Seven years follow-up of early repolarisation patterns in French elite special forces.

PubMed

Roche, Nicolas-Charles; Massoure, Pierre-Laurent; Deharo, Jean-Claude; Paule, Philippe; Fourcade, Laurent

2018-06-01

The early repolarization pattern (ERP) may be a marker of increased risk for sudden cardiac death (SCD). Influence of ethnicity on the ERP has not been extensively studied. The aim of this study was to evaluate the epidemiology of ERP in a male multiethnic population. ECG analysis was performed among consecutive recruits from the French Foreign Legion. ERP was characterized by a J-point elevation ≥0.1 mV in two continuous inferior-lateral leads, and high amplitude early repolarization (HAER-potentially malignant pattern) by an elevation ≥0.2 mV. Ethnical affiliation and level of physical activity were recorded. A total of 2508 healthy men (24 ± 5 years old) from 105 different native countries were divided into three ethnic groups: 1689 Whites, 388 Afro-Caribbean, and 431 Asians. ERP was found in 489 recruits (19%), 14% in Whites, 33% in Afro-Caribbeans, and 27% in Asians without any difference according to age and physical activity. Sub-Saharan Africans or Caribbeans had the highest rate of ERP (30%), and Hispanics the lowest (8%). People from occidental countries, Middle East, Central Asia or India had a rate of 12%-18%, East and South-Asia 20%-25%. Madagascar was an exception with only 16% of ERP. HAER (2.9%) was more frequent among Asian recruits. After 5 ± 2 years of follow up, one SCD occurred in the ERP group (p = 0.042). This study reports a large multiethnic analysis of ERP. HAER was more frequent in recruits from East and South-East Asia where sudden unexplained nocturnal death syndrome is endemic. © 2018 Wiley Periodicals, Inc.

High Frequency of Early Repolarization and Brugada-Type Electrocardiograms in Hypercalcemia.

PubMed

Sonoda, Keiko; Watanabe, Hiroshi; Hisamatsu, Takashi; Ashihara, Takashi; Ohno, Seiko; Hayashi, Hideki; Horie, Minoru; Minamino, Tohru

2016-01-01

J wave, or early repolarization has recently been associated with an increased risk of lethal arrhythmia and sudden death, both in idiopathic ventricular fibrillation and in the general population. Hypercalcemia is one of the causes of J point and ST segment elevation, but the relationship has not been well studied. The aim of this study was to examine the effects of hypercalcemia on J point elevation. Electrocardiographic findings were compared in 89 patients with hypercalcemia and 267 age- and sex-matched healthy controls with normocalcemia. The association of J point elevation with arrhythmia events in patients with hypercalcemia was also studied. The PR interval and the QRS duration were longer in patients with hypercalcemia than in normocalcemic controls. Both the QT and the corrected QT intervals were shorter in patients with hypercalcemia compared with normocalcemic controls. Conduction disorders, ST-T abnormalities, and J point elevation were more common in patients with hypercalcemia than normocalcemic controls. Following the resolution of hypercalcemia, the frequency of J point elevation decreased to a level similar to that noted in controls. During hospitalization, no arrhythmia event occurred in patients with hypercalcemia. Hypercalcemia was associated with J point elevation. © 2015 Wiley Periodicals, Inc.

A reliability analysis of cardiac repolarization time markers.

PubMed

Scacchi, S; Franzone, P Colli; Pavarino, L F; Taccardi, B

2009-06-01

Only a limited number of studies have addressed the reliability of extracellular markers of cardiac repolarization time, such as the classical marker RT(eg) defined as the time of maximum upslope of the electrogram T wave. This work presents an extensive three-dimensional simulation study of cardiac repolarization time, extending the previous one-dimensional simulation study of a myocardial strand by Steinhaus [B.M. Steinhaus, Estimating cardiac transmembrane activation and recovery times from unipolar and bipolar extracellular electrograms: a simulation study, Circ. Res. 64 (3) (1989) 449]. The simulations are based on the bidomain - Luo-Rudy phase I system with rotational fiber anisotropy and homogeneous or heterogeneous transmural intrinsic membrane properties. The classical extracellular marker RT(eg) is compared with the gold standard of fastest repolarization time RT(tap), defined as the time of minimum derivative during the downstroke of the transmembrane action potential (TAP). Additionally, a new extracellular marker RT90(eg) is compared with the gold standard of late repolarization time RT90(tap), defined as the time when the TAP reaches 90% of its resting value. The results show a good global match between the extracellular and transmembrane repolarization markers, with small relative mean discrepancy (or=0.92), ensuring a reasonably good global match between the associated repolarization sequences. However, large local discrepancies of the extracellular versus transmembrane markers may ensue in regions where the curvature of the repolarization front changes abruptly (e.g. near front collisions) or is negligible (e.g. where repolarization proceeds almost uniformly across fiber). As a consequence, the spatial distribution of activation-recovery intervals (ARI) may provide an inaccurate estimate of (and weakly correlated with) the spatial distribution of action potential durations (APD).

Components of action potential repolarization in cerebellar parallel fibres.

PubMed

Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten

2014-11-15

Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter.We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K(+) channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K(+) channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K(+) channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.

Identification of local myocardial repolarization time by bipolar electrode potential.

PubMed

Namba, Tsunetoyo; Todo, Takahiro; Yao, Takenori; Ashihara, Takashi; Haraguchi, Ryo; Nakazawa, Kazuo; Ikeda, Takanori; Ohe, Tohru

2007-01-01

The aim of this study was to investigate whether bipolar electrode potentials (BEPs) reflect local myocardial repolarization dynamics, using computer simulation. Simulated action potential and BEP mapping of myocardial tissue during fibrillation was performed. The BEP was modified to make all the fluctuations have the same polarity. Then, the modified BEP (mBEP) was transformed to "dynamic relative amplitude" (DRA) designed to make all the fluctuations have the similar amplitude. The repolarization end point corresponded to the end of the repolarization-related small fluctuation that clearly appeared in the DRA of mBEP. Using the DRA of mBEP, we could reproduce the repolarization dynamics in the myocardial tissue during fibrillation. The BEP may facilitate identifying the repolarization time. Furthermore, BEP mapping has the possibility that it would be available for evaluating repolarization behavior in myocardial tissue even during fibrillation. The accuracy of activation-recovery interval was also reconfirmed.

Microvolt T-wave alternans and beat-to-beat variability of repolarization during early postischemic remodeling in a pig heart.

PubMed

Floré, Vincent; Claus, Piet; Antoons, Gudrun; Oosterhoff, Peter; Holemans, Patricia; Vos, Marc A; Sipido, Karin R; Willems, Rik

2011-07-01

Repolarization variability is considered to predict sudden cardiac death. T-wave alternans (TWA) has been the subject of exhaustive research, whereas beat-to-beat variability of repolarization (BVR) is a new parameter that possibly predicts proarrhythmia. How these parameters interact has not been tested. The purpose of this study was to compare TWA and BVR as predictors of proarrhythmic substrate early after myocardial infarction (MI). In nine pigs, MI was induced by 1-hour occlusion of the left anterior descending coronary artery. Cardiac magnetic resonance imaging was performed at day 21. Six sham pigs served as control. Spectral TWA was tested during right atrial pacing before induction of MI and after 21 days. BVR was calculated from 60 consecutive QT intervals. Magnetic resonance imaging showed transmural MI. TWA was negative in all pigs at clinical threshold rate and equally present in MI versus sham pigs at higher rates (170 bpm: 55% vs 50% positive TWA). In MI pigs, BVR of QT intervals increased significantly during acute ischemia (2.44 ± 0.43 ms vs 3.55 ± 0.41 ms, P <.01) and even more on day 21 (5.80 ± 1.12 ms), but it differed significantly from sham (2.14 ± 0.54 ms, P <.01). A clinical ventricular tachycardia induction protocol was positive in 2 of 8 MI pigs and in none of 6 shams. In early remodeling after MI, BVR at intrinsic heart rate was a consistent phenomenon, whereas TWA during atrial pacing or baseline QT-interval changes were not. TWA and BVR could reflect different post-MI remodeling processes. BVR may be a new technique for predicting a potentially proarrhythmic substrate in the early postinfarction period. Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Six-Year Outcome of Subjects Without Overt Heart Disease With an Early Repolarization/J Wave Electrocardiographic Pattern.

PubMed

Lanza, Gaetano Antonio; Argirò, Alessia; Mollo, Roberto; De Vita, Antonio; Spera, Francesco; Golino, Michele; Rota, Elisabetta; Filice, Monica; Crea, Filippo

2017-12-01

"Early repolarization" (ER) is a frequent finding at standard electrocardiogram (ECG). In this study we assessed whether ER is associated with an increased risk of events, as recently suggested by some studies. We prospectively enrolled 4,176 consecutive subjects without any heart disease who underwent routine ECG recording. ER was diagnosed in case of typical concave ST-segment elevation ≥0.1 mV; a J wave was diagnosed when the QRS showed a notch or a slur in its terminal part. In this study we compared the 6-year outcome of all 687 subjects with ER/J wave and 687 matched subjects without ER/J wave (controls). Both groups included 335 males and 352 females, and age was 48.8 ± 18 years. Overall, 145 deaths occurred (11%), only 11 of which attributed to cardiac causes. No sudden death was reported. Cardiac deaths occurred in 5 (0.8%) and 6 (0.9%) ER/J wave subjects and controls, respectively (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.26 to 2.80, p = 0.79). Both ER (OR 1.68, 95% CI 0.21 to 13.3, p = 0.62) and J wave (OR 0.91, 95% CI 0.28 to 3.00, p = 0.88) showed no association with cardiac death. Total mortality was 11.5% in the ER/J wave group and 10.6% in the control group (OR 1.10, 95% CI 0.78 to 1.56, p = 0.58). Both ER (OR 0.44, 95% CI 0.16 to 1.24, p = 0.12) and J wave (OR 1.20, 95% CI 0.85 to 1.70, p = 0.30) showed also no association with all-cause death. In subjects without any evidence of heart disease, we found no significant association of ER/J wave with the risk of cardiac, as well as all-cause, death at medium-term follow-up. Copyright © 2017 Elsevier Inc. All rights reserved.

Excess centrosomes perturb dynamic endothelial cell repolarization during blood vessel formation

PubMed Central

Kushner, Erich J.; Ferro, Luke S.; Yu, Zhixian; Bautch, Victoria L.

2016-01-01

Blood vessel formation requires dynamic movements of endothelial cells (ECs) within sprouts. The cytoskeleton regulates migratory polarity, and centrosomes organize the microtubule cytoskeleton. However, it is not well understood how excess centrosomes, commonly found in tumor stromal cells, affect microtubule dynamics and interphase cell polarity. Here we find that ECs dynamically repolarize during sprouting angiogenesis, and excess centrosomes block repolarization and reduce migration and sprouting. ECs with excess centrosomes initially had more centrosome-derived microtubules but, paradoxically, fewer steady-state microtubules. ECs with excess centrosomes had elevated Rac1 activity, and repolarization was rescued by blockade of Rac1 or actomyosin blockers, consistent with Rac1 activity promoting cortical retrograde actin flow and actomyosin contractility, which precludes cortical microtubule engagement necessary for dynamic repolarization. Thus normal centrosome numbers are required for dynamic repolarization and migration of sprouting ECs that contribute to blood vessel formation. PMID:27099371

Bifurcation diagrams of frequency dependence of repolarization during long QT syndrome using the Luo-Rudy model of cardiac repolarization

NASA Astrophysics Data System (ADS)

Bondarenko, V. E.; Doedel, E. J.; Rasmusson, R. L.

2000-02-01

We applied bifurcation analysis to the Luo-Rudy model of the guinea pig cardiac ventricular cell to investigate the behavior of repolarization in response to a simulated form of inherited arrhythmia, long QT syndrome. In this paper, we simulate pathological changes in cardiac repolarization through reductions in IKr. Decreased expression of this current has been linked to an inherited form of long QT syndrome which results in a high mortality, presumably due to sudden cardiac death from ventricular fibrillation.

Effects of sildenafil on cardiac repolarization.

PubMed

Chiang, Chern-En; Luk, Hsiang-Ning; Wang, Tsui-Min; Ding, Philip Yu-An

2002-08-01

Sudden death has occasionally been reported in patients taking sildenafil. The objective of this study was to investigate the effect of sildenafil on cardiac repolarization. We used conventional microelectrode recording technique in isolated guinea pig papillary muscles and canine Purkinje fibers, whole-cell patch clamp techniques in guinea pig ventricular myocytes, and in vivo ECG measurements in guinea pigs. Action potential duration at 90% repolarization (APD(90)) was not affected by sildenafil in the therapeutic ranges (< or =1 microM), but shortened by higher concentration (> or =10 microM) in both guinea pig papillary muscles and canine Purkinje fibers. D-Sotalol prolonged APD(90) in the same preparations with concentrations > or =1 microM in a reverse frequency-dependent manner. Co-administration of sildenafil (10 and 30 microM) abolished the APD-prolonging effects of D-sotalol (30 microM) and amiodarone (100 microM). Sildenafil, with concentrations up to 30 microM, had no significant effect on both the rapid (I(Kr)) and the slow (I(Ks)) components of the delayed rectifier potassium currents in guinea pig ventricular myocytes. Sildenafil dose-dependently blocked L-type Ca(2+) current (I(Ca,L)), but had no effect on persistent Na(+) current in guinea pig ventricular myocytes. ECG recordings in intact guinea pigs revealed significant shortening of QTc interval by sildenafil (10 and 30 mg/kg orally). The QT-prolonging effects by D,L-sotalol (50 mg/kg) and amiodarone (100 mg/kg) were abolished by sildenafil (30 mg/kg). Sildenafil does not prolong cardiac repolarization. Instead, in supra-therapeutic concentrations, it accelerates cardiac repolarization, presumably through its blocking effect on I(Ca,L).

Re-polarization of nuclear spins using selective SABRE-INEPT

NASA Astrophysics Data System (ADS)

Knecht, Stephan; Kiryutin, Alexey S.; Yurkovskaya, Alexandra V.; Ivanov, Konstantin L.

2018-02-01

A method is proposed for significant improvement of NMR pulse sequences used in high-field SABRE (Signal Amplification By Reversible Exchange) experiments. SABRE makes use of spin order transfer from parahydrogen (pH2, the H2 molecule in its singlet spin state) to a substrate in a transient organometallic Ir-based complex. The technique proposed here utilizes "re-polarization", i.e., multiple application of an NMR pulse sequence used for spin order transfer. During re-polarization only the form of the substrate, which is bound to the complex, is excited by selective NMR pulses and the resulting polarization is transferred to the free substrate via chemical exchange. Owing to the fact that (i) only a small fraction of the substrate molecules is in the bound form and (ii) spin relaxation of the free substrate is slow, the re-polarization scheme provides greatly improved NMR signal enhancement, ε . For instance, when pyridine is used as a substrate, single use of the SABRE-INEPT sequence provides ε ≈ 260 for 15N nuclei, whereas SABRE-INEPT with re-polarization yields ε > 2000 . We anticipate that the proposed method is useful for achieving maximal NMR enhancement with spin hyperpolarization techniques.

How the knowledge of genetic "makeup" and cellular data can affect the analysis of repolarization in surface electrocardiogram.

PubMed

Shimizu, Wataru

2010-01-01

This review article sought to describe patterns of repolarization on the surface electrocardiogram in inherited cardiac arrhythmias and to discuss how the knowledge of genetic makeup and cellular data can affect the analysis based on the data derived from the experimental studies using arterially perfused canine ventricular wedge preparations. Molecular genetic studies have established a link between a number of inherited cardiac arrhythmia syndromes and mutations in genes encoding cardiac ion channels or membrane components during the past 2 decades. Twelve forms of congenital long QT syndrome have been so far identified, and genotype-phenotype correlations have been investigated especially in the 3 major genotypes-LQT1, LQT2, and LQT3. Abnormal T waves are reported in the LQT1, LQT2, and LQT3, and the differences in the time course of repolarization of the epicardial, midmyocardial, and endocardial cells give rise to voltage gradients responsible for the manifestation of phenotypic appearance of abnormal T waves. Brugada syndrome is characterized by ST-segment elevation in leads V1 to V3 and an episode of ventricular fibrillation, in which 7 genotypes have been reported. An intrinsically prominent transient outward current (I(to))-mediated action potential notch and a subsequent loss of action potential dome in the epicardium, but not in the endocardium of the right ventricular outflow tract, give rise to a transmural voltage gradient, resulting in ST-segment elevation, and a subsequent phase 2 reentry-induced ventricular fibrillation. In conclusion, transmural electrical heterogeneity of repolarization across the ventricular wall profoundly affects the phenotypic manifestation of repolarization patterns on the surface electrocardiogram in inherited cardiac arrhythmias. Copyright © 2010 Elsevier Inc. All rights reserved.

A Novel Lead Configuration for Optimal Spatio-Temporal Detection of Intracardiac Repolarization Alternans

PubMed Central

Weiss, Eric H.; Merchant, Faisal M.; d’Avila, Andre; Foley, Lori; Reddy, Vivek Y.; Singh, Jagmeet P.; Mela, Theofanie; Ruskin, Jeremy N.; Armoundas, Antonis A.

2011-01-01

Background Electrical alternans is a pattern of variation in the shape of electrocardiographic waveform that occurs every other beat. In humans, alternation in ventricular repolarization, known as repolarization alternans (RA), has been associated with increased vulnerability to ventricular tachycardia/fibrillation and sudden cardiac death. Methods and Results This study investigates the spatio-temporal variability of intracardiac RA and its relationship to body surface RA in an acute myocardial ischemia model in swine. We developed a real-time multi-channel repolarization signal acquisition, display and analysis system to record electrocardiographic signals from catheters in the right ventricle, coronary sinus, left ventricle, and epicardial surface prior to and following circumflex coronary artery balloon occlusion. We found that RA is detectable within 4 minutes following the onset ischemia, and is most prominently seen during the first half of the repolarization interval. Ischemia-induced RA was detectable on unipolar and bipolar leads (both in near- and far-field configurations) and on body surface leads. Far-field bipolar intracardiac leads were more sensitive for RA detection than body surface leads, with the probability of body surface RA detection increasing as the number of intracardiac leads detecting RA increased, approaching 100% when at least three intracardiac leads detected RA. We developed a novel, clinically-applicable intracardiac lead system based on a triangular arrangement of leads spanning the right ventricular (RV) and coronary sinus (CS) catheters which provided the highest sensitivity for intracardiac RA detection when compared to any other far-field bipolar sensing configurations (p < 0.0001). Conclusions In conclusion, intracardiac alternans, a complex spatio-temporal phenomenon associated with arrhythmia susceptibility and sudden cardiac death, can be reliably detected through a novel triangular RV-CS lead configuration. PMID:21430127

Re-polarization of nuclear spins using selective SABRE-INEPT.

PubMed

Knecht, Stephan; Kiryutin, Alexey S; Yurkovskaya, Alexandra V; Ivanov, Konstantin L

2018-02-01

A method is proposed for significant improvement of NMR pulse sequences used in high-field SABRE (Signal Amplification By Reversible Exchange) experiments. SABRE makes use of spin order transfer from parahydrogen (pH 2 , the H 2 molecule in its singlet spin state) to a substrate in a transient organometallic Ir-based complex. The technique proposed here utilizes "re-polarization", i.e., multiple application of an NMR pulse sequence used for spin order transfer. During re-polarization only the form of the substrate, which is bound to the complex, is excited by selective NMR pulses and the resulting polarization is transferred to the free substrate via chemical exchange. Owing to the fact that (i) only a small fraction of the substrate molecules is in the bound form and (ii) spin relaxation of the free substrate is slow, the re-polarization scheme provides greatly improved NMR signal enhancement, ε. For instance, when pyridine is used as a substrate, single use of the SABRE-INEPT sequence provides ε≈260 for 15 N nuclei, whereas SABRE-INEPT with re-polarization yields ε>2000. We anticipate that the proposed method is useful for achieving maximal NMR enhancement with spin hyperpolarization techniques. Copyright © 2017 Elsevier Inc. All rights reserved.

Kinetics of atrial repolarization alternans in a free-behaving ovine model.

PubMed

Jousset, Florian; Tenkorang, Joanna; Vesin, Jean-Marc; Pascale, Patrizio; Ruchat, Patrick; Rollin, Anne Garderes; Fromer, Martin; Narayan, Sanjiv M; Pruvot, Etienne

2012-09-01

Kinetics of Atrial Repolarization Alternans. Repolarization alternans (Re-ALT), a beat-to-beat alternation in action potential repolarization, promotes dispersion of repolarization, wavebreaks, and reentry. Recently, Re-ALT has been shown to play an important role in the transition from rapid pacing to atrial fibrillation (AF) in humans. The detailed kinetics of atrial Re-ALT, however, has not been reported so far. We developed a chronic free-behaving ovine pacing model to study the kinetics of atrial Re-ALT as a function of pacing rate. Thirteen sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms and delivery of rapid pacing protocols. Beat-to-beat differences in the atrial T-wave apex amplitude as a measure of Re-ALT and activation time were analyzed at incremental pacing rates until the effective refractory period (ERP) defined as stable 2:1 capture. Atrial Re-ALT appeared intermittently but without periodicity, and increased in amplitude as a function of pacing rate until ERP. Intermittent 2:1 atrial capture was observed at pacing cycle lengths 40 ms above ERP, and increased in duration as a function of pacing rate. Episodes of rapid pacing-induced AF were rare, and were preceded by Re-ALT or complex oscillations of atrial repolarization, but without intermittent capture. We show in vivo that atrial Re-ALT developed and increased in magnitude with rate until stable 2:1 capture. In rare instances where capture failure did not occur, Re-ALT and complex oscillations of repolarization surged and preceded AF initiation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1003-1012, September 2012). © 2012 Wiley Periodicals, Inc.

Sensitivity and specificity of automated detection of early repolarization in standard 12-lead electrocardiography.

PubMed

Kenttä, Tuomas; Porthan, Kimmo; Tikkanen, Jani T; Väänänen, Heikki; Oikarinen, Lasse; Viitasalo, Matti; Karanko, Hannu; Laaksonen, Maarit; Huikuri, Heikki V

2015-07-01

Early repolarization (ER) is defined as an elevation of the QRS-ST junction in at least two inferior or lateral leads of the standard 12-lead electrocardiogram (ECG). Our purpose was to create an algorithm for the automated detection and classification of ER. A total of 6,047 electrocardiograms were manually graded for ER by two experienced readers. The automated detection of ER was based on quantification of the characteristic slurring or notching in ER-positive leads. The ER detection algorithm was tested and its results were compared with manual grading, which served as the reference. Readers graded 183 ECGs (3.0%) as ER positive, of which the algorithm detected 176 recordings, resulting in sensitivity of 96.2%. Of the 5,864 ER-negative recordings, the algorithm classified 5,281 as negative, resulting in 90.1% specificity. Positive and negative predictive values for the algorithm were 23.2% and 99.9%, respectively, and its accuracy was 90.2%. Inferior ER was correctly detected in 84.6% and lateral ER in 98.6% of the cases. As the automatic algorithm has high sensitivity, it could be used as a prescreening tool for ER; only the electrocardiograms graded positive by the algorithm would be reviewed manually. This would reduce the need for manual labor by 90%. © 2014 Wiley Periodicals, Inc.

Fractional diffusion models of cardiac electrical propagation: role of structural heterogeneity in dispersion of repolarization

PubMed Central

Bueno-Orovio, Alfonso; Kay, David; Grau, Vicente; Rodriguez, Blanca; Burrage, Kevin

2014-01-01

Impulse propagation in biological tissues is known to be modulated by structural heterogeneity. In cardiac muscle, improved understanding on how this heterogeneity influences electrical spread is key to advancing our interpretation of dispersion of repolarization. We propose fractional diffusion models as a novel mathematical description of structurally heterogeneous excitable media, as a means of representing the modulation of the total electric field by the secondary electrical sources associated with tissue inhomogeneities. Our results, analysed against in vivo human recordings and experimental data of different animal species, indicate that structural heterogeneity underlies relevant characteristics of cardiac electrical propagation at tissue level. These include conduction effects on action potential (AP) morphology, the shortening of AP duration along the activation pathway and the progressive modulation by premature beats of spatial patterns of dispersion of repolarization. The proposed approach may also have important implications in other research fields involving excitable complex media. PMID:24920109

Histone Deacetylase Inhibitors Prolong Cardiac Repolarization through Transcriptional Mechanisms.

PubMed

Spence, Stan; Deurinck, Mark; Ju, Haisong; Traebert, Martin; McLean, LeeAnne; Marlowe, Jennifer; Emotte, Corinne; Tritto, Elaine; Tseng, Min; Shultz, Michael; Friedrichs, Gregory S

2016-09-01

Histone deacetylase (HDAC) inhibitors are an emerging class of anticancer agents that modify gene expression by altering the acetylation status of lysine residues of histone proteins, thereby inducing transcription, cell cycle arrest, differentiation, and cell death or apoptosis of cancer cells. In the clinical setting, treatment with HDAC inhibitors has been associated with delayed cardiac repolarization and in rare instances a lethal ventricular tachyarrhythmia known as torsades de pointes. The mechanism(s) of HDAC inhibitor-induced effects on cardiac repolarization is unknown. We demonstrate that administration of structurally diverse HDAC inhibitors to dogs causes delayed but persistent increases in the heart rate corrected QT interval (QTc), an in vivo measure of cardiac repolarization, at timepoints far removed from the Tmax for parent drug and metabolites. Transcriptional profiling of ventricular myocardium from dogs treated with various HDAC inhibitors demonstrated effects on genes involved in protein trafficking, scaffolding and insertion of various ion channels into the cell membrane as well as genes for specific ion channel subunits involved in cardiac repolarization. Extensive in vitro ion channel profiling of various structural classes of HDAC inhibitors (and their major metabolites) by binding and acute patch clamp assays failed to show any consistent correlations with direct ion channel blockade. Drug-induced rescue of an intracellular trafficking-deficient mutant potassium ion channel, hERG (G601S), and decreased maturation (glycosylation) of wild-type hERG expressed by CHO cells in vitro correlated with prolongation of QTc intervals observed in vivo The results suggest that HDAC inhibitor-induced prolongation of cardiac repolarization may be mediated in part by transcriptional changes of genes required for ion channel trafficking and localization to the sarcolemma. These data have broad implications for the development of these drug classes and

Electrophysiological and structural determinants of electrotonic modulation of repolarization by the activation sequence

PubMed Central

Walton, Richard D.; Benson, Alan P.; Hardy, Matthew E. L.; White, Ed; Bernus, Olivier

2013-01-01

Spatial dispersion of repolarization is known to play an important role in arrhythmogenesis. Electrotonic modulation of repolarization by the activation sequence has been observed in some species and tissue preparations, but to varying extents. Our study sought to determine the mechanisms underlying species- and tissue-dependent electrotonic modulation of repolarization in ventricles. Epi-fluorescence optical imaging of whole rat hearts and pig left ventricular wedges were used to assess epicardial spatial activation and repolarization characteristics. Experiments were supported by computer simulations using realistic geometries. Tight coupling between activation times (AT) and action potential duration (APD) were observed in rat experiments but not in pig. Linear correlation analysis found slopes of −1.03 ± 0.59 and −0.26 ± 0.13 for rat and pig, respectively (p < 0.0001). In rat, maximal dispersion of APD was 11.0 ± 3.1 ms but dispersion of repolarization time (RT) was relatively homogeneous (8.2 ± 2.7, p < 0.0001). However, in pig no such difference was observed between the dispersion of APD and RT (17.8 ± 6.1 vs. 17.7 ± 6.5, respectively). Localized elevations of APD (12.9 ± 8.3%) were identified at ventricular insertion sites of rat hearts both in experiments and simulations. Tissue geometry and action potential (AP) morphology contributed significantly to determining influence of electrotonic modulation. Simulations of a rat AP in a pig geometry decreased the slope of AT and APD relationships by 70.6% whereas slopes were increased by 75.0% when implementing a pig AP in a rat geometry. A modified pig AP, shortened to match the rat APD, showed little coupling between AT and APD with greatly reduced slope compared to the rat AP. Electrotonic modulation of repolarization by the activation sequence is especially pronounced in small hearts with murine-like APs. Tissue architecture and AP morphology play an important role in electrotonic modulation of

T-wave alternans and beat-to-beat variability of repolarization: pathophysiological backgrounds and clinical relevance.

PubMed

Floré, Vincent; Willems, Rik

2012-12-01

In this review, we focus on temporal variability of cardiac repolarization. This phenomenon has been related to a higher risk for ventricular arrhythmia and is therefore interesting as a marker of sudden cardiac death risk. We review two non-invasive clinical techniques quantifying repolarization variability: T-wave alternans (TWA) and beat-to-beat variability of repolarization (BVR). We discuss their pathophysiological link with ventricular arrhythmia and the current clinical relevance of these techniques.

Timing of myocardial trpm7 deletion during cardiogenesis variably disrupts adult ventricular function, conduction, and repolarization.

PubMed

Sah, Rajan; Mesirca, Pietro; Mason, Xenos; Gibson, William; Bates-Withers, Christopher; Van den Boogert, Marjolein; Chaudhuri, Dipayan; Pu, William T; Mangoni, Matteo E; Clapham, David E

2013-07-09

Transient receptor potential (TRP) channels are a superfamily of broadly expressed ion channels with diverse physiological roles. TRPC1, TRPC3, and TRPC6 are believed to contribute to cardiac hypertrophy in mouse models. Human mutations in TRPM4 have been linked to progressive familial heart block. TRPM7 is a divalent-permeant channel and kinase of unknown function, recently implicated in the pathogenesis of atrial fibrillation; however, its function in ventricular myocardium remains unexplored. We generated multiple cardiac-targeted knockout mice to test the hypothesis that TRPM7 is required for normal ventricular function. Early cardiac Trpm7 deletion (before embryonic day 9; TnT/Isl1-Cre) results in congestive heart failure and death by embryonic day 11.5 as a result of hypoproliferation of the compact myocardium. Remarkably, Trpm7 deletion late in cardiogenesis (about embryonic day 13; αMHC-Cre) produces viable mice with normal adult ventricular size, function, and myocardial transcriptional profile. Trpm7 deletion at an intermediate time point results in 50% of mice developing cardiomyopathy associated with heart block, impaired repolarization, and ventricular arrhythmias. Microarray analysis reveals elevations in transcripts of hypertrophy/remodeling genes and reductions in genes important for suppressing hypertrophy (Hdac9) and for ventricular repolarization (Kcnd2) and conduction (Hcn4). These transcriptional changes are accompanied by action potential prolongation and reductions in transient outward current (Ito; Kcnd2). Similarly, the pacemaker current (If; Hcn4) is suppressed in atrioventricular nodal cells, accounting for the observed heart block. Trpm7 is dispensable in adult ventricular myocardium under basal conditions but is critical for myocardial proliferation during early cardiogenesis. Loss of Trpm7 at an intermediate developmental time point alters the myocardial transcriptional profile in adulthood, impairing ventricular function, conduction

Recent advances in understanding sex differences in cardiac repolarization.

PubMed

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

2007-07-01

A number of gender differences exist in the human electrocardiogram (ECG): the P-wave and P-R intervals are slightly longer in men than in women, whilst women have higher resting heart rates than do men, but a longer rate-corrected QT (QT(C)) interval. Women with the LQT1 and LQT2 variants of congenital long-QT syndrome (LQTS) are at greater risk of adverse cardiac events. Similarly, many drugs associated with acquired LQTS have a greater risk of inducing torsades de pointes (TdP) arrhythmia in women than in men. There are also male:female differences in Brugada syndrome, early repolarisation syndrome and sudden cardiac death. The differences in the ECG between men and women, and in particular those relating to the QT interval, have been explored experimentally and provide evidence of differences in the processes underlying ventricular repolarization. The data available from rabbit, canine, rat, mouse and guinea pig models are reviewed and highlight involvement of male:female differences in Ca and K currents, although the possible involvement of rapid and persistent Na current and Na-Ca exchange currents cannot yet be excluded. The mechanisms underlying observed differences remain to be elucidated fully, but are likely to involve the influence of gonadal steroids. With respect to the QT interval and risk of TdP, a range of evidence implicates a protective role of testosterone in male hearts, possibly by both genomic and non-genomic pathways. Evidence regarding oestrogen and progesterone is less unequivocal, although the interplay between these two hormones may influence both repolarization and pro-arrhythmic risk.

Role of suppression of the inward rectifier current in terminal action potential repolarization in the failing heart.

PubMed

Klein, Michael G; Shou, Matie; Stohlman, Jayna; Solhjoo, Soroosh; Haigney, Myles; Tidwell, Richard R; Goldstein, Robert E; Flagg, Thomas P; Haigney, Mark C

2017-08-01

The failing heart exhibits an increased arrhythmia susceptibility that is often attributed to action potential (AP) prolongation due to significant ion channel remodeling. The inwardly rectifying K + current (I K1 ) has been reported to be reduced, but its contribution to shaping the AP waveform and cell excitability in the failing heart remains unclear. The purpose of this study was to define the effect of I K1 suppression on the cardiac AP and excitability in the normal and failing hearts. We used electrophysiological and pharmacological approaches to investigate I K1 function in a swine tachy-pacing model of heart failure (HF). Terminal repolarization of the AP (TRAP; the time constant of the exponential fit to terminal repolarization) was markedly prolonged in both myocytes and arterially perfused wedges from animals with HF. TRAP was increased by 54.1% in HF myocytes (P < .001) and 26.2% in HF wedges (P = .014). The increase in TRAP was recapitulated by the potent and specific I K1 inhibitor, PA-6 (pentamidine analog 6), indicating that I K1 is the primary determinant of the final phase of repolarization. Moreover, we find that I K1 suppression reduced the ratio of effective refractory period to AP duration at 90% of repolarization, permitting re-excitation before full repolarization, reduction of AP upstroke velocity, and likely promotion of slow conduction. Using an objective measure of terminal repolarization, we conclude that I K1 is the major determinant of the terminal repolarization time course. Moreover, suppression of I K1 prolongs repolarization and reduces postrepolarization refractoriness without marked effects on the overall AP duration. Collectively, these findings demonstrate how I K1 suppression may contribute to arrhythmogenesis in the failing heart. Published by Elsevier Inc.

[The influence of occupational lead exposure on transmural repolarization dispersion].

PubMed

Zyśko, Dorota; Gajek, Jacek; Chlebda, Ewa; Mazurek, Walentyna

2005-02-01

The parts of QT interval: time from Q wave to the peak of T wave (QTp) representing the de- and repolarization of subepicardial layer and the time from the peak of T wave to its end (QTp-e) building the transmural dispersion of repolarization enable more exact assessment of repolarization period of the heart muscle. Occupational exposure to lead influences the electrophysiologic properties of the heart. The aim of our study was to assess the QTp and QTp-e interval in workers occupationally exposed to lead. The study was carried out in 22 copper smelters aged 41.8 +/- 8.7 years, occupationally exposed to lead. The control group consisted of 14 healthy men. In all studied subjects blood lead concentration (Pb) and the concentration of free protoporphyrins in erytrocytes were assessed. 24-hour ECG holter monitoring was done to study rhythm disturbances and the duration in lead CM5 of QT interval, QTp interval, RR interval preceding the assessed QT interval (pRR) during sleep, rest during the awake state and moderate daily activity. The QTp-e interval is the difference between the duration of QT and QTp interval. The duration of QTp and QTp-e in occupationally exposed workers and healthy persons did not differ significantly. These parameters were significantly lower in both groups during moderately physical activity comparing to the values during sleep. The QTp-e/ QTp ratio in occupationally exposed workers during night hours was significantly lower than during daily activity what was not the case in control persons. Occupational exposure to lead do not change significantly the transmural dispersion of repolarization. Occupational exposure to lead diminishes the QTp-e/QTp ratio during the night.

Modeling and quantification of repolarization feature dependency on heart rate.

PubMed

Minchole, A; Zacur, E; Pueyo, E; Laguna, P

2014-01-01

This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular and Respiratory Systems". This work aims at providing an efficient method to estimate the parameters of a non linear model including memory, previously proposed to characterize rate adaptation of repolarization indices. The physiological restrictions on the model parameters have been included in the cost function in such a way that unconstrained optimization techniques such as descent optimization methods can be used for parameter estimation. The proposed method has been evaluated on electrocardiogram (ECG) recordings of healthy subjects performing a tilt test, where rate adaptation of QT and Tpeak-to-Tend (Tpe) intervals has been characterized. The proposed strategy results in an efficient methodology to characterize rate adaptation of repolarization features, improving the convergence time with respect to previous strategies. Moreover, Tpe interval adapts faster to changes in heart rate than the QT interval. In this work an efficient estimation of the parameters of a model aimed at characterizing rate adaptation of repolarization features has been proposed. The Tpe interval has been shown to be rate related and with a shorter memory lag than the QT interval.

The Role of Transmural Repolarization Gradient in the Inversion of Cardiac Electric Field: Model Study of ECG in Hypothermia.

PubMed

Arteyeva, Natalia V; Azarov, Jan E

2017-01-01

The changes in ventricular repolarization gradients lead to significant alterations of the electrocardiographic body surface T waves up to the T wave inversion. However, the contribution of a specific gradient remains to be elucidated. The objective of the present investigation was to study the role of the transmural repolarization gradient in the inversion of the body surface T wave with a mathematical model of the hypothermia-induced changes of ventricular repolarization. By means of mathematical simulation, we set the hypothermic action potential duration (APD) distribution on the rabbit ventricular epicardium as it was previously experimentally documented. Then the parameters of the body surface potential distribution were tested with the introduction of different scenarios of the endocardial and epicardial APD behavior in hypothermia resulting in the unchanged, reversed or enlarged transmural repolarization gradient. The reversal of epicardial repolarization gradients (apicobasal, anterior-posterior and interventricular) caused the inversion of the T waves regardless of the direction of the transmural repolarization gradient. However, the most realistic body surface potentials were obtained when the endocardial APDs were not changed under hypothermia while the epicardial APDs prolonged. This produced the reversed and increased transmural repolarization gradient in absolute magnitude. The body surface potentials simulated under the unchanged transmural gradient were reduced in comparison to those simulated under the reversed transmural gradient. The simulations demonstrated that the transmural repolarization gradient did not play a crucial role in the cardiac electric field inversion under hypothermia, but its magnitude and direction contribute to the T wave amplitude. © 2016 Wiley Periodicals, Inc.

Variants of Brugada Syndrome and Early Repolarization Syndrome: An Expanded Concept of J-Wave Syndrome.

PubMed

Kim, Sung-Hwan; Nam, Gi-Byoung; Yun, Sung-Cheol; Choi, Hyung Oh; Choi, Kee-Joon; Joung, Boyoung; Pak, Hui-Nam; Lee, Moon-Hyoung; Kim, Sung Soon; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Oh, Il-Young; Choi, Eue-Keun; Oh, Seil; Choi, Yun-Shik; Choi, Jong Il; Park, Sang Weon; Kim, Young-Hoon; Oh, Yong-Seog; Lee, Man Young; Lim, Hong Euy; Lee, Young-Soo; Cho, Yongkeun; Kim, Jun; Rhee, Kyoung-Suk; Lee, Dong-Il; Cho, Dae Kyoung; Kim, You-Ho

2017-02-01

The role of J-waves in the pathogenesis of ventricular fibrillation (VF) occurring in structurally normal hearts is important. We evaluated 127 patients who received an implantable cardioverter-defibrillator (ICD) for Brugada syndrome (BS, n = 53), early repolarization syndrome (ERS, n = 24), and patients with unknown or deferred diagnosis (n = 50). Electrocardiography (ECG), clinical characteristics, and ICD data were analyzed. J-waves were found in 27/50 patients with VF of unknown/deferred diagnosis. The J-waves were reminiscent of those seen in BS or ERS, and this subgroup of patients was termed variants of ERS and BS (VEB). In 12 VEB patients, the J/ST/T-wave morphology was coved, although amplitudes were <0.2 mV. In 15 patients, noncoved-type J/ST/T-waves were present in the right precordial leads. In the remaining 23 patients, no J-waves were identified. VEB patients exhibited clinical characteristics similar to those of BS and ERS patients. Phenotypic transition and overlap were observed among patients with BS, ERS, and VEB. Twelve patients with BS had background inferolateral ER, while five ERS patients showed prominent right precordial J-waves. Patients with this transient phenotype overlap showed a significantly lower shock-free survival than the rest of the study patients. VEB patients demonstrate ECG phenotype similar to but distinct from those of BS and ERS. The spectral nature of J-wave morphology/distribution and phenotypic transition/overlap suggest a common pathophysiologic background in patients with VEB, BS, and ERS. Prognostic implication of these ECG variations requires further investigation. © 2016 Wiley Periodicals, Inc.

Remodeling of repolarization and arrhythmia susceptibility in a myosin-binding protein C knockout mouse model.

PubMed

Toib, Amir; Zhang, Chen; Borghetti, Giulia; Zhang, Xiaoxiao; Wallner, Markus; Yang, Yijun; Troupes, Constantine D; Kubo, Hajime; Sharp, Thomas E; Feldsott, Eric; Berretta, Remus M; Zalavadia, Neil; Trappanese, Danielle M; Harper, Shavonn; Gross, Polina; Chen, Xiongwen; Mohsin, Sadia; Houser, Steven R

2017-09-01

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac diseases and among the leading causes of sudden cardiac death (SCD) in the young. The cellular mechanisms leading to SCD in HCM are not well known. Prolongation of the action potential (AP) duration (APD) is a common feature predisposing hypertrophied hearts to SCD. Previous studies have explored the roles of inward Na + and Ca 2+ in the development of HCM, but the role of repolarizing K + currents has not been defined. The objective of this study was to characterize the arrhythmogenic phenotype and cellular electrophysiological properties of mice with HCM, induced by myosin-binding protein C (MyBPC) knockout (KO), and to test the hypothesis that remodeling of repolarizing K + currents causes APD prolongation in MyBPC KO myocytes. We demonstrated that MyBPC KO mice developed severe hypertrophy and cardiac dysfunction compared with wild-type (WT) control mice. Telemetric electrocardiographic recordings of awake mice revealed prolongation of the corrected QT interval in the KO compared with WT control mice, with overt ventricular arrhythmias. Whole cell current- and voltage-clamp experiments comparing KO with WT mice demonstrated ventricular myocyte hypertrophy, AP prolongation, and decreased repolarizing K + currents. Quantitative RT-PCR analysis revealed decreased mRNA levels of several key K + channel subunits. In conclusion, decrease in repolarizing K + currents in MyBPC KO ventricular myocytes contributes to AP and corrected QT interval prolongation and could account for the arrhythmia susceptibility. NEW & NOTEWORTHY Ventricular myocytes isolated from the myosin-binding protein C knockout hypertrophic cardiomyopathy mouse model demonstrate decreased repolarizing K + currents and action potential and QT interval prolongation, linking cellular repolarization abnormalities with arrhythmia susceptibility and the risk for sudden cardiac death in hypertrophic cardiomyopathy. Copyright © 2017

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

PubMed

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Constitutional rho-kinase regulates atrioventricular nodal conduction and ventricular repolarization of the canine heart.

PubMed

Sugiyama, Atsushi; Takahara, Akira; Yatomi, Yutaka; Satoh, Yoshioki; Nakamura, Yuji; Hashimoto, Keitaro

2003-06-01

Given the limited information, physiological roles of Rho-kinase in the cardiac conduction system and ventricular repolarization process were assessed in comparison with those in the coronary vascular tone. A specific Rho-kinase inhibitor Y-27632 was administered to the nutrient coronary artery of the canine isolated, blood-perfused atrioventricular node preparation under the monitoring of the ventricular monophasic action potentials. Administration of Y-27632 moderately suppressed the atrioventricular nodal conduction, slightly but significantly accelerated the repolarization process, and potently increased the coronary blood flow, whereas it hardly affected the intraventricular conduction. The estimated concentrations of Y-27632 causing the currently observed effects were enough to inhibit Rho-kinase. These results suggest that constitutional Rho-kinase functions to moderately facilitate the atrioventricular nodal conduction, slightly delay ventricular repolarization process, and significantly increase the coronary vascular tone.

Dofetilide promotes repolarization abnormalities in perfused Guinea-pig heart.

PubMed

Osadchii, Oleg E

2012-12-01

Dofetilide is class III antiarrhythmic agent which prolongs cardiac action potential duration because of selective inhibition of I (Kr), the rapid component of the delayed rectifier K(+) current. Although clinical studies reported on proarrhythmic risk associated with dofetilide treatment, the contributing electrophysiological mechanisms remain poorly understood. This study was designed to determine if dofetilide-induced proarrhythmia may be attributed to abnormalities in ventricular repolarization and refractoriness. The monophasic action potential duration and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated, perfused guinea-pig heart preparations. Dofetilide was found to produce the reverse rate-dependent prolongation of ventricular repolarization, increased the steepness of action potential duration rate adaptation, and amplified transepicardial variability in electrical restitution kinetics. Dofetilide also prolonged the T peak-to-end interval on ECG, and elicited a greater prolongation of endocardial than epicardial ERP, thereby increasing transmural dispersion of refractoriness. At epicardium, dofetilide prolonged action potential duration to a greater extent than ERP, thus extending the critical interval for ventricular re-excitation. This change was associated with triangulation of epicardial action potential because of greater dofetilide-induced prolonging effect at 90 % than 30 % repolarization. Premature ectopic beats and spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 44 % of dofetilide-treated heart preparations. Proarrhythmic potential of dofetilide in guinea-pig heart is attributed to steepened electrical restitution, increased transepicardial variability in electrical restitution kinetics, amplified transmural dispersion of refractoriness, increased critical interval for ventricular re-excitation, and

Flecainide-induced proarrhythmia is attributed to abnormal changes in repolarization and refractoriness in perfused guinea-pig heart.

PubMed

Osadchii, Oleg E

2012-11-01

Flecainide is nonselective Na(+) channel blocker which may also inhibit I(Kr), the rapid component of the delayed rectifier. This study was designed to explore if proarrhythmic responses to flecainide noted in cardiac patients may be partly attributed to abnormal changes in repolarization and refractoriness. Monophasic action potential duration (APD) and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated perfused guinea-pig heart preparations. Flecainide was found to prolong ventricular repolarization, with effect being greater at the left ventricular compared with the right ventricular epicardium. This change translated to reversal of the normal right ventricular-to-left ventricular transepicardial APD difference determined before drug infusion. An inverse correlation between local epicardial APD and corresponding activation time values seen at baseline was eliminated in flecainide-treated hearts, indicating the activation-to-repolarization uncoupling. Over transmural plane, flecainide produced a greater ERP lengthening at endocardium than epicardium, thus markedly increasing ERP dispersion across ventricular wall. Spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 45% of heart preparations upon flecainide infusion. In conclusion, in nonischemic guinea-pig heart, flecainide-induced proarrhythmia may be partly attributed to abnormal spatial gradients in repolarization and refractoriness and impaired transepicardial activation-to-repolarization coupling.

Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart.

PubMed

Osadchii, Oleg E

2016-01-01

Flecainide is class Ic antiarrhythmic agent that was found to increase the risk of sudden cardiac death. Arrhythmic responses to flecainide could be precipitated by exercise, suggesting a role played by inappropriate rate adaptation of ventricular repolarization. This study therefore examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length. ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation. Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged ventricular repolarization, delayed its rate adaptation, and decreased the amplitude of QT interval and APD shortening upon rapid cardiac pacing. During extrasystolic stimulation, flecainide attenuated APD shortening in premature ventricular beats, with effect being greater upon using a longer basic drive cycle length (S1-S1=550 ms versus S1-S1=300 ms). Flecainide-induced arrhythmia may be partly accounted for by attenuated adaptation of ventricular repolarization to sudden changes in cardiac cycle length provoked by transient tachycardia or ectopic beats.

Hyperventilation assists proarrhythmia development during delayed repolarization in clofilium-treated, anaesthetized, mechanically ventilated rabbits.

PubMed

Papp, H; Sarusi, A; Farkas, A S; Takacs, H; Kui, P; Vincze, D; Ivany, E; Varro, A; Papp, J G; Forster, T; Farkas, A

2016-10-01

Hyperventilation reduces partial pressure of CO 2 (PCO 2 ) in the blood, which results in hypokalaemia. Hypokalaemia helps the development of the life-threatening torsades de pointes type ventricular arrhythmia (TdP) evoked by repolarization delaying drugs. This implies that hyperventilation may assist the development of proarrhythmic events. Therefore, this study experimentally investigated the effect of hyperventilation on proarrhythmia development during delayed repolarization. Phenylephrine (an α 1 -adrenoceptor agonist) and clofilium (as a representative repolarization delaying agent inhibiting the rapid component of the delayed rectifier potassium current, I Kr ) were administered intravenously to pentobarbital-anaesthetized, mechanically ventilated, open chest rabbits. ECG was recorded, and the onset times and incidences of the arrhythmias were determined. Serum K + , pH and PCO 2 were measured in arterial blood samples. Clofilium prolonged the rate corrected QT interval. TdP occurred in 15 animals (TdP+ group), and did not occur in 14 animals (TdP- group). We found a strong, positive, linear correlation between serum K + and PCO 2 . There was no relationship between the occurrence of TdP and the baseline K + and PCO 2 values. However, a positive, linear correlation was found between the onset time of the first arrhythmias and the K + and PCO 2 values. The regression lines describing the relationship between PCO 2 and onset time of first arrhythmias were parallel in the TdP+ and TdP- groups, but the same PCO 2 resulted in earlier arrhythmia onset in the TdP+ group than in the TdP- group. We conclude that hyperventilation and hypocapnia with the resultant hypokalaemia assist the multifactorial process of proarrhythmia development during delayed repolarization. This implies that PCO 2 and serum K + should be controlled tightly during mechanical ventilation in experimental investigations and clinical settings when repolarization-delaying drugs are applied.

The Role of Serotonin in Ventricular Repolarization in Pregnant Mice

PubMed Central

Park, Hyelim; Mun, Dasom; Lee, Seung-Hyun; Kim, Hyoeun; Yun, Nuri; Kim, Hail; Kim, Michael; Pak, Hui-Nam; Lee, Moon-Hyoung

2018-01-01

Purpose The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. Materials and Methods We measured current amplitudes and the expression levels of voltage-gated K+ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a−/−-NP). Results During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT interval in WT-NP mice, but not in WT-LP and Htr3a−/−-NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increased the trafficking of Kv4.3 channels to the cellular membrane in WT-NP. Conclusion Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents. PMID:29436197

The Role of Serotonin in Ventricular Repolarization in Pregnant Mice.

PubMed

Cui, Shanyu; Park, Hyewon; Park, Hyelim; Mun, Dasom; Lee, Seung Hyun; Kim, Hyoeun; Yun, Nuri; Kim, Hail; Kim, Michael; Pak, Hui Nam; Lee, Moon Hyoung; Joung, Boyoung

2018-03-01

The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. We measured current amplitudes and the expression levels of voltage-gated K⁺ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a(-/-)-NP). During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT interval in WT-NP mice, but not in WT-LP and Htr3a(-/-)-NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increased the trafficking of Kv4.3 channels to the cellular membrane in WT-NP. Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents. © Copyright: Yonsei University College of Medicine 2018

Pharmacokinetics and repolarization effects of intravenous and transdermal granisetron.

PubMed

Mason, Jay W; Selness, Daniel S; Moon, Thomas E; O'Mahony, Bridget; Donachie, Peter; Howell, Julian

2012-05-15

The need for greater clarity about the effects of 5-HT(3) receptor antagonists on cardiac repolarization is apparent in the changing product labeling across this therapeutic class. This study assessed the repolarization effects of granisetron, a 5-HT(3) receptor antagonist antiemetic, administered intravenously and by a granisetron transdermal system (GTDS). In a parallel four-arm study, healthy subjects were randomized to receive intravenous granisetron, GTDS, placebo, or oral moxifloxacin (active control). The primary endpoint was difference in change from baseline in mean Fridericia-corrected QT interval (QTcF) between GTDS and placebo (ddQTcF) on days 3 and 5. A total of 240 subjects were enrolled, 60 in each group. Adequate sensitivity for detection of QTc change was shown by a 5.75 ms lower bound of the 90% confidence interval (CI) for moxifloxacin versus placebo at 2 hours postdose on day 3. Day 3 ddQTcF values varied between 0.2 and 1.9 ms for GTDS (maximum upper bound of 90% CI, 6.88 ms), between -1.2 and 1.6 ms for i.v. granisetron (maximum upper bound of 90% CI, 5.86 ms), and between -3.4 and 4.7 ms for moxifloxacin (maximum upper bound of 90% CI, 13.45 ms). Day 5 findings were similar. Pharmacokinetic-ddQTcF modeling showed a minimally positive slope of 0.157 ms/(ng/mL), but a very low correlation (r = 0.090). GTDS was not associated with statistically or clinically significant effects on QTcF or other electrocardiographic variables. This study provides useful clarification on the effect of granisetron delivered by GTDS on cardiac repolarization. ©2012 AACR.

A simultaneous multichannel monophasic action potential electrode array for in vivo epicardial repolarization mapping.

PubMed

Sahakian, A V; Peterson, M S; Shkurovich, S; Hamer, M; Votapka, T; Ji, T; Swiryn, S

2001-03-01

While the recording of extracellular monophasic action potentials (MAPs) from single epicardial or endocardial sites has been performed for over a century, we are unaware of any previous successful attempt to record MAPs simultaneously from a large number of sites in vivo. We report here the design and validation of an array of MAP electrodes which records both depolarization and repolarization simultaneously at up to 16 epicardial sites in a square array on the heart in vivo. The array consists of 16 sintered Ag-AgCl electrodes mounted in a common housing with individual suspensions allowing each electrode to exert a controlled pressure on the epicardial surface. The electrodes are arranged in a square array, with each quadrant of four having an additional recessed sintered Ag-AgCl reference electrode at its center. A saline-soaked sponge establishes ionic contact between the reference electrodes and the tissue. The array was tested on six anesthetized open-chested pigs. Simultaneous diagnostic-quality MAP recordings were obtained from up to 13 out of 16 ventricular sites. Ventricular MAPs had amplitudes of 10-40 mV with uniform morphologies and stable baselines for up to 30 min. MAP duration at 90% repolarization was measured and shown to vary as expected with cycle length during sustained pacing. The relationship between MAP duration and effective refractory period was also confirmed. The ability of the array to detect local differences in repolarization was tested in two ways. Placement of the array straddling the atrioventricular (AV) junction yielded simultaneous atrial or ventricular recordings at corresponding sites during 1:1 and 2:1 AV conduction. Localized ischemia via constriction of a coronary artery branch resulted in shortening of the repolarization phase at the ischemic, but not the nonischemic, sites. In conclusion, these results indicate that the simultaneous multichannel MAP electrode array is a viable method for in vivo epicardial repolarization

Evaluation of the acute electrophysiologic effects of intravenous dronedarone, an amiodarone-like agent, with special emphasis on ventricular repolarization and acquired torsade de pointes arrhythmias.

PubMed

Verduyn, S C; Vos, M A; Leunissen, H D; van Opstal, J M; Wellens, H J

1999-02-01

In the anesthetized dog with complete chronic AV block (CAVB), we evaluated and compared the acute electrophysiologic effects of dronedarone i.v. (Dron, 2 times 2.5 mg/kg/10 min) and amiodarone i.v. (Amio, 2 times 5 mg/kg/10 min). This canine model with a high sensitivity for acquired torsade de pointes (TdP) provides an ideal substrate to evaluate ventricular repolarization abnormalities. Six ECG leads and two endocardial monophasic action potential (MAP) recordings in the left and right ventricle (LV and RV) were simultaneously recorded to measure QT time, action-potential duration (APD), interventricular dispersion (deltaAPD = LV(APD) - RV(APD)), early afterdepolarizations (EADs), ectopic beats (EBs), and TdP. Measurements were made at the spontaneous idioventricular rhythm (IVR) and 1,000-ms steady-state pacing. To investigate its short-term, antiarrhythmic properties, Dron was given after almokalant (0.12 mg/kg)-induced TdP. Furthermore, in another set of experiments, oral Dron (20 mg/kg, b.i.d) was given for 3 weeks to conscious CAVB dogs. Dron, i.v., shortened ventricular repolarization (QT, 435 +/- 60 to 360 +/- 55; LV(APD) 395 +/- 75 to 335 +/- 60 ms; p < 0.05), whereas IVR and ventricular effective refractory period (VERP, 225 +/- 30 to 230 +/- 30 ms) remained similar. Therefore the VERP/QT ratio increased (0.55 +/- 0.04 to 0.61 +/- 0.03; p < 0.05). Similar results were obtained with Amio, i.v.. Almokalant-induced TdP was characterized by an increased repolarization duration, deltaAPD, and EADs. Dron, i.v., suppressed the EADs, EBs, and TdP by a reduction and homogenization of repolarization (LV(APD), 505 +/- 110 to 455 +/- 80 ms, and deltaAPD, 110 +/- 55 to 65 +/- 40 ms). Long-term oral Dron increased the PP interval, CL-IVR, and QT(c) time. In contrast to oral treatment, Dron i.v. shortens ventricular repolarization parameters, resulting in suppression of EAD-dependent acquired TdP. The increased VERP/QT ratio after Dron i.v. may indicate an important

The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction.

PubMed

Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

2015-01-01

To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X(2) test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group

Impact of Ancillary Subunits on Ventricular Repolarization

PubMed Central

Abbott, Geoffrey W.; Xu, Xianghua; Roepke, Torsten K.

2007-01-01

Voltage-gated potassium (Kv) channels generate the outward K+ ion currents that constitute the primary force in ventricular repolarization. Kv channels comprise tetramers of pore-forming α subunits and, in probably the majority of cases in vivo, ancillary or β subunits that help define the properties of the Kv current generated. Ancillary subunits can be broadly categorized as cytoplasmic or transmembrane, and can modify Kv channel trafficking, conductance, gating, ion selectivity, regulation and pharmacology. Because of their often profound effects on Kv channel function, studies of the molecular correlates of ventricular repolarization must take into account ancillary subunits as well as α subunits. Cytoplasmic ancillary subunits include the Kvβ subunits, which regulate a range of Kv channels and may link channel gating to redox potential; and the KChIPs, which appear most often associated with Kv4 subfamily channels that generate the ventricular Ito current. Transmembrane ancillary subunits include the MinK-related proteins (MiRPs) encoded by KCNE genes, which modulate members of most Kv α subunit subfamilies; and the putative 12-transmembrane domain KCR1 protein which modulates hERG. In some cases, such as the ventricular IKs channel complex, it is well-established that the KCNQ1 α subunit must co-assemble with the MinK (KCNE1) single transmembrane domain ancillary subunit for recapitulation of the characteristic, unusually slowly-activating IKs current. In other cases it is not so clear-cut, and in particular the roles of the other MinK-related proteins (MiRPs 1–4) in regulating cardiac Kv channels such as KCNQ1 and hERG in vivo are under debate. MiRP1 alters hERG function and pharmacology, and inherited MiRP1 mutations are associated with inherited and acquired arrhythmias, but controversy exists over the native role of MiRP1 in regulating hERG (and therefore ventricular IKr) in vivo. Some ancillary subunits may exhibit varied expression to shape

Glucose ingestion causes cardiac repolarization disturbances in type 1 long QT syndrome patients and healthy subjects.

PubMed

Hyltén-Cavallius, Louise; Iepsen, Eva W; Christiansen, Michael; Graff, Claus; Linneberg, Allan; Pedersen, Oluf; Holst, Jens J; Hansen, Torben; Torekov, Signe S; Kanters, Jørgen K

2017-08-01

Both hypoglycemia and severe hyperglycemia constitute known risk factors for cardiac repolarization changes potentially leading to malignant arrhythmias. Patients with loss of function mutations in KCNQ1 are characterized by long QT syndrome (LQTS) and may be at increased risk for glucose-induced repolarization disturbances. The purpose of this study was to test the hypothesis that KCNQ1 LQTS patients are at particular risk for cardiac repolarization changes during the relative hyperglycemia that occurs after an oral glucose load. Fourteen KCNQ1 LQTS patients and 28 control participants matched for gender, body mass index, and age underwent a 3-hour oral 75-g glucose tolerance test with ECGs obtained at 7 time points. Fridericia corrected QT interval (QTcF), Bazett corrected QT interval (QTcB), and the Morphology Combination Score (MCS) were calculated. QTc and MCS increased in both groups. MCS remained elevated until 150 minutes after glucose ingestion, and the maximal change from baseline was larger among KCNQ1 LQTS patients compared with control subjects (0.28 ± 0.27 vs 0.15 ± 0.13; P <.05). Relative hyperglycemia induced by ingestion of 75-g glucose caused cardiac repolarization disturbances that were more severe in KCNQ1 LQTS patients compared with control subjects. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Impact of Hypokalemia on Electromechanical Window, Excitation Wavelength and Repolarization Gradients in Guinea-Pig and Rabbit Hearts

PubMed Central

Osadchii, Oleg E.

2014-01-01

Normal hearts exhibit a positive time difference between the end of ventricular contraction and the end of QT interval, which is referred to as the electromechanical (EM) window. Drug-induced prolongation of repolarization may lead to the negative EM window, which was proposed to be a novel proarrhythmic marker. This study examined whether abnormal changes in the EM window may account for arrhythmogenic effects produced by hypokalemia. Left ventricular pressure, electrocardiogram, and epicardial monophasic action potentials were recorded in perfused hearts from guinea-pig and rabbit. Hypokalemia (2.5 mM K+) was found to prolong repolarization, reduce the EM window, and promote tachyarrhythmia. Nevertheless, during both regular pacing and extrasystolic excitation, the increased QT interval invariably remained shorter than the duration of mechanical systole, thus yielding positive EM window values. Hypokalemia-induced arrhythmogenicity was associated with slowed ventricular conduction, and shortened effective refractory periods, which translated to a reduced excitation wavelength index. Hypokalemia also evoked non-uniform prolongation of action potential duration in distinct epicardial regions, which resulted in increased spatial variability in the repolarization time. These findings suggest that arrhythmogenic effects of hypokalemia are not accounted for by the negative EM window, and are rather attributed to abnormal changes in ventricular conduction times, refractoriness, excitation wavelength, and spatial repolarization gradients. PMID:25141124

Myocyte repolarization modulates myocardial function in aging dogs

PubMed Central

Sorrentino, Andrea; Signore, Sergio; Borghetti, Giulia; Meo, Marianna; Cannata, Antonio; Zhou, Yu; Wybieralska, Ewa; Luciani, Marco; Kannappan, Ramaswamy; Zhang, Eric; Matsuda, Alex; Webster, Andrew; Cimini, Maria; Kertowidjojo, Elizabeth; D'Alessandro, David A.; Wunimenghe, Oriyanhan; Michler, Robert E.; Royer, Christopher; Goichberg, Polina; Leri, Annarosa; Barrett, Edward G.; Anversa, Piero; Hintze, Thomas H.

2016-01-01

Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions. PMID:26801307

Cardiac Autonomic Regulation and Repolarization During Acute Experimental Hypoglycemia in Type 2 Diabetes

PubMed Central

Chow, Elaine; Bernjak, Alan; Walkinshaw, Emma; Lubina-Solomon, Alexandra; Freeman, Jenny; Macdonald, Ian A.; Sheridan, Paul J.

2017-01-01

Hypoglycemia is associated with increased cardiovascular mortality in trials of intensive therapy in type 2 diabetes mellitus (T2DM). We previously observed an increase in arrhythmias during spontaneous prolonged hypoglycemia in patients with T2DM. We examined changes in cardiac autonomic function and repolarization during sustained experimental hypoglycemia. Twelve adults with T2DM and 11 age- and BMI-matched control participants without diabetes underwent paired hyperinsulinemic clamps separated by 4 weeks. Glucose was maintained at euglycemia (6.0 mmol/L) or hypoglycemia (2.5 mmol/L) for 1 h. Heart rate, blood pressure, and heart rate variability were assessed every 30 min and corrected QT intervals and T-wave morphology every 60 min. Heart rate initially increased in participants with T2DM but then fell toward baseline despite maintained hypoglycemia at 1 h accompanied by reactivation of vagal tone. In control participants, vagal tone remained depressed during sustained hypoglycemia. Participants with T2DM exhibited greater heterogeneity of repolarization during hypoglycemia as demonstrated by T-wave symmetry and principal component analysis ratio compared with control participants. Epinephrine levels during hypoglycemia were similar between groups. Cardiac autonomic regulation during hypoglycemia appears to be time dependent. Individuals with T2DM demonstrate greater repolarization abnormalities for a given hypoglycemic stimulus despite comparable sympathoadrenal responses. These mechanisms could contribute to arrhythmias during clinical hypoglycemic episodes. PMID:28137792

Cardiac Repolarization Changes in the Children with Breath-Holding Spells

PubMed Central

Amoozgar, Hamid; Saleh, Fazl; Farhani, Nahal; Rafiei, Mohammad; Inaloo, Soroor; Asadipooya, Ali-Akbar

2013-01-01

Objective Breath-holding spells are known as benign attacks, frequencies of which decrease by the development of the autonomic nervous system. The present study aims to compare the electrocardiographic repolarization in children with breath-holding spells. Methods In this study, QT dispersion, QTc dispersion, T peak to T end dispersion, and P wave dispersion of the twelve-lead surface electrocardiography of fifty children who had breath-holding spells were measured and compared with normal children from April 2011 to August 2012. Findings Forty-four (88%) patients had cyanotic spells, while 6 (12%) had pallid spells. QTc dispersion was increased in the patients with breath-holding spells (148.2±33.1) compared to the healthy children (132±27.3) and the difference was statically significant (P = 0.01). Meanwhile, no statistically significant differences were observed between the patients and the control subjects regarding the other parameters (P > 0.05). Conclusion QTc dispersion was significantly increased in the patients with breath-holding spells compared to normal children and this is a sign of cardiac repolarization abnormality as well as the increased risk of cardiac arrhythmia in patients with breath-holding spells. PMID:24910749

The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction

PubMed Central

Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

2015-01-01

Objective: To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. Background: QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. Material and methods: We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X2 test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. Results: QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max

Estrogen Contributes to Gender Differences in Mouse Ventricular Repolarization

PubMed Central

Saito, Tomoaki; Ciobotaru, Andrea; Bopassa, Jean Chrisostome; Toro, Ligia; Stefani, Enrico; Eghbali, Mansoureh

2010-01-01

Rationale Fast-transient outward K+ (Ito,f) and ultra-rapid delayed rectifier K+ currents (IKur or IK,slow) contribute to mouse cardiac repolarization. Gender studies on these currents have reported conflicting results. Objective One key missing piece information in these studies is the animals’ estral stage. We decided to revisit gender-related differences in K+ currents, taking into consideration the females’ estral stage. Methods and Results We hypothesized that changes in estrogen levels during the estral cycle could play a role in determining the densities of K+ currents underlying ventricular repolarization. Peak total K+ current (IK,total) densities (pA/pF, at +40 mV) were much higher in males (48.6±3.0) than in females at estrus (27.2±2.3) but not at diestrus-2 (39.1±3.4). Underlying this change, Ito,f and IK,slow were lower in females at estrus vs males and diestrus-2 (IK,slow: male 21.9±1.8, estrus 14.6±0.6, diestrus-2 20.3±1.4; Ito,f: male 26.8±1.9, estrus 14.9±1.6, diestrus-2 22.1±2.1). The lower IK,slow in estrus was only due to IK,slow1 reduction without changes of IK,slow2. Estrogen treatment of ovariectomized mice decreased IK,total (46.4±3.0 to 28.4±1.6), Ito,f (26.6±1.6 to 12.8±1.0) and IK,slow (22.2±1.6 to 17.2±1.4). Transcript levels of Kv4.3 and Kv1.5 (underlying Ito,f and IK,slow, respectively) were lower in estrus vs. diestrus-2 and male. In ovariectomized mice, estrogen treatment resulted in downregulation of Kv4.3 and Kv1.5, but not Kv4.2, KChIP2 and Kv2.1 transcripts. K+ current reduction in high estrogenic conditions were associated with prolongation of the action potential duration and corrected QT interval. Conclusion Downregulation of Kv4.3 and Kv1.5 transcripts by estrogen are one mechanism defining gender-related differences in mouse ventricular repolarization. PMID:19608983

Measurement and regulation of cardiac ventricular repolarization: from the QT interval to repolarization morphology

PubMed Central

Couderc, Jean-Philippe

2009-01-01

Ventricular repolarization (VR) is a crucial step in cardiac electrical activity because it corresponds to a recovery period setting the stage for the next heart contraction. Small perturbations of the VR process can predispose an individual to lethal arrhythmias. In this review, I aim to provide an overview of the methods developed to analyse static and dynamic aspects of the VR process when recorded from a surface electrocardiogram (ECG). The first section describes the list of physiological and clinical factors that can affect the VR. Technical aspects important to consider when digitally processing ECGs are provided as well. Special attention is given to the analysis of the effect of heart rate on the VR and its regulation by the autonomic nervous system. The final section provides the rationale for extending the analysis of the VR from its duration to its morphology. Several modelling techniques and measurement methods will be presented and their role within the arena of cardiac safety will be discussed. PMID:19324709

Kinetics of cycle length dependence of ventricular repolarization: effect of autonomic blockade

NASA Technical Reports Server (NTRS)

Raeder, E. A.; Albrecht, P.; Perrott, M.; Cohen, R. J.

1995-01-01

INTRODUCTION: Beat-to-beat adaptation of ventricular repolarization duration to cardiac cycle length and autonomic activity has not been previously characterized in the spontaneously beating human heart. METHODS AND RESULTS: The ECG of 14 healthy subjects was recorded from the supine and upright positions. Autonomic blockade was accomplished by atropine and propranolol. RR and RT intervals were measured by a computer algorithm, and the impulse response (h) from RR to RT computed. In the supine position the maximal adjustment of the RT interval occurred in the first beat following a change in cycle length (hpeak = 17.8 +/- 1.6 msec/sec), but continued to be detectable for 3.8 seconds (2.9-4.7 sec). Propranolol attenuated the peak impulse response to 15.8 +/- 4.0 msec/sec (P = NS). In the standing position the peak impulse response was increased to 25.2 +/- 5.0 msec/sec (P = 0.004 vs supine), and the impulse response duration (hdur) shortened to 1.4 seconds (1.3-1.6). This was reversed by beta blockade (hpeak = 10.7 +/- 3.6 [P = 0.005 vs standing]; hdur = 5.5 sec [4.8-6.1]). Parasympathetic and combined autonomic blockade resulted in too little residual heart rate variability to estimate the impulse response accurately. The slope of the regression of delta RT and delta RR in the supine position was 0.0177 +/- 0.0016, which was closely correlated with the peak impulse response (r = 0.91). CONCLUSIONS: System identification techniques can assist in characterizing the cycle dependence of ventricular repolarization and may provide new insights into conditions associated with abnormal repolarization.

Early rheumatoid disease. II. Patterns of joint involvement.

