In parallel with numerical simulations of epidemic dynamics, we also show that the effect of observer placement can be assessed by the size of the largest connected component of networks remaining after removing observer nodes and links between their neighboring nodes.

Sentinel lymph node biopsy from the vantage point of an oncologic surgeon.

PubMed

Wilson, Lori L

2009-01-01

Sentinel lymph node biopsy has greatly influenced the surgical management of clinically localized primary melanoma. Lymphatic mapping and sentinel lymph node biopsy have been used for the selective management of the draining regional lymph node basin of primary cutaneous melanoma. Oncologic surgeons have adopted this procedure to selectively identify occult nodal status in melanoma patients who are at a higher risk of regional metastasis. The current standard of treatment of tumor-positive sentinel lymph node metastasis is immediate completion lymphadenectomy, but considerable debate surrounds the utility of this procedure. This contribution reviews development, technical aspects, selective management of the lymph node basin, and sentinel lymph node biopsy techniques.

Suppressing epidemics on networks by exploiting observer nodes

NASA Astrophysics Data System (ADS)

Takaguchi, Taro; Hasegawa, Takehisa; Yoshida, Yuichi

2014-07-01

To control infection spreading on networks, we investigate the effect of observer nodes that recognize infection in a neighboring node and make the rest of the neighbor nodes immune. We numerically show that random placement of observer nodes works better on networks with clustering than on locally treelike networks, implying that our model is promising for realistic social networks. The efficiency of several heuristic schemes for observer placement is also examined for synthetic and empirical networks. In parallel with numerical simulations of epidemic dynamics, we also show that the effect of observer placement can be assessed by the size of the largest connected component of networks remaining after removing observer nodes and links between their neighboring nodes.

A transmission power optimization with a minimum node degree for energy-efficient wireless sensor networks with full-reachability.

PubMed

Chen, Yi-Ting; Horng, Mong-Fong; Lo, Chih-Cheng; Chu, Shu-Chuan; Pan, Jeng-Shyang; Liao, Bin-Yih

2013-03-20

Transmission power optimization is the most significant factor in prolonging the lifetime and maintaining the connection quality of wireless sensor networks. Un-optimized transmission power of nodes either interferes with or fails to link neighboring nodes. The optimization of transmission power depends on the expected node degree and node distribution. In this study, an optimization approach to an energy-efficient and full reachability wireless sensor network is proposed. In the proposed approach, an adjustment model of the transmission range with a minimum node degree is proposed that focuses on topology control and optimization of the transmission range according to node degree and node density. The model adjusts the tradeoff between energy efficiency and full reachability to obtain an ideal transmission range. In addition, connectivity and reachability are used as performance indices to evaluate the connection quality of a network. The two indices are compared to demonstrate the practicability of framework through simulation results. Furthermore, the relationship between the indices under the conditions of various node degrees is analyzed to generalize the characteristics of node densities. The research results on the reliability and feasibility of the proposed approach will benefit the future real deployments.

A Transmission Power Optimization with a Minimum Node Degree for Energy-Efficient Wireless Sensor Networks with Full-Reachability

PubMed Central

Chen, Yi-Ting; Horng, Mong-Fong; Lo, Chih-Cheng; Chu, Shu-Chuan; Pan, Jeng-Shyang; Liao, Bin-Yih

2013-01-01

Transmission power optimization is the most significant factor in prolonging the lifetime and maintaining the connection quality of wireless sensor networks. Un-optimized transmission power of nodes either interferes with or fails to link neighboring nodes. The optimization of transmission power depends on the expected node degree and node distribution. In this study, an optimization approach to an energy-efficient and full reachability wireless sensor network is proposed. In the proposed approach, an adjustment model of the transmission range with a minimum node degree is proposed that focuses on topology control and optimization of the transmission range according to node degree and node density. The model adjusts the tradeoff between energy efficiency and full reachability to obtain an ideal transmission range. In addition, connectivity and reachability are used as performance indices to evaluate the connection quality of a network. The two indices are compared to demonstrate the practicability of framework through simulation results. Furthermore, the relationship between the indices under the conditions of various node degrees is analyzed to generalize the characteristics of node densities. The research results on the reliability and feasibility of the proposed approach will benefit the future real deployments. PMID:23519351

IMHRP: Improved Multi-Hop Routing Protocol for Wireless Sensor Networks

NASA Astrophysics Data System (ADS)

Huang, Jianhua; Ruan, Danwei; Hong, Yadong; Zhao, Ziming; Zheng, Hong

2017-10-01

Wireless sensor network (WSN) is a self-organizing system formed by a large number of low-cost sensor nodes through wireless communication. Sensor nodes collect environmental information and transmit it to the base station (BS). Sensor nodes usually have very limited battery energy. The batteries cannot be charged or replaced. Therefore, it is necessary to design an energy efficient routing protocol to maximize the network lifetime. This paper presents an improved multi-hop routing protocol (IMHRP) for homogeneous networks. In the IMHRP protocol, based on the distances to the BS, the CH nodes are divided into internal CH nodes and external CH nodes. The set-up phase of the protocol is based on the LEACH protocol and the minimum distance between CH nodes are limited to a special constant distance, so a more uniform distribution of CH nodes is achieved. In the steady-state phase, the routes of different CH nodes are created on the basis of the distances between the CH nodes. The energy efficiency of communication can be maximized. The simulation results show that the proposed algorithm can more effectively reduce the energy consumption of each round and prolong the network lifetime compared with LEACH protocol and MHT protocol.

Key-Node-Separated Graph Clustering and Layouts for Human Relationship Graph Visualization.

PubMed

Itoh, Takayuki; Klein, Karsten

2015-01-01

Many graph-drawing methods apply node-clustering techniques based on the density of edges to find tightly connected subgraphs and then hierarchically visualize the clustered graphs. However, users may want to focus on important nodes and their connections to groups of other nodes for some applications. For this purpose, it is effective to separately visualize the key nodes detected based on adjacency and attributes of the nodes. This article presents a graph visualization technique for attribute-embedded graphs that applies a graph-clustering algorithm that accounts for the combination of connections and attributes. The graph clustering step divides the nodes according to the commonality of connected nodes and similarity of feature value vectors. It then calculates the distances between arbitrary pairs of clusters according to the number of connecting edges and the similarity of feature value vectors and finally places the clusters based on the distances. Consequently, the technique separates important nodes that have connections to multiple large clusters and improves the visibility of such nodes' connections. To test this technique, this article presents examples with human relationship graph datasets, including a coauthorship and Twitter communication network dataset.

Self-assembly of the yeast actomyosin contractile ring as an aggregation process: kinetics of formation and instability regimes

NASA Astrophysics Data System (ADS)

Ojkic, Nikola; Vavylonis, Dimitrios

2009-03-01

Fission yeast cells assemble an equatorial contractile ring for cytokinesis, the last step of mitosis. The ring assembles from ˜ 65 membrane-bound ``nodes''' containing myosin motors and other proteins. Actin filaments that grow out from the nodes establish transient connections among the nodes and aid in pulling them together in a process that appears as pair-wise attraction (Vavylonis et al. Science 97:319, 2008). We used scaling arguments, coarse grained stability analysis of homogeneous states, and Monte Carlo simulations of simple models, to explore the conditions that yield fast and efficient ring formation, as opposed to formation of isolated clumps. We described our results as a function of: number of nodes, rate of establishing connections, range of node interaction, distance traveled per node interaction and broad band width, w. Uniform cortical 2d distributions of nodes are stable over short times due to randomness of connections among nodes, but become unstable over long times due to fluctuations in the initial node distribution. Successful condensation of nodes into a ring requires sufficiently small w such that lateral contraction occurs faster then clump formation.

Executing a gather operation on a parallel computer

DOEpatents

Archer, Charles J [Rochester, MN; Ratterman, Joseph D [Rochester, MN

2012-03-20

Methods, apparatus, and computer program products are disclosed for executing a gather operation on a parallel computer according to embodiments of the present invention. Embodiments include configuring, by the logical root, a result buffer or the logical root, the result buffer having positions, each position corresponding to a ranked node in the operational group and for storing contribution data gathered from that ranked node. Embodiments also include repeatedly for each position in the result buffer: determining, by each compute node of an operational group, whether the current position in the result buffer corresponds with the rank of the compute node, if the current position in the result buffer corresponds with the rank of the compute node, contributing, by that compute node, the compute node's contribution data, if the current position in the result buffer does not correspond with the rank of the compute node, contributing, by that compute node, a value of zero for the contribution data, and storing, by the logical root in the current position in the result buffer, results of a bitwise OR operation of all the contribution data by all compute nodes of the operational group for the current position, the results received through the global combining network.

Reputation-Based Secure Sensor Localization in Wireless Sensor Networks

PubMed Central

He, Jingsha; Xu, Jing; Zhu, Xingye; Zhang, Yuqiang; Zhang, Ting; Fu, Wanqing

2014-01-01

Location information of sensor nodes in wireless sensor networks (WSNs) is very important, for it makes information that is collected and reported by the sensor nodes spatially meaningful for applications. Since most current sensor localization schemes rely on location information that is provided by beacon nodes for the regular sensor nodes to locate themselves, the accuracy of localization depends on the accuracy of location information from the beacon nodes. Therefore, the security and reliability of the beacon nodes become critical in the localization of regular sensor nodes. In this paper, we propose a reputation-based security scheme for sensor localization to improve the security and the accuracy of sensor localization in hostile or untrusted environments. In our proposed scheme, the reputation of each beacon node is evaluated based on a reputation evaluation model so that regular sensor nodes can get credible location information from highly reputable beacon nodes to accomplish localization. We also perform a set of simulation experiments to demonstrate the effectiveness of the proposed reputation-based security scheme. And our simulation results show that the proposed security scheme can enhance the security and, hence, improve the accuracy of sensor localization in hostile or untrusted environments. PMID:24982940

Effect of variation in active route timeout and my route timeout on the performance of AODV-ETX protocol in mobile adhoc network

NASA Astrophysics Data System (ADS)

Purnomo, A.; Widyawan; Najib, W.; Hartono, R.; Hartatik

2018-03-01

Mobile adhoc network (MANET) consists of nodes that are independent. A node can communicate each other without the presence of network infrastructure. A node can act as a transmitter and receiver as well as a router. This research has been variation in active route timeout and my route timeout on the performance of AODV-ETX protocol in MANET. The AODV-ETX protocol is the AODV protocol that uses the ETX metric. Performance testing is done on the static node topology with 5 m x 5 m node grid model where the distance between nodes is 100 m and node topology that consists of 25 nodes moves randomly with a moving speed of 1.38 m/s in an area of 1500 m x 300 m. From the test result, on the static node, AODV protocol-ETX shows optimal performance at a value MRT and ART of 10 s and 15 s, but showed a stable performance in the value of MRT and ART ≥60 s, while in randomly moved node topology shows stable performance in the value of MRT and ART ≥80 s.

Data-based reconstruction of complex geospatial networks, nodal positioning and detection of hidden nodes

PubMed Central

Su, Ri-Qi; Wang, Wen-Xu; Wang, Xiao; Lai, Ying-Cheng

2016-01-01

Given a complex geospatial network with nodes distributed in a two-dimensional region of physical space, can the locations of the nodes be determined and their connection patterns be uncovered based solely on data? We consider the realistic situation where time series/signals can be collected from a single location. A key challenge is that the signals collected are necessarily time delayed, due to the varying physical distances from the nodes to the data collection centre. To meet this challenge, we develop a compressive-sensing-based approach enabling reconstruction of the full topology of the underlying geospatial network and more importantly, accurate estimate of the time delays. A standard triangularization algorithm can then be employed to find the physical locations of the nodes in the network. We further demonstrate successful detection of a hidden node (or a hidden source or threat), from which no signal can be obtained, through accurate detection of all its neighbouring nodes. As a geospatial network has the feature that a node tends to connect with geophysically nearby nodes, the localized region that contains the hidden node can be identified. PMID:26909187

A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection.

PubMed

Nguyen, Daniel P; Huber, Philipp M; Metzger, Tobias A; Genitsch, Vera; Schudel, Hans H; Thalmann, George N

2016-11-01

Sentinel lymph node (SLN) detection techniques have the potential to change the standard of surgical care for patients with prostate cancer. We performed a lymphatic mapping study and determined the value of fluorescence SLN detection with indocyanine green (ICG) for the detection of lymph node metastases in intermediate- and high-risk patients undergoing radical prostatectomy and extended pelvic lymph node dissection. A total of 42 patients received systematic or specific ICG injections into the prostate base, the midportion, the apex, the left lobe, or the right lobe. We found (1) that external and internal iliac regions encompass the majority of SLNs, (2) that common iliac regions contain up to 22% of all SLNs, (3) that a prostatic lobe can drain into the contralateral group of pelvic lymph nodes, and (4) that the fossa of Marcille also receives significant drainage. Among the 12 patients who received systematic ICG injections, 5 (42%) had a total of 29 lymph node metastases. Of these, 16 nodes were ICG positive, yielding 55% sensitivity. The complex drainage pattern of the prostate and the low sensitivity of ICG for the detection of lymph node metastases reported in our study highlight the difficulties related to the implementation of SNL techniques in prostate cancer. There is controversy about how extensive lymph node dissection (LND) should be during prostatectomy. We investigated the lymphatic drainage of the prostate and whether sentinel node fluorescence techniques would be useful to detect node metastases. We found that the drainage pattern is complex and that the sentinel node technique is not able to replace extended pelvic LND. Copyright © 2016. Published by Elsevier B.V.

Prognostic significance of number of nodes removed in patients with node-negative early cervical cancer.

PubMed

Mao, Siyue; Dong, Jun; Li, Sheng; Wang, Yiqi; Wu, Peihong

2016-10-01

The aim of this study was to investigate whether the number of removed lymph nodes was associated with survival of patients with node-negative early cervical cancer and to analyze the prognostic significance of clinical and pathologic features in these patients. Patients with FIGO stage IA-IIB cervical cancer who underwent radical hysterectomy with lymphadenectomy without receiving preoperative therapy were reviewed retrospectively. Patients were all proved to have lymph-node-negative disease and classified into five groups based on the number of nodes removed. The Kaplan-Meier method and Cox's proportional hazards regression model were used in prognostic analysis. The final dataset included 359 patients: 45 (12.5%) patients had ≤10 nodes removed, 93 (25.9%) had 11-15, 98 (27.3%) had 16-20, 64 (17.8%) had 21-25, and 59 (16.4%) had >25 nodes removed. There was no association between the number of nodes removed and survival of patients with node-negative early cervical cancer (χ 2  = 6.19, P = 0.185). Similarly, subgroup analyses for FIGO stage IB1-IIB also showed that the number of lymph nodes was not significantly related to survival in each stage. Multivariate analyses showed that histology and depth of invasion were independent prognostic factors for survival in these patients. If a standardized lymphadenectomy is performed, the number of lymph nodes removed is not an independent prognostic factor for patients with node-negative early cervical cancer. Our study suggests that there is inconclusive evidence to support survival benefit of complete lymphadenectomy among these patients. © 2016 Japan Society of Obstetrics and Gynecology.

A critical evaluation of lymph node ratio in head and neck cancer.