PubMed Central

Fleming, A; Benn, R T; Corbett, M; Wood, P H

1976-01-01

Data from the first research clinic visit (Fleming and others, 1976) have been subjected to factor analysis to identify early patterns of joint involvement. Nine patterns emerged. Two patterns, if present early, were found to have prognostic significance. An eventually more severe disease was associated with a pattern of large joint involvement (shoulder, elbow, wrist, knee) and a pattern based on metatarsophalangeal joints I and III. PMID:970995

Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex

PubMed Central

Pathak, Dhruba; Guan, Dongxu

2016-01-01

The action potential (AP) is a fundamental feature of excitable cells that serves as the basis for long-distance signaling in the nervous system. There is considerable diversity in the appearance of APs and the underlying repolarization mechanisms in different neuronal types (reviewed in Bean BP. Nat Rev Neurosci 8: 451–465, 2007), including among pyramidal cell subtypes. In the present work, we used specific pharmacological blockers to test for contributions of Kv1, Kv2, or Kv4 channels to repolarization of single APs in two genetically defined subpopulations of pyramidal cells in layer 5 of mouse somatosensory cortex (etv1 and glt) as well as pyramidal cells from layer 2/3. These three subtypes differ in AP properties (Groh A, Meyer HS, Schmidt EF, Heintz N, Sakmann B, Krieger P. Cereb Cortex 20: 826–836, 2010; Guan D, Armstrong WE, Foehring RC. J Neurophysiol 113: 2014–2032, 2015) as well as laminar position, morphology, and projection targets. We asked what the roles of Kv1, Kv2, and Kv4 channels are in AP repolarization and whether the underlying mechanisms are pyramidal cell subtype dependent. We found that Kv4 channels are critically involved in repolarizing neocortical pyramidal cells. There are also pyramidal cell subtype-specific differences in the role for Kv1 channels. Only Kv4 channels were involved in repolarizing the narrow APs of glt cells. In contrast, in etv1 cells and layer 2/3 cells, the broader APs are partially repolarized by Kv1 channels in addition to Kv4 channels. Consistent with their activation in the subthreshold range, Kv1 channels also regulate AP voltage threshold in all pyramidal cell subtypes. PMID:26864770

Sleep-disordered breathing is associated with disturbed cardiac repolarization in patients with a coronary artery bypass graft surgery.

PubMed

Schmidleitner, Christina; Arzt, Michael; Tafelmeier, Maria; Ripfel, Sarah; Fauser, Miriam; Weizenegger, Teresa; Flörchinger, Bernhard; Camboni, Daniele; Wittmann, Sigrid; Zeman, Florian; Schmid, Christof; Maier, Lars S; Wagner, Stefan; Fisser, Christoph

2018-02-01

The development of malignant ventricular arrhythmias due to abnormal cardiac repolarization is a major complication after coronary artery bypass graft surgery (CABG). Sleep-disordered breathing (SDB) is linked to prolonged cardiac repolarization in non-surgical patients. This study evaluates cardiac repolarization in patients with and without SDB who underwent CABG. 100 patients who had received CABG (84% men, age 68 ± 10 years, body-mass-index [BMI] 28.7 ± 4.2 kg/m 2 ) were retrospectively evaluated. Polygraphy was recorded the night before CABG. SDB was defined as an apnea-hypopnea index (AHI) of ≥15/h and differentiated into central (CSA) and obstructive (OSA) sleep apnea. Cardiac repolarization was assessed by means of T-peak-to-end (TpTe) and QTc-intervals and TpTe/QT-ratios derived from 12-lead electrocardiography (ECG). 37% of patients had SDB, 14% CSA and 23% OSA. Before CABG, patients with CSA and OSA had longer TpTe intervals than those without SDB (TpTe: CSA 100 ± 26 vs. OSA 97 ± 19 vs. no SDB 85 ± 14 ms, p = 0.013). QTc intervals and TpTe/QT ratios differed between the two groups (QTc: 444 ± 54 vs. 462 ± 36 vs. 421 ± 32 ms, p < 0.001; TpTe/QT ratio: 0.24 ± 0.04 vs. 0.23 ± 0.05 vs. 0.21 ± 0.03, p = 0.045). SDB was associated with abnormal cardiac repolarization independent of known risk factors for cardiac arrhythmias, such as age, sex, BMI, N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), and heart failure (TpTe: B-coefficient [95%CI]: 16.0, [7.6-24.3], p < 0.001; QTc: 27.2 [9.3-45.1], p = 0.003; TpTe/QT ratio: 2.9 [1.2-4.6], p < 0.001). Independent of known risk factors for cardiac arrhythmias, SDB was significantly associated with abnormal cardiac repolarization before CABG. Data suggest that SDB may contribute to an increased risk of ventricular arrhythmias after CABG. Copyright © 2018 Elsevier B.V. All rights reserved.

Cardiac repolarization during fingolimod treatment in patients with relapsing-remitting multiple sclerosis.

PubMed

Laiho, Aapo; Laitinen, Tiina M; Hartikainen, Päivi; Hartikainen, Juha E K; Laitinen, Tomi P; Simula, Sakari

2018-02-01

Fingolimod is a sphingosine-1-phosphate receptor modulator for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite an established effect on heart rate, the effect of fingolimod on cardiac repolarization is not completely known. Twenty-seven patients with RRMS underwent 24-hr ambulatory ECG before fingolimod (baseline), at the day of fingolimod initiation (1D) and after three-month treatment (3M). The mean values of RR-interval as well as QT-interval corrected by Bazzet's (QTcBaz) and Fridericia's (QTcFri) formula were compared between baseline, 1D, and 3M over 24-hr period as well as at daytime and nighttime. QTcBaz over 24-hr was shorter at 1D (414 ± 20 ms, p  < .001) and at 3M (414 ± 20 ms, p  < .001) than at baseline (418 ± 20 ms). In contrast, QTcFri over 24-hr was longer at 1D (410 ± 19 ms, p  < .001) but similar at 3M (406 ± 19 ms, p  = .355) compared to baseline (407 ± 19 ms). Daytime QTcBaz was shorter at 1D ( p  < .001) and at 3M ( p  = .007), whereas daytime QTcFri was longer at 1D ( p  < .05) but similar at 3M ( p  = ns) compared to baseline. During the night, changes were observed neither in QTcBaz nor in QTcFri between baseline, 1D, and 3M. Changes in cardiac repolarization after fingolimod initiation were mild and occurred at daytime. Ambiguously, QTcBaz demonstrated shortening, whereas QTcFri showed prolongation in cardiac repolarization after fingolimod initiation. The formula applied for QT-interval correction needs to be taken carefully into account as evaluating pharmacovigilance issues related to fingolimod.

Effect of clebopride, antidopaminergic gastrointestinal prokinetics, on cardiac repolarization.

PubMed

Kim, Ki-Suk; Shin, Won-Ho; Park, Sang-joon; Kim, Eun-Joo

2007-01-01

The inhibition of the potassium current I(Kr) and QT prolongation has been known to be associated with drug-induced torsades de pointes arrhythmias (TdP) and sudden cardiac death. In this study, the authors investigated the cardiac electrophysiological effects of clebopride, a class of antidopaminergic gastrointestinal prokinetic, that has been reported to prolong the QT interval by using the conventional microelectrode recording techniques in isolated rabbit Purkinje fiber and whole-cell patch clamp techniques in human ether-à-go-go-related gene (hERG)-stably transfected Chinese hamster ovarian (CHO) cells. Clebopride at 10 microM significantly decreased the Vmax of phase 0 depolarization (p < .05) and significantly prolonged the action potential duration at 90% repolarization (APD90) (p < .01), whereas the action potential duration at 50% repolarization (APD50) was not prolonged. For hERG potassium channel currents, the IC50 value was 0.62 +/- 0.30 microM. Clebopride was found to have no effect on sodium channel currents. When these results were compared with Cmax (1.02 nM) of clinical dosage (1 mg, [p.o.]), it can be suggested that clebopride is safe at the clinical dosage of 1 mg from the electrophysiological aspect. These findings indicate that clebopride, an antidopaminergic gastrointestinal prokinetic drug, may provide a sufficient "safety factor" in terms of the electrophysiological threshold concentration. But, in a supratherapeutic concentration that might possibly be encountered during overdose or impaired metabolism, clebopride may have torsadogenic potency.

Cardiac Repolarization Instability during Psychological Stress in Patients with Ventricular Arrhythmias

PubMed Central

Abisse, Saddam S.; Lampert, Rachel; Burg, Mattew; Soufer, Robert; Shusterman, Vladimir

2011-01-01

Introduction Changes in the autonomic nervous system activity (ANS) are a major trigger of life-threatening ventricular tachyarrhythmias (VTA). Mental arithmetic, a condition administered in a laboratory setting, can provide insight into the ANS effects on cardiac physiology. We examined the responses of cardiac repolarization to laboratory-induced psychological stressors in patients with implantable cardioverter defibrillators (ICDs) with the objective of identifying the indices that differentiate patients with and without subsequent VTA in follow-up. Methods Continuous ECG signals were recorded using 3 standard bipolar (Holter) leads in 56 patients (age: 63.6±11.9, female: 12%, LVEF: 32.3±11) with ICDs during mental arithmetic. The patients were separated into those with subsequent VTA during 3–4 years of follow-up (Group 1: N=9 pts) and those without VTA (Group 2: N=47 pts). Changes in repolarization (QT-interval, mean T-wave amplitude (Tamp), and T-wave area (Tarea) were analyzed during 5min of baseline, stress and recovery. The temporal instability of Tamp and Tarea was examined using the range (Δ) and variance (σ2) of beat-to-beat variations of the corresponding parameters. Results There were no significant differences in HR between the two groups at baseline (61 vs. 63 bpm, p=0.97), during stress (64 vs. 65 bpm, p=0.40), and recovery (62 vs. 61 bpm, p= 0.88). However, during mental stress and post-stress recovery ΔTamp was almost 2-fold greater in Group 1 compared with Group 2 (111 (57–203)) vs. 68 (44–94) μV p=0.04, respectively). Changes in QT-intervals were also greater in Group 1 compared with Group 2 (p=0.02). Conclusion Among patients with ICDs, changes of T-wave amplitude after psychological stress were greater in those with subsequent arrhythmic events. This might signal proarrhythmic repolarization response and help identify patients who would benefit the most from ICD implantation and proactive management. PMID:21920534

Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa.

PubMed

Padfield, Gareth J; Escudero, Carolina A; DeSouza, Astrid M; Steinberg, Christian; Gibbs, Karen; Puyat, Joseph H; Lam, Pei Yoong; Sanatani, Shubhayan; Sherwin, Elizabeth; Potts, James E; Sandor, George; Krahn, Andrew D

2016-02-09

Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; P<0.001) and lower peak heart rates (159±20 versus 184±9 beats/min; P<0.001). The mean QTc intervals were longer at peak exercise in patients (442±29 versus 422±19 ms; P<0.001). During submaximal exertion at comparable heart rates (114±6 versus 115±11 beats/min; P=0.54), the QTc interval had prolonged significantly more in patients than controls (37±28 versus 24±25 ms; P<0.016). The RR/QT slope, best described by a curvilinear relationship, was more gradual in patients than in controls (13.4; 95% confidence interval, 12.8-13.9 versus 15.8; 95% confidence interval, 15.3-16.4 ms QT change per 10% change in RR interval; P<0.001) and steepest in patients within the highest body mass index tertile versus the lowest (13.9; 95% confidence interval, 12.9-14.9 versus 12.3; 95% confidence interval, 11.3-13.3; P=0.026). Despite the absence of manifest QT prolongation, adolescent anorexic females have impaired repolarization reserve in comparison with healthy controls. Further study may identify impaired QT dynamics as a risk factor for arrhythmias in anorexia nervosa. © 2016 American Heart Association, Inc.

An Early Mathematical Patterning Assessment: identifying young Australian Indigenous children's patterning skills

NASA Astrophysics Data System (ADS)

Papic, Marina

2015-12-01

This paper presents an Early Mathematical Patterning Assessment (EMPA) tool that provides early childhood educators with a valuable opportunity to identify young children's mathematical thinking and patterning skills through a series of hands-on and drawing tasks. EMPA was administered through one-to-one assessment interviews to children aged 4 to 5 years in the year prior to formal school. Two hundred and seventeen assessments indicated that the young low socioeconomic and predominantly Australian Indigenous children in the study group had varied patterning and counting skills. Three percent of the study group was able to consistently copy and draw an ABABAB pattern made with coloured blocks. Fifty percent could count to six by ones and count out six items with 4 % of the total group able to identify six items presented in regular formations without counting. The integration of patterning into early mathematics learning is critical to the abstraction of mathematical ideas and relationships and to the development of mathematical reasoning in young children. By using the insights into the children's thinking that the EMPA tool provides, early childhood educators can better inform mathematics teaching and learning and so help close the persistent gap in numeracy between Indigenous and non-Indigenous children.

Protection against severe hypokalemia but impaired cardiac repolarization after intense rowing exercise in healthy humans receiving salbutamol.

PubMed

Atanasovska, Tania; Smith, Robert; Graff, Claus; Tran, Cao Thach; Melgaard, Jacob; Kanters, Jørgen K; Petersen, Aaron C; Tobin, Antony; Kjeldsen, Keld P; McKenna, Michael John

2018-05-10

Intense exercise induces pronounced hyperkalemia, followed by transient hypokalemia in recovery. We investigated whether the β 2 -agonist salbutamol attenuated the exercise-hyperkalemia, and exacerbated the post-exercise hypokalemia, and whether hypokalemia was associated with impaired cardiac repolarization (QT hysteresis). Eleven healthy adults participated in a randomized, counterbalanced, double-blind trial receiving either 1000 µg salbutamol (SAL) or placebo (PLAC) by inhalation. Arterial plasma potassium concentration ([K + ] a ) was measured at rest, during 3 min intense rowing exercise and 60 min recovery. QT hysteresis was calculated from ECG (n=8). [K + ] a increased above baseline during exercise (rest, 3.72{plus minus}0.7 vs end-exercise, 6.81{plus minus}1.4 mM, P<0.001, mean{plus minus}SD) and decreased rapidly during early recovery to below baseline; restoration was incomplete at 60 min post-exercise (P<0.05). [K + ] a was less during SAL than PLAC (4.39{plus minus}0.13 vs. 4.73{plus minus}0.19 mM, pooled across all times, P=0.001, treatment main effect). [K + ] a was lower after SAL than PLAC, from 2 min pre-exercise until 2.5 min during exercise, and at 50 and 60 min post-exercise (P<0.05). The post-exercise decline in [K + ] a was correlated with QT hysteresis (r=0.343, n=112, pooled data, P=0.001). Thus the decrease in [K + ] a from end-exercise by ~4 mM was associated with reduced QT hysteresis by ~75 ms. Whilst salbutamol lowered [K + ] a during exercise, no additive hypokalemic effects occurred in early recovery, suggesting there may be a protective mechanism against severe or prolonged hypokalemia after exercise when treated by salbutamol. This is important since post-exercise hypokalemia impaired cardiac repolarization, which could potentially trigger arrhythmias and sudden cardiac death in susceptible individuals with pre-existing hypokalemia and/or heart disease.

Characterization of ventricular depolarization and repolarization changes in a porcine model of myocardial infarction.

PubMed

Romero, Daniel; Ringborn, Michael; Demidova, Marina; Koul, Sasha; Laguna, Pablo; Platonov, Pyotr G; Pueyo, Esther

2012-12-01

In this study, several electrocardiogram (ECG)-derived indices corresponding to both ventricular depolarization and repolarization were evaluated during acute myocardial ischemia in an experimental model of myocardial infarction produced by 40 min coronary balloon inflation in 13 pigs. Significant changes were rapidly observed from minute 4 after the start of coronary occlusion, achieving their maximum values between 11 and 22 min for depolarization and between 9 and 12 min for repolarization indices, respectively. Subsequently, these maximum changes started to decrease during the latter part of the occlusion. Depolarization changes associated with the second half of the QRS complex showed a significant but inverse correlation with the myocardium at risk (MaR) estimated by scintigraphic images. The correlation between MaR and changes of the downward slope of the QRS complex, [Formula: see text], evaluated at the two more relevant peaks observed during the occlusion, was r = -0.75, p < 0.01 and r = -0.79, p < 0.01 for the positive and negative deflections observed in [Formula: see text], temporal evolution, respectively. Repolarization changes, analyzed by evaluation of ST segment elevation at the main observed positive peak, also showed negative, however non-significant correlation with MaR: r = -0.34, p = 0.28. Our results suggest that changes evaluated in the latter part of the depolarization, such as those described by [Formula: see text], which are influenced by R-wave amplitude, QRS width and ST level variations simultaneously, correlate better with the amount of ischemia than other indices evaluated in the earlier part of depolarization or during the ST segment.

Heart rate variability alters cardiac repolarization and electromechanical dynamics.

PubMed

Phadumdeo, Vrishti M; Weinberg, Seth H

2018-04-07

Heart rate continuously varies due to autonomic regulation, stochasticity in pacemaking, and circadian rhythm, collectively termed heart rate variability (HRV), during normal physiological conditions. Low HRV is clinically associated with an elevated risk of cardiac arrhythmias. Alternans, a beat-to-beat alternation in action potential duration (APD) and/or intracellular calcium (Ca) transient, is a well-known risk factor associated with cardiac arrhythmias that is typically studied under conditions of a constant pacing rate, i.e., the absence of HRV. In this study, we investigate the effects of HRV on the interplay between APD, Ca, and electromechanical properties, employing a nonlinear discrete-time map model that governs APD and intracellular Ca cycling with a stochastic pacing period. We find that HRV can decrease variation in APD and peak Ca at fast pacing rates for which alternans is present. Further, increased HRV typically disrupts the alternating pattern for both APD and peak Ca and weakens the correlation between APD and peak Ca, thus decoupling Ca-mediated instabilities from repolarization alternation. We find that the efficacy of these effects is regulated by the sarcoplasmic reticulum Ca uptake rate. Overall, these results demonstrate that HRV disrupts arrhythmogenic alternans and suggests that HRV may be a significant factor in preventing life-threatening arrhythmias. Copyright © 2018 Elsevier Ltd. All rights reserved.

Coronary Artery Disease Alters Ventricular Repolarization Dynamics in Type 2 Diabetes

NASA Technical Reports Server (NTRS)

Vrtovec, Bojan; Sinkovec, Matjaz; Starc, Vito; Radovancevic, Branislav; Schlegel, Todd T.

2005-01-01

Ventricular repolarization dynamics (VRD) is an important predictor of outcome in diabetes. We examined the potential impact of coronary artery disease (CAD) on VRD in type 2 diabetic patients. We recorded 5-min high-resolution resting electrocardiograms (ECG) in 38 diabetic patients undergoing elective coronary angiography, and in 38 age- and gender- matched apparently healthy subjects (Controls). Using leads I and II, time-domain indices of VRD were calculated. Coronary angiography was regarded as positive if a 350% stenosis was found. Angiography was positive in 21 diabetic patients (55%). Patients with CAD had a significantly higher degree of VRD than Controls (SDNN(QT): 15.81+/-7.22 ms vs. 8.94+/-6.04 ms; P <0.001, rMSSD(QT): 21.02k7.07 ms vs. 11.18k7.45 ms; P <0.001). VRD in diabetic patients with negative angiograms did not differ from VRD in Controls (SDNN(QT): 8.94+/-6.04 ms vs. 7.44+/-5.72 ms; P=0.67, rMSSD(QT): 11.18+/-7.45 ms vs. 10.22+/-5.35 ms; P=O. 82). CAD increases VRD in patients with type 2 diabetes. Therefore, changes in ventricular repolarization in diabetic patients may be due to silent CAD rather than to diabetes per se.

Changes in autonomic regulation and ventricular repolarization induced by subclinical hyperthyroidism.

PubMed

Galetta, F; Franzoni, F; Fallahi, P; Tocchini, L; Graci, F; Gaddeo, C; Rossi, M; Cini, G; Carpi, A; Santoro, G; Antonelli, A

2010-10-01

The aim of the present study was to evaluate the effect of subclinical hyperthyroidism (SHT) on cardiovascular autonomic function and ventricular repolarization. Thirty subjects (25 females; mean age 49.6 ± 9.8 years) with SHT, as judged by reduced TSH serum levels and normal free T4 and T3 serum levels, and 30 age and sex-matched control subjects underwent standard 12-lead ECG, and 24h ambulatory ECG monitoring. The dispersion of the QT interval, an index of inhomogeneity of repolarization, and the heart rate variability (HRV), a measure of cardiac autonomic modulation, were studied. Patients with SHT showed higher QT dispersion (p<0.001) and lower HRV measures (0.01>p<0.001) than controls. In SHT patients, QT dispersion was inversely related to HRV (r=-0.47, p<0.01). The results of the present study demonstrated that SHT is associated with a sympathovagal imbalance, characterized by increased sympathetic activity in the presence of diminished vagal tone, and with an increased inhomogeneity of ventricular recovery times. The assessment of HRV and QT dispersion in patients with SHT may represent a useful tool in monitoring the cardiovascular risk of this condition. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

Short-term action potential memory and electrical restitution: A cellular computational study on the stability of cardiac repolarization under dynamic pacing

PubMed Central

2018-01-01

Electrical restitution (ER) is a major determinant of repolarization stability and, under fast pacing rate, it reveals memory properties of the cardiac action potential (AP), whose dynamics have never been fully elucidated, nor their ionic mechanisms. Previous studies have looked at ER mainly in terms of changes in AP duration (APD) when the preceding diastolic interval (DI) changes and described dynamic conditions where this relationship shows hysteresis which, in turn, has been proposed as a marker of short-term AP memory and repolarization stability. By means of numerical simulations of a non-propagated human ventricular AP, we show here that measuring ER as APD versus the preceding cycle length (CL) provides additional information on repolarization dynamics which is not contained in the companion formulation. We focus particularly on fast pacing rate conditions with a beat-to-beat variable CL, where memory properties emerge from APD vs CL and not from APD vs DI and should thus be stored in APD and not in DI. We provide an ion-currents characterization of such conditions under periodic and random CL variability, and show that the memory stored in APD plays a stabilizing role on AP repolarization under pacing rate perturbations. The gating kinetics of L-type calcium current seems to be the main determinant of this safety mechanism. We also show that, at fast pacing rate and under otherwise identical pacing conditions, a periodically beat-to-beat changing CL is more effective than a random one in stabilizing repolarization. In summary, we propose a novel view of short-term AP memory, differentially stored between systole and diastole, which opens a number of methodological and theoretical implications for the understanding of arrhythmia development. PMID:29494628

Detection and evaluation of ventricular repolarization alternans: an approach to combined ECG, thoracic impedance, and beat-to-beat heart rate variability analysis.

PubMed

Kriščiukaitis, Algimantas; Šimoliūnienė, Renata; Macas, Andrius; Petrolis, Robertas; Drėgūnas, Kęstutis; Bakšytė, Giedrė; Pieteris, Linas; Bertašienė, Zita; Žaliūnas, Remigijus

2014-01-01

Beat-to-beat alteration in ventricles repolarization reflected by alternans of amplitude and/or shape of ECG S-T,T segment (TWA) is known as phenomena related with risk of severe arrhythmias leading to sudden cardiac death. Technical difficulties have caused limited its usage in clinical diagnostics. Possibilities to register and analyze multimodal signals reflecting heart activity inspired search for new technical solutions. First objective of this study was to test whether thoracic impedance signal and beat-to-beat heart rate reflect repolarization alternans detected as TWA. The second objective was revelation of multimodal signal features more comprehensively representing the phenomena and increasing its prognostic usefulness. ECG, and thoracic impedance signal recordings made during 24h follow-up of the patients hospitalized in acute phase of myocardial infarction were used for investigation. Signal morphology variations reflecting estimates were obtained by the principal component analysis-based method. Clinical outcomes of patients (survival and/or rehospitalization in 6 and 12 months) were compared to repolarization alternans and heart rate variability estimates. Repolarization alternans detected as TWA was also reflected in estimates of thoracic impedance signal shape and variation in beat-to-beat heart rate. All these parameters showed correlation with clinical outcomes of patients. The strongest significant correlation showed magnitude of alternans in estimates of thoracic impedance signal shape. The features of ECG, thoracic impedance signal and beat-to-beat variability of heart rate, give comprehensive estimates of repolarization alternans, which correlate, with clinical outcomes of the patients and we recommend using them to improve diagnostic reliability. Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

PubMed Central

Liu, Pin W.

2014-01-01

Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

New descriptors of homogeneity of the propagation of ventricular repolarization.

PubMed

Batchvarov, V; Dilaveris, P; Färbom, P; Ghuran, A; Acar, B; Hnatkova, K; Camm, A J; Malik, M

2000-11-01

Available descriptors of irregularities of ventricular repolarization are of limited clinical value. We studied the effect of autonomic variations on several new descriptors of the three-dimensional T loop. Twelve-lead digital ECGs were recorded continuously in 40 healthy subjects at baseline in the supine position, during postural changes (supine-->sitting-->standing-->supine-->standing), and during Valsalva maneuver performed three times in the supine and three times in the standing positions. A minimum dimensional space was constructed from the 12-lead ECG, using singular value decomposition, on the basis of median ECG beats constructed from 10-second consecutive ECG recordings. Temporal variations (TLA and PL, which measure the T loop area, and LD, the interlead relationship during repolarization) and wavefront direction descriptors (TCRT, the deviation between the QRS and T vectors) were calculated and expressed as normalized values. Values of TLA, PL, and TCRT were significantly lower in the sitting than in the supine position (-38,139 +/- 9099 vs 47,133 +/- 7511, -0.017 +/- 0.005 vs 0.033 +/- 0.005 and -0.032 +/- 0.019 vs 0.071 +/- 0.015, respectively, P < 0.001 for all) and decreased further in the standing position (-88,288 +/- 14,468, -0.067 +/- 0.013, -0.198 +/- 0.025, respectively, P < 0.001 for all). LD increased from supine to sitting (98.7 +/- 29.4 vs -87.5 +/- 15.2, P < 0.001) and increased further, though nonsignificantly in the standing position (118.3 +/- 35.2). TLA, PL, and TCRT decreased from baseline during Valsalva in the supine (-34,118 +/- 11,424 vs 62,234 +/- 12,215, -0.038 +/- 0.014 vs 0.065 +/- 0.010, -0.08 +/- 0.03 vs 0.10 +/- 0.02, respectively, P < 0.001 for all) and standing positions (-108,263 +/- 21,051 vs -68,909 +/- 10,271, -0.109 +/- 0.014 vs -0.048 +/- 0.009, -0.30 +/- 0.035 vs -015 +/- 0.016, respectively, P < 0.05 for all). LD was significantly increased by Valsalva in the supine position (13 +/- 46 vs -153 +/- 30, P < 0

Aging modulates dispersion of ventricular repolarization in the very old of the geriatric population.

PubMed

Huang, Jen-Hung; Lin, Ying-Qin; Pan, Nan-Hung; Chen, Yi-Jen

2010-11-01

Aging plays an essential role in cardiac pathophysiology. Knowledge on the ventricular repolarization in very old individuals is limited. An increase of QT dispersion is associated with higher cardiovascular mortality. The purpose of this study is to investigate whether aging changes the QT dispersion in the very old. Heart rate, P wave duration, PR interval, QRS axis, QRS duration, QT interval, and QTc interval were measured from 12-lead resting ECG. QT dispersion (46 ± 21, 47 ± 17, 69 ± 31 ms, p < 0.005) was significantly increased in the age group ≧85 years (n = 29, 89 ± 4 years) than in the age group 75-84 years (n = 33, 79 ± 3 years) and the age group 65-74 years (n = 32, 68 ± 3 years). Aging modulates dispersion of ventricular repolarization, which may contribute to the cardiac mortality in the very old Asian population.

Indexes of temporal myocardial repolarization dispersion and sudden cardiac death in heart failure: any difference?

PubMed

Piccirillo, Gianfranco; Rossi, Pietro; Mitra, Marilena; Quaglione, Raffaele; Dell'Armi, Annalaura; Di Barba, Daniele; Maisto, Damiana; Lizio, Andrea; Barillà, Francesco; Magrì, Damiano

2013-03-01

The QT variability index, calculated between Q- and the T-wave end (QTend VI), is an index of temporal myocardial repolarization lability associated with sudden cardiac death (SCD) in chronic heart failure (CHF). Little is known about temporal variability in the other two temporal myocardial repolarization descriptors obtained from Q-Tpeak and Tpeak -Tend intervals. We therefore investigated differences between these indexes in patients with CHF who died suddenly and in those who survived with a left ventricular ejection fraction (LVEF) ≤35% or >35%. We selected 127 ECG and systolic blood pressure (SPB) recordings from outpatients with CHF all of whom had been followed up for 30 months. We calculated RR and SPB variability by power spectral analysis and QTend VI, QTpeak VI, Tpeak Tend VI. We then subdivided data patients into three groups SCD, LVEF ≤ 35%, and LVEF > 35%. The LVEF was higher in the SCD than in the LVEF ≤ 35% group, whereas no difference was found between the SCD and LVEF > 35% groups. QTend VI, QTpeak VI, and Tpeak Tend VI were higher in the SCD and LVEF ≤ 35% groups than in the LVEF > 35% group. Multivariate analysis detected a negative relationship between all repolarization variability indexes, low frequency obtained from RR intervals and LVEF. Our data show that variability in the first (QTpeak VI) and second halves of the QT interval (Tpeak -Tend VI) significantly contributes to the QTend VI in patients with CHF. Further studies should investigate whether these indexes might help stratify the risk of SCD in patients with a moderately depressed LVEF. ©2012, Wiley Periodicals, Inc.

Intramural activation and repolarization sequences in canine ventricles. Experimental and simulation studies.

PubMed

Taccardi, Bruno; Punske, Bonnie B; Sachse, Frank; Tricoche, Xavier; Colli-Franzone, Piero; Pavarino, Luca F; Zabawa, Christine

2005-10-01

There are no published data showing the three-dimensional sequence of repolarization and the associated potential fields in the ventricles. Knowledge of the sequence of repolarization has medical relevance because high spatial dispersion of recovery times and action potential durations favors cardiac arrhythmias. In this study we describe measured and simulated 3-D excitation and recovery sequences and activation-recovery intervals (ARIs) (measured) or action potential durations (APDs) (simulated) in the ventricular walls. We recorded from 600 to 1400 unipolar electrograms from canine ventricular walls during atrial and ventricular pacing at 350-450 ms cycle length. Measured excitation and recovery times and ARIs were displayed as 2-D maps in transmural planes or 3-D maps in the volume explored, using specially developed software. Excitation and recovery sequences and APD distributions were also simulated in parallelepipedal slabs using anisotropic monodomain or bidomain models based on the Lou-Rudy version 1 model with homogeneous membrane properties. Simulations showed that in the presence of homogeneous membrane properties, the sequence of repolarization was similar but not identical to the excitation sequence. In a transmural plane perpendicular to epicardial fiber direction, both activation and recovery pathways starting from an epicardial pacing site returned toward the epicardium at a few cm distance from the pacing site. However, APDs were not constant, but had a dispersion of approximately 14 ms in the simulated domain. The maximum APD value was near the pacing site and two minima appeared along a line perpendicular to fiber directions, passing through the pacing site. Electrical measurements in dog ventricles showed that, for short cycle lengths, both excitation and recovery pathways, starting from an epicardial pacing site, returned toward the epicardium. For slower pacing rates, pathways of recovery departed from the pathway of excitation. Highest ARI

Acute effects of Red Bull energy drink on ventricular repolarization in healthy young volunteers: a prospective study

PubMed Central

Elitok, Ali; Öz, Fahrettin; Panc, Cafer; Sarıkaya, Remzi; Sezikli, Selim; Pala, Yasin; Bugan, Övgü Sinem; Ateş, Müge; Parıldar, Hilal; Ayaz, Mustafa Buğra; Atıcı, Adem; Oflaz, Hüseyin

2016-01-01

Objective: Energy drinks (EDs) are widely consumed products of the beverage industry and are often chosen by teenagers and young adults. Several adverse cardiovascular events and malignant cardiac arrhythmias following consumption of EDs have been reported in the literature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the dispersion of repolarization and that an increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. This study investigated the acute effects of Red Bull ED on ventricular repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. Methods: A prospective, open-label study design was used. After an 8-h fast, 50 young, healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc ratio, and several other electrocardiographic parameters were measured at baseline and 2 h after ingestion of Red Bull ED. Results: No significant changes in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED consumption. Red Bull ED consumption led to increases in both systolic and diastolic blood pressures, which were associated with an increased heart rate. Conclusion: Although ingestion of Red Bull ED increases the heart rate and diastolic and systolic blood pressures, it does not cause alterations in ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio. PMID:25868042

Acute effects of Red Bull energy drink on ventricular repolarization in healthy young volunteers: a prospective study.

PubMed

Elitok, Ali; Öz, Fahrettin; Panc, Cafer; Sarıkaya, Remzi; Sezikli, Selim; Pala, Yasin; Bugan, Övgü Sinem; Ateş, Müge; Parıldar, Hilal; Ayaz, Mustafa Buğra; Atıcı, Adem; Oflaz, Hüseyin

2015-11-01

Energy drinks (EDs) are widely consumed products of the beverage industry and are often chosen by teenagers and young adults. Several adverse cardiovascular events and malignant cardiac arrhythmias following consumption of EDs have been reported in the literature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the dispersion of repolarization and that an increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. This study investigated the acute effects of Red Bull ED on ventricular repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. A prospective, open-label study design was used. After an 8-h fast, 50 young, healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc ratio, and several other electrocardiographic parameters were measured at baseline and 2 h after ingestion of Red Bull ED. No significant changes in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED consumption. Red Bull ED consumption led to increases in both systolic and diastolic blood pressures, which were associated with an increased heart rate. Although ingestion of Red Bull ED increases the heart rate and diastolic and systolic blood pressures, it does not cause alterations in ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio.

Heterogeneity of ventricular repolarization in newborns with intrauterine growth restriction.

PubMed

Fouzas, Sotirios; Karatza, Ageliki A; Davlouros, Periklis A; Chrysis, Dionisios; Alexopoulos, Dimitrios; Mantagos, Stefanos; Dimitriou, Gabriel

2014-12-01

Intrauterine growth restriction (IUGR) is associated with structural and functional cardiac alterations but the electrophysiological consequences of these disturbances remain unknown. To explore the distribution of ventricular repolarization and its relation to myocardial mechanics in newborns with IUGR. STUDY DESIGN, SUBJECTS AND OUTCOME MEASUREMENTS: Conventional and tissue Doppler echocardiographic data, and electrocardiographic parameters used to describe the distribution of ventricular repolarization (dispersion of QT [QTd] and JT [JTd]), were obtained on the second (D2) and fifth (D5) postnatal day and compared between 25 IUGR newborns and 25 matched-for-gestational age controls. IUGR was associated with relative interventricular septum hypertrophy, increased left ventricular (LV) E/E' ratio and higher LV myocardial performance index (MPI). On both study days, the IUGR infants presented higher QTd and JTd compared to controls (QTd-D2: 66±20 ms vs. 36±12 ms, P<0.001; JTd-D2: 54±13 ms vs. 34±9 ms, P<0.001; QTd-D5: 61±14 ms vs. 27±12 ms, P<0.001; JTd-D5: 54±13 ms vs. 27±9 ms, P<0.001). The association between QTd and LV E/E' (D2: regression coefficient beta 0.747, R(2) 0.585; D5: beta 0.843, R(2) 0.646) and QTd and MPI (D2: beta 0.680, R(2) 0.576; D5: beta 0.698, R(2) 0.650) was also significant (P<0.001 for all analyses). Our findings suggest that IUGR is associated with electrophysiological remodeling of the neonatal heart, a process which is closely related to the underlying alterations in ventricular mechanics and might predispose to adverse electrophysiological events. Copyright © 2014 Elsevier Ltd. All rights reserved.

A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node--ablated, His bundle-paced dog.

PubMed

Nolan, Emily R; Feng, Meihua Rose; Koup, Jeffrey R; Liu, Jing; Turluck, Daniel; Zhang, Yiqun; Paulissen, Jerome B; Olivier, N Bari; Miller, Teresa; Bailie, Marc B

2006-01-01

Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation was generated from these data. Three male beagle dogs underwent radiofrequency AV nodal ablation, and placement of a His bundle-pacing lead and programmable pacemaker under anesthesia. Each dog was restrained in a sling for a series of increasing dose infusions of each drug while maintained at a constant heart rate of 80 beats/min. RT interval, a surrogate for QT interval in His bundle-paced dogs, was recorded throughout the experiment. E-4031 induced a statistically significant RT prolongation at the highest three doses. Cisapride resulted in a dose-dependent increase in RT interval, which was statistically significant at the two highest doses. Terfenadine induced a dose-dependent RT interval prolongation with a statistically significant change occurring only at the highest dose. The relationship between drug concentration and RT interval change was described by a sigmoid E(max) model with an effect site. Maximum RT change (E(max)), free drug concentration at half of the maximum effect (EC(50)), and free drug concentration associated with a 10 ms RT prolongation (EC(10 ms)) were estimated. A linear correlation between EC(10 ms) and HERG IC(50) values was identified. The conscious dog with His bundle-pacing detects delayed cardiac repolarization related to I(Kr) inhibition, and detects repolarization change induced by drugs with activity at multiple ion channels. A clinically relevant sensitivity and a linear correlation with in vitro HERG data make the conscious His bundle-paced dog a valuable tool for detecting repolarization effect of new chemical entities.

Underwater refraction-polarization patterns of skylight perceived by aquatic animals through Snell's window of the flat water surface.

PubMed

Horváth, G; Varjú, D

1995-06-01

The grass shrimp (Palaemonetes vulgaris) orients itself by means of the polarization pattern of the sky visible through Snell's window of the water surface. The celestial polarization pattern viewed from water is distorted and modified because of refraction and repolarization of skylight at the air-water interface. This work provides a quantitative account of the repolarization of skylight transmitted through a flat water surface. The degree and direction of linear polarization, the transmissivity and the shape of the refraction-polarization oval are calculated at the air-water interface as functions of the polarization characteristics and the incident angle of partially linearly polarized incoming light. Two-dimensional patterns of linear polarization ellipses and of the degree and direction of polarization of skylight are presented for different zenith distances of the sun. The corresponding underwater refraction-polarization patterns are computed. Transmissivity patterns of a flat water surface are calculated for unpolarized light of an overcast sky and for partially polarized light of clear skies as a function of the zenith distance of the sun. The role of these refraction-polarization patterns in orientation and polarization vision of the grass shrimp (P. vulgaris) and rainbow trout (Oncorhyncus mykiss) is reviewed. The effects of cloud cover, surface waves and water turbidity on the refraction-polarization patterns are briefly discussed.

Hysteresis effect implicates calcium cycling as a mechanism of repolarization alternans.

PubMed

Walker, Mariah L; Wan, Xiaoping; Kirsch, Glenn E; Rosenbaum, David S

2003-11-25

T-wave alternans is due to alternation of membrane repolarization at the cellular level and is a risk factor for sudden cardiac death. Recently, a hysteresis effect has been reported in patients whereby T-wave alternans, once induced by rapid heart rate, persists even when heart rate is subsequently slowed. We hypothesized that alternans hysteresis is an intrinsic property of cardiac myocytes, directly related to an underlying mechanism for repolarization alternans that involves intracellular calcium cycling. Stepwise pacing was used to induce alternans in Langendorff-perfused guinea pig hearts from which optical action potentials were recorded simultaneously at 256 ventricular sites with voltage-sensitive dyes and in whole-cell patch-clamped cardiac myocytes treated with or without BAPTA-AM (1,2-bis[2-aminophenoxy]ethane-N,N,N',N'-tetraacetic acid tetrakis [acetoxymethyl ester]). Alternans hysteresis was observed in every isolated heart: threshold heart rate for alternans was 280+/-12 bpm, but during subsequent deceleration of pacing, alternans persisted to significantly slower heart rates (238+/-5 bpm, P<0.05). Optical mapping showed that this effect also applied to the threshold for spatially discordant alternans (313+/-2.2 bpm during acceleration versus 250+/-6.6 bpm during deceleration, P<0.05). Alternans hysteresis was also observed in isolated cardiac myocytes. Moreover, calcium chelation by BAPTA-AM raised the threshold for alternans and inhibited hysteresis in a dose-dependent manner with no effect on baseline action potential duration. Alternans hysteresis is an intrinsic property of cardiac myocytes that can lead to persistence of arrhythmogenic discordant alternans even after heart rate is slowed. These results also support an important underlying role of calcium cycling in the mechanism of alternans.

Assessment of cardiac autonomic regulation and ventricular repolarization after off-pump coronary artery bypass grafting.

PubMed

Kalisnik, Jurij M; Avbelj, Viktor; Trobec, Roman; Ivaskovic, Daroslav; Vidmar, Gaj; Troise, Giovanni; Gersak, Borut

2006-01-01

Altered autonomic regulation precipitates cardiac arrhythmias and increases the risk of sudden cardiac death. This risk is further increased by changes in ventricular repolarization. Autonomic regulation is deranged in patients after myocardial on-pump revascularization. We aimed to clarify how off-pump coronary artery bypass grafting (CABG) affects postoperative cardiac autonomic regulation and ventricular repolarization within 4 weeks after CABG. Forty-two patients (mean age, 61.9 +/- 9.3 years; mean EURO score 2.6 +/- 1.9) were electively admitted for off-pump CABG. The electrocardiographic and respiratory waveform recordings were performed in the afternoon in the supine position for 10 minutes. Autonomic modulation was assessed using heart rate variability analysis. Power spectra were computed from 5-minute stable RR intervals using Fourier Transform analysis. Total power of spectra was defined in the range of 0.01 to 0.40 Hz, high-frequency power within 0.15 to 0.40 Hz, and low-frequency power within 0.04 to 0.15 Hz. Normalized power was defined as a ratio of power in each band/total power. The high- and low-frequency power as well as their normalized values indicated cardiac vagal and sympathetic modulation, respectively. Ventricular repolarization was assessed using QT interval, QT interval variability, and QT-RR interdependence analysis. QT intervals were determined from the beginning of the 5-minute segments. QT interval variability was evaluated by a T-wave template-matching algorithm. Pearson correlation between length of RR and QT interval was applied to study QT-RR characteristics. The results were tested for significance using the Fisher exact test, nonpaired t test, and analysis of variance; a P <.05 was considered significant. The frequency of arrhythmic events and heart rate increased from the fourth to the seventh postoperative day and returned to preoperative levels 4 weeks after CABG. Heart rate variability measures indicating autonomic

Can non‐clinical repolarization assays predict the results of clinical thorough QT studies? Results from a research consortium

PubMed Central

Park, Eunjung; Gintant, Gary A; Bi, Daoqin; Kozeli, Devi; Pettit, Syril D; Skinner, Matthew; Willard, James; Wisialowski, Todd; Koerner, John; Valentin, Jean‐Pierre

2018-01-01

Background and Purpose Translation of non‐clinical markers of delayed ventricular repolarization to clinical prolongation of the QT interval corrected for heart rate (QTc) (a biomarker for torsades de pointes proarrhythmia) remains an issue in drug discovery and regulatory evaluations. We retrospectively analysed 150 drug applications in a US Food and Drug Administration database to determine the utility of established non‐clinical in vitro IKr current human ether‐à‐go‐go‐related gene (hERG), action potential duration (APD) and in vivo (QTc) repolarization assays to detect and predict clinical QTc prolongation. Experimental Approach The predictive performance of three non‐clinical assays was compared with clinical thorough QT study outcomes based on free clinical plasma drug concentrations using sensitivity and specificity, receiver operating characteristic (ROC) curves, positive (PPVs) and negative predictive values (NPVs) and likelihood ratios (LRs). Key Results Non‐clinical assays demonstrated robust specificity (high true negative rate) but poor sensitivity (low true positive rate) for clinical QTc prolongation at low‐intermediate (1×–30×) clinical exposure multiples. The QTc assay provided the most robust PPVs and NPVs (ability to predict clinical QTc prolongation). ROC curves (overall test accuracy) and LRs (ability to influence post‐test probabilities) demonstrated overall marginal performance for hERG and QTc assays (best at 30× exposures), while the APD assay demonstrated minimal value. Conclusions and Implications The predictive value of hERG, APD and QTc assays varies, with drug concentrations strongly affecting translational performance. While useful in guiding preclinical candidates without clinical QT prolongation, hERG and QTc repolarization assays provide greater value compared with the APD assay. PMID:29181850

Syllabic Patterns in the Early Vocalizations of Quichua Children

ERIC Educational Resources Information Center

Gildersleeve-Neumann, Christina E.; Davis, Barbara L.; Macneilage, Peter F.

2013-01-01

To understand the interactions between production patterns common to children regardless of language environment and the early appearance of production effects based on perceptual learning from the ambient language requires the study of languages with diverse phonological properties. Few studies have evaluated early phonological acquisition…

The Role of Spatial Dispersion of Repolarization in Inherited and Acquired Sudden Cardiac Death Syndromes

PubMed Central

Antzelevitch, Charles

2007-01-01

This review examines the role of spatial electrical heterogeneity within ventricular myocardium on the function of the heart in health and disease. The cellular basis for transmural dispersion of repolarization (TDR) is reviewed and the hypothesis that amplification of spatial dispersion of repolarization underlies the development of life-threatening ventricular arrhythmias associated with inherited ion channelopathies is evaluated. The role of TDR in the long QT, short QT and Brugada syndromes as well as catecholaminergic polymorphic ventricular tachycardia (CPVT) are critically examined. In the long QT Syndrome, amplification of TDR is often secondary to preferential prolongation of the action potential duration (APD) of M cells, whereas in the Brugada Syndrome, it is thought to be due to selective abbreviation of the APD of right ventricular (RV) epicardium. Preferential abbreviation of APD of either endocardium or epicardium appears to be responsible for amplification of TDR in the short QT syndrome. In catecholaminergic polymorphic VT, reversal of the direction of activation of the ventricular wall is responsible for the increase in TDR. In conclusion, the long QT, short QT, Brugada and catecholaminergic polymorphic VT syndromes are pathologies with very different phenotypes and etiologies, but which share a common final pathway in causing sudden cardiac death. PMID:17586620

Acquisition of English word stress patterns in early and late bilinguals

NASA Astrophysics Data System (ADS)

Guion, Susan G.

2004-05-01

Given early acquisition of prosodic knowledge as demonstrated by infants' sensitivity to native language accentual patterns, the question of whether learners can acquire new prosodic patterns across the life span arises. Acquisition of English stress by early and late Spanish-English and Korean-English bilinguals was investigated. In a production task, two-syllable nonwords were produced in noun and verb sentence frames. In a perception task, preference for first or last syllable stress on the nonwords was indicated. Also, real words that were phonologically similar to the nonwords were collected. Logistic regression analyses and ANOVAs were conducted to determine the effect of three factors (syllable structure, lexical class, and stress patterns of phonologically similar words) on the production and perception responses. In all three groups, stress patterns of phonologically similar real words predicted stress on nonwords. For the two other factors, early bilinguals patterned similarly to the native-English participants. Late Spanish-English bilinguals demonstrated less learning of stress patterns based on syllabic structure, and late Korean-English bilinguals demonstrated less learning of stress patterns based on lexical class than native-English speakers. Thus, compared to native speakers, late bilinguals' ability to abstract stress patterns is reduced and affected by the first language. [Work supported by NIH.

Early sound patterns in the speech of two Brazilian Portuguese speakers.

PubMed

Teixeira, Elizabeth Reis; Davis, Barbara L

2002-06-01

Sound patterns in the speech of two Brazilian-Portuguese speaking children are compared with early production patterns in English-learning children as well as English and Brazilian-Portuguese (BP) characteristics. The relationship between production system effects and ambient language influences in the acquisition of early sound patterns is of primary interest, as English and BP are characterized by differing phonological systems. Results emphasize the primacy of production system effects in early acquisition, although even the earliest word forms show evidence of perceptual effects from the ambient language in both BP children. Use of labials and coronals and low and midfront vowels in simple syllable shapes is consistent with acquisition data for this period across languages. However, potential ambient language influences include higher frequencies of dorsals, use of multisyllabic words, and different phone types in syllable-offset position. These results suggest that to fully understand early acquisition of sound systems one must account for both production system effects and perceptual effects from the ambient language.

Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction.

PubMed

Cho, Jae Hyung; Zhang, Rui; Kilfoil, Peter J; Gallet, Romain; de Couto, Geoffrey; Bresee, Catherine; Goldhaber, Joshua I; Marbán, Eduardo; Cingolani, Eugenio

2017-11-21

Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression. After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats ( P <0.001 versus controls). The arrhythmogenicity index was increased ( P <0.001) and the corrected QT interval on ECG was prolonged ( P <0.001) in HFpEF rats. Optical mapping of HFpEF hearts demonstrated prolonged action potentials ( P <0.05) and multiple reentry circuits during induced VA. Single-cell recordings of cardiomyocytes isolated from HFpEF rats confirmed a delay of repolarization ( P =0.001) and revealed downregulation of transient outward potassium current ( I to ; P <0.05). The rapid components of the delayed rectifier potassium current ( I Kr ) and the inward rectifier potassium current ( I K1 ) were also downregulated ( P <0.05), but the current densities were much lower than for I to . In accordance with the reduction of I to , both Kcnd3 transcript and Kv4.3 protein levels

Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

NASA Astrophysics Data System (ADS)

Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

2016-06-01

Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

Organ involvement in Argentinian systemic sclerosis patients with "late" pattern as compared to patients with "early/active" pattern by nailfold capillaroscopy.

PubMed

Marino Claverie, Lucila; Knobel, Elizabeth; Takashima, Lorena; Techera, Lorena; Oliver, Marina; Gonzalez, Paula; Romanini, Félix E; Fonseca, María L; Mamani, Marta N

2013-06-01

Changes in nailfold capillaroscopy in systemic sclerosis patients could be related to the disease severity. The aim of this study was to investigate whether patients with "late" scleroderma (SD) pattern have more organ involvement than patients with "early/active" SD pattern. Forty-six Argentinian patients (44 women and 2 men), with a diagnosis of systemic sclerosis, were distributed in two groups based on the presence of late and early/active patterns. Organ involvement was assessed as follows: pulmonary function by chest radiography, high-resolution chest tomography (HRCT), lung volume tests, and diffusing capacity for carbon monoxide (DLCO); esophageal involvement by manometry; and pulmonary arterial hypertension (PAH) by Doppler echocardiography and six-minute walk test. Honeycombing of the lungs evaluated by HRCT was more frequently present in patients with late pattern compared with early/active patients (p = 0.01). We also found statistically significant differences in lung volume tests (p = 0.03) and DLCO (p = 0.02) between the two SD pattern groups. Esophageal manometry showed a significantly higher frequency of motility disorders in the group with late pattern (p = 0.0024). In this study, patients with late pattern had higher frequency of pulmonary and esophageal involvement compared with patients with early/active pattern.

Targeting RAW 264.7 macrophages (M1 type) with Withaferin-A decorated mannosylated liposomes induces repolarization via downregulation of NF-κB and controlled elevation of STAT-3.

PubMed

Neog, Manoj Kumar; Sultana, Farhath; Rasool, Mahaboobkhan

2018-05-25

In the present study, we intend to gain an insight into the mechanism of Withaferin-A (WA), a steroidal lactone with reference to repolarization of RAW 264.7 macrophages (M1 to M2 type). We found that successful internalization of WA via mannosylated liposomal delivery system (ML-WA) reduced the RAW 264.7 macrophage (M1) mediated pro-inflammatory cytokines (IL-1β, IL-6, IL-23, and TNF-α) through the attenuation of transcription factor NF-κB-p65 expression. Whereas, ML-WA treatment induced a controlled upregulation of p-STAT3, and ablated the key oxidative stress markers (NO, iNOS, and ROS) in M1 → M2 RAW 264.7 macrophage repolarization, which suggested the recalibration of M1 macrophage metabolic function. Further, the elevated expression of M2 macrophage associated CD163 over the M1 macrophage related CD86 concluded that ML-WA induces an anti-inflammatory response by repolarizing the M1 → M2 RAW 264.7 macrophage. Copyright © 2018 Elsevier B.V. All rights reserved.

E2F4 is required for early eye patterning.

PubMed

Ruzhynsky, Vladimir A; Furimsky, Marosh; Park, David S; Wallace, Valerie A; Slack, Ruth S

2009-01-01

Increasingly, studies reveal novel functions for cell cycle proteins during development. Here, we investigated the role of E2F4 in eye development. E2F4-deficient mouse embryos exhibit severe early eye patterning defects, which are evident from embryonic day 11.5 and characterized by aberrant shape of the optic cup, coloboma as well as abnormal eye pigmentation. Loss of E2F4 is associated with proximal-distal patterning defects in the optic vesicle. These defects are characterized by the expansion of optic stalk marker gene expression to the optic cup and reduced expression of ventral optic cup markers. These defects are associated with a split of Shh expression domain at the ventral midline of the forebrain and expansion of the Shh activity into the ventral optic cup. Despite these patterning defects, early neuronal differentiation and Shh expression in the retina are not affected by E2F4 deletion. Overall, the results of our studies show a novel role of E2F4 in the early eye development. 2009 S. Karger AG, Basel.

Influence of aging and chronic heart failure on temporal dispersion of myocardial repolarization.

PubMed

Piccirillo, Gianfranco; Moscucci, Federica; Pascucci, Matteo; Pappadà, Maria Antonella; D'Alessandro, Gaetana; Rossi, Pietro; Quaglione, Raffaele; Di Barba, Daniele; Barillà, Francesco; Magrì, Damiano

2013-01-01

QT and T(peak)-T(end) (Te) intervals are associated with sudden cardiac death in patients with chronic heart failure (CHF). We studied age-dependent influence on short-term temporal dispersion of these two variables in patients with postischemic CHF. We grouped 75 CHF and 53 healthy control subjects into three age subsets: ≤ 50 years, >50 years and ≤ 65 years, and >65 years. We then calculated the following indices: QT and Te variability index (QTVI and TeVI), the ratio between the short-term variability (STV) of QT or Te, and the STV of resting rate (RR) (QT/RR STV and Te/RR STV). In all different age subgroups, patients with CHF showed a higher level of QTVI than age-matched control subjects (≤ 50 years: P < 0.0001; >50 years and ≤ 65 years: P < 0.05; >65 years: P < 0.05). Patients with CHF < 50 years old also had all repolarization variability indices higher than normal age-matched controls (TeVI, P < 0.05; QT/RR STV, P < 0.05; Te/RR STV, P < 0.05), whereas we did not find any difference between the two older classes of subjects. Both QTVI (r²: 0.178, P < 0.05) and TeVI (r²: 0.433, P < 0.001) were positively related to age in normal subjects, even if the first correlation was weaker than the second one. Our data showed that QTVI could be used in all ages to evaluate repolarization temporal liability, whereas the other indices are deeply influenced by age. Probably, the age-dependent increase in QTVI was more influenced by a reduction of RR variability reported in older normal subjects.

Rhinovirus Delays Cell Repolarization in a Model of Injured/Regenerating Human Airway Epithelium

PubMed Central

Faris, Andrea N.; Ganesan, Shyamala; Chattoraj, Asamanja; Chattoraj, Sangbrita S.; Comstock, Adam T.; Unger, Benjamin L.; Hershenson, Marc B.

2016-01-01

Rhinovirus (RV), which causes exacerbation in patients with chronic airway diseases, readily infects injured airway epithelium and has been reported to delay wound closure. In this study, we examined the effects of RV on cell repolarization and differentiation in a model of injured/regenerating airway epithelium (polarized, undifferentiated cells). RV causes only a transient barrier disruption in a model of normal (mucociliary-differentiated) airway epithelium. However, in the injury/regeneration model, RV prolongs barrier dysfunction and alters the differentiation of cells. The prolonged barrier dysfunction caused by RV was not a result of excessive cell death but was instead associated with epithelial-to-mesenchymal transition (EMT)-like features, such as reduced expression of the apicolateral junction and polarity complex proteins, E-cadherin, occludin, ZO-1, claudins 1 and 4, and Crumbs3 and increased expression of vimentin, a mesenchymal cell marker. The expression of Snail, a transcriptional repressor of tight and adherence junctions, was also up-regulated in RV-infected injured/regenerating airway epithelium, and inhibition of Snail reversed RV-induced EMT-like features. In addition, compared with sham-infected cells, the RV-infected injured/regenerating airway epithelium showed more goblet cells and fewer ciliated cells. Inhibition of epithelial growth factor receptor promoted repolarization of cells by inhibiting Snail and enhancing expression of E-cadherin, occludin, and Crumbs3 proteins, reduced the number of goblet cells, and increased the number of ciliated cells. Together, these results suggest that RV not only disrupts barrier function, but also interferes with normal renewal of injured/regenerating airway epithelium by inducing EMT-like features and subsequent goblet cell hyperplasia. PMID:27119973

Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.

PubMed

Langenickel, Thomas H; Jordaan, Pierre; Petruck, Jesika; Kode, Kiran; Pal, Parasar; Vaidya, Soniya; Chandra, Priya; Rajman, Iris

2016-08-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization. This randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control. The primary assessment was mean baseline- and placebo-corrected QTcF (∆∆QTcF; Fridericia correction). Additional assessments included the ∆∆QTcB (Bazett's correction), PR interval, QRS duration, heart rate (HR), LCZ696 pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and safety. Of the 84 subjects enrolled, 81 completed the study. The maximum upper bound of the two-sided 90 % confidence interval for ∆∆QTcF for LCZ696 400 mg and 1200 mg were <10 ms, and assay sensitivity was confirmed with moxifloxacin. No relevant treatment-emergent changes were observed in any of the ECG-derived parameters with LCZ696 or placebo, and the incidence of adverse events was comparable among the treatment groups. Single therapeutic and supratherapeutic doses of LCZ696 did not affect cardiac repolarization as defined by the E14 ICH guidelines.

The prevalence, distribution, and clinical outcomes of electrocardiographic repolarization patterns in male athletes of African/Afro-Caribbean origin.

PubMed

Papadakis, Michael; Carre, Francois; Kervio, Gaelle; Rawlins, John; Panoulas, Vasileios F; Chandra, Navin; Basavarajaiah, Sandeep; Carby, Lorna; Fonseca, Tiago; Sharma, Sanjay

2011-09-01

Athletic training in male black athletes (BAs) is associated with marked ECG repolarization changes that overlap with hypertrophic cardiomyopathy (HCM). Differentiating between the two entities is prudent since BAs exhibit a higher prevalence of exercise-related sudden death from HCM compared with white athletes (WAs). Between 1996 and 2010, 904 BAs underwent serial cardiac evaluations including ECG and echocardiography. Athletes exhibiting T-wave inversions were investigated further for HCM. Results were compared with 1819 WAs, 119 black controls (BCs), and 52 black HCM patients. Athletes were followed up for 69.7 ± 29.6 months. T-wave inversions were present in 82.7% HCM patients, 22.8% BAs, 10.1% BCs, and 3.7% WAs. In athletes, the major determinant of T-wave inversions was black ethnicity. T-wave inversions in BAs (12.7%) were predominantly confined to contiguous anterior leads (V1-V4). Only 4.1% of BAs exhibited T-wave inversions in the lateral leads. In contrast, both BCs and HCM patients exhibited lower prevalence of T-wave inversions in leads V1-V4 (4.2 and 3.8%, respectively) with most T-wave inversions in HCM patients (76.9%) involving the lateral leads. During follow-up one BA survived cardiac arrest and two athletes (one BA, one WA) were diagnosed with HCM. All three exhibited T-wave inversions in the lateral leads. T-wave inversions in leads V1-V4 appear to represent an ethnic variant of 'athlete's heart'. Conversely, T-wave inversions in the lateral leads may represent the initial expression of underlying cardiomyopathy and merit further evaluation and regular surveillance.

Electrocardiographic features of sudden unexpected death in epilepsy.

PubMed

Chyou, Janice Y; Friedman, Daniel; Cerrone, Marina; Slater, William; Guo, Yu; Taupin, Daniel; O'Rourke, Sean; Priori, Silvia G; Devinsky, Orrin

2016-07-01

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related mortality. We hypothesized that electrocardiography (ECG) features may distinguish SUDEP cases from living subjects with epilepsy. Using a matched case-control design, we compared ECG studies of 12 consecutive cases of SUDEP over 10 years and 22 epilepsy controls matched for age, sex, epilepsy type (focal, generalized, or unknown/mixed type), concomitant antiepileptic, and psychotropic drug classes. Conduction intervals and prevalence of abnormal ventricular conduction diagnosis (QRS ≥110 msec), abnormal ventricular conduction pattern (QRS <110 msec, morphology of incomplete right or left bundle branch block or intraventricular conduction delay), early repolarization, and features of inherited cardiac channelopathies were assessed. Abnormal ventricular conduction diagnosis and pattern distinguished SUDEP cases from matched controls. Abnormal ventricular conduction diagnosis was present in two cases and no controls. Abnormal ventricular conduction pattern was more common in cases than controls (58% vs. 18%, p = 0.04). Early repolarization was similarly prevalent in cases and controls, but the overall prevalence exceeded that of published community-based cohorts. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Efficacy and safety of dextrose-insulin in unmasking non-diagnostic Brugada ECG patterns.

PubMed

Velázquez-Rodríguez, Enrique; Rodríguez-Piña, Horacio; Pacheco-Bouthillier, Alex; Jiménez-Cruz, Marcelo Paz

Typical diagnostic, coved-type 1, Brugada ECG patterns fluctuate spontaneously over time with a high proportion of non-diagnostic ECG patterns. Insulin modulates ion transport mechanisms and causes hyperpolarization of the resting potential. We report our experience with unmasking J-ST changes in response to a dextrose-insulin test. Nine patients, mean age 40.5±19.4years (range: 15-65years), presented initially with a non-diagnostic ECG pattern, which was suggestive of Brugada syndrome (group I). They were compared with 10 patients with normal ECG patterns (group II). Participants received an infusion of 50g of 50% dextrose, followed by 10IU of intravenous regular insulin. Positive changes were defined by conversion to a diagnostic ECG pattern. The dextrose-insulin test was positive in six of seven (85.7%) patients (kappa 0.79, p=0.02) that was confirmed with a pharmacologic test (kappa 1, p=0.003). One had an inconclusive test, and two with a negative test had an early repolarization ECG pattern. All subjects in group II had a negative test (p<0.01). The maximum changes of the J-ST segment were observed 41.3±31.4minutes (range 3-90minutes) after dextrose-insulin infusion. One patient had monomorphic ventricular bigeminy without spontaneous or induced ventricular fibrillation. Changes in J-ST segment in the Brugada syndrome are influenced by glucose-insulin, and this report reproduces and supports the efficacy and safety of this metabolic test in the differential diagnosis of patients with non-diagnostic ECG patterns. Copyright © 2016 Elsevier Inc. All rights reserved.

Ventricular stimulus site influences dynamic dispersion of repolarization in the intact human heart

PubMed Central

Orini, Michele; Simon, Ron B.; Providência, Rui; Khan, Fakhar Z.; Segal, Oliver R.; Babu, Girish G.; Bradley, Richard; Rowland, Edward; Ahsan, Syed; Chow, Anthony W.; Lowe, Martin D.; Taggart, Peter

2016-01-01

The spatial variation in restitution properties in relation to varying stimulus site is poorly defined. This study aimed to investigate the effect of varying stimulus site on apicobasal and transmural activation time (AT), action potential duration (APD) and repolarization time (RT) during restitution studies in the intact human heart. Ten patients with structurally normal hearts, undergoing clinical electrophysiology studies, were enrolled. Decapolar catheters were placed apex to base in the endocardial right ventricle (RVendo) and left ventricle (LVendo), and an LV branch of the coronary sinus (LVepi) for transmural recording. S1–S2 restitution protocols were performed pacing RVendo apex, LVendo base, and LVepi base. Overall, 725 restitution curves were analyzed, 74% of slopes had a maximum slope of activation recovery interval (ARI) restitution (Smax) > 1 (P < 0.001); mean Smax = 1.76. APD was shorter in the LVepi compared with LVendo, regardless of pacing site (30-ms difference during RVendo pacing, 25-ms during LVendo, and 48-ms during LVepi; 50th quantile, P < 0.01). Basal LVepi pacing resulted in a significant transmural gradient of RT (77 ms, 50th quantile: P < 0.01), due to loss of negative transmural AT-APD coupling (mean slope 0.63 ± 0.3). No significant transmural gradient in RT was demonstrated during endocardial RV or LV pacing, with preserved negative transmural AT-APD coupling (mean slope −1.36 ± 1.9 and −0.71 ± 0.4, respectively). Steep ARI restitution slopes predominate in the normal ventricle and dynamic ARI; RT gradients exist that are modulated by the site of activation. Epicardial stimulation to initiate ventricular activation promotes significant transmural gradients of repolarization that could be proarrhythmic. PMID:27371682

Influence of aging and chronic heart failure on temporal dispersion of myocardial repolarization

PubMed Central

Piccirillo, Gianfranco; Moscucci, Federica; Pascucci, Matteo; Pappadà, Maria Antonella; D’Alessandro, Gaetana; Rossi, Pietro; Quaglione, Raffaele; Di Barba, Daniele; Barillà, Francesco; Magrì, Damiano

2013-01-01

Background and purpose: QT and Tpeak-Tend (Te) intervals are associated with sudden cardiac death in patients with chronic heart failure (CHF). We studied age-dependent influence on short-term temporal dispersion of these two variables in patients with postischemic CHF. Method: We grouped 75 CHF and 53 healthy control subjects into three age subsets: ≤50 years, >50 years and ≤65 years, and >65 years. We then calculated the following indices: QT and Te variability index (QTVI and TeVI), the ratio between the short-term variability (STV) of QT or Te, and the STV of resting rate (RR) (QT/RR STV and Te/RR STV). Results: In all different age subgroups, patients with CHF showed a higher level of QTVI than age-matched control subjects (≤50 years: P < 0.0001; >50 years and ≤65 years: P < 0.05; >65 years: P < 0.05). Patients with CHF < 50 years old also had all repolarization variability indices higher than normal age-matched controls (TeVI, P < 0.05; QT/RR STV, P < 0.05; Te/RR STV, P < 0.05), whereas we did not find any difference between the two older classes of subjects. Both QTVI (r2: 0.178, P < 0.05) and TeVI (r2: 0.433, P < 0.001) were positively related to age in normal subjects, even if the first correlation was weaker than the second one. Conclusion: Our data showed that QTVI could be used in all ages to evaluate repolarization temporal liability, whereas the other indices are deeply influenced by age. Probably, the age-dependent increase in QTVI was more influenced by a reduction of RR variability reported in older normal subjects. PMID:23662051

Early stage hot spot analysis through standard cell base random pattern generation

NASA Astrophysics Data System (ADS)

Jeon, Joong-Won; Song, Jaewan; Kim, Jeong-Lim; Park, Seongyul; Yang, Seung-Hune; Lee, Sooryong; Kang, Hokyu; Madkour, Kareem; ElManhawy, Wael; Lee, SeungJo; Kwan, Joe

2017-04-01

Due to limited availability of DRC clean patterns during the process and RET recipe development, OPC recipes are not tested with high pattern coverage. Various kinds of pattern can help OPC engineer to detect sensitive patterns to lithographic effects. Random pattern generation is needed to secure robust OPC recipe. However, simple random patterns without considering real product layout style can't cover patterning hotspot in production levels. It is not effective to use them for OPC optimization thus it is important to generate random patterns similar to real product patterns. This paper presents a strategy for generating random patterns based on design architecture information and preventing hotspot in early process development stage through a tool called Layout Schema Generator (LSG). Using LSG, we generate standard cell based on random patterns reflecting real design cell structure - fin pitch, gate pitch and cell height. The output standard cells from LSG are applied to an analysis methodology to assess their hotspot severity by assigning a score according to their optical image parameters - NILS, MEEF, %PV band and thus potential hotspots can be defined by determining their ranking. This flow is demonstrated on Samsung 7nm technology optimizing OPC recipe and early enough in the process avoiding using problematic patterns.

Left ventricular epicardial activation increases transmural dispersion of repolarization in healthy, long QT, and dilated cardiomyopathy dogs.

PubMed

Bai, Rong; Lü, Jiagao; Pu, Jun; Liu, Nian; Zhou, Qiang; Ruan, Yanfei; Niu, Huiyan; Zhang, Cuntai; Wang, Lin; Kam, Ruth

2005-10-01

Benefits of cardiac resynchronization therapy (CRT) are well established. However, less is understood concerning its effects on myocardial repolarization and the potential proarrhythmic risk. Healthy dogs (n = 8) were compared to a long QT interval (LQT) model (n = 8, induced by cesium chloride, CsCl) and a dilated cardiomyopathy with congestive heart failure (DCM-CHF, induced by rapid ventricular pacing, n = 5). Monophasic action potential (MAP) recordings were obtained from the subendocardium, midmyocardium, subepicardium, and the transmural dispersion of repolarization (TDR) was calculated. The QT interval and the interval from the peak to the end of the T wave (T(p-e)) were measured. All these characteristics were compared during left ventricular epicardial (LV-Epi), right ventricular endocardial (RV-Endo), and biventricular (Bi-V) pacing. In healthy dogs, TDR prolonged to 37.54 ms for Bi-V pacing and to 47.16 ms for LV-Epi pacing as compared to 26.75 ms for RV-Endo pacing (P < 0.001), which was parallel to an augmentation in T(p-e) interval (Bi-V pacing, 64.29 ms; LV-Epi pacing, 57.89 ms; RV-Endo pacing, 50.29 ms; P < 0.01). During CsCl exposure, Bi-V and LV-Epi pacing prolonged MAPD, TDR, and T(p-e) interval as compared to RV-Endo pacing. The midmyocardial MAPD (276.30 ms vs 257.35 ms, P < 0.0001) and TDR (33.80 ms vs 27.58 ms, P=0.002) were significantly longer in DCM-CHF dogs than those in healthy dogs. LV-Epi and Bi-V pacing further prolonged the MAPD and TDR in this model. LV-Epi and Bi-V pacing result in prolongation of ventricular repolarization time, and increase of TDR accounted for a parallel augmentation of the T(p-e) interval, which provides evidence that T(p-e) interval accurately represents TDR. These effects are magnified in the LQT and DCM-CHF canine models in addition to their intrinsic transmural heterogeneity in the intact heart. This mechanism may contribute to the development of malignant ventricular arrhythmias, such as torsades de

Early growth patterns are associated with intelligence quotient scores in children born small-for-gestational age.

PubMed

Varella, Marcia H; Moss, William J

2015-08-01

To assess whether patterns of growth trajectory during infancy are associated with intelligence quotient (IQ) scores at 4 years of age in children born small-for-gestational age (SGA). Children in the Collaborative Perinatal Project born SGA were eligible for analysis. The primary outcome was the Stanford-Binet IQ score at 4 years of age. Growth patterns were defined based on changes in weight-for-age z-scores from birth to 4 months and 4 to 12 months of age and consisted of steady, early catch-up, late catch-up, constant catch-up, early catch-down, late catch-down, constant catch-down, early catch-up & late catch-down, and early catch-down & late catch-up. Multivariate linear regression was used to assess associations between patterns of growth and IQ. We evaluated patterns of growth and IQ in 5640 children. Compared with children with steady growth, IQ scores were 2.9 [standard deviation (SD)=0.54], 1.5 (SD=0.63), and 2.2 (SD=0.9) higher in children with early catch-up, early catch-up and later catch-down, and constant catch-up growth patterns, respectively, and 4.4 (SD=1.4) and 3.9 (SD=1.5) lower in children with early catch-down & late catch-up, and early catch-down growth patterns, respectively. Patterns in weight gain before 4 months of age were associated with differences in IQ scores at 4 years of age, with children with early catch-up having slightly higher IQ scores than children with steady growth and children with early catch-down having slightly lower IQ scores. These findings have implications for early infant nutrition in children born SGA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Ca2+ signalling and early embryonic patterning during zebrafish development.

PubMed

Webb, Sarah E; Miller, Andrew L

2007-09-01

1. It has been proposed that Ca2+ signalling, in the form of pulses, waves and steady gradients, may play a crucial role in key pattern-forming events during early vertebrate development. 2. With reference to the embryo of the zebrafish (Danio rerio), herein we review the Ca2+ transients reported from the cleavage to segmentation periods. This time-window includes most of the major pattern-forming events of early development, which transform a single-cell zygote into a complex multicellular embryo with established primary germ layers and body axes. 3. Data are presented to support our proposal that intracellular Ca2+ waves are an essential feature of embryonic cytokinesis and that propagating intercellular Ca2+ waves (both long and short range) may play a crucial role in: (i) the establishment of the embryonic periderm and the coordination of cell movements during epiboly, convergence and extension; (ii) the establishment of the basic embryonic axes and germ layers; and (iii) definition of the morphological boundaries of specific tissue domains and embryonic structures, including future organ anlagen. 4. The potential downstream targets of these Ca2+ transients are also discussed, as well as how they may integrate with other pattern-forming signalling pathways known to modulate early developmental events.