PubMed

de Ridder, M; Marres, C C M; Smeele, L E; van den Brekel, M W M; Hauptmann, M; Balm, A J M; van Velthuysen, M L F

2016-12-01

In head and neck squamous cell carcinoma (HNSCC), the search for better prognostic factors beyond TNM-stage is ongoing. Lymph node ratio (LNR) (positive lymph nodes/total lymph nodes) is gaining interest in view of its potential prognostic significance. All HNSCC patients at the Netherlands Cancer Institute undergoing neck dissection for lymph node metastases in the neck region between 2002 and 2012 (n = 176) were included. Based on a protocol change in specimen processing, the cohort was subdivided in two distinct consecutive periods (pre and post 2007). The prognostic value of LNR, N-stage, and number of positive lymph nodes for overall survival was assessed. The mean number of examined lymph nodes after 2007 was significantly higher (42.3) than before (35.8) (p = 0.024). The higher number concerned mostly lymph nodes in level V. The mean number of positive lymph nodes before 2007 was 3.3 vs. 3.6 after 2007 (p = 0.745). By multivariate analysis of both pre- and post-2007 cohort data, two factors remained associated with an increased hazard of dying: N2 [HR 2.1 (1.1-4.1) and 2.4 (1.0-5.8)] and >3 positive lymph nodes [HR 2.0 (1.1-3.5) and 3.1 (1.4-6.9)]. Hazard ratio for LNR >7 % was not significantly different: pre 2007 at 2.2 (1.3-3.8) and post 2007 at 2.1 (1.0-4.8, p = 0.053). In this study, changes in specimen processing influenced LNR values, but not the total number of tumor positive nodes found. Therefore, in HNSCC, the number of positive nodes seems a more reliable parameter than LNR, provided a minimum number of lymph nodes are examined.

10 % fluorescein sodium vs 1 % isosulfan blue in breast sentinel lymph node biopsy.

PubMed

Ren, Lidong; Liu, Zhao; Liang, Mengdi; Wang, Li; Song, Xingli; Wang, Shui

2016-11-03

Sentinel lymph node biopsy (SLNB) is well accepted to be a standard procedure in breast cancer surgery with clinically negative lymph nodes. Isosulfan blue is the first dye approved by the USA Food and Drug Administration for the localization of the lymphatic system. Few alternative tracers have been investigated. In this study, we aimed to compare the differences between 10 % fluorescein sodium and 1 % isosulfan blue in breast sentinel lymph node biopsy and to investigate the feasibility of using 10 % fluorescein sodium as a new dye for breast sentinel lymph node biopsy. A total of 30 New Zealand rabbits were randomly divided into the fluorescein sodium group and the isosulfan blue group (15 rabbits per group). Fluorescein sodium or isosulfan blue was injected subcutaneously into the second pair of mammary areolas. The average fading time of the second lymph nodes in the isosulfan blue group was significantly shorter than that in the fluorescein sodium group. Moreover, the detection rates of SLNs were higher in the fluorescein sodium group than in the isosulfan blue group. No significant differences between the fluorescein sodium group and isosulfan blue group were observed regarding the distances between the detected sentinel lymph nodes and second pair of mammary areolas, the distances between the second lymph nodes and second pair of mammary areolas, the number of detected sentinel lymph nodes and second lymph nodes, the average dyeing time of the sentinel and the second lymph nodes, and the average fading time of the second lymph nodes. In summary, we first reported that fluorescein sodium is a potential new tracer for breast sentinel lymph node biopsy.

Previous conization on patient eligibility of sentinel lymph node detection for early invasive cervical cancer.

PubMed

Kato, Hidenori; Todo, Yukiharu; Minobe, Shin-Ichiro; Suzuki, Yoshihiro; Nakatani, Makiko; Ohba, Yoko; Yamashiro, Katsusige; Okamoto, Kazuhira

2011-11-01

Sentinel lymph node (SLN) detection has been accepted as a common strategy to preserve the quality of life of the patients with gynecologic cancers. However, the feasibility of SLN detection after conization is not yet clarified. Accuracy of SLN after conization was evaluated. Eighteen cases with prior conization (cone group) and 32 cases without conization (noncone group), all of which belonged to IB1 except 1 case in IA stage, underwent SLN detection. Systemic pelvic and para-aortic lymphadenectomy was coincidently performed for the estimation of negative and positive predictive values. Detection rate in which at least unilateral nodes were identified or bilaterally identified was 100% and 72.2% in the cone group, 90.6% and 71.9% in the noncone group, respectively. The average number of the detected SLN was 2.4 in the cone group and 2.1 in the noncone group. Negative and positive predictive value was 100% in both groups. On the distribution of sentinel node stations, most of the detected nodes were internal iliac and obturator node in both groups. Less frequent detection was observed in superficial common iliac node (5.4% in the cone group, 3.1% in the noncone group), external iliac node (2.7% and 9.5%), and parauterine artery node (5.4% and 1.6%).In both groups, no other lymph nodes were identified as SLN except 1 case in the cone group with the node in cardinal ligament. No significant difference was observed on detection rate, predictive value, and the distribution of sentinel node between the cone and noncone groups. Sentinel lymph node detection after conization can be performed with a certain reliability.

A Distributed and Energy-Efficient Algorithm for Event K-Coverage in Underwater Sensor Networks

PubMed Central

Jiang, Peng; Xu, Yiming; Liu, Jun

2017-01-01

For event dynamic K-coverage algorithms, each management node selects its assistant node by using a greedy algorithm without considering the residual energy and situations in which a node is selected by several events. This approach affects network energy consumption and balance. Therefore, this study proposes a distributed and energy-efficient event K-coverage algorithm (DEEKA). After the network achieves 1-coverage, the nodes that detect the same event compete for the event management node with the number of candidate nodes and the average residual energy, as well as the distance to the event. Second, each management node estimates the probability of its neighbor nodes’ being selected by the event it manages with the distance level, the residual energy level, and the number of dynamic coverage event of these nodes. Third, each management node establishes an optimization model that uses expectation energy consumption and the residual energy variance of its neighbor nodes and detects the performance of the events it manages as targets. Finally, each management node uses a constrained non-dominated sorting genetic algorithm (NSGA-II) to obtain the Pareto set of the model and the best strategy via technique for order preference by similarity to an ideal solution (TOPSIS). The algorithm first considers the effect of harsh underwater environments on information collection and transmission. It also considers the residual energy of a node and a situation in which the node is selected by several other events. Simulation results show that, unlike the on-demand variable sensing K-coverage algorithm, DEEKA balances and reduces network energy consumption, thereby prolonging the network’s best service quality and lifetime. PMID:28106837

Node Deployment Algorithm Based on Connected Tree for Underwater Sensor Networks

PubMed Central

Jiang, Peng; Wang, Xingmin; Jiang, Lurong

2015-01-01

Designing an efficient deployment method to guarantee optimal monitoring quality is one of the key topics in underwater sensor networks. At present, a realistic approach of deployment involves adjusting the depths of nodes in water. One of the typical algorithms used in such process is the self-deployment depth adjustment algorithm (SDDA). This algorithm mainly focuses on maximizing network coverage by constantly adjusting node depths to reduce coverage overlaps between two neighboring nodes, and thus, achieves good performance. However, the connectivity performance of SDDA is irresolute. In this paper, we propose a depth adjustment algorithm based on connected tree (CTDA). In CTDA, the sink node is used as the first root node to start building a connected tree. Finally, the network can be organized as a forest to maintain network connectivity. Coverage overlaps between the parent node and the child node are then reduced within each sub-tree to optimize coverage. The hierarchical strategy is used to adjust the distance between the parent node and the child node to reduce node movement. Furthermore, the silent mode is adopted to reduce communication cost. Simulations show that compared with SDDA, CTDA can achieve high connectivity with various communication ranges and different numbers of nodes. Moreover, it can realize coverage as high as that of SDDA with various sensing ranges and numbers of nodes but with less energy consumption. Simulations under sparse environments show that the connectivity and energy consumption performances of CTDA are considerably better than those of SDDA. Meanwhile, the connectivity and coverage performances of CTDA are close to those depth adjustment algorithms base on connected dominating set (CDA), which is an algorithm similar to CTDA. However, the energy consumption of CTDA is less than that of CDA, particularly in sparse underwater environments. PMID:26184209

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

PubMed

Koen Talsma, A; Shapiro, Joel; Looman, Caspar W N; van Hagen, Pieter; Steyerberg, Ewout W; van der Gaast, Ate; van Berge Henegouwen, Mark I; Wijnhoven, Bas P L; van Lanschot, J Jan B; Hulshof, Maarten C C M; van Laarhoven, Hanneke W M; Nieuwenhuijzen, Grard A P; Hospers, Geke A P; Bonenkamp, Johannes J; Cuesta, Miguel A; Blaisse, Reinoud J B; Busch, Olivier R C; ten Kate, Fiebo J W; Creemers, Geert-Jan; Punt, Cornelis J A; Plukker, John T M; Verheul, Henk M W; van Dekken, Herman; van der Sangen, Maurice J C; Rozema, Tom; Biermann, Katharina; Beukema, Jannet C; Piet, Anna H M; van Rij, Caroline M; Reinders, Janny G; Tilanus, Hugo W

2014-11-01

We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

Masked Proportional Routing

NASA Technical Reports Server (NTRS)

Wolpert, David H. (Inventor)

2003-01-01

Distributed approach for determining a path connecting adjacent network nodes, for probabilistically or deterministically transporting an entity, with entity characteristic mu from a source node to a destination node. Each node i is directly connected to an arbitrary number J(mu) of nodes, labeled or numbered j=jl, j2, .... jJ(mu). In a deterministic version, a J(mu)-component baseline proportion vector p(i;mu) is associated with node i. A J(mu)-component applied proportion vector p*(i;mu) is determined from p(i;mu) to preclude an entity visiting a node more than once. Third and fourth J(mu)-component vectors, with components iteratively determined by Target(i;n(mu);mu),=alpha(mu).Target(i;n(mu)-1;mu)j+beta(mu).p* (i;mu)j and Actual(i;n(mu);+a(mu)j. Actual(i;n(mu)-l;mu)j+beta(mu).Sent(i;j'(mu);n(mu)-1;mu)j, are computed, where n(mu) is an entity sequence index and alpha(mu) and beta(mu) are selected numbers. In one embodiment, at each node i, the node j=j'(mu) with the largest vector component difference, Target(i;n(mu);mu)j'- Actual (i;n(mu);mu)j'. is chosen for the next link for entity transport, except in special gap circumstances, where the same link is optionally used for transporting consecutively arriving entities. The network nodes may be computer-controlled routers that switch collections of packets, frames, cells or other information units. Alternatively, the nodes may be waypoints for movement of physical items in a network or for transformation of a physical item. The nodes may be states of an entity undergoing state transitions, where allowed transitions are specified by the network and/or the destination node.

Partial axillary lymph node dissection inferior to the intercostobrachial nerves complements sentinel node biopsy in patients with clinically node-negative breast cancer.

PubMed

Li, Jianyi; Jia, Shi; Zhang, Wenhai; Qiu, Fang; Zhang, Yang; Gu, Xi; Xue, Jinqi

2015-06-30

The practice of breast cancer diagnosis and treatment in China varies to that in western developed countries. With the unavailability of radioactive tracer technique for sentinel lymph nodes biopsy (SLNB), using blue dye alone has been the only option in China. Also, the diagnosis of breast malignant tumor in most Chinese centres heavily relies on intraoperative instant frozen histology which is normally followed by sentinel lymph nodes mapping, SLNB and the potential breast and axillary operations in one consecutive session. This practice appears to cause a high false negative rate (FNR) for SLNB. The present study aimed to investigate the impact of the current practice in China on the accuracy of SLNB, and whether partial axillary lymph node dissection (PALND), dissection of lymph nodes inferior to the intercostobrachial nerve (ICBN), was a good complementary procedure following SLNB using blue dye. 289 patients with clinically node-negative breast cancer were identified and recruited. Tumorectomy, intraoperative instant frozen histological diagnosis, SLNB using methylene blue dye, and PALND or complete axillary node dissection (ALND) were performed in one consecutive operative session. The choice of SLNB only, SLNB followed by PALND or by ALND was based on the pre-determined protocol and preoperative choice by the patient. Clinical parameters were analyzed and survival analysis was performed. 37% patients with clinically negative nodes were found nodes positive. 59 patients with positive SLN underwent ALND, including 47 patients with up to two positive nodes which were all located inferior to the ICBN. 9 patients had failed SLNB and underwent PALND. Among them, 3 (33.3%) patients were found to have one metastatic node. 149 patients showed negative SLNB but chose PALND. Among them, 30 (20.1%), 14 (9.4) and 1 (0.7%) patients were found to have one, two and three metastatic node(s), respectively. PALND detected 48 (30.4%) patients who had either failed SLNB or negative SLNB to have additional positive nodes. All the patients with up to two positive nodes had their nodes located inferior to the ICBN. The FNR of SLNB was 43%. The accuracy rate was 58%. The follow-up ranged 12-33 months. The incidence of lymphedema for SLNB, PALND, and ALND was 0%, 0%, and 25.4%, respectively (P < 0.005). The disease-free survivals for SLNB, PALND, and ALND groups were 95.8%, 96.8%, and 94.9%, respectively (p > 0.05). Under the circumstances of current practice in China, PALND is a good complementary procedure following SLNB in clinically node-negative breast cancer.

Broadband Control of Topological Nodes in Electromagnetic Fields

NASA Astrophysics Data System (ADS)

Song, Alex Y.; Catrysse, Peter B.; Fan, Shanhui

2018-05-01

We study topological nodes (phase singularities) in electromagnetic wave interactions with structures. We show that, when the nodes exist, it is possible to bind certain nodes to a specific plane in the structure by a combination of mirror and time-reversal symmetry. Such binding does not rely on any resonances in the structure. As a result, the nodes persist on the plane over a wide wavelength range. As an implication of such broadband binding, we demonstrate that the topological nodes can be used for hiding of metallic objects over a broad wavelength range.

Profiling an application for power consumption during execution on a compute node

DOEpatents

Archer, Charles J; Blocksome, Michael A; Peters, Amanda E; Ratterman, Joseph D; Smith, Brian E

2013-09-17

Methods, apparatus, and products are disclosed for profiling an application for power consumption during execution on a compute node that include: receiving an application for execution on a compute node; identifying a hardware power consumption profile for the compute node, the hardware power consumption profile specifying power consumption for compute node hardware during performance of various processing operations; determining a power consumption profile for the application in dependence upon the application and the hardware power consumption profile for the compute node; and reporting the power consumption profile for the application.

Sentinel Node and Ovarian Tumors: A Series of 20 Patients.