Ranolazine improves abnormal repolarization and contraction in left ventricular myocytes of dogs with heart failure by inhibiting late sodium current

PubMed Central

Undrovinas, Albertas I.; Belardinelli, Luiz; Undrovinas, Nidas A.; Sabbah, Hani N.

2005-01-01

Background Ventricular repolarization and contractile function are frequently abnormal in ventricular myocytes from human failing hearts as well as canine hearts with experimentally induced heart failure (HF). These abnormalities have been attributed to dysfunction involving various steps of the excitation-contraction coupling process, leading to impaired intracellular sodium and calcium homeostasis. We previously reported that the slow inactivating component of the Na+ current (late INa) is augmented in myocytes from failing hearts, and this appears to play a significant role in abnormal ventricular myocytes repolarization and function. We tested the effect of ranolazine, a novel drug being developed to treat angina, on 1) action potential duration (APD), 2) peak transient and late INa (INaT and INaL respectively), 3) early afterdepolarizations (EADs), and 4) twitch contraction (TC) including aftercontractions and contracture. Methods: Myocytes were isolated from the left ventricle of normal dogs and of dogs with chronic HF caused by multiple sequential intracoronary microembolizations. INaT and INaL were recorded using conventional whole-cell patch-clamp techniques. APs were recorded using the β-escin perforated patch-clamp configuration at frequencies of 0.25 and 0.5 Hz. TCs were recorded using an edge movement detector at stimulation frequencies ranging from 0.5 to 2.0 Hz. Results Ranolazine significantly (p < 0.05) and reversibly shortened the APD of myocytes stimulated at either 0.5 or 0.25 Hz in a concentration-dependent manner. At a stimulation frequency of 0.5 Hz, 5, 10 and 20 μM ranolazine shortened the APD90 (APD measured at 90% repolarization) from 516 ± 51 to 304 ± 22, 212 ± 34 and 160 ± 11 ms, respectively, and markedly decreased beat-to-beat variability of APD90, EADs and dispersion of APDs. Ranolazine preferentially blocked INaL relative to INaT in a state-dependent manner; with a ~ 38-fold greater potency against INaL to produce tonic block

Full Transcriptome Analysis of Early Dorsoventral Patterning in Zebrafish

PubMed Central

Horváth, Balázs; Molnár, János; Nagy, István; Tóth, Gábor; Wilson, Stephen W.; Varga, Máté

2013-01-01

Understanding the molecular interactions that lead to the establishment of the major body axes during embryogenesis is one of the main goals of developmental biology. Although the past two decades have revolutionized our knowledge about the genetic basis of these patterning processes, the list of genes involved in axis formation is unlikely to be complete. In order to identify new genes involved in the establishment of the dorsoventral (DV) axis during early stages of zebrafish embryonic development, we employed next generation sequencing for full transcriptome analysis of normal embryos and embryos lacking overt DV pattern. A combination of different statistical approaches yielded 41 differentially expressed candidate genes and we confirmed by in situ hybridization the early dorsal expression of 32 genes that are transcribed shortly after the onset of zygotic transcription. Although promoter analysis of the validated genes suggests no general enrichment for the binding sites of early acting transcription factors, most of these genes carry “bivalent” epigenetic histone modifications at the time when zygotic transcription is initiated, suggesting a “poised” transcriptional status. Our results reveal some new candidates of the dorsal gene regulatory network and suggest that a plurality of the earliest upregulated genes on the dorsal side have a role in the modulation of the canonical Wnt pathway. PMID:23922899

The analysis of QT interval and repolarization morphology of the heart in chronic exposure to lead.

PubMed

Kiełtucki, J; Dobrakowski, M; Pawlas, N; Średniawa, B; Boroń, M; Kasperczyk, S

2017-10-01

There are no common recommendations regarding electrocardiographic monitoring in occupationally exposed workers. Therefore, the present study was designed to investigate whether exposure to lead results in an increase of selected electrocardiography (ECG) pathologies, such as QT interval prolongation and repolarization disorders, in occupationally exposed workers. The study group included 180 workers occupationally exposed to lead compounds. The exposed group was divided according to the median of the mean blood lead level (PbB mean ) calculated based on a series of measurements performed during 5-year observation period (35 µg/dl) into two subgroups: low exposure (LE, PbB mean = 20.0-35.0 µg/dl) and high exposure (HE, PbB mean = 35.1-46.4 µg/dl). The control group consisted of 69 healthy workers without occupational exposure to lead. ECG evaluation included the analysis of heart rate (HR), QT interval and repolarization abnormalities. Mean QT interval was significantly greater in the exposed population than in the control group by 2%. In the HE group, mean QT interval was significantly greater than in the control group by 4% and significantly different from those noted in the LE group. Positive correlations between QT interval and lead exposure indices were also reported. Besides, there was a negative correlation between HR and blood lead level. Increased concentration of lead in the blood above 35 μg/dl is associated with the QT interval prolongation, which may trigger arrhythmias when combined with other abnormalities, such as long QT syndrome. Therefore, electrocardiographic evaluation should be a part of a routine monitoring of occupationally exposed populations.

Macrophage Repolarization with Targeted Alginate Nanoparticles Containing IL-10 Plasmid DNA for the Treatment of Experimental Arthritis

PubMed Central

Jain, Shardool; Tran, Thanh-Huyen; Amiji, Mansoor

2015-01-01

In this study, we have shown for the first time the effectiveness of a non-viral gene transfection strategy to re-polarize macrophages from M1 to M2 functional sub-type for the treatment of rheumatoid arthritis (RA). An anti-inflammatory (IL-10) cytokine encoding plasmid DNA was successfully encapsulated into non-condensing alginate based nanoparticles and the surface of the nano-carriers was modified with tuftsin peptide to achieve active macrophage targeting. Enhanced localization of tuftsin-modified alginate nanoparticles was observed in the inflamed paws of arthritic rats upon intraperitoneal administration. Importantly, targeted nanoparticle treatment was successful in reprogramming macrophage phenotype balance as ~66% of total synovial macrophages from arthritic rats treated with the IL-10 plasmid DNA loaded tuftsin/alginate nanoparticles were in the M2 state compared to ~9% of macrophages in the M2 state from untreated arthritic rats. Treatment significantly reduced systemic and joint tissue pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression and prevented the progression of inflammation and joint damage as revealed by magnetic resonance imaging and histology. Treatment enabled animals to retain their mobility throughout the course of study, whereas untreated animals suffered from impaired mobility. Overall, this study demonstrates that targeted alginate nanoparticles loaded with IL-10 plasmid DNA can efficiently re-polarize macrophages from an M1 to an M2 state, offering a novel treatment paradigm for treatment of chronic inflammatory diseases. PMID:26004232

Design space exploration for early identification of yield limiting patterns

NASA Astrophysics Data System (ADS)

Li, Helen; Zou, Elain; Lee, Robben; Hong, Sid; Liu, Square; Wang, JinYan; Du, Chunshan; Zhang, Recco; Madkour, Kareem; Ali, Hussein; Hsu, Danny; Kabeel, Aliaa; ElManhawy, Wael; Kwan, Joe

2016-03-01

In order to resolve the causality dilemma of which comes first, accurate design rules or real designs, this paper presents a flow for exploration of the layout design space to early identify problematic patterns that will negatively affect the yield. A new random layout generating method called Layout Schema Generator (LSG) is reported in this paper, this method generates realistic design-like layouts without any design rule violation. Lithography simulation is then used on the generated layout to discover the potentially problematic patterns (hotspots). These hotspot patterns are further explored by randomly inducing feature and context variations to these identified hotspots through a flow called Hotspot variation Flow (HSV). Simulation is then performed on these expanded set of layout clips to further identify more problematic patterns. These patterns are then classified into design forbidden patterns that should be included in the design rule checker and legal patterns that need better handling in the RET recipes and processes.

Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization.

PubMed

Lee, Hsiang-Chun; Rudy, Yoram; Po-Yuan, Phd; Sheu, Sheng-Hsiung; Chang, Jan-Gowth; Cui, Jianmin

2013-08-01

Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown. To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes. Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol. With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram. Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Perspectives and Open Problems in the Early Phases of Left-Right Patterning

PubMed Central

Vandenberg, Laura N.; Levin, Michael

2009-01-01

Summary Embryonic left-right (LR) patterning is a fascinating aspect of embryogenesis. The field currently faces important questions about the origin of LR asymmetry, the mechanisms by which consistent asymmetry is imposed on the scale of the whole embryo, and the degree of conservation of early phases of LR patterning among model systems. Recent progress on planar cell polarity and cellular asymmetry in a variety of tissues and species provides a new perspective on the early phases of LR patterning. Despite the huge diversity in body-plans over which consistent LR asymmetry is imposed, and the apparent divergence in molecular pathways that underlie laterality, the data reveal conservation of physiological modules among phyla and a basic scheme of cellular chirality amplified by a planar cell polarity-like pathway over large cell fields. PMID:19084609

Recognition Alters the Spatial Pattern of fMRI Activation in Early Retinotopic Cortex

PubMed Central

Vul, E.; Kanwisher, N.

2010-01-01

Early retinotopic cortex has traditionally been viewed as containing a veridical representation of the low-level properties of the image, not imbued by high-level interpretation and meaning. Yet several recent results indicate that neural representations in early retinotopic cortex reflect not just the sensory properties of the image, but also the perceived size and brightness of image regions. Here we used functional magnetic resonance imaging pattern analyses to ask whether the representation of an object in early retinotopic cortex changes when the object is recognized compared with when the same stimulus is presented but not recognized. Our data confirmed this hypothesis: the pattern of response in early retinotopic visual cortex to a two-tone “Mooney” image of an object was more similar to the response to the full grayscale photo version of the same image when observers knew what the two-tone image represented than when they did not. Further, in a second experiment, high-level interpretations actually overrode bottom-up stimulus information, such that the pattern of response in early retinotopic cortex to an identified two-tone image was more similar to the response to the photographic version of that stimulus than it was to the response to the identical two-tone image when it was not identified. Our findings are consistent with prior results indicating that perceived size and brightness affect representations in early retinotopic visual cortex and, further, show that even higher-level information—knowledge of object identity—also affects the representation of an object in early retinotopic cortex. PMID:20071627

Patterns and mechanisms of early Pliocene warmth.

PubMed

Fedorov, A V; Brierley, C M; Lawrence, K T; Liu, Z; Dekens, P S; Ravelo, A C

2013-04-04

About five to four million years ago, in the early Pliocene epoch, Earth had a warm, temperate climate. The gradual cooling that followed led to the establishment of modern temperature patterns, possibly in response to a decrease in atmospheric CO2 concentration, of the order of 100 parts per million, towards preindustrial values. Here we synthesize the available geochemical proxy records of sea surface temperature and show that, compared with that of today, the early Pliocene climate had substantially lower meridional and zonal temperature gradients but similar maximum ocean temperatures. Using an Earth system model, we show that none of the mechanisms currently proposed to explain Pliocene warmth can simultaneously reproduce all three crucial features. We suggest that a combination of several dynamical feedbacks underestimated in the models at present, such as those related to ocean mixing and cloud albedo, may have been responsible for these climate conditions.

Abnormal early dynamic individual patterns of functional networks in low gamma band for depression recognition.

PubMed

Bi, Kun; Chattun, Mahammad Ridwan; Liu, Xiaoxue; Wang, Qiang; Tian, Shui; Zhang, Siqi; Lu, Qing; Yao, Zhijian

2018-06-13

The functional networks are associated with emotional processing in depression. The mapping of dynamic spatio-temporal brain networks is used to explore individual performance during early negative emotional processing. However, the dysfunctions of functional networks in low gamma band and their discriminative potentialities during early period of emotional face processing remain to be explored. Functional brain networks were constructed from the MEG recordings of 54 depressed patients and 54 controls in low gamma band (30-48 Hz). Dynamic connectivity regression (DCR) algorithm analyzed the individual change points of time series in response to emotional stimuli and constructed individualized spatio-temporal patterns. The nodal characteristics of patterns were calculated and fed into support vector machine (SVM). Performance of the classification algorithm in low gamma band was validated by dynamic topological characteristics of individual patterns in comparison to alpha and beta band. The best discrimination accuracy of individual spatio-temporal patterns was 91.01% in low gamma band. Individual temporal patterns had better results compared to group-averaged temporal patterns in all bands. The most important discriminative networks included affective network (AN) and fronto-parietal network (FPN) in low gamma band. The sample size is relatively small. High gamma band was not considered. The abnormal dynamic functional networks in low gamma band during early emotion processing enabled depression recognition. The individual information processing is crucial in the discovery of abnormal spatio-temporal patterns in depression during early negative emotional processing. Individual spatio-temporal patterns may reflect the real dynamic function of subjects while group-averaged data may neglect some individual information. Copyright © 2018. Published by Elsevier B.V.

Preference for Geometric Patterns Early in Life as a Risk Factor for Autism

PubMed Central

Pierce, Karen; Conant, David; Hazin, Roxana; Stoner, Richard; Desmond, Jamie

2016-01-01

Context Early identification efforts are essential for the early treatment of the symptoms of autism but can only occur if robust risk factors are found. Children with autism often engage in repetitive behaviors and anecdotally prefer to visually examine geometric repetition, such as the moving blade of a fan or the spinning of a car wheel. The extent to which a preference for looking at geometric repetition is an early risk factor for autism has yet to be examined. Objectives To determine if toddlers with an autism spectrum disorder (ASD) aged 14 to 42 months prefer to visually examine dynamic geometric images more than social images and to determine if visual fixation patterns can correctly classify a toddler as having an ASD. Design Toddlers were presented with a 1-minute movie depicting moving geometric patterns on 1 side of a video monitor and children in high action, such as dancing or doing yoga, on the other. Using this preferential looking paradigm, total fixation duration and the number of saccades within each movie type were examined using eye tracking technology. Setting University of California, San Diego Autism Center of Excellence. Participants One hundred ten toddlers participated in final analyses (37 with an ASD, 22 with developmental delay, and 51 typical developing toddlers). Main Outcome Measure Total fixation time within the geometric patterns or social images and the number of saccades were compared between diagnostic groups. Results Overall, toddlers with an ASD as young as 14 months spent significantly more time fixating on dynamic geometric images than other diagnostic groups. If a toddler spent more than 69% of his or her time fixating on geometric patterns, then the positive predictive value for accurately classifying that toddler as having an ASD was 100%. Conclusion A preference for geometric patterns early in life may be a novel and easily detectable early signature of infants and toddlers at risk for autism. PMID:20819977

Romantic Relationship Patterns from Adolescence to Emerging Adulthood: Associations with Family and Peer Experiences in Early Adolescence.

PubMed

Boisvert, Stéphanie; Poulin, François

2016-05-01

The present study identifies and describes romantic relationship patterns from adolescence to adulthood and examines their associations with family and peer experiences in early adolescence. In a 13-year longitudinal study, 281 youth (58 % girls) identified all their romantic partners each year from the ages of 16-24. Dimensions of family relationships (family cohesion, parent-child conflict) and peer relationships (peer likeability, social withdrawal, close friendships, other-sex friendships) were assessed at age 12. Latent class analyses brought out five distinct romantic relationship patterns and significant associations were found with family and peer relationships in early adolescence. These five romantic relationship patterns appeared to follow a continuum of romantic involvement, with romantic relationship patterns situated a both ends of this continuum (later involvement pattern and intense involvement pattern) being associated with more interpersonal experiences in early adolescence.

Central cell-derived peptides regulate early embryo patterning in flowering plants.

PubMed

Costa, Liliana M; Marshall, Eleanor; Tesfaye, Mesfin; Silverstein, Kevin A T; Mori, Masashi; Umetsu, Yoshitaka; Otterbach, Sophie L; Papareddy, Ranjith; Dickinson, Hugh G; Boutiller, Kim; VandenBosch, Kathryn A; Ohki, Shinya; Gutierrez-Marcos, José F

2014-04-11

Plant embryogenesis initiates with the establishment of an apical-basal axis; however, the molecular mechanisms accompanying this early event remain unclear. Here, we show that a small cysteine-rich peptide family is required for formation of the zygotic basal cell lineage and proembryo patterning in Arabidopsis. EMBRYO SURROUNDING FACTOR 1 (ESF1) peptides accumulate before fertilization in central cell gametes and thereafter in embryo-surrounding endosperm cells. Biochemical and structural analyses revealed cleavage of ESF1 propeptides to form biologically active mature peptides. Further, these peptides act in a non-cell-autonomous manner and synergistically with the receptor-like kinase SHORT SUSPENSOR to promote suspensor elongation through the YODA mitogen-activated protein kinase pathway. Our findings demonstrate that the second female gamete and its sexually derived endosperm regulate early embryonic patterning in flowering plants.

Association between a social-business eating pattern and early asymptomatic atherosclerosis

USDA-ARS?s Scientific Manuscript database

BACKGROUND: The importance of a healthy diet in relation to cardiovascular health promotion is widely recognized. Identifying specific dietary patterns related to early atherosclerosis would contribute greatly to inform effective primary prevention strategies. OBJECTIVES: This study sought to quanti...

Cortical atrophy patterns in early Parkinson's disease patients using hierarchical cluster analysis.

PubMed

Uribe, Carme; Segura, Barbara; Baggio, Hugo Cesar; Abos, Alexandra; Garcia-Diaz, Anna Isabel; Campabadal, Anna; Marti, Maria Jose; Valldeoriola, Francesc; Compta, Yaroslau; Tolosa, Eduard; Junque, Carme

2018-05-01

Cortical brain atrophy detectable with MRI in non-demented advanced Parkinson's disease (PD) is well characterized, but its presence in early disease stages is still under debate. We aimed to investigate cortical atrophy patterns in a large sample of early untreated PD patients using a hypothesis-free data-driven approach. Seventy-seven de novo PD patients and 50 controls from the Parkinson's Progression Marker Initiative database with T1-weighted images in a 3-tesla Siemens scanner were included in this study. Mean cortical thickness was extracted from 360 cortical areas defined by the Human Connectome Project Multi-Modal Parcellation version 1.0, and a hierarchical cluster analysis was performed using Ward's linkage method. A general linear model with cortical thickness data was then used to compare clustering groups using FreeSurfer software. We identified two patterns of cortical atrophy. Compared with controls, patients grouped in pattern 1 (n = 33) were characterized by cortical thinning in bilateral orbitofrontal, anterior cingulate, and lateral and medial anterior temporal gyri. Patients in pattern 2 (n = 44) showed cortical thinning in bilateral occipital gyrus, cuneus, superior parietal gyrus, and left postcentral gyrus, and they showed neuropsychological impairment in memory and other cognitive domains. Even in the early stages of PD, there is evidence of cortical brain atrophy. Neuroimaging clustering analysis is able to detect two subgroups of cortical thinning, one with mainly anterior atrophy, and the other with posterior predominance and worse cognitive performance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Potassium channel KCNH2 K897T polymorphism and cardiac repolarization during exercise test: The Finnish Cardiovascular Study.

PubMed

Koskela, J; Laiho, J; KäHönen, M; Rontu, R; Lehtinen, R; Viik, J; Niemi, M; Niemelä, K; Kööbi, T; Turjanmaa, V; Pörsti, I; Lehtimäki, T; Nieminen, T

2008-01-01

Cardiac repolarization is regulated, in part, by the KCNH2 gene, which encodes a rapidly activating component of the delayed rectifier potassium channel. The gene expresses a functional single nucleotide polymorphism, K897T, which changes the biophysical properties of the channel. The objective of this study was to evaluate whether this polymorphism influences two indices of repolarization--the QT interval and T-wave alternans (TWA)--during different phases of a physical exercise test. The cohort consisted of 1,975 patients undergoing an exercise test during which on-line electrocardiographic data were registered. Information on coronary risk factors and medication was recorded. The 2690A>C nucleotide variation in the KCNH2 gene corresponding to the K897T amino acid change was analysed after polymerase chain reaction with allele-specific TaqMan probes. Among all subjects, the QTc intervals did not differ between the three genotype groups (p> or =0.31, RANOVA). Women with the CC genotype tended to have longer QT intervals during the exercise test, but the difference was statistically significant only at rest (p = 0.011, ANOVA). This difference was also detected when the analysis was adjusted for several factors influencing the QT interval. No statistically significant effects of the K897T polymorphism on TWA were observed among all subjects (p = 0.16, RANOVA), nor in men and women separately. The K897T polymorphism of the KCNH2 gene may not be a major genetic determinant for the TWA, but the influence of the CC genotype on QT interval deserves further research among women.

Age at Menarche Is Associated with Divergent Alcohol Use Patterns in Early Adolescence and Early Adulthood

ERIC Educational Resources Information Center

Richards, Meghan A.; Oinonen, Kirsten A.

2011-01-01

A cross-sectional retrospective design was employed to examine the relationship between age at menarche (AAM) and alcohol use patterns from middle childhood (age 7) to early adulthood in 265 University-aged women. Earlier menarche was associated with: (a) earlier ages at first drink and first intoxication, (b) greater use between ages 9 and 14…

An Early Algebra Approach to Pattern Generalisation: Actualising the Virtual through Words, Gestures and Toilet Paper

ERIC Educational Resources Information Center

Ferrara, Francesca; Sinclair, Nathalie

2016-01-01

This paper focuses on pattern generalisation as a way to introduce young students to early algebra. We build on research on patterning activities that feature, in their work with algebraic thinking, both looking for sameness recursively in a pattern (especially figural patterns, but also numerical ones) and conjecturing about function-based…

Intermittent atrial tachycardia promotes repolarization alternans and conduction slowing during rapid rates, and increases susceptibility to atrial fibrillation in a free-behaving sheep model.

PubMed

Monigatti-Tenkorang, Joanna; Jousset, Florian; Pascale, Patrizio; Vesin, Jean-Marc; Ruchat, Patrick; Fromer, Martin; Narayan, Sanjiv M; Pruvot, Etienne

2014-04-01

Paroxysmal atrial fibrillation (AF) may be triggered by intermittent atrial tachycardia, and ultimately lead to persistent AF. However, the mechanisms by which intermittent atrial tachycardia promotes sustained AF are not well understood. Eight sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms, and for the delivery of electrophysiological stimulation protocols and intermittent right atrial tachycardia. Right atrial kinetics of activation recovery interval (ARI) as a surrogate for action potential duration, of conduction time and velocity, and of repolarization alternans were analyzed at incremental pacing rates during the remodeling process induced by weeks of intermittent atrial tachycardia until the development of sustained AF. Intermittent atrial tachycardia decreased ARI and blunted its rate adaptation, facilitated atrial capture, and slowed conduction at high rates, and increased susceptibility to pacing-induced AF. In spite of blunted ARI rate adaptation, right atrial repolarization alternans was maintained during remodeling, and further increased in magnitude just before rapid pacing-induced AF. This study suggests that weeks of intermittent right atrial tachycardia result in a gradual electrical remodeling favorable for wavebreaks and reentry that may facilitate fibrillation. © 2014 Wiley Periodicals, Inc.

Patterns of Practice: Case Studies of Early Childhood Education & Family Engagement in Community Schools

ERIC Educational Resources Information Center

Jacobson, Linda; Rollins, S. Kwesi; Brown, Janet; Naviasky, Heather

2016-01-01

This "Patterns of Practice: Case Studies of Early Childhood Education & Family Engagement in Community Schools" report updates the community school case studies through a description of ongoing developments in Cincinnati, OH; Evansville, IN; Multnomah County, OR; and Tulsa, OK and adds to that knowledge base of early learning and…

Electrocardiographic left ventricular strain pattern: everything old is new again.

PubMed

Schocken, Douglas D

2014-01-01

Electrocardiographic left ventricular hypertrophy (LVH) has many faces with countless features. Beyond the classic measures of LVH, including QRS voltage and duration, the left ventricular (LV) strain pattern is an element whereby characteristic R-ST depression is followed by a concave ST segment that ends in an asymmetrically inverted T wave. The LV strain pattern generally appears in states of increased systemic blood pressure and must be differentiated from similar but not identical ST-T waves indicating ischemia. The LV strain pattern has been found in population studies to be associated with poor prognosis and increased risk of adverse cardiovascular outcomes. Regression of LV strain pattern parallels decline in systemic BP during clinical trials of anti-hypertensive therapies but does not indicate or serve as a surrogate for decrease in LV mass. Newer techniques in data collection and processing may allow the process of strain to be studied in more detail to determine the ways in which electrical remodeling of the left ventricle as characterized by LVH with 'repolarization abnormalities' indicates how CV risk might be managed by using LV strain pattern as an electrocardiographic biomarker. Copyright © 2014 Elsevier Inc. All rights reserved.

Sex differences in repolarization and slow delayed rectifier potassium current and their regulation by sympathetic stimulation in rabbits.

PubMed

Zhu, Yujie; Ai, Xun; Oster, Robert A; Bers, Donald M; Pogwizd, Steven M

2013-06-01

Slow delayed rectifier potassium current (IKs) is important in action potential (AP) repolarization and repolarization reserve. We tested the hypothesis that there are sex-specific differences in IKs, AP, and their regulation by β-adrenergic receptors (β-AR's) using whole-cell patch-clamp. AP duration (APD90) was significantly longer in control female (F) than in control male (M) myocytes. Isoproterenol (ISO, 500 nM) shortened APD90 comparably in M and F, and was largely reversed by β1-AR blocker CGP 20712A (CGP, 300 nM). Inhibition of IKs with chromanol 293B (10 μM) resulted in less APD prolongation in F at baseline (3.0 vs 8.9 %, p < 0.05 vs M) and even in the presence of ISO (5.4 vs 20.9 %, p < 0.05). This suggests that much of the ISO-induced APD abbreviation in F is independent of IKs. In F, baseline IKs was 42 % less and was more weakly activated by ISO (19 vs 68 % in M, p < 0.01). ISO enhancement of IKs was comparably attenuated by CGP in M and F. After ovariectomy, IKs in F had greater enhancement by ISO (72 %), now comparable to control M. After orchiectomy, IKs in M was only slightly enhanced by ISO (23 %), comparable to control F. Pretreatment with thapsigargin (to block SR Ca release) had bigger impact on ISO-induced APD shortening in F than that in M (p < 0.01). In conclusion, we found that there are sex differences in IKs, AP, and their regulation by β-AR's that are modulated by sex hormones, suggesting the potential for sex-specific antiarrhythmic therapy.

Basis for the Induction of Tissue-Level Phase-2 Reentry as a Repolarization Disorder in the Brugada Syndrome

PubMed Central

Bueno-Orovio, Alfonso; Cherry, Elizabeth M.; Evans, Steven J.; Fenton, Flavio H.

2015-01-01

Aims. Human action potentials in the Brugada syndrome have been characterized by delayed or even complete loss of dome formation, especially in the right ventricular epicardial layers. Such a repolarization pattern is believed to trigger phase-2 reentry (P2R); however, little is known about the conditions necessary for its initiation. This study aims to determine the specific mechanisms that facilitate P2R induction in Brugada-affected cardiac tissue in humans. Methods. Ionic models for Brugada syndrome in human epicardial cells were developed and used to study the induction of P2R in cables, sheets, and a three-dimensional model of the right ventricular free wall. Results. In one-dimensional cables, P2R can be induced by adjoining lost-dome and delayed-dome regions, as mediated by tissue excitability and transmembrane voltage profiles, and reduced coupling facilitates its induction. In two and three dimensions, sustained reentry can arise when three regions (delayed-dome, lost-dome, and normal epicardium) are present. Conclusions. Not only does P2R induction by Brugada syndrome require regions of action potential with delayed-dome and lost-dome, but in order to generate a sustained reentry from a triggered waveback multiple factors are necessary, including heterogeneity in action potential distribution, tissue coupling, direction of stimulation, the shape of the late plateau, the duration of lost-dome action potentials, and recovery of tissue excitability, which is predominantly modulated by tissue coupling. PMID:26583094

Early patterning in a chondrichthyan model, the small spotted dogfish: towards the gnathostome ancestral state

PubMed Central

Godard, B G; Mazan, S

2013-01-01

In the past few years, the small spotted dogfish has become the primary model for analyses of early development in chondrichthyans. Its phylogenetic position makes it an ideal outgroup to reconstruct the ancestral gnathostome state by comparisons with established vertebrate model organisms. It is also a suitable model to address the molecular bases of lineage-specific diversifications such as the rise of extraembryonic tissues, as it is endowed with a distinct extraembryonic yolk sac and yolk duct ensuring exchanges between the embryo and a large undivided vitelline mass. Experimental or functional approaches such as cell marking or in ovo pharmacological treatments are emerging in this species, but recent analyses of early development in this species have primarily concentrated on molecular descriptions. These data show the dogfish embryo exhibits early polarities reflecting the dorso-ventral axis of amphibians and teleosts at early blastula stages and an atypical anamniote molecular pattern during gastrulation, independently of the presence of extraembryonic tissues. They also highlight unexpected relationships with amniotes, with a strikingly similar Nodal-dependent regional pattern in the extraembryonic endoderm. In this species, extraembryonic cell fates seem to be determined by differential cell behaviors, which lead to cell allocation in extraembryonic and embryonic tissues, rather than by cell regional identity. We suggest that this may exemplify an early evolutionary step in the rise of extraembryonic tissues, possibly related to quantitative differences in the signaling activities, which shape the early embryo. These results highlight the conservation across gnathostomes of a highly constrained core genetic program controlling early patterning. This conservation may be obscured in some lineages by taxa-specific diversifications such as specializations of extraembryonic nutritive tissues. PMID:22905913

Patterns of protein synthesis in oocytes and early embryos of Rana esculenta complex.

PubMed

Chen, P S; Stumm-Zollinger, E

1986-01-01

We have used isotopic labelling and both one-and two-dimensional electrophoretic procedures to analyse the protien synthesis patterns in oocytes and early embryos of three phenotypes of the European green frogs. The results demonstrated that protein patterns of Rana ridibunda and R. esculenta are identical, but that they differ from those of R. lessonae. Progeny of the lethal cross R. esculenta × R. esculenta showed a distinct delay in the appearance of stage-specific proteins during early embryogenesis. The heat-shock response of R. ridibunda and R. esculenta oocytes was found to be identical, but different from that of Xenopus laevis. The implications of these findings, with respect to hybridogenesis in R. esculenta complex and variations in the regulations of heat shock genes in different amphibian species, are discussed.

Effect of action potential duration on Tpeak-Tend interval, T-wave area and T-wave amplitude as indices of dispersion of repolarization: Theoretical and simulation study in the rabbit heart.

PubMed

Arteyeva, Natalia V; Azarov, Jan E

The aim of the study was to differentiate the effect of dispersion of repolarization (DOR) and action potential duration (APD) on T-wave parameters being considered as indices of DOR, namely, Tpeak-Tend interval, T-wave amplitude and T-wave area. T-wave was simulated in a wide physiological range of DOR and APD using a realistic rabbit model based on experimental data. A simplified mathematical formulation of T-wave formation was conducted. Both the simulations and the mathematical formulation showed that Tpeak-Tend interval and T-wave area are linearly proportional to DOR irrespectively of APD range, while T-wave amplitude is non-linearly proportional to DOR and inversely proportional to the minimal repolarization time, or minimal APD value. Tpeak-Tend interval and T-wave area are the most accurate DOR indices independent of APD. T-wave amplitude can be considered as an index of DOR when the level of APD is taken into account. Copyright © 2017 Elsevier Inc. All rights reserved.

Shock wave compression and self-generated electric field repolarization in ferroelectric ceramics Pb0.99[(Zr0.90Sn0.10)0.96Ti0.04]0.98Nb0.02O3

NASA Astrophysics Data System (ADS)

Jiang, Dongdong; Du, Jinmei; Gu, Yan; Feng, Yujun

2012-03-01

The shock wave induced depoling current of Pb0.99[(Zr0.90Sn0.10)0.96Ti0.04]0.98Nb0.02O3 ceramics was investigated with a system composed of a resistive load and an unpoled ceramic. Disparity in the depoling current was explained by considering the drawing charge effect of unpoled ceramic. The drawing effect for poled ceramics was analysed by developing a model incorporating a time- and electric-field-dependent repolarization. This model predicts that the high-impedance current eventually becomes higher than the short-circuit current, which is consistent with the experimental results in the literature. This work indicates that both the repolarization of uncompressed ceramics caused by the self-generated electric field and depolarization of compressed ceramics caused by the shock wave govern the output current.

Defining and Predicting Patterns of Early Response in a Web-Based Intervention for Depression

PubMed Central

Arndt, Alice; Rubel, Julian; Berger, Thomas; Schröder, Johanna; Späth, Christina; Meyer, Björn; Greiner, Wolfgang; Gräfe, Viola; Hautzinger, Martin; Fuhr, Kristina; Rose, Matthias; Nolte, Sandra; Löwe, Bernd; Hohagen, Fritz; Klein, Jan Philipp; Moritz, Steffen

2017-01-01

Background Web-based interventions for individuals with depressive disorders have been a recent focus of research and may be an effective adjunct to face-to-face psychotherapy or pharmacological treatment. Objective The aim of our study was to examine the early change patterns in Web-based interventions to identify differential effects. Methods We applied piecewise growth mixture modeling (PGMM) to identify different latent classes of early change in individuals with mild-to-moderate depression (n=409) who underwent a CBT-based web intervention for depression. Results Overall, three latent classes were identified (N=409): Two early response classes (n=158, n=185) and one early deterioration class (n=66). Latent classes differed in terms of outcome (P<.001) and adherence (P=.03) in regard to the number of modules (number of modules with a duration of at least 10 minutes) and the number of assessments (P<.001), but not in regard to the overall amount of time using the system. Class membership significantly improved outcome prediction by 24.8% over patient intake characteristics (P<.001) and significantly added to the prediction of adherence (P=.04). Conclusions These findings suggest that in Web-based interventions outcome and adherence can be predicted by patterns of early change, which can inform treatment decisions and potentially help optimize the allocation of scarce clinical resources. PMID:28600278

A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds.

PubMed

Knoll, Fabien; Chiappe, Luis M; Sanchez, Sophie; Garwood, Russell J; Edwards, Nicholas P; Wogelius, Roy A; Sellers, William I; Manning, Phillip L; Ortega, Francisco; Serrano, Francisco J; Marugán-Lobón, Jesús; Cuesta, Elena; Escaso, Fernando; Sanz, Jose Luis

2018-03-05

Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages of development. Comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.

Changes in left ventricular repolarization and ion channel currents following a transient rate increase superimposed on bradycardia in anesthetized dogs.

PubMed

Rubart, M; Lopshire, J C; Fineberg, N S; Zipes, D P

2000-06-01

We previously demonstrated in dogs that a transient rate increase superimposed on bradycardia causes prolongation of ventricular refractoriness that persists for hours after resumption of bradycardia. In this study, we examined changes in membrane currents that are associated with this phenomenon. The whole cell, patch clamp technique was used to record transmembrane voltages and currents, respectively, in single mid-myocardial left ventricular myocytes from dogs with 1 week of complete AV block; dogs either underwent 1 hour of left ventricular pacing at 120 beats/min or did not undergo pacing. Pacing significantly heightened mean phase 1 and peak plateau amplitudes by approximately 6 and approximately 3 mV, respectively (P < 0.02), and prolonged action potential duration at 90% repolarization from 235+/-8 msec to 278+/-8 msec (1 Hz; P = 0.02). Rapid pacing-induced changes in transmembrane ionic currents included (1) a more pronounced cumulative inactivation of the 4-aminopyridine-sensitive transient outward K+ current, Ito, over the range of physiologic frequencies, resulting from a approximately 30% decrease in the population of quickly reactivating channels; (2) increases in peak density of L-type Ca2+ currents, I(Ca.L), by 15% to 35 % between +10 and +60 mV; and (3) increases in peak density of the Ca2+-activated chloride current, I(Cl.Ca), by 30% to 120% between +30 and +50 mV. Frequency-dependent reduction in Ito combined with enhanced I(Ca.L) causes an increase in net inward current that may be responsible for the observed changes in ventricular repolarization. This augmentation of net cation influx is partially antagonized by an increase in outward I(Ca.Cl).

Cardiac memory in patients with Wolff-Parkinson-White syndrome: noninvasive imaging of activation and repolarization before and after catheter ablation.

PubMed

Ghosh, Subham; Rhee, Edward K; Avari, Jennifer N; Woodard, Pamela K; Rudy, Yoram

2008-08-26

Cardiac memory refers to a change in ventricular repolarization induced by and persisting for minutes to months after cessation of a period of altered ventricular activation (eg, resulting from pacing or preexcitation in patients with Wolff-Parkinson-White syndrome). ECG imaging (ECGI) is a novel imaging modality for noninvasive electroanatomic mapping of epicardial activation and repolarization. Fourteen pediatric patients with Wolff-Parkinson-White syndrome and no other congenital disease, were imaged with ECGI a day before and 45 minutes, 1 week, and 1 month after successful catheter ablation. ECGI determined that preexcitation sites were consistent with sites of successful ablation in all cases to within a 1-hour arc of each atrioventricular annulus. In the preexcited rhythm, activation-recovery interval (ARI) was the longest (349+/-6 ms) in the area of preexcitation leading to high average base-to-apex ARI dispersion of 95+/-9 ms (normal is approximately 40 ms). The ARI dispersion remained the same 45 minutes after ablation, although the activation sequence was restored to normal. ARI dispersion was still high (79+/-9 ms) 1 week later and returned to normal (45+/-6 ms) 1 month after ablation. The study demonstrates that ECGI can noninvasively localize ventricular insertion sites of accessory pathways to guide ablation and evaluate its outcome in pediatric patients with Wolff-Parkinson-White syndrome. Wolff-Parkinson-White is associated with high ARI dispersion in the preexcited rhythm that persists after ablation and gradually returns to normal over a period of 1 month, demonstrating the presence of cardiac memory. The 1-month time course is consistent with transcriptional reprogramming and remodeling of ion channels.

SELDI-TOF-based serum proteomic pattern diagnostics for early detection of cancer.

PubMed

Petricoin, Emanuel F; Liotta, Lance A

2004-02-01

Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity-based processes. Serum proteomic pattern diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. This approach has recently shown tremendous promise in the detection of early-stage cancers. The biomarkers found by SELDI-TOF-based pattern recognition analysis are mostly low molecular weight fragments produced at the specific tumor microenvironment.

Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

PubMed

Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

2017-07-01

Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P < .001; right: 0.810, 0.753; P < .01). Altered location and depth patterns of sulcal basins were the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds

DOE PAGES

Knoll, Fabien; Chiappe, Luis M.; Sanchez, Sophie; ...

2018-03-05

Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages ofmore » development. Finally, comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.« less

A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds

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

Knoll, Fabien; Chiappe, Luis M.; Sanchez, Sophie

Fossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages ofmore » development. Finally, comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.« less

Patterns of early transmission of pandemic influenza in London – link with deprivation

PubMed Central

Balasegaram, Sooria; Ogilvie, Flora; Glasswell, Amy; Anderson, Charlotte; Cleary, Vivien; Turbitt, Deborah; McCloskey, Brian

2012-01-01

Please cite this paper as: Balasegaram et al. (2012) Patterns of early transmission of pandemic influenza in London – link with deprivation. Influenza and Other Respiratory Viruses 6(3), e35–e41. Background  During the early containment phase in England from April to June 2009, the national strategy for H1N1 pandemic influenza involved case investigation and treatment, and tracing and prophylaxis of contacts. Objective  To describe the relationship between early transmission of H1N1 pandemic influenza in London and age and socio‐economic status. Methods  Epidemiological data on cases of pandemic flu in London reported to the London Flu Response Centre were analysed to determine patterns of transmission. Results  There were 3487 reported cases (2202 confirmed, 1272 presumed and 14 probable) from 20 April to 28 June 2009, during the ‘containment’ period. The highest report rate of 206 per 100 000 (95% CI 195–218) was seen in primary school–age children (5−11 years) followed by 129 (95% CI 119–139) in secondary school–age children (12–18 years). Reports of cases were initially concentrated in affluent areas but overall showed a clear trend with deprivation and risk ratio of 2·32 (95% CI 1·94–2·78) between the most deprived and the least deprived. Conclusion  Early transmissions were highest amongst school‐aged children but linked with socio‐economic deprivation across all age groups. PMID:22236079

Differences in personality and patterns of recidivism between early starters and other serious male offenders.

PubMed

Ge, Xiaojia; Donnellan, M Brent; Wenk, Ernst

2003-01-01

In this study, the differences in personality and patterns of recidivism were compared between individuals with an early incidence of offending ("early starters") and their later-starting counterparts ("later starters"). Results indicated that early starters were significantly different from later starters in several personality characteristics, as measured by the California Personality Inventory (CPI) and the Minnesota Multiphasic Personality Inventory (MMPI). Specifically, early starters scored lower on the responsibility and socialization scales of the CPI and higher on the paranoia, schizophrenia, and hypomania scales of the MMPI. Moreover, results indicated that early starters were at a significantly higher risk for recidivism than later starters, both at a 15-month and a 20-year follow-up.

Ventricular repolarization alterations in women with angina pectoris and suspected coronary microvascular dysfunction.

PubMed

Dose, Nynne; Michelsen, Marie Mide; Mygind, Naja Dam; Pena, Adam; Ellervik, Christina; Hansen, Peter R; Kanters, Jørgen K; Prescott, Eva; Kastrup, Jens; Gustafsson, Ida; Hansen, Henrik Steen

CMD could be the explanation of angina pectoris with no obstructive CAD and may cause ventricular repolarization changes. We compared T-wave morphology and QTc interval in women with angina pectoris with a control group as well as the associations with CMD. Women with angina pectoris and no obstructive coronary artery disease (n=138) and age-matched controls were compared in regard to QTc interval and morphology combination score (MCS) based on T-wave asymmetry, flatness and presence of T-wave notch. CMD was assessed as a coronary flow velocity reserve (CFVR) by transthoracic echocardiography. Women with angina pectoris had significantly longer QTc intervals (429±20ms) and increased MCS (IQR) (0.73 [0.64-0.80]) compared with the controls (419±20ms) and (0.63 [(0.53-0.73]), respectively (both p<0.001). CFVR was associated with longer QTc interval (p=0.02), but the association was attenuated after multivariable adjustment (p=0.08). This study suggests that women with angina pectoris have alterations in T-wave morphology as well as longer QTc interval compared with a reference population. CMD might be an explanation. Copyright © 2017 Elsevier Inc. All rights reserved.

Early and Late Recurrent Epistaxis Admissions: Patterns of Incidence and Risk Factors.

PubMed

Cohen, Oded; Shoffel-Havakuk, Hagit; Warman, Meir; Tzelnick, Sharon; Haimovich, Yaara; Kohlberg, Gavriel D; Halperin, Doron; Lahav, Yonatan

2017-09-01

Objective Epistaxis is a common complaint, yet few studies have focused on the incidence and risk factors of recurrent epistaxis. Our objective was to determine the patterns of incidence and risk factors for recurrent epistaxis admission (REA). Study Design Case series with chart review. Settings Single academic center. Subjects and Methods The medical records of patients admitted for epistaxis between 1999 and 2015 were reviewed. The follow-up period was defined as 3 years following initial admission. REAs were categorized as early (30 days) and late (31 days to 3 years) following initial admission. Logistic regression was used to identify potential predictors of REAs. Results A total of 653 patients were included. Eighty-six patients (14%) had REAs: 48 (7.5%) early and 38 (6.5%) late. Nonlinear incidence curve was demonstrated for both early and late REAs. Based on logistic regression, prior nasal surgery and anemia were independent risk factors for early REAs. According to multivariate analysis, thrombocytopenia was significantly associated with late REAs. Conclusion Early and late REAs demonstrate different risk predictors. Knowledge of such risk factors may help in risk stratification for this selected group of patients. All patients at risk should be advised on possible preventive measures. Patients at risk for early REA may benefit from a more proactive approach.

Electrical storm in idiopathic ventricular fibrillation is associated with early repolarization.

PubMed

Aizawa, Yoshifusa; Chinushi, Masaomi; Hasegawa, Kanae; Naiki, Nobu; Horie, Minoru; Kaneko, Yoshiaki; Kurabayashi, Masahiko; Ito, Shogo; Imaizumi, Tsutomu; Aizawa, Yoshiyasu; Takatsuki, Seiji; Joo, Kunitake; Sato, Masahito; Ebe, Katsuya; Hosaka, Yukio; Haissaguerre, Michel; Fukuda, Keiichi

2013-09-10

This study sought to characterize patients with idiopathic ventricular fibrillation (IVF) who develop electrical storms. Some IVF patients develop ventricular fibrillation (VF) storms, but the characteristics of these patients are poorly known. Ninety-one IVF patients (86% male) were selected after the exclusion of structural heart diseases, primary electrical diseases, and coronary spasm. Electrocardiogram features were compared between the patients with and without electrical storms. A VF storm was defined as VF occurring ≥3 times in 24 h and J waves >0.1 mV above the isoelectric line in contiguous leads. Fourteen (15.4%) patients had VF storms occurring out-of-hospital at night or in the early morning. J waves were more closely associated with VF storms compared to patients without VF storms: 92.9% versus 36.4% (p < 0.0001). VF storms were controlled by intravenous isoproterenol, which attenuated the J-wave amplitude. After the subsidence of VF storms, the J waves decreased to the nondiagnostic level during the entire follow-up period. Implantable cardioverter-defibrillator therapy was administered to all patients during follow-up. Quinidine therapy was limited, but the patients on disopyramide (n = 3), bepridil (n = 1), or isoprenaline (n = 1) were free from VF recurrence, while VF recurred in 5 of the 9 patients who were not given antiarrhythmic drugs. The VF storms in the IVF patients were highly associated with J waves that showed augmentation prior to the VF onset. Isoproterenol was effective in controlling VF and attenuated the J waves, which diminished to below the diagnostic level during follow-up. VF recurred in patients followed up without antiarrhythmic agents. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Slow adaptation of ventricular repolarization as a cause of arrhythmia?

PubMed

Bueno-Orovio, A; Hanson, B M; Gill, J S; Taggart, P; Rodriguez, B

2014-01-01

This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular and Respiratory Systems". Adaptation of the QT-interval to changes in heart rate reflects on the body-surface electrocardiogram the adaptation of action potential duration (APD) at the cellular level. The initial fast phase of APD adaptation has been shown to modulate the arrhythmia substrate. Whether the slow phase is potentially proarrhythmic remains unclear. To analyze in-vivo human data and use computer simulations to examine effects of the slow APD adaptation phase on dispersion of repolarization and reentry in the human ventricle. Electrograms were acquired from 10 left and 10 right ventricle (LV/RV) endocardial sites in 15 patients with normal ventricles during RV pacing. Activation-recovery intervals, as a surrogate for APD, were measured during a sustained increase in heart rate. Observed dynamics were studied using computer simulations of human tissue electrophysiology. Spatial heterogeneity of rate adaptation was observed in all patients. Inhomogeneity in slow APD adaptation time constants (Δτ(s)) was greater in LV than RV (Δτ(s)(LV) = 31.8 ± 13.2, Δτ(s)(RV) = 19.0 ± 12.8 s , P< 0.01). Simulations showed that altering local slow time constants of adaptation was sufficient to convert partial wavefront block to block with successful reentry. Using electrophysiological data acquired in-vivo in human and computer simulations, we identify heterogeneity in the slow phase of APD adaptation as an important component of arrhythmogenesis.

[Caries patterns and diet in early childhood caries].

PubMed

Faye, M; Ba, A A; Yam, A A; Ba, I

2006-01-01

Early childhood caries (EEC) are multiple carious lesions affecting the primary teeth of infants and preschool children. They are related to a prolonged and night bottle-feeding rich in fermentable carbohydrates. The carious lesions characterised by their patterns and the rapidity of their process can lead to a widespread tooth destruction. The aim of this study was to evaluate the patterns of the carious lesions and their relationship to the diet. This prospective study was carried out in Dakar in public heath structures that have a dental office. It has included 68 children of both sex aged from two to 6 years consisted of 35 boys (51% of the sample) and 33 girls (49%) with the predominance of the 5-year-old children. These children were examined using a plan mouth mirror and probes and their mothers were interviewed. The observed carious lesions were distributed on all tooth surfaces but the complete coronal destruction was the most common lesions observed and represented 25 of the lesions, followed by lesions in three faces of the tooth (17%). The most frequently affected tooth was the association maxillar incisors and molars and the mandibular molars (32.4%). The incisor alone represented 22.1% of the affected teeth. The children were breast-fed associated with either pap or with hard food (52.9%). The bottle was added to this association in 32.4% of the cases and 10% of the children were exclusively breast-fed. The carious lesions were more severe and more frequent in children fed with breast associated with pap and hard food and in those fed with breast associated with the bottle pap and food than to children exclusively breast-fed. These differences were not statistically significant (p = 0.73 > 0.05). Early childhood caries are related to a diet rich in carbon hydrate. They lead to severe tooth destruction. The treatments cost are very high thus prevention by information on the bad effects of sugar on diet and the baby bottle are of great interest.

Training and Psychosocial Patterns during the Early Development of Portuguese National Team Athletes

ERIC Educational Resources Information Center

Barreiros, Andre; Cote, Jean; Fonseca, Antonio Manuel

2013-01-01

This study explored the early development of expert athletes compared to a group of athletes that did not achieve an expert level of performance despite being involved in youth events with their national squads. In particular, the activities, training patterns, and psychosocial influences that characterized their paths in competitive sports were…

The genetics of early telencephalon patterning: some assembly required

PubMed Central

Hébert, Jean M.; Fishell, Gord

2009-01-01

The immense range of human behaviours is rooted in the complex neural networks of the cerebrum. The creation of these networks depends on the precise integration of specific neuronal subtypes that are born in different regions of the telencephalon. Here, using the mouse as a model system, we review how these proliferative zones are established. Moreover, we discuss how these regions can be traced back in development to the function of a few key genes, including those that encode fibroblast growth factors (FGFs), sonic hedgehog (SHH), bone morphogenetic proteins (BMPs), forkhead box G1 (FoxG1), paired box 6 (PAX6) and LIM homeobox protein 2 (LHX2), that pattern the early telencephalon. PMID:19143049

Geologically Controlled Isotope-Time Patterns Reveal Early Differentiation and Crust Formation Processes

NASA Astrophysics Data System (ADS)

Bennett, V. C.; Nutman, A. P.

2014-12-01

The mechanisms of continental crust production and evolution in the early Earth remain controversial, as are questions of the relative roles of early differentiation versus subsequent tectonic procssing in creating Earth's chemical signatures. Here we present geologic observations integrated with whole rock major, trace element and Sm-Nd isotopic signatures and combined with U-Pb and Lu-Hf isotopic compositions of zircon populations from the same rocks, from the most extensive early rock record comprising the 3.9 Ga to 3.6 Ga terranes of southwest Greenland. These data reveal repeated patterns of formation of juvenile TTG crust and associated mafic and ultramafic rocks in convergent margin settings followed by formation of more evolved granites [1]. Our new zircon Lu-Hf data from rare 3.6-3.7 Ga tonalites within the Itsaq Gneiss Complex, obtained from single component, non-migmatitic gneisses with simple zircon populations, limited within sample Hf isotopic variability and accurate U-Pb ages, now document extraction of juvenile tonalites from a near chondritic mantle source between 3.9 Ga and 3.6 Ga. The more evolved, granitic rocks in each area show slightly negative initial ɛHf in accord with crustal reworking of the older (3.8-3.9 Ga) gniesses. There is no evidence for Hadean material in the sources of the granitoids. The Hf isotope-time patterns are consistent with juvenile crust production from a mantle source that experienced only modest amounts of prior crustal extraction. They are distinct from those predicted by reprocessing of an enriched Hadean mafic crust, as has been proposed for this region [2] and for the source of the Hadean Jack Hills zircons [3]. The well-documented, time decreasing, positive 142Nd anomalies [e.g., 4] from these rocks are further evidence of crustal derivation from a convecting mantle source, rather than reworking of an enriched mafic lithosphere. The 143Nd isotopic -time patterns are more complex, reflecting the interplay

A Study of Early Afterdepolarizations in a Model for Human Ventricular Tissue

PubMed Central

Vandersickel, Nele; Kazbanov, Ivan V.; Nuitermans, Anita; Weise, Louis D.; Pandit, Rahul; Panfilov, Alexander V.

2014-01-01

Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium. PMID:24427289

Curvature effects on activation speed and repolarization in an ionic model of cardiac myocytes

NASA Astrophysics Data System (ADS)

Comtois, P.; Vinet, A.

1999-10-01

Reentry is a major mechanism underlying the initiation and perpetuation of many cardiac arrhythmias 12345. Stimulated ventricular myocytes give action potential characterized by a fast upstroke, a long-lasting plateau, and a late repolarization phase. The plateau phase determines the action potential duration (APD) during which the system remains refractory, a property essential to the synchronization of the heart cycle. The APD varies much with prematurity and this change has been shown to be the main determinant of the dynamics in models of paced cells and cable, and during reentry in the one-dimensional loop. Curvature has also been shown to be an important factor for propagation in experimental and theoretical cardiac extended tissue. The objective of this paper is to combine both curvature and prematurity effects in a kinematical model of propagation in cardiac tissue. First, an approximation of the ionic model is used to obtain the effects of curvature and prematurity on the speed of propagation, the APD, and the absolute refractory period. Two versions of the ionic model are studied that differ in their rate of excitability recovery. The functions are used in a kinematical model describing the propagation of period-1 solutions around an annulus.

Early childhood growth patterns and school-age respiratory resistance, fractional exhaled nitric oxide and asthma.

PubMed

Casas, Maribel; den Dekker, Herman T; Kruithof, Claudia J; Reiss, Irwin K; Vrijheid, Martine; de Jongste, Johan C; Jaddoe, Vincent W V; Duijts, Liesbeth

2016-12-01

Greater infant weight gain is associated with lower lung function and increased risk of childhood asthma. The role of early childhood peak growth patterns is unclear. We assessed the associations of individually derived early childhood peak growth patterns with respiratory resistance, fractional exhaled nitric oxide, wheezing patterns, and asthma until school-age. We performed a population-based prospective cohort study among 5364 children. Repeated growth measurements between 0 and 3 years of age were used to derive standard deviation scores (s.d.s) of peak height and weight velocities (PHV and PWV, respectively), and body mass index (BMI) and age at adiposity peak. Respiratory resistance and fractional exhaled nitric oxide were measured at 6 years of age. Wheezing patterns and asthma were prospectively assessed by annual questionnaires. We also assessed whether any association was explained by childhood weight status. Greater PHV was associated with lower respiratory resistance [Z-score (95% CI): -0.03 (-0.04, -0.01) per s.d.s increase] (n = 3382). Greater PWV and BMI at adiposity peak were associated with increased risks of early wheezing [relative risk ratio (95% CI): 1.11 (1.06, 1.16), 1.26 (1.11, 1.43), respectively] and persistent wheezing [relative risk ratio (95% CI): 1.09 (1.03, 1.16), 1.37 (1.17, 1.60), respectively] (n = 3189 and n = 3005, respectively). Childhood weight status partly explained these associations. No other associations were observed. PWV and BMI at adiposity peak are critical for lung developmental and risk of school-age wheezing. Follow-up studies at older ages are needed to elucidate whether these effects persist at later ages. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Does Violence in Adolescence Differentially Predict Offending Patterns in Early Adulthood?

PubMed

Cardwell, Stephanie M; Piquero, Alex R

2018-05-01

Previous research is mixed on whether the commission of a violent offense in adolescence is predictive of criminal career characteristics. In the current study, we addressed the following: (a) What factors predict the commission of serious violence in mid-adolescence? and (b) Does involvement in serious violence in mid-adolescence lead to more chronic and/or more heterogeneous patterns of offending in early adulthood? Data were obtained from the Pathways to Desistance Study, a longitudinal study of serious adolescent offenders in Philadelphia, Pennsylvania, and Phoenix, Arizona. Prior arrests, violence exposure, and gang involvement distinguished adolescents who engaged in violence at baseline. A violent offense at baseline was not predictive of a higher frequency of rearrests but was associated with membership in the low offending trajectory. In conclusion, violent offending in adolescence might be a poor predictor of chronic and heterogeneous patterns of offending throughout the life course.

Early dyadic patterns of mother-infant interactions and outcomes of prematurity at 18 months.

PubMed

Forcada-Guex, Margarita; Pierrehumbert, Blaise; Borghini, Ayala; Moessinger, Adrien; Muller-Nix, Carole

2006-07-01

With the increased survival of very preterm infants, there is a growing concern for their developmental and socioemotional outcomes. The quality of the early mother-infant relationship has been noted as 1 of the factors that may exacerbate or soften the potentially adverse impact of preterm birth, particularly concerning the infant's later competencies and development. The first purpose of the study was to identify at 6 months of corrected age whether there were specific dyadic mother-infant patterns of interaction in preterm as compared with term mother-infant dyads. The second purpose was to examine the potential impact of these dyadic patterns on the infant's behavioral and developmental outcomes at 18 months of corrected age. During a 12-month period (January-December 1998), all preterm infants who were <34 weeks of gestational age and hospitalized at the NICU of the Lausanne University Hospital were considered for inclusion in this longitudinal prospective follow-up study. Control healthy term infants were recruited during the same period from the maternity ward of our hospital. Mother-infant dyads with preterm infants (n = 47) and term infants (n = 25) were assessed at 6 months of corrected age during a mother-infant play interaction and coded according to the Care Index. This instrument evaluates the mother's interactional behavior according to 3 scales (sensitivity, control, and unresponsiveness) and the child's interactional behavior according to 4 scales (cooperation, compliance, difficult, and passivity). At 18 months, behavioral outcomes of the children were assessed on the basis of a semistructured interview of the mother, the Symptom Check List. The Symptom Check List explores 4 groups of behavioral symptoms: sleeping problems, eating problems, psychosomatic symptoms, and behavioral and emotional disorders. At the same age, developmental outcomes were evaluated using the Griffiths Developmental Scales. Five areas were evaluated: locomotor, personal

Effects of sildenafil citrate (viagra) on cardiac repolarization and on autonomic control in subjects with chronic heart failure.

PubMed

Piccirillo, Gianfranco; Nocco, Marialuce; Lionetti, Marco; Moisè, Antonio; Naso, Camilla; Marigliano, Vincenzo; Cacciafesta, Mauro

2002-04-01

Cases of sudden death associated with sildenafil citrate use have been reported in men with coronary artery disease. The aim of this study was to investigate the drug's effect on cardiac repolarization and sinus autonomic and vascular control in men with mild chronic heart failure (CHF; New York Heart Association classification II). Changes in these variables could predispose patients to malignant ventricular arrhythmias. We measured QT dispersion, the QT-RR slope, and the index of QT variability (QTVI) and analyzed spectral power of RR and systolic blood pressure variability in 10 men with dilated cardiomyopathy and in 10 control subjects after administration of a single 50-mg oral dose of sildenafil citrate or placebo at rest (not followed with any attempt at intercourse). In both groups, oral sildenafil citrate decreased the systolic blood pressure (P <.05) and increased the heart rate (P <.05). In subjects with CHF, it also increased the QT-RR (P <.001) and QTVI (from -0.45 +/- 0.07 to -0.27 +/- 0.07; P <.001), but in controls, it increased the QTVI (from -1.20 +/- 0.08 to -0.78 +/-.014; P <.001). In these subjects and controls, oral sildenafil citrate induced a significant reduction in high frequency, expressed in absolute power (subjects with CHF: from 4.04 +/- 0.14 to 3.43 +/- 0.16 natural logarithm ms2; P <.001; controls: from 5.61 +/- 0.44 to 4.98 +/- 0.32 natural logarithm ms2; P <.05) and in normalized units (P <.05). In subjects with CHF but not in controls, it also significantly increased the low frequency to high frequency ratio (from 1.3 +/- 0.12 to 1.89 +/- 0.16; P <.001) and low frequency expressed in normalized units (P <.05). Sildenafil citrate caused no significant changes in the QT interval or dispersion. These findings indicate that, in men with heart failure, sildenafil citrate reduces vagal modulation and increases sympathetic modulation, probably through its reflex vasodilatory action. The autonomic system changes induced with sildenafil

Skeletal Morphogenesis of Microbrachis and Hyloplesion (Tetrapoda: Lepospondyli), and Implications for the Developmental Patterns of Extinct, Early Tetrapods

PubMed Central

Olori, Jennifer C.

2015-01-01

The ontogeny of extant amphibians often is used as a model for that of extinct early tetrapods, despite evidence for a spectrum of developmental modes in temnospondyls and a paucity of ontogenetic data for lepospondyls. I describe the skeletal morphogenesis of the extinct lepospondyls Microbrachis pelikani and Hyloplesion longicostatum using the largest samples examined for either taxon. Nearly all known specimens were re-examined, allowing for substantial anatomical revisions that affect the scoring of characters commonly used in phylogenetic analyses of early tetrapods. The palate of H. longicostatum is re-interpreted and suggested to be more similar to that of M. pelikani, especially in the nature of the contact between the pterygoids. Both taxa possess lateral lines, and M. pelikani additionally exhibits branchial plates. However, early and rapid ossification of the postcranial skeleton, including a well-developed pubis and ossified epipodials, suggests that neither taxon metamorphosed nor were they neotenic in the sense of branchiosaurids and salamanders. Morphogenetic patterns in the foot suggest that digit 5 was developmentally delayed and the final digit to ossify in M. pelikani and H. longicostatum. Overall patterns of postcranial ossification may indicate postaxial dominance in limb and digit formation, but also more developmental variation in early tetrapods than has been appreciated. The phylogenetic position and developmental patterns of M. pelikani and H. longicostatum are congruent with the hypothesis that early tetrapods lacked metamorphosis ancestrally and that stem-amniotes exhibited derived features of development, such as rapid and complete ossification of the skeleton, potentially prior to the evolution of the amniotic egg. PMID:26083733

Early first trimester maternal 'high fish and olive oil and low meat' dietary pattern is associated with accelerated human embryonic development.

PubMed

Parisi, Francesca; Rousian, Melek; Steegers-Theunissen, Régine P M; Koning, Anton H J; Willemsen, Sten P; de Vries, Jeanne H M; Cetin, Irene; Steegers, Eric A P

2018-04-20

Maternal dietary patterns were associated with embryonic growth and congenital anomalies. We aim to evaluate associations between early first trimester maternal dietary patterns and embryonic morphological development among pregnancies with non-malformed outcome. A total of 228 strictly dated, singleton pregnancies without congenital malformations were enrolled in a periconceptional hospital-based cohort. Principal component analysis was performed to extract early first trimester maternal dietary patterns from food frequency questionnaires. Serial transvaginal three-dimensional ultrasound (3D US) scans were performed between 6 +0 and 10 +2 gestational weeks and internal and external morphological criteria were used to define Carnegie stages in a virtual reality system. Associations between dietary patterns and Carnegie stages were investigated using linear mixed models. A total of 726 3D US scans were included (median: three scans per pregnancy). The 'high fish and olive oil and low meat' dietary pattern was associated with accelerated embryonic development in the study population (β = 0.12 (95%CI: 0.00; 0.24), p < 0.05). Weak adherence to this dietary pattern delayed embryonic development by 2.1 days (95%CI: 1.6; 2.6) compared to strong adherence. The 'high vegetables, fruit and grain' dietary pattern accelerated embryonic development in the strictly dated spontaneous pregnancy subgroup without adjustment for energy intake. Early first trimester maternal dietary patterns impacts human embryonic morphological development among pregnancies without congenital malformations. The clinical meaning of delayed embryonic development needs further investigation.

Complementary Gli activity mediates early patterning of the mouse visual system.

PubMed

Furimsky, Marosh; Wallace, Valerie A

2006-03-01

The Sonic hedgehog (Shh) signaling pathway plays a key role in the development of the vertebrate central nervous system, including the eye. This pathway is mediated by the Gli transcription factors (Gli1, Gli2, and Gli3) that differentially activate and repress the expression of specific downstream target genes. In this study, we investigated the roles of the three vertebrate Glis in mediating midline Shh signaling in early ocular development. We examined the ocular phenotypes of Shh and Gli combination mutant mouse embryos and monitored proximodistal and dorsoventral patterning by the expression of specific eye development regulatory genes using in situ hybridization. We show that midline Shh signaling relieves the repressor activity of Gli3 adjacent to the midline and then promotes eye pattern formation through the nonredundant activities of all three Gli proteins. Gli3, in particular, is required to specify the dorsal optic stalk and to define the boundary between the optic stalk and the optic cup.

Early Obstacle Detection and Avoidance for All to All Traffic Pattern in Wireless Sensor Networks

NASA Astrophysics Data System (ADS)

Huc, Florian; Jarry, Aubin; Leone, Pierre; Moraru, Luminita; Nikoletseas, Sotiris; Rolim, Jose

This paper deals with early obstacles recognition in wireless sensor networks under various traffic patterns. In the presence of obstacles, the efficiency of routing algorithms is increased by voluntarily avoiding some regions in the vicinity of obstacles, areas which we call dead-ends. In this paper, we first propose a fast convergent routing algorithm with proactive dead-end detection together with a formal definition and description of dead-ends. Secondly, we present a generalization of this algorithm which improves performances in all to many and all to all traffic patterns. In a third part we prove that this algorithm produces paths that are optimal up to a constant factor of 2π + 1. In a fourth part we consider the reactive version of the algorithm which is an extension of a previously known early obstacle detection algorithm. Finally we give experimental results to illustrate the efficiency of our algorithms in different scenarios.

Daily Physical Activity Patterns During the Early Stage of Alzheimer's Disease.

PubMed

Varma, Vijay R; Watts, Amber

2017-01-01

Alzheimer's disease (AD) is a neurodegenerative disease that results in severe disability. Very few studies have explored changes in daily physical activity patterns during early stages of AD when components of physical function and mobility may be preserved. Our study explored differences in daily physical activity profiles, independent of the effects of non-cognitive factors including physical function and age, among individuals with mild AD compared to controls. Patients with mild AD and controls (n = 92) recruited from the University of Kansas Alzheimer's Disease Center Registry, wore the Actigraph GT3X+ for seven days, and provided objective physical function (VO2 max) and mobility data. Using multivariate linear regression, we explored whether individuals with mild AD had different daily average and diurnal physical activity patterns compared to controls independent of non-cognitive factors that may affect physical activity, including physical function and mobility. We found that mild AD was associated with less moderate-intensity physical activity (p < 0.05), lower peak activity (p < 0.01), and lower physical activity complexity (p < 0.05) particularly during the morning. Mild AD was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for non-cognitive covariates. These findings suggest that factors independent of physical capacity and mobility may drive declines in moderate-intensity physical activity, and not lower-intensity or sedentary activity, during the early stage of AD. This underscores the importance of a better mechanistic understanding of how cognitive decline and AD pathology impact physical activity. Findings emphasize the potential value of designing and testing time-of-day specific physical activity interventions targeting individuals in the early stages of AD, prior to significant declines in mobility and physical function.

Prediction of rhythmic and periodic EEG patterns and seizures on continuous EEG with early epileptiform discharges.

PubMed

Koren, J; Herta, J; Draschtak, S; Pötzl, G; Pirker, S; Fürbass, F; Hartmann, M; Kluge, T; Baumgartner, C

2015-08-01

Continuous EEG (cEEG) is necessary to document nonconvulsive seizures (NCS), nonconvulsive status epilepticus (NCSE), as well as rhythmic and periodic EEG patterns of 'ictal-interictal uncertainty' (RPPIIU) including periodic discharges, rhythmic delta activity, and spike-and-wave complexes in neurological intensive care patients. However, cEEG is associated with significant recording and analysis efforts. Therefore, predictors from short-term routine EEG with a reasonably high yield are urgently needed in order to select patients for evaluation with cEEG. The aim of this study was to assess the prognostic significance of early epileptiform discharges (i.e., within the first 30 min of EEG recording) on the following: (1) incidence of ictal EEG patterns and RPPIIU on subsequent cEEG, (2) occurrence of acute convulsive seizures during the ICU stay, and (3) functional outcome after 6 months of follow-up. We conducted a separate analysis of the first 30 min and the remaining segments of prospective cEEG recordings according to the ACNS Standardized Critical Care EEG Terminology as well as NCS criteria and review of clinical data of 32 neurological critical care patients. In 17 patients with epileptiform discharges within the first 30 min of EEG (group 1), electrographic seizures were observed in 23.5% (n = 4), rhythmic or periodic EEG patterns of 'ictal-interictal uncertainty' in 64.7% (n = 11), and neither electrographic seizures nor RPPIIU in 11.8% (n = 2). In 15 patients with no epileptiform discharges in the first 30 min of EEG (group 2), no electrographic seizures were recorded on subsequent cEEG, RPPIIU were seen in 26.7% (n = 4), and neither electrographic seizures nor RPPIIU in 73.3% (n = 11). The incidence of EEG patterns on cEEG was significantly different between the two groups (p = 0.008). Patients with early epileptiform discharges developed acute seizures more frequently than patients without early epileptiform discharges (p = 0.009). Finally, functional

Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas

PubMed Central

Schroeder, Diane I.; Jayashankar, Kartika; Douglas, Kory C.; Thirkill, Twanda L.; York, Daniel; Dickinson, Pete J.; Williams, Lawrence E.; Samollow, Paul B.; Ross, Pablo J.; Bannasch, Danika L.; Douglas, Gordon C.; LaSalle, Janine M.

2015-01-01

Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs) and highly methylated domains (HMDs) with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq) analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo. PMID:26241857

Breast cancer early detection via tracking of skin back-scattered secondary speckle patterns

NASA Astrophysics Data System (ADS)

Bennett, Aviya; Sirkis, Talia; Beiderman, Yevgeny; Agdarov, Sergey; Beiderman, Yafim; Zalevsky, Zeev

2018-02-01

Breast cancer has become a major cause of death among women. The lifetime risk of a woman developing this disease has been established as one in eight. The most useful way to reduce breast cancer death is to treat the disease as early as possible. The existing methods of early diagnostics of breast cancer are mainly based on screening mammography or Magnetic Resonance Imaging (MRI) periodically conducted at medical facilities. In this paper the authors proposing a new approach for simple breast cancer detection. It is based on skin stimulation by sound waves, illuminating it by laser beam and tracking the reflected secondary speckle patterns. As first approach, plastic balls of different sizes were placed under the skin of chicken breast and detected by the proposed method.

Major Maternal Dietary Patterns during Early Pregnancy and Their Association with Neonatal Anthropometric Measurement

PubMed Central

Hajianfar, Hossein; Esmaillzadeh, Ahmad; Feizi, Awat; Shahshahan, Zahra

2018-01-01

Background Anthropometric measurements of newborn infant are widely assessed as determinants of maternal nutrition. Although earlier studies have mostly examined the effects of particular nutrients or foods during gestational period on neonatal anthropometric measurements, there are few studies regarding the association of dietary patterns and mentioned measurements. So, the purpose of the current study was to investigate the association between major maternal dietary patterns and neonatal anthropometric measurements including body weight, head circumference, and height. Methods The current prospective observational study is based on the data collected from 812 pregnant women. Dietary data was collected using a validated semiquantitative food frequency questionnaire. Results Three identified major dietary patterns according to the results obtained from the factor loading matrix were (i) “western dietary pattern”; (ii) “traditional dietary pattern”; (iii) “healthy dietary pattern”. Overall, this study demonstrated a positive significant association between high adherences to western dietary pattern and chance of having low birth weight infant. However, such associations were not seen in women taking healthy and traditional dietary patterns. Conclusion We found that healthier maternal dietary patterns during early pregnancy might be associated with lower risk of low birth weight. Further studies are required to confirm these findings.