PubMed

Nyberg, Reita H; Korkola, Pasi; Mäenpää, Johanna U

2017-05-01

Intraoperative detection of ovarian sentinel nodes has been shown to be feasible. We examined the detection rate and locations of sentinel nodes in patients with ovarian tumors. We also aimed to assess the reliability of sentinel node method in predicting regional lymph node metastasis. Twenty patients scheduled for laparotomy because of a pelvic mass were recruited to the study. In the beginning of the laparotomy, radioisotope and blue dye were injected under the serosa next to the junction of the ovarian tumor and suspensory ligament. The number and locations of the hot and/or blue nodes/spots were recorded during the operation. If the tumor was malignant according to the frozen section, systematic lymphadenectomies were performed, the sentinel nodes sampled separately, and their status compared with other regional lymph nodes. Eleven patients had a right-sided ovarian tumor, 7 patients a left-sided tumor, and 2 patients had bilateral tumors. A median of 2 sentinel nodes/locations per patient (range, 1-3) were found. Sixty percent of all sentinel nodes were located in the para-aortic region only, compared with 30% in both para-aortic and pelvic areas and 10% in pelvic area only. Both unilateral and bilateral locations were found. In 83% of the cases with more than 1 sentinel node location, they were located in separate anatomical regions. In 3 patients, systematic lymphadenectomies were performed. One of them had nodal metastases in 2 regions and also a metastasis in 1 of her 2 sentinel nodes in 1 of those regions. In patients with ovarian tumor(s), the detection of sentinel nodes is feasible. They are located in different anatomic areas both ipsilaterally and contralaterally, although most of them are found in the para-aortic region. The reliability of the sentinel node concept should be evaluated in the framework of a multicenter trial.

Cross-Disciplinary Analysis of Lymph Node Classification in Lung Cancer on CT Scanning.

PubMed

El-Sherief, Ahmed H; Lau, Charles T; Obuchowski, Nancy A; Mehta, Atul C; Rice, Thomas W; Blackstone, Eugene H

2017-04-01

Accurate and consistent regional lymph node classification is an important element in the staging and multidisciplinary management of lung cancer. Regional lymph node definition sets-lymph node maps-have been created to standardize regional lymph node classification. In 2009, the International Association for the Study of Lung Cancer (IASLC) introduced a lymph node map to supersede all preexisting lymph node maps. Our aim was to study if and how lung cancer specialists apply the IASLC lymph node map when classifying thoracic lymph nodes encountered on CT scans during lung cancer staging. From April 2013 through July 2013, invitations were distributed to all members of the Fleischner Society, Society of Thoracic Radiology, General Thoracic Surgical Club, and the American Association of Bronchology and Interventional Pulmonology to participate in an anonymous online image-based and text-based 20-question survey regarding lymph node classification for lung cancer staging on CT imaging. Three hundred thirty-seven people responded (approximately 25% participation). Respondents consisted of self-reported thoracic radiologists (n = 158), thoracic surgeons (n = 102), and pulmonologists who perform endobronchial ultrasonography (n = 77). Half of the respondents (50%; 95% CI, 44%-55%) reported using the IASLC lymph node map in daily practice, with no significant differences between subspecialties. A disparity was observed between the IASLC definition sets and their interpretation and application on CT scans, in particular for lymph nodes near the thoracic inlet, anterior to the trachea, anterior to the tracheal bifurcation, near the ligamentum arteriosum, between the bronchus intermedius and esophagus, in the internal mammary space, and adjacent to the heart. Use of older lymph node maps and inconsistencies in interpretation and application of definitions in the IASLC lymph node map may potentially lead to misclassification of stage and suboptimal management of lung cancer in some patients. Published by Elsevier Inc.

The pattern of lymphatic metastasis of breast cancer and its influence on the delineation of radiation fields

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

Yu Jinming; Li Gong; Li Jianbin

2005-03-01

Purpose: The delineation of radiation fields should cover the clinical target volume (CTV) and minimally irradiate the surrounding normal tissues and organs. This study was designed to explore the pattern of lymphatic metastasis of breast cancer and indications for radiotherapy after radical or modified radical mastectomy and to discuss the rational delineation of radiation fields. Methods and materials: Between September 1980 and December 2003, 78 breast cancer patients receiving extended radical mastectomy in the Margottini model and 61 cases with complete data were analyzed to investigate the internal mammary lymphatic metastatic status. Between March 1988 and December 1988, 46 patientsmore » with clinical negative supraclavicular nodes received radical mastectomy plus supraclavicular lymph node dissection. The supraclavicular lymph nodes and axillary lymph nodes were labeled as S and levels I, II, or III, respectively, and examined pathologically. Between January 1996 and April 1999, 412 patients who had radical or modified radical mastectomy underwent the pathologic examination of axillary or levels I, II, or III nodes. Results: The incidence of internal mammary lymph node metastasis was 24.6%. It was 36.7% for the patients with positive axillary lymph nodes and 12.9% for the patients with negative axillary lymph nodes. All the metastatic internal mammary lymph nodes were located at the first, second, and third intercostal spaces. Skipping metastasis of the supraclavicular and axillary lymph nodes was observed in 3.8% and 8.1% of patients, respectively. Conclusions: According to our data, we suggest that the radiation field for internal mammary lymph nodes should exclude the fourth and fifth intercostal spaces, which may help to reduce the radiation damage to heart. It is unnecessary to irradiate the supraclavicular lymph nodes for the patients with negative axillary level III nodes, even with positive level I and level II nodes.« less

[Establishment of lymph node metastasis of MDA-MB-231 breast cancer model in nude mice].

PubMed

Wang, Le; Mi, Chengrong; Wang, Wen

2015-06-16

To establish lymph node metastasis of breast cancer model in nude mices using MDA-MB-231 cell lines or tumor masses. Divided twelve female nude mices of five weeks into A, B groups randomly. A group had seven nude mices, B group had five nude mices. A group nude mices were injected with MDA-MB-231 cells suspension into the second right mammary fat pad. Two weeks after emerged tumors, the orthotopic tumors of two nude mices of A group were dissected and then implanted into the second right mammary fat pad of B group nude mices. The other mices of A group continued to be fed. After six weeks of inoculation, we excised the tumors and the swollen lymph nodes in right axilla of all nude mices to make pathological examination. ① A group have a 7/7 tumor formation rate 7 days after implanted, B group was 5/5 5 days after implanted. ② The tumor volumes between the two groups had evident difference (P = 0.023), and the tumor volume of B group was bigger than A group. ③ A group had three nude mices which had one tumid lymph node respectively, the lymph node enlargement rate was 3/5; B group only had one nude mice that had one tumid lymph node, the lymph node enlargement rate was 1/5, the lymph node enlargement rate between the two groups showed no significant difference (P = 0.524). ④ The result of pathology in the two groups testified the tumors were invasive ductal carcinoma. The swollen lymph nodes in A group were reactive hyperplasia lymph nodes; the swollen lymph nodes in B group was metastatic lymph node. The method of orthotopic implantation with MDA-MB-231 tumor mass to establish lymph node metastasis of breast cancer model in nude mice, can provide a useful mean to research the lymph node metastasis mechanism of breast cancer.

Small size of metastatic lymph nodes with extracapsular spread greatly impacts treatment outcomes in oral squamous cell carcinoma patients.

PubMed

Michikawa, C; Izumo, T; Sumino, J; Morita, T; Ohyama, Y; Michi, Y; Uzawa, N

2018-07-01

Extracapsular spread (ECS) of metastatic lymph nodes from oral carcinoma is the most significant prognostic predictor of a poor treatment outcome. However, only a few reports on prognostic factors in ECS-positive cases have been investigated. To address this problem, a detailed examination of ECS pathology was conducted to determine the prognostic factors of oral squamous cell carcinoma (OSCC) with ECS of metastatic lymph nodes. This study involved 63 OSCC patients with at least one pathologically metastatic node with ECS. Among the 229 metastatic lymph nodes, 149 exhibited ECS. Univariate analysis revealed that a poor outcome and recurrence were significantly associated with the number of ECS-positive nodes, density of ECS, and the minor axis of the smallest ECS-positive node. However, multivariate analysis identified only small size of ECS-positive nodes as a significant and independent factor predicting recurrence and a poor outcome. Thus, small size of ECS-positive nodes is the most important prognostic indicator for OSCC with ECS in metastatic lymph nodes. The classification of ECS status using the minor axis of ECS-positive nodes may be useful for further prediction of a poorer prognosis in OSCC cases. Standardization of ECS diagnosis and multicenter prospective studies will be required to confirm and refine these findings. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Proposal for optimal placement platform of bikes using queueing networks.

PubMed

Mizuno, Shinya; Iwamoto, Shogo; Seki, Mutsumi; Yamaki, Naokazu

2016-01-01

In recent social experiments, rental motorbikes and rental bicycles have been arranged at nodes, and environments where users can ride these bikes have been improved. When people borrow bikes, they return them to nearby nodes. Some experiments have been conducted using the models of Hamachari of Yokohama, the Niigata Rental Cycle, and Bicing. However, from these experiments, the effectiveness of distributing bikes was unclear, and many models were discontinued midway. Thus, we need to consider whether these models are effectively designed to represent the distribution system. Therefore, we construct a model to arrange the nodes for distributing bikes using a queueing network. To adopt realistic values for our model, we use the Google Maps application program interface. Thus, we can easily obtain values of distance and transit time between nodes in various places in the world. Moreover, we apply the distribution of a population to a gravity model and we compute the effective transition probability for this queueing network. If the arrangement of the nodes and number of bikes at each node is known, we can precisely design the system. We illustrate our system using convenience stores as nodes and optimize the node configuration. As a result, we can optimize simultaneously the number of nodes, node places, and number of bikes for each node, and we can construct a base for a rental cycle business to use our system.

Energy efficient sensor scheduling with a mobile sink node for the target tracking application.

PubMed

Maheswararajah, Suhinthan; Halgamuge, Saman; Premaratne, Malin

2009-01-01

Measurement losses adversely affect the performance of target tracking. The sensor network's life span depends on how efficiently the sensor nodes consume energy. In this paper, we focus on minimizing the total energy consumed by the sensor nodes whilst avoiding measurement losses. Since transmitting data over a long distance consumes a significant amount of energy, a mobile sink node collects the measurements and transmits them to the base station. We assume that the default transmission range of the activated sensor node is limited and it can be increased to maximum range only if the mobile sink node is out-side the default transmission range. Moreover, the active sensor node can be changed after a certain time period. The problem is to select an optimal sensor sequence which minimizes the total energy consumed by the sensor nodes. In this paper, we consider two different problems depend on the mobile sink node's path. First, we assume that the mobile sink node's position is known for the entire time horizon and use the dynamic programming technique to solve the problem. Second, the position of the sink node is varied over time according to a known Markov chain, and the problem is solved by stochastic dynamic programming. We also present sub-optimal methods to solve our problem. A numerical example is presented in order to discuss the proposed methods' performance.

Energy Efficient Sensor Scheduling with a Mobile Sink Node for the Target Tracking Application

PubMed Central

Maheswararajah, Suhinthan; Halgamuge, Saman; Premaratne, Malin

2009-01-01

Measurement losses adversely affect the performance of target tracking. The sensor network's life span depends on how efficiently the sensor nodes consume energy. In this paper, we focus on minimizing the total energy consumed by the sensor nodes whilst avoiding measurement losses. Since transmitting data over a long distance consumes a significant amount of energy, a mobile sink node collects the measurements and transmits them to the base station. We assume that the default transmission range of the activated sensor node is limited and it can be increased to maximum range only if the mobile sink node is out-side the default transmission range. Moreover, the active sensor node can be changed after a certain time period. The problem is to select an optimal sensor sequence which minimizes the total energy consumed by the sensor nodes. In this paper, we consider two different problems depend on the mobile sink node's path. First, we assume that the mobile sink node's position is known for the entire time horizon and use the dynamic programming technique to solve the problem. Second, the position of the sink node is varied over time according to a known Markov chain, and the problem is solved by stochastic dynamic programming. We also present sub-optimal methods to solve our problem. A numerical example is presented in order to discuss the proposed methods' performance PMID:22399934

Node Depth Adjustment Based Target Tracking in UWSNs Using Improved Harmony Search.

PubMed

Liu, Meiqin; Zhang, Duo; Zhang, Senlin; Zhang, Qunfei

2017-12-04

Underwater wireless sensor networks (UWSNs) can provide a promising solution to underwater target tracking. Due to the limited computation and bandwidth resources, only a small part of nodes are selected to track the target at each interval. How to improve tracking accuracy with a small number of nodes is a key problem. In recent years, a node depth adjustment system has been developed and applied to issues of network deployment and routing protocol. As far as we know, all existing tracking schemes keep underwater nodes static or moving with water flow, and node depth adjustment has not been utilized for underwater target tracking yet. This paper studies node depth adjustment method for target tracking in UWSNs. Firstly, since a Fisher Information Matrix (FIM) can quantify the estimation accuracy, its relation to node depth is derived as a metric. Secondly, we formulate the node depth adjustment as an optimization problem to determine moving depth of activated node, under the constraint of moving range, the value of FIM is used as objective function, which is aimed to be minimized over moving distance of nodes. Thirdly, to efficiently solve the optimization problem, an improved Harmony Search (HS) algorithm is proposed, in which the generating probability is modified to improve searching speed and accuracy. Finally, simulation results are presented to verify performance of our scheme.

Node Depth Adjustment Based Target Tracking in UWSNs Using Improved Harmony Search

PubMed Central

Zhang, Senlin; Zhang, Qunfei

2017-01-01

Underwater wireless sensor networks (UWSNs) can provide a promising solution to underwater target tracking. Due to the limited computation and bandwidth resources, only a small part of nodes are selected to track the target at each interval. How to improve tracking accuracy with a small number of nodes is a key problem. In recent years, a node depth adjustment system has been developed and applied to issues of network deployment and routing protocol. As far as we know, all existing tracking schemes keep underwater nodes static or moving with water flow, and node depth adjustment has not been utilized for underwater target tracking yet. This paper studies node depth adjustment method for target tracking in UWSNs. Firstly, since a Fisher Information Matrix (FIM) can quantify the estimation accuracy, its relation to node depth is derived as a metric. Secondly, we formulate the node depth adjustment as an optimization problem to determine moving depth of activated node, under the constraint of moving range, the value of FIM is used as objective function, which is aimed to be minimized over moving distance of nodes. Thirdly, to efficiently solve the optimization problem, an improved Harmony Search (HS) algorithm is proposed, in which the generating probability is modified to improve searching speed and accuracy. Finally, simulation results are presented to verify performance of our scheme. PMID:29207541

Management of well-differentiated thyroid cancer in 2010: perspectives of a head and neck surgical oncologist.

PubMed

Urken, Mark L

2010-01-01

To review the terminology and controversy regarding the performance of prophylactic lymph node dissection for patients without evidence suggestive of pathologic adenopathy. Terminology of lymph node levels in the neck and chest, and the issues regarding lymph node dissection, are reviewed. In addition, differences between lymph nodes are reviewed and discussed. Management of lymph nodes in this disease process has become the most contentious aspect of surgical decision-making due to the ambiguity of their prognostic significance and the prevalence of nodal metastases in very early primary tumors. Performance of prophylactic central compartment node dissection is not technically any more difficult than therapeutic node dissection when clinically significant nodes are encountered. It is therefore reasonable to consider this technique as an important adjunct to a total thyroidectomy for the purpose of enhanced disease staging, prevention of nodal recurrence, and avoidance of having to re-enter the previously operated central compartment. A recent study is reviewed and discussed in detail. The literature regarding the prognostic significance of extracapsular spread in lymph nodes is also presented. Morphologic characteristics of metastatic lymph nodes in thyroid cancer vary greatly. However, the reporting of these differences is lacking. The presence of extracapsular extension in a lymph node has prognostic significance. The clinician should be aware of these variations and the impact that they may have on recurrence risk and disease-specific survival.