Cadherin Switch during EMT in Neural Crest Cells Leads to Contact Inhibition of Locomotion via Repolarization of Forces.

PubMed

Scarpa, Elena; Szabó, András; Bibonne, Anne; Theveneau, Eric; Parsons, Maddy; Mayor, Roberto

2015-08-24

Contact inhibition of locomotion (CIL) is the process through which cells move away from each other after cell-cell contact, and it contributes to malignant invasion and developmental migration. Various cell types exhibit CIL, whereas others remain in contact after collision and may form stable junctions. To investigate what determines this differential behavior, we study neural crest cells, a migratory stem cell population whose invasiveness has been likened to cancer metastasis. By comparing pre-migratory and migratory neural crest cells, we show that the switch from E- to N-cadherin during EMT is essential for acquisition of CIL behavior. Loss of E-cadherin leads to repolarization of protrusions, via p120 and Rac1, resulting in a redistribution of forces from intercellular tension to cell-matrix adhesions, which break down the cadherin junction. These data provide insight into the balance of physical forces that contributes to CIL in cells in vivo. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Cadherin Switch during EMT in Neural Crest Cells Leads to Contact Inhibition of Locomotion via Repolarization of Forces

PubMed Central

Scarpa, Elena; Szabó, András; Bibonne, Anne; Theveneau, Eric; Parsons, Maddy; Mayor, Roberto

2015-01-01

Summary Contact inhibition of locomotion (CIL) is the process through which cells move away from each other after cell-cell contact, and it contributes to malignant invasion and developmental migration. Various cell types exhibit CIL, whereas others remain in contact after collision and may form stable junctions. To investigate what determines this differential behavior, we study neural crest cells, a migratory stem cell population whose invasiveness has been likened to cancer metastasis. By comparing pre-migratory and migratory neural crest cells, we show that the switch from E- to N-cadherin during EMT is essential for acquisition of CIL behavior. Loss of E-cadherin leads to repolarization of protrusions, via p120 and Rac1, resulting in a redistribution of forces from intercellular tension to cell-matrix adhesions, which break down the cadherin junction. These data provide insight into the balance of physical forces that contributes to CIL in cells in vivo. PMID:26235046

Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer's disease.

PubMed

Schöll, Michael; Ossenkoppele, Rik; Strandberg, Olof; Palmqvist, Sebastian; Jögi, Jonas; Ohlsson, Tomas; Smith, Ruben; Hansson, Oskar

2017-09-01

Patients with Alzheimer's disease can present with different clinical phenotypes. Individuals with late-onset Alzheimer's disease (>65 years) typically present with medial temporal lobe neurodegeneration and predominantly amnestic symptomatology, while patients with early-onset Alzheimer's disease (<65 years) exhibit greater neocortical involvement associated with a clinical presentation including dyspraxia, executive dysfunction, or visuospatial impairment. We recruited 20 patients with early-onset Alzheimer's disease, 21 with late-onset Alzheimer's disease, three with prodromal early-onset Alzheimer's disease and 13 with prodromal late-onset Alzheimer's disease, as well as 30 cognitively healthy elderly controls, that had undergone 18F-AV-1451 tau positron emission tomography and structural magnetic resonance imaging to explore whether early- and late-onset Alzheimer's disease exhibit differential regional tau pathology and atrophy patterns. Strong associations of lower age at symptom onset with higher 18F-AV-1451 uptake were observed in several neocortical regions, while higher age did not yield positive associations in neither patient group. Comparing patients with early-onset Alzheimer's disease with controls resulted in significantly higher 18F-AV-1451 retention throughout the neocortex, while comparing healthy controls with late-onset Alzheimer's disease patients yielded a distinct pattern of higher 18F-AV-1451 retention, predominantly confined to temporal lobe regions. When compared against each other, the early-onset Alzheimer's disease group exhibited greater uptake than the late-onset group in prefrontal and premotor, as well as in inferior parietal cortex. These preliminary findings indicate that age may constitute an important contributor to Alzheimer's disease heterogeneity highlighting the potential of tau positron emission tomography to capture phenotypic variation across patients with Alzheimer's disease. © The Author (2017). Published by Oxford

Choline-modulated arsenic trioxide-induced prolongation of cardiac repolarization in Guinea pig.

PubMed

Sun, Hong-Li; Chu, Wen-Feng; Dong, De-Li; Liu, Yan; Bai, Yun-Long; Wang, Xiao-Hui; Zhou, Jin; Yang, Bao-Feng

2006-04-01

Arsenic trioxide (As(2)O(3)) has been found to be effective for relapsed or refractory acute promyelocytic leukaemia, but its clinical use is burdened by QT prolongation, Torsade de pointes tachycardias, and sudden cardiac death. The aim of the present study was to elucidate the ionic mechanisms of As(2)O(3)-induced abnormalities of cardiac electrophysiology and the therapeutic action of choline on As(2)O(3)-caused QT prolongation in guinea pig. Intravenous administration of As(2)O(3) prolonged the QT interval in a dose- and time-dependent manner in guinea pig hearts, and the QT prolongation could be modulated by choline. By using whole-cell patch clamp technique and confocal laser scanning microscopy, we found that As(2)O(3) significantly lengthened action potential duration measured at 50 and 90% of repolarization, enhanced L-type calcium currents (I(Ca-L)), inhibited delayed rectifier potassium currents (I(K)), and increased intracellular calcium concentration ([Ca(2+)](i)) in guinea pig ventricular myocytes. Choline corrected As(2)O(3)-mediated alterations of action potential duration, I(Ca-L) and [Ca(2+)](i), but had no effect on the I(K) inhibition. As(2)O(3) markedly disturbed the normal equilibrium of transmembrane currents (increasing I(Ca-L) and suppressing I(K)) in guinea pig cardiomyocyte, and induced prolongation of action potential duration, further degenerated into QT prolongation. Choline normalized QT interval abnormality and corrected lengthened action potential duration by inhibiting the elevated I(Ca-L) and [Ca(2+)](i) in ventricular myocytes during As(2)O(3) application.

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor.

PubMed

Lin, Yen-Chang; Huang, Jianying; Hileman, Stan; Martin, Karen H; Hull, Robert; Davis, Mary; Yu, Han-Gang

2015-11-15

Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1-30 μg/kg) decreased resting heart rate; at high doses (150-300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03-0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias. Copyright © 2015 the American Physiological Society.

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor

PubMed Central

Lin, Yen-Chang; Huang, Jianying; Hileman, Stan; Martin, Karen H.; Hull, Robert; Davis, Mary

2015-01-01

Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1–30 μg/kg) decreased resting heart rate; at high doses (150–300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03–0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias. PMID:26408544

Pattern recognition applied to infrared images for early alerts in fog

NASA Astrophysics Data System (ADS)

Boucher, Vincent; Marchetti, Mario; Dumoulin, Jean; Cord, Aurélien

2014-09-01

Fog conditions are the cause of severe car accidents in western countries because of the poor induced visibility. Its forecast and intensity are still very difficult to predict by weather services. Infrared cameras allow to detect and to identify objects in fog while visibility is too low for eye detection. Over the past years, the implementation of cost effective infrared cameras on some vehicles has enabled such detection. On the other hand pattern recognition algorithms based on Canny filters and Hough transformation are a common tool applied to images. Based on these facts, a joint research program between IFSTTAR and Cerema has been developed to study the benefit of infrared images obtained in a fog tunnel during its natural dissipation. Pattern recognition algorithms have been applied, specifically on road signs which shape is usually associated to a specific meaning (circular for a speed limit, triangle for an alert, …). It has been shown that road signs were detected early enough in images, with respect to images in the visible spectrum, to trigger useful alerts for Advanced Driver Assistance Systems.

Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients.

PubMed

Singh, Prashant K; Preus, Leah; Hu, Qiang; Yan, Li; Long, Mark D; Morrison, Carl D; Nesline, Mary; Johnson, Candace S; Koochekpour, Shahriar; Kohli, Manish; Liu, Song; Trump, Donald L; Sucheston-Campbell, Lara E; Campbell, Moray J

2014-02-15

We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of CaP patients following RP. A greater than two-fold increase in hazard of biochemical progression associated with altered expression of miR-103, miR-125b and miR-222 (p<.0008) in the serum of CaP patients. Prediction models based on penalized regression analyses showed that the levels of the miRNAs and PSA together were better at detecting false positives than models without miRNAs, for similar level of sensitivity. Analyses of publically available data revealed significant and reciprocal relationships between changes in CpG methylation and miRNA expression patterns suggesting a role for CpG methylation to regulate miRNA. Exploratory validation supported roles for miR-222 and miR-125b to predict progression risk in CaP. The current study established that expression patterns of serum-detectable miRNAs taken at the time of RP are prognostic for men who are at risk of experiencing subsequent early biochemical progression. These non-invasive approaches could be used to augment treatment decisions.

Evaluation of inhomogeneities of repolarization in patients with psoriasis vulgaris

PubMed Central

İnci, Sinan; Aksan, Gökhan; Nar, Gökay; Yüksel, Esra Pancar; Ocal, Hande Serra; Çapraz, Mustafa; Yüksel, Serkan; Şahin, Mahmut

2016-01-01

Introduction The arrhythmia potential has not been investigated adequately in psoriatic patients. In this study, we assessed the ventricular repolarization dispersion, using the Tp-e interval and the Tp-e/QT ratio, and investigated the association with inflammation. Material and methods Seventy-one psoriasis vulgaris patients and 70 age- and gender-matched healthy individuals were enrolled in the study. The severity of the disease was calculated using Psoriasis Area and Severity Index scoring. The QTd was defined as the difference between the maximum and minimum QT intervals. The Tp-e interval was defined as the interval from the peak of the T wave to the end of the T wave. The Tp-e interval was corrected for heart rate. The Tp-e/QT ratio was calculated using these measurements. Results There were no significant differences between the groups with respect to basal clinical and laboratory characteristics (p > 0.05). The Tp-e interval, the corrected Tp-e interval (cTp-e) and the Tp-e/QT ratio were also significantly higher in psoriasis patients compared to the control group (78.5 ±8.0 ms vs. 71.4 ±7.6 ms, p < 0.001, 86.3 ±13.2 ms vs. 77.6 ±9.0 ms, p < 0.001 and 0.21 ±0.02 vs. 0.19 ±0.02, p < 0.001 respectively). A significant correlation was detected between the cTp-e time and the Tp-e/QT ratio and the PASI score in the group of psoriatic patients (r = 0.51, p < 0.001; r = 0.59, p < 0.001, respectively). Conclusions In our study, we detected a significant increase in the Tp-e interval and the Tp-e/QT ratio in patients with psoriasis vulgaris. The Tp-e interval and the Tp-e/QT ratio may be predictors for ventricular arrhythmias in patients with psoriasis vulgaris. PMID:27904512

The Use of Poetry in a Spiral-Patterned Methodology for Research about Love in Early Childhood

ERIC Educational Resources Information Center

Cousins, Sarah

2017-01-01

Research about love in early childhood education and care is rare. Love is difficult topic to research and write about in scholarly contexts. In order to properly explore love in professional contexts, practitioner narratives on the topic were sought through individual, unstructured interviews. A spiral-patterned methodological approach was…

Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.

PubMed

Drolet, Benoit; Yang, Tao; Daleau, Pascal; Roden, Dan M; Turgeon, Jacques

2003-06-01

Cases of QT prolongation and sudden death have been reported with risperidone, a neuroleptic agent increasingly prescribed worldwide. Although hypokalemia was present in some of these events, we hypothesized that risperidone may have unsuspected electrophysiologic effects predisposing patients to proarrhythmia. In six isolated guinea pig hearts, risperidone elicited prolongation of cardiac repolarization: action potential duration increased from a baseline value of 128 ms +/- 5 to 147 ms +/- 5 (15%) with risperidone 1 microM during pacing at 250-ms cycle length, whereas the increase was only 10%, from 101 ms +/- 2 to 111 ms +/- 4, with pacing at a cycle length of 150 ms. In human ether-a-go-go (HERG)-transfected Chinese hamster ovary cells (n = 16), risperidone caused concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current with an IC(50) for tail block of 261 nM. Risperidone did not block I(Ks). Risperidone exerts cardiac electrophysiologic effects similar to those of Class III antiarrhythmic drugs. These effects are observed at clinically relevant concentrations. Because risperidone is metabolized primarily by CYP2D6, these actions likely enhance risk for risperidone-related QT prolongation and proarrhythmia in specific patient subsets (e.g., poor metabolizers and those taking interacting drugs).

The early inflorescence of Arabidopsis thaliana demonstrates positional effects in floral organ growth and meristem patterning.

PubMed

Plackett, Andrew R G; Powers, Stephen J; Phillips, Andy L; Wilson, Zoe A; Hedden, Peter; Thomas, Stephen G

2018-06-01

Linear modelling approaches detected significant gradients in organ growth and patterning across early flowers of the Arabidopsis inflorescence and uncovered evidence of new roles for gibberellin in floral development. Most flowering plants, including the genetic model Arabidopsis thaliana, produce multiple flowers in sequence from a reproductive shoot apex to form a flower spike (inflorescence). The development of individual flowers on an Arabidopsis inflorescence has typically been considered as highly stereotypical and uniform, but this assumption is contradicted by the existence of mutants with phenotypes visible in early flowers only. This phenomenon is demonstrated by mutants partially impaired in the biosynthesis of the phytohormone gibberellin (GA), in which floral organ growth is retarded in the first flowers to be produced but has recovered spontaneously by the 10th flower. We presently lack systematic data from multiple flowers across the Arabidopsis inflorescence to explain such changes. Using mutants of the GA 20-OXIDASE (GA20ox) GA biosynthesis gene family to manipulate endogenous GA levels, we investigated the dynamics of changing floral organ growth across the early Arabidopsis inflorescence (flowers 1-10). Modelling of floral organ lengths identified a significant, GA-independent gradient of increasing stamen length relative to the pistil in the wild-type inflorescence that was separable from other, GA-dependent effects. It was also found that the first flowers exhibited unstable organ patterning in contrast to later flowers and that this instability was prolonged by exogenous GA treatment. These findings indicate that the development of individual flowers is influenced by hitherto unknown factors acting across the inflorescence and also suggest novel functions for GA in floral patterning.

Early headgear effects on the eruption pattern of the maxillary canines.

PubMed

Silvola, Anna-Sofia; Arvonen, Päivi; Julku, Johanna; Lähdesmäki, Raija; Kantomaa, Tuomo; Pirttiniemi, Pertti

2009-05-01

To test the null hypothesis that early headgear (HG) treatment has no effect on the eruption pattern of the maxillary canines in the early mixed dentition. Sixty-eight children (40 boys and 28 girls) with a Class II tendency in occlusion and moderate crowding of the dental arches were randomized into two groups. HG treatment was initiated immediately in the first group. In the second group only minor interceptive procedures were performed during the first follow-up period of 2 years. Orthopantomograms were taken at the baseline, three times at 1-year intervals, and after growth at the age of 16. Eruption geometry was performed. The space from the maxillary first molar to the lateral incisor was measured on the dental casts. The inclination of the maxillary canine in relation to the midline appeared to be significantly more vertically oriented on the right side in the HG group 1 and 2 years after starting the HG therapy (P = .0098 and P = .0003, respectively). The inclination in relation to the lateral incisors was smaller in the HG group bilaterally after 1 year and 2 years of HG treatment, and on the right side after 3 years of treatment. The hypothesis is rejected. Early HG treatment significantly affects the inclination of the maxillary canine during eruption. The strongest influence was seen after 2 years of HG use, more prominently in the right-side canine.

Ca2+ signaling and early embryonic patterning during the blastula and gastrula periods of zebrafish and Xenopus development.

PubMed

Webb, Sarah E; Miller, Andrew L

2006-11-01

It has been proposed that Ca(2+) signaling, in the form of pulses, waves and steady gradients, may play a crucial role in key pattern forming events during early vertebrate development [L.F. Jaffe, Organization of early development by calcium patterns, BioEssays 21 (1999) 657-667; M.J. Berridge, P. Lipp, M.D. Bootman, The versatility and universality of calcium signaling, Nat. Rev. Mol. Cell Biol. 1 (2000) 11-21; S.E. Webb, A.L. Miller, Calcium signalling during embryonic development, Nat. Rev. Mol. Cell Biol. 4 (2003) 539-551]. With reference to the embryos of zebrafish (Danio rerio) and the frog, Xenopus laevis, we review the Ca(2+) signals reported during the Blastula and Gastrula Periods. This developmental window encompasses the major pattern forming events of epiboly, involution, and convergent extension, which result in the establishment of the basic germ layers and body axes [C.B. Kimmel, W.W. Ballard, S.R. Kimmel, B. Ullmann, T.F. Schilling, Stages of embryonic development of the zebrafish, Dev. Dyn. 203 (1995) 253-310]. Data will be presented to support the suggestion that propagating waves (both long and short range) of Ca(2+) release, followed by sequestration, may play a crucial role in: (1) Coordinating cell movements during these pattern forming events and (2) Contributing to the establishment of the basic embryonic axes, as well as (3) Helping to define the morphological boundaries of specific tissue domains and embryonic structures, including future organ anlagen [E. Gilland, A.L. Miller, E. Karplus, R. Baker, S.E. Webb, Imaging of multicellular large-scale rhythmic calcium waves during zebrafish gastrulation, Proc. Natl. Acad. Sci. USA 96 (1999) 157-161; J.B. Wallingford, A.J. Ewald, R.M. Harland, S.E. Fraser, Calcium signaling during convergent extension in Xenopus, Curr. Biol. 11 (2001) 652-661]. The various potential targets of these Ca(2+) transients will also be discussed, as well as how they might integrate with other known pattern forming

Environmental cues and symbiont microbe-associated molecular patterns function in concert to drive the daily remodelling of the crypt-cell brush border of the Euprymna scolopes light organ

PubMed Central

Heath-Heckman, Elizabeth A.C.; Foster, Jamie; Apicella, Michael A.; Goldman, William E.; McFall-Ngai, Margaret

2016-01-01

Summary Recent research has shown that the microbiota affects the biology of associated host epithelial tissues, including their circadian rhythms, although few data are available on how such influences shape the microarchitecture of the brush border. The squid-vibrio system exhibits two modifications of the brush border that supports the symbionts: effacement and repolarization. Together these occur on a daily rhythm in adult animals, at the dawn expulsion of symbionts into the environment, and symbiont colonization of the juvenile host induces an increase in microvillar density. Here we sought to define how these processes are related and the roles of both symbiont colonization and environmental cues. Ultrastructural analyses showed that the juvenile-organ brush borders also efface concomitantly with daily dawn-cued expulsion of symbionts. Manipulation of the environmental light cue and juvenile symbiotic state demonstrated that this behaviour requires the light cue, but not colonization. In contrast, symbionts were required for the observed increase in microvillar density that accompanies post dawn brush-border repolarization; this increase was induced solely by host exposure to phosphorylated lipid A of symbiont cells. These data demonstrate that a partnering of environmental and symbiont cues shapes the brush border and that microbe-associated molecular patterns play a role in the regulation of brush-border microarchitecture. PMID:27062511

Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender

PubMed Central

Xu, Wanli; Janton, Susan; Henderson, Wendy A.; Matson, Adam; McGrath, Jacqueline M.; Maas, Kendra; Graf, Joerg

2016-01-01

Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05–0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother’s own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion

Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender.

PubMed

Cong, Xiaomei; Xu, Wanli; Janton, Susan; Henderson, Wendy A; Matson, Adam; McGrath, Jacqueline M; Maas, Kendra; Graf, Joerg

2016-01-01

Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05-0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother's own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion

Touchscreen typing-pattern analysis for detecting fine motor skills decline in early-stage Parkinson's disease.

PubMed

Iakovakis, Dimitrios; Hadjidimitriou, Stelios; Charisis, Vasileios; Bostantzopoulou, Sevasti; Katsarou, Zoe; Hadjileontiadis, Leontios J

2018-05-16

Parkinson's disease (PD) is a degenerative movement disorder causing progressive disability that severely affects patients' quality of life. While early treatment can produce significant benefits for patients, the mildness of many early signs combined with the lack of accessible high-frequency monitoring tools may delay clinical diagnosis. To meet this need, user interaction data from consumer technologies have recently been exploited towards unsupervised screening for PD symptoms in daily life. Similarly, this work proposes a method for detecting fine motor skills decline in early PD patients via analysis of patterns emerging from finger interaction with touchscreen smartphones during natural typing. Our approach relies on low-/higher-order statistical features of keystrokes timing and pressure variables, computed from short typing sessions. Features are fed into a two-stage multi-model classification pipeline that reaches a decision on the subject's status (PD patient/control) by gradually fusing prediction probabilities obtained for individual typing sessions and keystroke variables. This method achieved an AUC = 0.92 and 0.82/0.81 sensitivity/specificity (matched groups of 18 early PD patients/15 controls) with discriminant features plausibly correlating with clinical scores of relevant PD motor symptoms. These findings suggest an improvement over similar approaches, thereby constituting a further step towards unobtrusive early PD detection from routine activities.

An Electromechanical Left Ventricular Wedge Model to Study the Effects of Deformation on Repolarization during Heart Failure

PubMed Central

Rocha, B. M.; Toledo, E. M.; Barra, L. P. S.; dos Santos, R. Weber

2015-01-01

Heart failure is a major and costly problem in public health, which, in certain cases, may lead to death. The failing heart undergo a series of electrical and structural changes that provide the underlying basis for disturbances like arrhythmias. Computer models of coupled electrical and mechanical activities of the heart can be used to advance our understanding of the complex feedback mechanisms involved. In this context, there is a lack of studies that consider heart failure remodeling using strongly coupled electromechanics. We present a strongly coupled electromechanical model to study the effects of deformation on a human left ventricle wedge considering normal and hypertrophic heart failure conditions. We demonstrate through a series of simulations that when a strongly coupled electromechanical model is used, deformation results in the thickening of the ventricular wall that in turn increases transmural dispersion of repolarization. These effects were analyzed in both normal and failing heart conditions. We also present transmural electrograms obtained from these simulations. Our results suggest that the waveform of electrograms, particularly the T-wave, is influenced by cardiac contraction on both normal and pathological conditions. PMID:26550570

Differences in early speech patterns between Parkinson variant of multiple system atrophy and Parkinson's disease.

PubMed

Huh, Young Eun; Park, Jongkyu; Suh, Mee Kyung; Lee, Sang Eun; Kim, Jumin; Jeong, Yuri; Kim, Hee-Tae; Cho, Jin Whan

2015-08-01

In Parkinson variant of multiple system atrophy (MSA-P), patterns of early speech impairment and their distinguishing features from Parkinson's disease (PD) require further exploration. Here, we compared speech data among patients with early-stage MSA-P, PD, and healthy subjects using quantitative acoustic and perceptual analyses. Variables were analyzed for men and women in view of gender-specific features of speech. Acoustic analysis revealed that male patients with MSA-P exhibited more profound speech abnormalities than those with PD, regarding increased voice pitch, prolonged pause time, and reduced speech rate. This might be due to widespread pathology of MSA-P in nigrostriatal or extra-striatal structures related to speech production. Although several perceptual measures were mildly impaired in MSA-P and PD patients, none of these parameters showed a significant difference between patient groups. Detailed speech analysis using acoustic measures may help distinguish between MSA-P and PD early in the disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

Lack of early pattern stimulation prevents normal development of the alpha (Y) retinal ganglion cell population in the cat.

PubMed

Burnat, Kalina; Van Der Gucht, Estelle; Waleszczyk, Wioletta J; Kossut, Malgorzata; Arckens, Lutgarde

2012-08-01

Binocular deprivation of pattern vision (BD) early in life permanently impairs global motion perception. With the SMI-32 antibody against neurofilament protein (NFP) as a marker of the motion-sensitive Y-cell pathway (Van der Gucht et al. [2001] Cereb. Cortex 17:2805-2819), we analyzed the impact of early BD on the retinal circuitry in adult, perceptually characterized cats (Burnat et al. [2005] Neuroreport 16:751-754). In controls, large retinal ganglion cells exhibited a strong NFP signal in the soma and in the proximal parts of the dendritic arbors. The NFP-immunoreactive dendrites typically branched into sublamina a of the inner plexiform layer (IPL), i.e., the OFF inner plexiform sublamina. In the retina of adult BD cats, however, most of the NFP-immunoreactive ganglion cell dendrites branched throughout the entire IPL. The NFP-immunoreactive cell bodies were less regularly distributed, often appeared in pairs, and had a significantly larger diameter compared with NFP-expressing cells in control retinas. These remarkable differences in the immunoreactivity pattern were typically observed in temporal retina. In conclusion, we show that the anatomical organization typical of premature Y-type retinal ganglion cells persists into adulthood even if normal visual experience follows for years upon an initial 6-month period of BD. Binocular pattern deprivation possibly induces a lifelong OFF functional domination, normally apparent only during development, putting early high-quality vision forward as a premise for proper ON-OFF pathway segregation. These new observations for pattern-deprived animals provide an anatomical basis for the well-described motion perception deficits in congenital cataract patients. Copyright © 2012 Wiley Periodicals, Inc.

Enhanced dispersion of repolarization explains increased arrhythmogenesis in severe versus therapeutic hypothermia.

PubMed

Piktel, Joseph S; Jeyaraj, Darwin; Said, Tamer H; Rosenbaum, David S; Wilson, Lance D

2011-02-01

Hypothermia is proarrhythmic, and, as the use of therapeutic hypothermia (TH) increases, it is critically important to understand the electrophysiological effects of hypothermia on cardiac myocytes and arrhythmia substrates. We tested the hypothesis that hypothermia-enhanced transmural dispersion of repolarization (DOR) is a mechanism of arrhythmogenesis in hypothermia. In addition, we investigated whether the degree of hypothermia, the rate of temperature change, and cooling versus rewarming would alter hypothermia-induced arrhythmia substrates. Optical action potentials were recorded from cells spanning the transmural wall of canine left ventricular wedge preparations at baseline (36°C), during cooling and during rewarming. Electrophysiological parameters were examined while varying the depth of hypothermia. On cooling to 26°C, DOR increased from 26±4 ms to 93±18 ms (P=0.021); conduction velocity decreased from 35±5 cm/s to 22±5 cm/s (P=0.010). On rewarming to 36°C, DOR remained prolonged, whereas conduction velocity returned to baseline. Conduction block and reentry was observed in all severe hypothermia preparations. Ventricular fibrillation/ventricular tachycardia was seen more during rewarming (4/5) versus cooling (2/6). In TH (n=7), cooling to 32°C mildly increased DOR (31±6 to 50±9, P=0.012), with return to baseline on rewarming and was associated with decreased arrhythmia susceptibility. Increased rate of cooling did not further enhance DOR or arrhythmogenesis. Hypothermia amplifies DOR and is a mechanism for arrhythmogenesis. DOR is directly dependent on the depth of cooling and rewarming. This provides insight into the clinical observation of a low incidence of arrhythmias in TH and has implications for protocols for the clinical application of TH.

Zif268 mRNA Expression Patterns Reveal a Distinct Impact of Early Pattern Vision Deprivation on the Development of Primary Visual Cortical Areas in the Cat.

PubMed

Laskowska-Macios, Karolina; Zapasnik, Monika; Hu, Tjing-Tjing; Kossut, Malgorzata; Arckens, Lutgarde; Burnat, Kalina

2015-10-01

Pattern vision deprivation (BD) can induce permanent deficits in global motion perception. The impact of timing and duration of BD on the maturation of the central and peripheral visual field representations in cat primary visual areas 17 and 18 remains unknown. We compared early BD, from eye opening for 2, 4, or 6 months, with late onset BD, after 2 months of normal vision, using the expression pattern of the visually driven activity reporter gene zif268 as readout. Decreasing zif268 mRNA levels between months 2 and 4 characterized the normal maturation of the (supra)granular layers of the central and peripheral visual field representations in areas 17 and 18. In general, all BD conditions had higher than normal zif268 levels. In area 17, early BD induced a delayed decrease, beginning later in peripheral than in central area 17. In contrast, the decrease occurred between months 2 and 4 throughout area 18. Lack of pattern vision stimulation during the first 4 months of life therefore has a different impact on the development of areas 17 and 18. A high zif268 expression level at a time when normal vision is restored seems to predict the capacity of a visual area to compensate for BD. © The Author 2014. Published by Oxford University Press.

Ventricular Repolarization Adaptation to Abrupt Changes in Heart Rate after Microgravity Simulation by 5-Day Head-Down Bed Rest

NASA Astrophysics Data System (ADS)

Bolea, J.; Almeida, R.; Pueyo, E.; Laguna, P.; Caiani, E. G.

2013-02-01

Microgravity exposure for long periods of time leads to body deconditioning and it increases the risk of experiencing life-threatening arrhythmias. The study of ventricular repolarization dependence on heart rate has been used to stratify patients according to their arrhythmic risk. The QTp adaptation to HR changes is characterized by M90 (90% of the adaptation). The QTp=HR , after compensation for the adaptation lag, is modeled using a set of regression functions (a , kind of slope of relationship). Subjects with lower orthostatic tolerance time showed a non significant decrease in the adaptation lag (M90 from 148 to 108 beats), which may be due to an extra deconditioning in the sympathovagal response. Nevertheless an increase in the QTp=HR adaptation lag (M90 from 108 to 117 beats with a p = 0.06) and a significant reduction in the slope (a from 0.53 to 0.35 with a p < 0.005), which in previous studies have been correlated with an increased arrhytimic risk, were observed for subjects with higher orthostatic tolerance time.

Is It a Pattern?

ERIC Educational Resources Information Center

McGarvey, Lynn M.

2013-01-01

This article describes how in early mathematics learning, young children are often asked to recognize and describe visual patterns in their environment--perhaps on their clothing, a toy, or the carpet; around a picture frame; or in the playground equipment. Exploring patterns in the early years is seen as an important introduction to algebraic…

Comparison of microbial pattern in early and late onset neonatal sepsis in referral center Haji Adam Malik hospital Medan Indonesia

NASA Astrophysics Data System (ADS)

Hasibuan, B. S.

2018-03-01

Neonatal sepsis contributes a significant rate of infants mortality and morbidity. The pathogens are diverse from region to another and change time to time even in the same place. To analyze the microbial pattern in early and late onset neonatal sepsis andthe pattern of antibiotic resistance of the causative microbes at one of referral center hospital in Indonesia, Haji Adam Malik Hospital, a cross-sectional descriptive study was conducted on neonates with sepsis diagnosis proven with positive blood culture within one year period (2015-2016). Among 626 neonates admitted to perinatology unit, the total of 154 neonates was proven to have neonatal sepsis with positive blood culture with the incidence rate 24.6%. Seventy-nine (51.3%) neonates were diagnosed with early onset sepsis while 75 (48,7%) neonates had late-onset sepsis. Klebsiella pneumonia was the most commonly isolated organism in both early and late onset sepsis, encompassing 19.5% of cases. Periodic surveillance of the causative agents of neonatal sepsis is needed to implement the rational, empirical choice of antibiotic prescription while waiting for blood culture result to come out.

Rationale, objectives, and design of the EUTrigTreat clinical study: a prospective observational study for arrhythmia risk stratification and assessment of interrelationships among repolarization markers and genotype

PubMed Central

Seegers, Joachim; Vos, Marc A.; Flevari, Panagiota; Willems, Rik; Sohns, Christian; Vollmann, Dirk; Lüthje, Lars; Kremastinos, Dimitrios T.; Floré, Vincent; Meine, Mathias; Tuinenburg, Anton; Myles, Rachel C.; Simon, Dirk; Brockmöller, Jürgen; Friede, Tim; Hasenfuß, Gerd; Lehnart, Stephan E.; Zabel, Markus

2012-01-01

Aims The EUTrigTreat clinical study has been designed as a prospective multicentre observational study and aims to (i) risk stratify patients with an implantable cardioverter defibrillator (ICD) for mortality and shock risk using multiple novel and established risk markers, (ii) explore a link between repolarization biomarkers and genetics of ion (Ca2+, Na+, K+) metabolism, (iii) compare the results of invasive and non-invasive electrophysiological (EP) testing, (iv) assess changes of non-invasive risk stratification tests over time, and (v) associate arrythmogenomic risk through 19 candidate genes. Methods and results Patients with clinical ICD indication are eligible for the trial. Upon inclusion, patients will undergo non-invasive risk stratification, including beat-to-beat variability of repolarization (BVR), T-wave alternans, T-wave morphology variables, ambient arrhythmias from Holter, heart rate variability, and heart rate turbulence. Non-invasive or invasive programmed electrical stimulation will assess inducibility of ventricular arrhythmias, with the latter including recordings of monophasic action potentials and assessment of restitution properties. Established candidate genes are screened for variants. The primary endpoint is all-cause mortality, while one of the secondary endpoints is ICD shock risk. A mean follow-up of 3.3 years is anticipated. Non-invasive testing will be repeated annually during follow-up. It has been calculated that 700 patients are required to identify risk predictors of the primary endpoint, with a possible increase to 1000 patients based on interim risk analysis. Conclusion The EUTrigTreat clinical study aims to overcome current shortcomings in sudden cardiac death risk stratification and to answer several related research questions. The initial patient recruitment is expected to be completed in July 2012, and follow-up is expected to end in September 2014. Clinicaltrials.gov identifier: NCT01209494. PMID:22117037

Early In Vitro Differentiation of Mouse Definitive Endoderm Is Not Correlated with Progressive Maturation of Nuclear DNA Methylation Patterns

PubMed Central

Tajbakhsh, Jian; Gertych, Arkadiusz; Fagg, W. Samuel; Hatada, Seigo; Fair, Jeffrey H.

2011-01-01

The genome organization in pluripotent cells undergoing the first steps of differentiation is highly relevant to the reprogramming process in differentiation. Considering this fact, chromatin texture patterns that identify cells at the very early stage of lineage commitment could serve as valuable tools in the selection of optimal cell phenotypes for regenerative medicine applications. Here we report on the first-time use of high-resolution three-dimensional fluorescence imaging and comprehensive topological cell-by-cell analyses with a novel image-cytometrical approach towards the identification of in situ global nuclear DNA methylation patterns in early endodermal differentiation of mouse ES cells (up to day 6), and the correlations of these patterns with a set of putative markers for pluripotency and endodermal commitment, and the epithelial and mesenchymal character of cells. Utilizing this in vitro cell system as a model for assessing the relationship between differentiation and nuclear DNA methylation patterns, we found that differentiating cell populations display an increasing number of cells with a gain in DNA methylation load: first within their euchromatin, then extending into heterochromatic areas of the nucleus, which also results in significant changes of methylcytosine/global DNA codistribution patterns. We were also able to co-visualize and quantify the concomitant stochastic marker expression on a per-cell basis, for which we did not measure any correlation to methylcytosine loads or distribution patterns. We observe that the progression of global DNA methylation is not correlated with the standard transcription factors associated with endodermal development. Further studies are needed to determine whether the progression of global methylation could represent a useful signature of cellular differentiation. This concept of tracking epigenetic progression may prove useful in the selection of cell phenotypes for future regenerative medicine

Archaeogeophysical investigations of early Caddo settlement patterning at the Crenshaw site (3MI6)

NASA Astrophysics Data System (ADS)

Samuelsen, John R.

The Teran map, made during Don Domingo Teran de los Rios' expedition for New Spain, shows a Caddo settlement in 1691 with a vacant mound center and many small farmsteads dispersed across the countryside along both banks of the Red River. This map, combined with the 19th Century photographs taken by William Soule, provides a testable model for the settlement pattern of the Caddo people called the Teran-Soule model. This model states that large numbers of people besides a small caretaker population did not inhabit the mound centers, supporting a vacant mound center hypothesis. Recent studies have begun to challenge this hypothesis, using archaeogeophysical techniques to find structures near Middle to Late Caddo mounds. An archaeogeophysical survey of the Crenshaw site along the Great Bend of the Red River was conducted to determine if structures could be found there. Is the settlement pattern at this early Caddo site, occupied between A.D. 700 and 1400, consistent with the late historic model of a vacant mound center? Is there evidence that both Caddo and Fourche Maline occupations existed in horizontally distinct components? The 3.2 hectare survey identified more than 100 possible structures, of which more than 50 are probably structures associated with the Fourche Maline or early Caddo occupations of the site. Several structures were found in linear patterns, including an oval series of possible structures measuring 90 x 85 m in diameter. While cultural affiliation was not determined for most of these features, some can be attributed to Caddo origin based on architectural attributes, such as extended entranceways. This suggests that Crenshaw was not literally vacant, but the presence of extended entranceways suggests that some of the identified features were special use structures, which does not conflict with the vacant mound center hypothesis. However, the large number of possible structures present with unknown cultural affiliations provides ample opportunities

Lifestyle patterns in early pregnancy linked to gestational diabetes mellitus diagnoses when using IADPSG criteria. The St Carlos gestational study.

PubMed

Ruiz-Gracia, Teresa; Duran, Alejandra; Fuentes, Manuel; Rubio, Miguel A; Runkle, Isabelle; Carrera, Evelyn F; Torrejón, María J; Bordiú, Elena; Valle, Laura Del; García de la Torre, Nuria; Bedia, Ana R; Montañez, Carmen; Familiar, Cristina; Calle-Pascual, Alfonso L

2016-06-01

Early-pregnancy lifestyle (EPL) could influence the development of gestational diabetes mellitus(GDM), depending on the diagnostic criteria used. We studied EPL in 1750 pregnant women using Carpenter-Coustan criteria(CCc), and in 1526 with the International Association of Diabetes and Pregnancy Study Groups criteria(IADPSGc). GDM risk factors were assessed in women between 24 and 28 weeks of gestational age during two consecutive years. A semiquantitative frequent-food-consumption questionnaire was used to evaluate lifestyle during pregnancy. Multiple logistic regression analysis was conducted to assess GDM risk with different lifestyle patterns. Using IADPSGc, the GDM ORs (95%CI) for intake/week were: nuts >3 times: 0.59 (0.39-0.91; p < 0.015), refined cereals ≤1 serving: 0.72(0.58-0.89; p < 0.003), juices <4 servings: 0.77 (0.62-0.95; p < 0.017), cookies and pastries <4 servings: 0.71(0.57-0.89; p < 0.003) as compared to opposite habits. No significant nutritional patterns were found to be significant using CCc. The OR (95%CI) for GDM with none of the four risk patterns as compared to having three-four risk factors was 0.21(0.07-0.62; p < 0.005), remaining significant after stratification by BMI, age, obstetric events, parity and family history. The multiple logistic regression model including nutritional categories and pregestational BMI, age, obstetric history, parity, personal/family history, had an area under the curve(AUC) of the receiver operating curve(ROC) for the probability to predict GDM of 0.66 (CI 95%: 0.63-0.69; p < 0.001). Our study is the first to identify four early-pregnancy nutritional patterns associated with the GDM when using IADPSGc. Adherence to a low-risk nutritional pattern from early pregnancy on could be an effective strategy for GDM prevention. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Legacy of Pre-Disturbance Spatial Pattern Determines Early Structural Diversity following Severe Disturbance in Montane Spruce Forests

PubMed Central

Bače, Radek; Svoboda, Miroslav; Janda, Pavel; Morrissey, Robert C.; Wild, Jan; Clear, Jennifer L.; Čada, Vojtěch; Donato, Daniel C.

2015-01-01

Background Severe canopy-removing disturbances are native to many temperate forests and radically alter stand structure, but biotic legacies (surviving elements or patterns) can lend continuity to ecosystem function after such events. Poorly understood is the degree to which the structural complexity of an old-growth forest carries over to the next stand. We asked how pre-disturbance spatial pattern acts as a legacy to influence post-disturbance stand structure, and how this legacy influences the structural diversity within the early-seral stand. Methods Two stem-mapped one-hectare forest plots in the Czech Republic experienced a severe bark beetle outbreak, thus providing before-and-after data on spatial patterns in live and dead trees, crown projections, down logs, and herb cover. Results Post-disturbance stands were dominated by an advanced regeneration layer present before the disturbance. Both major species, Norway spruce (Picea abies) and rowan (Sorbus aucuparia), were strongly self-aggregated and also clustered to former canopy trees, pre-disturbance snags, stumps and logs, suggesting positive overstory to understory neighbourhood effects. Thus, although the disturbance dramatically reduced the stand’s height profile with ~100% mortality of the canopy layer, the spatial structure of post-disturbance stands still closely reflected the pre-disturbance structure. The former upper tree layer influenced advanced regeneration through microsite and light limitation. Under formerly dense canopies, regeneration density was high but relatively homogeneous in height; while in former small gaps with greater herb cover, regeneration density was lower but with greater heterogeneity in heights. Conclusion These findings suggest that pre-disturbance spatial patterns of forests can persist through severe canopy-removing disturbance, and determine the spatial structure of the succeeding stand. Such patterns constitute a subtle but key legacy effect, promoting structural

The clinical significance of hyperkalaemia-associated repolarization abnormalities in end-stage renal disease.

PubMed

Green, Darren; Green, Heather D; New, David I; Kalra, Philip A

2013-01-01

Hyperkalaemia is a common potentially fatal complication of chronic kidney disease (CKD). It may manifest as electrocardiogram (ECG) changes, the earliest of which is T-wave 'tenting'. However, this occurs in less than half of episodes of hyperkalaemia. The aim of this study was to determine what other clinical features relate to the probability of T-wave tenting; and if there is a longer-term survival difference between patients who develop tenting and those who do not. One hundred and forty-five patients with end-stage renal disease who had standard 12-lead ECG and concurrent serum potassium measurement were enrolled. The presence of tenting and the ratio of the amplitude of the tallest precordial T-wave and R-wave were determined (T:R). Tenting was as common in normal range serum potassium as hyperkalaemia (33 versus 31%) and less common than in left ventricular hypertrophy (44%). T:R was less sensitive (24 versus 33%) but more specific (85 versus 67%) than tenting at correctly identifying hyperkalaemia ≥ 6.0 mmol/L. Tenting became less common with increasing age. Dialysis patients were more likely to show increased T:R that pre-dialysis Stage 5 CKD. Elevated T:R was not associated with worse cardiovascular outcome but was associated with increased risk of sudden death over a mean follow-up of 3.8 years (hazard ratio = 8.3, P = 0.021). The reason for the variability in T-wave changes is not clear. The ratio of precordial T-wave to R-wave amplitude is a more specific measure than tenting but both are poorly sensitive at detecting hyperkalaemia. The greater risk for sudden death may represent a susceptibility to cardiac arrhythmia during repolarization.

Inverse Correlation between the Atrial Fibrillatory Rate and the Ventricular Repolarization Time: Observations at Baseline and after an Intravenous Infusion of a Combined Potassium and Sodium Current Blocker.

PubMed

Edvardsson, Nils; Aunes, Maria; Frison, Lars; Berggren, Anders R

2016-05-01

The atrial fibrillatory rate (AFR) and the ventricular rate and repolarization (QTcF) were studied at baseline and under the influence of the combined potassium and sodium current blocker AZD7009. Ninety-two patients with atrial fibrillation (AF) were randomized to an intravenous infusion of AZD7009 or placebo. The atrial fibrillatory activity in lead V1 was extracted using spatiotemporal QRST cancellation. The exponential decay (ED) characterized the degree of atrial signal organization. The mean (SD) AFR at baseline was 396  ±  57 (range 253-584) and 410 ± 33 (range 363-469) bpm in patients randomized to AZD7009 and placebo, respectively. The AFR decreased within the first minutes of the AZD7009 infusion and reached its minimum of 235 ± 34 bpm after 18 minutes. On placebo, the AFR was unchanged. On AZD7009, the ED decreased from 1.2 ± 0.3 to reach its lowest level at 0.7 ± 0.2 after 14 minutes. The ventricular rate did not change significantly over time. The AFR was statistically significantly related to the ventricular repolarization at baseline, the QTcF being longer at lower AFR values, and this relationship remained during and after AZD7009. In the full multivariate linear regression model, including age, sex, left ventricular ejection fraction, QRS duration, heart rate, QTcF, AF episode duration, AF history duration, and right atrial or left atrial size, only QTcF and age were statistically significantly correlated with the AFR. The correlation remained when the uncorrected QT interval was used. The QTcF was inversely correlated with AFR, both at baseline and during administration of AZD7009. The AFR was not correlated with the ventricular rate. © 2015 Wiley Periodicals, Inc.

Dietary patterns in early childhood and child cognitive and psychomotor development: the Rhea mother-child cohort study in Crete.

PubMed

Leventakou, Vasiliki; Roumeliotaki, Theano; Sarri, Katerina; Koutra, Katerina; Kampouri, Mariza; Kyriklaki, Andriani; Vassilaki, Maria; Kogevinas, Manolis; Chatzi, Leda

2016-04-01

Early-life nutrition is critical for optimal brain development; however, few studies have evaluated the impact of diet as a whole in early childhood on neurological development with inconsistent results. The present analysis is a cross-sectional study nested within an ongoing prospective birth cohort, the Rhea study, and aims to examine the association of dietary patterns with cognitive and psychomotor development in 804 preschool (mean age 4·2 years) children. Parents completed a validated FFQ, and dietary patterns were identified using principal component analysis. Child cognitive and psychomotor development was assessed by the McCarthy Scales of Children's Abilities (MSCA). Multivariable linear regression models were used to investigate the associations of dietary patterns with the MSCA scales. After adjustment for a large number of confounding factors, the 'Snacky' pattern (potatoes and other starchy roots, salty snacks, sugar products and eggs) was negatively associated with the scales of verbal ability (β=-1·31; 95 % CI -2·47, -0·16), general cognitive ability (β=-1·13; 95 % CI -2·25, -0·02) and cognitive functions of the posterior cortex (β=-1·20; 95 % CI -2·34, -0·07). Further adjustment for maternal intelligence, folic acid supplementation and alcohol use during pregnancy attenuated the observed associations, but effect estimates remained at the same direction. The 'Western' and the 'Mediterranean' patterns were not associated with child neurodevelopmental scales. The present findings suggest that poorer food choices at preschool age characterised by foods high in fat, salt and sugar are associated with reduced scores in verbal and cognitive ability.

Maternal Patterns of Marijuana Use and Early Sexual Behavior in Offspring of Teenage Mothers

PubMed Central

Goldschmidt, Lidush; Cornelius, Marie D.

2015-01-01

Teenage mothers use marijuana more frequently than older mothers, and marijuana use may predict HIV risk behavior in offspring. Our goals were to (1) describe trajectories of marijuana use in teenage mothers and (2) determine if these trajectories were associated with early sexual behavior in their offspring. Pregnant adolescents (12–18 years) were recruited at a prenatal clinic and interviewed during pregnancy, at delivery, and during follow-up visits when offspring were 6, 10, 14 and 16 years old. At 16 years, 332 women (71 % Black, 29 % White) and their offspring were assessed. Mothers were asked about their marijuana use at each time point. Offspring reported on their sexual behavior at age 14. Trajectory analyses using growth mixture models revealed four maternal patterns of marijuana use: no use, only at the 6 year follow-up, quit by the 16 year follow-up, and used across most of the time points. The children of chronic users were more likely to have early sex. The maternal marijuana trajectory group variable remained a statistically significant predictor in multivariate models controlling for race, gender, socioeconomic status, child pubertal timing, child externalizing behavior problems, and child marijuana use. These findings suggest that a minority of teenage mothers continue to use marijuana over time. Chronic maternal marijuana use across a decade was associated with early sex in offspring (oral or vaginal sex by age 14). Early sexual behavior places these children at significantly higher risk of teenage pregnancy and HIV risk behaviors. PMID:24942139

Maternal anxiety from pregnancy to 2 years postpartum: transactional patterns of maternal early adversity and child temperament.

PubMed

Agrati, Daniella; Browne, Dillon; Jonas, Wibke; Meaney, Michael; Atkinson, Leslie; Steiner, Meir; Fleming, Alison S

2015-10-01

The aims of this study were to examine the anxiety trajectories of women from pregnancy to 2 years postpartum and to assess the influence of their early life experiences and the temperament of the child on these trajectories. We evaluated state anxiety (State-Trait Anxiety Inventory) at pregnancy and 3, 6, 12, 18, and 24 months postpartum and determined its course as a function of self-reported early adverse experiences (Childhood Trauma Questionnaire) and the temperament of the child at 18 months (Early Child Behavior Questionnaire). Based on growth curve modeling, we found that anxiety followed a general U-shape pattern from gestation to 2 years postpartum, which was modified by early life experience of women. Greater early adversity was associated with higher gestational anxiety, followed by a marked decrease once the baby was born, and subsequent increase during the later postpartum period. The temperament of the child also modulated anxiety trajectories. Thus, mothers of children high in negative affectivity and who also experienced greater early adversity had elevated and flat anxiety trajectories, while child extraversion was associated with increasing anxiety courses approaching 2 years postpartum. These results show that maternal anxiety dynamically changes through the postpartum period with a course that is affected by previous and current experiences.

Rich do not rise early: spatio-temporal patterns in the mobility networks of different socio-economic classes

PubMed Central

Hurtado, Rafael G.; Floría, Luis Mario

2016-01-01

We analyse the urban mobility in the cities of Medellín and Manizales (Colombia). Each city is represented by six mobility networks, each one encoding the origin-destination trips performed by a subset of the population corresponding to a particular socio-economic status. The nodes of each network are the different urban locations whereas links account for the existence of a trip between two different areas of the city. We study the main structural properties of these mobility networks by focusing on their spatio-temporal patterns. Our goal is to relate these patterns with the partition into six socio-economic compartments of these two societies. Our results show that spatial and temporal patterns vary across these socio-economic groups. In particular, the two datasets show that as wealth increases the early-morning activity is delayed, the midday peak becomes smoother and the spatial distribution of trips becomes more localized. PMID:27853531

Sex and strategy use matters for pattern separation, adult neurogenesis, and immediate early gene expression in the hippocampus.

PubMed

Yagi, Shunya; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

2016-01-01

Adult neurogenesis in the dentate gyrus (DG) plays a crucial role for pattern separation, and there are sex differences in the regulation of neurogenesis. Although sex differences, favoring males, in spatial navigation have been reported, it is not known whether there are sex differences in pattern separation. The current study was designed to determine whether there are sex differences in the ability for separating similar or distinct patterns, learning strategy choice, adult neurogenesis, and immediate early gene (IEG) expression in the DG in response to pattern separation training. Male and female Sprague-Dawley rats received a single injection of the DNA synthesis marker, bromodeoxyuridine (BrdU), and were tested for the ability of separating spatial patterns in a spatial pattern separation version of delayed nonmatching to place task using the eight-arm radial arm maze. Twenty-seven days following BrdU injection, rats received a probe trial to determine whether they were idiothetic or spatial strategy users. We found that male spatial strategy users outperformed female spatial strategy users only when separating similar, but not distinct, patterns. Furthermore, male spatial strategy users had greater neurogenesis in response to pattern separation training than all other groups. Interestingly, neurogenesis was positively correlated with performance on similar pattern trials during pattern separation in female spatial strategy users but negatively correlated with performance in male idiothetic strategy users. These results suggest that the survival of new neurons may play an important positive role for pattern separation of similar patterns in females. Furthermore, we found sex and strategy differences in IEG expression in the CA1 and CA3 regions in response to pattern separation. These findings emphasize the importance of studying biological sex on hippocampal function and neural plasticity. © 2015 Wiley Periodicals, Inc.

Early Diet and Later Cancer Risk: Prospective Associations of Dietary Patterns During Critical Periods of Childhood with the GH-IGF Axis, Insulin Resistance and Body Fatness in Younger Adulthood.

PubMed

Günther, Anke L B; Schulze, Matthias B; Kroke, Anja; Diethelm, Katharina; Joslowski, Gesa; Krupp, Danika; Wudy, Stefan; Buyken, Anette E

2015-01-01

Early life, adiposity rebound, and puberty represent critical growth periods when food choices could have long-term relevance for cancer risk. We aimed to relate dietary patterns during these periods to the growth hormone-insulin-like-growth-factor (GH-IGF) axis, insulin resistance, and body fatness in adulthood. Data from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study participants with outcome data at 18-37 years, and ≥2 dietary records during early life (1-2 yr; n = 128), adiposity rebound (4-6 years, n = 179), or puberty (girls 9-14, boys 10-15 yr; n = 213) were used. Dietary patterns at these ages were derived by 1) reduced rank regression (RRR) to explain variation in adult IGF-I, IGF-binding protein-3 (IGFBP-3), homoeostasis model assessment for insulin resistance (HOMA-IR) and fat-mass index; 2) principal component analysis (PCA). Regarding RRR, the patterns "cake/canned fruit/cheese & eggs" (early life), "sweets & dairy" (adiposity rebound) and "high-fat foods" (pubertal boys) were independently associated with higher adult HOMA-IR. Furthermore, the patterns "favorable carbohydrate sources" (early life), "snack & convenience foods" (adiposity rebound), and "traditional & convenience carbohydrates" (pubertal boys) were related to adult IGFBP-3 (P trend < 0.01). PCA identified "healthy" patterns for all periods, but none was associated with the outcomes (P trend > 0.1). In conclusion, dietary patterns during sensitive growth periods may be of long-term relevance for adult insulin resistance and IGFBP-3.

Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current.

PubMed

Geelen, P; Drolet, B; Rail, J; Bérubé, J; Daleau, P; Rousseau, G; Cardinal, R; O'Hara, G E; Turgeon, J

2000-07-18

BACKGROUND-Several cases of unexpected death have been reported with sildenafil in patients predisposed to ischemic cardiac events. Although acute episodes of ischemia could account for some of these deaths, we hypothesized that sildenafil may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia. METHODS AND RESULTS-Studies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 mcmol/L. Action potential duration increased 15% from baseline 117+/-3 to 134+/-2 ms with sildenafil during pacing at 250 ms cycle length, whereas a 6% increase from 99+/-2 to 105+/-2 ms was seen with pacing at 150 ms cycle length. Experiments in human ether-a-go-go-related gene (HERG)-transfected HEK293 cells (n=30) demonstrated concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current: activating current was 50% decreased at 100 mcmol/L. This effect was confirmed using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no endogenous I(K)-like current. CONCLUSIONS-Sildenafil possesses direct cardiac electrophysiological effects similar to class III antiarrhythmic drugs. These effects are observed at concentrations that may be found in conditions of impaired drug elimination such as renal or hepatic insufficiency, during coadministration of another CYP3A substrate/inhibitor, or after drug overdose and offer a new potential explanation for sudden death during sildenafil treatment.

Patterns of Organized Activity Participation in Urban, Early Adolescents: Associations with Academic Achievement, Problem Behaviors, and Perceived Adult Support

ERIC Educational Resources Information Center

Metzger, Aaron; Crean, Hugh F.; Forbes-Jones, Emma L.

2009-01-01

This study examines patterns of organized activity and their concurrent association with academic achievement, problem behavior, and perceived adult support in a sample of urban, early adolescent, middle school students (mean age = 13.01; N = 2,495). Cluster analyses yielded six activity profiles: an uninvolved group (n = 775, 31.1%), a multiply…

A prospective cohort study among new Chinese coal miners: the early pattern of lung function change.

PubMed

Wang, M-L; Wu, Z-E; Du, Q-G; Petsonk, E L; Peng, K-L; Li, Y-D; Li, S-K; Han, G-H; Atffield, M D

2005-11-01

To investigate the early pattern of longitudinal change in forced expiratory volume in 1 second (FEV1) among new Chinese coal miners, and the relation between coal mine dust exposure and the decline of lung function. The early pattern of lung function changes in 317 newly hired Chinese underground coal miners was compared to 132 referents. This three year prospective cohort study involved a pre-employment and 15 follow up health surveys, including a questionnaire and spirometry tests. Twice a month, total and respirable dust area sampling was done. The authors used a two stage analysis and a linear mixed effects model approach to analyse the longitudinal spirometry data, and to investigate the changes in FEV1 over time, controlling for age, height, pack years of smoking, mean respirable dust concentration, the room temperature during testing, and the groupxtime interaction terms. FEV1 change over time in new miners is non-linear. New miners experience initial rapid FEV1 declines, primarily during the first year of mining, little change during the second year, and partial recovery during the third year. Both linear and quadratic time trends in FEV1 change are highly significant. Smoking miners lost more FEV1 than non-smokers. Referents, all age less than 20 years, showed continued lung growth, whereas the miners who were under age 20 exhibited a decline in FEV1. Dust and smoking affect lung function in young, newly hired Chinese coal miners. FEV1 change over the first three years of employment is non-linear. The findings have implications for both methods and interpretation of medical screening in coal mining and other dusty work: during the first several years of employment more frequent testing may be desirable, and caution is required in interpreting early FEV1 declines.

Brugada syndrome: diagnosis, risk stratification, and management.

PubMed

Adler, Arnon

2016-01-01

Asymptomatic patients with Brugada syndrome (BrS) have a small, but not trivial, risk of cardiac events. Their risk stratification and its impact on their management are controversial. The review focuses on the clinical aspects of BrS with special emphasis on the asymptomatic patient. Emerging data suggest that drug and fever-induced type I Brugada patterns are more common than previously appreciated. Although preliminary, these data may imply that asymptomatic patients with induced Brugada pattern are at an even lower risk than currently estimated.The latest data regarding induced ventricular arrhythmias during electrophysiological studies support its use as an indication for an implantable cardioverter defibrillator; however, this issue remains highly controversial.Several new risk markers, such as presence of the Brugada pattern in infero-lateral leads or the concomitant finding of an early repolarization pattern, have recently been proposed. Most asymptomatic BrS patients are at low risk of cardiac events. The presence of new risk markers in this population may prompt consideration of primary prevention measures; however, data supporting this approach are still limited.

Partnership Patterns: Addressing Emotional Needs in Early Intervention

ERIC Educational Resources Information Center

Brotherson, Mary Jane; Summers, Jean Ann; Naig, Lisa A.; Kyzar, Kathleen; Friend, Anna; Epley, Pamela; Gotto, George S., IV; Turnbull, Ann P.

2010-01-01

Home visiting in early intervention is the primary model for delivering services and building partnerships with children and families. Using interviews with early interventionists and family members, this study investigated the extent to which families' and professionals' emotional needs were met during home visits and what factors contributed to…

Entropy of cardiac repolarization predicts ventricular arrhythmias and mortality in patients receiving an implantable cardioverter-defibrillator for primary prevention of sudden death.

PubMed

DeMazumder, Deeptankar; Limpitikul, Worawan B; Dorante, Miguel; Dey, Swati; Mukhopadhyay, Bhasha; Zhang, Yiyi; Moorman, J Randall; Cheng, Alan; Berger, Ronald D; Guallar, Eliseo; Jones, Steven R; Tomaselli, Gordon F

2016-12-01

The need for a readily available, inexpensive, non-invasive method for improved risk stratification of heart failure (HF) patients is paramount. Prior studies have proposed that distinct fluctuation patterns underlying the variability of physiological signals have unique prognostic value. We tested this hypothesis in an extensively phenotyped cohort of HF patients using EntropyX QT , a novel non-linear measure of cardiac repolarization dynamics. In a prospective, multicentre, observational study of 852 patients in sinus rhythm undergoing clinically indicated primary prevention implantable cardioverter-defibrillator (ICD) implantation (2003-10), exposures included demographics, history, physical examination, medications, laboratory results, serum biomarkers, ejection fraction, conventional electrocardiographic (ECG) analyses of heart rate and QT variability, and EntropyX QT . The primary outcome was first 'appropriate' ICD shock for ventricular arrhythmias. The secondary outcome was composite events (appropriate ICD shock and all-cause mortality). After exclusions, the cohort (n = 816) had a mean age of 60 ± 13 years, 28% women, 36% African Americans, 56% ischaemic cardiomyopathy, and 29 ± 16% Seattle HF risk score (SHFS) 5-year predicted mortality. Over 45 ± 24 months, there were 134 appropriate shocks and 166 deaths. After adjusting for 30 exposures, the hazard ratios (comparing the 5th to 1st quintile of EntropyX QT ) for primary and secondary outcomes were 3.29 (95% CI 1.74-6.21) and 2.28 (1.53-3.41), respectively. Addition of EntropyX QT to a model comprised of the exposures or SHFS significantly increased net reclassification and the ROC curve area. EntropyX QT measured during ICD implantation strongly and independently predicts appropriate shock and all-cause mortality over follow-up. EntropyX QT complements conventional risk predictors and has the potential for broad clinical application. Published on behalf of the European Society of Cardiology. All

Toxicoproteomics: serum proteomic pattern diagnostics for early detection of drug induced cardiac toxicities and cardioprotection.

PubMed

Petricoin, Emanuel F; Rajapaske, Vinodh; Herman, Eugene H; Arekani, Ali M; Ross, Sally; Johann, Donald; Knapton, Alan; Zhang, J; Hitt, Ben A; Conrads, Thomas P; Veenstra, Timothy D; Liotta, Lance A; Sistare, Frank D

2004-01-01

Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry which communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity based processes as cascades of reinforcing information percolate through the system and become reflected in changing proteomic information content of the circulation. Serum Proteomic Pattern Diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. While this approach has shown tremendous promise in early detection of cancers, detection of drug-induced toxicity may also be possible with this same technology. Analysis of serum from rat models of anthracycline and anthracenedione induced cardiotoxicity indicate the potential clinical utility of diagnostic proteomic patterns where low molecular weight peptides and protein fragments may have higher accuracy than traditional biomarkers of cardiotoxicity such as troponins. These fragments may one day be harvested by circulating nanoparticles designed to absorb, enrich and amplify the diagnostic biomarker repertoire generated even at the critical initial stages of toxicity.

Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias

ClinicalTrials.gov

2017-08-10

Inherited Cardiac Arrythmias; Long QT Syndrome (LQTS); Brugada Syndrome (BrS); Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT); Early Repolarization Syndrome (ERS); Arrhythmogenic Cardiomyopathy (AC, ARVD/C); Hypertrophic Cardiomyopathy (HCM); Dilated Cardiomyopathy (DCM); Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy); Normal Control Subjects

[Early total care pattern for intertrochanteric fracture of femur in the elderly].

PubMed

Gu, Jie; Kang, Xin-yong; Xu, Hong-wei; Li, Yong-fu; Zahng, Bin; Guo, Jian; He, Zhen-nian

2016-06-01

To evaluate clinical results of early total care (ETC) treatment for elderly patients with intertrochanteric femur fractures. Clinical data of 106 elderly patients with intertrochanteric fracture treated from January 2012 and February 2015 were retrospectively studied. According to whether receiving the early total care mode, the patients were divided into 2 groups, 34 cases were diagnosed and treated with early total care pattern (ETC group), including 14 males and 20 females with an average age of (74.88 ± 4.38) years old ranging from 70 to 86. According to Evans types, 4 cases were type I, 5 cases were type II, 13 cases were type III, 11 cases were type IV, 1 case was type V. Seventy-two patients were treated with conventional trauma method (conventional group), including 35 males and 37 females with an average age of (74.46 ± 3.63) years old ranging from 70 to 85. According to Evans type, 8 cases were type I ,13 cases were type II, 25 cases were type III, 25 cases were type IV, and 1 case was type V. All fractures were treated with proximal femoral nails anti-rotation (PFNA). Operative time, hospital stays, leaving bed time, complications, cases of death at 1 year after operation, postoperative Harris score at 12 months were observed and compared. All patients were followed up, the time of ETC group ranged from 9 to 18 months with an average of 13.29 ± 1.51, and the time in conventional group ranged from 12 to 16 months with an average 12.93 ± 1.15, while there was no significant difference between two groups in time of following-up (t = 1.368, P = 0.174). There was no significant meaning in cases of death between ETC group (2 cases) and conventional group (8 cases). Three cases occurred complications in ETC group, and 20 cases in conventional group,there was obvious meaning between two groups (χ² = 0.739, P = 0.318). Operative time,hospital stays,leaving bed time in ETC group respectively was (2.03 ± 0.67) d, (15.41 ± 2.87) d and (3.62 ± 0.74) d

Cross-Modal Multivariate Pattern Analysis

PubMed Central

Meyer, Kaspar; Kaplan, Jonas T.

2011-01-01

Multivariate pattern analysis (MVPA) is an increasingly popular method of analyzing functional magnetic resonance imaging (fMRI) data1-4. Typically, the method is used to identify a subject's perceptual experience from neural activity in certain regions of the brain. For instance, it has been employed to predict the orientation of visual gratings a subject perceives from activity in early visual cortices5 or, analogously, the content of speech from activity in early auditory cortices6. Here, we present an extension of the classical MVPA paradigm, according to which perceptual stimuli are not predicted within, but across sensory systems. Specifically, the method we describe addresses the question of whether stimuli that evoke memory associations in modalities other than the one through which they are presented induce content-specific activity patterns in the sensory cortices of those other modalities. For instance, seeing a muted video clip of a glass vase shattering on the ground automatically triggers in most observers an auditory image of the associated sound; is the experience of this image in the "mind's ear" correlated with a specific neural activity pattern in early auditory cortices? Furthermore, is this activity pattern distinct from the pattern that could be observed if the subject were, instead, watching a video clip of a howling dog? In two previous studies7,8, we were able to predict sound- and touch-implying video clips based on neural activity in early auditory and somatosensory cortices, respectively. Our results are in line with a neuroarchitectural framework proposed by Damasio9,10, according to which the experience of mental images that are based on memories - such as hearing the shattering sound of a vase in the "mind's ear" upon seeing the corresponding video clip - is supported by the re-construction of content-specific neural activity patterns in early sensory cortices. PMID:22105246

Patterns of Early and Delayed Visual Response to Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration.

PubMed

Stoller, Glenn L; Kokame, Gregg T; Dreyer, Richard F; Shapiro, Howard; Tuomi, Lisa L

2016-05-12

Understanding the range of temporal responses to ranibizumab is critical for the assessment of individualized treatment regimens for neovascular age-related macular degeneration. To examine patterns of visual and anatomical response to ranibizumab treatment. This study is a retrospective subanalysis of HARBOR (a phase 3, double-masked, multicenter, randomized, active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg ranibizumab administered monthly or on an as-needed basis (PRN) in patients with subfoveal neovascular age-related macular degeneration). A total of 1097 patients with neovascular age-related macular degeneration were randomized to intravitreal ranibizumab, 0.5 or 2.0 mg, administered monthly or as needed (PRN) with monthly monitoring. Of the 1097 patients, 1057 were included in the analysis for early responders (best-corrected visual acuity [BCVA] obtained at baseline and month 3), and 988 patients were included in the analysis for delayed responders (BCVA obtained at baseline, month 3, and month 12). The HARBOR study began July 7, 2009, with the primary 12-month end point completed on August 5, 2011, ongoing to 24 months. Data analysis for the subgroup was performed from January 4, 2013, through December 17, 2015. Patients were categorized based on BCVA outcomes as early 15-letter responders (gained ≥15 letters from baseline at month 3) or delayed 15-letter responders (did not gain ≥15 letters from baseline at month 3 but did so at month 12). Changes from baseline in BCVA and central foveal thickness (CFT). In total, 266 early and 135 delayed 15-letter responders were identified. In the 0.5-mg monthly, 0.5-mg PRN, 2.0-mg monthly, and 2.0-mg PRN treatment groups, 63 (24.0%) of 263, 65 (24.6%) of 264, 68 (25.7%) of 265, and 70 (26.4%) of 265 patients were early responders, respectively, and 40 (16.3%) of 246, 31 (12.6%) of 247, 35 (14.1%) of 248, and 29 (11.7%) of 247 patients were delayed responders, respectively. By month

Tissue distribution and early developmental expression patterns of aldolase A, B, and C in grass carp Ctenopharyngodon idellus.

PubMed

Fan, J J; Bai, J J; Ma, D M; Yu, L Y; Jiang, P

2017-09-27

Aldolase is a key enzyme involved in glycolysis, gluconeogenesis, and the pentose phosphate pathway. To establish the expression patterns of all three aldolase isozyme genes in different tissues and during early embryogenesis in lower vertebrates, as well as to explore the functional differences between these three isozymes, the grass carp was selected as a model owing to its relatively high glucose-metabolizing capability. Based on the cDNA sequences of the aldolase A, B, and C genes, the expression patterns of these three isozymes were analyzed in different tissues and during early embryogenesis using quantitative real-time polymerase chain reaction (qRT-PCR). Sequence analysis of cDNAs indicated that aldolase A, B, and C (GenBank accession numbers: KM192250, KM192251, and KM192252) consist of 364, 364, and 363 amino acids, respectively. The qRT-PCR results showed that the expression levels of aldolase A, B, and C were highest in the muscle, liver, and brain, respectively. Aldolase A and C exhibited similar expression patterns during embryogenesis, with high levels observed in unfertilized and fertilized eggs and at the blastocyst stage, followed by a decline and then increase after organogenesis. In contrast, aldolase B transcript was not detected during the unfertilized egg stage, and appeared only from gastrulation; the expression increased markedly during the feeding period (72 h after hatching), at which point the level was higher than those of aldolase A and C. These data suggest that the glucose content of grass carp starter feed should be adjusted according to the metabolic activity of aldolase B.

Irregular oscillatory patterns in the early-time region of coherent phonon generation in silicon

NASA Astrophysics Data System (ADS)

Watanabe, Yohei; Hino, Ken-ichi; Hase, Muneaki; Maeshima, Nobuya

2017-09-01

Coherent phonon (CP) generation in an undoped Si crystal is theoretically investigated to shed light on unexplored quantum-mechanical effects in the early-time region immediately after the irradiation of ultrashort laser pulses. We examine time signals attributed to an induced charge density of an ionic core, placing the focus on the effects of the Rabi frequency Ω0 c v on the signals; this frequency corresponds to the peak electric-field of the pulse. It is found that at specific Ω0 c v's, where the energy of plasmon caused by photoexcited carriers coincides with the longitudinal-optical phonon energy, the energetically resonant interaction between these two modes leads to striking anticrossings, revealing irregular oscillations with anomalously enhanced amplitudes in the observed time signals. Also, the oscillatory pattern is subject to the Rabi flopping of the excited carrier density that is controlled by Ω0 c v. These findings show that the early-time region is enriched with quantum-mechanical effects inherent in the CP generation, though experimental signals are more or less masked by the so-called coherent artifact due to nonlinear optical effects.

Practice Patterns and Long-Term Survival for Early-Stage Rectal Cancer

PubMed Central

Stitzenberg, Karyn B.; Sanoff, Hanna K.; Penn, Dolly C.; Meyers, Michael O.; Tepper, Joel E.

2013-01-01

Purpose Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. Methods All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. Results LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Conclusion Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE. PMID:24166526

Practice patterns and long-term survival for early-stage rectal cancer.