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience

PubMed Central

Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R.; Chagpar, Anees B.

2017-01-01

Background. Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods. Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results. At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1–15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion. Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient. PMID:28492062

Consistency mapping of 16 lymph node stations in gastric cancer by CT-based vessel-guided delineation of 255 patients.

PubMed

Xu, Shuhang; Feng, Lingling; Chen, Yongming; Sun, Ying; Lu, Yao; Huang, Shaomin; Fu, Yang; Zheng, Rongqin; Zhang, Yujing; Zhang, Rong

2017-06-20

In order to refine the location and metastasis-risk density of 16 lymph node stations of gastric cancer for neoadjuvant radiotherapy, we retrospectively reviewed the initial images and pathological reports of 255 gastric cancer patients with lymphatic metastasis. Metastatic lymph nodes identified in the initial computed tomography images were investigated by two radiologists with gastrointestinal specialty. A circle with a diameter of 5 mm was used to identify the central position of each metastatic lymph node, defined as the LNc (the central position of the lymph node). The LNc was drawn at the equivalent location on the reference images of a standard patient based on the relative distances to the same reference vessels and the gastric wall using a Monaco® version 5.0 workstation. The image manipulation software Medi-capture was programmed for image analysis to produce a contour and density atlas of 16 lymph node stations. Based on a total of 2846 LNcs contoured (31-599 per lymph node station), we created a density distribution map of 16 lymph node drainage stations of the stomach on computed tomography images, showing the detailed radiographic delineation of each lymph node station as well as high-risk areas for lymph node metastasis. Our mapping can serve as a template for the delineation of gastric lymph node stations when defining clinical target volume in pre-operative radiotherapy for gastric cancer.

Improvement of the SEP protocol based on community structure of node degree

NASA Astrophysics Data System (ADS)

Li, Donglin; Wei, Suyuan

2017-05-01

Analyzing the Stable election protocol (SEP) in wireless sensor networks and aiming at the problem of inhomogeneous cluster-heads distribution and unreasonable cluster-heads selectivity and single hop transmission in the SEP, a SEP Protocol based on community structure of node degree (SEP-CSND) is proposed. In this algorithm, network node deployed by using grid deployment model, and the connection between nodes established by setting up the communication threshold. The community structure constructed by node degree, then cluster head is elected in the community structure. On the basis of SEP, the node's residual energy and node degree is added in cluster-heads election. The information is transmitted with mode of multiple hops between network nodes. The simulation experiments showed that compared to the classical LEACH and SEP, this algorithm balances the energy consumption of the entire network and significantly prolongs network lifetime.

Signaling completion of a message transfer from an origin compute node to a target compute node

DOEpatents

Blocksome, Michael A [Rochester, MN; Parker, Jeffrey J [Rochester, MN

2011-05-24

Signaling completion of a message transfer from an origin node to a target node includes: sending, by an origin DMA engine, an RTS message, the RTS message specifying an application message for transfer to the target node from the origin node; receiving, by the origin DMA engine, a remote get message containing a data descriptor for the message and a completion notification descriptor, the completion notification descriptor specifying a local direct put transfer operation for transferring data locally on the origin node; inserting, by the origin DMA engine in an injection FIFO buffer, the data descriptor followed by the completion notification descriptor; transferring, by the origin DMA engine to the target node, the message in dependence upon the data descriptor; and notifying, by the origin DMA engine, the application that transfer of the message is complete in dependence upon the completion notification descriptor.

Dedicated heterogeneous node scheduling including backfill scheduling

DOEpatents

Wood, Robert R [Livermore, CA; Eckert, Philip D [Livermore, CA; Hommes, Gregg [Pleasanton, CA

2006-07-25

A method and system for job backfill scheduling dedicated heterogeneous nodes in a multi-node computing environment. Heterogeneous nodes are grouped into homogeneous node sub-pools. For each sub-pool, a free node schedule (FNS) is created so that the number of to chart the free nodes over time. For each prioritized job, using the FNS of sub-pools having nodes useable by a particular job, to determine the earliest time range (ETR) capable of running the job. Once determined for a particular job, scheduling the job to run in that ETR. If the ETR determined for a lower priority job (LPJ) has a start time earlier than a higher priority job (HPJ), then the LPJ is scheduled in that ETR if it would not disturb the anticipated start times of any HPJ previously scheduled for a future time. Thus, efficient utilization and throughput of such computing environments may be increased by utilizing resources otherwise remaining idle.

Chaining direct memory access data transfer operations for compute nodes in a parallel computer

DOEpatents

Archer, Charles J.; Blocksome, Michael A.

2010-09-28

Methods, systems, and products are disclosed for chaining DMA data transfer operations for compute nodes in a parallel computer that include: receiving, by an origin DMA engine on an origin node in an origin injection FIFO buffer for the origin DMA engine, a RGET data descriptor specifying a DMA transfer operation data descriptor on the origin node and a second RGET data descriptor on the origin node, the second RGET data descriptor specifying a target RGET data descriptor on the target node, the target RGET data descriptor specifying an additional DMA transfer operation data descriptor on the origin node; creating, by the origin DMA engine, an RGET packet in dependence upon the RGET data descriptor, the RGET packet containing the DMA transfer operation data descriptor and the second RGET data descriptor; and transferring, by the origin DMA engine to a target DMA engine on the target node, the RGET packet.

Signaling completion of a message transfer from an origin compute node to a target compute node

DOEpatents

Blocksome, Michael A [Rochester, MN

2011-02-15

Signaling completion of a message transfer from an origin node to a target node includes: sending, by an origin DMA engine, an RTS message, the RTS message specifying an application message for transfer to the target node from the origin node; receiving, by the origin DMA engine, a remote get message containing a data descriptor for the message and a completion notification descriptor, the completion notification descriptor specifying a local memory FIFO data transfer operation for transferring data locally on the origin node; inserting, by the origin DMA engine in an injection FIFO buffer, the data descriptor followed by the completion notification descriptor; transferring, by the origin DMA engine to the target node, the message in dependence upon the data descriptor; and notifying, by the origin DMA engine, the application that transfer of the message is complete in dependence upon the completion notification descriptor.

Method and computer product to increase accuracy of time-based software verification for sensor networks

DOEpatents

Foo Kune, Denis [Saint Paul, MN; Mahadevan, Karthikeyan [Mountain View, CA

2011-01-25

A recursive verification protocol to reduce the time variance due to delays in the network by putting the subject node at most one hop from the verifier node provides for an efficient manner to test wireless sensor nodes. Since the software signatures are time based, recursive testing will give a much cleaner signal for positive verification of the software running on any one node in the sensor network. In this protocol, the main verifier checks its neighbor, who in turn checks its neighbor, and continuing this process until all nodes have been verified. This ensures minimum time delays for the software verification. Should a node fail the test, the software verification downstream is halted until an alternative path (one not including the failed node) is found. Utilizing techniques well known in the art, having a node tested twice, or not at all, can be avoided.

Multihop teleportation of two-qubit state via the composite GHZ-Bell channel

NASA Astrophysics Data System (ADS)

Zou, Zhen-Zhen; Yu, Xu-Tao; Gong, Yan-Xiao; Zhang, Zai-Chen

2017-01-01

A multihop teleportation protocol in quantum communication network is introduced to teleport an arbitrary two-qubit state, between two nodes without directly sharing entanglement pairs. Quantum channels are built among neighbor nodes based on a five-qubit entangled system composed of GHZ and Bell pairs. The von Neumann measurements in all intermediate nodes and the source node are implemented, and then the measurement outcomes are sent to the destination node independently. After collecting all the measurement outcomes at the destination node, an efficient method is proposed to calculate the unitary operations for transforming the receiver's states to the state teleported. Therefore, only adopting the proper unitary operations at the destination node, the desired quantum state can be recovered perfectly. The transmission flexibility and efficiency of quantum network with composite GHZ-Bell channel are improved by transmitting measurement outcomes of all nodes in parallelism and reducing hop-by-hop teleportation delay.

Support Vector Machines Model of Computed Tomography for Assessing Lymph Node Metastasis in Esophageal Cancer with Neoadjuvant Chemotherapy.

PubMed

Wang, Zhi-Long; Zhou, Zhi-Guo; Chen, Ying; Li, Xiao-Ting; Sun, Ying-Shi

The aim of this study was to diagnose lymph node metastasis of esophageal cancer by support vector machines model based on computed tomography. A total of 131 esophageal cancer patients with preoperative chemotherapy and radical surgery were included. Various indicators (tumor thickness, tumor length, tumor CT value, total number of lymph nodes, and long axis and short axis sizes of largest lymph node) on CT images before and after neoadjuvant chemotherapy were recorded. A support vector machines model based on these CT indicators was built to predict lymph node metastasis. Support vector machines model diagnosed lymph node metastasis better than preoperative short axis size of largest lymph node on CT. The area under the receiver operating characteristic curves were 0.887 and 0.705, respectively. The support vector machine model of CT images can help diagnose lymph node metastasis in esophageal cancer with preoperative chemotherapy.

Parallel compression of data chunks of a shared data object using a log-structured file system

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

Bent, John M.; Faibish, Sorin; Grider, Gary

2016-10-25

Techniques are provided for parallel compression of data chunks being written to a shared object. A client executing on a compute node or a burst buffer node in a parallel computing system stores a data chunk generated by the parallel computing system to a shared data object on a storage node by compressing the data chunk; and providing the data compressed data chunk to the storage node that stores the shared object. The client and storage node may employ Log-Structured File techniques. The compressed data chunk can be de-compressed by the client when the data chunk is read. A storagemore » node stores a data chunk as part of a shared object by receiving a compressed version of the data chunk from a compute node; and storing the compressed version of the data chunk to the shared data object on the storage node.« less

Low latency, high bandwidth data communications between compute nodes in a parallel computer

DOEpatents

Blocksome, Michael A

2014-04-01

Methods, systems, and products are disclosed for data transfers between nodes in a parallel computer that include: receiving, by an origin DMA on an origin node, a buffer identifier for a buffer containing data for transfer to a target node; sending, by the origin DMA to the target node, a RTS message; transferring, by the origin DMA, a data portion to the target node using a memory FIFO operation that specifies one end of the buffer from which to begin transferring the data; receiving, by the origin DMA, an acknowledgement of the RTS message from the target node; and transferring, by the origin DMA in response to receiving the acknowledgement, any remaining data portion to the target node using a direct put operation that specifies the other end of the buffer from which to begin transferring the data, including initiating the direct put operation without invoking an origin processing core.

Low latency, high bandwidth data communications between compute nodes in a parallel computer

DOEpatents

Blocksome, Michael A

2014-04-22

Methods, systems, and products are disclosed for data transfers between nodes in a parallel computer that include: receiving, by an origin DMA on an origin node, a buffer identifier for a buffer containing data for transfer to a target node; sending, by the origin DMA to the target node, a RTS message; transferring, by the origin DMA, a data portion to the target node using a memory FIFO operation that specifies one end of the buffer from which to begin transferring the data; receiving, by the origin DMA, an acknowledgement of the RTS message from the target node; and transferring, by the origin DMA in response to receiving the acknowledgement, any remaining data portion to the target node using a direct put operation that specifies the other end of the buffer from which to begin transferring the data, including initiating the direct put operation without invoking an origin processing core.

Low latency, high bandwidth data communications between compute nodes in a parallel computer

DOEpatents

Blocksome, Michael A

2013-07-02

Methods, systems, and products are disclosed for data transfers between nodes in a parallel computer that include: receiving, by an origin DMA on an origin node, a buffer identifier for a buffer containing data for transfer to a target node; sending, by the origin DMA to the target node, a RTS message; transferring, by the origin DMA, a data portion to the target node using a memory FIFO operation that specifies one end of the buffer from which to begin transferring the data; receiving, by the origin DMA, an acknowledgement of the RTS message from the target node; and transferring, by the origin DMA in response to receiving the acknowledgement, any remaining data portion to the target node using a direct put operation that specifies the other end of the buffer from which to begin transferring the data, including initiating the direct put operation without invoking an origin processing core.

Architecture and method for a burst buffer using flash technology

DOEpatents

Tzelnic, Percy; Faibish, Sorin; Gupta, Uday K.; Bent, John; Grider, Gary Alan; Chen, Hsing-bung

2016-03-15

A parallel supercomputing cluster includes compute nodes interconnected in a mesh of data links for executing an MPI job, and solid-state storage nodes each linked to a respective group of the compute nodes for receiving checkpoint data from the respective compute nodes, and magnetic disk storage linked to each of the solid-state storage nodes for asynchronous migration of the checkpoint data from the solid-state storage nodes to the magnetic disk storage. Each solid-state storage node presents a file system interface to the MPI job, and multiple MPI processes of the MPI job write the checkpoint data to a shared file in the solid-state storage in a strided fashion, and the solid-state storage node asynchronously migrates the checkpoint data from the shared file in the solid-state storage to the magnetic disk storage and writes the checkpoint data to the magnetic disk storage in a sequential fashion.

Endometrial Cancer and the Role of Lymphadenectomy.

PubMed

Clark, Leslie H; Soper, John T

2016-06-01

The role of lymph node dissection in early-stage endometrial cancer is highly debated, but staging and prognosis are dependent on knowledge of lymph node metastasis. We sought to review the available data on the use of lymph node assessment in presumed early-stage endometrial cancer. A comprehensive literature review was performed using MEDLINE, the Cochrane Collaborative Database, and PubMed. There is limited retrospective data that suggest a therapeutic benefit to lymphadenectomy. Prospective randomized trials have not shown a benefit to lymphadenectomy in low-risk patients, but found significant morbidity in patients undergoing lymphadenectomy. Selective lymph node assessment should be used in low-risk endometrial cancer. Sentinel lymph node assessment is emerging as a potential strategy for lymph node assessment. Selective use of lymphadenectomy in early-stage endometrial cancer can reduce the morbidity associated with lymph node dissection without compromising clinical outcomes. Multiple strategies are available including sentinel lymph nodes and risk factor based lymphadenectomy.

High Occurrence of Aberrant Lymph Node Spread on Magnetic Resonance Lymphography in Prostate Cancer Patients With a Biochemical Recurrence After Radical Prostatectomy

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

Meijer, Hanneke J.M., E-mail: H.Meijer@rther.umcn.nl; Lin, Emile N. van; Debats, Oscar A.

2012-03-15

Purpose: To investigate the pattern of lymph node spread in prostate cancer patients with a biochemical recurrence after radical prostatectomy, eligible for salvage radiotherapy; and to determine whether the clinical target volume (CTV) for elective pelvic irradiation in the primary setting can be applied in the salvage setting for patients with (a high risk of) lymph node metastases. Methods and Materials: The charts of 47 prostate cancer patients with PSA recurrence after prostatectomy who had positive lymph nodes on magnetic resonance lymphography (MRL) were reviewed. Positive lymph nodes were assigned to a lymph node region according to the guidelines ofmore » the Radiation Therapy Oncology Group (RTOG) for delineation of the CTV for pelvic irradiation (RTOG-CTV). We defined four lymph node regions for positive nodes outside this RTOG-CTV: the para-aortal, proximal common iliac, pararectal, and paravesical regions. They were referred to as aberrant lymph node regions. For each patient, clinical and pathologic features were recorded, and their association with aberrant lymph drainage was investigated. The distribution of positive lymph nodes was analyzed separately for patients with a prostate-specific antigen (PSA) <1.0 ng/mL. Results: MRL detected positive aberrant lymph nodes in 37 patients (79%). In 20 patients (43%) a positive lymph node was found in the pararectal region. Higher PSA at the time of MRL was associated with the presence of positive lymph nodes in the para-aortic region (2.49 vs. 0.82 ng/mL; p = 0.007) and in the proximal common iliac region (1.95 vs. 0.59 ng/mL; p = 0.009). There were 18 patients with a PSA <1.0 ng/mL. Ten of these patients (61%) had at least one aberrant positive lymph node. Conclusion: Seventy-nine percent of the PSA-recurrent patients had at least one aberrant positive lymph node. Application of the standard RTOG-CTV for pelvic irradiation in the salvage setting therefore seems to be inappropriate.« less

A prospective investigation of fluorescence imaging to detect sentinel lymph nodes at robotic-assisted endometrial cancer staging.