PubMed

Stitzenberg, Karyn B; Sanoff, Hanna K; Penn, Dolly C; Meyers, Michael O; Tepper, Joel E

2013-12-01

Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

Opposite patterns of hemisphere dominance for early auditory processing of lexical tones and consonants

PubMed Central

Luo, Hao; Ni, Jing-Tian; Li, Zhi-Hao; Li, Xiao-Ou; Zhang, Da-Ren; Zeng, Fan-Gang; Chen, Lin

2006-01-01

In tonal languages such as Mandarin Chinese, a lexical tone carries semantic information and is preferentially processed in the left brain hemisphere of native speakers as revealed by the functional MRI or positron emission tomography studies, which likely measure the temporally aggregated neural events including those at an attentive stage of auditory processing. Here, we demonstrate that early auditory processing of a lexical tone at a preattentive stage is actually lateralized to the right hemisphere. We frequently presented to native Mandarin Chinese speakers a meaningful auditory word with a consonant-vowel structure and infrequently varied either its lexical tone or initial consonant using an odd-ball paradigm to create a contrast resulting in a change in word meaning. The lexical tone contrast evoked a stronger preattentive response, as revealed by whole-head electric recordings of the mismatch negativity, in the right hemisphere than in the left hemisphere, whereas the consonant contrast produced an opposite pattern. Given the distinct acoustic features between a lexical tone and a consonant, this opposite lateralization pattern suggests the dependence of hemisphere dominance mainly on acoustic cues before speech input is mapped into a semantic representation in the processing stream. PMID:17159136

Responses of landscape pattern of China's two largest freshwater lakes to early dry season after the impoundment of Three-Gorges Dam

NASA Astrophysics Data System (ADS)

Wu, Haipeng; Zeng, Guangming; Liang, Jie; Chen, Jin; Xu, Jijun; Dai, Juan; Sang, Lianhai; Li, Xiaodong; Ye, Shujing

2017-04-01

The effects of hydrologic cycle change (caused by human activity and global climate change) on ecosystems attract the increasing attention around the world. As a result of impounding of the Three Gorges Dam (TGD), climate change and sand mining, the dry season of Poyang Lake and Dongting Lake (China's two largest freshwater lakes) came early after the TGD impoundment. It was the primary cause of the increasing need for sluice/dam construction to store water in the Lakes and attracted increasing attention. In this paper, we compared the landscape pattern between three hydrologic years with early dry season (EY) and three normal hydrologic years (NY) of each lake by remote sensing technology, to reveal the effect of early dry season on landscape pattern. The results showed that early dry season caused expanding of Phalaris to mudflat zone in Poyang Lake, while caused expanding of Carex to Phalaris zone and expanding of Phalaris to mudflat zone in Dongting Lake. In landscape level, there was no significant difference in landscape grain size, landscape grain shape, habitat connectivity and landscape diversity between EY and NY in the two lakes. While in habitat class level, there were significant changes in area of mudflat and Phalaris and grain size of mudflat in Poyang Lake, and in area of Carex, grain size of Phalaris and grain shape of Carex and Phalaris in Dongting Lake. These changes will impact migrating birds of East Asian and migratory fishes of Yangtze River.

Early headgear effect on the eruption pattern of maxillary second molars.

PubMed

Abed, Yossi; Brin, Ilana

2010-07-01

To test the hypothesis that the use of a combination headgear (HG) during the first phase of orthodontic treatment has no effect on the eruption pattern of the maxillary second permanent molars. The records of the patients in a two-phase randomized clinical trial of early Class II treatment were utilized. The HG group comprised 47 patients, and the control (CON) group comprised 52 patients. The mean age of both groups was 9.4 years at the beginning of the clinical trial (T1). Cephalograms and panoramic views obtained at T1 and at the end of 15 months of phase I treatment or observation (T2) were utilized. The vertical and horizontal movements of the first and second upper molars (U6 and U7, respectively) were measured. The beginning of phase II (T3) and the end of phase II (T4) records were visually reviewed for follow-up of the eruption of the U7. The pattern of movement for the distal and vertical displacement of the U6 and U7 was significantly different in the HG and CON groups (P < .001). At the end of phase I, none of the U7 in either group were diagnosed as malposed or suspected for impaction. At the end of phase II, all but one U7 with a possible cystic lesion had erupted. The hypothesis is rejected. Forces exerted by combination headgear to the U6 in phase I have a distalizing effect and a transitory slowing down effect on the eruption of the U7 buds. These latter teeth always erupted except when pathology occurred.

β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.

PubMed

Wang, Yao; Yuan, Jiamin; Qian, Zhiyong; Zhang, Xiwen; Chen, Yanhong; Hou, Xiaofeng; Zou, Jiangang

2015-01-08

β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.

β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure

PubMed Central

Wang, Yao; Yuan, Jiamin; Qian, Zhiyong; Zhang, Xiwen; Chen, Yanhong; Hou, Xiaofeng; Zou, Jiangang

2015-01-01

β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways. PMID:25567365

Ranolazine Shortens Repolarization in Patients with Sustained Inward Sodium Current Due To Type-3 Long QT Syndrome

PubMed Central

Moss, Arthur J.; Zareba, Wojciech; Schwarz, Karl Q.; Rosero, Spencer; McNitt, Scott; Robinson, Jennifer L.

2008-01-01

Introduction One form of the hereditary long QT-syndrome, LQT3-ΔKPQ, is associated with sustained inward sodium current during membrane depolarization. Ranolazine reduces late sodium channel current, and we hypothesized that ranolazine would have beneficial effects on electrical and mechanical cardiac function in LQT3 patients with the SCN5A-ΔKPQ mutation. Methods We assessed the effects of 8-hour intravenous ranolazine infusions (45mg/hr for 3 hours followed by 90mg/hr for 5 hours) on ventricular repolarization and myocardial relaxation in five LQT3 patients with the SCN5A-ΔKPQ mutation. Changes in electrocardiographic QTc parameters from before to during ranolazine infusion were evaluated by time-matched, paired t-test analyses. Cardiac ultrasound recordings were obtained before ranolazine infusion and just before completion of the 8-hour ranolazine infusion. Results Ranolazine shortened QTc by 26±3ms (p<0.0001) in a concentration-dependent manner. At peak ranolazine infusion, there was a significant 13% shortening in left ventricular isovolumic relaxation time, a significant 25% increase in mitral E-wave velocity, and a meaningful 22% decrease in mitral E-wave deceleration time compared to baseline. No adverse effects of ranolazine were observed in the study patients. Conclusion Ranolazine at therapeutic concentrations shortened a prolonged QTc interval and improved diastolic relaxation in patients with the LQT3-ΔKPQ mutation, a genetic disorder that is known to cause an increase of late sodium current. PMID:18662191

Distinguishing early and late brain aging from the Alzheimer's disease spectrum: consistent morphological patterns across independent samples.

PubMed

Doan, Nhat Trung; Engvig, Andreas; Zaske, Krystal; Persson, Karin; Lund, Martina Jonette; Kaufmann, Tobias; Cordova-Palomera, Aldo; Alnæs, Dag; Moberget, Torgeir; Brækhus, Anne; Barca, Maria Lage; Nordvik, Jan Egil; Engedal, Knut; Agartz, Ingrid; Selbæk, Geir; Andreassen, Ole A; Westlye, Lars T

2017-09-01

Alzheimer's disease (AD) is a debilitating age-related neurodegenerative disorder. Accurate identification of individuals at risk is complicated as AD shares cognitive and brain features with aging. We applied linked independent component analysis (LICA) on three complementary measures of gray matter structure: cortical thickness, area and gray matter density of 137 AD, 78 mild (MCI) and 38 subjective cognitive impairment patients, and 355 healthy adults aged 18-78 years to identify dissociable multivariate morphological patterns sensitive to age and diagnosis. Using the lasso classifier, we performed group classification and prediction of cognition and age at different age ranges to assess the sensitivity and diagnostic accuracy of the LICA patterns in relation to AD, as well as early and late healthy aging. Three components showed high sensitivity to the diagnosis and cognitive status of AD, with different relationships with age: one reflected an anterior-posterior gradient in thickness and gray matter density and was uniquely related to diagnosis, whereas the other two, reflecting widespread cortical thickness and medial temporal lobe volume, respectively, also correlated significantly with age. Repeating the LICA decomposition and between-subject analysis on ADNI data, including 186 AD, 395 MCI and 220 age-matched healthy controls, revealed largely consistent brain patterns and clinical associations across samples. Classification results showed that multivariate LICA-derived brain characteristics could be used to predict AD and age with high accuracy (area under ROC curve up to 0.93 for classification of AD from controls). Comparison between classifiers based on feature ranking and feature selection suggests both common and unique feature sets implicated in AD and aging, and provides evidence of distinct age-related differences in early compared to late aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Do Aphids Alter Leaf Surface Temperature Patterns During Early Infestation?

PubMed Central

Cahon, Thomas; Caillon, Robin

2018-01-01

Arthropods at the surface of plants live in particular microclimatic conditions that can differ from atmospheric conditions. The temperature of plant leaves can deviate from air temperature, and leaf temperature influences the eco-physiology of small insects. The activity of insects feeding on leaf tissues, may, however, induce changes in leaf surface temperatures, but this effect was only rarely demonstrated. Using thermography analysis of leaf surfaces under controlled environmental conditions, we quantified the impact of presence of apple green aphids on the temperature distribution of apple leaves during early infestation. Aphids induced a slight change in leaf surface temperature patterns after only three days of infestation, mostly due to the effect of aphids on the maximal temperature that can be found at the leaf surface. Aphids may induce stomatal closure, leading to a lower transpiration rate. This effect was local since aphids modified the configuration of the temperature distribution over leaf surfaces. Aphids were positioned at temperatures near the maximal leaf surface temperatures, thus potentially experiencing the thermal changes. The feedback effect of feeding activity by insects on their host plant can be important and should be quantified to better predict the response of phytophagous insects to environmental changes. PMID:29538342

Use patterns among early adopters of adaptive cruise control.

PubMed

Xiong, Huimin; Boyle, Linda Ng; Moeckli, Jane; Dow, Benjamin R; Brown, Timothy L

2012-10-01

The objective of this study was to investigate use patterns among early adopters of adaptive cruise control (ACC). Extended use ofACC may influence a driver's behavior in the long-term, which can have unintended safety consequences. The authors examined the use of a motion-based simulator by 24 participants (15 males and 9 females). Cluster analysis was performed on drivers' use of ACC and was based on their gap settings, speed settings, number of warnings issued, and ACC disengaged. The data were then examined on the basis of driving performance measures and drivers' subjective responses to trust in ACC, understanding of system operations, and driving styles. Driving performance measures included minimum time headway, adjusted minimum time to collision, and drivers' reaction time to critical events. Three groups of drivers were observed on the basis of risky behavior, moderately risky behavior, and conservative behavior. Drivers in the conservative group stayed farther behind the lead vehicle than did drivers in the other two groups. Risky drivers responded later to critical events and had more ACC warnings issued. Safety consequences with ACC may be more prevalent in some driver groups than others. The findings suggest that these safety implications are related to trust in automation, driving styles, understanding of system operations, and personalities. Potential applications of this research include enhanced design for next-generation ACC systems and countermeasures to improve safe driving with ACC.

Typology of emergent eating patterns in early childhood.

PubMed

Hittner, James B; Faith, Myles S

2011-12-01

The stability of eating patterns from infancy through childhood is largely unknown. This study identified subgroups of children based on emergent eating patterns from ages 1 to 3 years and examined differences between groups in demographic, anthropometric and temperamental variables. We conducted secondary analyses of 262 boys and 225 girls from the Colorado Adoption Project. Three eating styles (Reactivity to Food, Predictable Appetite, Distractibility at Mealtime) and five temperaments were assessed at ages 1 and 3 years. Weight and height (length) were assessed on children and mothers. Correlations examined the stability of eating patterns, cluster analysis identified subgroups of emergent eating styles, and analysis of variance identified variables differentiating the derived subgroups. Eating styles were moderately stable over time, although all increased on average. Four subgroups were identified: Diet Expanding and Preference Establishing Eaters (37%), Emerging Reactive Tendency Eaters (23%), Emerging Food-Indifferent and Non-Fussy Eaters (31%), and Emerging High-Reactive and Fussy Eaters (9%). The subgroups differed in year 1 Wt/L and Reaction to Food, and year 1-to-3 changes in Emotionality and Reaction to Food. Four emergent eating patterns were identified. How these subgroups of children differ in later weight and health trajectories warrants research. Copyright © 2011 Elsevier Ltd. All rights reserved.

AN EXAMINATION OF DATA ON IOWA SCHOOL CHILDREN TO DETERMINE PATTERNS OF PERFORMANCE AND "DOWNSTREAM EFFECTS" OF EARLY DEPRESSED SCORES.

ERIC Educational Resources Information Center

FITZSIMMONS, STEPHEN J.

VARIOUS PERFORMANCE PATTERNS WERE STUDIED TO DETERMINE IF EARLY LIMITED FAILURE LEADS TO GENERALIZED FAILURE IN A NUMBER OF AREAS. THE SUBJECTS, 258 DISADVANTAGED URBAN CHILDREN FROM FOUR SCHOOL DISTRICTS IN IOWA, HAD ONE OR MORE SCORES ON THE IOWA TEST OF BASIC SKILLS (ITBS) AT OR BELOW THE 33D PERCENTILE ON NATIONAL NORMS. THEIR PERFORMANCES ON…

Emerging Career Experiences: A Qualitative Exploration of the Career Patterns of Early Career Professionals Living in a Southeast United States Community

ERIC Educational Resources Information Center

Simmons, Steven F.

2013-01-01

The purpose of this qualitative study was to gain insight into the career patterns of early career professionals living in Aiken County, South Carolina. Two theoretical frameworks were selected for this study; Patton and McMahon's (1999) Career Development Systems Theory and Higgins and Kram's (2001) Developmental Network Theory. The researcher…

Transcription mapping and expression patterns of genes in the major immediate-early region of Kaposi's sarcoma-associated herpesvirus.

PubMed

Saveliev, Alexei; Zhu, Fan; Yuan, Yan

2002-08-01

Viral immediate-early (IE) genes are the first class of viral genes expressed during primary infection or reactivation from latency. They usually encode regulatory proteins that play crucial roles in viral life cycle. In a previous study, four regions in the KSHV genome were found to be actively transcribed in the immediate-early stage of viral reactivation in primary effusion lymphoma cells. Three immediate-early transcripts were characterized in these regions, as follows: mRNAs for ORF50 (KIE-1), ORF-45 (KIE-2), and ORF K4.2 (KIE-3) (F. X. Zhu, T. Cusano, and Y. Yuan, 1999, J. Virol. 73, 5556-5567). In the present study, we further analyzed the expression of genes in these IE regions in BC-1 and BCBL-1 cells. One of the immediate-early regions (KIE-1) that encompasses ORF50 and other genes was intensively studied to establish a detailed transcription map and expression patterns of genes in this region. This study led to identification of several novel IE transcripts in this region. They include a 2.6-kb mRNA which encodes ORF48/ORF29b, a family of transcripts that are complementary to ORF50 mRNA and a novel K8 IE mRNA of 1.5 kb. Together with the IE mRNA for ORF50 which was identified previously, four immediate-early genes have been mapped to KIE-1 region. Therefore, we would designate KIE-1 the major immediate-early region of KSHV. In addition, we showed that transcription of K8 gene is controlled by two promoters, yielding two transcripts, an immediate-early mRNA of 1.5 kb and a delayed-early mRNA of 1.3 kb.

Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1.

PubMed

Hoppe, U C; Marbán, E; Johns, D C

2001-04-24

The long QT syndrome (LQTS) is a heritable disorder that predisposes to sudden cardiac death. LQTS is caused by mutations in ion channel genes including HERG and KCNE1, but the precise mechanisms remain unclear. To clarify this situation we injected adenoviral vectors expressing wild-type or LQT mutants of HERG and KCNE1 into guinea pig myocardium. End points at 48-72 h included electrophysiology in isolated myocytes and electrocardiography in vivo. HERG increased the rapid component, I(Kr), of the delayed rectifier current, thereby accelerating repolarization, increasing refractoriness, and diminishing beat-to-beat action potential variability. Conversely, HERG-G628S suppressed I(Kr) without significantly delaying repolarization. Nevertheless, HERG-G628S abbreviated refractoriness and increased beat-to-beat variability, leading to early afterdepolarizations (EADs). KCNE1 increased the slow component of the delayed rectifier, I(Ks), without clear phenotypic sequelae. In contrast, KCNE1-D76N suppressed I(Ks) and markedly slowed repolarization, leading to frequent EADs and electrocardiographic QT prolongation. Thus, the two genes predispose to sudden death by distinct mechanisms: the KCNE1 mutant flagrantly undermines cardiac repolarization, and HERG-G628S subtly facilitates the genesis and propagation of premature beats. Our ability to produce electrocardiographic long QT in vivo with a clinical KCNE1 mutation demonstrates the utility of somatic gene transfer in creating genotype-specific disease models.

Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection.

PubMed

Rossenkhan, Raabya; MacLeod, Iain J; Brumme, Zabrina L; Magaret, Craig A; Sebunya, Theresa K; Musonda, Rosemary; Gashe, Berhanu A; Edlefsen, Paul T; Novitsky, Vlad; Essex, M

Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission.

Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

PubMed Central

Rossenkhan, Raabya; MacLeod, Iain J.; Brumme, Zabrina L.; Magaret, Craig A.; Sebunya, Theresa K.; Musonda, Rosemary; Gashe, Berhanu A.; Edlefsen, Paul T.; Novitsky, Vlad

2016-01-01

Abstract Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission. PMID:27349335

Electronic Monitoring of Medication Adherence in Early Maintenance Phase Treatment for Pediatric Leukemia and Lymphoma: Identifying Patterns of Nonadherence

PubMed Central

Drotar, Dennis; Alderfer, Melissa; Donewar, Crista Wetherington; Ewing, Linda; Katz, Ernest R.; Muriel, Anna

2015-01-01

Objective To describe patterns of treatment adherence to early maintenance phase therapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). Methods Using an objective observational method (electronic monitoring), adherence was examined for 139 patients aged 7–19 years diagnosed with ALL or LBL across 6 centers. Results The mean adherence percentage was 86.2%. Adherence rates declined over the 1-month of follow-up to 83%. 3 linear trajectories of 6-mercaptopurine adherence were identified: (1) exemplary adherence (n = 99): Averaging nearly 100%; (2) deteriorating (n = 23): Adherence decreased from 100 to 60%; and (3) chronically poor adherence (n = 9): Averaging 40%. Conclusions Adherence promotion interventions might be tailored to subgroups of patients who demonstrated problematic patterns of treatment adherence that could place them at risk for relapse. This research demonstrates the importance of using objective real-time measures of medication adherence for measuring and documenting adherence patterns. PMID:24365698

A Qualitative Study of the Context of Child and Adolescent Substance Use Initiation and Patterns of Use in the First Year for Early and Later Initiators

PubMed Central

Rose, Maya; Cohen-Serrins, Julian; Knight, Emily

2017-01-01

Individuals who initiate substance use before high school are at higher risk of negative outcomes. Eighty-six young adults between the ages of 18 and 28 participated in semi-structured qualitative interviews focused on the circumstances surrounding participants’ first use of substances and their pattern of use in the year following initiation in order to investigate similarities and differences between early versus later initiators. Initiation and use among early initiators were more likely to be encouraged by poor parental monitoring or active facilitation of use by parents. Early initiators were more likely to report risky patterns of use such as daily use and using alone. The data suggest that interventions targeting this population should focus on improving parental monitoring and decreasing positive parental attitudes toward adolescent substance use and efforts to increase identification and intervention by middle school staff to reach youth from high-risk families. PMID:28122018

Notch and Delta mRNAs in early-stage and mid-stage Drosophila embryos exhibit complementary patterns of protein producing potentials

PubMed Central

Shepherd, Andrew; Wesley, Uma; Wesley, Cedric

2010-01-01

Notch and Delta proteins generate Notch signaling that specifies cell fates during animal development. There is an intriguing phenomenon in Drosophila embryogenesis that has not received much attention and whose significance to embryogenesis is unknown. Notch and Delta mRNAs expressed in early-stage embryos are shorter than their counterparts in mid-stage embryos. We show here that the difference in sizes is due to mRNA 3′ processing at alternate polyadenylation sites. While the early-stage Notch mRNA has a lower protein-producing potential than the mid-stage Notch mRNA, the early-stage Delta mRNA has a higher protein-producing potential than the mid-stage Delta mRNA. Our data can explain the complementary patterns of Notch and Delta protein levels in early-stage and mid-stage embryos. Our data also raise the possibility that the manner and regulation of Notch signaling change in the course of embryogenesis and that this change is effected by 3′ UTR and mRNA 3′ processing factors. PMID:20201103

Early Dietary Patterns and Microbiota Development: Still a Way to Go from Descriptive Interactions to Health-Relevant Solutions.

PubMed

Iozzo, Patricia; Sanguinetti, Elena

2018-01-01

Early nutrition and growth in the initial years of life are important determinants of later body weight and metabolic health in humans, and the current epidemic of obesity involving children requires a better understanding of causal and protective mechanisms and components in infant foods. This review focuses on recent evidence implicating feeding modes (e.g., breast milk and formula milk) and dietary transitions toward complementary foods in the progression of microbiota maturation in children. The literature exploring body weight outcomes of microbiota changes induced by diet in early life is limited. Representative studies addressing the use of probiotics in pregnant women and infants are also examined. Methodological and geo-cultural variations make it difficult to avoid (apparently) controversial findings. Most studies indicate differences in the microbiota of formula versus breastfed infants, but some do not. Duration of breastfeeding delays the maturation of the microbiota toward an adult-like profile. However, the effect size of the early feeding pattern on microbial function was found to be very small, and absent after the third year of life. There are several interesting mediators whereby milk composition can affect infants' microbiota and their optimization is a desirable strategy for prevention. But prevention of what? Although there are few correlative evaluations relating microbiota and body weight in early life, studies demonstrating a cause-effect relationship between diet-induced changes in early microbiota development and subsequent metabolic health outcomes in humans are still missing.

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

PubMed

Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

2016-03-01

Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding.

PubMed

Sharma, Jyoti; Rathnayaka, Nuvan; Green, Charles; Moeller, F Gerard; Schmitz, Joy M; Shoham, Daniel; Dougherty, Anne Hamilton

2016-01-01

Few studies have examined the effects of chronic cocaine use on the resting surface electrocardiogram (ECG) between exposures to cocaine. Researchers compared 12-lead ECGs from 97 treatment-seeking cocaine-dependent patients, with ECG parameters from 8,513 non-cocaine-using control patients from the Atherosclerosis Risk in Communities study. After matching and adjusting for relevant covariates, cocaine use demonstrated large and statistically reliable effects on early repolarization, bradycardia, severe bradycardia, and heart rate. Current cocaine dependence corresponds to an increased odds of demonstrating early repolarization by a factor of 4.92 and increased odds of bradycardia and severe bradycardia by factors 3.02 and 5.11, respectively. This study demonstrates the novel finding that long-lasting effects of cocaine use on both the cardiac conduction and the autonomic nervous system pose a risk of adverse cardiovascular events between episodes of cocaine use, and that bradycardia is a marker of chronic cocaine use.

Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding

PubMed Central

Sharma, Jyoti; Rathnayaka, Nuvan; Green, Charles; Moeller, F. Gerard; Schmitz, Joy M.; Shoham, Daniel; Dougherty, Anne Hamilton

2014-01-01

Background Few studies have examined the effects of chronic cocaine use on the resting surface electrocardiogram (ECG) between exposures to cocaine. Methods 12-lead ECGs from 97 treatment-seeking cocaine-dependent subjects were compared to ECG parameters from 8513 non-cocaine-using control subjects from the Atherosclerosis Risk in Communities study. Results After matching and adjusting for relevant covariates, cocaine use demonstrated large and statistically reliable effects on early repolarization, bradycardia, severe bradycardia, and heart rate. Current cocaine dependence corresponds to an increased odds of demonstrating early repolarization by a factor of 4.92 and increased odds of bradycardia and severe bradycardia by factors 3.02 and 5.11, respectively. Conclusion This study demonstrates the novel finding that long-lasting effects of cocaine use on both the cardiac conduction and the autonomic nervous system pose a risk of adverse cardiovascular events between episodes of cocaine use, and that bradycardia is a marker of chronic cocaine use. PMID:24621090

Patterns and drivers of Early Holocene vegetation dynamics in Central Europe

NASA Astrophysics Data System (ADS)

Theuerkauf, Martin

2015-04-01

The rapid warming of the Holocene induced the rearrangement of vegetation across Europe, including the widely synchronous and rapid expansion of hazel (Corylus avellana) at around 10.6 ka BP (Giesecke et al., 2011). The simultaneity of the hazel expansion across large parts of Europe suggests that a climate shift has triggered that expansion. However, it remains poorly understood, which climate parameter has been effective (Huntley, 1993) because hazel expanded simultaneously in areas that today clearly differ in climate. To better understand the causes we studied Early Holocene vegetation dynamics in NE Germany in high temporal and spatial resolution. Analysis combines pollen data from 60 sites, including high resolution data sets, with present-day site patterns of soil and relief using the extended downscaling approach. Using forward modeling of pollen deposition in each sample site the method seeks that vegetation composition on each site type that produces modeled pollen deposition most similar to empiric pollen deposition. The results (Theuerkauf et al., 2014) indicate that first populations of hazel established soon after the Holocene warming at 11.2 ka. These populations were still small and possibly restricted to warm loving slopes, indicating that low summer warmth was the limiting factor. The widespread expansion of hazel started only after 10.8 ka, possibly following a shift to greater summer warmth. Hazel primarily expanded on sites that are today covered by gleyic soils, from which it largely expelled tree birch. Hazel thus obviously could only expand on sites that received additional wetness from ground- and stagnant water. Giesecke T., Bennett K.D., Birks H.J.B., Bjune A.E., Bozilova E., Feurdean A., Finsinger W., Froyd C., Pokorný P., Rösch M., Seppä H., Tonkov S., Valsecchi V., & Wolters S. (2011) The pace of Holocene vegetation change - testing for synchronous developments. Quaternary Science Reviews, 30, 2805-2814. Huntley B. (1993) Rapid

The role of Mixer in patterning the early Xenopus embryo.

PubMed

Kofron, Matt; Wylie, Chris; Heasman, Janet

2004-05-01

The transcription factor VegT, is required in early Xenopus embryos for the formation of both the mesoderm and endoderm germ layers. Inherited as a maternal mRNA localized only in vegetal cells, VegT activates the transcription of a large number of transcription factors, as well as signaling ligands that induce cells in the vegetal mass to form endoderm, and the marginal zone to form mesoderm. It is important now to understand the extent to which transcription factors downstream of VegT play individual, or overlapping, roles in the specification and patterning of the endoderm and mesoderm. In addition, it is important to understand the mechanism that specifies the boundary between endoderm and mesoderm. One of the downstream targets of VegT, the homeodomain protein Mixer, is expressed at high levels at the mesoderm/endoderm boundary at the late blastula stage. We therefore examined its functions by blocking its translation using morpholino oligos. In Mixer-depleted embryos, the expression of many signaling ligands and transcription factors was affected. In particular, we found that the expression of several genes, including several normally expressed in mesoderm, was upregulated. Functional assays of Mixer-depleted vegetal cells showed that they have increased mesoderm-inducing activity. This demonstrates that Mixer plays an essential role in controlling the amount of mesoderm induction by the vegetal cells.

Analysis of serial coronary artery flow patterns early after primary angioplasty: new insights into the dynamics of the microcirculation.

PubMed

Sharif, Dawod; Rofe, Guy; Sharif-Rasslan, Amal; Goldhammer, Ehud; Makhoul, Nabeel; Shefer, Arie; Hassan, Amin; Rauchfleisch, Shmuel; Rosenschein, Uri

2008-06-01

The temporal behavior of the coronary microcirculation in acute myocardial infarction may affect outcome. Diastolic deceleration time and early systolic flow reversal derived from coronary artery blood flow velocity patterns reflect microcirculatory function. To assess left anterior descending coronary artery flow velocity patterns using Doppler transthoracic echocardiography after primary percutaneous coronary intervention, in patients with anterior AMI. Patterns of flow velocity patterns of the LAD were obtained using transthoracic echocardiography-Doppler in 31 consecutive patients who presented with anterior AMI. Measurements were done at 6 hours, 36-48 hours, and 5 days after successful PPCI. Measurements of DDT and pressure half times (Pt%), as well as observation for ESFR were performed. In the first 2 days following PPCI, the average DDT (600 +/- 340 msec) was shorter than on day 5 (807 +/- 332 msec) (P < 0.012), FVP in the first 2 days were dynamic and bidirectional: from short DDT (< 600 msec) to long DDT (> 600 msec) and vice versa. On day 5 most DDTs became longer. Pt1/2 at 6 hours was not different than at day 2 (174 +/- 96 vs. 193 +/- 99 msec, P = NS) and became longer on day 5 (235 +/- 98 msec, P = 0.012). Bidirectional patterns were also observed in the ESFR in 6 patients (19%) at baseline, in 4 (13%) at 36 hours, and in 2 (6.5%) on day 5 after PPCI. Flow velocity patterns of the LAD after PPCI in AMI are dynamic and reflect unpredictable changes in microcirculation.

Spatial harmonics and pattern specification in early Drosophila development. Part II. The four colour wheels model.

PubMed

Kauffman, S A; Goodwin, B C

1990-06-07

We review the evidence presented in Part I showing that transcripts and protein products of maternal, gap, pair-rule, and segment polarity genes exhibit increasingly complex, multipeaked longitudinal waveforms in the early Drosophila embryo. The central problem we address in Part II is the use the embryo makes of these wave forms to specify longitudinal pattern. Based on the fact that mutants of many of these genes generate deletions and mirror symmetrical duplications of pattern elements on length scales ranging from about half the egg to within segments, we propose that position is specified by measuring a "phase angle" by use of the ratios of two or more variables. Pictorially, such a phase angle can be thought of as a colour on a colour wheel. Any such model contains a phaseless singularity where all or many phases, or colours, come together. We suppose as well that positional values sufficiently close to the singularity are meaningless, hence a "dead zone". Duplications and deletions are accounted for by deformation of the cycle of morphogen values occurring along the antero-posterior axis. If the cycle of values surrounds the singularity and lies outside the dead zone, pattern is normal. If the curve transects the dead zone, pattern elements are deleted. If the curve lies entirely on one side of the singularity, pattern elements are deleted and others are duplicated with mirror symmetry. The existence of different wavelength transcript patterns in maternal, gap, pair-rule, and segment polarity genes and the roles of those same genes in generating deletions and mirror symmetrical duplications on a variety of length scales lead us to propose that position is measured simultaneously on at least four colour wheels, which cycle different numbers of times along the anterior-posterior axis. These yield progressively finer grained positional information. Normal pattern specification requires a unique angle, outside of the dead zone, from each of the four wheels

Effect of Retosiban on Cardiac Repolarization in a Randomized, Placebo- and Positive-controlled, Crossover Thorough QT/QTc Study in Healthy Men and Women.

PubMed

Stier, Brendt; Fossler, Michael; Liu, Feng; Caltabiano, Stephen

2015-07-01

Retosiban is a small molecule oxytocin receptor antagonist that is under evaluation in clinical studies for treatment of spontaneous preterm labor. A Thorough QT/QTc study was conducted to evaluate the effect of retosiban on cardiac repolarization according to International Conference on Harmonization E14 guidance. This was a randomized, placebo- and positive-controlled, single-dose, crossover study of healthy men and women. All study participants received a 100 mg dose of retosiban (therapeutic target exposure), a 800 mg dose of retosiban (supratherapeutic target exposure), a 400 mg dose of moxifloxacin (positive control), and placebo with an appropriate washout. Holter monitoring data at baseline (predose) and at 13 subsequent time points during the next 24 hours were extracted and manually read by a central ECG reader who was blinded to the treatment assignment and corrected for heart rate by using the Fridericia formula (QTcF). A linear exposure-QTc response model was developed: ΔΔQTcF=RI+Cp,R⋅RS+MI+Cp,M⋅MS, where RI and MI are intercept terms for retosiban and moxifloxacin, respectively, RS and MS are slope terms for retosiban and moxifloxacin, respectively, and Cp,R and Cp,M are plasma concentrations for retosiban and moxifloxacin, respectively. A total of 52 healthy men (n = 27) and women (n = 25), with a mean age of 32 years, were enrolled in the study, and 43 (83%) completed all treatment periods and assessments. Mean placebo-corrected change from baseline QT (ΔΔQTcF) for the 2 retosiban dose groups revealed statistically significant decreases in ΔΔQTcF between 2 and 3 hours after administration, reaching a value of -2.5 msec for both retosiban dose groups. The 400 mg moxifloxacin group had a statistically significant increase in the ΔΔQTcF value at 0.75 hours after administration, reaching a maximal increase of 11.10 msec at 4 hours after administration. Results of the exposure-QTc response modeling revealed that there was no significant

Dental Pulp Stem Cells Model Early Life and Imprinted DNA Methylation Patterns.

PubMed

Dunaway, Keith; Goorha, Sarita; Matelski, Lauren; Urraca, Nora; Lein, Pamela J; Korf, Ian; Reiter, Lawrence T; LaSalle, Janine M

2017-04-01

Early embryonic stages of pluripotency are modeled for epigenomic studies primarily with human embryonic stem cells (ESC) or induced pluripotent stem cells (iPSCs). For analysis of DNA methylation however, ESCs and iPSCs do not accurately reflect the DNA methylation levels found in preimplantation embryos. Whole genome bisulfite sequencing (WGBS) approaches have revealed the presence of large partially methylated domains (PMDs) covering 30%-40% of the genome in oocytes, preimplantation embryos, and placenta. In contrast, ESCs and iPSCs show abnormally high levels of DNA methylation compared to inner cell mass (ICM) or placenta. Here we show that dental pulp stem cells (DPSCs), derived from baby teeth and cultured in serum-containing media, have PMDs and mimic the ICM and placental methylome more closely than iPSCs and ESCs. By principal component analysis, DPSC methylation patterns were more similar to two other neural stem cell types of human derivation (EPI-NCSC and LUHMES) and placenta than were iPSCs, ESCs or other human cell lines (SH-SY5Y, B lymphoblast, IMR90). To test the suitability of DPSCs in modeling epigenetic differences associated with disease, we compared methylation patterns of DPSCs derived from children with chromosome 15q11.2-q13.3 maternal duplication (Dup15q) to controls. Differential methylation region (DMR) analyses revealed the expected Dup15q hypermethylation at the imprinting control region, as well as hypomethylation over SNORD116, and novel DMRs over 147 genes, including several autism candidate genes. Together these data suggest that DPSCs are a useful model for epigenomic and functional studies of human neurodevelopmental disorders. Stem Cells 2017;35:981-988. © 2016 AlphaMed Press.

Bradycardia alters Ca2+ dynamics enhancing dispersion of repolarization and arrhythmia risk

PubMed Central

Kim, Jong J.; Němec, Jan; Papp, Rita; Strongin, Robert; Abramson, Jonathan J.

2013-01-01

Bradycardia prolongs action potential (AP) durations (APD adaptation), enhances dispersion of repolarization (DOR), and promotes tachyarrhythmias. Yet, the mechanisms responsible for enhanced DOR and tachyarrhythmias remain largely unexplored. Ca2+ transients and APs were measured optically from Langendorff rabbit hearts at high (150 × 150 μm2) or low (1.5 × 1.5 cm2) magnification while pacing at a physiological (120 beats/min) or a slow heart rate (SHR = 50 beats/min). Western blots and pharmacological interventions were used to elucidate the regional effects of bradycardia. As a result, bradycardia (SHR 50 beats/min) increased APDs gradually (time constant τf→s = 48 ± 9.2 s) and caused a secondary Ca2+ release (SCR) from the sarcoplasmic reticulum during AP plateaus, occurring at the base on average of 184.4 ± 9.7 ms after the Ca2+ transient upstroke. In subcellular imaging, SCRs were temporally synchronous and spatially homogeneous within myocytes. In diastole, SHR elicited variable asynchronous sarcoplasmic reticulum Ca2+ release events leading to subcellular Ca2+ waves, detectable only at high magnification. SCR was regionally heterogeneous, correlated with APD prolongation (P < 0.01, n = 5), enhanced DOR (r = 0.9277 ± 0.03, n = 7), and was gradually reversed by pacing at 120 beats/min along with APD shortening (P < 0.05, n = 5). A stabilizer of leaky ryanodine receptors (RyR2), 3-(4-benzylcyclohexyl)-1-(7-methoxy-2,3-dihydrobenzo[f][1,4]thiazepin-4(5H)-yl)propan-1-one (K201; 1 μM), suppressed SCR and reduced APD at the base, thereby reducing DOR (P < 0.02, n = 5). Ventricular ectopy induced by bradycardia (n = 5/15) was suppressed by K201. Western blot analysis revealed spatial differences of voltage-gated L-type Ca2+ channel protein (Cav1.2α), Na+-Ca2+ exchange (NCX1), voltage-gated Na+ channel (Nav1.5), and rabbit ether-a-go-go-related (rERG) protein [but not RyR2 or sarcoplasmic reticulum Ca2+ ATPase 2a] that correlate with the SCR distribution

Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head.

PubMed

Bekri, Abdelhamid; Billaud, Marc; Thélu, Jacques

2014-01-01

Several human diseases are associated with the NUAK1 and NUAK2 genes. These genes encode kinases, members of the AMPK-related kinases (ARK) gene family. Both NUAK1 and NUAK2 are known targets of the serine threonine kinase LKB1, a tumor suppressor involved in regulating cell polarity. While much is known about their functions in disease, their expression pattern in normal development has not been extensively studied. Here, we present the expression patterns for NUAK1 and NUAK2 in the chick during early-stage embryogenesis, until day 3 (Hamburger and Hamilton stage HH20). Several embryonic structures, in particular the nascent head, showed distinct expression levels. NUAK1 expression was first detected at stage HH6 in the rostral neural folds. It was then expressed (HH7-11) throughout the encephalalon, predominantly in the telencephalon and mesencephalon. NUAK1 expression was also detected in the splanchnic endoderm area at HH8-10, and in the vitellin vein derived from this area, but not in the heart. NUAK2 expression was first detected at stage HH6 in the neural folds. It was then found throughout the encephalon at stage HH20. Particular attention was paid in this study to the dorsal ectoderm at stages HH7 and HH8, where a local deficit or accumulation of NUAK2 mRNA were found to correlate with the direction of curvature of the neural plate. This is the first description of NUAK1 and NUAK2 expression patterns in the chick during early development; it reveals non-identical expression profiles for both genes in neural development.

Early Career Patterns for Social Work Graduates

ERIC Educational Resources Information Center

Choi, Mi Jin; Urbanski, Paul; Fortune, Anne E.; Rogers, Crystal

2015-01-01

This study examines master's of social work graduates' early careers. Six cohorts graduating from 2002 through 2007 (N = 246) completed a questionnaire 9-15 months after graduation. Most reported adequate or exceptional preparation on both generalist and advanced concentration practice behaviors. Almost all direct practice graduates and 2/3 of…

HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner

PubMed Central

Pai, Vaibhav P.; Willocq, Valerie; Pitcairn, Emily J.; Lemire, Joan M.; Paré, Jean-François; Shi, Nian-Qing; McLaughlin, Kelly A.

2017-01-01

ABSTRACT Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4) is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels (Ih currents) with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10) and not by a later block (post-stage 10). Injections of HCN4-DN (dominant-negative) mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal, Lefty, and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning. PMID:28818840

HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner.

PubMed

Pai, Vaibhav P; Willocq, Valerie; Pitcairn, Emily J; Lemire, Joan M; Paré, Jean-François; Shi, Nian-Qing; McLaughlin, Kelly A; Levin, Michael

2017-10-15

Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4) is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels ( I h currents) with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10) and not by a later block (post-stage 10). Injections of HCN4-DN (dominant-negative) mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal , Lefty , and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning. © 2017. Published by The Company of Biologists Ltd.

Development and Early Usage Patterns of a Consumer-Facing Family Health History Tool

PubMed Central

Hulse, Nathan C.; Ranade-Kharkar, Pallavi; Post, Herman; Wood, Grant M.; Williams, Marc S.; Haug, Peter J.

2011-01-01

Personalized medicine will require detailed clinical patient profiles, and a particular focus on capturing data that is useful in forecasting risk. A detailed family health history is considered a critical component of these profiles, insomuch that it has been coined as ‘the best genetic test available’. Despite this, tools aimed at capturing this information for use in electronic health records have been characterized as inadequate. In this manuscript we detail the creation of a patient-facing family health history tool known as OurFamilyHealth, whose long-term emphasis is to facilitate risk assessment and clinical decision support. We present the rationale for such a tool, describe its development and release as a component of Intermountain Healthcare’s patient portal, and detail early usage statistics surrounding the application. Data derived from the tool since its release are also compared against family history charting patterns in Intermountain’s electronic health records, revealing differences in data availability. PMID:22195113

Electronic monitoring of medication adherence in early maintenance phase treatment for pediatric leukemia and lymphoma: identifying patterns of nonadherence.

PubMed

Rohan, Jennifer M; Drotar, Dennis; Alderfer, Melissa; Donewar, Crista Wetherington; Ewing, Linda; Katz, Ernest R; Muriel, Anna

2015-01-01

To describe patterns of treatment adherence to early maintenance phase therapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). Using an objective observational method (electronic monitoring), adherence was examined for 139 patients aged 7-19 years diagnosed with ALL or LBL across 6 centers. The mean adherence percentage was 86.2%. Adherence rates declined over the 1-month of follow-up to 83%. 3 linear trajectories of 6-mercaptopurine adherence were identified: (1) exemplary adherence (n = 99): Averaging nearly 100%; (2) deteriorating (n = 23): Adherence decreased from 100 to 60%; and (3) chronically poor adherence (n = 9): Averaging 40%. Adherence promotion interventions might be tailored to subgroups of patients who demonstrated problematic patterns of treatment adherence that could place them at risk for relapse. This research demonstrates the importance of using objective real-time measures of medication adherence for measuring and documenting adherence patterns. © The Author 2013. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Movement and Movement Patterns of Early Childhood.

ERIC Educational Resources Information Center

Sinclair, Caroline B.

This study was undertaken to determine the progressive development in movement and movement patterns (coordinated movements of body parts used involuntarily to achieve an objective) of children 2- to 6-years-old, to identify general characteristics which may be studied for appraisal of growth and development, and to study variations in movement…

Early Exposure to Dynamic Environments Alters Patterns of Motor Exploration throughout the Lifespan

PubMed Central

Hong, S. Lee; Estrada-Sánchez, Ana María; Barton, Scott J.; Rebec, George V.

2016-01-01

We assessed early rearing conditions on aging-related changes in mouse behavior. Two isolated-housing groups, Running Wheel (IHRW) and Empty Cage (IHEC), were compared against two enriched environments, Static (EEST) and Dynamic (EEDY), both of which included toys and other mice. For EEDY, the location of toys and sources of food and water changed daily, but remained constant for EEST. All mice, randomly assigned to one of the four groups at ~4 weeks of age, remained in their respective environments for 25 weeks followed by single housing in empty cages. Beginning at ~40 weeks of age, all mice were tested at monthly intervals in a plus-shaped maze in which we measured the number of arm entries and the probability of entering a perpendicular arm. Despite making significantly more arm entries than any other group, IHEC mice also were less likely to turn into the left or right arm, a sign of motor inflexibility. Both EEDY and EEST mice showed enhanced turning relative to IHRW and IHEC groups, but only EEDY mice maintained their turning performance for up to ~100 weeks of age. EEDY and EEST mice also were unique in showing an increase in expression of the major glutamate transporter (GLT1) in striatum, but a decrease in motor cortex, suggesting a need for further assessment of environmental manipulations on long-term changes in forebrain glutamate transmission. Our behavioral results indicate that early exposure to continually changing environments, rather than socialization or exercise alone, results in life-long changes in patterns of motor exploration. PMID:26778790

Low extracellular potassium prolongs repolarization and evokes early afterdepolarization in human induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Kuusela, Jukka; Larsson, Kim; Shah, Disheet; Prajapati, Chandra; Aalto-Setälä, Katriina

2017-06-15

Long QT syndrome (LQTS) is characterized by a prolonged QT-interval on electrocardiogram and by increased risk of sudden death. One of the most common and potentially life-threatening electrolyte disturbances is hypokalemia, characterized by low concentrations of K + Using a multielectrode array platform and current clamp technique, we investigated the effect of low extracellular K + concentration ([K + ] Ex ) on the electrophysiological properties of hiPSC-derived cardiomyocytes (CMs) generated from a healthy control subject (WT) and from two symptomatic patients with type 1 of LQTS carrying G589D (LQT1A) or IVS7-2A>G mutation (LQT1B) in KCNQ1 The baseline prolongations of field potential durations (FPDs) and action potential durations (APDs) were longer in LQT1-CMs than in WT-CMs. Exposure to low [K + ] Ex prolonged FPDs and APDs in a concentration-dependent fashion. LQT1-CMs were found to be more sensitive to low [K + ] Ex compared to WT-CMs. At baseline, LQT1A-CMs had more prolonged APDs than LQT1B-CMs, but low [K + ] Ex caused more pronounced APD prolongation in LQT1B-CMs. Early afterdepolarizations in the action potentials were observed in a subset of LQT1A-CMs with further prolonged baseline APDs and triangular phase 2 profiles. This work demonstrates that the hiPSC-derived CMs are sensitive to low [K + ] Ex and provide a platform to study acquired LQTS. © 2017. Published by The Company of Biologists Ltd.

Diffusion and scaling during early embryonic pattern formation.

PubMed

Gregor, Thomas; Bialek, William; de Ruyter van Steveninck, Rob R; Tank, David W; Wieschaus, Eric F

2005-12-20

Development of spatial patterns in multicellular organisms depends on gradients in the concentration of signaling molecules that control gene expression. In the Drosophila embryo, Bicoid (Bcd) morphogen controls cell fate along 70% of the anteroposterior axis but is translated from mRNA localized at the anterior pole. Gradients of Bcd and other morphogens are thought to arise through diffusion, but this basic assumption has never been rigorously tested in living embryos. Furthermore, because diffusion sets a relationship between length and time scales, it is hard to see how patterns of gene expression established by diffusion would scale proportionately as egg size changes during evolution. Here, we show that the motion of inert molecules through the embryo is well described by the diffusion equation on the relevant length and time scales, and that effective diffusion constants are essentially the same in closely related dipteran species with embryos of very different size. Nonetheless, patterns of gene expression in these different species scale with egg length. We show that this scaling can be traced back to scaling of the Bcd gradient itself. Our results, together with constraints imposed by the time scales of development, suggest that the mechanism for scaling is a species-specific adaptation of the Bcd lifetime.

Diffusion and scaling during early embryonic pattern formation

PubMed Central

Gregor, Thomas; Bialek, William; van Steveninck, Rob R. de Ruyter; Tank, David W.; Wieschaus, Eric F.

2005-01-01

Development of spatial patterns in multicellular organisms depends on gradients in the concentration of signaling molecules that control gene expression. In the Drosophila embryo, Bicoid (Bcd) morphogen controls cell fate along 70% of the anteroposterior axis but is translated from mRNA localized at the anterior pole. Gradients of Bcd and other morphogens are thought to arise through diffusion, but this basic assumption has never been rigorously tested in living embryos. Furthermore, because diffusion sets a relationship between length and time scales, it is hard to see how patterns of gene expression established by diffusion would scale proportionately as egg size changes during evolution. Here, we show that the motion of inert molecules through the embryo is well described by the diffusion equation on the relevant length and time scales, and that effective diffusion constants are essentially the same in closely related dipteran species with embryos of very different size. Nonetheless, patterns of gene expression in these different species scale with egg length. We show that this scaling can be traced back to scaling of the Bcd gradient itself. Our results, together with constraints imposed by the time scales of development, suggest that the mechanism for scaling is a species-specific adaptation of the Bcd lifetime. PMID:16352710

Alterations of functional connectivities from early to middle adulthood: Clues from multivariate pattern analysis of resting-state fMRI data.

PubMed

Tian, Lixia; Ma, Lin; Wang, Linlin

2016-04-01

In contrast to extended research interests in the maturation and aging of human brain, alterations of brain structure and function from early to middle adulthood have been much less studied. The aim of the present study was to investigate the extent and pattern of the alterations of functional interactions between brain regions from early to middle adulthood. We carried out the study by multivariate pattern analysis of resting-state fMRI (RS-fMRI) data of 63 adults aged 18 to 45 years. Specifically, using elastic net, we performed brain age estimation and age-group classification (young adults aged 18-28 years vs. middle-aged adults aged 35-45 years) based on the resting-state functional connectivities (RSFCs) between 160 regions of interest (ROIs) evaluated on the RS-fMRI data of each subject. The results indicate that the estimated brain ages were significantly correlated with the chronological age (R=0.78, MAE=4.81), and a classification rate of 94.44% and area under the receiver operating characteristic curve (AUC) of 0.99 were obtained when classifying the young and middle-aged adults. These results provide strong evidence that functional interactions between brain regions undergo notable alterations from early to middle adulthood. By analyzing the RSFCs that contribute to brain age estimation/age-group classification, we found that a majority of the RSFCs were inter-network, and we speculate that inter-network RSFCs might mature late but age early as compared to intra-network ones. In addition, the strengthening/weakening of the RSFCs associated with the left/right hemispheric ROIs, the weakening of cortico-cerebellar RSFCs and the strengthening of the RSFCs between the default mode network and other networks contributed much to both brain age estimation and age-group classification. All these alterations might reflect that aging of brain function is already in progress in middle adulthood. Overall, the present study indicated that the RSFCs undergo notable

Differences in the Association between Segment and Language: Early Bilinguals Pattern with Monolinguals and Are Less Accurate than Late Bilinguals

PubMed Central

Blanco, Cynthia P.; Bannard, Colin; Smiljanic, Rajka

2016-01-01

Early bilinguals often show as much sensitivity to L2-specific contrasts as monolingual speakers of the L2, but most work on cross-language speech perception has focused on isolated segments, and typically only on neighboring vowels or stop contrasts. In tasks that include sounds in context, listeners’ success is more variable, so segment discrimination in isolation may not adequately represent the phonetic detail in stored representations. The current study explores the relationship between language experience and sensitivity to segmental cues in context by comparing the categorization patterns of monolingual English listeners and early and late Spanish–English bilinguals. Participants categorized nonce words containing different classes of English- and Spanish-specific sounds as being more English-like or more Spanish-like; target segments included phonemic cues, cues for which there is no analogous sound in the other language, or phonetic cues, cues for which English and Spanish share the category but for which each language varies in its phonetic implementation. Listeners’ language categorization accuracy and reaction times were analyzed. Our results reveal a largely uniform categorization pattern across listener groups: Spanish cues were categorized more accurately than English cues, and phonemic cues were easier for listeners to categorize than phonetic cues. There were no differences in the sensitivity of monolinguals and early bilinguals to language-specific cues, suggesting that the early bilinguals’ exposure to Spanish did not fundamentally change their representations of English phonology. However, neither did the early bilinguals show more sensitivity than the monolinguals to Spanish sounds. The late bilinguals however, were significantly more accurate than either of the other groups. These findings indicate that listeners with varying exposure to English and Spanish are able to use language-specific cues in a nonce-word language categorization

Gestational dietary patterns are not associated with blood pressure changes during pregnancy and early postpartum in a Brazilian prospective cohort.

PubMed

Eshriqui, Ilana; Vilela, Ana Amélia Freitas; Rebelo, Fernanda; Farias, Dayana Rodrigues; Castro, Maria Beatriz Trindade; Kac, Gilberto

2016-02-01

To identify gestational dietary patterns and evaluate the association between these patterns and the blood pressure (BP) rate of change during pregnancy and the postpartum. Prospective cohort study composed of 191 healthy pregnant women. Systolic BP (SBP) and diastolic BP (DBP) were obtained at the 5th-13th, 20th-26th, 30th-36th gestational weeks, and with 30-45 days postpartum. A food frequency questionnaire administered at the 30th-36th gestational week was used to measure dietary intake during pregnancy. Principal component analysis was performed to identify the dietary patterns. A longitudinal linear mixed-effects regression model was used to evaluate the association between the dietary patterns and BP (adjusted for time elapsed after conception and the women's age, education, parity, body mass index and total energy intake). Three gestational dietary patterns were identified: healthy, common-Brazilian and processed. SBP/DBP mean values (SD) were 110.1 (9.0)/66.9 (7.5), 108.7 (9.0)/64.9 (6.7), 111.3 (9.2)/67.0 (6.9) and 115.0 (10.7)/73.7 (8.6) mmHg at the first, second and third gestational trimesters and postpartum, respectively. Women with higher/lower adherence to the processed pattern presented SBP of 117.9 and 113.0 mmHg (P = 0.037), respectively, during postpartum. No association was found between any of the three dietary patterns and SBP in the multiple longitudinal linear regression models, whereas 1 SD increase in the common-Brazilian pattern was associated with a small change of DBP (β = 0.0006; 95% CI 4.66e-06, 0.001; P = 0.048). The three dietary patterns identified revealed no association with changes of SBP and DBP levels during pregnancy and at early postpartum in this sample of healthy Brazilian women.

Electrocardiographic repolarization-related variables as predictors of coronary heart disease death in the women's health initiative study.

PubMed

Rautaharju, Pentti M; Zhang, Zhu-Ming; Vitolins, Mara; Perez, Marco; Allison, Matthew A; Greenland, Philip; Soliman, Elsayed Z

2014-07-28

We evaluated 25 repolarization-related ECG variables for the risk of coronary heart disease (CHD) death in 52 994 postmenopausal women from the Women's Health Initiative study. Hazard ratios from Cox regression were computed for subgroups of women with and without cardiovascular disease (CVD). During the average follow-up of 16.9 years, 941 CHD deaths occurred. Based on electrophysiological considerations, 2 sets of ECG variables with low correlations were considered as candidates for independent predictors of CHD death: Set 1, Ѳ(Tp|Tref), the spatial angle between T peak (Tp) and normal T reference (Tref) vectors; Ѳ(Tinit|Tterm), the angle between the initial and terminal T vectors; STJ depression in V6 and rate-adjusted QTp interval (QTpa); and Set 2, TaVR and TV1 amplitudes, heart rate, and QRS duration. Strong independent predictors with over 2-fold increased risk for CHD death in women with and without CVD were Ѳ(Tp|Tref) >42° from Set 1 and TaVR amplitude >-100 μV from Set 2. The risk for these CHD death predictors remained significant after multivariable adjustment for demographic/clinical factors. Other significant predictors for CHD death in fully adjusted risk models were Ѳ(Tinit|Tterm) >30°, TV1 >175 μV, and QRS duration >100 ms. Ѳ(Tp|Tref) angle and TaVR amplitude are associated with CHD mortality in postmenopausal women. The use of these measures to identify high-risk women for further diagnostic evaluation or more intense preventive intervention warrants further study. http://www.clinicaltrials.gov. Unique identifier: NCT00000611. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Early Holocene humidity patterns in the Iberian Peninsula reconstructed from lake, pollen and speleothem records

NASA Astrophysics Data System (ADS)

Morellón, Mario; Aranbarri, Josu; Moreno, Ana; González-Sampériz, Penélope; Valero-Garcés, Blas L.

2018-02-01

Comparison of selected, well-dated, lacustrine, speleothem and terrestrial pollen records spanning the Holocene onset and the Early Holocene (ca. 11.7-8 cal kyrs BP) in the Iberian Peninsula shows large hydrological fluctuations and landscape changes with a complex regional pattern in timing and intensity. Marine pollen records from Alboran, the Mediterranean and off shore Atlantic sites show a step-wise increase in moisture and forest during this transition. However, available continental records point to two main patterns of spatial and temporal hydrological variability: i) Atlantic-influenced sites located at the northwestern areas (Enol, Sanabria, Lucenza, PRD-4), characterized by a gradual increase in humidity from the end of the Younger Dryas to the Mid Holocene, similarly to most North Atlantic records; and ii) continental and Mediterranean-influenced sites (Laguna Grande, Villarquemado, Fuentillejo, Padul, Estanya, Banyoles, Salines), with prolonged arid conditions of variable temporal extension after the Younger Dryas, followed by an abrupt increase in moisture at 10-9 cal kyrs BP. Different local climate conditions influenced by topography or the variable sensitivity (gradual versus threshold values) of the proxies analyzed in each case are evaluated. Vegetation composition (conifers versus mesothermophilous taxa) and resilience would explain a subdued response of vegetation in central continental areas while in Mediterranean sites, insufficient summer moisture availability could not maintain high lake levels and promote mesophyte forest, in contrast to Atlantic-influenced areas. Comparison with available climate models, Greenland ice cores, North Atlantic marine sequences and continental records from Central and Northern Europe and the whole Mediterranean region underlines the distinctive character of the hydrological changes occurred in inner Iberia throughout the Early Holocene. The persistent arid conditions might be explained by the intensification

Early male partnership patterns, social support, and sexual risk behavior among young men who have sex with men.

PubMed

Glick, Sara Nelson; Golden, Matthew R

2014-08-01

Few data exist on the early sexual behavior patterns of contemporary young men who have sex with men (YMSM), the social context of these patterns, and which of these factors influence risk for HIV and other sexually transmitted infections (STI). We enrolled 94 YMSM (age 16-30) into a 1-year cohort study with serial online retrospective surveys and HIV/STI testing. The first three partnerships of YMSM were characterized by relatively high rates of unprotected anal sex and a rapidly expanding sexual repertoire, but also increasing rates of HIV status disclosure. During follow-up, 17 % of YMSM reported any nonconcordant unprotected anal intercourse (NCUAI) and 15 % were newly diagnosed with HIV/STI. Sex education in high school and current maternal support were protective against HIV/STI, while isolation from family and friends was associated with recent NCUAI. Social support-including from parents, peers, and school-based sex education-may help mitigate HIV/STI risk in this population.

Early Warning Signals of Ecological Transitions: Methods for Spatial Patterns

PubMed Central

Brock, William A.; Carpenter, Stephen R.; Ellison, Aaron M.; Livina, Valerie N.; Seekell, David A.; Scheffer, Marten; van Nes, Egbert H.; Dakos, Vasilis

2014-01-01

A number of ecosystems can exhibit abrupt shifts between alternative stable states. Because of their important ecological and economic consequences, recent research has focused on devising early warning signals for anticipating such abrupt ecological transitions. In particular, theoretical studies show that changes in spatial characteristics of the system could provide early warnings of approaching transitions. However, the empirical validation of these indicators lag behind their theoretical developments. Here, we summarize a range of currently available spatial early warning signals, suggest potential null models to interpret their trends, and apply them to three simulated spatial data sets of systems undergoing an abrupt transition. In addition to providing a step-by-step methodology for applying these signals to spatial data sets, we propose a statistical toolbox that may be used to help detect approaching transitions in a wide range of spatial data. We hope that our methodology together with the computer codes will stimulate the application and testing of spatial early warning signals on real spatial data. PMID:24658137

Screening methods for delirium: early diagnosis by means of objective quantification of motor activity patterns using wrist-actigraphy.

PubMed

Osse, Robert Jan; Tulen, Joke H M; Hengeveld, Michiel W; Bogers, Ad J J C

2009-03-01

Delirium after cardiac surgery is a risk factor for adverse outcome and even death. Disturbance of motor activity is a core feature of delirium, but hypoactive delirium often remains unrecognized. We explored wrist-actigraphy as a tool to objectively quantify postoperative recovery of 24-h rest-activity patterns to improve the early recognition of delirium after surgery. Motor activity was recorded by wrist-actigraphy after cardiac surgery in 88 patients over 65 years of age. Patients were assessed daily by using the CAM-ICU. Our final analyses were based on 32 non-delirious patients and 38 patients who were delirious on the first day after surgery. The delirious patients showed lower mean activity levels during the first postoperative night (P<0.05), reduced restlessness during the first day (P<0.05), and a lower mean activity of the 5 h with lowest activity within the first 24 h (P=0.01), as compared to the non-delirious patients. Already at a very early stage after cardiac surgery, a difference in motor activity was observed between patients with and without a delirium. As an unobtrusive method, actigraphy has the potential to be a screening method that may lead to early diagnosis and treatment of delirium.

BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells

PubMed Central

Gu, Ning; Vervaeke, Koen; Storm, Johan F

2007-01-01

Neuronal potassium (K+) channels are usually regarded as largely inhibitory, i.e. reducing excitability. Here we show that BK-type calcium-activated K+ channels enhance high-frequency firing and cause early spike frequency adaptation in neurons. By combining slice electrophysiology and computational modelling, we investigated functions of BK channels in regulation of high-frequency firing in rat CA1 pyramidal cells. Blockade of BK channels by iberiotoxin (IbTX) selectively reduced the initial discharge frequency in response to strong depolarizing current injections, thus reducing the early spike frequency adaptation. IbTX also blocked the fast afterhyperpolarization (fAHP), slowed spike rise and decay, and elevated the spike threshold. Simulations with a computational model of a CA1 pyramidal cell confirmed that the BK channel-mediated rapid spike repolarization and fAHP limits activation of slower K+ channels (in particular the delayed rectifier potassium current (IDR)) and Na+ channel inactivation, whereas M-, sAHP- or SK-channels seem not to be important for the early facilitating effect. Since the BK current rapidly inactivates, its facilitating effect diminishes during the initial discharge, thus producing early spike frequency adaptation by an unconventional mechanism. This mechanism is highly frequency dependent. Thus, IbTX had virtually no effect at spike frequencies < 40 Hz. Furthermore, extracellular field recordings demonstrated (and model simulations supported) that BK channels contribute importantly to high-frequency burst firing in response to excitatory synaptic input to distal dendrites. These results strongly support the idea that BK channels play an important role for early high-frequency, rapidly adapting firing in hippocampal pyramidal neurons, thus promoting the type of bursting that is characteristic of these cells in vivo, during behaviour. PMID:17303637

Early repolarization, localization of J point elevation on ECG and arrhythmias.

PubMed

Matoshvili, Z; Petriashvili, Sh; Archvadze, A; Azaladze, I

2015-04-01

Final aim of this observational study was to determine correlation between localization of J point elevation and number of premature ventricular beats. The 52 patients (19-68 years old; 31 men and 21 women) were divided in two groups based on localization of J point elevation. First Group - 9 patients (5 men and 4 women) with J-point elevation ≥1 mm in ≥2 contiguous inferior and/or lateral leads on a standard 12-lead ECG reading, Second Group - other 43 (26 men and 17 women) patients with another localization of J point elevation. Total summarized number of premature ventricular contractions for each group was compared and analyzed. The results of the study shows that the number of premature ventricular beats in first group was 61% higher. Thus, in our opinion J-point elevation ≥1 mm in ≥2 contiguous inferior and/or lateral leads, is more arrhythmogenic. Data shows that this difference is statistically significant.

CD64-Neutrophil expression and stress metabolic patterns in early sepsis and severe traumatic brain injury in children.

PubMed

Fitrolaki, Diana-Michaela; Dimitriou, Helen; Kalmanti, Maria; Briassoulis, George

2013-03-01

Critical illness constitutes a serious derangement of metabolism. The aim of our study was to compare acute phase metabolic patterns in children with sepsis (S) or severe sepsis/septic shock (SS) to those with severe traumatic brain injury (TBI) and healthy controls (C) and to evaluate their relations to neutrophil, lymphocyte and monocyte expressions of CD64 and CD11b. Sixty children were enrolled in the study. Forty-five children with systemic inflammatory response syndrome (SIRS) were classified into three groups: TBI (n = 15), S (n = 15), and SS (n = 15). C consisted of 15 non- SIRS patients undergoing screening tests for minor elective surgery. Blood samples were collected within 6 hours after admission for flow cytometry of neutrophil, lymphocyte and monocyte expression of CD64 and CD11b (n = 60). Procalcitonin (PCT), C-reactive protein (CRP), glucose, triglycerides (TG), total cholesterol (TC), high (HDL) or low-density-lipoproteins (LDL) were also determined in all groups, and repeated on day 2 and 3 in the 3 SIRS groups (n = 150). CRP, PCT and TG (p < 0.01) were significantly increased in S and SS compared to TBI and C; glucose did not differ among critically ill groups. Significantly lower were the levels of TC, LDL, and HDL in septic groups compared to C and to moderate changes in TBI (p < 0.0001) but only LDL differed between S and SS (p < 0.02). Among septic patients, PCT levels declined significantly (p < 0.02) with time, followed by parallel decrease of HDL (p < 0.03) and increase of TG (p < 0.02) in the SS group. Neutrophil CD64 (nCD64) expression was higher in patients with SS (81.2%) and S (78.8%) as compared to those with TBI (5.5%) or C (0.9%, p < 0.0001). nCD64 was positively related with CRP, PCT, glucose, and TG (p < 0.01) and negatively with TC, LDL, and HDL (p < 0.0001), but not with severity of illness, hematologic indices, length of stay or mechanical ventilation duration. In sepsis, the early stress-metabolic pattern is characterized by

Survival After Early and Normal Retirement

ERIC Educational Resources Information Center

Haynes, Suzanne G.; And Others

1978-01-01

Describes an epidemiological study of the patterns and correlates of survival after early (age 62 to 64) and normal retirement (age 65). Death rates were significantly elevated during the first, fourth, and fifth years after early retirement. Pre-retirement health status was the only significant predictor of survival after early retirement.…

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

PubMed Central

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-01-01

Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action. PMID:23610573

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction.

PubMed

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-03-01

To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (I to), the rapidly activated omponent of delayed rectifier potassium current (I Kr), the slowly activated component of delayed rectifier potassium current (I Ks), and the L-type calcium current (I CaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca(2+) current are likely the underlying mechanism of action.

Early Childhood Education in Taiwan.

ERIC Educational Resources Information Center

Barclay, Lisa K.

1989-01-01

Describes early childhood education in Taiwan, focusing on living patterns and child care arrangements, the position of the individual within the family and community, and the application of cultural norms to early childhood education. Compares the behavior of Chinese preschool children to that of American preschool children. (RJC)

Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart.

PubMed

Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Ardell, Jeffrey L; Armour, J Andrew

2009-01-28

Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.

Disturbance of DNA methylation patterns in the early phase of hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined diet in rats.

PubMed

Shimizu, Kyoko; Onishi, Mariko; Sugata, Eriko; Sokuza, Yui; Mori, Chiharu; Nishikawa, Tomoki; Honoki, Kanya; Tsujiuchi, Toshifumi

2007-09-01

The authors investigated the DNA methylation patterns of the E-cadherin, Connexin 26 (Cx26), Rassf1a and c-fos genes in the early phase of rat hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined (CDAA) diet. Six-week-old F344 male rats were continuously fed with the CDAA diet, and three animals were then killed at each of 4 and 8 days and 3 weeks. Genomic DNA was extracted from livers for assessment of methylation status in the 5' upstream regions of E-cadherin, Cx26, Rassf1a and c-fos genes by bisulfite sequencing, compared with normal livers. The livers of rats fed the CDAA diet for 4 and 8 days and 3 weeks were methylated in E-cadherin, Cx26 and Rassf1a genes, while normal livers were all unmethylated. In contrast, normal livers were highly methylated in c-fos gene. Although the livers at 4 days were weakly methylated, those at 8 days and 3 weeks were markedly unmethylated. Methylation patterns of CpG sites in E-cadherin, Cx26 and Rassf1a were sparse and the methylation was not associated with gene repression. These results indicate that gene-specific DNA methylation patterns were found in livers of rats after short-term feeding of the CDAA diet, suggesting gene-specific hypermethylation might be involved in the early phase of rat hepatocarcinogenesis induced by the CDAA diet.

Multivariate pattern analysis of fMRI: the early beginnings.

PubMed

Haxby, James V

2012-08-15

In 2001, we published a paper on the representation of faces and objects in ventral temporal cortex that introduced a new method for fMRI analysis, which subsequently came to be called multivariate pattern analysis (MVPA). MVPA now refers to a diverse set of methods that analyze neural responses as patterns of activity that reflect the varying brain states that a cortical field or system can produce. This paper recounts the circumstances and events that led to the original study and later developments and innovations that have greatly expanded this approach to fMRI data analysis, leading to its widespread application. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of Early Adult Patterns of Physical Activity and Television Viewing on Midlife Cognitive Function.

PubMed

Hoang, Tina D; Reis, Jared; Zhu, Na; Jacobs, David R; Launer, Lenore J; Whitmer, Rachel A; Sidney, Stephen; Yaffe, Kristine

2016-01-01

Sedentary behaviors and physical inactivity are not only increasing worldwide but also are critical risk factors for adverse health outcomes. Yet, few studies have examined the effects of sedentary behavior on cognition or the long-term role of either behavior in early to middle adulthood. To investigate the association between 25-year patterns of television viewing and physical activity and midlife cognition. Prospective study of 3247 adults (black and white races; aged 18-30 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (March 25, 1985, to August 31, 2011). Data analysis was performed June 1, 2014, through April 15, 2015. We assessed television viewing and physical activity at repeated visits (≥3 assessments) over 25 years using a validated questionnaire. A 25-year pattern of high television viewing was defined as watching TV above the upper baseline quartile (>3 hours/d) for more than two-thirds of the visits, and a 25-year pattern of low physical activity was defined as activity levels below the lower, sex-specific baseline quartile for more than two-thirds of the of the visits. We evaluated cognitive function at year 25 using the Digit Symbol Substitution Test (DSST), Stroop test, and Rey Auditory Verbal Learning Test. At baseline, the mean (SD) age of the 3247 study participants was 25.1 (3.6) years, 1836 (56.5%) were female, 1771 (54.5%) were white, and 3015 (92.9%) had completed at least high school. Compared with participants with low television viewing, those with high television viewing during 25 years (353 of 3247 [10.9%]) were more likely to have poor cognitive performance (<1 SD below the race-specific mean) on the DSST and Stroop test, with findings reported as adjusted odds ratio (95% CI): DSST, 1.64 (1.21-2.23) and Stroop test, 1.56 (1.13-2.14), but not the Rey Auditory Verbal Learning Test, adjusted for age, race, sex, educational level, smoking, alcohol use, body mass index, and hypertension. Low

Rosettes, Engrailed Edges, and Star-Shaped Patterns: Between Rediscovery and Forgetfulness in the Early Accounts of Vibrating Liquid Drops Floating over Hot Surfaces.

PubMed

Stewart, Seán M

2017-12-01

Small drops of liquid brought into contact with very hot surfaces float above it as beautiful, slightly flattened spheroids without coming to the boil. An example of film boiling, drops that are sessile can often suddenly and quite unexpectedly start to oscillate forming highly symmetric patterns of surprising pulchritude. The rim of these oscillating drops take on "star-shaped" patterns with many different modes of vibration possible. Still an object of study today, their discovery, early accounts, rediscovery and ensuing controversies over claims of priority, before quietly slipping away from the collective memory of the scientific community to become all but forgotten makes for a compelling story in the early history of film boiling. The episode serves not only as a valuable reminder of the importance the history of science can play in highlighting past achievements that would otherwise remain unknown to the modern practitioner. It also provides an example of how external pressures and personal ambition can often influence the work of a scientist in their pursuit of self-recognition and acclaim amongst their peers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Post-repolarization refractoriness increases vulnerability to block and initiation of reentrant impulses in heterogeneous infarcted myocardium.

PubMed

Cabo, Candido

2015-10-01

Myocardial infarction causes remodeling of the tissue structure and the density and kinetics of several ion channels in the cell membrane. Heterogeneities in refractory period (ERP) have been shown to occur in the infarct border zone and have been proposed to lead to initiation of arrhythmias. The purpose of this study is to quantify the window of vulnerability (WV) to block and initiation of reentrant impulses in myocardium with ERP heterogeneities using computer simulations. We found that ERP transitions at the border between normal ventricular cells (NZ) with different ERPs are smooth, whereas ERP transitions between NZ and infarct border zone cells (IZ) are abrupt. The profile of the ERP transitions is a combination of electrotonic interaction between NZ and IZ cells and the characteristic post-repolarization refractoriness (PRR) of IZ cells. ERP heterogeneities between NZ and IZ cells are more vulnerable to block and initiation of reentrant impulses than ERP heterogeneities between NZ cells. The relationship between coupling intervals of premature impulses (V1V2) and coupling intervals between premature and first reentrant impulses (V2T1) at NZ/NZ and NZ/IZ borders is inverse (i.e. the longer the coupling intervals of premature impulses the shorter the coupling interval between the premature and first reentrant impulses); this is in contrast with the reported V1V2/V2T1 relationship measured during initiation of reentrant impulses in canine infarcted hearts which is direct. (1) ERP transitions at the NZ-IZ border are abrupt as a consequence of PRR; (2) PRR increases the vulnerability to block and initiation of reentrant impulses in heterogeneous myocardium; (3) V1V2/V2T1 relationships measured at ERP heterogeneities in the computer model and in experimental canine infarcts are not consistent. Therefore, it is likely that other mechanisms like micro and/or macro structural heterogeneities also contribute to initiation of reentrant impulses in infarcted hearts

Cumulative impact of axial, structural, and repolarization ECG findings on long-term cardiovascular mortality among healthy individuals in Japan: National Integrated Project for Prospective Observation of Non-Communicable Disease and its Trends in the Aged, 1980 and 1990.

PubMed

Inohara, Taku; Kohsaka, Shun; Okamura, Tomonori; Watanabe, Makoto; Nakamura, Yasuyuki; Higashiyama, Aya; Kadota, Aya; Okuda, Nagako; Murakami, Yoshitaka; Ohkubo, Takayoshi; Miura, Katsuyuki; Okayama, Akira; Ueshima, Hirotsugu

2014-12-01

Various cohort studies have shown a close association between long-term cardiovascular disease (CVD) outcomes and individual electrocardiographic (ECG) abnormalities such as axial, structural, and repolarization changes. The combined effect of these ECG abnormalities, each assumed to be benign, has not been thoroughly investigated. Community-dwelling Japanese residents from the National Integrated Project for Perspective Observation of Non-Communicable Disease and its Trends in the Aged, 1980-2004 and 1990-2005 (NIPPON DATA80 and 90), were included in this study. Baseline ECG findings were classified using the Minnesota Code and categorized into axial (left axis deviation, clockwise rotation), structural (left ventricular hypertrophy, atrial enlargement), and repolarization (minor and major ST-T changes) abnormalities. The hazard ratios of the cumulative impacts of ECG findings on long-term CVD death were estimated by stratified Cox proportional hazard models, including adjustments for cohort strata. In all, 16,816 participants were evaluated. The average age was 51.2 ± 13.5 years; 42.7% participants were male. The duration of follow up was 300,924 person-years (mean 17.9 ± 5.8 years); there were 1218 CVD deaths during that time. Overall, 4203 participants (25.0%) had one or more categorical ECG abnormalities: 3648 (21.7%) had a single abnormality, and 555 (3.3%) had two or more. The risk of CVD mortality increased as the number of abnormalities accumulated (single abnormality HR 1.29, 95% CI 1.13-1.48; ≥2 abnormalities HR 2.10, 95% CI 1.73-2.53). Individual ECG abnormalities had an additive effect in predicting CVD outcome risk in our large-scale cohort study. © The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Event Perception and Pattern Perception in Early Infancy.

ERIC Educational Resources Information Center

Vurpillot, Eliane

Human infants are sensitive from birth to some intrinsic properties of objects; they are also sensitive to position. During the first weeks of life, pertinent dimensions of differentiation between objects are relative to global properties of the entire object or pattern. Position is defined by the direction of a displacement: the trajectory…

CD64-Neutrophil expression and stress metabolic patterns in early sepsis and severe traumatic brain injury in children

PubMed Central

2013-01-01

ventilation duration. Conclusions In sepsis, the early stress-metabolic pattern is characterized by a high (nCD64, glucose, TG) - low (TC, HDL, LDL) combination in contrast to the moderate pattern of TBI in which only glucose increases combined with a moderate cholesterol - lipoprotein decrease. These early metabolic patterns persist the first 3 days of acute illness and are associated with the acute phase CD64 expression on neutrophils. PMID:23452299

Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma

PubMed Central

Yates, Katherine P.; Zhou, Xiaobo; Guo, Feng; Sternberg, Alice L.; Van Natta, Mark L.; Wise, Robert A.; Szefler, Stanley J.; Sharma, Sunita; Kho, Alvin T.; Cho, Michael H.; Croteau-Chonka, Damien C.; Castaldi, Peter J.; Jain, Gaurav; Sanyal, Amartya; Zhan, Ye; Lajoie, Bryan R.; Dekker, Job; Stamatoyannopoulos, John; Covar, Ronina A.; Zeiger, Robert S.; Adkinson, N. Franklin; Williams, Paul V.; Kelly, H. William; Grasemann, Hartmut; Vonk, Judith M.; Koppelman, Gerard H.; Postma, Dirkje S.; Raby, Benjamin A.; Houston, Isaac; Lu, Quan; Fuhlbrigge, Anne L.; Tantisira, Kelan G.; Silverman, Edwin K.; Tonascia, James; Strunk, Robert C.; Weiss, Scott T.

2016-01-01

Rationale: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease. Objectives: To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma. Methods: We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline). The strongest association was also measured in two additional cohorts: a small asthma cohort and a large chronic obstructive pulmonary disease metaanalysis cohort. Interaction between the genomic region encompassing the most strongly associated single-nucleotide polymorphism and nearby genes was assessed by two chromosome conformation capture assays. Measurements and Main Results: An intergenic single-nucleotide polymorphism (rs4445257) on chromosome 8 was strongly associated with the normal growth with early decline pattern compared with all other pattern groups (P = 6.7 × 10−9; odds ratio, 2.8; 95% confidence interval, 2.0–4.0); replication analysis suggested this variant had opposite effects in normal growth with early decline and reduced growth with early decline pattern groups. Chromosome conformation capture experiments indicated a chromatin interaction between rs4445257 and the promoter of the distal CSMD3 gene. Conclusions: Early decline in lung function after normal growth is associated with a genetic polymorphism that may also protect against early decline in reduced growth groups. Clinical trial registered with www.clinicaltrials.gov (NCT00000575). PMID:27367781

Bumblebees distinguish floral scent patterns, and can transfer these to corresponding visual patterns.

PubMed

Lawson, David A; Chittka, Lars; Whitney, Heather M; Rands, Sean A

2018-06-13

Flowers act as multisensory billboards to pollinators by using a range of sensory modalities such as visual patterns and scents. Different floral organs release differing compositions and quantities of the volatiles contributing to floral scent, suggesting that scent may be patterned within flowers. Early experiments suggested that pollinators can distinguish between the scents of differing floral regions, but little is known about how these potential scent patterns might influence pollinators. We show that bumblebees can learn different spatial patterns of the same scent, and that they are better at learning to distinguish between flowers when the scent pattern corresponds to a matching visual pattern. Surprisingly, once bees have learnt the spatial arrangement of a scent pattern, they subsequently prefer to visit novel unscented flowers that have an identical arrangement of visual marks, suggesting that multimodal floral signals may exploit the mechanisms by which learnt information is stored by the bee. © 2018 The Authors.

Patterns of larval source distribution and mixing in early life stages of Pacific cod (Gadus macrocephalus) in the southeastern Bering Sea

NASA Astrophysics Data System (ADS)

Miller, Jessica A.; DiMaria, Ruth A.; Hurst, Thomas P.

2016-12-01

Effective and sustainable management depends on knowledge of spawning locations and their relative contributions to marine fish populations. Pacific cod (Gadus macrocephalus) in the southeastern Bering Sea aggregate at discrete spawning locations but there is little information on patterns of larval dispersal and the relative contribution of specific spawning areas to nursery habitats. Age-0 Pacific cod from two cohorts (2006 and 2008) were examined to address the following questions: (1) does size, age, and otolith chemistry vary among known capture locations; (2) can variation in elemental composition of the otolith cores (early larval signatures) be used to infer the number of chemically distinct sources contributing to juvenile recruits in the Bering Sea; and (3) to what extent are juvenile collection locations represented by groups of fish with similar chemical histories throughout their early life history? Hierarchical cluster (HCA) and discriminant function analyses (DFA) were used to examine variation in otolith chemistry at discrete periods throughout the early life history. HCA identified five chemically distinct groups of larvae in the 2006 cohort and three groups in 2008; however, three sources accounted for 80-100% of the juveniles in each year. DFA of early larval signatures indicated that there were non-random spatial distributions of early larvae in both years, which may reflect interannual variation in regional oceanography. There was also a detectable and substantial level of coherence in chemical signatures within groups of fish throughout the early life history. The variation in elemental signatures throughout the early life history (hatch to capture) indicates that otolith chemical analysis could be an effective tool to further clarify larval sources and dispersal, identify juvenile nursery habitats, and estimate the contributions of juvenile nursery habitats to the adult population within the southeastern Bering Sea.

Early changes of left ventricular filling pattern after reperfused ST-elevation myocardial infarction and doxycycline therapy: Insights from the TIPTOP trial.

PubMed

Cerisano, Giampaolo; Buonamici, Piergiovanni; Parodi, Guido; Santini, Alberto; Moschi, Guia; Valenti, Renato; Migliorini, Angela; Colonna, Paolo; Bellandi, Benedetta; Gori, Anna Maria; Antoniucci, David

2017-08-01

Metalloproteinases inhibition by doxycycline reduces cardiac protein degradation at extracellular and intracellular level in the experimental model ischemia/reperfusion injury. Since both extracellular cardiac matrix and titin filaments inside the cardiomyocyte are responsible for the myocardial stiffness, we hypothesized that doxycycline could favorably act on left ventricular (LV) filling pressures in patients after reperfused acute ST-elevation myocardial infarction (STEMI). Seventy-three of 110 patients of the TIPTOP trial underwent a 2D-Echo-Doppler on admission, and at pre-discharge and at 6-month after a primary PCI for STEMI and LV dysfunction. From admission to pre-discharge, LV filling changed from a high filling pressure (HFP) to a normal filling pressure (NFP) pattern in 91% of the doxycycline-group, and in 67% of the control-group. Conversely, 1% of the doxycycline-group, and 37% of the control-group changed the LV filling from NFP to HFP pattern. Overall, a pre-discharge HFP pattern was present in 4 patients (11%) of the doxycycline-group and in 13 patients (36%) of the control-group (p=0.025). The evaluation of metalloproteinases and their tissue inhibitors plasma concentrations provide possible favorable action of doxycycline. On the multivariate analyses, troponine I peak (p=0.026), doxycycline (p=0.033), and on admission to pre-discharge LVEF changes (p=0.044) were found to be associated with pre-discharge HFP pattern. Independently of their baseline LV filling behavior, the 6-month remodeling was less in patients with pre-discharge NFP pattern than in patients with HFP pattern. In patients with STEMI and LV dysfunction doxycycline can favorably modulate the LV filling pattern early after primary PCI. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Distinct expression patterns for type II topoisomerases IIA and IIB in the early foetal human telencephalon.

PubMed

Harkin, Lauren F; Gerrelli, Dianne; Gold Diaz, Diana C; Santos, Chloe; Alzu'bi, Ayman; Austin, Caroline A; Clowry, Gavin J

2016-03-01

TOP2A and TOP2B are type II topoisomerase enzymes that have important but distinct roles in DNA replication and RNA transcription. Recently, TOP2B has been implicated in the transcription of long genes in particular that play crucial roles in neural development and are susceptible to mutations contributing to neurodevelopmental conditions such as autism and schizophrenia. This study maps their expression in the early foetal human telencephalon between 9 and 12 post-conceptional weeks. TOP2A immunoreactivity was restricted to cell nuclei of the proliferative layers of the cortex and ganglionic eminences (GE), including the ventricular zone and subventricular zone (SVZ) closely matching expression of the proliferation marker KI67. Comparison with sections immunolabelled for NKX2.1, a medial GE (MGE) marker, and PAX6, a cortical progenitor cell and lateral GE (LGE) marker, revealed that TOP2A-expressing cells were more abundant in MGE than the LGE. In the cortex, TOP2B is expressed in cell nuclei in both proliferative (SVZ) and post-mitotic compartments (intermediate zone and cortical plate) as revealed by comparison with immunostaining for PAX6 and the post-mitotic neuron marker TBR1. However, co-expression with KI67 was rare. In the GE, TOP2B was also expressed by proliferative and post-mitotic compartments. In situ hybridisation studies confirmed these patterns of expression, except that TOP2A mRNA is restricted to cells in the G2/M phase of division. Thus, during early development, TOP2A is likely to have a role in cell proliferation, whereas TOP2B is expressed in post-mitotic cells and may be important in controlling expression of long genes even at this early stage. © 2015 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

A dominant bursting electromyograph pattern in dystonic conditions predicts an early response to pallidal stimulation.

PubMed

Yianni, John; Wang, Shou Yan; Liu, Xuguang; Bain, Peter G; Nandi, Dipankar; Gregory, Ralph; Joint, Carole; Stein, John F; Aziz, Tipu Z

2006-08-01

Although chronic pallidal deep brain stimulation (DBS) is effective in the treatment of medically intractable dystonia, there is no way of predicting the variations in clinical outcome, partly due to our limited understanding of the pathophysiological mechanisms underlying this condition. We recorded electromyographic (EMG) activity from the most severely affected muscle groups in seven dystonia patients before and after pallidal DBS. Patient EMG recordings could be classified into two groups: one consisting of patients who at rest demonstrated a dominant low frequency component of activity on power spectral analysis (ranging from 2 to 5 Hz), and one group in which this dominant pattern was absent. Early postoperative improvements (within 2-3 days) were observed in the former group, whereas the latter group benefited more gradually (over several months). Analysis of EMG activity may provide a sensitive means of identifying dystonic patients who are likely to be most responsive to functional neurosurgical intervention.

Effects of 4-aminopyridine on cardiac repolarization, PR interval, and heart rate in patients with spinal cord injury.

PubMed

Isoda, Wakana C; Segal, Jack L

2003-02-01

To determine the effects of 4-aminopyridine (4-AP) on heart rate and PR, QT, and QTc intervals in patients with longstanding spinal cord injury (SCI). Randomized, active-treatment-controlled, dose level-blinded study, with allocation concealed. University-affiliated, tertiary care medical center. Sixty otherwise healthy male and female outpatients with traumatic SCI of more than 1 year's duration. Intervention. Oral administration and dose titration to tolerance of an immediate-release formulation of 4-AP. The PR interval, heart rate, QT interval, and QTc interval obtained from standard 12-lead electrocardiograms (ECGs) at baseline (before administration of 4-AP) and after 1 month of treatment were compared. The QTc intervals were derived by using Bazett's formula (equation) incorporated into standard computerized analyses of 12-lead ECG printouts. The paired t test was performed to test for the significance of differences between means and variances. No statistically significant differences were noted in heart rate or between ECG time intervals measured at baseline and after 1 month of treatment with 4-AP among all patients with SCI or between subgroups stratified by injury level (tetraplegia, paraplegia) or sex. During the 1-month period that 4-AP was administered, the heart rate and PR, QT, and QTc intervals all remained unchanged and stayed well within normal range in comparison to literature-derived control values. 4-Aminopyridine does not appear to influence the length of cardiac time intervals or heart rate and, hence, is unlikely to cause potentially life-threatening ventricular dysrrhythmias when administered long-term and taken orally in dosages of up to 30 mg/day. Specifically, cardiac repolarization (QTc interval) is unaffected in patients with SCI who continuously receive 4-AP for up to 1 month.

Replication labeling patterns and chromosome territories typical of mammalian nuclei are conserved in the early metazoan Hydra.

PubMed

Alexandrova, Olga; Solovei, Irina; Cremer, Thomas; David, Charles N

2003-12-01

To investigate the evolutionary conservation of higher order nuclear architecture previously described for mammalian cells we have analyzed the nuclear architecture of the simple polyp Hydra. These diploblastic organisms have large nuclei (8-10 microm) containing about 3x10(9) bp of DNA organized in 15 chromosome pairs. They belong to the earliest metazoan phylum and are separated from mammals by at least 600 million years. Single and double pulse labeling with halogenated nucleotides (bromodeoxyuridine, iododeoxyuridine and chlorodeoxyuridine) revealed striking similarities to the known sequence of replication labeling patterns in mammalian nuclei. These patterns reflect a persistent nuclear arrangement of early, mid-, and late replicating chromatin foci that could be identified during all stages of interphase over at least 5-10 cell generations. Segregation of labeled chromatids led after several cell divisions to nuclei with single or a few labeled chromosome territories. In such nuclei distinct clusters of labeled chromatin foci were separated by extended nuclear areas with non-labeled chromatin, which is typical of a territorial arrangement of interphase chromosomes. Our results indicate the conservation of fundamental features of higher order chromatin arrangements throughout the evolution of metazoan animals and suggest the existence of conserved mechanism(s) controlling this architecture.

Treatment Patterns and Early Outcomes of ALK-Positive Non-Small Cell Lung Cancer Patients Receiving Ceritinib: A Chart Review Study.

PubMed

Bendaly, Edmond; Dalal, Anand A; Culver, Kenneth; Galebach, Philip; Bocharova, Iryna; Foster, Rebekah; Sasane, Medha; Macalalad, Alexander R; Guérin, Annie

2017-05-01

This study aimed to provide the first real-world description of the characteristics, treatments, dosing patterns, and early outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US clinical practice. US oncologists provided data from medical charts of adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC who received ceritinib following crizotinib. Patient characteristics, treatment patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal adverse events (AEs) by dose and instructions on food intake were assessed, and Kaplan-Meier analysis was used to describe clinician-defined progression-free survival (PFS) on ceritinib. Medical charts of 58 ALK-positive NSCLC patients treated with ceritinib were reviewed (median age 63 years; 41% male; 21% with prior chemotherapy experience). At ceritinib initiation, 44 patients had multiple distant metastases, most commonly in the liver (60%), bone (53%), and brain (38%). Initial ceritinib dose varied: 71% received 750 mg, 19% 600 mg, and 10% 450 mg. Although median follow-up after ceritinib initiation was short (3.8 months), most patients achieved either a complete or partial response (69%) on ceritinib, regardless of metastatic sites present at initiation or initial dose. Median PFS on ceritinib was 12.9 months. 17% of patients had a gastrointestinal AE reported during follow-up. The majority of events occurred in patients instructed to fast; no patients instructed to take a lower dose of ceritinib with food reported gastrointestinal AEs. These early findings of ceritinib use in clinical practice suggest that ceritinib is effective at treating crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic sites or initial dose, and dosing ceritinib with food may lead to fewer gastrointestinal AEs. Future studies with larger sample size and longer follow-up are warranted, including an ongoing randomized trial to

Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo

PubMed Central

Woda, Juliana M; Calzonetti, Teresa; Hilditch-Maguire, Paige; Duyao, Mabel P; Conlon, Ronald A; MacDonald, Marcy E

2005-01-01

Background Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Conclusion Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease. PMID:16109169

Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo.

PubMed

Woda, Juliana M; Calzonetti, Teresa; Hilditch-Maguire, Paige; Duyao, Mabel P; Conlon, Ronald A; MacDonald, Marcy E

2005-08-18

Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdh(ex4/5) huntingtin deficient embryos. In the absence of huntingtin, expression of nutritive genes appears normal but E7.0-7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease.

Development of Food Acceptance Patterns.

ERIC Educational Resources Information Center

Birch, Leann L.

1990-01-01

Provides a rationale for the significance of the study of early feeding and delineates major issues that require investigation. Includes a list of acquisition processes implicated in the development of food acceptance patterns. (RH)

Local transmural action potential gradients are absent in the isolated, intact dog heart but present in the corresponding coronary-perfused wedge.

PubMed

Boukens, Bastiaan J; Meijborg, Veronique M F; Belterman, Charly N; Opthof, Tobias; Janse, Michiel J; Schuessler, Richard B; Coronel, Ruben; Efimov, Igor R

2017-05-01

The left ventricular (LV) coronary-perfused canine wedge preparation is a model commonly used for studying cardiac repolarization. In wedge studies, transmembrane potentials typically are recorded; whereas, extracellular electrical recordings are commonly used in intact hearts. We compared electrically measured activation recovery interval (ARI) patterns in the intact heart with those recorded at the same location in the LV wedge preparation. We also compared electrically recorded and optically obtained ARIs in the LV wedge preparation. Five Langendorff-perfused canine hearts were paced from the right atrium. Local activation and repolarization times were measured with eight transmural needle electrodes. Subsequently, left ventricular coronary-perfused wedge preparations were prepared from these hearts while the electrodes remained in place. Three electrodes remained at identical positions as in the intact heart. Both electrograms and optical action potentials were recorded (pacing cycle length 400-4000 msec) and activation and repolarization patterns were analyzed. ARIs found in the subepicardium were shorter than in the subendocardium in the LV wedge preparation but not in the intact heart. The transmural ARI gradient recorded at the cut surface of the wedge was not different from that recorded internally. ARIs recorded internally and at the cut surface in the LV wedge preparation, both correlated with optically recorded action potentials. ARI and RT gradients in the LV wedge preparation differed from those in the intact canine heart, implying that those observations in human LV wedge preparations also should be extrapolated to the intact human heart with caution. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context

PubMed Central

Ajijola, Olujimi A.; Yagishita, Daigo; Patel, Krishan J.; Vaseghi, Marmar; Zhou, Wei; Yamakawa, Kentaro; So, Eileen; Lux, Robert L.; Mahajan, Aman

2013-01-01

Myocardial infarction (MI) induces neural and electrical remodeling at scar border zones. The impact of focal MI on global functional neural remodeling is not well understood. Sympathetic stimulation was performed in swine with anteroapical infarcts (MI; n = 9) and control swine (n = 9). A 56-electrode sock was placed over both ventricles to record electrograms at baseline and during left, right, and bilateral stellate ganglion stimulation. Activation recovery intervals (ARIs) were measured from electrograms. Global and regional ARI shortening, dispersion of repolarization, and activation propagation were assessed before and during sympathetic stimulation. At baseline, mean ARI was shorter in MI hearts than control hearts (365 ± 8 vs. 436 ± 9 ms, P < 0.0001), dispersion of repolarization was greater in MI versus control hearts (734 ± 123 vs. 362 ± 32 ms2, P = 0.02), and the infarcted region in MI hearts showed longer ARIs than noninfarcted regions (406 ± 14 vs. 365 ± 8 ms, P = 0.027). In control animals, percent ARI shortening was greater on anterior than posterior walls during right stellate ganglion stimulation (P = 0.0001), whereas left stellate ganglion stimulation showed the reverse (P = 0.0003). In infarcted animals, this pattern was completely lost. In 50% of the animals studied, sympathetic stimulation, compared with baseline, significantly altered the direction of activation propagation emanating from the intramyocardial scar during pacing. In conclusion, focal distal anterior MI alters regional and global pattern of sympathetic innervation, resulting in shorter ARIs in infarcted hearts, greater repolarization dispersion, and altered activation propagation. These conditions may underlie the mechanisms by which arrhythmias are initiated when sympathetic tone is enhanced. PMID:23893167

Longitudinal patterns of poverty and health in early childhood: exploring the influence of concurrent, previous, and cumulative poverty on child health outcomes.

PubMed

Béatrice, Nikiéma; Lise, Gauvin; Victoria, Zunzunegui Maria; Louise, Séguin

2012-09-04

Although the links between poverty and health have often been studied , the dynamics of poverty and physical health in early childhood remain under-investigated. In particular, it is not known whether the health of young children is affected differently from that of adults by patterns of poverty unique to them. We examined patterns of health from 5 to 41 months of age as a function of concurrent, lagged, and chronic exposure to insufficient income. Using data from the first four rounds of the Quebec Longitudinal Study of Child Development, we performed multilevel logistic and multilevel Poisson regressions and latent growth curve analyses to explore associations between exposure to poverty and mother-reported asthma-like attacks, and maternal perception of health status controlling for neonatal, maternal, and environmental characteristics. The mean number of mother-reported asthma-like attacks significantly decreased as children aged. The likelihood of being perceived in a poorer health status also decreased across time. Concurrent poverty was associated with more mother-reported asthma-like attacks and with a higher risk of being perceived in poorer health status. One-period-lagged poverty was associated with more mother-reported asthma-like attacks and this remained significant after controlling for concurrent poverty. The number of mother-reported asthma-like attacks was significantly higher among children in the chronic poverty class compared to those in the never-poor class, particularly at 17 and 29 months. Perceived health status at 5-months was significantly poorer among chronically poor children compared to never-poor children. Exposure to poverty negatively affects two major health indicators in early childhood - maternal perception of child health and mother-reported asthma-like attacks. Patterns of the effects vary according to timing and duration of poverty exposure. Further longitudinal research is warranted to disentangle time-specific from

Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current

PubMed Central

Liu, Pin W.; Blair, Nathaniel T.

2017-01-01

Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC50 <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons. SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike

Right precordial-directed electrocardiographical markers identify arrhythmogenic right ventricular cardiomyopathy in the absence of conventional depolarization or repolarization abnormalities.

PubMed

Cortez, Daniel; Svensson, Anneli; Carlson, Jonas; Graw, Sharon; Sharma, Nandita; Brun, Francesca; Spezzacatene, Anita; Mestroni, Luisa; Platonov, Pyotr G

2017-10-13

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries a risk of sudden death. We aimed to assess whether vectorcardiographic (VCG) parameters directed toward the right heart and a measured angle of the S-wave would help differentiate ARVD/C with otherwise normal electrocardiograms from controls. Task Force 2010 definite ARVD/C criteria were met for all patients. Those who did not fulfill Task Force depolarization or repolarization criteria (-ECG) were compared with age and gender-matched control subjects. Electrocardiogram measures of a 3-dimentional spatial QRS-T angle, a right-precordial-directed orthogonal QRS-T (RPD) angle, a root mean square of the right sided depolarizing forces (RtRMS-QRS), QRS duration (QRSd) and the corrected QT interval (QTc), and a measured angle including the upslope and downslope of the S-wave (S-wave angle) were assessed. Definite ARVD/C was present in 155 patients by 2010 Task Force criteria (41.7 ± 17.6 years, 65.2% male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.7 ± 17.6 years, 65.2% male). All parameters tested except the QRSd and QTc significantly differentiated -ECG ARVD/C from control patients (p < 0.004 to p < 0.001). The RPD angle and RtRMS-QRS best differentiated the groups. Combined, the 2 novel criteria gave 81.8% sensitivity, 90.9% specificity and odds ratio of 45.0 (95% confidence interval 15.8 to 128.2). ARVD/C disease process may lead to development of subtle ECG abnormalities that can be distinguishable using right-sided VCG or measured angle markers better than the spatial QRS-T angle, the QRSd or QTc, in the absence of Taskforce ECG criteria.

A Punctate Magnetic Resonance Imaging Pattern in a Patient with Systemic Lupus Erythematosus is an Early Sign of Progressive Multifocal Leukoencephalopathy: A Clinicopathological Study.

PubMed

Ishii, Junko; Shishido-Hara, Yukiko; Kawamoto, Michi; Fujiwara, Satoru; Imai, Yukihiro; Nakamichi, Kazuo; Kohara, Nobuo

2018-04-27

A 37-year-old woman with systemic lupus erythematosus (SLE) presented with gait disturbance and cognitive dysfunction. Brain magnetic resonance imaging (MRI) revealed small, punctate, T2-/fluid-attenuated inversion recovery-hyperintense and T1-hypointense lesions without gadolinium enhancement, which is atypical for progressive multifocal leukoencephalopathy (PML). On a pathological examination of biopsied brain tissues, JC virus-infected cells were hardly detected via immunohistochemistry but were certainly detected via in situ hybridization, conclusively verifying the PML diagnosis. After tapering off the immunosuppressant and mefloquine administration, the MRI findings revealed gradual improvement, and she has been stable for over 18 months. A punctate MRI pattern is not specific to natalizumab-associated PML but may be a ubiquitous early sign useful for the early diagnosis of PML.

Long-term blockade of L/N-type Ca2+ channels by cilnidipine ameliorates repolarization abnormality of the canine hypertrophied heart

PubMed Central

Takahara, A; Nakamura, Y; Wagatsuma, H; Aritomi, S; Nakayama, A; Satoh, Y; Akie, Y; Sugiyama, A

2009-01-01

Background and purpose: The heart of the canine model of chronic atrioventricular block is known to have a ventricular electrical remodelling, which mimics the pathophysiology of long QT syndrome. Using this model, we explored a new pharmacological therapeutic strategy for the prevention of cardiac sudden death. Experimental approach: The L-type Ca2+ channel blocker amlodipine (2.5 mg·day−1), L/N-type Ca2+ channel blocker cilnidipine (5 mg·day−1), or the angiotensin II receptor blocker candesartan (12 mg·day−1) was administered orally to the dogs with chronic atrioventricular block for 4 weeks. Electropharmacological assessments with the monophasic action potential (MAP) recordings and blood sample analyses were performed before and 4 weeks after the start of drug administration. Key results: Amlodipine and cilnidipine decreased the blood pressure, while candesartan hardly affected it. The QT interval, MAP duration and beat-to-beat variability of the ventricular repolarization period were shortened only in the cilnidipine group, but such effects were not observed in the amlodipine or candesartan group. Plasma concentrations of adrenaline, angiotensin II and aldosterone decreased in the cilnidipine group. In contrast, plasma concentrations of angiotensin II and aldosterone were elevated in the amlodipine group, whereas in the candesartan group an increase in plasma levels of angiotensin II and a decrease in noradrenaline and adrenaline concentrations were observed. Conclusions and implications: Long-term blockade of L/N-type Ca2+ channels ameliorated the ventricular electrical remodelling in the hypertrophied heart which causes the prolongation of the QT interval. This could provide a novel therapeutic strategy for the treatment of cardiovascular diseases. PMID:19785655

Library-based illumination synthesis for critical CMOS patterning.

PubMed

Yu, Jue-Chin; Yu, Peichen; Chao, Hsueh-Yung

2013-07-01

In optical microlithography, the illumination source for critical complementary metal-oxide-semiconductor layers needs to be determined in the early stage of a technology node with very limited design information, leading to simple binary shapes. Recently, the availability of freeform sources permits us to increase pattern fidelity and relax mask complexities with minimal insertion risks to the current manufacturing flow. However, source optimization across many patterns is often treated as a design-of-experiments problem, which may not fully exploit the benefits of a freeform source. In this paper, a rigorous source-optimization algorithm is presented via linear superposition of optimal sources for pre-selected patterns. We show that analytical solutions are made possible by using Hopkins formulation and quadratic programming. The algorithm allows synthesized illumination to be linked with assorted pattern libraries, which has a direct impact on design rule studies for early planning and design automation for full wafer optimization.

Maternal and early life factors of tooth emergence patterns and number of teeth at one and two years of age

PubMed Central

Ntani, Georgia; Day, Peter F; Baird, Janis; Godfrey, Keith M; Robinson, Sian M; Cooper, Cyrus; Inskip, Hazel M

2015-01-01

Various environmental factors have been associated with the timing of eruption of primary dentition, but the evidence to date comes from small studies with limited information on potential risk factors. We aimed to investigate associations between tooth emergence patterns and pre-conception, pregnancy and post-natal influences. Dentition patterns were recorded at ages one and two years in 2,915 children born to women in the Southampton Women’s Survey from whom information had been collected on maternal factors before conception and during pregnancy. In mutually adjusted regression models we found that: children were more dentally advanced at ages one and two years if their mothers had smoked during pregnancy or they were longer at birth; mothers of children whose dental development was advanced at age two years tended to have poorer socioeconomic circumstances, and to have reported a slower walking speed pre-pregnancy; and children of mothers of Asian ethnicity had later tooth development than those of white mothers. The findings add to the evidence of environmental impacts on the timing of the eruption of primary dentition in indicating that maternal smoking during pregnancy, socio-economic status and physical activity (assessed by reported walking speed) may influence the child’s primary dentition. Early life factors, including size at birth are also associated with dentition patterns, as is maternal ethnicity. PMID:25936832

The role of eggshell and underlying vitelline membrane for normal pattern formation in the early C. elegans embryo.

PubMed

Schierenberg, Einhard; Junkersdorf, Bernd

1992-12-01

The embryo of the nematode Caenorhabditis elegans is surrounded by an inconspicuous inner vitelline membrane and a prominent outer chitinous eggshell proper. We demonstrate that the complete removal of the chitinous eggshell does not interfere with successful development to yield a normal worm. The same result can be obtained when the vitelline membrane is penetrated with laser microbeam irradiation of only the eggshell proper, gently enough to permit its resealing after a while. However, when large holes are made into the eggshell the concomitantly penetrated vitelline membrane does not reseal. While early development is quite normal under these conditions, gastrulation is defective in that gut precursor cells do not migrate in properly, eventually leading to embryonic arrest. This suggests a crucial role for pattern formation of the "micro-environment" around the embryo preserved by the intact vitelline membrane. Removing both eggshell and vitelline membrane results in a string-like arrangement of founder cells and subsequent grossly abnormal cell patterns. Our experiments support the idea that the prominent eggshell proper just functions as a mechanical protection while the thin vitelline membrane directly or indirectly serves as a necessary control element affecting the positions of cells which to begin with are determined by the orientation of the cleavage spindle.

Contraceptive Patterns of College Students Who Experienced Early Coitus.

ERIC Educational Resources Information Center

Vincent, Murray L.; And Others

1981-01-01

A study investigated the coital behavior, contraceptive use, and attitudes of 20-year-old male and female college students who experienced sexual intercourse early in adolescence (at 16 or younger) as contrasted to those who experienced coitus in late adolescence. Results indicate that older adolescents were more likely to use contraceptives and,…

Sox5 is a DNA binding co-factor for BMP R-Smads that directs target specificity during patterning of the early ectoderm

PubMed Central

Nordin, Kara; LaBonne, Carole

2014-01-01

SUMMARY The SoxD factor, Sox5, is expressed in ectodermal cells at times and places where BMP signaling is active, including the cells of the animal hemisphere at blastula stages, and the neural plate border (NPB) and neural crest (NC) at neurula stages. Sox5 is required for proper ectoderm development, and deficient embryos display patterning defects characteristic of perturbations of BMP signaling, including loss of neural crest and epidermis and expansion of the neural plate. We show that Sox5 is essential for activation of BMP target genes in embryos and explants, that it physically interacts with BMP R-Smads, and that it is essential for recruitment of Smad1/4 to BMP regulatory elements. Our findings identify Sox5 as the long sought DNA binding partner for BMP R-Smads essential to plasticity and pattern in the early ectoderm. PMID:25453832

Emerging Understanding of Patterning in 4-Year-Olds

ERIC Educational Resources Information Center

Rittle-Johnson, Bethany; Fyfe, Emily R.; McLean, Laura E.; McEldoon, Katherine L.

2013-01-01

Young children have an impressive amount of mathematics knowledge, but past psychological research has focused primarily on their number knowledge. Preschoolers also spontaneously engage in a form of early algebraic thinking-patterning. In the current study, we assessed 4-year-old children's knowledge of repeating patterns on two occasions…

Patterning roadmap: 2017 prospects

NASA Astrophysics Data System (ADS)

Neisser, Mark

2017-06-01

Road mapping of semiconductor chips has been underway for over 20 years, first with the International Technology Roadmap for Semiconductors (ITRS) roadmap and now with the International Roadmap for Devices and Systems (IRDS) roadmap. The original roadmap was mostly driven bottom up and was developed to ensure that the large numbers of semiconductor producers and suppliers had good information to base their research and development on. The current roadmap is generated more top-down, where the customers of semiconductor chips anticipate what will be needed in the future and the roadmap projects what will be needed to fulfill that demand. The More Moore section of the roadmap projects that advanced logic will drive higher-resolution patterning, rather than memory chips. Potential solutions for patterning future logic nodes can be derived as extensions of `next-generation' patterning technologies currently under development. Advanced patterning has made great progress, and two `next-generation' patterning technologies, EUV and nanoimprint lithography, have potential to be in production as early as 2018. The potential adoption of two different next-generation patterning technologies suggests that patterning technology is becoming more specialized. This is good for the industry in that it lowers overall costs, but may lead to slower progress in extending any one patterning technology in the future.

The detection of T-wave variation linked to arrhythmic risk: an industry perspective.

PubMed

Xue, Joel; Rowlandson, Ian

2013-01-01

Although the scientific literature contains ample descriptions of peculiar patterns of repolarization linked to arrhythmic risk, the objective quantification and classification of these patterns continues to be a challenge that impacts their widespread adoption in clinical practice. To advance the science, computerized algorithms spawned in the academic environment have been essential in order to find, extract and measure these patterns. However, outside the strict control of a core lab, these algorithms are exposed to poor quality signals and need to be effective in the presence of different forms of noise that can either obscure or mimic the T-wave variation (TWV) of interest. To provide a practical solution that can be verified and validated for the market, important tradeoffs need to be made that are based on an intimate understanding of the end-user as well as the key characteristics of either the signal or the noise that can be used by the signal processing engineer to best differentiate them. To illustrate this, two contemporary medical devices used for quantifying T-wave variation are presented, including the modified moving average (MMA) for the detection of T-wave Alternans (TWA) and the quantification of T-wave shape as inputs to the Morphology Combination Score (MCS) for the trending of drug-induced repolarization abnormalities. © 2013 Elsevier Inc. All rights reserved.

Binocular rivalry from invisible patterns

PubMed Central

Zou, Jinyou; He, Sheng; Zhang, Peng

2016-01-01

Binocular rivalry arises when incompatible images are presented to the two eyes. If the two eyes’ conflicting features are invisible, leading to identical perceptual interpretations, does rivalry competition still occur? Here we investigated whether binocular rivalry can be induced from conflicting but invisible spatial patterns. A chromatic grating counterphase flickering at 30 Hz appeared uniform, but produced significant tilt aftereffect and orientation-selective adaptation. The invisible pattern also generated significant BOLD activities in the early visual cortex, with minimal response in the parietal and frontal cortical areas. Compared with perceptually matched uniform stimuli, a monocularly presented invisible chromatic grating enhanced the rivalry competition with a low-contrast visible grating presented to the other eye. Furthermore, switching from a uniform field to a perceptually matched invisible chromatic grating produced interocular suppression at approximately 200 ms after onset of the invisible grating. Experiments using briefly presented monocular probes revealed evidence for sustained rivalry competition between two invisible gratings during continuous dichoptic presentations. These findings indicate that even without visible interocular conflict, and with minimal engagement of frontoparietal cortex and consciousness related top-down feedback, perceptually identical patterns with invisible conflict features produce rivalry competition in the early visual cortex. PMID:27354535

HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC.

PubMed

Wood, Natasha; Bhattacharya, Tanmoy; Keele, Brandon F; Giorgi, Elena; Liu, Michael; Gaschen, Brian; Daniels, Marcus; Ferrari, Guido; Haynes, Barton F; McMichael, Andrew; Shaw, George M; Hahn, Beatrice H; Korber, Bette; Seoighe, Cathal

2009-05-01

The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide

HIV Evolution in Early Infection: Selection Pressures, Patterns of Insertion and Deletion, and the Impact of APOBEC

PubMed Central

Wood, Natasha; Bhattacharya, Tanmoy; Keele, Brandon F.; Giorgi, Elena; Liu, Michael; Gaschen, Brian; Daniels, Marcus; Ferrari, Guido; Haynes, Barton F.; McMichael, Andrew; Shaw, George M.; Hahn, Beatrice H.; Korber, Bette; Seoighe, Cathal

2009-01-01

The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions

PubMed Central

Hendrickx, Debbie A. E.; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G.; van Eden, Corbert G.; Hol, Elly M.; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1, and ANO4. Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16, and OLR1, and lipid uptake, such as CHIT1, GPNMB, and CCL18. Except CCL18, these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion. PMID:29312322

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions.

PubMed

Hendrickx, Debbie A E; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G; van Eden, Corbert G; Hol, Elly M; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1 , and ANO4 . Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16 , and OLR1 , and lipid uptake, such as CHIT1, GPNMB , and CCL18 . Except CCL18 , these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion.

A new 4-variable formula to differentiate normal variant ST segment elevation in V2-V4 (early repolarization) from subtle left anterior descending coronary occlusion - Adding QRS amplitude of V2 improves the model.

PubMed

Driver, Brian E; Khalil, Ayesha; Henry, Timothy; Kazmi, Faraz; Adil, Amina; Smith, Stephen W

Precordial normal variant ST elevation (NV-STE), previously often called "early repolarization," may be difficult to differentiate from subtle ischemic STE due to left anterior descending (LAD) occlusion. We previously derived and validated a logistic regression formula that was far superior to STE alone for differentiating the two entities on the ECG. The tool uses R-wave amplitude in lead V4 (RAV4), ST elevation at 60 ms after the J-point in lead V3 (STE60V3) and the computerized Bazett-corrected QT interval (QTc-B). The 3-variable formula is: 1.196 x STE60V3 + 0.059 × QTc-B - 0.326 × RAV4 with a value ≥23.4 likely to be acute myocardial infarction (AMI). Adding QRS voltage in V2 (QRSV2) would improve the accuracy of the formula. 355 consecutive cases of proven LAD occlusion were reviewed, and those that were obvious ST elevation myocardial infarction were excluded. Exclusion was based on one straight or convex ST segment in V2-V6, 1 millimeter of summed inferior ST depression, any anterior ST depression, Q-waves, "terminal QRS distortion," or any ST elevation >5 mm. The NV-STE group comprised emergency department patients with chest pain who ruled out for AMI by serial troponins, had a cardiologist ECG read of "NV-STE," and had at least 1 mm of STE in V2 and V3. R-wave amplitude in lead V4 (RAV4), ST elevation at 60 ms after the J-point in lead V3 (STE60V3) and the computerized Bazett-corrected QT interval (QTc-B) had previously been measured in all ECGs; physicians blinded to outcome then measured QRSV2 in all ECGs. A 4-variable formula was derived to more accurately classify LAD occlusion vs. NV-STE and optimize area under the curve (AUC) and compared with the previous 3-variable formula. There were 143 subtle LAD occlusions and 171 NV-STE. A low QRSV2 added diagnostic utility. The derived 4-variable formula is: 0.052*QTc-B - 0.151*QRSV2 - 0.268*RV4 + 1.062*STE60V3. The 3-variable formula had an AUC of 0.9538 vs. 0.9686 for the 4-variable formula (p = 0

Patterns and trends of early successional forests in the Eastern United States

Treesearch

Margaret K. Trani; Robert T. Brooks; Thomas L. Schmidt; Victor A. Rudis; Christine M. Gabbard

2001-01-01

We assessed the status of early successional forest conditions for 33 Eastern States within the New England, Middle Atlantic, Great Lakes, Central Plains, Coastal South, and Interior South subregions. We used Forest Inventory and Analysis surveys to analyze trends from 1946 to 1998. Dramatic regional differences occurred in distribution of early successional forests....

Luteal phase deficiency: abnormal gonadotropin and progesterone secretion patterns.

PubMed

Soules, M R; Clifton, D K; Cohen, N L; Bremner, W J; Steiner, R A

1989-10-01

Luteal phase deficiency (LPD) is a reproductive disorder associated with infertility and spontaneous abortion. This study was undertaken to determine whether LPD might be related to an abnormal pattern of gonadotropin secretion. We tested this hypothesis by evaluating the pattern of pulsatile LH secretion in both the follicular and luteal phases of the menstrual cycle in normal women (n = 21) and women with LPD (n = 20), which was diagnosed on the basis of two out of phase endometrial biopsies. In addition, we sought to determine whether changes in progesterone (P) pulse patterns could account for the decrease in average serum P levels in women with LPD. To this end, we examined the pulse patterns of P and compared these patterns between normal women and those with LPD. Frequent blood sampling was performed in both groups to determine their respective hormone secretion patterns. In the follicular phase, blood samples were obtained every 10 min for 12 h; in the luteal phase the samples were obtained every 10 min for 12 h; in the luteal LH, FSH, and P were assayed in each sample. Pulse detection was performed by an adaptive threshold method of pulse analysis. The LH pulse frequency was significantly higher in the women with LPD than in the normal women in the early follicular phase [P less than 0.05; LPD, 12.8 +/- 1.4 (+/- SE); normal, 8.2 +/- 0.7 pulses/12 h]. LH pulse frequency was similar in the early and late follicular phases in the women with LPD, whereas it was higher in the late follicular phase in normal women. Mean serum FSH levels were not different between groups in both the early and late follicular phases. In the luteal phase the P pulse amplitude and mean serum P level were significantly lower in the LPD group than in the normal women (P less than 0.01). We conclude that 1) a too rapid LH pulse pattern in the early follicular phase may lead to inadequate LH support of the corpus luteum and become manifest as LPD; 2) the mechanism for inadequate P

Visualization of Dietary Patterns and Their Associations With Age-Related Macular Degeneration.

PubMed

Chiu, Chung-Jung; Chang, Min-Lee; Li, Tricia; Gensler, Gary; Taylor, Allen

2017-03-01

We aimed to visualize the relationship of predominant dietary patterns and their associations with AMD. A total of 8103 eyes from 4088 participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into three groups: control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765). Using principle component analysis, two major dietary patterns and eight minor dietary patterns were characterized. Applying logistic regression in our analysis, we related dietary patterns to the prevalence of AMD. Qualitative comparative analysis by operating Boolean algebra and drawing Venn diagrams was used to visualize our findings. In general, the eight minor patterns were subsets or extensions of either one of the two major dietary patterns (Oriental and Western patterns) and consisted of fewer characteristic foods than the two major dietary patterns. Unlike the two major patterns, which were more strongly associated with both early and advanced AMD, none of the eight minors were associated with early AMD and only four minor patterns, including the Steak pattern (odds ratio comparing the highest to lowest quintile of the pattern score = 1.73 [95% confidence interval: 1.24 to 2.41; Ptrend = 0.02]), the Breakfast pattern (0.60 [0.44 to 0.82]; Ptrend = 0.004]), the Caribbean pattern (0.64 [0.47 to 0.89; Ptrend = 0.009]), and the Peanut pattern (0.64 [0.46 to 0.89; Ptrend = 0.03]), were significantly associated with advanced AMD. Our data also suggested several potential beneficial (peanuts, pizza, coffee, and tea) and harmful (salad dressing) foods for AMD. Our data indicate that a diet of various healthy foods may be optimal for reducing AMD risk. The effects of some specific foods in the context of overall diet warrant further study.

Mechanism linking T-wave alternans to the genesis of cardiac fibrillation.

PubMed

Pastore, J M; Girouard, S D; Laurita, K R; Akar, F G; Rosenbaum, D S

1999-03-16

Although T-wave alternans has been closely associated with vulnerability to ventricular arrhythmias, the cellular processes underlying T-wave alternans and their role, if any, in the mechanism of reentry remain unclear. -T-wave alternans on the surface ECG was elicited in 8 Langendorff-perfused guinea pig hearts during fixed-rate pacing while action potentials were recorded simultaneously from 128 epicardial sites with voltage-sensitive dyes. Alternans of the repolarization phase of the action potential was observed above a critical threshold heart rate (HR) (209+/-46 bpm) that was significantly lower (by 57+/-36 bpm) than the HR threshold for alternation of action potential depolarization. The magnitude (range, 2.7 to 47.0 mV) and HR threshold (range, 171 to 272 bpm) of repolarization alternans varied substantially between cells across the epicardial surface. T-wave alternans on the surface ECG was explained primarily by beat-to-beat alternation in the time course of cellular repolarization. Above a critical HR, membrane repolarization alternated with the opposite phase between neighboring cells (ie, discordant alternans), creating large spatial gradients of repolarization. In the presence of discordant alternans, a small acceleration of pacing cycle length produced a characteristic sequence of events: (1) unidirectional block of an impulse propagating against steep gradients of repolarization, (2) reentrant propagation, and (3) the initiation of ventricular fibrillation. Repolarization alternans at the level of the single cell accounts for T-wave alternans on the surface ECG. Discordant alternans produces spatial gradients of repolarization of sufficient magnitude to cause unidirectional block and reentrant ventricular fibrillation. These data establish a mechanism linking T-wave alternans of the ECG to the pathogenesis of sudden cardiac death.

Stress Patterns in High-Frequency Russian Nouns and Verbs.

ERIC Educational Resources Information Center

Cubberley, Paul

1987-01-01

Analyses for stress patterns of the first 1,000 nouns and 500 verbs from a high-frequency Russian vocabulary list. The most irregular patterns are seen in the most frequently occurring items and, therefore, should be learned early in the study of Russian. (Author/LMO)

Dermatoglyphics: a genetic marker of early childhood caries.

PubMed

Anitha, C; Konde, Sapna; Raj, N Sunil; Kumar, N C; Peethamber, Preetha

2014-01-01

It is an accepted fact that genetics plays an important role in determination of palmar dermatoglyphic patterns. Since caries is a multifactorial disease with the influence of genetic pattern, this study was undertaken to explore the possibility of dermatoglyphics as a noninvasive and early predictor of dental caries in children, so as to initiate preventive oral health measures at an early age. The study group comprised of 200 children aged between 4 and 5 years. The dmfs score was evaluated. The experimental group (Group 1), comprised of 100 children with early childhood caries (ECC) with dmfs >5. The control group (Group 2) comprised of 100 children with dmfs score of 0. An increased frequency of ulnar loops in caries-free children and whorls in children with ECC was observed. Low mean atd angle and low mean. Total ridge count was observed in the ECC group. There is definite variation in dermatoglyphics between the ECC and caries-free group, indicating that dermatoglyphic patterns can be used as a predictive tool for children with ECC.

Withaferin-A, a steroidal lactone encapsulated mannose decorated liposomes ameliorates rheumatoid arthritis by intriguing the macrophage repolarization in adjuvant-induced arthritic rats.

PubMed

Sultana, Farhath; Neog, Manoj Kumar; Rasool, MahaboobKhan

2017-07-01

In order to develop a better therapeutic approach for the treatment of rheumatoid arthritis (RA), withaferin-A; a steroidal lactone incorporated with mannosylated liposomes (ML-WA) was administered to adjuvant induced arthritic rats in intent to target the synovial macrophages. The confocal microscopy studies showed a successful internalization of ML-WA in the primarily isolated synovial macrophages. Consequently, targeting synovial macrophages via ML-WA reduced the oxidative stress (ROS and NO), and paw edema, however, a progressive gain in the body weight was observed in AIA rats. ML-WA treatment upregulated the production of osteoprotegerin (OPG) and downregulated the release of receptor activator of nuclear factor-κB ligand (RANKL), favoring osteoclastogenesis negatively. Correspondingly, the ankle joints were found intact with no bone erosion and cartilage degradation in ML-WA treated AIA rats as evidenced by histopathological analysis. Also, synovial macrophage assessment showed that the concentration and the gene amplification of M1 macrophage mediated pro-inflammatory mediators (TNF-α, IL-1β, IL-6, MCP-1 and VEGF) were curtailed in ML-WA treated AIA rats. In contrast, anti-inflammatory cytokine (IL-10) was found abundantly released. Furthermore, the mRNA expression of the M1 surface marker (CD86) was found down regulated, whereas, M2 marker (CD163) was highly amplified in ML-WA treated synovial macrophages of arthritic rats. Cumulatively, our result signified that targeted delivery of ML-WA ameliorated the severity of inflammation and bone resorption in AIA rats via M1 to M2 macrophage repolarization. Copyright © 2017 Elsevier B.V. All rights reserved.

Automatic classification of thermal patterns in diabetic foot based on morphological pattern spectrum

NASA Astrophysics Data System (ADS)

Hernandez-Contreras, D.; Peregrina-Barreto, H.; Rangel-Magdaleno, J.; Ramirez-Cortes, J.; Renero-Carrillo, F.

2015-11-01

This paper presents a novel approach to characterize and identify patterns of temperature in thermographic images of the human foot plant in support of early diagnosis and follow-up of diabetic patients. Composed feature vectors based on 3D morphological pattern spectrum (pecstrum) and relative position, allow the system to quantitatively characterize and discriminate non-diabetic (control) and diabetic (DM) groups. Non-linear classification using neural networks is used for that purpose. A classification rate of 94.33% in average was obtained with the composed feature extraction process proposed in this paper. Performance evaluation and obtained results are presented.

Pattern separation in the hippocampus

PubMed Central

Yassa, Michael A.; Stark, Craig E. L.

2011-01-01

The ability to discriminate among similar experiences is a critical feature of episodic memory. This ability has long been hypothesized to require the hippocampus, with computational models suggesting it is dependent on pattern separation. However, empirical data for the hippocampus’ role in pattern separation was not available until recently. This review summarizes data from electrophysiological recordings, lesion studies, immediate early gene imaging, transgenic mouse models, as well as human functional neuroimaging that provide convergent evidence for the involvement of particular hippocampal subfields in this key process. We discuss the impact of aging and adult neurogenesis on pattern separation, as well as highlight several challenges to linking across species and approaches and suggest future directions for investigation. PMID:21788086

Longitudinal patterns of poverty and health in early childhood: exploring the influence of concurrent, previous, and cumulative poverty on child health outcomes

PubMed Central

2012-01-01

Background Although the links between poverty and health have often been studied , the dynamics of poverty and physical health in early childhood remain under-investigated. In particular, it is not known whether the health of young children is affected differently from that of adults by patterns of poverty unique to them. Methods We examined patterns of health from 5 to 41 months of age as a function of concurrent, lagged, and chronic exposure to insufficient income. Using data from the first four rounds of the Quebec Longitudinal Study of Child Development, we performed multilevel logistic and multilevel Poisson regressions and latent growth curve analyses to explore associations between exposure to poverty and mother-reported asthma-like attacks, and maternal perception of health status controlling for neonatal, maternal, and environmental characteristics. Results The mean number of mother-reported asthma-like attacks significantly decreased as children aged. The likelihood of being perceived in a poorer health status also decreased across time. Concurrent poverty was associated with more mother-reported asthma-like attacks and with a higher risk of being perceived in poorer health status. One-period-lagged poverty was associated with more mother-reported asthma-like attacks and this remained significant after controlling for concurrent poverty. The number of mother-reported asthma-like attacks was significantly higher among children in the chronic poverty class compared to those in the never-poor class, particularly at 17 and 29 months. Perceived health status at 5-months was significantly poorer among chronically poor children compared to never-poor children. Conclusion Exposure to poverty negatively affects two major health indicators in early childhood – maternal perception of child health and mother-reported asthma-like attacks. Patterns of the effects vary according to timing and duration of poverty exposure. Further longitudinal research is warranted

Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis.

PubMed

Pérez-García, Georgina; Guzmán-Quevedo, Omar; Da Silva Aragão, Raquel; Bolaños-Jiménez, Francisco

2016-02-17

Numerous epidemiological studies indicate that malnutrition during in utero development and/or childhood induces long-lasting learning disabilities and enhanced susceptibility to develop psychiatric disorders. However, animal studies aimed to address this question have yielded inconsistent results due to the use of learning tasks involving negative or positive reinforces that interfere with the enduring changes in emotional reactivity and motivation produced by in utero and neonatal malnutrition. Consequently, the mechanisms underlying the learning deficits associated with malnutrition in early life remain unknown. Here we implemented a behavioural paradigm based on the combination of the novel object recognition and the novel object location tasks to define the impact of early protein-restriction on the behavioural, cellular and molecular basis of memory processing. Adult rats born to dams fed a low-protein diet during pregnancy and lactation, exhibited impaired encoding and consolidation of memory resulting from impaired pattern separation. This learning deficit was associated with reduced production of newly born hippocampal neurons and down regulation of BDNF gene expression. These data sustain the existence of a causal relationship between early malnutrition and impaired learning in adulthood and show that decreased adult neurogenesis is associated to the cognitive deficits induced by childhood exposure to poor nutrition.

Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis

PubMed Central

Pérez-García, Georgina; Guzmán-Quevedo, Omar; Da Silva Aragão, Raquel; Bolaños-Jiménez, Francisco

2016-01-01

Numerous epidemiological studies indicate that malnutrition during in utero development and/or childhood induces long-lasting learning disabilities and enhanced susceptibility to develop psychiatric disorders. However, animal studies aimed to address this question have yielded inconsistent results due to the use of learning tasks involving negative or positive reinforces that interfere with the enduring changes in emotional reactivity and motivation produced by in utero and neonatal malnutrition. Consequently, the mechanisms underlying the learning deficits associated with malnutrition in early life remain unknown. Here we implemented a behavioural paradigm based on the combination of the novel object recognition and the novel object location tasks to define the impact of early protein-restriction on the behavioural, cellular and molecular basis of memory processing. Adult rats born to dams fed a low-protein diet during pregnancy and lactation, exhibited impaired encoding and consolidation of memory resulting from impaired pattern separation. This learning deficit was associated with reduced production of newly born hippocampal neurons and down regulation of BDNF gene expression. These data sustain the existence of a causal relationship between early malnutrition and impaired learning in adulthood and show that decreased adult neurogenesis is associated to the cognitive deficits induced by childhood exposure to poor nutrition. PMID:26882991

Beyond the Length and Look of Repolarization: Defining the Non-QTc Electrocardiographic Profiles of Patients with Congenital Long QT Syndrome.

PubMed

Lane, Conor M; Bos, J Martijn; Rohatgi, Ram K; Ackerman, Michael J

2018-04-30

Little is known about the spectrum and prevalence of ECG features beyond the length and morphology of repolarization in patients with congenital long QT syndrome (LQTS). To characterize the full ECG phenotype of LQTS patients and evaluate differences by age and LQTS genotype. Retrospective review of 943 patients with LQTS (57% female, median age 25 years; IQR 9 - 34 years) was performed. Comprehensive analysis of their initial evaluation ECG was performed using definitions outlined in Heart Rhythm Society guidelines. Bradycardia was common (n=320; 34%), regardless of beta-blocker use. Left axis deviation (n=33, 3.5%) and bundle branch block (n=5, 0.5%) were uncommon. T-wave inversion (TWI) involving leads V1 and V3 was more common in LQT2 compared to LQT1 or LQT3 [OR for V1: 2.67 (95% CI 1.8 - 3.9) and OR for V3: 1.76 (95% CI 1.2 - 2.6)], while TWI in lead III and aVF was most common in LQT3 [OR for III: 2.38 (95% CI 1.4 - 4.2) and OR for aVF: 3.14 (95% CI 1.6 - 6.4)]. Notched T-waves were most apparent at younger ages (48% in patients between ages 4-10 compared to 12% in over 40s, p <0.0001). Beyond the QT interval and bradycardia, ECG abnormalities are uncommon in LQTS patients and patients almost never have concomitant bundle branch block. Notably, 19% of LQTS patients overall and 27% of LQT2 patients exhibit anterior TWI that would satisfy a diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy creating the potential for diagnostic miscues. Copyright © 2018. Published by Elsevier Inc.

Electrocardiographic measures of repolarization dispersion and their relationships with echocardiographic indices of ventricular remodeling and premature ventricular beats in hypertension

PubMed Central

Ciobanu, Ana; Tse, Gary; Liu, Tong; Deaconu, Maria V; Gheorghe, Gabriela S; Ilieşiu, Adriana M; Nanea, Ioan T

2017-01-01

Objective To examine the relationship between Tpeak- Tend interval (Tpe) and Tpe/QT ratio with occurrence of ventricular premature beats (VPBs) and left ventricular remodeling in hypertension. Methods A total of 52 patients with mild to moderate essential hypertension were included, undergoing echocardiography and 24-hours Holter monitoring. Ventricular remodeling was assessed by left ventricular mass index (LVMI) using the Devereux formula and diastolic function by transmitral E and A wave velocities and E/A ratio. Tpe was measured in the precordial leads. The end of the T wave was set by the method of the tangent to the steepest descending slope of the T wave. Results Tpe and Tpe/QT in leads V2 (r = 0.33, P = 0.01; r = 0.27, P = 0.04 respectively) and V3 (r = 0.40, P = 0.002; r = 0.40, P = 0.003, respectively) correlated significantly with LVMI. A significant inverse relationship was observed between E/A ratio and QT (r = −0.33, P = 0.01), Tpe in V3 (r = −0.39, P = 0.003) and Tpe/QT in V3 (r = −0.31, P = 0.02). Tpe in V3, V5, mean Tpe and maximum Tpe with cut-off values of 60 ms, 59 ms, 62 ms and 71 ms, respectively, associated with the occurrence of ventricular premature beats. Conclusions The repolarization parameters Tpe interval and Tpe/QT ratio correlate with LVMI and indices of left ventricular diastolic function and show better predictive values than traditional parameters such as QT interval and QT dispersion. Lead V3 is the best lead for measuring Tpe and Tpe/QT. These ECG indices can therefore be used in clinical practice to monitor LV remodeling and predict occurrence of VPBs. PMID:29581710

The proteome pattern cGvHD_MS14 allows early and accurate prediction of chronic GvHD after allogeneic stem cell transplantation.

PubMed

Weissinger, E M; Human, C; Metzger, J; Hambach, L; Wolf, D; Greinix, H T; Dickinson, A M; Mullen, W; Jonigk, D; Kuzmina, Z; Kreipe, H; Schweier, P; Böhm, O; Türüchanow, I; Ihlenburg-Schwarz, D; Raad, J; Durban, A; Schiemann, M; Könecke, C; Diedrich, H; Holler, E; Beutel, G; Krauter, J; Ganser, A; Stadler, M

2017-03-01

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be curative, but is associated with significant morbidity and mortality. Chronic graft-versus-host disease (cGvHD), characterized by inflammation and fibrosis of multiple target organs, considerably contributes to the morbidity and mortality even years after allo-HSCT. Diagnosis of cGvHD is based on clinical features and histology of biopsies. Here, we report the generation of a urinary cGvHD-specific proteome-pattern (cGvHD_MS14) established by capillary electrophoresis-mass spectrometry to predict onset and severity of cGvHD as an unbiased laboratory test. cGvHD_MS14 was evaluated on samples from 412 patients collected prospectively in four transplant centers. Sensitivity and specificity was 84 and 76% by cGvHD_MS14 classification. Sensitivity further increased to 93% by combination of cGvHD_MS14 with relevant clinical variables to a logistic regression model. cGvHD was predicted up to 55 days prior to clinical diagnosis. Acute GvHD is not recognized by cGvHD_MS14. cGvHD_MS14 consists of 14 differentially excreted peptides, six of those have been sequenced to date and are fragments from thymosin β-4, eukaryotic translation initiation factor 4γ2, fibrinogen β-chain or collagens. In conclusion, the cGvHD_MS14-pattern allows early, highly sensitive and specific prediction of cGvHD as an independent diagnostic criterion of clinical diagnosis potentially allowing early therapeutic intervention.

Image projection optical system for measuring pattern electroretinograms

NASA Astrophysics Data System (ADS)

Starkey, Douglas E.; Taboada, John; Peters, Daniel

1994-06-01

The use of the pattern-electroretinogram (PERG) as a noninvasive diagnostic tool for the early detection of glaucoma has been supported by a number of recent studies. We have developed a unique device which uses a laser interferometer to generate a sinusoidal fringe pattern that is presented to the eye in Maxwellian view for the purpose of producing a PERG response. The projection system stimulates a large visual field and is designed to bypass the optics of the eye in order to measure the true retinal response to a temporally alternating fringe pattern. The contrast, spatial frequency, total power output, orientation, alternating temporal frequency, and field location of the fringe pattern presented to the eye can all be varied by the device. It is critical for these parameters to be variable so that optimal settings may be determined for the normal state and any deviation from it, i.e. early or preclinical glaucoma. Several interferometer designs and optical projection systems were studied in order to design a compact system which provided the desired variable pattern stimulus to the eye. This paper will present a description of the clinical research instrument and its performance with the primary emphasis on the optical system design as it relates to the fringe pattern generation and other optical parameters. Examples of its use in the study of glaucoma diagnosis will also be presented.

Early Admissions at Selective Colleges. NBER Working Paper No. 14844

ERIC Educational Resources Information Center

Avery, Christopher; Levin, Jonathan D.

2009-01-01

Early admissions is widely used by selective colleges and universities. We identify some basic facts about early admissions policies, including the admissions advantage enjoyed by early applicants and patterns in application behavior, and propose a game-theoretic model that matches these facts. The key feature of the model is that colleges want to…

Diverse Pathways in Early Childhood Professional Development: An Exploration of Early Educators in Public Preschools, Private Preschools, and Family Child Care Homes

PubMed Central

Fuligni, Allison Sidle; Howes, Carollee; Lara-Cinisomo, Sandraluz; Karoly, Lynn

2009-01-01

This paper presents a naturalistic investigation of the patterns of formal education, early childhood education training, and mentoring of a diverse group of urban early childhood educators participating in the Los Angeles: Exploring Children's Early Learning Settings (LA ExCELS) study. A total of 103 preschool teachers and family child care providers serving primarily low-income 3- and 4-year-old children in Los Angeles County provided data on their education, training, and beliefs about teaching. This sample worked in public center based preschool programs including Head Start classrooms and State preschool classrooms (N=42), private non-profit preschools including community based organizations and faith-based preschools (N=42), and licensed family child care homes (N=19). This study uses a person-centered approach to explore patterns of teacher preparation, sources of support, supervision, and mentoring across these 3 types of education settings, and how these patterns are associated with early childhood educators' beliefs and practices. Findings suggest a set of linkages between type of early education setting, professional development, and supervision of teaching. Public preschools have the strongest mandates for formal professional development and typically less variation in levels of monitoring, whereas family child care providers on average have less formal education and more variability in their access to and use of other forms of training and mentorship. Four distinct patterns of formal education, child development training, and ongoing mentoring or support were identified among the educators in this study. Associations between professional development experiences and teachers' beliefs and practices suggested the importance of higher levels of formal training for enhancing the quality of teacher-child interactions. Implications of the findings for changing teacher behaviors are discussed with respect to considering the setting context. PMID:20072719

Early patterning and specification of cardiac progenitors in gastrulating mesoderm

PubMed Central

Devine, W Patrick; Wythe, Joshua D; George, Matthew; Koshiba-Takeuchi, Kazuko; Bruneau, Benoit G

2014-01-01

Mammalian heart development requires precise allocation of cardiac progenitors. The existence of a multipotent progenitor for all anatomic and cellular components of the heart has been predicted but its identity and contribution to the two cardiac progenitor ‘fields’ has remained undefined. Here we show, using clonal genetic fate mapping, that Mesp1+ cells in gastrulating mesoderm are rapidly specified into committed cardiac precursors fated for distinct anatomic regions of the heart. We identify Smarcd3 as a marker of early specified cardiac precursors and identify within these precursors a compartment boundary at the future junction of the left and right ventricles that arises prior to morphogenesis. Our studies define the timing and hierarchy of cardiac progenitor specification and demonstrate that the cellular and anatomical fate of mesoderm-derived cardiac cells is specified very early. These findings will be important to understand the basis of congenital heart defects and to derive cardiac regeneration strategies. DOI: http://dx.doi.org/10.7554/eLife.03848.001 PMID:25296024

Trajectories of BMI from early childhood through early adolescence: SES and psychosocial predictors.

PubMed

Lane, Sean P; Bluestone, Cheryl; Burke, Christopher T

2013-02-01

This study examined the ways in which body mass index (BMI) percentile - an identified risk factor for overweight and cardiovascular disease in adulthood - develops from birth through early adolescence. In addition, we examined whether psychosocial factors, such as parenting style and maternal depression, mediated the link between socio-economic status (SES) and BMI growth. Design. Data were obtained from phases 1-3 of the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (SECCYD) - a longitudinal study that followed children from 10 communities in the United States from birth to age 11. We applied growth mixture models to identify distinct subtypes of BMI development. Within these models, we performed between- and within-class mediation analyses to examine whether SES predicted class membership or differences in development within each class via maternal depression and parenting styles. Results identified three prototypic trajectories of BMI percentile growth, elevated, steady increase, and stable. We found evidence for both between- and within-class mediation, suggesting multiple pathways by which SES can affect BMI development. These findings add to the research that suggests that being in a family with a low SES is associated with falling into patterns of development characterized by early and lasting increases in BMI relative to one's peers, and that this association is partly accounted for by maternal depression and parenting styles. What is already known? Past research has found evidence that patterns of childhood overweight are impacted by socioeconomic status through psychosocial factors like parenting and depression. This evidence is often limited to individual points in time where neglectful, permissive, and authoritarian parenting and higher levels of maternal depression are associated with higher levels of overweight status among children from infancy to adolescence. However, little

Oldest known cranium of a juvenile New World monkey (Early Miocene, Patagonia, Argentina): implications for the taxonomy and the molar eruption pattern of early platyrrhines.

PubMed

Perry, Jonathan M G; Kay, Richard F; Vizcaíno, Sergio F; Bargo, M Susana

2014-09-01

A juvenile cranium of Homunculus patagonicus Ameghino, 1891a from the late Early Miocene of Santa Cruz Province (Argentina) provides the first evidence of developing cranial anatomy for any fossil platyrrhine. The specimen preserves the rostral part of the cranium with deciduous and permanent alveoli and teeth. The dental eruption sequence in the new specimen and a reassessment of eruption patterns in living and fossil platyrrhines suggest that the ancestral platyrrhine pattern of tooth replacement was for the permanent incisors to erupt before M(1), not an accelerated molar eruption (before the incisors) as recently proposed. Two genera and species of Santacrucian monkeys are now generally recognized: H. patagonicus Ameghino, 1891a and Killikaike blakei Tejedor et al., 2006. Taxonomic allocation of Santacrucian monkeys to these species encounters two obstacles: 1) the (now lost) holotype and a recently proposed neotype of H. patagonicus are mandibles from different localities and different geologic members of the Santa Cruz Formation, separated by approximately 0.7 million years, whereas the holotype of K. blakei is a rostral part of a cranium without a mandible; 2) no Santacrucian monkey with associated cranium and mandible has ever been found. Bearing in mind these uncertainties, our examination of the new specimen as well as other cranial specimens of Santacrucian monkeys establishes the overall dental and cranial similarity between the holotype of Killikaike blakei, adult cranial material previously referred to H. patagonicus, and the new juvenile specimen. This leads us to conclude that Killikaike blakei is a junior subjective synonym of H. patagonicus. Copyright © 2014 Elsevier Ltd. All rights reserved.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

PubMed

McGeachie, M J; Yates, K P; Zhou, X; Guo, F; Sternberg, A L; Van Natta, M L; Wise, R A; Szefler, S J; Sharma, S; Kho, A T; Cho, M H; Croteau-Chonka, D C; Castaldi, P J; Jain, G; Sanyal, A; Zhan, Y; Lajoie, B R; Dekker, J; Stamatoyannopoulos, J; Covar, R A; Zeiger, R S; Adkinson, N F; Williams, P V; Kelly, H W; Grasemann, H; Vonk, J M; Koppelman, G H; Postma, D S; Raby, B A; Houston, I; Lu, Q; Fuhlbrigge, A L; Tantisira, K G; Silverman, E K; Tonascia, J; Weiss, S T; Strunk, R C

2016-05-12

Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

PubMed

Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

2014-10-13

Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (<1 hr) P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

Early Menarche and Gestational Diabetes Mellitus at First Live Birth.

PubMed

Shen, Yun; Hu, Hui; D Taylor, Brandie; Kan, Haidong; Xu, Xiaohui

2017-03-01

To examine the association between early menarche and gestational diabetes mellitus (GDM). Data from the National Health and Nutrition Examination Survey 2007-2012 were used to investigate the association between age at menarche and the risk of GDM at first birth among 5914 women. A growth mixture model was used to detect distinctive menarche onset patterns based on self-reported age at menarche. Logistic regression models were then used to examine the associations between menarche initiation patterns and GDM after adjusting for sociodemographic factors, family history of diabetes mellitus, lifetime greatest Body Mass Index, smoking status, and physical activity level. Among the 5914 first-time mothers, 3.4 % had self-reported GDM. We detected three groups with heterogeneous menarche onset patterns, the Early, Normal, and Late Menarche Groups. The regression model shows that compared to the Normal Menarche Group, the Early Menarche Group had 1.75 (95 % CI 1.10, 2.79) times the odds of having GDM. No statistically significant difference was observed between the Normal and the Late Menarche Group. This study suggests that early menarche may be a risk factor of GDM. Future studies are warranted to examine and confirm this finding.

Dorsoventral patterning in hemichordates: insights into early chordate evolution.