PubMed

Paley, Pamela J; Veljovich, Dan S; Press, Joshua Z; Isacson, Christina; Pizer, Ellen; Shah, Chirag

2016-07-01

The accuracy of sentinel lymph node mapping has been shown in endometrial cancer, but studies to date have primarily focused on cohorts at low risk for nodal involvement. In our practice, we acknowledge the lack of benefit of lymphadenectomy in the low-risk subgroup and omit lymph node removal in these patients. Thus, our aim was to evaluate the feasibility and accuracy of sentinel node mapping in women at sufficient risk for nodal metastasis warranting lymphadenectomy and in whom the potential benefit of avoiding nodal procurement could be realized. To evaluate the detection rate and accuracy of fluorescence-guided sentinel lymph node mapping in endometrial cancer patients undergoing robotic-assisted staging. One hundred twenty-three endometrial cancer patients undergoing sentinel lymph node sentinel node mapping using indocyanine green were prospectively evaluated. Two mL (1.0 mg/mL) of dye were injected into the cervical stroma divided between the 2-3 and 9-10 o'clock positions at the time of uterine manipulator placement. Before hysterectomy, the retroperitoneal spaces were developed and fluorescence imaging was used for sentinel node detection. Identified sentinel nodes were removed and submitted for touch prep intraoperatively, followed by permanent assessment with routine hematoxylin and eosin levels. Patients then underwent hysterectomy, bilateral salpingo-oophorectomy, and completion bilateral pelvic and periaortic lymphadenectomy based on intrauterine risk factors determined intraoperatively (tumor size >2 cm, >50% myometrial invasion, and grade 3 histology). Of 123 patients enrolled, at least 1 sentinel node was detected in 119 (96.7%). Ninety-nine patients (80%) had bilateral pelvic or periaortic sentinel nodes detected. A total of 85 patients met criteria warranting completion lymphadenectomy. In 14 patients (16%) periaortic lymphadenectomy was not feasible, and the mean number of pelvic nodes procured was 13 (6-22). Of the 71 patients undergoing pelvic and periaortic lymphadenectomy, the mean nodal count was 23.2 (8-51). Of patients undergoing lymphadenectomy, 10.6% had lymph node metastasis on final hematoxylin and eosin evaluation. Notably, the sentinel node was the only positive node in 44% of cases. There were no cases in which final pathology of the sentinel node was negative and metastatic disease was detected upon completion lymphadenectomy in the non-sentinel nodes (no false negatives), yielding a sensitivity of 100%. Of the 14 sentinel nodes ultimately found to harbor metastases, 3 were negative on touch prep, yielding a sensitivity of 78.6% for intraoperative detection of sentinel node involvement. In all 3 of the false-negative touch preps, final pathology detected a single micrometastasis (0.24 mm, 1.4 mm, 1.5 mm). As expected, there were no false-positive results, yielding a specificity of 100%. No complications related to sentinel node mapping or allergic reactions to the dye were encountered. Intraoperative sentinel node mapping using fluorescence imaging with indocyanine green in endometrial cancer patients is feasible and yields high detection rates. In our pilot study, sentinel node mapping identified all women with Stage IIIC disease. Low false-negative rates are encouraging, and if confirmed in multi-institutional trials, this approach would be anticipated to reduce the morbidity, operative times, and costs associated with complete pelvic and periaortic lymphadenectomy. Copyright © 2015 Elsevier Inc. All rights reserved.

[Measurement of intrafraction displacement of the mediastinal metastatic lymph nodes of non-small cell lung cancer based on four-dimensional computed tomography (4D-CT)].

PubMed

Wang, Su-zhen; Li, Jian-bin; Zhang, Ying-jie; Li, Feng-xiang; Wang, Wei; Liu, Tong-hai

2012-09-01

To measure the intrafraction displacement of the mediastinal metastatic lymph nodes of non-small cell lung cancer (NSCLC) based on four-dimensional computed tomography (4D-CT), and to provide the basis for the internal margin of metastatic mediastinal lymph nodes. Twenty-four NSCLC patients with mediastinal metastatic lymph nodes confirmed by contrast enhanced CT (short axis diameter ≥ 1 cm) were included in this study. 4D-CT simulation was carried out during free breathing and 10 image sets were acquired. The mediastinal metastatic lymph nodes and the dome of ipsilateral diaphragma were separately delineated on the CT images of 10 phases of breath cycle, and the lymph nodes were grouped as the upper, middle and lower mediastinal groups depending on the mediastinal station. Then the displacements of the lymph nodes in the left-right, anterior-posterior, superior-inferior directions and the 3-dimensional vector were measured. The differences of displacement in three directions for the same group of metastatic lymph nodes and in the same direction for different groups of metastatic lymph nodes were compared. The correlation between the displacement of ipsilateral diaphragma and mediastinal lymph nodes was analyzed in superior-inferior direction. The displacements in left-right, anterior-posterior and superior-inferior directions were (2.24 ± 1.55) mm, (1.87 ± 0.92) mm and (3.28 ± 2.59) mm for the total (53) mediastinal lymph nodes, respectively. The vectors were (4.70 ± 2.66) mm, (3.87 ± 2.45) mm, (4.97 ± 2.75) mm and (5.23 ± 2.67) mm for the total, upper, middle and lower mediastinal lymph nodes, respectively. For the upper mediastinal lymph nodes, the displacements in left-right, anterior-posterior and superior-inferior directions showed no significant difference between each other (P > 0.05). For the middle mediastinal lymph nodes, the displacements merely in anterior-posterior and superior-inferior directions showed significant difference (P = 0.005), while the displacements were not significantly different in the left-right and anterior-posterior, left-right and superior-inferior directions (P > 0.05). The displacements of the total and the lower mediastinal lymph nodes in left-right and superior-inferior, or anterior-posterior and superior-inferior directions were significantly different (P < 0.05), but was not significantly different in left-right and anterior-posterior directions (P > 0.05). The displacements of different group of mediastinal lymph nodes in a single direction or vector showed no significant difference (P > 0.05). In the superior-inferior direction, the correlation between the displacements of ipsilateral diaphragma and mediastinal lymph nodes were not statistically significant (P > 0.05). During free breathing, the differences between the intrafractional displacement of mediastinal metastatic lymph nodes in the same direction and its station were not statistically significant. The displacements of the total mediastinal metastatic lymph nodes in the superior-inferior direction were greater than that in the left-right and anterior-posterior directions, especially for the middle and lower mediastinal metastatic lymph nodes. There was no significant correlation between the displacements of ipsilateral diaphragma and the mediastinal metastatic lymph nodes in the superior-inferior direction, so it was unreasonable to estimate and predict the displacement of mediastinal metastatic lymph nodes by the displacement of ipsilateral diaphragma.

Utilization and Outcomes of Sentinel Lymph Node Biopsy for Vulvar Cancer.

PubMed

Cham, Stephanie; Chen, Ling; Burke, William M; Hou, June Y; Tergas, Ana I; Hu, Jim C; Ananth, Cande V; Neugut, Alfred I; Hershman, Dawn L; Wright, Jason D

2016-10-01

To examine the use and predictors of sentinel node biopsy in women with vulvar cancer. The Perspective database, an all-payer database that collects data from more than 500 hospitals, was used to perform a retrospective cohort study of women with vulvar cancer who underwent vulvectomy and lymph node assessment from 2006 to 2015. Multivariable models were used to determine factors associated with sentinel node biopsy. Length of stay and cost were compared between women who underwent sentinel node biopsy and lymphadenectomy. Among 2,273 women, sentinel node biopsy was utilized in 618 (27.2%) and 1,655 (72.8%) underwent inguinofemoral lymphadenectomy. Performance of sentinel node biopsy increased from 17.0% (95% confidence interval [CI] 12.0-22.0%) in 2006 to 39.1% (95% CI 27.1-51.0%) in 2015. In a multivariable model, women treated more recently were more likely to have undergone sentinel node biopsy, whereas women with more comorbidities and those treated at rural hospitals were less likely to have undergone the procedure. The median length of stay was shorter for those undergoing sentinel node biopsy (median 2 days, interquartile range 1-3) compared with women who underwent inguinofemoral lymphadenectomy (median 3 days, interquartile range 2-4). The cost of sentinel node biopsy was $7,599 (interquartile range $5,739-9,922) compared with $8,095 (interquartile range $5,917-11,281) for lymphadenectomy. The use of sentinel node biopsy for vulvar cancer has more than doubled since 2006. Sentinel lymph node biopsy is associated with a shorter hospital stay and decreased cost compared with inguinofemoral lymphadenectomy.

Breast cancer sentinel node scintigraphy: differences between imaging results 1 and 2 h after injection.

PubMed

Wondergem, Maurits; Hobbelink, Monique G G; Witkamp, Arjen J; van Hillegersberg, Richard; de Keizer, Bart

2012-11-01

Timing of image acquisition in breast cancer sentinel node scintigraphy remains a subject of debate. Therefore, the performance of our protocol in which images are acquired 1 and 2 h after injection was evaluated. The results of sentinel node scintigraphy 1 and 2 h after injection were compared with regard to the sentinel lymph nodes visualized. We studied 132 patients who were consecutively referred for sentinel lymph node biopsy. 99mTc-albumine nanocolloid (120 MBq) was injected peritumourally into patients with palpable tumours and intratumourally into patients with nonpalpable tumours. All scintigraphic images taken for the sentinel node procedure were evaluated. The number of sentinel nodes per anatomic localization and the interpretability of the images were scored. A total of 132 patients underwent sentinel node scintigraphy 1 h after injection. Of these, 117 patients also underwent sentinel node scintigraphy 2 h after injection. An axillary sentinel node was visualized in 79.5 and 95.7% of patients, respectively, 1 and 2 h after injection. In 20.5% of the patients the images acquired 1 h after injection did not show a sentinel node. Furthermore, in all procedures, the images 1 h after injection were of no added value to those acquired 2 h after injection. Scintigraphic imaging 2 h after a single peritumoural or intratumoural administration of about 120 MBq 99mTc-albumine nanocolloid yields an axillary sentinel node in over 95% of cases. Imaging 1 h after injection is of no additional value and can be omitted.

Sentinel lymph node biopsy as a prognostic factor in non-metastatic colon cancer: a prospective study.

PubMed

Estrada, O; Pulido, L; Admella, C; Hidalgo, L-A; Clavé, P; Suñol, X

2017-04-01

Around a third of node-negative patients with colon cancer experience a recurrence after surgery, suggesting poor staging. Sentinel lymph node techniques combined with immunochemistry could improve colon cancer staging. We prospectively assessed the effect of Sentinel node mapping on staging and survival in patients with non-metastatic colon cancer. An observational and prospective study was designed. 105 patients with colon cancer were selected. Patients were classified according to node involvement as: N1, with node invasion detected by the conventional techniques; up-staged, with node invasion detected only by sentinel node mapping; and N0, with negative lymph node involvement by both techniques. Five-year survival and disease-free survival rates were analysed. Multivariate regression analyses were performed to identify prognostic factors for disease-free and overall survival. Sentinel node mapping was successfully applied in 78 patients: 33 % were N1; 24.5 % were up-staged (18 patients with isolated tumour cells and 1 patient with micrometastases); and 42.5 % were N0. N1 patients had the poorest overall 5-year survival (65.4 %) and 5-year disease-free survival (69.2 %) rates compared with the other two groups. No significant 5-year survival differences were observed between N0 patients (87.9 %) and up-staged patients (84.2 %). Patients up-staged after sentinel node mapping do not have a poorer prognosis than patients without node involvement. Detection of isolated cancer cells was not a poor prognosis factor in these patients.

DoS detection in IEEE 802.11 with the presence of hidden nodes

PubMed Central

Soryal, Joseph; Liu, Xijie; Saadawi, Tarek

2013-01-01

The paper presents a novel technique to detect Denial of Service (DoS) attacks applied by misbehaving nodes in wireless networks with the presence of hidden nodes employing the widely used IEEE 802.11 Distributed Coordination Function (DCF) protocols described in the IEEE standard [1]. Attacker nodes alter the IEEE 802.11 DCF firmware to illicitly capture the channel via elevating the probability of the average number of packets transmitted successfully using up the bandwidth share of the innocent nodes that follow the protocol standards. We obtained the theoretical network throughput by solving two-dimensional Markov Chain model as described by Bianchi [2], and Liu and Saadawi [3] to determine the channel capacity. We validated the results obtained via the theoretical computations with the results obtained by OPNET simulator [4] to define the baseline for the average attainable throughput in the channel under standard conditions where all nodes follow the standards. The main goal of the DoS attacker is to prevent the innocent nodes from accessing the channel and by capturing the channel’s bandwidth. In addition, the attacker strives to appear as an innocent node that follows the standards. The protocol resides in every node to enable each node to police other nodes in its immediate wireless coverage area. All innocent nodes are able to detect and identify the DoS attacker in its wireless coverage area. We applied the protocol to two Physical Layer technologies: Direct Sequence Spread Spectrum (DSSS) and Frequency Hopping Spread Spectrum (FHSS) and the results are presented to validate the algorithm. PMID:25685510

DoS detection in IEEE 802.11 with the presence of hidden nodes.

PubMed

Soryal, Joseph; Liu, Xijie; Saadawi, Tarek

2014-07-01

The paper presents a novel technique to detect Denial of Service (DoS) attacks applied by misbehaving nodes in wireless networks with the presence of hidden nodes employing the widely used IEEE 802.11 Distributed Coordination Function (DCF) protocols described in the IEEE standard [1]. Attacker nodes alter the IEEE 802.11 DCF firmware to illicitly capture the channel via elevating the probability of the average number of packets transmitted successfully using up the bandwidth share of the innocent nodes that follow the protocol standards. We obtained the theoretical network throughput by solving two-dimensional Markov Chain model as described by Bianchi [2], and Liu and Saadawi [3] to determine the channel capacity. We validated the results obtained via the theoretical computations with the results obtained by OPNET simulator [4] to define the baseline for the average attainable throughput in the channel under standard conditions where all nodes follow the standards. The main goal of the DoS attacker is to prevent the innocent nodes from accessing the channel and by capturing the channel's bandwidth. In addition, the attacker strives to appear as an innocent node that follows the standards. The protocol resides in every node to enable each node to police other nodes in its immediate wireless coverage area. All innocent nodes are able to detect and identify the DoS attacker in its wireless coverage area. We applied the protocol to two Physical Layer technologies: Direct Sequence Spread Spectrum (DSSS) and Frequency Hopping Spread Spectrum (FHSS) and the results are presented to validate the algorithm.