PubMed

Lowe, Christopher J; Terasaki, Mark; Wu, Michael; Freeman, Robert M; Runft, Linda; Kwan, Kristen; Haigo, Saori; Aronowicz, Jochanan; Lander, Eric; Gruber, Chris; Smith, Mark; Kirschner, Marc; Gerhart, John

2006-09-01

We have compared the dorsoventral development of hemichordates and chordates to deduce the organization of their common ancestor, and hence to identify the evolutionary modifications of the chordate body axis after the lineages split. In the hemichordate embryo, genes encoding bone morphogenetic proteins (Bmp) 2/4 and 5/8, as well as several genes for modulators of Bmp activity, are expressed in a thin stripe of ectoderm on one midline, historically called "dorsal." On the opposite midline, the genes encoding Chordin and Anti-dorsalizing morphogenetic protein (Admp) are expressed. Thus, we find a Bmp-Chordin developmental axis preceding and underlying the anatomical dorsoventral axis of hemichordates, adding to the evidence from Drosophila and chordates that this axis may be at least as ancient as the first bilateral animals. Numerous genes encoding transcription factors and signaling ligands are expressed in the three germ layers of hemichordate embryos in distinct dorsoventral domains, such as pox neuro, pituitary homeobox, distalless, and tbx2/3 on the Bmp side and netrin, mnx, mox, and single-minded on the Chordin-Admp side. When we expose the embryo to excess Bmp protein, or when we deplete endogenous Bmp by small interfering RNA injections, these expression domains expand or contract, reflecting their activation or repression by Bmp, and the embryos develop as dorsalized or ventralized limit forms. Dorsoventral patterning is independent of anterior/posterior patterning, as in Drosophila but not chordates. Unlike both chordates and Drosophila, neural gene expression in hemichordates is not repressed by high Bmp levels, consistent with their development of a diffuse rather than centralized nervous system. We suggest that the common ancestor of hemichordates and chordates did not use its Bmp-Chordin axis to segregate epidermal and neural ectoderm but to pattern many other dorsoventral aspects of the germ layers, including neural cell fates within a diffuse

Dorsoventral Patterning in Hemichordates: Insights into Early Chordate Evolution

PubMed Central

Lowe, Christopher J; Terasaki, Mark; Wu, Michael; Freeman, Robert M; Runft, Linda; Kwan, Kristen; Haigo, Saori; Aronowicz, Jochanan; Lander, Eric; Gruber, Chris; Smith, Mark; Kirschner, Marc; Gerhart, John

2006-01-01

We have compared the dorsoventral development of hemichordates and chordates to deduce the organization of their common ancestor, and hence to identify the evolutionary modifications of the chordate body axis after the lineages split. In the hemichordate embryo, genes encoding bone morphogenetic proteins (Bmp) 2/4 and 5/8, as well as several genes for modulators of Bmp activity, are expressed in a thin stripe of ectoderm on one midline, historically called “dorsal.” On the opposite midline, the genes encoding Chordin and Anti-dorsalizing morphogenetic protein (Admp) are expressed. Thus, we find a Bmp-Chordin developmental axis preceding and underlying the anatomical dorsoventral axis of hemichordates, adding to the evidence from Drosophila and chordates that this axis may be at least as ancient as the first bilateral animals. Numerous genes encoding transcription factors and signaling ligands are expressed in the three germ layers of hemichordate embryos in distinct dorsoventral domains, such as pox neuro, pituitary homeobox, distalless, and tbx2/3 on the Bmp side and netrin, mnx, mox, and single-minded on the Chordin-Admp side. When we expose the embryo to excess Bmp protein, or when we deplete endogenous Bmp by small interfering RNA injections, these expression domains expand or contract, reflecting their activation or repression by Bmp, and the embryos develop as dorsalized or ventralized limit forms. Dorsoventral patterning is independent of anterior/posterior patterning, as in Drosophila but not chordates. Unlike both chordates and Drosophila, neural gene expression in hemichordates is not repressed by high Bmp levels, consistent with their development of a diffuse rather than centralized nervous system. We suggest that the common ancestor of hemichordates and chordates did not use its Bmp-Chordin axis to segregate epidermal and neural ectoderm but to pattern many other dorsoventral aspects of the germ layers, including neural cell fates within a diffuse

Early meteorological results from the viking 2 lander.

PubMed

Hess, S L; Henry, R M; Leovy, C B; Mitchell, J L; Ryan, J A; Tillman, J E

1976-12-11

Early results from the meteorological instruments on the Viking 2 lander are presented. As on lander 1, the daily patterns of temperature, wind, and pressure have been highly repetitive during the early summer period. The average daily maximum temperature was 241 degrees K and the diurnal minimum was 191 degrees K. The wind has a vector mean of 0.7 meter per second from the southeast with a diurnal amplitude of 3 meters per second. Pressure exhibits both diurnal and semidiurnal oscillations, although of substantially smaller amplitude than those of lander 1. Departures from the repetitive diurnal patterns begin to appear on sol 37.

Regulation of early human growth: impact on long-term health.

PubMed

Koletzko, Berthold; Chourdakis, Michael; Grote, Veit; Hellmuth, Christian; Prell, Christine; Rzehak, Peter; Uhl, Olaf; Weber, Martina

2014-01-01

Growth and development are central characteristics of childhood. Deviations from normal growth can indicate serious health challenges. The adverse impact of early growth faltering and malnutrition on later health has long been known. In contrast, the impact of rapid early weight and body fat gain on programming of later disease risk have only recently received increased attention. Numerous observational studies related diet in early childhood and rapid early growth to the risk of later obesity and associated disorders. Causality was confirmed in a large, double-blind randomised trial testing the 'Early Protein Hypothesis'. In this trial we found that attenuation of protein supply in infancy normalized early growth and markedly reduced obesity prevalence in early school age. These results indicate the need to describe and analyse growth patterns and their regulation through diet in more detail and to characterize the underlying metabolic and epigenetic mechanisms, given the potential major relevance for public health and policy. Better understanding of growth patterns and their regulation could have major benefits for the promotion of public health, consumer-orientated nutrition recommendations, and the development of improved food products for specific target populations. © 2014 S. Karger AG, Basel.

Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance

PubMed Central

Scarmeas, Nikolaos; Habeck, Christian G.; Zarahn, Eric; Anderson, Karen E.; Park, Aileen; Hilton, John; Pelton, Gregory H.; Tabert, Matthias H.; Honig, Lawrence S.; Moeller, James R.; Devanand, Davangere P.; Stern, Yaakov

2011-01-01

Although multivariate analytic techniques might identify diagnostic patterns that are not captured by univariate methods, they have rarely been used to study the neural correlates of Alzheimer's disease (AD) or cognitive impairment. Nonquantitative H215O PET scans were acquired during rest in 17 probable AD subjects selected for mild severity [mean-modified Mini Mental Status Examination (mMMS) 46/57; SD 5.1], 16 control subjects (mMMS 54; SD 2.5) and 23 subjects with minimal to mild cognitive impairment but no dementia (mMMS 53; SD 2.8). Expert clinical reading had low success in discriminating AD and controls. There were no significant mean flow differences among groups in traditional univariate SPM Voxel-wise analyses or region of interest (ROI) analyses. A covariance pattern was identified whose mean expression was significantly higher in the AD as compared to controls (P = 0.03; sensitivity 76–94%; specificity 63–81%). Sites of increased concomitant flow included insula, cuneus, pulvinar, lingual, fusiform, superior occipital and parahippocampal gyri, whereas decreased concomitant flow was found in cingulate, inferior parietal lobule, middle and inferior frontal, supramarginal and precentral gyri. The covariance analysis-derived pattern was then prospectively applied to the cognitively impaired subjects: as compared to subjects with Clinical Dementia Rating (CDR) = 0, subjects with CDR = 0.5 had significantly higher mean covariance pattern expression (P = 0.009). Expression of this pattern correlated inversely with Selective Reminding Test total recall (r = −0.401, P = 0.002), delayed recall (r = −0.351, P = 0.008) and mMMS scores (r = −0.401, P = 0.002) in all three groups combined. We conclude that patients with AD may differentially express resting cerebral blood flow covariance patterns even at very early disease stages. Significant alterations in expression of resting flow covariance patterns occur even for subjects with cognitive impairment

Diagnostic Transitions from Childhood to Adolescence to Early Adulthood

ERIC Educational Resources Information Center

Copeland, William E.; Adair, Carol E.; Smetanin, Paul; Stiff, David; Briante, Carla; Colman, Ian; Fergusson, David; Horwood, John; Poulton, Richie; Costello, E. Jane; Angold, Adrian

2013-01-01

Background: Quantifying diagnostic transitions across development is needed to estimate the long-term burden of mental illness. This study estimated patterns of diagnostic transitions from childhood to adolescence and from adolescence to early adulthood. Methods: Patterns of diagnostic transitions were estimated using data from three prospective,…

Early development of Xenopus embryos is affected by simulated gravity

NASA Technical Reports Server (NTRS)

Yokota, Hiroki; Neff, Anton W.; Malacinski, George M.

1994-01-01

Early amphibian (Xenopus laevis) development under clinostat-simulated weightlessness and centrifuge-simulated hypergravity was studied. The results revealed significant effects on (i) 'morphological patterning' such as the cleavage furrow pattern in the vegetal hemisphere at the eight-cell stage and the shape of the dorsal lip in early gastrulae and (ii) 'the timing of embryonic events' such as the third cleavage furrow completion and the dorsal lip appearance. Substantial variations in sensitivity to simulated force fields were observed, which should be considered in interpreting spaceflight data.

Spatial distributions of Kv4 channels and KChip2 isoforms in the murine heart based on laser capture microdissection.

PubMed

Teutsch, Christine; Kondo, Richard P; Dederko, Dorothy A; Chrast, Jacqueline; Chien, Kenneth R; Giles, Wayne R

2007-03-01

Regional differences in repolarizing K(+) current densities and expression levels of their molecular components are important for coordinating the pattern of electrical excitation and repolarization of the heart. The small size of hearts from mice may obscure these interventricular and/or transmural expression differences of K(+) channels. We have examined this possibility in adult mouse ventricle using a technology that provides very high spatial resolution of tissue collection. Conventional manual dissection and laser capture microdissection (LCM) were utilized to dissect tissue from distinct ventricular regions. RNA was isolated from epicardial, mid-myocardial and endocardial layers of both the right and left ventricles. Real-time RT-PCR was used to quantify the transcript expression in these different regions. LCM revealed significant interventricular and transmural gradients for both Kv4.2 and the alpha-subunit of KChIP2. The expression profile of a second K(+) channel transcript, Kir2.1, which is responsible for the inwardly rectifying K(+) current I(k1), showed no interventricular or transmural gradients and therefore served as a negative control. Our findings are in contrast to previous reports of a relatively uniform left ventricular transmural pattern of expression of Kv4.2, Kv4.3 and KChIP2 in adult mouse heart, which appear to be different than that in larger mammals. Specifically, our results demonstrate significant epi- to endocardial differences in the patterns of expression of both Kv4.2 and KChIP2.

Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.

PubMed

Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P

2017-10-04

Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons. SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike

Divergent RNA Localisation Patterns of Maternal Genes Regulating Embryonic Patterning in the Butterfly Pararge aegeria

PubMed Central

Carter, Jean-Michel; Gibbs, Melanie; Breuker, Casper J.

2015-01-01

The maternal effect genes responsible for patterning the embryo along the antero-posterior (AP) axis are broadly conserved in insects. The precise function of these maternal effect genes is the result of the localisation of their mRNA in the oocyte. The main developmental mechanisms involved have been elucidated in Drosophila melanogaster, but recent studies have shown that other insect orders often diverge in RNA localisation patterns. A recent study has shown that in the butterfly Pararge aegeria the distinction between blastodermal embryonic (i.e. germ band) and extra-embryonic tissue (i.e. serosa) is already specified in the oocyte during oogenesis in the ovariole, long before blastoderm cellularisation. To examine the extent by which a female butterfly specifies and patterns the AP axis within the region fated to be the germ band, and whether she specifies a germ plasm, we performed in situ hybridisation experiments on oocytes in P. aegeria ovarioles and on early embryos. RNA localisation of the following key maternal effect genes were investigated: caudal (cad), orthodenticle (otd), hunchback (hb) and four nanos (nos) paralogs, as well as TDRD7 a gene containing a key functional domain (OST-HTH/LOTUS) shared with oskar. TDRD7 was mainly confined to the follicle cells, whilst hb was exclusively zygotically transcribed. RNA of some of the nos paralogs, otd and cad revealed complex localisation patterns within the cortical region prefiguring the germ band (i.e. germ cortex). Rather interestingly, otd was localised within and outside the anterior of the germ cortex. Transcripts of nos-O formed a distinct granular ring in the middle of the germ cortex possibly prefiguring the region where germline stem cells form. These butterfly RNA localisation patterns are highly divergent with respect to other insects, highlighting the diverse ways in which different insect orders maternally regulate early embryogenesis of their offspring. PMID:26633019

New insights into roles of cell wall invertase in early seed development revealed by comprehensive spatial and temporal expression patterns of GhCWIN1 in cotton.

PubMed

Wang, Lu; Ruan, Yong-Ling

2012-10-01

Despite substantial evidence on the essential roles of cell wall invertase (CWIN) in seed filling, it remains largely unknown how CWIN exerts its regulation early in seed development, a critical stage that sets yield potential. To fill this knowledge gap, we systematically examined the spatial and temporal expression patterns of a major CWIN gene, GhCWIN1, in cotton (Gossypium hirsutum) seeds from prefertilization to prestorage phase. GhCWIN1 messenger RNA was abundant at the innermost seed coat cell layer at 5 d after anthesis but became undetectable at 10 d after anthesis, at the onset of its differentiation into transfer cells characterized by wall ingrowths, suggesting that CWIN may negatively regulate transfer cell differentiation. Within the filial tissues, GhCWIN1 transcript was detected in endosperm cells undergoing nuclear division but not in those cells at the cellularization stage, with similar results observed in Arabidopsis (Arabidopsis thaliana) endosperm for CWIN, AtCWIN4. These findings indicate a function of CWIN in nuclear division but not cell wall biosynthesis in endosperm, contrasting to the role proposed for sucrose synthase (Sus). Further analyses revealed a preferential expression pattern of GhCWIN1 and AtCWIN4 in the provascular region of the torpedo embryos in cotton and Arabidopsis seed, respectively, indicating a role of CWIN in vascular initiation. Together, these novel findings provide insights into the roles of CWIN in regulating early seed development spatially and temporally. By comparing with previous studies on Sus expression and in conjunction with the expression of other related genes, we propose models of CWIN- and Sus-mediated regulation of early seed development.

Early Childhood Malaria Prevention and Children's Patterns of School Leaving in the Gambia

ERIC Educational Resources Information Center

Zuilkowski, Stephanie S.; Jukes, Matthew C. H.

2014-01-01

Background: Early childhood malaria is often fatal, but its impact on the development and education of survivors has not received much attention. Malaria impacts cognitive development in a number of ways that may impact later educational participation. Aims: In this study, we examine the long-term educational effects of preventing early childhood…

Participation Patterns among Families Receiving Part C Early Intervention Services

ERIC Educational Resources Information Center

Khetani, Mary Alunkal

2010-01-01

Participation in the natural settings of home and community is one of four major goals for families receiving Part C early intervention services. While participation has been formally recognized as an important service-related outcome, there is a need to build knowledge about its key features to adequately apply the concept in practice. The need…

Investigating skin-to-skin care patterns with extremely preterm infants in the NICU and their effect on early cognitive and communication performance: a retrospective cohort study.

PubMed

Gonya, Jenn; Ray, William C; Rumpf, R Wolfgang; Brock, Guy

2017-03-20

The primary objective of the study was to investigate how patterns of skin-to-skin care might impact infant early cognitive and communication performance. This was a retrospective cohort study. This study took place in a level-IV all-referral neonatal intensive care unit in the Midwest USA specialising in the care of extremely preterm infants. Data were collected from the electronic medical records of all extremely preterm infants (gestational age <27 weeks) admitted to the unit during 2010-2011 and who completed 6-month and 12-month developmental assessments in the follow-up clinic (n=97). Outcome measures included the cognitive and communication subscales of the Bayley Scales of Infant Development, Third Edition (Bayley-III); and skin-to-skin patterns including: total hours of maternal and paternal participation throughout hospitalisation, total duration in weeks and frequency (hours per week). Extracted data were analysed through a multistep process of logistic regressions, t-tests, χ 2 tests and Fisher's exact tests followed with exploratory network analysis using novel visual analytic software. Infants who received above the sample median in total hours, weekly frequency and total hours from mothers and fathers of skin-to-skin care were more likely to score ≥80 on the cognitive and communication scales of the Bayley-III. However, the results were not statistically significant (p>0.05). Mothers provided the majority of skin-to-skin care with a sharp decline at 30 weeks corrected age, regardless of when extremely preterm infants were admitted. Additional exploratory network analysis suggests that medical and skin-to-skin factors play a parallel, non-synergistic role in contributing to early cognitive and communication performance as assessed through the Bayley-III. This study suggests an association between early and frequent skin-to-skin care with extremely preterm infants and early cognitive and communication performance. Published by the BMJ Publishing

Children's Task Oriented Patterns in Early Childhood: A Latent Transition Analysis

ERIC Educational Resources Information Center

Wang, Feihong; Algina, James; Snyder, Patricia; Cox, Martha; Vernon-Feagans, Lynne; Cox, Martha; Blair, Clancy; Burchinal, Margaret; Burton, Linda; Crnic, Keith; Crouter, Ann; Garrett-Peters, Patricia; Greenberg, Mark; Lanza, Stephanie; Mills-Koonce, Roger; Werner, Emily; Willoughby, Michael

2017-01-01

We examined individual differences and predictions of children's patterns in behavioral, emotional and attentional efforts toward challenging puzzle tasks at 24 and 35 months using data from a large longitudinal rural representative sample. Using latent transition analysis, we found four distinct task-oriented patterns in problem-solving tasks…

Characterization of atypical language activation patterns in focal epilepsy.

PubMed

Berl, Madison M; Zimmaro, Lauren A; Khan, Omar I; Dustin, Irene; Ritzl, Eva; Duke, Elizabeth S; Sepeta, Leigh N; Sato, Susumu; Theodore, William H; Gaillard, William D

2014-01-01

Functional magnetic resonance imaging is sensitive to the variation in language network patterns. Large populations are needed to rigorously assess atypical patterns, which, even in neurological populations, are a minority. We studied 220 patients with focal epilepsy and 118 healthy volunteers who performed an auditory description decision task. We compared a data-driven hierarchical clustering approach to the commonly used a priori laterality index (LI) threshold (LI < 0.20 as atypical) to classify language patterns within frontal and temporal regions of interest. We explored (n = 128) whether IQ varied with different language activation patterns. The rate of atypical language among healthy volunteers (2.5%) and patients (24.5%) agreed with previous studies; however, we found 6 patterns of atypical language: a symmetrically bilateral, 2 unilaterally crossed, and 3 right dominant patterns. There was high agreement between classification methods, yet the cluster analysis revealed novel correlations with clinical features. Beyond the established association of left-handedness, early seizure onset, and vascular pathology with atypical language, cluster analysis identified an association of handedness with frontal lateralization, early seizure onset with temporal lateralization, and left hemisphere focus with a unilateral right pattern. Intelligence quotient was not significantly different among patterns. Language dominance is a continuum; however, our results demonstrate meaningful thresholds in classifying laterality. Atypical language patterns are less frequent but more variable than typical language patterns, posing challenges for accurate presurgical planning. Language dominance should be assessed on a regional rather than hemispheric basis, and clinical characteristics should inform evaluation of atypical language dominance. Reorganization of language is not uniformly detrimental to language functioning. © 2014 American Neurological Association.

Early Communication Development and Intervention for Children with Autism

ERIC Educational Resources Information Center

Landa, Rebecca

2007-01-01

Autism is a neurodevelopmental disorder defined by impairments in social and communication development, accompanied by stereotyped patterns of behavior and interest. The focus of this paper is on the early development of communication in autism, and early intervention for impairments in communication associated with this disorder. An overview of…

Tuning up mind's pattern to nature's own idea: Eddington's early twenties case for variational derivatives

NASA Astrophysics Data System (ADS)

Smadja, Ivahn

This paper sets out to show how Eddington's early twenties case for variational derivatives significantly bears witness to a steady and consistent shift in focus from a resolute striving for objectivity towards "selective subjectivism" and structuralism. While framing his so-called "Hamiltonian derivatives" along the lines of previously available variational methods allowing to derive gravitational field equations from an action principle, Eddington assigned them a theoretical function of his own devising in The Mathematical Theory of Relativity (1923). I make clear that two stages should be marked out in Eddington's train of thought if the meaning of such variational derivatives is to be adequately assessed. As far as they were originally intended to embody the mind's collusion with nature by linking atomicity of matter with atomicity of action, variational derivatives were at first assigned a dual role requiring of them not only to express mind's craving for permanence but also to tune up mind's privileged pattern to "Nature's own idea". Whereas at a later stage, as affine field theory would provide a framework for world-building, such "Hamiltonian differentiation" would grow out of tune through gauge-invariance and, by disregarding how mathematical theory might precisely come into contact with actual world, would be turned into a mere heuristic device for structural knowledge.

Nonlocal grazing in patterned ecosystems.

PubMed

Siero, E

2018-01-07

Many ecosystems exhibit gapped, labyrinthine, striped or spotted patterns. Important examples are vegetation patterns in drylands: these patterns are viewed as precursors of a catastrophic transition to a degraded state. A possible source of degradation is overgrazing, but many current spatially extended models include grazing in a local linear way. In this article nonlocal grazing responses are derived, taking into account (1) how many consumers there are (demographic response) (2) where they are (aggregative response) and (3) how much they forage (functional response). Different assumptions lead to different grazing responses, the type of grazing has a large influence on how ecosystems adapt to changing environmental conditions. In dryland simulations the different types of grazing are shown to alter the desertification process driven by decreasing rainfall. A sufficiently strong aggregative response leads to the suppression of vegetation patterns, nuancing their role as generic early warning signals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metallicities and Nucleosynthesis Patterns in Early Generation Halo Stars

NASA Astrophysics Data System (ADS)

Beers, T.

2004-05-01

I review our present knowledge of the Metallicity Distribution Function of stars in the low-metallicity tail of the halo population of the Galaxy, and the variety of observed elemental signatures that might be associated with particular astrophysical origins in the early Universe. Such signatures include stars that exhibit (a) highly and mildly enhanced r-process element ratios, as compared to the solar ratios, (b) highly s-process enriched stars, (c) stars showing large enrichments of both the r- and and s-process elements, and (d) stars that are greatly enhanced in the light element species, such as CNO, and (in some cases) the alpha elements. Because the stars in which these characteristics are observed all have metallicity [Fe/H] ≤ -2.5, they are inferred to have formed no more than 0.5-1 Gyrs after the Big Bang, prior to the final assemblage of the Milky Way. As such, they provide our best available probes of the nature of early element producers, such as Type II SN and hypernovae, as well as binaries that included (now deceased) stars of intermediate (1.5 - 3 Mo) masses. I outline ongoing and future plans for dramatically accelerating the pace of discovery of these rare, but clearly important, objects. Partial support for this work has been received from NSF grants AST 00-98508 and AST 00-98549, and from JINA, the Joint Institute for Nuclear Astrophysics, an NSF Physics Frontier Center.

[Proton nuclear magnetic resonance spectroscopy recognition of metabolic patterns in fecal extracts for early diagnosis of colorectal cancer].

PubMed

Lin, Y; Wang, Z N; Ma, C C; Liu, C K; Yang, J R; Shen, Z W; Wu, R H

2016-09-06

Objective: To characterize the metabolic " fingerprint" of fecal extracts for diagnosis of early-stage colorectal cancer(CRC)using proton nuclear magnetic resonance spectroscopy( 1 H-NMR)-based metabolomics coupled with pattern recognition. Methods: From January 2014 to December 2014, we collected fecal samples at the Second Affiliated Hospital of Shantou University Medical College, from 25 patients with colorectal adenomas(CR-Ad), 20 with stage Ⅰ/Ⅱ CRC, and 32 healthy controls(HCs). The patients were diagnosed by histopathology. No subjects had any complicating diseases. HCs showed no abnormalities from blood tests, endoscopic examination, diagnostic imaging, and/or medical interviews. We excluded participants who used antibiotics, NSAIDS, statins, or probiotics within two months of study participation, and any patients who underwent chemotherapy or radiation treatments prior to surgery. We used orthogonal partial least-squares-discriminant analysis(OPLS-DA)for pattern recognition(dimension reduction)on 1 H-NMR processed data( 1 H frequency of 400.13 MHz), to find metabolic differences among CR-Ad, carcinoma and HC fecal samples; and receiver operating characteristic(ROC)analysis to determine the diagnostic value of the fecal metabolic biomarkers. Results: Fecal samples were collected from 20 patients with Stage Ⅰ/Ⅱ CRC(11 M, 9 F, median age(52±13)years), 25 with CR-Ad(14 M, 11 F, median age(53 ± 11)years)and 32 HCs(15 M, 17 F, median age(53 ± 14)years). OPLS-DA clearly distinguished CR-Ad and stage Ⅰ/Ⅱ CRC from HC samples, based on their metabolomic profiles. Relative signal intensities in HCs were significantly lower than in the cancer patients for butyrate(HC: 23.0±6.0; CR-Ad: 18.0±5.0; CRC: 14.0±6.0; Z =-2.07, P =0.008), acetate(HC: 45.0±11.0; CR-Ad: 31.0±11.0; CRC: 24.0±8.0; Z =- 2.32, P =0.011), propionate(HC: 26.0 ± 7.0; CR-Ad: 22.0 ± 6.0; CRC: 19.0 ± 5.0; Z =- 2.43, P =0.032), glucose(HC: 37.0±7.0; CR-Ad: 31.0±7.0; CRC: 26.0±8

Socio-economic patterning in early mortality of patients aged 0-49 years diagnosed with primary bone cancer in Great Britain, 1985-2008.

PubMed

Blakey, Karen; Feltbower, Richard G; James, Peter W; Libby, Gillian; Stiller, Charles; Norman, Paul; Gerrand, Craig; McNally, Richard J Q

2018-04-01

Studies have shown marked improvements in survival between 1981 and 2000 for Ewing sarcoma patients but not for osteosarcoma. This study aimed to explore socio-economic patterning in early mortality rates for both tumours. The study analysed all 2432 osteosarcoma and 1619 Ewing sarcoma cases, aged 0-49 years, diagnosed in Great Britain 1985-2008 and followed to 31/12/2009. Logistic regression models were used to calculate risk of dying within three months, six months, one year, three years and five years after diagnosis. Associations with Townsend deprivation score and its components were examined at small-area level. Urban/rural status was studied at larger regional level. For osteosarcoma, after age adjustment, mortality at three months, six months and one year was associated with higher area unemployment, OR = 1.05 (95% CI 1.00, 1.10), OR = 1.04 (95% CI 1.01, 1.08) and OR = 1.04 (95% CI 1.02, 1.06) respectively per 1% increase in unemployment. Mortality at six months was associated with greater household non-car ownership, OR = 1.02 (95% CI 1.00, 1.03). For Ewing sarcoma, there were no significant associations between mortality and overall Townsend score, nor its components for any time period. For both tumours increasing mortality was associated with less urban and more remote rural areas. This study found that for osteosarcoma, early mortality was associated with residence at diagnosis in areas of higher unemployment, suggesting risk of early death may be socio-economically determined. For both tumours, distance from urban centres may lead to greater risk of early death. Copyright © 2018 Elsevier Ltd. All rights reserved.

Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells.

PubMed

Mukherjee, Sumit; Baidoo, Juliet N E; Sampat, Samay; Mancuso, Andrew; David, Lovena; Cohen, Leah S; Zhou, Shuiqin; Banerjee, Probal

2018-01-18

Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12-15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM): 32:8:100 (termed 32 μM+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated that TrLp boosts activated p53 in cultured GL261 mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp administration into mice yielded a stable plasma concentration of 210 nM C for 60 min, which, though sub-lethal for cultured GL261 cells, was able to cause repolarization of M2-like tumor (GBM)-associated microglia/macrophages to the tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural killer cells. The intratumor presence of such tumoricidal immune cells was associated with concomitant suppression of tumor-load, and apoptosis of GBM and GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against GBM tumors.

The moderator-mediator role of social support in early adolescents.

PubMed

Yarcheski, A; Mahon, N E

1999-10-01

The purpose of this study was to examine social support as both a mediator and a moderator of the relationship between perceived stress and symptom patterns in early adolescents. Data were collected from 148 early adolescent boys and girls, ages 12 to 14, who responded to the Perceived Stress Scale, the Personal Resource Questionnaire 85-Part II, and the Symptom Pattern Scale. Using multiple regression analysis procedures specified for the testing of moderation and mediation, results indicated that social support did not play a moderating role in the relationship between perceived stress and symptom patterns, but social support did play a mediating role in this relationship. The findings are interpreted within the two major theoretical orientations that guided the study.

Early versus late GD-DTPA MRI enhancement in experimental glioblastomas.

PubMed

Farace, Paolo; Tambalo, Stefano; Fiorini, Silvia; Merigo, Flavia; Daducci, Alessandro; Nicolato, Elena; Conti, Giamaica; Degrassi, Anna; Sbarbati, Andrea; Marzola, Pasquina

2011-03-01

To compare early versus late enhancement in two glioblastoma models characterized by different infiltrative/edematous patterns. Three weeks after inoculation into nude mice of U87MG and U251 cells, T1-weighted images were acquired early (10.5 min), intermediate (21 min) and late (30.5 min) after a bolus injection of Gd-DTPA at 300 μ mol/kg dosage. EARLY(TH) and LATE(TH) were the corresponding volumes with an enhancement higher than a threshold TH, defined by the mean (μ) and standard deviation (σ) on a contralateral healthy area. ADD(TH) was the enhancing volume found in LATE(TH) but not in EARLY(TH). T2 imaging of both tumors was performed, and T2 mapping of U251. In all tumors, LATE(TH) was significantly higher than EARLY(TH) for TH ranging from μ+σ to μ+5σ. The ADD(TH) /EARLY(TH) ratio was not significantly different when U251 and U87MG tumors were compared. In the U87MG tumors, some enhancement was observed outside the regularly demarcated T2-hyperintense area. In the U251 tumors, irregularly T2 demarcated, a large portion of ADD(μ+3σ) had normal T2 values. At histology, U251 showed a higher infiltrative pattern than U87MG. In these models, the increase over time in the enhancing volume did not depend on the different infiltrative/edematous patterns and was not closely related with edema. Copyright © 2011 Wiley-Liss, Inc.

Academic and emotional functioning in early adolescence: longitudinal relations, patterns, and prediction by experience in middle school.

PubMed

Roeser, R W; Eccles, J S; Sameroff, A J

1998-01-01

Adopting a motivational perspective on adolescent development, these two companion studies examined the longitudinal relations between early adolescents' school motivation (competence beliefs and values), achievement, emotional functioning (depressive symptoms and anger), and middle school perceptions using both variable- and person-centered analytic techniques. Data were collected from 1041 adolescents and their parents at the beginning of seventh and the end of eight grade in middle school. Controlling for demographic factors, regression analyses in Study 1 showed reciprocal relations between school motivation and positive emotional functioning over time. Furthermore, adolescents' perceptions of the middle school learning environment (support for competence and autonomy, quality of relationships with teachers) predicted their eighth grade motivation, achievement, and emotional functioning after accounting for demographic and prior adjustment measures. Cluster analyses in Study 2 revealed several different patterns of school functioning and emotional functioning during seventh grade that were stable over 2 years and that were predictably related to adolescents' reports of their middle school environment. Discussion focuses on the developmental significance of schooling for multiple adjustment outcomes during adolescence.

Patterns of Early Skill Attainment and Loss in Young Children with Autism

PubMed Central

Thurm, Audrey; Manwaring, Stacy S.; Luckenbaugh, David A.; Lord, Catherine; Swedo, Susan E.

2015-01-01

The purpose of this study was to extend the literature on the ontogeny of autism spectrum disorder (ASD) by examining early attainment and loss of specific sociocommunicative skills in children with autism (AUT; n = 125), pervasive developmental disorder not otherwise specified (PDD-NOS; n = 42), nonspectrum developmental delays (n = 46), and typical development (n = 31). The ages of skill attainment and loss were obtained from a caregiver interview. The findings indicated that children with AUT, PDD-NOS, and developmental delays diverged from typically developing children in attainment of sociocommunicative skills early in the first year of life. Loss of at least one skill was reported in a majority of children with AUT and PDD-NOS. Significant delays in attainment of skills were also reported in children who lost skills. The wide variation in skill attainment and loss reported across children indicates that symptom onset and regression may be best represented continuously, with at least some early delay and loss present for a great majority of children with ASD. PMID:24274034

Individual and Day-to-Day Differences in Active Coping Predict Diurnal Cortisol Patterns among Early Adolescent Girls.

PubMed

Sladek, Michael R; Doane, Leah D; Stroud, Catherine B

2017-01-01

Prior work has identified alterations in activity of the hypothalamic-pituitary-adrenal axis as a potential mechanism underlying stress-induced emotional health problems, which disproportionately impact girls beginning in mid-adolescence. How adolescent girls differ from one another in dispositional coping tendencies and shift specific coping strategies in response to varying stressors have been theorized as important predictors of their adaptation, health, and well-being during this dynamic period of development. The goal of this study was to examine whether individual and day-to-day (within-person) differences in adolescent girls' coping responses are associated with daily patterns of hypothalamic-pituitary-adrenal axis activity, indexed by cortisol. Participants were 122 early adolescent girls (M age  = 12.39) who provided three saliva samples per day for 3 days and completed daily coping reports, as well as a standard coping survey. Participants and primary caregivers also completed objective life stress interviews. On average, girls who were more likely to respond to interpersonal stress with voluntary engagement (active) coping exhibited generally adaptive daily physiological regulation-steeper diurnal cortisol slopes, lower total diurnal cortisol output, and lower cortisol awakening responses. Chronic interpersonal stress level significantly moderated these associations in different ways for two distinct components of the diurnal pattern-the slope and cortisol awakening responses. Regarding within-person differences, using active coping more than usual was associated with higher waking cortisol the following morning, which may help to prepare adolescent girls for perceived daily demands. These findings highlight the interactive influence of stress and coping in the prediction of daily hypothalamic-pituitary-adrenal axis activity and support the stress-buffering role of active coping for adolescent girls.

Early patterns of commercial activity in graphene

NASA Astrophysics Data System (ADS)

Shapira, Philip; Youtie, Jan; Arora, Sanjay

2012-03-01

Graphene, a novel nanomaterial consisting of a single layer of carbon atoms, has attracted significant attention due to its distinctive properties, including great strength, electrical and thermal conductivity, lightness, and potential benefits for diverse applications. The commercialization of scientific discoveries such as graphene is inherently uncertain, with the lag time between the scientific development of a new technology and its adoption by corporate actors revealing the extent to which firms are able to absorb knowledge and engage in learning to implement applications based on the new technology. From this perspective, we test for the existence of three different corporate learning and activity patterns: (1) a linear process where patenting follows scientific discovery; (2) a double-boom phenomenon where corporate (patenting) activity is first concentrated in technological improvements and then followed by a period of technology productization; and (3) a concurrent model where scientific discovery in publications occurs in parallel with patenting. By analyzing corporate publication and patent activity across country and application lines, we find that, while graphene as a whole is experiencing concurrent scientific development and patenting growth, country- and application-specific trends offer some evidence of the linear and double-boom models.

Female pattern hair loss.

PubMed

Ioannides, Dimitrios; Lazaridou, Elizabeth

2015-01-01

Female pattern hair loss, or female pattern androgenetic alopecia, is a nonscarring alopecia with a multi-factorial etiology that mostly affects postmenopausal women and is characterized by a reduction in hair density over the crown and frontal scalp. The clinical picture is characterized by a diffuse rarefaction of scalp hair over the mid-frontal scalp and a more-or-less intact frontal hairline without any signs of inflammation or scarring. Although the disease poses only a cosmetic concern, it is chronic and may have a significant negative psychological impact on the affected person. The aim of treating female pattern hair loss is to reduce hair loss and, to a certain extent, succeed in promoting hair regrowth. Various treatment methods are available, but it remains unclear which are the most effective. Early initiation of treatment and the combination of various modalities seem to be more efficacious than monotherapy. © 2015 S. Karger AG, Basel.

Update on the evaluation of a new drug for effects on cardiac repolarization in humans: issues in early drug development

PubMed Central

Salvi, Vaibhav; Karnad, Dilip R; Panicker, Gopi Krishna; Kothari, Snehal

2010-01-01

Following reports of death from cardiac arrhythmias with drugs like terfenadine and cisapride, the International Conference for Harmonization formulated a guidance (E14) document. This specifies that all new drugs must undergo a ‘thorough QT/QTc’ (TQT) study to detect drug-induced QT prolongation, a surrogate marker of ventricular tachycardia, especially torsades de pointes (TdPs). With better understanding of data from several completed TQT studies, regulatory requirements have undergone some changes since the E14 guidance was implemented in October 2005. This article reviews the implications of the E14 guidance and the changes in its interpretation including choice of baseline QT, demonstration of assay sensitivity, statistical analysis of the effect of new drug and positive control, and PK-PD modelling. Some issues like use of automated QT measurements remain unresolved. Pharmaceutical companies too are modifying Phase 1 studies to detect QTc liability early in order to save time and resources. After the E14 guidance, development of several drugs that prolong QTc by >5 ms is being abandoned by sponsors. However, all drugs that prolong the QT interval do not increase risk of TdP. Researchers in regulatory agencies, academia and industry are working to find better biomarkers of drug-induced TdP which could prevent many useful drugs from being prematurely abandoned. Drug-induced TdP is a rare occurrence. With fewer drugs that prolong QT interval reaching the licensing stage, knowing which of these drugs are torsadogenic is proving to be elusive. Thus, paradoxically, the effectiveness of the E14 guidance itself has made prospective validation of new biomarkers difficult. This article is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010 PMID:19775279

Early hominin biogeography in Island Southeast Asia.

PubMed

Larick, Roy; Ciochon, Russell L

2015-01-01

Island Southeast Asia covers Eurasia's tropical expanse of continental shelf and active subduction zones. Cutting between island landmasses, Wallace's Line separates Sunda and the Eastern Island Arc (the Arc) into distinct tectonic and faunal provinces. West of the line, on Sunda, Java Island yields many fossils of Homo erectus. East of the line, on the Arc, Flores Island provides one skeleton and isolated remains of Homo floresiensis. Luzon Island in the Philippines has another fossil hominin. Sulawesi preserves early hominin archeology. This insular divergence sets up a unique regional context for early hominin dispersal, isolation, and extinction. The evidence is reviewed across three Pleistocene climate periods. Patterns are discussed in relation to the pulse of global sea-level shifts, as well as regional geo-tectonics, catastrophes, stegodon dispersal, and paleogenomics. Several patterns imply evolutionary processes typical of oceanic islands. Early hominins apparently responded to changing island conditions for a million-and-a-half years, likely becoming extinct during the period in which Homo sapiens colonized the region. © 2015 Wiley Periodicals, Inc.

Impact of pacing and high-pass filter settings on ventricular bipolar electrograms in implantable cardioverter defibrillator systems. - Implication of predictors for inappropriate therapy caused by oversensing of repolarization electrograms-.

PubMed

Maesato, Akira; Higa, Satoshi; Lin, Yenn-Jiang; Chinen, Ichiro; Ishigaki, Sugako; Yajima, Machiko; Masuzaki, Hiroaki; Chen, Shih-Ann

2011-01-01

Predictors of T wave oversensing with implantable cardioverter-defibrillator (ICD) systems remains to be clarified. Thirteen consecutive patients who underwent ICD implantations were included. The depolarization (R) and repolarization (T) of bipolar electrograms during baseline, AAI and DDD modes, and an isoproterenol (ISO) infusion were evaluated. The R wave amplitude during DDD was significantly lower as compared to that during the other conditions in all high-pass filter settings. In contrast, there was no significant difference in the T wave amplitude during the DDD as compared to the other conditions. With the DDD, there was a significantly higher incidence of a T/R ratio of greater than 0.25 as compared to that with the other conditions. T wave amplitude in Brugada syndrome was significantly higher than that in non-Brugada syndrome. The existence of Brugada syndrome and T/R ratio during the AAI with a high-pass filter setting of 10/20 Hz was an excellent predictor of T wave oversensing in the follow-up period. DDD had a significant impact on the R wave amplitude reduction and the T/R ratio during AAI can be predictors of T wave oversensing. These findings have important implications for inappropriate shocks due to T wave oversensing.

Patterns of everyday technology use and activity involvement in mild cognitive impairment: a five-year follow-up study.

PubMed

Hedman, Annicka; Kottorp, Anders; Nygård, Louise

2018-05-01

The aims were to describe longitudinal patterns in terms of perceived ability to use everyday technology (ET) and involvement in everyday activities over five years in older adults with mild cognitive impairment (MCI), and to examine the predictive value of these patterns regarding diagnostic outcomes. Thirty older adults diagnosed with MCI at inclusion, reported their perceived ability in using ET and involvement in everyday activities on seven occasions over five years. Individual longitudinal case plots and a pattern-oriented analysis were used to compare the participants' distribution in earlier identified stable/ascending, fluctuating and descending patterns of functioning (year 0-2). Fisher's exact test was used for testing the relation between pattern and diagnostic outcomes. An initial descending pattern of functioning tended to continue; none of these participants later developed a more stable pattern. More congruent trajectories of change appeared over time. Pattern affinity years 0-2 and diagnostic outcome were significantly related (p = .05), with a dementia diagnosis being more likely for those initially displaying an early descending pattern Conclusion: These findings point to a need for early support focusing on the use of ET for persons with MCI who early after diagnosis descend in functioning.

Promoting Repeating Patterns with Young Children--More than Just Alternating Colours!

ERIC Educational Resources Information Center

Papic, Marina

2007-01-01

Patterning is an essential skill in early mathematics learning, particularly in the development of spatial awareness, sequencing and ordering, comparison, and classification. This includes the ability to identify and describe attributes of objects and similarities and differences between them. Patterning is also integral to the development of…

Size-dependent regulation of dorsal-ventral patterning in the early Drosophila embryo

PubMed Central

Garcia, Mayra; Nahmad, Marcos; Reeves, Gregory T.; Stathopoulos, Angelike

2013-01-01

How natural variation in embryo size affects patterning of the Drosophila embryo dorsal-ventral (DV) axis is not known. Here we examined quantitatively the relationship between nuclear distribution of the Dorsal transcription factor, boundary positions for several target genes, and DV axis length. Data were obtained from embryos of a wild-type background as well as from mutant lines inbred to size select embryos of smaller or larger sizes. Our data show that the width of the nuclear Dorsal gradient correlates with DV axis length. In turn, for some genes expressed along the DV axis, the boundary positions correlate closely with nuclear Dorsal levels and with DV axis length; while the expression pattern of others is relatively constant and independent of the width of the Dorsal gradient. In particular, the patterns of snail (sna) and ventral nervous-system defective (vnd) correlate with nuclear Dorsal levels and exhibit scaling to DV length; while the pattern of intermediate neuroblasts defective (ind) remains relatively constant with respect to changes in Dorsal and DV length. However, in mutants that exhibit an abnormal expansion of the Dorsal gradient which fails to scale to DV length, only sna follows the Dorsal distribution and exhibits overexpansion; in contrast, vnd and ind do not overexpand suggesting some additional mechanism acts to refine the dorsal boundaries of these two genes. Thus, our results argue against the idea that the Dorsal gradient works as a global system of relative coordinates along the DV axis and suggest that individual targets respond to changes in embryo size in a gene-specific manner. PMID:23800450

Infant obesity and severe obesity growth patterns in the first two years of life.

PubMed

Gittner, Lisaann S; Ludington-Hoe, Susan M; Haller, Harold S

2014-04-01

Distinguishing an obesity growth pattern that originates during infancy is clinically important. Infancy based obesity prevention interventions may be needed while precursors of later health are forming. Infant obesity and severe obesity growth patterns in the first 2-years are described and distinguished from a normal weight growth pattern. A retrospective chart review was conducted. Body mass index (BMI) growth patterns from birth to 2-years are described for children categorized at 5-years as normal weight (n = 61), overweight (n = 47), obese (n = 41) and severely obese (n = 72) cohorts using WHO reference standards. BMI values were calculated at birth, 1-week; 2-, 4-, 6-, 9-, 12-, 15-, 18-months; and 2- and 5-years. Graphs of the longitudinal Analysis of Variance of Means of BMI values identified the earliest significant divergence of a cohort's average BMI pattern from other cohorts' patterns. ANOVA and Pearson Product Moment correlations were also performed. Statistically significant differences in BMI values and differences in growth patterns between cohorts were evident as early as 2-6 months post-birth. Children who were obese or severely obese at 5-years demonstrated a BMI pattern that differed within the first 2-years of life from that of children who were normal weight at 5-years. The earliest significant correlation between early BMI values and 5-year BMI value was at 4-months post-birth. The study fills an important gap by demonstrating early onset of an infant obesity growth pattern in full-term children who were healthy throughout their first 5 years of life.

Hazard-Rate Analysis and Patterns of Recurrence in Early Stage Melanoma: Moving towards a Rationally Designed Surveillance Strategy

PubMed Central

Scheri, Randall P.; Pruitt, Scott K.; Herndon, James E.; Marcello, Jennifer; Tyler, Douglas S.; Abernethy, Amy P.

2013-01-01

Background While curable at early stages, few treatment options exist for advanced melanoma. Currently, no consensus exists regarding the optimal surveillance strategy for patients after resection. The objectives of this study were to identify patterns of metastatic recurrence, to determine the influence of metastatic site on survival, and to identify high-risk periods for recurrence. Methods A retrospective review of the Duke Melanoma Database from 1970 to 2004 was conducted that focused on patients who were initially diagnosed without metastatic disease. The time to first recurrence was computed from the date of diagnosis, and the associated hazard function was examined to determine the peak risk period of recurrence. Metastatic sites were coded by the American Joint Committee on Cancer (AJCC) system including local skin, distant skin and nodes (M1a), lung (M1b), and other distant (M1c). Results Of 11,615 patients initially diagnosed without metastatic disease, 4616 (40%) had at least one recurrence. Overall the risk of initial recurrence peaked at 12 months. The risk of initial recurrence at the local skin, distant skin, and nodes peaked at 8 months, and the risk at lung and other distant sites peaked at 24 months. Patients with a cutaneous or nodal recurrence had improved survival compared to other recurrence types. Conclusions The risk of developing recurrent melanoma peaked at one year, and the site of first recurrence had a significant impact on survival. Defining the timing and expected patterns of recurrence will be important in creating an optimized surveillance strategy for this patient population. PMID:23516415

Patterns of Primary Tumor Invasion and Regional Lymph Node Spread Based on Magnetic Resonance Imaging in Early-Stage Nasal NK/T-cell Lymphoma: Implications for Clinical Target Volume Definition and Prognostic Significance

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

Wu, Run-Ye; Liu, Kang; Wang, Wei-Hu

Purpose: This study aimed to determine the pathways of primary tumor invasion (PTI) and regional lymph node (LN) spread based on magnetic resonance imaging (MRI) in early-stage nasal NK/T-cell lymphoma (NKTCL), to improve clinical target volume (CTV) delineation and evaluate the prognostic value of locoregional extension patterns. Methods and Materials: A total of 105 patients with newly diagnosed early-stage nasal NKTCL who underwent pretreatment MRI were retrospectively reviewed. All patients received radiation therapy with or without chemotherapy. Results: The incidences of PTI and regional LN involvement were 64.7% and 25.7%, respectively. Based on the incidence of PTI, involved sites surroundingmore » the nasal cavity were classified into 3 risk subgroups: high-risk (>20%), intermediate-risk (5%-20%), and low-risk (<5%). The most frequently involved site was the nasopharynx (35.2%), followed by the maxillary (21.9%) and ethmoid (21.9%) sinuses. Local disease and regional LN spread followed an orderly pattern without LN skipping. The retropharyngeal nodes (RPNs) were most frequently involved (19.0%), followed by level II (11.4%). The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) rates for all patients were 72.8%, 65.2%, and 90.0%, respectively. The presence of PTI and regional LN involvement based on MRI significantly and negatively affected PFS and OS. Conclusions: Early-stage nasal NKTCL presents with a high incidence of PTI but a relatively low incidence of regional LN spread. Locoregional spread followed an orderly pattern, and PTI and regional LN spread are powerful prognostic factors for poorer survival outcomes. CTV reduction may be feasible for selected patients.« less

Career patterns of healthcare executives.

PubMed

Fahey, D F; Myrtle, R C

2001-02-01

This research examines the job and career changes of healthcare executives and managers working in different segments of the healthcare industry in the western United States. The results suggest that the job and career patterns in the healthcare delivery sector are undergoing significant transformation. One third of the respondents reports that at least one of their last four job changes was involuntary or unplanned. One half of those attempted to make a career change. This study identifies four different executive and management career patterns. The most common was one of multiple career changes. The second pattern was that of a single career change, followed by a 'traditional' career in which one did not seek a career change. The final pattern was characterized as a movement back and forth between two different segments of the healthcare industry. Age, gender, marital status and education were not associated with any specific career pattern. The need to achieve results early in the respondent's career had a strong influence on career patterns. This study confirms the fluidity of career movement and the changing permeability between the various segments of the healthcare industry. It also suggests that career success increasingly will require broad management experience in those different segments.

Electrocardiographic signs of autonomic imbalance in medicated patients with first-episode schizophrenia spectrum disorders--relations to first treatment discontinuation and five-year remission status.

PubMed

Bodén, Robert; Lindström, Leif; Rautaharju, Pentti; Sundström, Johan

2012-04-01

To explore measures in electrocardiograms (ECG) influenced by autonomic balance in early schizophrenia spectrum disorders and to examine their relation to subsequent first antipsychotic pharmacotherapy discontinuation and five-year remission status. Twelve-lead ECGs were recorded at baseline in 58 patients with first-episode schizophrenia spectrum disorders and in 47 healthy controls of similar age. Selected ECG variables included heart rate and measures of repolarization. Pharmacotherapy data were extracted from medical records. At a five-year follow-up the patients were interviewed and assessed with the positive and negative syndrome scale. Patients had higher heart rate and a different ST-T pattern than the controls. High T-wave amplitudes in the leads aVF and V5 and ST-elevations in V5 were associated both with higher risk of an earlier discontinuation of first antipsychotic pharmacotherapy and with non-remission five years later. In this longitudinal cohort study, simple ECG measures influenced by autonomic balance in the early phase of schizophrenia spectrum disorders contained prognostic information. As this is the first report of this association and is based on a relatively small sample, the results should be interpreted with caution. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Global-scale tectonic patterns on Pluto

NASA Astrophysics Data System (ADS)

Matsuyama, I.; Keane, J. T.; Kamata, S.

2016-12-01

The New Horizons spacecraft revealed a global-scale tectonic pattern on the surface of Pluto which is presumably related to its formation and early evolution. Changes in the rotational and tidal potentials, expansion, and loading can generate stresses capable of producing global-scale tectonic patterns. The current alignment of Sputnik Planum with the tidal axis suggests a reorientation of Pluto relative to the rotation and tidal axes, or true polar wander. This reorientation can be driven by mass loading associated with Sputnik Planum. We developed a general theoretical formalism for the calculation of tectonic patterns due to a variety of process including true polar wander, loading, and expansion. The formalism is general enough to be applicable to non-axisymmetric loads. We illustrate that the observed global-scale tectonic pattern can be explained by stresses generated by true polar wander, Sputnik Planum loading, and expansion.

Research in Review. Children's Eating: The Development of Food-Acceptance Patterns.

ERIC Educational Resources Information Center

Birch, Leann L.; And Others

1995-01-01

Reviews what is known about the factors that influence child's food-acceptance patterns, including children's sensory responsiveness, innate preferences, and ability to learn about food; the consequences of eating; and the effect of child-feeding practices on children's food-acceptance patterns. Suggests that early experience contributes to the…

Multidimensionality of the relationship between social status and dietary patterns in early childhood: longitudinal results from the French EDEN mother-child cohort.

PubMed

Camara, Soumaïla; de Lauzon-Guillain, Blandine; Heude, Barbara; Charles, Marie-Aline; Botton, Jérémie; Plancoulaine, Sabine; Forhan, Anne; Saurel-Cubizolles, Marie-Josèphe; Dargent-Molina, Patricia; Lioret, Sandrine

2015-09-24

The association between socioeconomic position and diet in early childhood has mainly been addressed based on maternal education and household income. We aimed to assess the influence of a variety of social factors from different socio-ecological levels (parents, household and child-care) on multi-time point dietary patterns identified from 2 to 5 y. This study included 974 children from the French EDEN mother-child cohort. Two multi-time point dietary patterns were derived in a previous study: they correspond to consistent exposures to either core- or non-core foods across 2, 3 and 5 y and were labelled "Guidelines" and "Processed, fast-foods". The associations of various social factors collected during pregnancy (age, education level) or at 2-y follow-up (mother's single status, occupation, work commitments, household financial disadvantage, presence of older siblings and child-care arrangements) with each of the two dietary patterns, were assessed by multivariable linear regression analysis. The adherence to a diet close to "Guidelines" was positively and independently associated with both maternal and paternal education levels. The adherence to a diet consistently composed of processed and fast-foods was essentially linked with maternal variables (younger age and lower education level), household financial disadvantage, the presence of older sibling (s) and being cared for at home by someone other than the mother. Multiple social factors operating at different levels (parents, household, and child-care) were found to be associated with the diet of young children. Different independent predictors were found for each of the two longitudinal dietary patterns, suggesting distinct pathways of influence. Our findings further suggest that interventions promoting healthier dietary choices for young children should involve both parents and take into account not only household financial disadvantage but also maternal age, family size and options for child-care.

Methamphetamine-associated cardiomyopathy: patterns and predictors of recovery.

PubMed

Voskoboinik, A; Ihle, J F; Bloom, J E; Kaye, D M

2016-06-01

Methamphetamine abuse is a growing public health problem, and increasing numbers of patients are admitted with methamphetamine-associated cardiomyopathy (MAC). We sought to characterise the patterns of this disease and identify predictors of recovery. We retrospectively studied consecutive patients diagnosed with MAC between January 2006 and July 2015. We identified 20 patients (14 males, 6 females) with mean age 35 ± 9 years. Most had very severe systolic dysfunction (mean left ventricular ejection fraction (LVEF) 19.7 ± 11.4%) at presentation with 14 requiring inotropes and 5 requiring mechanical support. The pattern of systolic dysfunction was global in 14 patients, while 6 patients had a 'reverse Takotsubo' (RT) pattern with severely hypokinetic basal-mid segments and apical preservation. RT patients were predominantly female, had a short history of methamphetamine abuse and had higher cardiac enzyme levels. Patients with global dysfunction tended to have mid-wall fibrosis on cardiac magnetic resonance imaging. On follow-up transthoracic echocardiography, 6 out of 19 (32%) had normalisation of LVEF (LVEF ≥ 50%) within 6 weeks. Smaller left ventricular and left atrial size, shorter duration of methamphetamine use and RT pattern appeared to predict early recovery. A subset of MAC patients, particularly those with a RT pattern and lesser ventricular dilatation have the potential for early recovery of ventricular function. By contrast, those with evidence of myocardial fibrosis and ventricular enlargement have limited scope for recovery. © 2016 Royal Australasian College of Physicians.

Antenatal dietary patterns and depressive symptoms during pregnancy and early post-partum.

PubMed

Baskin, Rachel; Hill, Briony; Jacka, Felice N; O'Neil, Adrienne; Skouteris, Helen

2017-01-01

Perinatal depression is a debilitating disorder experienced during pregnancy and/or the first year post-partum. Recently, maternal dietary intake during pregnancy has emerged as a possible area of intervention for the prevention of mental disorders in women and their offspring. However, the relationship between antenatal diet quality and perinatal depressive symptoms remains poorly understood. The current study explored the predictive role of antenatal diet quality for antenatal and post-natal depressive symptoms. Pregnant women (n = 167) were recruited between February 2010 and December 2011. Women completed the Edinburgh Postnatal Depression Scale at time 1 [T1, mean weeks gestation = 16.70, standard deviation (SD) = 0.91], time 2 (T2, mean weeks gestation = 32.89, SD = 0.89) and time 3 (T3, mean weeks post-partum = 13.51, SD = 1.97) and a food frequency questionnaire at T1 and T2. Diet quality was determined by extracting dietary patterns via principal components analysis. Two dietary patterns were identified: 'healthy' (including fruit, vegetables, fish and whole grains) and 'unhealthy' (including sweets, refined grains, high-energy drinks and fast foods). Associations between dietary patterns and depressive symptoms were investigated by path analyses. While both 'healthy' and 'unhealthy' path models showed good fit, only one significant association consistent with study hypotheses was found, an 'unhealthy' diet was associated with increased depressive symptoms at 32 weeks gestation. Given that this association was cross-sectional, it was not possible to make any firm conclusions about the predictive nature of either dietary patterns or depressive symptoms. Dietary intervention studies or larger prospective studies are therefore recommended. © 2015 John Wiley & Sons Ltd.

Developmental patterns of spatial ability: an early sex difference.

PubMed

Johnson, E S; Meade, A C

1987-06-01

Over 1,800 public school students (grades K-12, ages 6-18) took a battery of 7 spatial tests tailored to their respective developmental levels. Analyses of resulting data indicate that it is feasible to measure spatial ability throughout this developmental range with modified versions of adult paper-and-pencil tests, that a male advantage in spatial performance appears reliably by age 10, and that the magnitude of the advantage remains constant through age 18. Analysis of covariance suggests that an early female precocity in language skills may mask a male advantage in spatial ability during the primary school years. There is no indication of a sex difference in kindergarten children.

Wildfire patterns and landscape changes in Mediterranean oak woodlands.

PubMed

Guiomar, N; Godinho, S; Fernandes, P M; Machado, R; Neves, N; Fernandes, J P

2015-12-01

Fire is infrequent in the oak woodlands of southern Portugal (montado) but large and severe fires affected these agro-forestry systems in 2003-2005. We hypothesised transition from forest to shrubland as a fire-driven process and investigated the links between fire incidence and montado change to other land cover types, particularly those related with the presence of pioneer communities (generically designed in this context as "transitions to early-successional communities"). We present a landscape-scale framework for assessing the probability of transition from montado to pioneer communities, considering three sets of explanatory variables: montado patterns in 1990 and prior changes from montado to early-successional communities (occurred between 1960 and 1990), fire patterns, and spatial factors. These three sets of factors captured 78.2% of the observed variability in the transitions from montado to pioneer vegetation. The contributions of fire patterns and spatial factors were high, respectively 60.6% and 43.4%, the influence of montado patterns and former changes in montado being lower (34.4%). The highest amount of explained variation in the occurrence of transitions from montado to early-successional communities was related to the pure effect of fire patterns (19.9%). Low spatial connectedness in montado landscape can increase vulnerability to changes, namely to pioneer vegetation, but the observed changes were mostly explained by fire characteristics and spatial factors. Among all metrics used to characterize fire patterns and extent, effective mesh size provided the best modelling results. Transitions from montado to pioneer communities are more likely in the presence of high values of the effective mesh size of total burned area. This cross-boundary metric is an indicator of the influence of large fires in the distribution of the identified transitions and, therefore, we conclude that the occurrence of large fires in montado increases its probability of

Early life socioeconomic determinants of dietary score and pattern trajectories across six waves of the Longitudinal Study of Australian Children.

PubMed

Gasser, Constantine E; Mensah, Fiona K; Kerr, Jessica A; Wake, Melissa

2017-12-01

Social patterning of dietary-related diseases may partly be explained by population disparities in children's diets. This study aimed to determine which early life socioeconomic factors best predict dietary trajectories across childhood. For waves 2-6 of the Baby (B) Cohort (ages 2-3 to 10-11 years) and waves 1-6 of the Kindergarten (K) Cohort (ages 4-5 to 14-15 years) of the Longitudinal Study of Australian Children, we constructed trajectories of dietary scores and of empirically derived dietary patterns. Dietary scores, based on the Australian Dietary Guidelines, summed children's consumption frequencies of seven groups of foods or drinks over the last 24 hours. Dietary patterns at each wave were derived using factor analyses of 12-16 food or drink items. Using multinomial logistic regression analyses, we examined associations of baseline single (parental education, remoteness area, parental employment, income, food security and home ownership) and composite (socioeconomic position and neighbourhood disadvantage) factors with adherence to dietary trajectories. All dietary trajectory outcomes across both cohorts showed profound gradients by composite socioeconomic position but not by neighbourhood disadvantage. For example, odds for children in the lowest relative to highest socioeconomic position quintile being in the 'never healthy' relative to the 'always healthy' score trajectory were OR=16.40, 95% CI 9.40 to 28.61 (B Cohort). Among the single variables, only parental education consistently predicted dietary trajectories. Child dietary trajectories vary profoundly by family socioeconomic position. If causal, reducing dietary inequities may require researching underlying pathways, tackling socioeconomic inequities and targeting health promoting interventions to less educated families. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

Children's Cortisol Patterns and the Quality of the Early Learning Environment

ERIC Educational Resources Information Center

Sajaniemi, Nina; Suhonen, Eira; Kontu, Elina; Rantanen, Pekka; Lindholm, Harri; Hyttinen, Sirpa; Hirvonen, Ari

2011-01-01

The aim of this study was to evaluate the influence of early educational quality on children's cortisol levels. It was hypothesised that the environmental stressors might load children's immature stress regulative systems thus affecting their diurnal cortisol levels. The study sample consisted of 146 preschool-aged children. Cortisol was measured…

Crustal Strain Patterns in Magmatic and Amagmatic Early Stage Rifts: Border Faults, Magma Intrusion, and Volatiles

NASA Astrophysics Data System (ADS)

Ebinger, C. J.; Keir, D.; Roecker, S. W.; Tiberi, C.; Aman, M.; Weinstein, A.; Lambert, C.; Drooff, C.; Oliva, S. J. C.; Peterson, K.; Bourke, J. R.; Rodzianko, A.; Gallacher, R. J.; Lavayssiere, A.; Shillington, D. J.; Khalfan, M.; Mulibo, G. D.; Ferdinand-Wambura, R.; Palardy, A.; Albaric, J.; Gautier, S.; Muirhead, J.; Lee, H.

2015-12-01

Rift initiation in thick, strong continental lithosphere challenges current models of continental lithospheric deformation, in part owing to gaps in our knowledge of strain patterns in the lower crust. New geophysical, geochemical, and structural data sets from youthful magmatic (Magadi-Natron, Kivu), weakly magmatic (Malawi, Manyara), and amagmatic (Tanganyika) sectors of the cratonic East African rift system provide new insights into the distribution of brittle strain, magma intrusion and storage, and time-averaged deformation. We compare and contrast time-space relations, seismogenic layer thickness variations, and fault kinematics using earthquakes recorded on local arrays and teleseisms in sectors of the Western and Eastern rifts, including the Natron-Manyara basins that developed in Archaean lithosphere. Lower crustal seismicity occurs in both the Western and Eastern rifts, including sectors on and off craton, and those with and without central rift volcanoes. In amagmatic sectors, lower crustal strain is accommodated by slip along relatively steep border faults, with oblique-slip faults linking opposing border faults that penetrate to different crustal levels. In magmatic sectors, seismicity spans surface to lower crust beneath both border faults and eruptive centers, with earthquake swarms around magma bodies. Our focal mechanisms and Global CMTs from a 2007 fault-dike episode show a local rotation from ~E-W extension to NE-SE extension in this linkage zone, consistent with time-averaged strain recorded in vent and eruptive chain alignments. These patterns suggest that strain localization via widespread magma intrusion can occur during the first 5 My of rifting in originally thick lithosphere. Lower crustal seismicity in magmatic sectors may be caused by high gas pressures and volatile migration from active metasomatism and magma degassing, consistent with high CO2 flux along fault zones, and widespread metasomatism of xenoliths. Volatile release and

Obituary Analysis of Early 20th Century Marriage and Family Patterns in Northwest Ohio.

ERIC Educational Resources Information Center

Matcha, Duane A.

1995-01-01

A content analysis of obituary notices spanning a one-year period. Examined marital and family patterns such as age at marriage, length of marriage, marital status at time of death, and other factors. Single women had the highest average age at death. Patterns were less consistent among men. (RJM)

Patterns of treatment response in newly diagnosed epilepsy

PubMed Central

Brodie, M.J.; Barry, S.J.E.; Bamagous, G.A.; Norrie, J.D.

2012-01-01

Objective: To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy. Methods: Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into 4 patterns: A) early and sustained seizure freedom; B) delayed but sustained seizure freedom; C) fluctuation between periods of seizure freedom and relapse; and D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for ≥1 year. Results: A total of 1,098 patients were included (median age 32 years, range 9–93). At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. Outcome pattern A was observed in 408 (37%), pattern B in 246 (22%), pattern C in 172 (16%), and pattern D in 272 (25%) patients. There was a higher probability of seizure freedom in patients receiving 1 compared to 2 drug regimens, and 2 compared to 3 regimens (p < 0.001). The difference was greater among patients with symptomatic or cryptogenic than with idiopathic epilepsy. Less than 2% of patients became seizure-free on subsequent regimens but a few did so on their sixth or seventh regimen. Conclusions: Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies. PMID:22573629

Evolutionary modification of T-brain (tbr) expression patterns in sand dollar.

PubMed

Minemura, Keiko; Yamaguchi, Masaaki; Minokawa, Takuya

2009-10-01

The sand dollars are a group of irregular echinoids that diverged from other regular sea urchins approximately 200 million years ago. We isolated two orthologs of T-brain (tbr), Smtbr and Pjtbr, from the indirect developing sand dollar Scaphechinus mirabilis and the direct developing sand dollar Peronella japonica, respectively. The expression patterns of Smtbr and Pjtbr during early development were examined by whole mount in situ hybridization. The expression of Smtbr was first detected in micromere descendants in early blastula stage, similar to tbr expression in regular sea urchins. However, unlike in regular sea urchin, Smtbr expression in middle blastula stage was detected in micromere-descendent cells and a subset of macromere-descendant cells. At gastrula stage, expression of Smtbr was detected in part of the archenteron as well as primary mesenchyme cells. A similar pattern of tbr expression was observed in early Peronella embryos. A comparison of tbr expression patterns between sand dollars and other echinoderm species suggested that broader expression in the endomesoderm is an ancestral character of echinoderms. In addition to the endomesoderm, Pjtbr expression was detected in the apical organ, the animal-most part of the ectoderm.

Evolution and inheritance of early embryonic patterning in Drosophila simulans and D. sechellia.

PubMed

Lott, Susan E; Ludwig, Michael Z; Kreitman, Martin

2011-05-01

Pattern formation in Drosophila is a widely studied example of a robust developmental system. Such robust systems pose a challenge to adaptive evolution, as they mask variation that selection may otherwise act upon. Yet we find variation in the localization of expression domains (henceforth "stripe allometry") in the pattern formation pathway. Specifically, we characterize differences in the gap genes giant and Kruppel, and the pair-rule gene even-skipped, which differ between the sibling species Drosophila simulans and D. sechellia. In a double-backcross experiment, stripe allometry is consistent with maternal inheritance of stripe positioning and multiple genetic factors, with a distinct genetic basis from embryo length. Embryos produced by F1 and F2 backcross mothers exhibit novel spatial patterns of gene expression relative to the parental species, with no measurable increase in positional variance among individuals. Buffering of novel spatial patterns in the backcross genotypes suggests that robustness need not be disrupted in order for the trait to evolve, and perhaps the system is incapable of evolving to prevent the expression of all genetic variation. This limitation, and the ability of natural selection to act on minute genetic differences that are within the "margin of error" for the buffering mechanism, indicates that developmentally buffered traits can evolve without disruption of robustness. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

Evolution and inheritance of early embryonic patterning in D. simulans and D. sechellia

PubMed Central

Lott, Susan E.; Ludwig, Michael Z.; Kreitman, Martin

2010-01-01

Pattern formation in Drosophila is a widely studied example of a robust developmental system. Such robust systems pose a challenge to adaptive evolution, as they mask variation which selection may otherwise act upon. Yet we find variation in the localization of expression domains (henceforth ‘stripe allometry’) in the pattern formation pathway. Specifically, we characterize differences in the gap genes giant and Kruppel, and the pair-rule gene even-skipped, which differ between the sibling species D. simulans and D. sechellia. In a double-backcross experiment, stripe allometry is consistent with maternal inheritance of stripe positioning and multiple genetic factors, with a distinct genetic basis from embryo length. Embryos produced by F1 and F2 backcross mothers exhibit novel spatial patterns of gene expression relative to the parental species, with no measurable increase in positional variance among individuals. Buffering of novel spatial patterns in the backcross genotypes suggests that robustness need not be disrupted in order for the trait to evolve, and perhaps the system is incapable of evolving to prevent the expression of all genetic variation. This limitation, and the ability of natural selection to act on minute genetic differences that are within the “margin of error” for the buffering mechanism, indicates that developmentally buffered traits can evolve without disruption of robustness PMID:21121913

A single-dose, crossover, placebo- and moxifloxacin-controlled study to assess the effects of neratinib (HKI-272) on cardiac repolarization in healthy adult subjects.

PubMed

Hug, Bruce; Abbas, Richat; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

2010-08-01

Neratinib is an orally administered, small-molecule, irreversible pan-ErbB inhibitor in development for the treatment of ErbB2-positive breast cancer. This study assessed the effects of therapeutic and supratherapeutic neratinib concentrations on cardiac repolarization, in accordance with current regulatory guidance. This was a two-part study in healthy subjects. In part 1, subjects were randomized to receive placebo, 400 mg moxifloxacin, or 240 mg neratinib (therapeutic dose) following a high-fat meal. In part 2, after a washout period, subjects received placebo plus 400 mg ketoconazole or 240 mg neratinib plus ketoconazole (supratherapeutic dose). ANOVA was used to compare the baseline-adjusted QTc interval for neratinib with that of placebo (reference), and for neratinib plus ketoconazole with that of placebo plus ketoconazole (reference). Pharmacokinetic/pharmacodynamic analyses and categorical summaries of interval data were done. Assay sensitivity was evaluated by the effect of moxifloxacin on QTc compared with placebo. Sixty healthy subjects were enrolled in this study. The upper bounds of the 90% confidence interval for baseline-adjusted QTcN (population-specific corrected QT) were 450 milliseconds or change from baseline >30 milliseconds. Moxifloxacin produced a significant increase in QTcN compared with placebo (P < 0.05). Therapeutic and supratherapeutic plasma concentrations of neratinib do not prolong the QTc interval in healthy subjects. (c) 2010 AACR.

Typical cerebral metabolic patterns in neurodegenerative brain diseases.

PubMed

Teune, Laura K; Bartels, Anna L; de Jong, Bauke M; Willemsen, Antoon T M; Eshuis, Silvia A; de Vries, Jeroen J; van Oostrom, Joost C H; Leenders, Klaus L

2010-10-30

The differential diagnosis of neurodegenerative brain diseases on clinical grounds is difficult, especially at an early disease stage. Several studies have found specific regional differences of brain metabolism applying [(18)F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), suggesting that this method can assist in early differential diagnosis of neurodegenerative brain diseases.We have studied patients who had an FDG-PET scan on clinical grounds at an early disease stage and included those with a retrospectively confirmed diagnosis according to strictly defined clinical research criteria. Ninety-six patients could be included of which 20 patients with Parkinson's disease (PD), 21 multiple system atrophy (MSA), 17 progressive supranuclear palsy (PSP), 10 corticobasal degeneration (CBD), 6 dementia with Lewy bodies (DLB), 15 Alzheimer's disease (AD), and 7 frontotemporal dementia (FTD). FDG PET images of each patient group were analyzed and compared to18 healthy controls using Statistical Parametric Mapping (SPM5).Disease-specific patterns of relatively decreased metabolic activity were found in PD (contralateral parietooccipital and frontal regions), MSA (bilateral putamen and cerebellar hemispheres), PSP (prefrontal cortex and caudate nucleus, thalamus, and mesencephalon), CBD (contralateral cortical regions), DLB (occipital and parietotemporal regions), AD (parietotemporal regions), and FTD (frontotemporal regions).The integrated method addressing a spectrum of various neurodegenerative brain diseases provided means to discriminate patient groups also at early disease stages. Clinical follow-up enabled appropriate patient inclusion. This implies that an early diagnosis in individual patients can be made by comparing each subject's metabolic findings with a complete database of specific disease related patterns.