Indocyanine green SPY elite-assisted sentinel lymph node biopsy in cutaneous melanoma.

PubMed

Korn, Jason M; Tellez-Diaz, Alejandra; Bartz-Kurycki, Marisa; Gastman, Brian

2014-04-01

Sentinel lymph node biopsy is the standard of care for intermediate-depth and high-risk thin melanomas. Recently, indocyanine green and near-infrared imaging have been used to aid in sentinel node biopsy. The present study aimed to determine the feasibility of sentinel lymph node biopsy with indocyanine green SPY Elite navigation and to critically evaluate the technique compared with the standard modalities. A retrospective review of 90 consecutive cutaneous melanoma patients who underwent sentinel lymph node biopsy was performed. Two cohorts were formed: group A, which had sentinel lymph node biopsy performed with blue dye and radioisotope; and group B, which had sentinel lymph node biopsy performed with radioisotope and indocyanine green SPY Elite navigation. The cohorts were compared to assess for differences in localization rates, sensitivity and specificity of sentinel node identification, and length of surgery. The sentinel lymph node localization rate was 79.4 percent using the blue dye method, 98.0 percent using the indocyanine green fluorescence method, and 97.8 percent using the radioisotope/handheld gamma probe method. Indocyanine green fluorescence detected more sentinel lymph nodes than the vital dye method alone (p = 0.020). A trend toward a reduction in length of surgery was noted in the SPY Elite cohort. Sentinel lymph node mapping and localization in cutaneous melanoma with the indocyanine green SPY Elite navigation system is technically feasible and may offer several advantages over current modalities, including higher sensitivity and specificity, decreased number of lymph nodes sampled, decreased operative time, and potentially lower false-negative rates. Diagnostic, II.

Paired-agent fluorescent imaging to detect micrometastases in breast sentinel lymph node biopsy: experiment design and protocol development

NASA Astrophysics Data System (ADS)

Li, Chengyue; Xu, Xiaochun; Basheer, Yusairah; He, Yusheng; Sattar, Husain A.; Brankov, Jovan G.; Tichauer, Kenneth M.

2018-02-01

Sentinel lymph node status is a critical prognostic factor in breast cancer treatment and is essential to guide future adjuvant treatment. The estimation that 20-60% of micrometastases are missed by conventional pathology has created a demand for the development of more accurate approaches. Here, a paired-agent imaging approach is presented that employs a control imaging agent to allow rapid, quantitative mapping of microscopic populations of tumor cells in lymph nodes to guide pathology sectioning. To test the feasibility of this approach to identify micrometastases, healthy pig lymph nodes were stained with targeted and control imaging agent solution to evaluate the potential for the agents to diffuse into and out of intact nodes. Aby-029, an anti-EGFR affibody was labeled with IRDye 800CW (LICOR) as targeted agent and IRDye 700DX was hydrolyzed as a control agent. Lymph nodes were stained and rinsed by directly injecting the agents into the lymph nodes after immobilization in agarose gel. Subsequently, lymph nodes were frozen-sectioned and imaged under an 80-um resolution fluorescence imaging system (Pearl, LICOR) to confirm equivalence of spatial distribution of both agents in the entire node. The binding potentials were acquired by a pixel-by-pixel calculation and was found to be 0.02 +/- 0.06 along the lymph node in the absence of binding. The results demonstrate this approach's potential to enhance the sensitivity of lymph node pathology by detecting fewer than 1000 cell in a whole human lymph node.

Community detection using preference networks

NASA Astrophysics Data System (ADS)

Tasgin, Mursel; Bingol, Haluk O.

2018-04-01

Community detection is the task of identifying clusters or groups of nodes in a network where nodes within the same group are more connected with each other than with nodes in different groups. It has practical uses in identifying similar functions or roles of nodes in many biological, social and computer networks. With the availability of very large networks in recent years, performance and scalability of community detection algorithms become crucial, i.e. if time complexity of an algorithm is high, it cannot run on large networks. In this paper, we propose a new community detection algorithm, which has a local approach and is able to run on large networks. It has a simple and effective method; given a network, algorithm constructs a preference network of nodes where each node has a single outgoing edge showing its preferred node to be in the same community with. In such a preference network, each connected component is a community. Selection of the preferred node is performed using similarity based metrics of nodes. We use two alternatives for this purpose which can be calculated in 1-neighborhood of nodes, i.e. number of common neighbors of selector node and its neighbors and, the spread capability of neighbors around the selector node which is calculated by the gossip algorithm of Lind et.al. Our algorithm is tested on both computer generated LFR networks and real-life networks with ground-truth community structure. It can identify communities accurately in a fast way. It is local, scalable and suitable for distributed execution on large networks.

Extraperitoneal lymph node dissection in locally advanced cervical cancer; the prognostic factors associated with survival

PubMed Central

Köse, Mehmet Faruk; Kiseli, Mine; Kimyon, Günsu; Öcalan, Reyhan; Yenen, Müfit Cemal; Tulunay, Gökhan; Turan, Ahmet Taner; Üreyen, Işın; Boran, Nurettin

2017-01-01

Objective: Surgical staging was recently recommended for the decision of treatment in locally advanced cervical cancer. We aimed to investigate clinical outcomes as well as factors associated with overall survival (OS) in patients with locally advanced cervical cancer who had undergone extraperitoneal lymph node dissection and were managed according to their lymph node status. Material and Methods: The medical records of 233 women with stage IIb-IVa cervical cancer who were clinically staged and underwent extraperitoneal lymph node dissection were retrospectively reviewed. Paraaortic lymph node status determined the appropriate radiotherapeutic treatment field. Surgery-related complications and clinical outcomes were evaluated. Results: The median age of the patients was 52 years (range, 26-88 years) and the median follow-up time was 28.4 months (range, 3-141 months). Thirty-one patients had laparoscopic extraperitoneal lymph node dissection and 202 patients underwent laparotomy. The number of paraaortic lymph nodes extracted was similar for both techniques. Sixty-two (27%) of the 233 patients had paraaortic lymph node metastases. The 3-year and 5-year OS rates were 55.1% and 46.5%, respectively. The stage of disease, number of metastatic paraaortic lymph nodes, tumor type, and paraaortic lymph node status were associated with OS. In multivariate Cox regression analyses, tumor type, stage, and presence of paraaortic lymph node metastases were the independent prognostic factors of OS. Conclusion: Paraaortic lymph node metastasis is the most important prognostic factor affecting survival. Surgery would give hints about the prognosis and treatment planning of the patient. PMID:28400350

International Space Station Node 1 is moved for leak test

NASA Technical Reports Server (NTRS)

1998-01-01

Node 1, the first element for the International Space Station, and attached Pressurized Mating Adapter-1 continue with prelaunch preparation activities at KSC's Space Station Processing Facility. Node 1 is a connecting passageway to the living and working areas of the space station. The node is seen here being moved into the Shuttle payload transportation canister, where the doors will be closed for a two-week leak check. The node was moved to the canister from the element rotation stand, or test stand, where it underwent an interim weight and center of gravity determination. The final determination is planned to be performed prior to transporting Node 1 to the launch pad. Node 1 is scheduled to fly on STS-88.

International Space Station Node 1 is moved for leak test

NASA Technical Reports Server (NTRS)

1998-01-01

Node 1, the first U.S. element for the International Space Station, and attached Pressurized Mating Adapter-1 continue with prelaunch preparation activities at KSC's Space Station Processing Facility. Node 1 is a connecting passageway to the living and working areas of the space station. The node and PMA-1 are being removed from the element rotation stand, or test stand, where they underwent an interim weight and center of gravity determination. (The final determination is planned to be performed prior to transporting Node 1 to the launch pad.) Now the node is being moved to the Shuttle payload transportation canister, where the doors will be closed for a two-week leak check. Node 1 is scheduled to fly on STS-88.

Bad data packet capture device

DOEpatents

Chen, Dong; Gara, Alan; Heidelberger, Philip; Vranas, Pavlos

2010-04-20

An apparatus and method for capturing data packets for analysis on a network computing system includes a sending node and a receiving node connected by a bi-directional communication link. The sending node sends a data transmission to the receiving node on the bi-directional communication link, and the receiving node receives the data transmission and verifies the data transmission to determine valid data and invalid data and verify retransmissions of invalid data as corresponding valid data. A memory device communicates with the receiving node for storing the invalid data and the corresponding valid data. A computing node communicates with the memory device and receives and performs an analysis of the invalid data and the corresponding valid data received from the memory device.

Low Latency MAC Protocol in Wireless Sensor Networks Using Timing Offset

NASA Astrophysics Data System (ADS)

Choi, Seung Sik

This paper proposes a low latency MAC protocol that can be used in sensor networks. To extend the lifetime of sensor nodes, the conventional solution is to synchronize active/sleep periods of all sensor nodes. However, due to these synchronized sensor nodes, packets in the intermediate nodes must wait until the next node wakes up before it can forward a packet. This induces a large delay in sensor nodes. To solve this latency problem, a clustered sensor network which uses two types of sensor nodes and layered architecture is considered. Clustered heads in each cluster are synchronized with different timing offsets to reduce the sleep delay. Using this concept, the latency problem can be solved and more efficient power usage can be obtained.

Compressed sensing based missing nodes prediction in temporal communication network

NASA Astrophysics Data System (ADS)

Cheng, Guangquan; Ma, Yang; Liu, Zhong; Xie, Fuli

2018-02-01

The reconstruction of complex network topology is of great theoretical and practical significance. Most research so far focuses on the prediction of missing links. There are many mature algorithms for link prediction which have achieved good results, but research on the prediction of missing nodes has just begun. In this paper, we propose an algorithm for missing node prediction in complex networks. We detect the position of missing nodes based on their neighbor nodes under the theory of compressed sensing, and extend the algorithm to the case of multiple missing nodes using spectral clustering. Experiments on real public network datasets and simulated datasets show that our algorithm can detect the locations of hidden nodes effectively with high precision.

Method for nonlinear optimization for gas tagging and other systems

DOEpatents

Chen, Ting; Gross, Kenny C.; Wegerich, Stephan

1998-01-01

A method and system for providing nuclear fuel rods with a configuration of isotopic gas tags. The method includes selecting a true location of a first gas tag node, selecting initial locations for the remaining n-1 nodes using target gas tag compositions, generating a set of random gene pools with L nodes, applying a Hopfield network for computing on energy, or cost, for each of the L gene pools and using selected constraints to establish minimum energy states to identify optimal gas tag nodes with each energy compared to a convergence threshold and then upon identifying the gas tag node continuing this procedure until establishing the next gas tag node until all remaining n nodes have been established.

Method for nonlinear optimization for gas tagging and other systems

DOEpatents

Chen, T.; Gross, K.C.; Wegerich, S.

1998-01-06

A method and system are disclosed for providing nuclear fuel rods with a configuration of isotopic gas tags. The method includes selecting a true location of a first gas tag node, selecting initial locations for the remaining n-1 nodes using target gas tag compositions, generating a set of random gene pools with L nodes, applying a Hopfield network for computing on energy, or cost, for each of the L gene pools and using selected constraints to establish minimum energy states to identify optimal gas tag nodes with each energy compared to a convergence threshold and then upon identifying the gas tag node continuing this procedure until establishing the next gas tag node until all remaining n nodes have been established. 6 figs.

[Anatomy and histology characteristics of lymph node in nude mice].

PubMed

Sun, R; Gao, B; Guo, C B

2017-10-18

To compare the differences of anatomical and histological characteristics of lymph nodes between BALB/c nude mice and BALB/c mice. Firstly, twenty BALB/c nude mice and twenty BALB/c mice were dissected by using a surgical microscope. Secondly, the differences of T cells and B cells at the lymph node were compared by the expressions of CD 3 and CD 20 immunohistochemistry dyes. There were, on average, 23 nodes per mouse contained within the large lymph node assembly in the BALB/c nude mouse. The anatomical features of the lymph node distribution in the nude mice were mainly found in the neck with relatively higher density. There were two lymph nodes both in the submandible lymph nodes group and in the superficial cervical lymph nodes group (the constituent ratios were 95% and 90%, respectively) in the BALB/c nude mice, but there were four lymph nodes (the constituent ratios were 95% and 90%, respectively) in the BALB/c mice. There were significant difference between the BALB/c nude mice and the BALB/c mice. Mostly there were two lymph nodes of deep cervical lymph nodes both in the BALB/c nude mice and the BALB/c mice (the constituent ratios were 95% and 100%, respectively). There were no significant difference between the BALB/c nude mice and the BALB/c mice. We confirmed that the number of CD 3 -positive T lymphocytes in lymph nodes of the nude mice decreased greatly as compared with the BALB/c mice. Expressions of CD3 in T cells were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively. There were significant differences between the BALB/c nude mice and the BALB/c mice. Expressions of CD20 in B cells were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively. There was no significant difference between the BALB/c nude mice and BALB/c mice. The anatomical pictures of lymph node distribution in the nude mouse will be benefit to those who are interested. The anatomical features of the lymph node local higher density in neck of the nude mouse and lack of CD3-positive T lymphocytes would be useful for obtaining a better understanding of localized lymph node metastasis of oral transplant tumors.

Dynamic resource allocation scheme for distributed heterogeneous computer systems

NASA Technical Reports Server (NTRS)

Liu, Howard T. (Inventor); Silvester, John A. (Inventor)

1991-01-01

This invention relates to a resource allocation in computer systems, and more particularly, to a method and associated apparatus for shortening response time and improving efficiency of a heterogeneous distributed networked computer system by reallocating the jobs queued up for busy nodes to idle, or less-busy nodes. In accordance with the algorithm (SIDA for short), the load-sharing is initiated by the server device in a manner such that extra overhead in not imposed on the system during heavily-loaded conditions. The algorithm employed in the present invention uses a dual-mode, server-initiated approach. Jobs are transferred from heavily burdened nodes (i.e., over a high threshold limit) to low burdened nodes at the initiation of the receiving node when: (1) a job finishes at a node which is burdened below a pre-established threshold level, or (2) a node is idle for a period of time as established by a wakeup timer at the node. The invention uses a combination of the local queue length and the local service rate ratio at each node as the workload indicator.

Automatic identification of IASLC-defined mediastinal lymph node stations on CT scans using multi-atlas organ segmentation

NASA Astrophysics Data System (ADS)

Hoffman, Joanne; Liu, Jiamin; Turkbey, Evrim; Kim, Lauren; Summers, Ronald M.

2015-03-01

Station-labeling of mediastinal lymph nodes is typically performed to identify the location of enlarged nodes for cancer staging. Stations are usually assigned in clinical radiology practice manually by qualitative visual assessment on CT scans, which is time consuming and highly variable. In this paper, we developed a method that automatically recognizes the lymph node stations in thoracic CT scans based on the anatomical organs in the mediastinum. First, the trachea, lungs, and spines are automatically segmented to locate the mediastinum region. Then, eight more anatomical organs are simultaneously identified by multi-atlas segmentation. Finally, with the segmentation of those anatomical organs, we convert the text definitions of the International Association for the Study of Lung Cancer (IASLC) lymph node map into patient-specific color-coded CT image maps. Thus, a lymph node station is automatically assigned to each lymph node. We applied this system to CT scans of 86 patients with 336 mediastinal lymph nodes measuring equal or greater than 10 mm. 84.8% of mediastinal lymph nodes were correctly mapped to their stations.

Towards the development of tamper-resistant, ground-based mobile sensor nodes

NASA Astrophysics Data System (ADS)

Mascarenas, David; Stull, Christopher; Farrar, Charles

2011-11-01

Mobile sensor nodes hold great potential for collecting field data using fewer resources than human operators would require and potentially requiring fewer sensors than a fixed-position sensor array. It would be very beneficial to allow these mobile sensor nodes to operate unattended with a minimum of human intervention. In order to allow mobile sensor nodes to operate unattended in a field environment, it is imperative that they be capable of identifying and responding to external agents that may attempt to tamper with, damage or steal the mobile sensor nodes, while still performing their data collection mission. Potentially hostile external agents could include animals, other mobile sensor nodes, or humans. This work will focus on developing control policies to help enable a mobile sensor node to identify and avoid capture by a hostile un-mounted human. The work is developed in a simulation environment, and demonstrated using a non-holonomic, ground-based mobile sensor node. This work will be a preliminary step toward ensuring the cyber-physical security of ground-based mobile sensor nodes that operate unattended in potentially unfriendly environments.

Node property of weighted networks considering connectability to nodes within two degrees of separation.

PubMed

Amano, Sun-Ichi; Ogawa, Ken-Ichiro; Miyake, Yoshihiro

2018-05-31

Weighted networks have been extensively studied because they can represent various phenomena in which the diversity of edges is essential. To investigate the properties of weighted networks, various centrality measures have been proposed, such as strength, weighted clustering coefficients, and weighted betweenness centrality. In such measures, only direct connections or entire network connectivity from arbitrary nodes have been used to calculate the connectivity of each node. However, in weighted networks composed of autonomous elements such as humans, middle ranges from each node are also considered to be meaningful for characterizing each node's connectability. In this study, we define a new node property in weighted networks to consider connectability to nodes within a range of two degrees of separation, then apply this new centrality to face-to-face human communication networks in corporate organizations. Our results show that the proposed centrality distinguishes inherent communities corresponding to the job types in each organization with a high degree of accuracy. This indicates the possibility that connectability to nodes within two degrees of separation reveals potential trends of weighted networks that are not apparent from conventional measures.

Comparative study between ultrasound-guided fine needle aspiration cytology of axillary lymph nodes and sentinel lymph node histopathology in early-stage breast cancer

PubMed Central

Cardoso-Coelho, Lívio Portela; Borges, Rafael Soares; Alencar, Airlane Pereira; Cardoso-Campos-Verdes, Larysse Maira; da Silva-Sampaio, João Paulo; Borges, Umbelina Soares; Gebrim, Luiz Henrique; da Silva, Benedito Borges

2017-01-01

The replacement of sentinel lymph node biopsy (SNB) by ultrasound-guided fine-needle aspiration (US-guided FNA) cytology of axillary lymph nodes is controversial, despite the simplicity and reduced cost of the latter. In the present study, US-guided FNA was performed in 27 patients with early-stage breast cancer for comparison with SNB. Data were analyzed by calculation of sample proportions. Tumor subtypes included invasive ductal carcinoma (85%), invasive lobular carcinoma (7%), and tubular and metaplastic carcinoma (4%). FNA had a sensitivity of 45%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 73%. Axillary lymph node cytology obtained by US guided-FNA in patients with breast cancer had a specificity similar to that of sentinel lymph node histopathology in the presence of axillary node metastases. However, when lymph node cytology is negative, it does not exclude the existence of metastatic implants, due to its low sensitivity in comparison to sentinel lymph node histopathology. PMID:28521436

Testnodes: a Lightweight Node-Testing Infrastructure

NASA Astrophysics Data System (ADS)

Fay, R.; Bland, J.

2014-06-01

A key aspect of ensuring optimum cluster reliability and productivity lies in keeping worker nodes in a healthy state. Testnodes is a lightweight node testing solution developed at Liverpool. While Nagios has been used locally for general monitoring of hosts and services, Testnodes is optimised to answer one question: is there any reason this node should not be accepting jobs? This tight focus enables Testnodes to inspect nodes frequently with minimal impact and provide a comprehensive and easily extended check with each inspection. On the server side, Testnodes, implemented in python, interoperates with the Torque batch server to control the nodes production status. Testnodes remotely and in parallel executes client-side test scripts and processes the return codes and output, adjusting the node's online/offline status accordingly to preserve the integrity of the overall batch system. Testnodes reports via log, email and Nagios, allowing a quick overview of node status to be reviewed and specific node issues to be identified and resolved quickly. This presentation will cover testnodes design and implementation, together with the results of its use in production at Liverpool, and future development plans.

Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided surgery.

PubMed

Ashitate, Yoshitomo; Hyun, Hoon; Kim, Soon Hee; Lee, Jeong Heon; Henary, Maged; Frangioni, John V; Choi, Hak Soo

2014-01-01

The resection of regional lymph nodes in the basin of a primary tumor is of paramount importance in surgical oncology. Although sentinel lymph node mapping is now the standard of care in breast cancer and melanoma, over 20% of patients require a completion lymphadenectomy. Yet, there is currently no technology available that can image all lymph nodes in the body in real time, or assess both the sentinel node and all nodes simultaneously. In this study, we report an optical fluorescence technology that is capable of simultaneous mapping of pan lymph nodes (PLNs) and sentinel lymph nodes (SLNs) in the same subject. We developed near-infrared fluorophores, which have fluorescence emission maxima either at 700 nm or at 800 nm. One was injected intravenously for identification of all regional lymph nodes in a basin, and the other was injected locally for identification of the SLN. Using the dual-channel FLARE intraoperative imaging system, we could identify and resect all PLNs and SLNs simultaneously. The technology we describe enables simultaneous, real-time visualization of both PLNs and SLNs in the same subject.

Function Allocation in a Robust Distributed Real-Time Environment

DTIC Science & Technology

1991-12-01

fundamental characteristic of a distributed system is its ability to map individual logical functions of an application program onto many physical nodes... how much of a node’s processor time is scheduled for function processing. IMC is the function- to -function communication required to facilitate...indicator of how much excess processor time a node has. The reconfiguration algorithms use these variables to determine the most appropriate node(s) to

Profiling an application for power consumption during execution on a plurality of compute nodes

DOEpatents

Archer, Charles J.; Blocksome, Michael A.; Peters, Amanda E.; Ratterman, Joseph D.; Smith, Brian E.

2012-08-21

Methods, apparatus, and products are disclosed for profiling an application for power consumption during execution on a compute node that include: receiving an application for execution on a compute node; identifying a hardware power consumption profile for the compute node, the hardware power consumption profile specifying power consumption for compute node hardware during performance of various processing operations; determining a power consumption profile for the application in dependence upon the application and the hardware power consumption profile for the compute node; and reporting the power consumption profile for the application.

Collectively loading an application in a parallel computer

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

Aho, Michael E.; Attinella, John E.; Gooding, Thomas M.

Collectively loading an application in a parallel computer, the parallel computer comprising a plurality of compute nodes, including: identifying, by a parallel computer control system, a subset of compute nodes in the parallel computer to execute a job; selecting, by the parallel computer control system, one of the subset of compute nodes in the parallel computer as a job leader compute node; retrieving, by the job leader compute node from computer memory, an application for executing the job; and broadcasting, by the job leader to the subset of compute nodes in the parallel computer, the application for executing the job.

Method and apparatus for routing data in an inter-nodal communications lattice of a massively parallel computer system by dynamically adjusting local routing strategies

DOEpatents

Archer, Charles Jens; Musselman, Roy Glenn; Peters, Amanda; Pinnow, Kurt Walter; Swartz, Brent Allen; Wallenfelt, Brian Paul

2010-03-16

A massively parallel computer system contains an inter-nodal communications network of node-to-node links. Each node implements a respective routing strategy for routing data through the network, the routing strategies not necessarily being the same in every node. The routing strategies implemented in the nodes are dynamically adjusted during application execution to shift network workload as required. Preferably, adjustment of routing policies in selective nodes is performed at synchronization points. The network may be dynamically monitored, and routing strategies adjusted according to detected network conditions.

Adaptive triangular mesh generation

NASA Technical Reports Server (NTRS)

Erlebacher, G.; Eiseman, P. R.

1984-01-01

A general adaptive grid algorithm is developed on triangular grids. The adaptivity is provided by a combination of node addition, dynamic node connectivity and a simple node movement strategy. While the local restructuring process and the node addition mechanism take place in the physical plane, the nodes are displaced on a monitor surface, constructed from the salient features of the physical problem. An approximation to mean curvature detects changes in the direction of the monitor surface, and provides the pulling force on the nodes. Solutions to the axisymmetric Grad-Shafranov equation demonstrate the capturing, by triangles, of the plasma-vacuum interface in a free-boundary equilibrium configuration.

Portable gamma camera guidance in sentinel lymph node biopsy: prospective observational study of consecutive cases.

PubMed

Peral Rubio, F; de La Riva, P; Moreno-Ramírez, D; Ferrándiz-Pulido, L

2015-06-01

Sentinel lymph node biopsy is the most important tool available for node staging in patients with melanoma. To analyze sentinel lymph node detection and dissection with radio guidance from a portable gamma camera. To assess the number of complications attributable to this biopsy technique. Prospective observational study of a consecutive series of patients undergoing radioguided sentinel lymph node biopsy. We analyzed agreement between nodes detected by presurgical lymphography, those detected by the gamma camera, and those finally dissected. A total of 29 patients (17 women [62.5%] and 12 men [37.5%]) were enrolled. The mean age was 52.6 years (range, 26-82 years). The sentinel node was dissected from all patients; secondary nodes were dissected from some. In 16 cases (55.2%), there was agreement between the number of nodes detected by lymphography, those detected by the gamma camera, and those finally dissected. The only complications observed were seromas (3.64%). No cases of wound dehiscence, infection, hematoma, or hemorrhage were observed. Portable gamma-camera radio guidance may be of use in improving the detection and dissection of sentinel lymph nodes and may also reduce complications. These goals are essential in a procedure whose purpose is melanoma staging. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Comparison of four staging systems of lymph node metastasis in gastric cancer.

PubMed

Zhang, Ming; Zhu, Guanyu; Ma, Yan; Xue, Yingwei

2009-11-01

The classification of lymph node metastasis in patients with gastric cancer is still controversial. Our aim was to evaluate the relative merits of four staging systems of lymph node metastasis. In our study, the nodal status was classified according to the 5th edition of the tumor node metastasis (TNM) system, the Japanese Classification of Gastric Carcinoma (JCGC), the ratio of metastatic lymph nodes, and the size of the largest metastatic lymph node. Each staging system was scored as good (+2), fair (+1), or poor (0) with respect to the theoretical value (extent of the anatomical lymphatic tumor spread), convenience (simplicity), surgical applicability (extent of lymph node dissection), and prognostic value (ability to predict survival rate). In the multivariate analysis including the four staging systems and other potential prognostic factors, stepwise Cox regression revealed that the ratio of metastatic lymph nodes was the most independent prognostic factor. The TNM, ratio, and size systems were convenient because they had no consideration for the location of the tumor and lymph node. Although the JCGC system had advantages in theoretical value and surgical application, it was most optional due to the complexity of the system. Although all different staging systems are comparable, the metastatic lymph node ratio system is convenient, reproducible, and has the highest ability to predict survival.

Service-Oriented Node Scheduling Scheme for Wireless Sensor Networks Using Markov Random Field Model

PubMed Central

Cheng, Hongju; Su, Zhihuang; Lloret, Jaime; Chen, Guolong

2014-01-01

Future wireless sensor networks are expected to provide various sensing services and energy efficiency is one of the most important criterions. The node scheduling strategy aims to increase network lifetime by selecting a set of sensor nodes to provide the required sensing services in a periodic manner. In this paper, we are concerned with the service-oriented node scheduling problem to provide multiple sensing services while maximizing the network lifetime. We firstly introduce how to model the data correlation for different services by using Markov Random Field (MRF) model. Secondly, we formulate the service-oriented node scheduling issue into three different problems, namely, the multi-service data denoising problem which aims at minimizing the noise level of sensed data, the representative node selection problem concerning with selecting a number of active nodes while determining the services they provide, and the multi-service node scheduling problem which aims at maximizing the network lifetime. Thirdly, we propose a Multi-service Data Denoising (MDD) algorithm, a novel multi-service Representative node Selection and service Determination (RSD) algorithm, and a novel MRF-based Multi-service Node Scheduling (MMNS) scheme to solve the above three problems respectively. Finally, extensive experiments demonstrate that the proposed scheme efficiently extends the network lifetime. PMID:25384005

Comparison of five systems for staging lymph node metastasis in gastric cancer.

PubMed

Yu, W; Choi, G S; Whang, I; Suh, I S

1997-09-01

There are several systems for staging lymph node metastasis in gastric cancer. Their relative merits are not clear. In this retrospective analysis, the nodal status was classified according to the Union Internacional Contra la Cancrum (UICC) and Japanese staging systems, the number and frequency of lymph node metastasis, and the level of involved nodes. Each staging system was scored as good (+1), fair (0) or poor (-1) with respect to prognostic value, theoretical value, convenience, reproducibility and surgical applicability. There were no differences between the five staging systems in predicting survival. The Japanese staging system was most arbitrary owing to the complexity of the system, although it had an advantage in surgical application. The same disadvantage was found in the UICC system and the level system. Determination of the number and frequency of involved nodes was convenient and reproducible, but the number of lymph nodes dissected must be considered when the number of positive nodes is used for staging. The classification of metastasis to the regional lymph nodes as N0 (no nodal metastasis), N1 (metastasis in 1-25 per cent of dissected nodes) and N2 (metastasis in more than 25 per cent of dissected nodes) would be a simple, convenient, reproducible staging system with an ability to predict surgical results.

A Scheduling Algorithm for Cloud Computing System Based on the Driver of Dynamic Essential Path.

PubMed

Xie, Zhiqiang; Shao, Xia; Xin, Yu

2016-01-01

To solve the problem of task scheduling in the cloud computing system, this paper proposes a scheduling algorithm for cloud computing based on the driver of dynamic essential path (DDEP). This algorithm applies a predecessor-task layer priority strategy to solve the problem of constraint relations among task nodes. The strategy assigns different priority values to every task node based on the scheduling order of task node as affected by the constraint relations among task nodes, and the task node list is generated by the different priority value. To address the scheduling order problem in which task nodes have the same priority value, the dynamic essential long path strategy is proposed. This strategy computes the dynamic essential path of the pre-scheduling task nodes based on the actual computation cost and communication cost of task node in the scheduling process. The task node that has the longest dynamic essential path is scheduled first as the completion time of task graph is indirectly influenced by the finishing time of task nodes in the longest dynamic essential path. Finally, we demonstrate the proposed algorithm via simulation experiments using Matlab tools. The experimental results indicate that the proposed algorithm can effectively reduce the task Makespan in most cases and meet a high quality performance objective.