Predicting and Detecting Emerging Cyberattack Patterns Using StreamWorks

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

Chin, George; Choudhury, Sutanay; Feo, John T.

2014-06-30

The number and sophistication of cyberattacks on industries and governments have dramatically grown in recent years. To counter this movement, new advanced tools and techniques are needed to detect cyberattacks in their early stages such that defensive actions may be taken to avert or mitigate potential damage. From a cybersecurity analysis perspective, detecting cyberattacks may be cast as a problem of identifying patterns in computer network traffic. Logically and intuitively, these patterns may take on the form of a directed graph that conveys how an attack or intrusion propagates through the computers of a network. Such cyberattack graphs could providemore » cybersecurity analysts with powerful conceptual representations that are natural to express and analyze. We have been researching and developing graph-centric approaches and algorithms for dynamic cyberattack detection. The advanced dynamic graph algorithms we are developing will be packaged into a streaming network analysis framework known as StreamWorks. With StreamWorks, a scientist or analyst may detect and identify precursor events and patterns as they emerge in complex networks. This analysis framework is intended to be used in a dynamic environment where network data is streamed in and is appended to a large-scale dynamic graph. Specific graphical query patterns are decomposed and collected into a graph query library. The individual decomposed subpatterns in the library are continuously and efficiently matched against the dynamic graph as it evolves to identify and detect early, partial subgraph patterns. The scalable emerging subgraph pattern algorithms will match on both structural and semantic network properties.« less

Recurrence Patterns and Second Primary Lung Cancers After Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Cancer: Implications for Surveillance.

PubMed

Spratt, Daniel E; Wu, Abraham J; Adeseye, Victoria; Din, Shaun U; Shaikh, Fauzia; Woo, Kaitlin M; Zhang, Zhigang; Foster, Amanda; Rosenzweig, Kenneth E; Gewanter, Richard; Huang, James; Rimner, Andreas

2016-05-01

Patients treated with stereotactic body radiation therapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) are subject to locoregional and distant recurrence, as well as the formation of second primary lung cancers (SPLCs). The optimal surveillance regimen for patients treated with SBRT for early-stage NSCLC remains unclear; we therefore investigated the posttreatment recurrence patterns and development of SPLCs. Three hundred sixty-six patients with pathologically proven inoperable early-stage NSCLC treated with SBRT between 2006 and 2013 were assessed. Patients underwent a computed tomographic (CT) scan of the chest every 3 months during years 1 and 2, every 6 months during years 3 and 4, and annually thereafter. Competing risk analysis was used for all time-to-event analyses. With a median follow-up of 23 months, the 2-year cumulative incidence of local, nodal, and distant treatment failures were 12.2%, 16.1%, and 15.5%, respectively. In patients with disease progression after SBRT (n = 108), 84% (n = 91) of cases occurred within the first 2 years. Five percent (n = 19) of patients experienced SPLCs. The median time to development of an SPLC was 16.5 months (range, 6.5-71.1 months), with 33% (n = 6) of these patients experiencing SPLCs after 2 years. None of the never smokers, but 4% of former tobacco smokers and 15% of current tobacco smokers, experienced an SPLC (P = .005). Close monitoring with routine CT scans within the first 2 years after SBRT is effective in detecting early disease progression. In contrast, the risk for the development of an SPLC remains elevated beyond 2 years, particularly in former and current smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

Phrenic motoneuron discharge patterns following chronic cervical spinal cord injury

PubMed Central

Lee, Kun-Ze; Dougherty, Brendan J.; Sandhu, Milapjit S.; Lane, Michael A.; Reier, Paul J.; Fuller, David D.

2013-01-01

Cervical spinal cord injury (SCI) dramatically disrupts synaptic inputs and triggers biochemical, as well as morphological, plasticity in relation to the phrenic motor neuron (PhMN) pool. Accordingly, our primary purpose was to determine if chronic SCI induces fundamental changes in the recruitment profile and discharge patterns of PhMNs. Individual PhMN action potentials were recorded from the phrenic nerve ipsilateral to lateral cervical (C2) hemisection injury (C2Hx) in anesthetized adult male rats at 2, 4 or 8 wks post-injury and in uninjured controls. PhMNs were phenotypically classified as early (Early-I) or late inspiratory (Late-I), or silent according to discharge patterns. Following C2Hx, the distribution of PhMNs was dominated by Late-I and silent cells. Late-I burst parameters (e.g., spikes per breath, burst frequency and duration) were initially reduced but returned towards control values by 8 wks post-injury. In addition, a unique PhMN burst pattern emerged after C2Hx in which Early-I cells burst tonically during hypocapnic inspiratory apnea. We also quantified the impact of gradual reductions in end-tidal CO2 partial pressure (PETCO2) on bilateral phrenic nerve activity. Compared to control rats, as PETCO2 declined, the C2Hx animals had greater inspiratory frequencies (breaths*min−1) and more substantial decreases in ipsilateral phrenic burst amplitude. We conclude that the primary physiological impact of C2Hx on ipsilateral PhMN burst patterns is a persistent delay in burst onset, transient reductions in burst frequency, and the emergence of tonic burst patterns. The inspiratory frequency data suggest that plasticity in brainstem networks is likely to play an important role in phrenic motor output after cervical SCI. PMID:23954215

Rate dependency of delayed rectifier currents during the guinea-pig ventricular action potential

PubMed Central

Rocchetti, Marcella; Besana, Alessandra; Gurrola, Georgina B; Possani, Lourival D; Zaza, Antonio

2001-01-01

The action potential clamp technique was exploited to evaluate the rate dependency of delayed rectifier currents (IKr and IKs) during physiological electrical activity. IKr and IKs were measured in guinea-pig ventricular myocytes at pacing cycle lengths (CL) of 1000 and 250 ms.A shorter CL, with the attendant changes in action potential shape, was associated with earlier activation and increased magnitude of both IKr and IKs. Nonetheless, the relative contributions of IKr and IKs to total transmembrane current were independent of CL.Shortening of diastolic interval only (constant action potential shape) enhanced IKs, but not IKr.IKr was increased by a change in the action potential shape only (constant diastolic interval).In ramp clamp experiments, IKr amplitude was directly proportional to repolarization rate at values within the low physiological range (< 1.0 V s−1); at higher repolarization rates proportionality became shallower and finally reversed.When action potential duration (APD) was modulated by constant current injection (I-clamp), repolarization rates > 1.0 V s−1 were associated with a reduced effect of IKr block on APD. The effect of changes in repolarization rate was independent of CL and occurred in the presence of IKs blockade.In spite of its complexity, the behaviour of IKr was accurately predicted by a numerical model based entirely on known kinetic properties of the current.Both IKr and IKs may be increased at fast heart rates, but this may occur through completely different mechanisms. The mechanisms identified are such as to contribute to abnormal rate dependency of repolarization in prolonged repolarization syndromes. PMID:11483703

Temporal patterns of phytoplankton abundance in the North Atlantic

NASA Technical Reports Server (NTRS)

Campbell, Janet W.

1989-01-01

A time series of CZCS images is being developed to study phytoplankton distribution patterns in the North Atlantic. The goal of this study is to observe temporal variability in phytoplankton pigments and other organic particulates, and to infer from these patterns the potential flux of biogenic materials from the euphotic layer to the deep ocean. Early results of this project are presented in this paper. Specifically, the satellite data used were 13 monthly composited images of CZCS data for the North Atlantic from January 1979 to January 1980. Results are presented for seasonal patterns along the 20 deg W meridian.

Metacarpophalangeal pattern profile analysis in Leri-Weill dyschondrosteosis.

PubMed

Laurencikas, E; Soderman, E; Grigelioniene, G; Hagenäs, L; Jorulf, H

2005-04-01

To analyze the metacarpophalangeal profile (MCPP) in individuals with Leri-Weill dyschondrosteosis (LWD) and to assess its value as a possible contributor to early diagnosis. Hand profiles of 39 individuals with a diagnosis of LWD were calculated and analyzed. Discriminant analysis was applied to differentiate between LWD and normal individuals. There was a distinct pattern profile in LWD. Mean pattern profile showed two bone-shortening gradients, with increasing shortening from distal to proximal and from medial to lateral. Distal phalanx 2 was disproportionately long and second metacarpal was disproportionately short. Discriminant analysis yielded correct classification in 72% of analyzed cases. MCPP is not age-related and the analysis can be applied at any age, facilitating early diagnosis of LWD. In view of its availability, low costs, and diagnostic value, MCPP analysis should be considered as a routine method in the patients of short stature where LWD is suspected.

Early Childhood Policy Focus: Healthy Eating and Physical Activity. Early Childhood Highlights. Volume 2, Issue 3

ERIC Educational Resources Information Center

Murphey, David; Mackintosh, Bonnie; McCoy-Roth, Marci

2011-01-01

The importance of good nutrition and exercise is well known, and parents have long worried about their children's diets and envied their high energy levels. Like so many life style habits, patterns of nutrition and exercise behaviors are typically established in early childhood. Poor diet and lack of exercise contribute to obesity, which has been…

The Expression Pattern of microRNAs in Granulosa Cells of Subordinate and Dominant Follicles during the Early Luteal Phase of the Bovine Estrous Cycle

PubMed Central

Gebremedhn, Samuel; Sahadevan, Sudeep; Hossain, MD Munir; Rings, Franca; Hoelker, Michael; Tholen, Ernst; Neuhoff, Christiane; Looft, Christian; Schellander, Karl; Tesfaye, Dawit

2014-01-01

This study aimed to investigate the miRNA expression patterns in granulosa cells of subordinate (SF) and dominant follicle (DF) during the early luteal phase of the bovine estrous cycle. For this, miRNA enriched total RNA isolated from granulosa cells of SF and DF obtained from heifers slaughtered at day 3 and day 7 of the estrous cycle was used for miRNAs deep sequencing. The results revealed that including 17 candidate novel miRNAs, several known miRNAs (n = 291–318) were detected in SF and DF at days 3 and 7 of the estrous cycle of which 244 miRNAs were common to all follicle groups. The let-7 families, bta-miR-10b, bta-miR-26a, bta-miR-99b and bta-miR-27b were among abundantly expressed miRNAs in both SF and DF at both days of the estrous cycle. Further analysis revealed that the expression patterns of 16 miRNAs including bta-miR-449a, bta-miR-449c and bta-miR-222 were differentially expressed between the granulosa cells of SF and DF at day 3 of the estrous cycle. However, at day 7 of the estrous cycle, 108 miRNAs including bta-miR-409a, bta-miR-383 and bta-miR-184 were differentially expressed between the two groups of granulosa cell revealing the presence of distinct miRNA expression profile changes between the two follicular stages at day 7 than day 3 of the estrous cycle. In addition, unlike the SF, marked temporal miRNA expression dynamics was observed in DF groups between day 3 and 7 of the estrous cycle. Target gene prediction and pathway analysis revealed that major signaling associated with follicular development including Wnt signaling, TGF-beta signaling, oocyte meiosis and GnRH signaling were affected by differentially expressed miRNAs. Thus, this study highlights the miRNA expression patterns of granulosa cells in subordinate and dominant follicles that could be associated with follicular recruitment, selection and dominance during the early luteal phase of the bovine estrous cycle. PMID:25192015

Early Childhood Teachers' Professional Learning in Early Algebraic Thinking: A Model that Supports New Knowledge and Pedagogy

ERIC Educational Resources Information Center

Warren, Elizabeth

2009-01-01

The implementation of a new mathematics syllabus in the elementary context is problematic, especially if it contains a new content area. A professional development model, Transformative Teaching in the Early Years Mathematics (TTEYM) was specifically developed to support the implementation of the new Patterns and Algebra strand. The model was…

Numerosity processing in early visual cortex.

PubMed

Fornaciai, Michele; Brannon, Elizabeth M; Woldorff, Marty G; Park, Joonkoo

2017-08-15

While parietal cortex is thought to be critical for representing numerical magnitudes, we recently reported an event-related potential (ERP) study demonstrating selective neural sensitivity to numerosity over midline occipital sites very early in the time course, suggesting the involvement of early visual cortex in numerosity processing. However, which specific brain area underlies such early activation is not known. Here, we tested whether numerosity-sensitive neural signatures arise specifically from the initial stages of visual cortex, aiming to localize the generator of these signals by taking advantage of the distinctive folding pattern of early occipital cortices around the calcarine sulcus, which predicts an inversion of polarity of ERPs arising from these areas when stimuli are presented in the upper versus lower visual field. Dot arrays, including 8-32dots constructed systematically across various numerical and non-numerical visual attributes, were presented randomly in either the upper or lower visual hemifields. Our results show that neural responses at about 90ms post-stimulus were robustly sensitive to numerosity. Moreover, the peculiar pattern of polarity inversion of numerosity-sensitive activity at this stage suggested its generation primarily in V2 and V3. In contrast, numerosity-sensitive ERP activity at occipito-parietal channels later in the time course (210-230ms) did not show polarity inversion, indicating a subsequent processing stage in the dorsal stream. Overall, these results demonstrate that numerosity processing begins in one of the earliest stages of the cortical visual stream. Copyright © 2017 Elsevier Inc. All rights reserved.

The die is cast - Arsenic exposure in early life and disease susceptibility

EPA Science Inventory

Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

New Fossil Evidence on the Sister-Group of Mammals and Early Mesozoic Faunal Distributions

NASA Astrophysics Data System (ADS)

Shubin, Neil H.; Crompton, A. W.; Sues, Hans-Dieter; Olsen, Paul E.

1991-03-01

Newly discovered remains of highly advanced mammal-like reptiles (Cynodontia: Tritheledontidae) from the Early Jurassic of Nova Scotia, Canada, have revealed that aspects of the characteristic mammalian occlusal pattern are primitive. Mammals and tritheledontids share an homologous pattern of occlusion that is not seen in other cynodonts. The new tritheledontids represent the first definite record of this family from North America. The extreme similarity of North American and African tritheledontids supports the hypothesis that the global distribution of terrestrial tetrapods was homogeneous in the Early Jurassic. This Early Jurassic cosmopolitanism represents the continuation of a trend toward increased global homogeneity among terrestrial tetrapod communities that began in the late Paleozoic.

Irregular vascular pattern by contrast-enhanced ultrasonography and high serum Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level predict poor outcome after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma.

PubMed

Takada, Hitomi; Tsuchiya, Kaoru; Yasui, Yutaka; Nakakuki, Natsuko; Tamaki, Nobuharu; Suzuki, Shoko; Nakanishi, Hiroyuki; Itakura, Jun; Takahashi, Yuka; Kurosaki, Masayuki; Asahina, Yasuhiro; Enomoto, Nobuyuki; Izumi, Namiki

2016-11-01

Radiofrequency ablation (RFA) is considered the most effective treatment for early-stage hepatocellular carcinoma (HCC) patients unsuitable for resection. However, poor outcome after RFA has occasionally been reported worldwide. To predict such an outcome, we investigated imaging findings using contrast-enhanced ultrasonography (CEUS) with Sonazoid and serum tumor markers before RFA. This study included 176 early-stage HCC patients who had initially achieved successful RFA. Patients were examined using CEUS; their levels of alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin before RFA were measured. Sonazoid provided parenchyma-specific contrast imaging and facilitated tumor vascular architecture imaging through maximum intensity projection (MIP). Kaplan-Meier analysis examined cumulative rates of local tumor progression, intrasubsegmental recurrence, and survival; factors associated with these were determined with Cox proportional hazards analysis. Local tumor progression (n = 15), intrasubsegmental recurrence (n = 46), and death (n = 18) were observed. Irregular pattern in MIP classification and serum AFP-L3 level (>10%) before RFA were identified as independent risk factors for local tumor progression and intrasubsegmental recurrence. These two factors were independently associated with poor survival after RFA (irregular pattern in MIP: hazard ratio, (HR) = 8.26; 95% confidence interval, (CI) = 2.24-30.3; P = 0.002 and AFP-L3 > 10%: HR = 2.94; 95% CI = 1.09-7.94; P = 0.033). Irregular MIP pattern by CEUS and high level of serum AFP-L3 were independent risk factors for poor outcome after successful RFA. The Patients with these findings should be considered as special high-risk group in early-stage HCC. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Safety of transvenous low energy cardioversion of atrial fibrillation in patients with a history of ventricular tachycardia: effects of rate and repolarization time on proarrhythmic risk.

PubMed

Simons, G R; Newby, K H; Kearney, M M; Brandon, M J; Natale, A

1998-02-01

The objective of this study was to assess the safety and efficacy of transvenous low energy cardioversion of atrial fibrillation in patients with ventricular tachycardia and atrial fibrillation and to study the mechanisms of proarrhythmia. Previous studies have demonstrated that cardioversion of atrial fibrillation using low energy, R wave synchronized, direct current shocks applied between catheters in the coronary sinus and right atrium is feasible. However, few data are available regarding the risk of ventricular proarrhythmia posed by internal atrial defibrillation shocks among patients with ventricular arrhythmias or structural heart disease. Atrial defibrillation was performed on 32 patients with monomorphic ventricular tachycardia and left ventricular dysfunction. Shocks were administered during atrial fibrillation (baseline shocks), isoproterenol infusion, ventricular pacing, ventricular tachycardia, and atrial pacing. Baseline shocks were also administered to 29 patients with a history of atrial fibrillation but no ventricular arrhythmias. A total of 932 baseline shocks were administered. No ventricular proarrhythmia was observed after well-synchronized baseline shocks, although rare inductions of ventricular fibrillation occurred after inappropriate T wave sensing. Shocks administered during wide-complex rhythms (ventricular pacing or ventricular tachycardia) frequently induced ventricular arrhythmias, but shocks administered during atrial pacing at identical ventricular rates did not cause proarrhythmia. The risk of ventricular proarrhythmia after well-synchronized atrial defibrillation shocks administered during narrow-complex rhythms is low, even in patients with a history of ventricular tachycardia. The mechanism of proarrhythmia during wide-complex rhythms appears not to be related to ventricular rate per se, but rather to the temporal relationship between shock delivery and the repolarization time of the previous QRS complex.

Clinical utility of T-wave alternans

NASA Technical Reports Server (NTRS)

Armoundas, A. A.; Cohen, R. J.

1997-01-01

Electrical alternans represents a variation in the morphology of electrocardiographic complexes on an every-other-beat basis in an ABABAB... pattern. Apparent electrical alternans associated with pericardial effusion results from rotation of the heart in the pericardial sac, and not true alternation in electrical conduction patterns. In contrast, true electrical alternans results from an alternation in electrical conduction patterns in the heart itself. Repolarization alternans is true electrical alternans associated with the ST segment and T wave of the electrocardiogram (ECG). Here we will focus on T-wave alternans (TWA) and its association with susceptibility to ventricular tachyarrhythmias. Electrical alternans was reported in the literature as early as 1909. Historically, electrical alternans has been regarded as a fairly rare electrocardiographic abnormality. Case reports of electrical alternans have been associated with a variety of disease states, including acute ischemia, Prinzmetal's angina, a variety of electrolyte abnormalities, and the long QT syndrome. Interestingly, patients born with the prolonged QT syndrome have a very high incidence of sudden cardiac death at an early age. Schwartz and Malliani showed that patients with the prolonged QT syndrome who do not demonstrate alternans at rest, may evidence alternans during stress such as emotional excitement. Thus, over the years electrical alternans has been associated anecdotally with conditions associated with an increased risk of ventricular arrhythmias. In 1948, Kalter reviewed the world literature on electrical alternans and found a total of 41 reported cases. In addition, he reviewed clinical ectrocardiograms from 6059 patients and found five new cases (incidence of less than 1 in 1000 patients). Interestingly, he found a very high mortality, 62%, associated with this condition. Despite the clinical associations reported in the literature, the consensus view of electrical alternans until recent

Characterizing and understanding body weight patterns in patients treated with pregabalin.

PubMed

Cabrera, Javier; Emir, Birol; Dills, Diana; Murphy, T Kevin; Whalen, Ed; Clair, Andrew

2012-06-01

We examined patterns of weight change among patients treated with pregabalin for up to 1 year. Patients with ≥1 pre-treatment weight measurement, ≥2 measurements in Period 1 (day 2-56), and ≥2 during Period 2 (day 57-356) were identified from pooled data of 106 studies including 43,525 patients. Seven patterns were developed and used for exploratory 'change point' analyses (day on-treatment when weight-change trend changed from initial trajectory) and to assess patterns of weight change by baseline weight/body mass index (BMI). A total of 3187 patients (from 41 studies) were eligible. 98.9% of patients were described by three of the seven patterns. The majority of patients (2607/3187 [81.8%]) remained within ±7% of baseline weight ('Pattern 4'). Fewer patients (463/3187 [14.5%]) were 'delayed weight gainers' (exceeded 7% weight gain in Period 2 but not Period 1 ['Pattern 6']), fewer still (82/3187 [2.6%]) were 'early weight gainers' (exceeded ≥7% baseline weight in Period 1 and remained above 7% or continued to gain weight in Period 2 ['Pattern 7']). Overall weight gainers (Patterns 6, 7) experienced 1-year weight gain (median [% change]) of +6.20 kg [+9.12%] and 5.46 kg [+13.9%] vs. 2.22 kg [+2.10%] for non-weight gainers (Pattern 4). Average baseline weight/BMI was lower for weight gainers (Patterns 6, 7) versus other patterns. Early weight gainers (Pattern 7) had change point day at day 40 versus day 54 for Pattern 4 and day 69 for Pattern 6. Use of concomitant medications and influence of comorbid conditions on weight should be considered as inherent variables when interpreting the study. The majority of patients treated with pregabalin (150-600 mg/day) for 1 year maintained weight within ±7% baseline weight. One in six patients gained ≥7% weight from baseline, and generally exceeded 7%, 2-12 months after treatment onset.

Identifying Differences in Early Mathematical Skills among Children in Head Start

ERIC Educational Resources Information Center

Wu, Qiong; Lei, Pui-wa; DiPerna, James C.; Morgan, Paul L.; Reid, Erin E.

2015-01-01

The purpose of this study was to examine early mathematical skill differences among preschool children in US Head Start classrooms. Latent class analysis based on six early mathematical subtest scores (i.e. counting aloud, measurement, counting objects, numbers and shapes, pattern recognition, and grouping) from a sample of 279 Head Start children…

The Influence of Relational Knowledge and Executive Function on Preschoolers' Repeating Pattern Knowledge

ERIC Educational Resources Information Center

Miller, Michael R.; Rittle-Johnson, Bethany; Loehr, Abbey M.; Fyfe, Emily R.

2016-01-01

Children's knowledge of repeating patterns (e.g., ABBABB) is a central component of early mathematics, but the developmental mechanisms underlying this knowledge are currently unknown. We sought clarity on the importance of relational knowledge and executive function (EF) to preschoolers' understanding of repeating patterns. One hundred…

Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas

PubMed Central

Müller, Sören; Agnihotri, Sameer; Shoger, Karsen E.; Myers, Max I.; Chaparala, Srilakshmi; Villanueva, Clarence R.; Chattopadhyay, Ansuman; Butterfield, Lisa H.; Okada, Hideho; Pollack, Ian F.

2018-01-01

Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine, which elicited consistent antigen-specific T cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD), partial response (PR), and near-complete/complete response (CR) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA sequencing on PBMC samples collected at multiple time points. Patients who showed CR demonstrated elevated levels of T cell activation markers, accompanied by a cytotoxic T cell response shortly after treatment initiation. At week 34, patients with CR demonstrated both IFN signaling and Poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T cell activation markers were associated with prolonged progression-free survival. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing phase II LGG vaccine immunotherapy, should monitor these response patterns. PMID:29618666

The compass rose pattern in electricity prices.

PubMed

Batten, Jonathan A; Hamada, Mahmoud

2009-12-01

The "compass rose pattern" is known to appear in the phase portraits, or scatter diagrams, of the high-frequency returns of financial series. We first show that this pattern is also present in the returns of spot electricity prices. Early researchers investigating these phenomena hoped that these patterns signaled the presence of rich dynamics, possibly chaotic or fractal in nature. Although there is a definite autoregressive and conditional heteroscedasticity structure in electricity returns, we find that after simple filtering no pattern remains. While the series is non-normal in terms of their distribution and statistical tests fail to identify significant chaos, there is evidence of fractal structures in periodic price returns when measured over the trading day. The phase diagram of the filtered returns provides a useful visual check on independence, a property necessary for pricing and trading derivatives and portfolio construction, as well as providing useful insights into the market dynamics.

Early Motherhood in an Intergenerational Perspective: The Experiences of a British Cohort.

ERIC Educational Resources Information Center

Manlove, Jennifer

1997-01-01

Uses nationally representative, longitudinal data from Great Britain to examine the fertility patterns of daughters (N=2,183) of teen mothers. Explores how early motherhood is reproduced across generations, including an earlier inherited age of menarche, poor family and educational environments, and an early ideal age of childbearing. (RJM)

Novel mechanisms of early upper and lower urinary tract patterning regulated by RetY1015 docking tyrosine in mice

PubMed Central

Hoshi, Masato; Batourina, Ekatherina; Mendelsohn, Cathy; Jain, Sanjay

2012-01-01

Mutations in the receptor tyrosine kinase RET are associated with congenital anomalies of kidneys or urinary tract (CAKUT). RET tyrosine Y1015 is the docking site for PLCγ, a major regulator of RET signaling. Abrogating signaling via Y1015 causes CAKUT that are markedly different than renal agenesis in Ret-null or RetY1062F mutant mice. We performed analysis of Y1015F mutant upper and lower urinary tracts in mice to delineate its molecular and developmental roles during early urinary tract formation. We found that the degeneration of the common nephric ducts (CND), the caudal-most Wolffian duct (WD) segment, depends on Y1015 signals. The CNDs in Y1015F mutants persist owing to increased proliferation and reduced apoptosis, and showed abundance of phospho-ERK-positive cells. In the upper urinary tract, the Y1015 signals are required for proper patterning of the mesonephros and metanephros. Timely regression of mesonephric mesenchyme and proper demarcation of mesonephric and metanephric mesenchyme from the WD depends on RetY1015 signaling. We show that the mechanism of de novo ectopic budding is via increased ERK activity due to abnormal mesenchymal GDNF expression. Although reduction in GDNF dosage improved CAKUT it did not affect delayed mesenchyme regression. Experiments using whole-mount immunofluorescence confocal microscopy and explants cultures of early embryos with ERK-specific inhibitors suggest an imbalance between increased proliferation, decreased apoptosis and increased ERK activity as a mechanism for WD defects in RetY1015F mice. Our work demonstrates novel inhibitory roles of RetY1015 and provides a possible mechanistic explanation for some of the confounding broad range phenotypes in individuals with CAKUT. PMID:22627285

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

PubMed

Maruyama, Mitsunori; Xiao, Jianmin; Zhou, Qiang; Vembaiyan, Kannan; Chua, Su-Kiat; Rubart-von der Lohe, Michael; Lin, Shien-Fong; Back, Thomas G; Chen, S R Wayne; Chen, Peng-Sheng

2013-01-01

Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2). To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs). Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects. Spontaneous intracellular Ca(2+) elevations (SCaEs) during diastole were induced by rapid ventricular pacing and isoproterenol infusion in intact rabbit ventricles. Systolic and diastolic SCaEs were simultaneously noted in Langendorff-perfused RyR2 R4496(+/-) mouse hearts after creating atrioventricular block. VK-II-36 effectively suppressed SCaEs and eliminated TAs observed in both mouse and rabbit ventricles. We tested the effect of VK-II-36 on EADs by using a rabbit model of acquired long QT syndrome, in which phase 2 and phase 3 EADs were observed in association with systolic SCaEs. VK-II-36 abolished the systolic SCaEs and phase 2 EADs, and greatly decreased the dispersion of repolarization and the amplitude of phase 3 EADs. VK-II-36 completely prevented EAD-mediated TAs in all ventricles studied. A carvedilol analogue, VK-II-36, inhibits ventricular tachyarrhythmias in intact mouse and rabbit ventricles by the suppression of SCaEs, independent of beta-blocking activity. The RyR2 may be a potential target for treating focal ventricular arrhythmias triggered by either EADs or DADs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Non-completion of secondary education and early disability in Norway: geographic patterns, individual and community risks.

PubMed

Myhr, Arnhild; Haugan, Tommy; Lillefjell, Monica; Halvorsen, Thomas

2018-05-31

School non-completion and early work disability is a great public health challenge in Norway, as in most western countries. This study aims to investigate how medically based disability pension (DP) among young adults varies geographically and how municipal socioeconomic conditions interact with non-completion of secondary education in determining DP risk. The study includes a nationally representative sample of 30% of all Norwegians (N = 350,699) aged 21-40 in 2010 from Statistic Norway's population registries. Multilevel models incorporating factors at the individual, neighbourhood and municipal levels were applied to estimate the neighbourhood and municipality general contextual effects in DP receipt, and detect possible differences in the impact of municipal socioeconomic conditions on DP risk between completers and non-completers of secondary education. A pattern of spatial clustering at the neighbourhood (ICC = 0.124) and municipality (ICC = 0.021) levels are clearly evident, indicating that the underlying causes of DP receipt have a systematic neighbourhood and municipality variation in Norway. Non-completion of secondary education is strongly correlated with DP receipt among those younger than 40. Socioeconomic characteristics of the municipality are also significantly correlated with DP risk, but these associations are conditioned by the completion of secondary education. Living in a socioeconomically advantageous municipality (i.e. high income, high education levels and low unemployment and social security payment rates) is associated with a higher risk of DP, but only among those who do not complete their secondary education. Although the proportion of DPs was equal in rural and urban areas, it is evident that young people living in urban settings are more at risk of early DP than their counterparts living in rural parts of the country when controlling for other risk factors. The association between school non-completion and DP risk varies

Form, function and environments of the early angiosperms: merging extant phylogeny and ecophysiology with fossils.

PubMed

Feild, Taylor S; Arens, Nan Crystal

2005-05-01

The flowering plants--angiosperms--appeared during the Early Cretaceous period and within 10-30 Myr dominated the species composition of many floras worldwide. Emerging insights into the phylogenetics of development and discoveries of early angiosperm fossils are shedding increased light on the patterns and processes of early angiosperm evolution. However, we also need to integrate ecology, in particular how early angiosperms established a roothold in pre-existing Mesozoic plant communities. These events were critical in guiding subsequent waves of angiosperm diversification during the Aptian-Albian. Previous pictures of the early flowering plant ecology have been diverse, ranging from large tropical rainforest trees, weedy drought-adapted and colonizing shrubs, disturbance- and sun-loving rhizomatous herbs, and, more recently, aquatic herbs; however, none of these images were tethered to a robust hypothesis of angiosperm phylogeny. Here, we synthesize our current understanding of early angiosperm ecology, focusing on patterns of functional ecology, by merging recent molecular phylogenetic studies and functional studies on extant 'basal angiosperms' with the picture of early angiosperm evolution drawn by the fossil record.

Trajectories of Early Childhood Developmental Skills and Early Adolescent Psychotic Experiences: Findings from the ALSPAC UK Birth Cohort.

PubMed

Hameed, Mohajer A; Lingam, Raghu; Zammit, Stanley; Salvi, Giovanni; Sullivan, Sarah; Lewis, Andrew J

2017-01-01

Objective: The aim of this study was to use prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine association between trajectories of early childhood developmental skills and psychotic experiences (PEs) in early adolescence. Method: This study examined data from n = 6790 children from the ALSPAC cohort who participated in a semi-structured interview to assess PEs at age 12. Child development was measured using parental report at 6, 18, 30, and 42 months of age using a questionnaire of items adapted from the Denver Developmental Screening Test - II. Latent class growth analysis was used to generate trajectories over time for measures of fine and gross motor development, social, and communication skills. Logistic regression was used to investigate associations between developmental trajectories in each of these early developmental domains and PEs at age 12. Results: The results provided evidence that decline rather than enduringly poor social (adjusted OR = 1.28, 95% CI = 1.10-1.92, p = 0.044) and communication skills (adjusted OR 1.12, 95% CI = 1.03-1.22, p = 0.010) is predictive of suspected or definite PEs in early adolescence, than those with stable and/or improving skills. Motor skills did not display the same pattern of association; although gender specific effects provided evidence that only declining pattern of fine motor skills was associated with suspected and definite PEs in males compared to females (interaction OR = 1.47, 95% CI = 1.09-1.97, p = 0.012). Conclusion: Findings suggest that decline rather than persistent impairment in social and communication skills were most predictive of PEs in early adolescence. Findings are discussed in terms of study's strengths, limitations, and clinical implications.

Trajectories of Early Childhood Developmental Skills and Early Adolescent Psychotic Experiences: Findings from the ALSPAC UK Birth Cohort

PubMed Central

Hameed, Mohajer A.; Lingam, Raghu; Zammit, Stanley; Salvi, Giovanni; Sullivan, Sarah; Lewis, Andrew J.

2018-01-01

Objective: The aim of this study was to use prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine association between trajectories of early childhood developmental skills and psychotic experiences (PEs) in early adolescence. Method: This study examined data from n = 6790 children from the ALSPAC cohort who participated in a semi-structured interview to assess PEs at age 12. Child development was measured using parental report at 6, 18, 30, and 42 months of age using a questionnaire of items adapted from the Denver Developmental Screening Test – II. Latent class growth analysis was used to generate trajectories over time for measures of fine and gross motor development, social, and communication skills. Logistic regression was used to investigate associations between developmental trajectories in each of these early developmental domains and PEs at age 12. Results: The results provided evidence that decline rather than enduringly poor social (adjusted OR = 1.28, 95% CI = 1.10–1.92, p = 0.044) and communication skills (adjusted OR 1.12, 95% CI = 1.03–1.22, p = 0.010) is predictive of suspected or definite PEs in early adolescence, than those with stable and/or improving skills. Motor skills did not display the same pattern of association; although gender specific effects provided evidence that only declining pattern of fine motor skills was associated with suspected and definite PEs in males compared to females (interaction OR = 1.47, 95% CI = 1.09–1.97, p = 0.012). Conclusion: Findings suggest that decline rather than persistent impairment in social and communication skills were most predictive of PEs in early adolescence. Findings are discussed in terms of study’s strengths, limitations, and clinical implications. PMID:29375433

Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis.

PubMed

Tyl, Benoît; Kabbaj, Meriam; Azzam, Sara; Sologuren, Ander; Valiente, Román; Reinbolt, Elizabeth; Roupe, Kathryn; Blanco, Nathalie; Wheeler, William

2012-06-01

The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time-matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16 extracted over 72 hours post day 4 dosing. Four QT/RR corrections were implemented: QTcB; QTcF; a linear individual correction (QTcNi), the primary correction; and a nonlinear one (QTcNnl). Moxifloxacin was associated with a significant increase in QTcNi at all time points between 1 and 12 hours, inclusively. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc (maximum increase in QTcNi, 5.02 ms; upper confidence limit [UCL] of the 1-sided, 95% confidence interval, 7.87 ms). Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc (maximum increase in QTcNi, 9.3 ms; UCL, 12.16 ms). This result was most likely related to the cardiac effect of ketoconazole because for all time points, bilastine plasma concentrations were lower than those observed following the supratherapeutic dose.

The Effect of Early Marriages and Early Childbearing on Women's Nutritional Status in India.

PubMed

Goli, Srinivas; Rammohan, Anu; Singh, Deepti

2015-08-01

The consequences of early childbearing on the growth and nutritional status of women in India has not been quantified in previous studies. Our study aimed to fill this gap by analysing the association between early marriage and early childbearing on nutritional status of Indian women, with a focus on Bihar and Andhra Pradesh, the two states accounting for the highest proportion of women marrying and giving first birth before 18 years of age. Our findings revealed that a substantial number of women were married before 18 years and thereby exposed to early pregnancy. Furthermore, a significantly higher proportion of women in the 'thin' category were married before 18 years, both in the Indian sample (33 %, p < 0.001) and in the selected states, Andhra Pradesh (31 %, p < 0.001) and Bihar (43 %, p < 0.001), compared to those women married at higher ages. Similarly, across all our samples women whose first birth was before age 18 years also had a significantly higher probability of being in the 'thin' category across all our samples. This pattern was also observed for associations between early childbirth and anemia levels. We conclude that the net effect of the early age at marriage and age at first birth on nutritional status is significant. Our results underline the need for preventing early marriages and the consequent high adolescent pregnancies in India, particularly in high prevalence states. This will help to improve nutritional status and health care utilisation among women, thereby, prevent maternal and child mortality and thus, achieve the MDGs 4-5.

Abundance, distribution, trends, and ownership patterns of early successional forests in the northeastern United States

Treesearch

Robert T. Brooks

2003-01-01

Early-successional forests are ephemeral and distinct forest communities, maintained by disturbance and dominated by small-sized trees and shrubs. These structural and compositional conditions form a unique habitat that is preferred by many wildlife species. Various sources have indicated that there have been declines in early-successional forest area and in the...

Repeating Patterns: Strategies to Assist Young Students to Generalise the Mathematical Structure

ERIC Educational Resources Information Center

Warren, Elizabeth; Miller, Jodie; Cooper, Thomas

2012-01-01

This paper focuses on very young students' ability to engage in repeating pattern tasks and identifying strategies that assist them to ascertain the structure of the pattern. It describes results of a study which is part of the Early Years Generalising Project (EYGP) and involves Australian students in Years 1 to 4 (ages 5-10). This paper reports…

Patterned variation in prehistoric chiefdoms

PubMed Central

Drennan, Robert D.; Peterson, Christian E.

2006-01-01

Comparative study of early complex societies (chiefdoms) conjures visions of a cultural evolutionary emphasis on similarities and societal typology. Variation within the group has not been as systematically examined but offers an even more productive avenue of approach to fundamental principles of organization and change. Three widely separated trajectories of early chiefdom development are compared here: the Valley of Oaxaca (Mexico), the Alto Magdalena (Colombia), and Northeast China. Archaeological data from all three regions are analyzed with the same tools to reveal variation in human activities, relationships, and interactions as these change in the emergence of chiefly communities. Patterning in this variation suggests the operation of underlying general principles, which are offered as hypotheses that merit further investigation and evaluation in comparative study of a much larger number of cases. PMID:16473941

The Cognitive Underpinnings of Emerging Mathematical Skills: Executive Functioning, Patterns, Numeracy, and Arithmetic

ERIC Educational Resources Information Center

Lee, Kerry; Ng, Swee Fong; Pe, Madeline Lee; Ang, Su Yin; Hasshim, Muhammad Nabil Azhar Mohd; Bull, Rebecca

2012-01-01

Background: Exposure to mathematical pattern tasks is often deemed important for developing children's algebraic thinking skills. Yet, there is a dearth of evidence on the cognitive underpinnings of pattern tasks and how early competencies on these tasks are related to later development. Aims: We examined the domain-specific and domain-general…

Patterns of Social Support in the Middle Childhood to Early Adolescent Transition: Implications for Adjustment

ERIC Educational Resources Information Center

Levitt, Mary J.; Levitt, Jerome; Bustos, Gaston L.; Crooks, Noel A.; Santos, Jennifer D.; Telan, Paige; Hodgetts, Jennifer; Milevsky, Avidan

2005-01-01

Children's social networks often include close family members, extended family members, and friends, but little is known about interindividual differences in the patterning of support from these sources. In this study, we used person-oriented analyses to differentiate patterns of support for children undergoing the transition to adolescence.…

Patterns of Movement in Foster Care: An Optimal Matching Analysis

PubMed Central

Havlicek, Judy

2011-01-01

Placement instability remains a vexing problem for child welfare agencies across the country. This study uses child welfare administrative data to retrospectively follow the entire placement histories (birth to age 17.5) of 474 foster youth who reached the age of majority in the state of Illinois and to search for patterns in their movement through the child welfare system. Patterns are identified through optimal matching and hierarchical cluster analyses. Multiple logistic regression is used to analyze administrative and survey data in order to examine covariates related to patterns. Five distinct patterns of movement are differentiated: Late Movers, Settled with Kin, Community Care, Institutionalized, and Early Entry. These patterns suggest high but variable rates of movement. Implications for child welfare policy and service provision are discussed. PMID:20873020

Early summer southern China rainfall variability and its oceanic drivers

NASA Astrophysics Data System (ADS)

Li, Weijing; Ren, Hong-Chang; Zuo, Jinqing; Ren, Hong-Li

2018-06-01

Rainfall in southern China reaches its annual peak in early summer (May-June) with strong interannual variability. Using a combination of observational analysis and numerical modeling, the present study investigates the leading modes of this variability and its dynamic drivers. A zonal dipole pattern termed the southern China Dipole (SCD) is found to be the dominant feature in early summer during 1979-2014, and is closely related to a low-level anomalous anticyclone over the Philippine Sea (PSAC) and a Eurasian wave-train pattern over the mid-high latitudes. Linear regressions based on observations and numerical experiments using the CAM5 model suggest that the associated atmospheric circulation anomalies in early summer are linked to decaying El Niño-Southern Oscillation-like sea surface temperature (SST) anomalies in the tropical Pacific, basin-scale SST anomalies in the tropical Indian Ocean, and meridional tripole-like SST anomalies in the North Atlantic in the previous winter to early summer. The tropical Pacific and Indian Ocean SST anomalies primarily exert an impact on the SCD through changing the polarity of the PSAC, while the North Atlantic tripole-like SST anomalies mainly exert a downstream impact on the SCD by inducing a Eurasian wave-train pattern. The North Atlantic tripole-like SST anomalies also make a relatively weak contribution to the variations of the PSAC and SCD through a subtropical teleconnection. Modeling results indicate that the three-basin combined forcing has a greater impact on the SCD and associated circulation anomalies than the individual influence from any single oceanic basin.

Early differential processing of material images: Evidence from ERP classification.

PubMed

Wiebel, Christiane B; Valsecchi, Matteo; Gegenfurtner, Karl R

2014-06-24

Investigating the temporal dynamics of natural image processing using event-related potentials (ERPs) has a long tradition in object recognition research. In a classical Go-NoGo task two characteristic effects have been emphasized: an early task independent category effect and a later task-dependent target effect. Here, we set out to use this well-established Go-NoGo paradigm to study the time course of material categorization. Material perception has gained more and more interest over the years as its importance in natural viewing conditions has been ignored for a long time. In addition to analyzing standard ERPs, we conducted a single trial ERP pattern analysis. To validate this procedure, we also measured ERPs in two object categories (people and animals). Our linear classification procedure was able to largely capture the overall pattern of results from the canonical analysis of the ERPs and even extend it. We replicate the known target effect (differential Go-NoGo potential at frontal sites) for the material images. Furthermore, we observe task-independent differential activity between the two material categories as early as 140 ms after stimulus onset. Using our linear classification approach, we show that material categories can be differentiated consistently based on the ERP pattern in single trials around 100 ms after stimulus onset, independent of the target-related status. This strengthens the idea of early differential visual processing of material categories independent of the task, probably due to differences in low-level image properties and suggests pattern classification of ERP topographies as a strong instrument for investigating electrophysiological brain activity. © 2014 ARVO.

The effects of early post-hatching changes of imprinting object on the pattern of monocular/unihemispheric sleep of domestic chicks.

PubMed

Bobbo, Daniela; Vallortigara, Giorgio; Mascetti, Gian Gastone

2006-06-03

The pattern of monocular/unihemispheric sleep (Mo-Un sleep) was studied behaviourally in male and female chicks after early post-hatching changes of the imprinting object. Chicks were reared with an imprinting object on day 1 post-hatching which was removed or changed on day 2. On day 1, time spent in binocular sleep (both eyes closed) was similar in male and female chicks, though the number of episodes was lower in females than in males. There was no eye-closure bias in the pattern of Mo-Un sleep (one eye shut and the other open) in chicks of both sexes. On day 2, chicks subjected to the removal of imprinting object showed less time and number of episodes of binocular sleep than control chicks and chicks subjected to changes of imprinting object. There was no eye-closure bias in control chicks whilst a significant bias for more right Mo-Un sleep was recorded in chicks after removal and changes of imprinting object of both sexes. It is suggested that the removal or changes of imprinting object would cause a decrease of binocular sleep and trigger processes associated to secondary imprinting involving the left hemisphere. The bias for more right Mo-Un sleep (right eye-closure) could be the by-product of consolidation processes of secondary imprinting memories in the left hemisphere and/or of more left eye-opening as a result of periodical awakening of right hemisphere to control the environment after a stressful condition such as the removal or change of imprinting object.

Early Foreign Language Learning: The Biological Perspective.

ERIC Educational Resources Information Center

Peltzer-Karpf, Annemarie

A discussion of the biological and developmental issues in early second language learning first looks at psycholinguistic research on brain growth patterns and the relationship of first and second language learning. Focus is on three phenomena observed in the self-organization of living systems: selection of input data; organization of specialized…

Recovery vs. Restructuring: Establishing Ecologic Patterns in Early and Middle Triassic Paleocommunities (Invited)

NASA Astrophysics Data System (ADS)

Fraiser, M.; Dineen, A.; Sheehan, P.

2013-12-01

Published data has been interpreted as indicating that marine ecological devastation following the end-Permian mass extinction was protracted and may have lasted 5 million years into the Middle Triassic (Anisian). However, a review of previous literature shows that understanding of biotic recovery is typically based on only a few components of the ecosystem, such as on taxonomic diversity, a single genus/phylum, or facies. Typically, paleocommunities are considered fully recovered when dominance and diversity are regained and normal ecosystem functioning has resumed. However, in addition to the biodiversity crash at the end of the Permian, taxonomic and ecologic structure also changed,with the extinction marking the faunal shift from brachiopod-rich Paleozoic Evolutionary Fauna (EF) to the mollusc-rich Modern EF. This suggests that the extreme reorganizational nature of the Triassic does not adhere to the standard definition of recovery, which is a return to previous conditions. Thus, we propose the term 'restructuring' to describe this interval, as Early and Middle Triassic communities might not exhibit the typical characteristics of a 'normal' Permian one. To more fully characterize Triassic ecologic restructuring, paleoecologists should take into account functional diversity and redundancy. We quantified functional richness and regularity in four different paleocommunities from classic Permian and Triassic sections. Functional richness was low in paleocommunities after the end-Permian mass extinction, but increased to high levels by the Middle Triassic. In contrast, functional regularity was low in the Middle Permian, but high in all the Triassic paleocommunities. The change from low to high functional regularity/redundancy at the P/T boundary may be a factor of the highly stressful Triassic environmental conditions (i.e. anoxia, hypercapnia), as high regularity in a community can boost survival in harsh environments. Parameters such as these will more

Consistency of a lumbar movement pattern across functional activities in people with low back pain.

PubMed

Marich, Andrej V; Hwang, Ching-Ting; Salsich, Gretchen B; Lang, Catherine E; Van Dillen, Linda R

2017-05-01

Limitation in function is a primary reason people with low back pain seek medical treatment. Specific lumbar movement patterns, repeated throughout the day, have been proposed to contribute to the development and course of low back pain. Varying the demands of a functional activity test may provide some insight into whether people display consistent lumbar movement patterns during functional activities. Our purpose was to examine the consistency of the lumbar movement pattern during variations of a functional activity test in people with low back pain and back-healthy people. 16 back-healthy adults and 32 people with low back pain participated. Low back pain participants were classified based on the level of self-reported functional limitations. Participants performed 5 different conditions of a functional activity test. Lumbar excursion in the early phase of movement was examined. The association between functional limitations and early phase lumbar excursion for each test condition was examined. People with low back pain and high levels of functional limitation demonstrated a consistent pattern of greater early phase lumbar excursion across test conditions (p<0.05). For each test condition, the amount of early phase lumbar excursion was associated with functional limitation (r=0.28-0.62). Our research provides preliminary evidence that people with low back pain adopt consistent movement patterns during the performance of functional activities. Our findings indicate that the lumbar spine consistently moves more readily into its available range in people with low back pain and high levels of functional limitation. How the lumbar spine moves during a functional activity may contribute to functional limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early innate immune responses to Sin Nombre hantavirus occur independently of IFN regulatory factor 3, characterized pattern recognition receptors, and viral entry.

PubMed

Prescott, Joseph B; Hall, Pamela R; Bondu-Hawkins, Virginie S; Ye, Chunyan; Hjelle, Brian

2007-08-01

Sin Nombre virus (SNV) is a highly pathogenic New World virus and etiologic agent of hantavirus cardiopulmonary syndrome. We have previously shown that replication-defective virus particles are able to induce a strong IFN-stimulated gene (ISG) response in human primary cells. RNA viruses often stimulate the innate immune response by interactions between viral nucleic acids, acting as a pathogen-associated molecular pattern, and cellular pattern-recognition receptors (PRRs). Ligand binding to PRRs activates transcription factors which regulate the expression of antiviral genes, and in all systems examined thus far, IFN regulatory factor 3 (IRF3) has been described as an essential intermediate for induction of ISG expression. However, we now describe a model in which IRF3 is dispensable for the induction of ISG transcription in response to viral particles. IRF3-independent ISG transcription in human hepatoma cell lines is initiated early after exposure to SNV virus particles in an entry- and replication-independent fashion. Furthermore, using gene knockdown, we discovered that this activation is independent of the best-characterized RNA- and protein-sensing PRRs including the cytoplasmic caspase recruitment domain-containing RNA helicases and the TLRs. SNV particles engage a heretofore unrecognized PRR, likely located at the cell surface, and engage a novel IRF3-independent pathway that activates the innate immune response.

A major reorganization of Asian climate by the early Miocene

NASA Astrophysics Data System (ADS)

Guo, Z. T.; Sun, B.; Zhang, Z. S.; Peng, S. Z.; Xiao, G. Q.; Ge, J. Y.; Hao, Q. Z.; Qiao, Y. S.; Liang, M. Y.; Liu, J. F.; Yin, Q. Z.; Wei, J. J.

2008-08-01

The global climate system experienced a series of drastic changes during the Cenozoic. In Asia, these include the climate transformation from a zonal pattern to a monsoon-dominated pattern, the disappearance of typical subtropical aridity, and the onset of inland deserts. Despite major advances in the last two decades in characterizing and understanding these climate phenomena, disagreements persist relative to the timing, behaviors and underlying causes. This paper addresses these issues mainly based on two lines of evidence. First, we compiled newly collected data from geological indicators of the Cenozoic environment in China as paleoenvironmental maps of ten intervals. In confirming the earlier observation that a zonal climate pattern was transformed into a monsoonal one, the maps within the Miocene indicate that this change was achieved by the early Miocene, roughly consistent with the onset of loess deposition in China. Although a monsoon-like regime would have existed in the Eocene, it was restricted to tropical-subtropical regions. The latitudinal oscillations of the climate zones during the Paleogene are likely attributable to the imbalance in evolution of polar ice-sheets between the two hemispheres. Secondly, we examine the relevant depositional and soil forming processes of the Miocene loess-soil sequences to determine the circulation characteristics with emphasis on the early Miocene. Continuous eolian deposition in the middle reaches of the Yellow River since the early Miocene firmly indicates the formation of inland deserts, which have been constantly maintained during the past 22 Ma. Grain-size gradients between loess sections indicate northerly dust-carrying winds from northern sources, a clear indication of an Asian winter monsoon system. Meanwhile, well-developed Luvisols show evidence that moisture from the oceans reached northern China. This evidence shows the coexistence of two kinds of circulations, one from the ocean carrying moisture and

Waves and patterning in developmental biology: vertebrate segmentation and feather bud formation as case studies

PubMed Central

Baker, Ruth E.; Schnell, Santiago; Maini, Philip K.

2014-01-01

In this article we will discuss the integration of developmental patterning mechanisms with waves of competency that control the ability of a homogeneous field of cells to react to pattern forming cues and generate spatially heterogeneous patterns. We base our discussion around two well known patterning events that take place in the early embryo: somitogenesis and feather bud formation. We outline mathematical models to describe each patterning mechanism, present the results of numerical simulations and discuss the validity of each model in relation to our example patterning processes. PMID:19557684

Reminiscing in the Early Years: Patterns of Maternal Elaborativeness and Children's Remembering

ERIC Educational Resources Information Center

Haden, Catherine A.; Ornstein, Peter A.; Rudek, David J.; Cameron, Danielle

2009-01-01

This study focused on individual differences in maternal style and children's developing recall abilities in early memory conversations. Within a longitudinal design, a sample of 56 mother-child dyads was observed while reminiscing, and the children's language skills were assessed when they were 18, 24, and 30 months old. In contrast to mothers…

Patterns of Individual Adjustment Changes During Middle School Transition.

ERIC Educational Resources Information Center

Chung, HyunHee; Elias, Maurice; Schneider, Kenneth

1998-01-01

Examines the patterns of individual adjustment changes in a sample of 99 early adolescents during an ecological transition from elementary school to middle school. Shows significant changes in adjustment as indicated by increased psychological distress or decreased academic achievement. Examines gender differences. Presents implications for…

Cognitive function in early HIV infection.

PubMed

Prakash, Aanchal; Hou, Jue; Liu, Lei; Gao, Yi; Kettering, Casey; Ragin, Ann B

2017-04-01

This study aimed to examine cognitive function in acute/early HIV infection over the subsequent 2 years. Fifty-six HIV+ subjects and 21 seronegative participants of the Chicago Early HIV Infection Study were evaluated using a comprehensive neuropsychological assessment at study enrollment and at 2-year follow-up. Cognitive performance measures were compared in the groups using t tests and mixed-effect models. Patterns of relationship with clinical measures were determined between cognitive function and clinical status markers using Spearman's correlations. At the initial timepoint, the HIV group demonstrated significantly weaker performance on measures of verbal memory, visual memory, psychomotor speed, motor speed, and executive function. A similar pattern was found when cognitive function was examined at follow-up and across both timepoints. The HIV subjects had generally weaker performance on psychomotor speed, executive function, motor speed, visual memory, and verbal memory. The rate of decline in cognitive function across the 2-year follow-up period did not differ between groups. Correlations between clinical status markers and cognitive function at both timepoints showed weaker performance associated with increased disease burden. Neurocognitive difficulty in chronic HIV infection may have very early onset and reflect consequences of initial brain viral invasion and neuroinflammation during the intense, uncontrolled viremia of acute HIV infection. Further characterization of the changes occurring in initial stages of infection and the risk and protective factors for cognitive function could inform new strategies for neuroprotection.

Longitudinal Changes in Spouses’ HPA Responses: Convergence in Cortisol Patterns During the Early Years of Marriage

PubMed Central

Laws, Holly; Sayer, Aline G.; Pietromonaco, Paula R.; Powers, Sally I.

2015-01-01

Objective Drawing on theories of bidirectional influence between relationship partners (Butler, 2011; Diamond & Aspinwall, 2003), the authors applied dyadic analytic methods to test convergence in cortisol patterns over time in newlywed couples. Methods Previous studies of bidirectional influence in couples’ cortisol levels (Liu, Rovine, Klein, & Almeida, 2013, Papp, Pendry, Simon, & Adam, 2013; Saxbe & Repetti, 2010) found significant covariation in couples’ daily cortisol levels over several days, but no studies have tested whether cortisol response similarity increases over time using a longitudinal design. In the present study, 183 opposite-sex couples (366 participants) engaged in a conflict discussion in a laboratory visit about 6 months after their marriage, and again about 2 years into the marriage. At each visit, spouses provided saliva samples that indexed cortisol levels before, during, and after the discussion. This multi-measure procedure enabled modeling of spouses’ cortisol trajectories around the conflict discussion. Results Findings showed significant convergence in couples’ cortisol trajectories across the early years of marriage; couples showed significantly greater similarity in cortisol trajectories around the conflict discussion as their relationship matured. Cohabitation length predicted stronger convergence in cortisol slopes prior to the conflict discussion. Couples’ relationship dissatisfaction was associated with a greater degree of convergence in spouses’ acute cortisol levels during the conflict discussion. Conclusions Findings suggest that spouses increasingly shape each other’s cortisol responses as their relationship matures. Findings also indicated that increased similarity in acute cortisol levels during conflict may be associated with poorer relationship functioning. PMID:26010721

Longitudinal changes in spouses' HPA responses: Convergence in cortisol patterns during the early years of marriage.

PubMed

Laws, Holly B; Sayer, Aline G; Pietromonaco, Paula R; Powers, Sally I

2015-11-01

Drawing on theories of bidirectional influence between relationship partners (Butler, 2011; Diamond & Aspinwall, 2003), the authors applied dyadic analytic methods to test convergence in cortisol patterns over time in newlywed couples. Previous studies of bidirectional influence in couples' cortisol levels (Liu, Rovine, Klein, & Almeida, 2013; Papp, Pendry, Simon, & Adam, 2013; Saxbe & Repetti, 2010) found significant covariation in couples' daily cortisol levels over several days, but no studies have tested whether cortisol response similarity increases over time using a longitudinal design. In the present study, 183 opposite sex couples (366 participants) engaged in a conflict discussion in a laboratory visit about 6 months after their marriage, and again about 2 years into the marriage. At each visit, spouses provided saliva samples that indexed cortisol levels before, during, and after the discussion. This multimeasure procedure enabled modeling of spouses' cortisol trajectories around the conflict discussion. Findings showed significant convergence in couples' cortisol trajectories across the early years of marriage; couples showed significantly greater similarity in cortisol trajectories around the conflict discussion as their relationship matured. Cohabitation length predicted stronger convergence in cortisol slopes prior to the conflict discussion. Couples' relationship dissatisfaction was associated with a greater degree of convergence in spouses' acute cortisol levels during the conflict discussion. Findings suggest that spouses increasingly shape each other's cortisol responses as their relationship matures. Findings also indicated that increased similarity in acute cortisol levels during conflict may be associated with poorer relationship functioning. (c) 2015 APA, all rights reserved).

The prevalence of early repolarization in Wolff-Parkinson-White syndrome with a special reference to J waves and the effects of catheter ablation.

PubMed

Yagihara, Nobue; Sato, Akinori; Iijima, Kenichi; Izumi, Daisuke; Furushima, Hiroshi; Watanabe, Hiroshi; Irie, Tadanobu; Kaneko, Yoshiaki; Kurabayashi, Masahiko; Chinushi, Masaomi; Satou, Masahito; Aizawa, Yoshifusa

2012-01-01

We determined the prevalence of J waves in the electrocardiograms (ECG) of 120 patients with Wolff-Parkinson-White syndrome in comparison with J-wave prevalence in a control group of 1936 men and women with comparable demographic and ECG characteristics and with normal atrioventricular conduction. J waves were present only during manifest preexcitation in 22 of 120 patients (18.3%), disappearing after catheter ablation and suggesting that J waves were associated with the presence of preexcitation. J waves were present in 19 (15.8%) of 120 patients only after ablation, apparently having been masked by early depolarization of the preexcited myocardial region, and in 22 patients (18.3%), J waves were not altered significantly by preexcitation. Thus, the overall J-wave prevalence was 52.5% (63/120) and, excluding those apparently due to preexcitation, 34.8% (41/120), both substantially higher than the prevalence (11.5%) in the control group (P < .001 for both). The patients with J waves appearing only during preexcitation were younger, predominantly females. The presence of J waves after ablation was associated with a history of atrial fibrillation and shorter ventricular effective refractory period. It is concluded that the prevalence of J waves is high in patients with Wolff-Parkinson-White syndrome and is influenced by manifest preexcitation. Copyright © 2012 Elsevier Inc. All rights reserved.

Multifinality of peer victimization: maladjustment patterns and transitions from early to mid-adolescence.

PubMed

Kretschmer, Tina; Barker, Edward D; Dijkstra, Jan Kornelis; Oldehinkel, Albertine J; Veenstra, René

2015-10-01

Peer victimization is a common and pervasive experience in childhood and adolescence and is associated with various maladjustment symptoms, including internalizing, externalizing, and somatic problems. This variety suggests that peer victimization is multifinal where exposure to the same risk leads to different outcomes. However, very little is known about the relative likelihood of each form of maladjustment. We used a latent profile approach to capture multiple possible outcomes and examined prediction by peer victimization. We also examined the role of peer victimization with regard to stability and change in maladjustment. Maladjustment symptoms and peer victimization were assessed from the participants of the large cohort study TRacking Adolescents' Individual Lives Survey in early and mid-adolescence. Latent profile and latent transition analyses were conducted to examine associations between victimization and maladjustment profile and to test the role of victimization in maladjustment profile transitions. Four maladjustment profiles were identified for early adolescence (Low, Internalizing, Externalizing, Comorbid) and three profiles (Low, Internalizing, Externalizing) were identified for mid-adolescence. Internalizing problems were more likely in victimized adolescents than low symptom levels or externalizing problems. Victimized adolescents were at greater risk to develop internalizing problems between early and mid-adolescence than non-victimized adolescents. Peer victimization is multifinal mostly when outcomes are examined separately. If multiple outcomes are tested simultaneously, internalizing problems seem to be the most likely outcome.

Paleoenvironments and climatic changes in the Italian Peninsula during the Early Pleistocene: evidence from dental wear patterns of the ungulate community of Coste San Giacomo

NASA Astrophysics Data System (ADS)

Strani, Flavia; DeMiguel, Daniel; Sardella, Raffaele; Bellucci, Luca

2015-08-01

Quaternary glacial/interglacial alternations, influenced by orbital obliquity cycles with a 41-ka long periodicity, started in the northern hemisphere around 2.6 Ma ago. Such alternations affected the terrestrial ecosystems, especially those of the Mediterranean region, with changes in the floristic communities and the dispersal and radiation of a number of large mammal open dwellers. Analyses of tooth wear patterns of ungulates from the Early Pleistocene site of Coste San Giacomo allow for a more objective reconstruction on the paleoenvironments and the climate in the Italian Peninsula during this epoch. Our results show that this area was composed by a mosaic of biomes, in particular by steppe and woodlands/wetlands. Evidence of such heterogeneity is provided by the wide spectrum of feeding behaviours found among the numerous ungulate herbivores here recorded, with cervids (Axis cf. lyra, Croizetoceros cf. ramosus and Eucladoceros sp.) exhibiting browser diets, most of the bovids (Gazella borbonica and Leptobos sp. and Gallogoral meneghinii) being intermediate feeders and the equid Equus stenonis showing a strict grazer behaviour. These results provide new insights for a timing of changing ecosystems in Southern Europe and reveal the environmental legacy of this global climatic shift, which is essential for understanding the early occupation of Homo in Europe. Thus, our data provide new evidence that such an environmental heterogeneity and a wide spectrum of available food resources could have been the main factors favouring the settlement of early species of Homo in this area.

The maturation of cortical sleep rhythms and networks over early development

PubMed Central

Chu, CJ; Leahy, J; Pathmanathan, J; Kramer, MA; Cash, SS

2014-01-01

Objective Although neuronal activity drives all aspects of cortical development, how human brain rhythms spontaneously mature remains an active area of research. We sought to systematically evaluate the emergence of human brain rhythms and functional cortical networks over early development. Methods We examined cortical rhythms and coupling patterns from birth through adolescence in a large cohort of healthy children (n=384) using scalp electroencephalogram (EEG) in the sleep state. Results We found that the emergence of brain rhythms follows a stereotyped sequence over early development. In general, higher frequencies increase in prominence with striking regional specificity throughout development. The coordination of these rhythmic activities across brain regions follows a general pattern of maturation in which broadly distributed networks of low-frequency oscillations increase in density while networks of high frequency oscillations become sparser and more highly clustered. Conclusion Our results indicate that a predictable program directs the development of key rhythmic components and physiological brain networks over early development. Significance This work expands our knowledge of normal cortical development. The stereotyped neurophysiological processes observed at the level of rhythms and networks may provide a scaffolding to support critical periods of cognitive growth. Furthermore, these conserved patterns could provide a sensitive biomarker for cortical health across development. PMID:24418219

Early Identification and Treatment of Antisocial Behavior.

PubMed

Frick, Paul J

2016-10-01

Severe and persistent antisocial behavior is a prevalent, serious, and costly mental health problem. Individuals who are most likely to show persistent antisocial behavior through adolescence and into adulthood often show patterns of severe and varied conduct problems early in childhood. Treatments that intervene early in the development of these problems are most effective and least costly. Furthermore, there appear to be several common causal pathways that differ in their genetic, emotional, cognitive, and contextual characteristics. These pathways are differentiated by the level of callous-unemotional traits displayed by the individual. Copyright © 2016 Elsevier Inc. All rights reserved.

Dietary patterns of early childhood and maternal socioeconomic status in a unique prospective sample from a randomized controlled trial of Prenatal DHA Supplementation.

PubMed

Hidaka, Brandon H; Kerling, Elizabeth H; Thodosoff, Jocelynn M; Sullivan, Debra K; Colombo, John; Carlson, Susan E

2016-11-25

Dietary habits established in early childhood and maternal socioeconomic status (SES) are important, complex, interrelated factors that influence a child's growth and development. The aim of this study was to define the major dietary patterns in a cohort of young US children, construct a maternal SES index, and evaluate their associations. The diets of 190 children from a randomized, controlled trial of prenatal supplementation of docosahexaenoic acid (DHA) were recorded at 6-mo intervals from 2-4.5 years by 24-h dietary recall. Hierarchical cluster analysis of age-adjusted, average daily intake of 24 food and beverage groups was used to categorize diet. Unrotated factor analysis generated an SES score from maternal race, ethnicity, age, education, and neighborhood income. We identified two major dietary patterns: "Prudent" and "Western." The 85 (45%) children with a Prudent diet consumed more whole grains, fruit, yogurt and low-fat milk, green and non-starchy vegetables, and nuts and seeds. Conversely, those with a Western diet had greater intake of red meat, discretionary fat and condiments, sweet beverages, refined grains, French fries and potato chips, eggs, starchy vegetables, processed meats, chicken and seafood, and whole-fat milk. Compared to a Western diet, a Prudent diet was associated with one standard deviation higher maternal SES (95% CI: 0.80 to 1.30). We found two major dietary patterns of young US children and defined a single, continuous axis of maternal SES that differed strongly between groups. This is an important first step to investigate how child diet, SES, and prenatal DHA supplementation interact to influence health outcomes. NCT00266825 . Prospectively registered on December 15, 2005.

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.

PubMed

Chen, Yuncai; Baram, Tallie Z

2016-01-01

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational

The Development of Self-Regulation across Early Childhood

PubMed Central

Montroy, Janelle J.; Bowles, Ryan P.; Skibbe, Lori E.; McClelland, Megan M.; Morrison, Frederick J.

2016-01-01

The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of three and seven, with a direct focus on possible heterogeneity in the developmental trajectories, and a set of potential indicators that distinguish unique behavioral self-regulation trajectories. Across three diverse samples, 1,386 children were assessed on behavioral self-regulation from preschool through first grade. Results indicated that majority of children develop self-regulation rapidly during early childhood, and that children follow three distinct developmental patterns of growth. These three trajectories were distinguishable based on timing of rapid gains, as well as child gender, early language skills, and maternal education levels. Findings highlight early developmental differences in how self-regulation unfolds with implications for offering individualized support across children. PMID:27709999

Early markers of adult obesity: a review

PubMed Central

Brisbois, T D; Farmer, A P; McCargar, L J

2012-01-01

Summary The purpose of this review was to evaluate factors in early childhood (≤5 years of age) that are the most significant predictors of the development of obesity in adulthood. Factors of interest included exposures/insults in the prenatal period, infancy and early childhood, as well as other socio-demographic variables such as socioeconomic status (SES) or birth place that could impact all three time periods. An extensive electronic and systematic search initially resulted in 8,880 citations, after duplicates were removed. Specific inclusion and exclusion criteria were set, and following two screening processes, 135 studies were retained for detailed abstraction and analysis. A total of 42 variables were associated with obesity in adulthood; however, of these, only seven variables may be considered as potential early markers of obesity based on the reported associations. Possible early markers of obesity included maternal smoking and maternal weight gain during pregnancy. Probable early markers of obesity included maternal body mass index, childhood growth patterns (early rapid growth and early adiposity rebound), childhood obesity and father's employment (a proxy measure for SES in many studies). Health promotion programmes/agencies should consider these factors as reasonable targets to reduce the risk of adult obesity. PMID:22171945

Auditory motion processing after early blindness

PubMed Central

Jiang, Fang; Stecker, G. Christopher; Fine, Ione

2014-01-01

Studies showing that occipital cortex responds to auditory and tactile stimuli after early blindness are often interpreted as demonstrating that early blind subjects “see” auditory and tactile stimuli. However, it is not clear whether these occipital responses directly mediate the perception of auditory/tactile stimuli, or simply modulate or augment responses within other sensory areas. We used fMRI pattern classification to categorize the perceived direction of motion for both coherent and ambiguous auditory motion stimuli. In sighted individuals, perceived motion direction was accurately categorized based on neural responses within the planum temporale (PT) and right lateral occipital cortex (LOC). Within early blind individuals, auditory motion decisions for both stimuli were successfully categorized from responses within the human middle temporal complex (hMT+), but not the PT or right LOC. These findings suggest that early blind responses within hMT+ are associated with the perception of auditory motion, and that these responses in hMT+ may usurp some of the functions of nondeprived PT. Thus, our results provide further evidence that blind individuals do indeed “see” auditory motion. PMID:25378368

Benthic foraminiferal and isotopic patterns during the Early Eocene Climatic Optimum (Aktulagay section, Kazakhstan)

NASA Astrophysics Data System (ADS)

Deprez, Arne; Tesseur, Steven; Stassen, Peter; D'haenens, Simon; Steurbaut, Etienne; King, Christopher; Claeys, Philippe; Speijer, Robert P.

2015-04-01

The early Eocene is characterized by long-term global warming culminating in the Early Eocene Climatic Optimum (EECO). During this time interval, the Peri-Tethys was connected to the Arctic and Atlantic Oceans by north-south and east-west trending seaways. The Aktulagay section in Kazakhstan provides an expanded record of the middle Ypresian (NP11-13, ~54-50 Ma; King et al., 2013), including the EECO. The marl sequence features a series of sapropel beds, observed throughout the Peri-Tethys, indicative of basin-wide episodic hypoxic events. In order to unravel paleoenvironmental changes, we carried out quantitative faunal studies and stable isotopic (C, O) investigations on excellently preserved foraminiferal assemblages. The period from 54 to 52.5 Ma (NP11 to lower NP12; Alashen Formation) is characterized by a diverse assemblage of deep outer neritic (~200-250 m) benthic foraminifera, with common Pulsiphonina prima and Paralabamina lunata. The initially (54 Ma) well-ventilated oligo- to mesotrophic seafloor conditions gradually changed to more eutrophic and oxygen-limited. These conditions were more permanent in the sapropel-bearing unit at 52.5-52 Ma (middle NP12; Aktulagay B1 unit). This observation is based on the dominance of Anomalinoides acutus and Bulimina aksuatica and the lower diversity. Also the upward migration of endobenthic species, as suggested by rising δ13Cendobenthic, supports this interpretation. These low-oxygen conditions might have been caused by a transgression, flooding lowlands. Benthic foraminiferal assemblages dominated by Epistominella minuta at ~52-50 Ma (top NP12-NP13; Aktulagay B2 unit) suggest an oligotrophic environment, with transient pulses of phytodetritus. Dinoflagellate blooms and Acarinina isotope values at ~50.5 Ma indicate lower salinity (lower δ18O) and higher productivity (higher δ13C), possibly due to riverine input. Large river plumes, episodically reaching the area, in a monsoonal climate context, might explain this