A Scheduling Algorithm for Cloud Computing System Based on the Driver of Dynamic Essential Path

PubMed Central

Xie, Zhiqiang; Shao, Xia; Xin, Yu

2016-01-01

To solve the problem of task scheduling in the cloud computing system, this paper proposes a scheduling algorithm for cloud computing based on the driver of dynamic essential path (DDEP). This algorithm applies a predecessor-task layer priority strategy to solve the problem of constraint relations among task nodes. The strategy assigns different priority values to every task node based on the scheduling order of task node as affected by the constraint relations among task nodes, and the task node list is generated by the different priority value. To address the scheduling order problem in which task nodes have the same priority value, the dynamic essential long path strategy is proposed. This strategy computes the dynamic essential path of the pre-scheduling task nodes based on the actual computation cost and communication cost of task node in the scheduling process. The task node that has the longest dynamic essential path is scheduled first as the completion time of task graph is indirectly influenced by the finishing time of task nodes in the longest dynamic essential path. Finally, we demonstrate the proposed algorithm via simulation experiments using Matlab tools. The experimental results indicate that the proposed algorithm can effectively reduce the task Makespan in most cases and meet a high quality performance objective. PMID:27490901

Distributed Sensor Nodes Charged by Mobile Charger with Directional Antenna and by Energy Trading for Balancing.

PubMed

Moraes, Celso; Myung, Sunghee; Lee, Sangkeum; Har, Dongsoo

2017-01-10

Provision of energy to wireless sensor networks is crucial for their sustainable operation. Sensor nodes are typically equipped with batteries as their operating energy sources. However, when the sensor nodes are sited in almost inaccessible locations, replacing their batteries incurs high maintenance cost. Under such conditions, wireless charging of sensor nodes by a mobile charger with an antenna can be an efficient solution. When charging distributed sensor nodes, a directional antenna, rather than an omnidirectional antenna, is more energy-efficient because of smaller proportion of off-target radiation. In addition, for densely distributed sensor nodes, it can be more effective for some undercharged sensor nodes to harvest energy from neighboring overcharged sensor nodes than from the remote mobile charger, because this reduces the pathloss of charging signal due to smaller distances. In this paper, we propose a hybrid charging scheme that combines charging by a mobile charger with a directional antenna, and energy trading, e.g., transferring and harvesting, between neighboring sensor nodes. The proposed scheme is compared with other charging scheme. Simulations demonstrate that the hybrid charging scheme with a directional antenna achieves a significant reduction in the total charging time required for all sensor nodes to reach a target energy level.

Distributed Sensor Nodes Charged by Mobile Charger with Directional Antenna and by Energy Trading for Balancing

PubMed Central

Moraes, Celso; Myung, Sunghee; Lee, Sangkeum; Har, Dongsoo

2017-01-01

Provision of energy to wireless sensor networks is crucial for their sustainable operation. Sensor nodes are typically equipped with batteries as their operating energy sources. However, when the sensor nodes are sited in almost inaccessible locations, replacing their batteries incurs high maintenance cost. Under such conditions, wireless charging of sensor nodes by a mobile charger with an antenna can be an efficient solution. When charging distributed sensor nodes, a directional antenna, rather than an omnidirectional antenna, is more energy-efficient because of smaller proportion of off-target radiation. In addition, for densely distributed sensor nodes, it can be more effective for some undercharged sensor nodes to harvest energy from neighboring overcharged sensor nodes than from the remote mobile charger, because this reduces the pathloss of charging signal due to smaller distances. In this paper, we propose a hybrid charging scheme that combines charging by a mobile charger with a directional antenna, and energy trading, e.g., transferring and harvesting, between neighboring sensor nodes. The proposed scheme is compared with other charging scheme. Simulations demonstrate that the hybrid charging scheme with a directional antenna achieves a significant reduction in the total charging time required for all sensor nodes to reach a target energy level. PMID:28075372

Superficial and deep lymph node dissection for stage III cutaneous melanoma: clinical outcome and prognostic factors

PubMed Central

2013-01-01

Background The aims of this retrospective analysis were to evaluate the effect of combined superficial and deep groin dissection on disease-free and melanoma-specific survival, and to identify the most important factors for predicting the involvement of deep nodes according to clinically or microscopically detected nodal metastases. Methods Between January 1996 and December 2005, 133 consecutive patients with groin lymph node metastases underwent superficial and deep dissection at the National Cancer Institute, Naples. Lymph node involvement was clinically evident in 84 patients and detected by sentinel node biopsy in 49 cases. Results The 5-year disease-free survival was significantly better for patients with superficial lymph node metastases than for patients with involvement of both superficial and deep lymph nodes (34.9% vs. 19.0%; P = 0.001). The 5-year melanoma-specific survival was also significantly better for patients with superficial node metastases only (55.6% vs. 33.3%; P = 0.001). Conclusions Metastasis in the deep nodes is the strongest predictor of both disease-free and melanoma-specific survival. Deep groin dissection should be considered for all patients with groin clinical nodal involvement, but might be spared in patients with a positive sentinel node. Prospective studies will clarify the issue further. PMID:23379355

Superficial and deep lymph node dissection for stage III cutaneous melanoma: clinical outcome and prognostic factors.

PubMed

Mozzillo, Nicola; Caracò, Corrado; Marone, Ugo; Di Monta, Gianluca; Crispo, Anna; Botti, Gerardo; Montella, Maurizio; Ascierto, Paolo Antonio

2013-02-04

The aims of this retrospective analysis were to evaluate the effect of combined superficial and deep groin dissection on disease-free and melanoma-specific survival, and to identify the most important factors for predicting the involvement of deep nodes according to clinically or microscopically detected nodal metastases. Between January 1996 and December 2005, 133 consecutive patients with groin lymph node metastases underwent superficial and deep dissection at the National Cancer Institute, Naples. Lymph node involvement was clinically evident in 84 patients and detected by sentinel node biopsy in 49 cases. The 5-year disease-free survival was significantly better for patients with superficial lymph node metastases than for patients with involvement of both superficial and deep lymph nodes (34.9% vs. 19.0%; P = 0.001). The 5-year melanoma-specific survival was also significantly better for patients with superficial node metastases only (55.6% vs. 33.3%; P = 0.001). Metastasis in the deep nodes is the strongest predictor of both disease-free and melanoma-specific survival. Deep groin dissection should be considered for all patients with groin clinical nodal involvement, but might be spared in patients with a positive sentinel node. Prospective studies will clarify the issue further.

Radical lymph node dissection and assessment: Impact on gallbladder cancer prognosis

PubMed Central

Liu, Gui-Jie; Li, Xue-Hua; Chen, Yan-Xin; Sun, Hui-Dong; Zhao, Gui-Mei; Hu, San-Yuan

2013-01-01

AIM: To investigate the lymph node metastasis patterns of gallbladder cancer (GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor. METHODS: From May 1995 to December 2010, a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People’s Hospital. A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder. Demographic, operative and pathologic data were recorded. The lymph nodes retrieved were examined histologically for metastases routinely from each node. The positive lymph node count (PLNC) as well as the total lymph node count (TLNC) was recorded for each patient. Then the metastatic to examined lymph nodes ratio (LNR) was calculated. Disease-specific survival (DSS) and predictors of outcome were analyzed. RESULTS: With a median follow-up time of 26.50 mo (range, 2-132 mo), median DSS was 29.00 ± 3.92 mo (5-year survival rate, 20.51%). Nodal disease was found in 37 patients (47.44%). DSS of node-negative patients was significantly better than that of node-positive patients (median DSS, 40 mo vs 17 mo, χ2 = 14.814, P < 0.001), while there was no significant difference between N1 patients and N2 patients (median DSS, 18 mo vs 13 mo, χ2 = 0.741, P = 0.389). Optimal TLNC was determined to be four. When node-negative patients were divided according to TLNC, there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup (median DSS, 37 mo vs 54 mo, χ2 = 0.715, P = 0.398). For node-positive patients, DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup (median DSS, 13 mo vs 21 mo, χ2 = 11.035, P < 0.001). Moreover, for node-positive patients, a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups (< 6 or ≥ 6, respectively; median DSS, 15 mo vs 33 mo, χ2 = 11.820, P < 0.001). DSS progressively worsened with increasing PLNC and LNR, but no definite cut-off value could be identified. Multivariate analysis revealed histological grade, tumor node metastasis staging, TNLC and LNR to be independent predictors of DSS. Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis. CONCLUSION: Both TLNC and LNR are strong predictors of outcome after curative resection for GBC. The retrieval and examination of at least 6 nodes can influence staging quality and DSS, especially in node-positive patients. PMID:23964151

Radical lymph node dissection and assessment: Impact on gallbladder cancer prognosis.

PubMed

Liu, Gui-Jie; Li, Xue-Hua; Chen, Yan-Xin; Sun, Hui-Dong; Zhao, Gui-Mei; Hu, San-Yuan

2013-08-21

To investigate the lymph node metastasis patterns of gallbladder cancer (GBC) and evaluate the optimal categorization of nodal status as a critical prognostic factor. From May 1995 to December 2010, a total of 78 consecutive patients with GBC underwent a radical resection at Liaocheng People's Hospital. A radical resection was defined as removing both the primary tumor and the regional lymph nodes of the gallbladder. Demographic, operative and pathologic data were recorded. The lymph nodes retrieved were examined histologically for metastases routinely from each node. The positive lymph node count (PLNC) as well as the total lymph node count (TLNC) was recorded for each patient. Then the metastatic to examined lymph nodes ratio (LNR) was calculated. Disease-specific survival (DSS) and predictors of outcome were analyzed. With a median follow-up time of 26.50 mo (range, 2-132 mo), median DSS was 29.00 ± 3.92 mo (5-year survival rate, 20.51%). Nodal disease was found in 37 patients (47.44%). DSS of node-negative patients was significantly better than that of node-positive patients (median DSS, 40 mo vs 17 mo, χ² = 14.814, P < 0.001), while there was no significant difference between N1 patients and N2 patients (median DSS, 18 mo vs 13 mo, χ² = 0.741, P = 0.389). Optimal TLNC was determined to be four. When node-negative patients were divided according to TLNC, there was no difference in DSS between TLNC < 4 subgroup and TLNC ≥ 4 subgroup (median DSS, 37 mo vs 54 mo, χ² = 0.715, P = 0.398). For node-positive patients, DSS of TLNC < 4 subgroup was worse than that of TLNC ≥ 4 subgroup (median DSS, 13 mo vs 21 mo, χ² = 11.035, P < 0.001). Moreover, for node-positive patients, a new cut-off value of six nodes was identified for the number of TLNC that clearly stratified them into 2 separate survival groups (< 6 or ≥ 6, respectively; median DSS, 15 mo vs 33 mo, χ² = 11.820, P < 0.001). DSS progressively worsened with increasing PLNC and LNR, but no definite cut-off value could be identified. Multivariate analysis revealed histological grade, tumor node metastasis staging, TNLC and LNR to be independent predictors of DSS. Neither location of positive lymph nodes nor PNLC were identified as an independent variable by multivariate analysis. Both TLNC and LNR are strong predictors of outcome after curative resection for GBC. The retrieval and examination of at least 6 nodes can influence staging quality and DSS, especially in node-positive patients.

[Numbers of lymph nodes in large intestinal resections for colorectal carcinoma].

PubMed

Motycka, V; Ferko, A; Tycová, V; Nikolov, Hadzi; Sotona, O; Cecka, F; Dusek, T; Chobola, M; Pospísil, I

2010-03-01

Precise evaluation of lymph nodes in the surgical specimen is crucial for the staging and subsequent decision about the adjuvant therapy in colorectal cancer. Prognosis of the patients can be assessed only in cases when at least 12 lymph nodes in the surgical specimen are examined. To evaluate the radicalism of resections for colorectal carcinoma after introducing laparoscopic approach. We compared all resections for primary colorectal cancer and rectal cancer (C 18-C20) performed in the Department of Surgery in University Hospital Hradec Králové in the years 2005 and 2008 and we evaluated numbers of examined lymph nodes in the surgical specimens. The patients with recurrent tumours and the patients with complete pathological response (negative histology) after neoadjuvant therapy were excluded from the study. 117 patients were included in the study in 2005, 2 of them were operated laparoscopically. 155 patients (more by 32.5%) were included in the study in 2008, 53 of them (34.2%) were operated laparoscopically. In tumours of the right part of the colon (C180-C184) treated by right hemicolectomy: on an average 7.9 (+/- 5.3) lymph nodes were examined in the specimens in 2005, and 15.3 (+/- 7.0) lymph nodes in 2008. In tumours of the left part of the colon (C185-C186) treated by left hemicolectomy: 6.5 (+/- 5.1) lymph nodes were examined in 2005, and 19.6 (+/- 15.6) in 2008. In tumours of the sigmoid colon (C187) 9.1 (+/- 6.9) lymph nodes were examined in 2005,and 15.4 (+/- 7.9) in 2008. In tumours of the rectosigmoid junction (C19) 8.0 (+/- 6.9) lymph nodes were examined in 2005, and 17.8 (+/- 11.2) in 2008. In rectal cancer (C20) 5.2 (+/- 4.5) lymph nodes were examined in 2005, and 13.6 (+/- 12.5) in 2008. There is a significant difference in a number of examined lymph nodes in patients without neodadjuvant treatment compared to those with neoadjuvant chemoradiotherapy and neoadjuvant radiotherapy. In 2005, in an average 3.7 (+/- 3.3) lymph nodes were removed in rectal resections after neoadjuvant chemoradiotherapy, in 2008 in an average 7.6 (+/- 6.1) lymph nodes were removed. In 2005, in an average 5.1 (+/- 3.7) lymph nodes in rectal resections after neoadjuvant radiotherapy were removed, in 2008 6.3 (+/- 4.3) lymph nodes were removed. In 2005, in an average 7.0 (+/- 5.5) lymph nodes in rectal resections without neoadjuvant therapy were removed, in 2008 20.9 (+/- 14.1) lymph nodes were removed. Laparoscopic resections were comparable with open resections regarding the number of examined lymph nodes in our group of patients. Introducing the laparoscopic approach to resections of colorectal carcinomas did not decrease radicalism of the operation as to the number of removed lymph nodes.

Parameters affecting the resilience of scale-free networks to random failures.

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

Link, Hamilton E.; LaViolette, Randall A.; Lane, Terran

2005-09-01

It is commonly believed that scale-free networks are robust to massive numbers of random node deletions. For example, Cohen et al. in (1) study scale-free networks including some which approximate the measured degree distribution of the Internet. Their results suggest that if each node in this network failed independently with probability 0.99, most of the remaining nodes would still be connected in a giant component. In this paper, we show that a large and important subclass of scale-free networks are not robust to massive numbers of random node deletions. In particular, we study scale-free networks which have minimum node degreemore » of 1 and a power-law degree distribution beginning with nodes of degree 1 (power-law networks). We show that, in a power-law network approximating the Internet's reported distribution, when the probability of deletion of each node is 0.5 only about 25% of the surviving nodes in the network remain connected in a giant component, and the giant component does not persist beyond a critical failure rate of 0.9. The new result is partially due to improved analytical accommodation of the large number of degree-0 nodes that result after node deletions. Our results apply to power-law networks with a wide range of power-law exponents, including Internet-like networks. We give both analytical and empirical evidence that such networks are not generally robust to massive random node deletions.« less